MICHlGAN s ATE mvensm LIBRARIES l l llllllll ll lll'llllll W. l. ll: l 3 293 01405 3254 . This is to certify that the thesis entitled Heavy Metals in the Ink Industry presented by Carla Maria Vidal has been accepted towards fulfillment of the requirements for Masters of ; Science—degree in Packaging 2 ’ m (J. 1 Major professor Date 07/24/95 0-7639 MS U is an Affirmative Action/Equal Opportunity Institution _ ... __ _ . _ _ *_._‘r'__‘__.__ LIBRARY Michigan State University PLACE IN RETURN BOX to remove thie checkout from your record. To AVOID FINES return on or before date due. DATE DUE DATE DUE DATE DUE ___IL_L_J fif—W—T MSU leAnAtfinnetiveActia'VEmel Oppommityinetituion HEAVY METALS IN THE INK INDUSTRY By Carla Maria Vidal A THESIS Submitted to Michigan State University in partial fulfillment of the requirements for the degree of MASTER OF SCIENCE School of Packaging 1995 ABSTRACT HEAVY METALS IN THE INK INDUSTRY By Carla Maria Vidal The objective of the present study was to determine how ink manufacturers for the packaging industry were affected by the Model Toxics in Packaging Legislation developed by the Coalition of Northeastern Governors (CONEG). The study was based upon six heavy metals: copper, zinc, cadmium, chromium (VI), and mercury. Health and environmental effects of the six metals were also summarized. A survey of ink manufacturers was conducted. Ninety percent of the ink industries responding limit total heavy metal content to less than 100 ppm to comply with CONEG types of regulation. Sixty two and forty one percent of the respondents said cost and price, respectively, were increased by the reduction of heavy metal content in their inks by an average of 9% and 8.8% respectively. Heavy metals are expected to be replaced totally in 5 to 20 years. Organic inks are the usual substitutes for heavy metal based pigments. ACKNOWLEDGMENTS I would like to thank my major professor, Dr. Susan Selke for the guidance and support she has given me during this project. I would also like to thank my other committee members, Dr. Harold Hugues and Dr. Mackenzie Davis, for their help. I am indebted to my parents for their continued support throughout my education. Without them, I could never have accomplished all that I have. Finally, I am specially thankful to my friends, Francisco and Andres, whose patience and encouragement helped me more than they know. ii TABLE OF CONTENTS Page ABSTRACT- ACKNOWLEDGMENTS - LIST OF TABLES- LIST OF FIGURES - CHAPTER 1. INTRODUCTION- - History ...................................................................................... Sources of Heavy Metals in Inks ............................................. Regulations ............................................................................... The Coalition of Northeastern Governors (CONEG) ............... Certificate of Compliance ......................................................... Substitutes ................................................................................. Disposal .................................................................................... CHAPTER 2. ENVIRONIVIENT AL EFFECTS ASSOCIATED WITH COPPER - Introduction ............................................................................. Sewage Treatment Plants ........................................................ Water Pollution ....................................................................... Soil Pollution .......................................................................... Air Pollution ........................................................................... Effect of Copper Pollution on Terrestrial Animal Life .......... Effects of Copper Pollution on Aquatic Life .......................... Copper Toxicity to Aquatic Invertebrates .................. Copper Toxicity to Fish .............................................. Effects of Copper Pollution in Plants ..................................... iv 0. ll iii xiii .— \INQMAUJN 10 10 ll l3 l4 14 15 16 l6 l7 l9 CHAPTER 3. HEALTH EFFECTS ASSOCIATED WITH COPPER IN HUMANS- - - - 21 Introduction .............................................................................. 21 Large Quantities of Copper Ingested ....................................... 22 Copper Fumes and Dust Toxicity ............................................ 23 Metal Fume Fever ........................................................ 24 Respiratory Effects ...................................................... 25 Anemia and Hemolytic Effects ................................... 25 Hepatic Effects ............................................................ 26 Dermal / Ocular Effects .............................................. 26 Gastrointestinal Effects ............................................... 26 Neurological Effects ................................................... 27 Reproductive Effects ................................................... 27 Other Systemic Effects ................................................ 27 Heart Disease ............................................................... 27 CHAPTER 4. ENVIRONMENTAL AND HEALTH EFFECTS ASSOCIATED WITH ZINC , - - - - - . 28 Environmental Effects Associated with Zinc ............................... 28 Animal Toxicity ............................................................. 28 Inhalation ........................................................... 28 Oral .................................................................... 29 Zinc Hazards to Fishes .................................................. 31 Plant Toxicity ................................................................ 33 Toxicity of Mixtures of Zinc and Copper ..................... 34 Health Effects Associated with Zinc in Humans ......................... 35 Exposure ........................................................................ 35 Inhalation Toxicity ........................................................ 35 Carcinogenic and teratogenic effects ............................. 36 Risk of progression to AIDS .......................................... 38 CHAPTER 5. ENVIRONMENTAL EFFECTS ASSOCIATED WITH I-IEXAVALENT CHROMIUM - 38 Landfill ....................................................................................... 39 Air ............................................................................................... 40 Water ........................................................................................... 41 Soil .............................................................................................. 42 Effects of Chromium on Vegetation ............................................ 42 Terrestrial Animals ..................................................................... 44 Aquatic Organism ........................................................................ 45 Invertebrates ................................................................. 45 Fish ............................................................................. 46 Regulations .................................................................................. 47 vi CHAPTER 6. HEALTH EFFECTS ASSOCIATED WITH HEXAVALENT CHROMIUM - - - ........ Introduction ............................................................................... Cancer ........................................................................................ Dermal Diseases ........................................................................ Respiratory Effects .................................................................... Mutation ..................................................................................... CHAPTER 7. ENVIRONMENTAL EFFECTS ASSOCIATED WITH CADMIUM - - - - Introduction ............................................................................. Plastics .................................................................................... Plasticizers ................................................................... Pigments ...................................................................... Water ...................................................................................... Air ........................................................................................... Soil .......................................................................................... Sewage Sludge and Land Disposal ........................................... Animal Toxicity ........................................................................ Birds ........................................................................... Aquatic Organisms ....................................................... Fish ........................................................................... Invertebrates ................................................................ Plant Toxicity ........................................................................... CHAPTER 8. HEALTH EFFECTS ASSOCIATED WITH CADMIUM.. Introduction ............................................................................. Acute Effects ........................................................................... Chronic Effects ........................................................................ Exposure Limits ....................................................................... Exposure Effects ...................................................................... Death .......................................................................... Musculoskeletal Effects ................................................ Immunological Effects .................................................. Development Effects .................................................... Genotoxic Effects ......................................................... Reproductive Effects .................................................... Respiratory Effects ....................................................... Cardiovascular Effects ................................................. Renal Effects ................................................................ Cancer ........................................................................ 49 49 50 53 54 56 57 57 58 59 59 61 62 62 63 63 65 66 68 68 69 7O 7O 7 l 7 l 7 1 72 72 72 72 73 73 74 75 vii CHAPTER 9. ENVIRONMENTAL EFFECTS ASSOCIATED WITH MERCURY - - Introduction ............................................................................. Catalysts .................................................................................. Air ........................................................................................... Water ...................................................................................... Landfills and Soil .................................................................... Animals ................................................................................... Aquatic Organisms ...................................................... Terrestrial Organisms ................................................. Birds ........................................................................... Plants ...................................................................................... CHAPTER 10. HEALTH EFFECTS ASSOCIATED WITH MERCURY Introduction ............................................................................. Mercury Concentration Limits ........................ . ........... Mercury Exposure Indicators ....................................... Acute Effects ........................................................................... Chronic Effects ........................................................................ Systematic Effects .................................................................... Gingivitis ..................................................................... Gastrointestinal Effects ................................................. Cardiovascular Effects ................................................. Renal Effects ................................................................ Dermal/Ocular Effects .................................................. Musculoskeletal Effects ................................................ Neurological Effects ..................................................... Respiratory Effects ................................................................... Developmental Effects .............................................................. Mutation .................................................................................... CHAPTER 11. ENVIRONMENTAL EFFECTS ASSOCIATED WITH LEAD Introduction ............................................................................. Uses ............................................................................ Packaging Inks ............................................................ Water ...................................................................................... Aquatic Organisms ................................................................. 76 76 77 77 78 79 80 80 82 82 82 84 84 85 85 86 87 87 87 88 88 88 89 89 91 92 93 93 93 94 96 96 97 97 viii Birds ....................................................................................... 98 Plants ...................................................................................... 98 CHAPTER 12. HEALTH EFFECTS ASSOCIATED WITH LEAD ......... 99 Introduction ............................................................................. 99 Neurotoxicity ........................................................................... 100 Reproductive Effects ............................................................... 101 Renal Effects ........................................................................... 102 Cancer ..................................................................................... 102 Gastrointestinal Effects ........................................................... 103 Cardiovascular Effects ............................................................. 103 Mutagenic Effects .................................................................... 103 Hematological Effects ............................................................... 104 CHAPTER 13. THE DESIGN OF THE INVESTIGATION AND ANALYSIS OF DATA. - -- - 105 The Study Population ............................................................... 105 The Instrument ......................................................................... 105 The Mailed Questionnaire Survey ............................................ 106 Describing the Data .................................................................. 107 Profile of the Respondents ........................................................ 108 CHAPTER 14. SUMMARY AND CONCLUSIONS - -- 134 Declaration 1. Solid Waste as a Hazard to Health and Environment ..................................................... 135 Declaration 2. Packaging as a Significant Percent of Solid Waste Stream ....................... 135 Declaration 3. Environmental Hazards of Heavy Metal Disposal 136 Copper ........................................................................ 136 Chromium ................................................................... 136 Cadmium .................................................................... 136 Mercury ...................................................................... 137 Lead ............................................................................ 137 Declaration 4. Heavy Metal Exposure as a Health Hazard ...... 138 Copper ......................................................................... 138 Chromium .................................................................... 138 Cadmium ...................................................................... 139 Mercury ........................................................................ 139 Lead .............................................................................. 140 Declaration 5. Heavy Metal Reduction ..................................... 140 ix Recommendations for Future Work ........................................ 141 GLOSSARY--- - - - - — - -- -- -- 143 APPENDICES APPENDIX A. Model Toxics Legislation as Developed by the CONEG Source Reduction Council ............. 148 APPENDIX B. Survey Questionnaire ....................................... 154 APPENDD( C. Summary of Substitutes for Heavy Metals in the Ink Industry .............................................. 172 LIST OF REFERENCES--- - - - - - -- 173 Table HI. IV. VI. VII. VIII. LIST OF TABLES WHICH OF THESE HAS YOUR COMPANY USED IN INK FORMULATION? QUANTITY OF HEAVY METALS ALLOWED IN INKS AND SOURCE OF LIMITATION HOW OFTEN DO YOUR CUSTOMERS IN THE PACKAGING NDUSTRY ASK YOUR COMPANY FOR A WRITTEN CERTIFICATION OF COMPLIANCE WITH TOXICS LEGISLATION? HOW OFTEN DO YOUR CUSTOMERS IN OTHER INDUSTRIES ASK YOUR COMPANY FOR A WRITTEN CERTIFICATE OF COMPLIANCE WITH TOXICS LEGISLATION? MAJOR INDUSTRIES WHICH ASK FOR CERTIFICATION WHICH ANALYTICAL METHODS DO YOU GENERALLY USE TO DETERMINE METAL CONTENT IN YOUR INKS? BY ABOUT WHAT PERCENT HAVE YOUR COSTS INCREASED DUE TO REDUCTION OF HEAVY METAL CONTENT? BY ABOUT WHAT PERCENT HAVE YOUR PRICES INCREASED DUE TO REDUCTION OF HEAVY METAL CONTENT? HAVE YOU REFORMULATED ANY OF YOUR INKS FOR THE PACKAGING INDUSTRY TO REDUCE OR ELIMIN ATE THEIR HEAVY METAL CONTENT? Page 109 111 112 113 114 114 115 116 118 X. HAVE YOU REFORMULATED ANY OF YOUR INKS FOR NON-PACKAGING INDUSTRIES TO REDUCE OR ELIMINATE THEIR HEAVY METAL CONTENT? 119 XI. CADMIUM RED REFORMULATION IN THE PAST 120 XII. CADMIUM RED REFORMULATION IN THE FUTURE 120 XHI. CADMIUM YELLOW REF ORMULATION XIV. XV. XVI. XVII. XVIII. XIX. XX. XXI. XXII. XXIII. IN THE PAST CADMIUM YELLOW REFORMULATION IN THE FUTURE CADMIUM ORANGE REFORMULATION IN THE PAST CADMIU M ORANGE REFORMULATION IN THE FUTURE LEAD BASED YELLOW REFORMULATION IN THE PAST LEAD BASED YELLOW REFORMULATION IN THE FUTURE CHROMATE YELLOW REFORMULATION IN THE PAST CHROMATE YELLOW REFORMULATION IN THE FUTURE LEAD ORANGE REFORMULATION IN THE PAST LEAD ORANGE REFORMULATION IN THE FUTURE LEAD MOLYBDATE REFORMULATION IN THE PAST LEAD MOLYB DATE REFORMULATION IN THE FUTURE 121 121 122 122 123 123 124 124 125 125 126 126 XXVII. XXVIII. XXIX. XXXI. XXXII. COPPER REFORMULATION IN THE PAST COPPER REFORMULATION IN THE FUTURE BRONZE REFORMULATION IN THE PAST REPLACEMENT OF HEAVY METAL INKS IN THE FUTURE ESTIMATION OF SALES OF HEAVY METALS REPLACEMENT OF PETROLEUM OIL INKS BY SOYBEAN OIL INKS IN THE PRESENT REPLACEMENT OF PETROLEUM OIL INKS BY SOYBEAN OIL INKS IN THE FUTURE AWARENESS OF TEST AND REGULATIONS RELATED TO USE OF HEAVY METAL IN THE INK DIDUSTRY 127 127 128 129 130 131 132 133 LIST OF FIGURES Figure Page 1. FREQUENCY OF USE OF WRITTEN CERTIFICATION OF COMPLIANCE WI I'H TOXICS LEGISLATION IN THE PACKAGING INDUSTRY 112 2. FREQUENCY OF USE OF WRITTEN CERTIFICATE OF COMPLIANCE WITH TOXICS LEGISLATION IN N ON-PACKAGING INDUSTRIES 113 3. PERCENTAGE COST INCREASED DUE TO REDUCTION OF HEAVY METAL CONTENT 115 4. PERCENTAGE PRICE INCREASED DUE TO REDUCTION OF HEAVY METAL CONTENT 116 5. REFORMULATION OF INKS FOR THE PACKAGING INDUSTRY TO REDUCE OR ELIMIN ATE HEAVY METAL CONTENT 1 18 6. REFORMULATION OF INKS FOR NON-PACKAGING INDUSTRIES TO REDUCE OR ELIMINATE HEAVY METAL CONTENT 1 19 7. CADMIUM RED REFORMULATION IN THE PAST 120 8. CADMIUM RED REFORMULATION IN THE FUTURE 120 9. CADMIUM YELLOW REFORMULATION IN THE PAST 121 10. CADMIUM YELLOW REFORMULATION IN THE FUTURE 121 11. CADMIUM ORANGE REFORMULATION IN THE PAST 122 xiii 12. 13. 14. 15. 16. 23. 24. 25. 26. xiv CADMIUM ORANGE REFORMULATION IN THE FUTURE LEAD BASED YELLOW REFORMULATION IN THE PAST LEAD BASED YELLOW REFORMULATION IN THE FUTURE CHROMATE YELLOW REFORMULATION IN THE PAST CHROMATE YELLOW REFORMULATION IN THE FUTURE LEAD ORANGE REFORMULATION IN THE PAST LEAD ORANGE REFORMULATION IN THE FUTURE LEAD MOLYBDAT E REFORMULATION IN THE PAST COPPER REFORM ULATION IN THE PAST COPPER REFORMULA'I‘ ION IN THE FUTURE BRONZE REFORMULATION IN THE PAST REPLACEMENT OF HEAVY METAL INKS IN THE FUTURE ESTIMATION or SALES OF HEAVY METALS REPLACEMENT OF PETROLEUM OIL INKS BY SOYBEAN OIL INKS IN THE PRESENT REPLACEMENT OF PETROLEUM on. INKS BY SOYBEAN OIL INKS IN THE FUTURE 124 124 5— M III 132 CHAPTER 1 INTRODUCTION Clogged landfills are a highly visible symptom of our nation's solid waste problem, and, as such, governmental and consumer pressure to reduce the packaging portion are intensifying. As a result, an industry-wide effort to minimize the environmental and health impact of packaging is in full force (F earncombe, 1995). One way to reduce the solid waste problem is source reduction applied to objectionable materials, such as heavy metals. The model toxics in packaging legislation as developed by the Coalition of Northeastern Governors (CONEG) focuses on environmental and health issues regarding heavy metal content in packages and packaging components. The CONEG types of regulation definitely ban the intentional introduction of cadmium, hexavalent chromium, lead and mercury in packaging. The following study will be based upon health and environmental effects of the four heavy metals addressed by the CONEG types of regulation, and additionally copper and zinc. The main purposes of including coma and zinc in this investigation are: 1. Increasing concern about zinc chromate as a lung carcinogen, as evidenced by cases of concern about zinc chromate as a cause of dermatitis through skin contact and lung cancer among ink manufacturing workers. 2. Increasing health and environmental concern about copper and zinc in gold and metallic inks. Exclusion of copper and zinc would eliminate all of the metallic printing presently used in package design, severely reducing the palette of colors available to package designers (Rusterholtz, 1992). A survey of ink manufacturers was conducted. The main purpose of the questionnaire was to record the effects of the CONEG types of legislation on ink manufacturers in terms of heavy metal content limitation, certification of compliance, price and cost increases, and pigment reformulation. History Rusterholtz (1992) states that the concern about heavy metals in flexo ink started in 1989 due to the increased awareness of post-consumer waste, recycling, and resource conservation. According to Czarnecki (1992), the first heavy metal that was considered for elimination was lead. Lead chromates and lead molybdates were removed at once. Czarnecki (1992) and Lusting (1990) listed six heavy metals whose contents in ink were limited by the industry in 1989. This list includes cadmium, arsenic, mercury, antimony, lead and selenium (CAMALS). This limitation caused the elimination of certain chrome yellow, molybdate orange and cadmium red pigments. According to Rusterholtz (1992), due to the current concern over waste generation and disposal, nine additional metals (aluminum, barium, cobalt, copper, lithium, manganese, molybdenum, silver, and zinc) will be added to the CAMALS list. Package users are taking extreme actions about heavy metals, because such metals are not easily disposable due to their environmental hazards. The inclusion of additional metals will eliminate some blue, green, and white colorations, and would decidedly constrict the list of available red pigments. Many ink companies have entirely eliminated the use of lead pigments in their inks. It seems that companies have added metals to their list at random, without regard to the possible technical consequences to printing. Sources of Heavy Metals in Inks Rusterholtz (1989, 1992) referred to metal-containing pigments (colorants) as the main source of metals in printing ink. Heavy metals are included in inks as: l.- Molecular constituents of some organic pigments such as copper phthalocyanine blue and green, barium red 23, and calcium lithol whine, and inorganic pigments such as lead chromate, iron oxide, chrome green and cadmium sulfide. 2.- Insolubilizers of rosin on the pigment surface. Rosin is used to treat the surface of the pigment during manufacturing to improve dispersability. 3 .- Inorganic extenders to promote standard color strength in the manufacture of organic, dry color pigments. Regulations F ishman and Adelsky (1992) discussed governmental and ink consumers‘ requirements about heavy metals in printed packaging. The limitations applied to manufacturing, use, and disposal of printed packaging. Ink manufacturers have been pressured by the packaging industry to control metal content in their inks. This action is in response to the proliferation of government regulations. There are a variety of regulations and policies that have impact, including: Resource Conservation and Recovery Act (RCRA), Clean Water Act, federal regulations originated by the Consumer Product Safety Commission (CPSC), Resource Conservation and Recovery Act (RCRA), Occupational Safety and Health Administration (OSHA), American Standards Association, Toy Manufacturers Specifications and Fast Food Industry Guidelines, and different state regulations originating in State Sewerage Guidelines, Proposition 65 and the Coalition of Northeastern Governors (CONEG). According to Abel (1992), in Europe, limitations on the amount of heavy metals in cosmetics, toys and graphic instruments, and proposed limitations on heavy metals in coatings which are used for food packaging, even where there is no direct contact due to dust, are a substantial problem in many industries. Hickman (1987) stated that the highly colored dusts associated with pigments are pelletised and low-dust forms of pigment are now widely used to improve the working environment. The United Kingdom has banned the inclusion of lead chromate and cadmium in pigments since 1972. The Coalition of Northeastern Governors (CONEG) In 1990, nine state governors came together to draft an act to reduce heavy metals in the packaging industry .As a result, It was written the Model Toxics in Packaging Legislation was written as a model for packaging legislation that can be adopted by any state (Johnston, 1992). The proposed legislation applies to packages, and to package components such as inks, ointment, dyes, etc, and bans the intentional presence of four heavy metals: lead, mercury, cadmium and hexavalent chromium. In addition, this legislation limits the non- intentional (incidental) presence of the four metals as trace contaminants (F ishrnan and Adelsky , 1992; and Renson, 1992). The Model Toxics in Packaging Regulation is a result of the increasing awareness of the overall solid waste stream. Heavy metals included in packaging are likely to be present in emissions or ash when packaging is incinerated and in leachate when packaging is landfilled (F ishman and Adelsky, 1992) . The incidental presence of these metals was limited to 600 ppm one year after enactment of the legislation, 250 ppm two years after, and 100 ppm four years after enactment of the state legislation. The proposed legislation has become effective in eleven states: Connecticut, Iowa, Massachusetts (1992), Maine (April 1, 1992), Minnesota (August 1, 1993), New Hampshire, New York (January 1992), Rhode Island, Vermont, Washington (July 1992), and Wisconsin, and has been proposed in eight additional states : California, Delaware, Georgia, Illinois, Maryland, New Jersey, Pennsylvania, and Oregon. It makes little difference which new states follow the lead of states that have already passed the proposed legislation. Since most goods are sold in many different states, the effective date in any one state effectively imposes limits on heavy metal content in packaging of those goods for all states. Therefore, today, many packagers and their converters are expecting their ink suppliers to certify to maximum heavy metal content of 100 ppm (Johnston, 1992 and Renson, 1992) . Certificates of Compliance According to Fishman and Adelsky (1992), the proposed regulation stipulates that "not later than two years from the adoption of this statute, a Certificate of Compliance of packaging components should be issued by its manufacturer." Johnston (1992) stated that such certificate of compliance needs to be supplied to purchasers of packaging or packaging components, such as ink manufacturer customers, and the converters need to provide this certificate to contractors that package products to be sent to retailers. A specific analytical method for testing was not specified by the proposed regulation The suppliers, therefore, are allowed to used different methods. Two types of analytical methods are used for measurement of heavy metal content. 1 . Measurement of soluble or leachable metals. Soluble heavy metals refer to the portion of a heavy metal that may leach into water and enter into a large water aquifer. Because landfill disposal is a issue, this test is commonly requested. Weak acid-extraction data is specified under EPA RCRA guidelines, and the strong acid- soluble data is specified in the voluntary toy standards, most fast food standards, the AS TM guidelines, and the European EN 7 1 standard. 2. Measurement of the total metals present. This category of analysis is the one most often used to satisfy the CONEG proposed guidelines. Within these two types of tests, there are different kinds of sampling or sample preparation (Rusterholtz, 1992 ). Reason (1992) evaluated batch-to-batch testing as uneconomic and time consuming testing. Random sampling is the most realistic way of sampling. The proposed regulation does not require analysis of every batch, but asks for random samming on a reasonable statistical basis. According to Czarnecki (1992), an ASTM standard should be followed to produce reproducible and accurate results. Substitutes Reduction of heavy metal content in pigments promoted the development of new pigments that may, to a certain degree, substitute for the present heavy metal based inks. In Spite of their low degree of brilliance, relatively poor flow properties and high price, organic substitutes are most commonly used in the ink industries, because they are the closest substitutes existing in the market (Larson, 1992). According to Abel (1992), heavy metal pigments are still a strong competitor against organic pigments for high- performance engineering thermoplastic components used in durable goods. Johnston (1992) states that substitutes such as hansa yellows, DNA orange, and A20 reds are used widely because they comply with the current legislation. Hill (1979) mentioned co-precipate pigments as a good substitute for chrome yellow. Co-precipate pigments have almost the same physical properties as chrome yellow. Other substitutes for this pigment are azo couplings, arylide and diarylide. Two disadvantages of these replacements are opacity and high cost. Disposal According to Flower et a1. (1978), sanitary landfills have been demonstrated to be the least expensive environmentally acceptable means of waste disposal, purportedly possessing attributes of neatness and safety in addition to relatively low cost. However, many landfills were (are) used improperly; illegal dumps of hazardous waste or insufficient disposal facilities are not unusual (Donker, 1994). One of the potentially dangerous sources of chemical release at waste sites is leachate. Landfill leachate carries a wide range of heavy metals and organic micropollutants. In general, landfills are originated by dumping domestic waste and clean industrial wastes into excavations. Because of their operation, magnitude, and large number, landfills represent an important threat to groundwater resources. Only starting during the 1980's in the US. and in a few European countries have new landfills been equipped with liners and other facilities to prevent soil and groundwater contamination (Donker, 1994). Flower et al. (1978) stated that the rapid urban and suburban development in the United States has caused many once remote dumping grounds to now be close to developed areas. As such, they provide an attractive source of land for many reasons. Conversion to recreational areas or other nonstructural applications has long been considered an acceptable end for completed landfill sites. Increasingly stringent federal and state laws have made dumping harder for the printing industry, and landfills are closing at a rapid clip because older dumps cannot meet stringent EPA regulations. In the past, the printing industry bought a barrel of oil for $20 and then needed to pay $300 a barrel to get rid of oil mixed with ink in landfills. Landfills are no longer accepting oily waste at all, so those who buy ink need to figure out how to dispose of it (Fitzgerald, 1987). According to Rusterholtz (1989), heavy metal content in inks is a concern since two-thirds of the total municipal waste in printing substrates. Municipal waste is composed of paper and paperboard (41%), metals (8.7%), glass (8.2%), plastic (6.6%), rubber and leather (8.1%), food waste (7.9%), grass, leaves and plants (18%) and miscellaneous (inorganic waste) (1.5%). Note that the first four categories are all packaging material and also are all printing substrates. Because packaging is disposable, one-third of landfilled waste originates from packaging applications. The number of landfills accepting solid waste has shrunk from 30,000 in 1968 to 6000 in 1989. Once the packaging is incinerated, the resulting inorganic ash contains heavy-metal oxides or sulfates. Such incinerator ash requires disposal. We can reduce the amount of heavy metals in the substrates to reduce pollution. Carcinogenic heavy metals such as lead, cadmium, chromium, arsenic, mercury, antimony, selenium and silver are worrisome when they appear in drinking water and consumer products that are, or might be, ingested or absorbed. In the firture, legislation is going to continue to grow on local, state, and federal levels. The industry as a whole has to become more proactive in legislation or they will drown in the aftermath of legislation (Johnston , 1992) CHAPTER 2 ENVIRONMENTAL EFFECTS ASSOCIATED WITH COPPER Introduction Copper has been recognized at 210 out of 1177 National Priorities List (NPL) hazardous waste sites in the United States (U. S. Department of Health and Human Services, 1990 a). According to Nriagu (1979 b), there are three main sources of pollutant cOpper in the atmosphere : 1. Copper production and handling (46% of the total anthropogenic emissions) 2. Iron and steel production (10%) 3. Fossil fuel combustion (1 1%) Nriagu (1979 b) estimated the total flux of copper to the atmosphere as 75 tonnes/year, 75% of which comes from anthropogenic sources. The primary anthropogenic emission sources of copper are waste incineration (5.3 tonnes/year) , copper production (20.84 tonnes/year), and wood combustion (1 1.5 tonnes/year). 10 11 In the printing industry, the presence of " soluble copper” has been limited for some time; but it appears that limits on total copper may come under consideration. If this comes about, the continued use of copper phthalocyanine ink, blue and green, would be in question (Benemelis, 1991). The phthalo blue has one atom of copper in every molecule of phthalo blue pigment. In this pigment form, the copper is completely insoluble and, in fact, phtalo blue is one of the most stable of all pigment types (Rusterholtz , 1987 ). Hyland (1990) and Rusterholt (1987) noted that the printing industry finds itself in an usually diflicult position because it is difficult to find an acceptable pigment that does not include the phthalo blue chemistries. Copper gives the inks the diverse shades of blue. This metal afl‘ects the lay of the ink, and attributes related to ink runnability and postpress performance. When copper-based pigments are replaced with other pigments, it requires a lot of money and effort to get color similar to copper-based pigments. It is significant to note that a non-copper-based phthalo blue has been presented on an experimental basis by the pigments division of Sun Chemical Corp. in an effort to maintain the attributes of phthalo-blue chemistry without the disadvantages of copper. Although progress in ink reformulation is coming along slowly, inks, in the next few years, will have lower levels of copper than they do today (Rusterholtz, 1987, and Hyland, 1990). Sewage Treatment Plants Since copper is a widely used material, there are many actual or possible sources of copper pollution. Considerable levels of copper may be found in municipal sewage. Perhaps the most dramatic portrayal of the mobility of copper contamination is the concentration of 24-690 ppm found in sewage sludge. The majority of this copper originates from industrial discharges which find their way into sewage works. Sewage 12 sludge is frequently applied to land, both as a method of disposal and as a soil ameliorant providing organic matter and the nutrients nitrogen and phosphorus (Nriagu, 1979b). According to Minear et al. (1981), the heavy metals, including copper, that are loaded to Publicly Owned Treatment Works (POTW‘s) are of interest because of the possible inhibitory impact on the biological treatment process, the effluent levels that can be reached as a fimction of concentration, and the practice of land dumping of waste sludge where the total metal load to the treatment plant is of interest. Around the United States, there are a few states which have had problems with the high concentration of copper in the environment. Leh and Lak (1974) cited high concentrations of copper, ranging from 4.5 to 16.3 ppm, in soil samples from the Grand Rapids, Michigan area. The Federal Government limited toxic discharges of copper and mercury fiom New York's 14 sewage treatment plants. The metals build up in the tissue of shellfish. New York Harbor shellfish have some of the highest levels of heavy metal contamination in the nation (Gols, 1990). Rusterholt (1987) stated that limitations on certain metal contents in municipal sewage systems have existed for some time. As more and more testing was undertaken by various state and local authorities, it became evident that the test methods used are an important factor. The standard methods that have evolved for evaluating sewage discharges utilize acid digestion as part of the process. Under these conditions, insoluble suspended solids are chemically broken down, converting all material to soluble form. Under such conditions, it is possible to obtain extraordinary high parts per million values of many chemicals. Hyland (1990) remarked that there are circumstances where box plants are close to closed because the local sewage authority is saying that the copper levels in their emuents are too high. Many companies are now closely examining the use of water and realizing that one area where economies can be made is in efiluent discharge. Rather than pay water l3 authorities to manage eflluent through public sewers, many companies with efiluent discharge problems are now processing their own liquid waste themselves. And where in- house effluent plants were formerly considered to be a refinement which only large-scale industry could afford to invest in, many smaller companies are now concluding that installing their own waste plant need not be as expensive or as disruptive as they originally thought (Environmental Data Services, 1980). Water Pollution The median concentration of copper in natural water is 0004-0010 ppm. It is primarily in the Cu (II) state. Most of it is complexed or tightly bound to organic matter; little is in the free (hydrated) or readily exchangeable form. Of special concern is copper that gets into drinking water from the water distribution system. When the system has not been flushed after a period of disuse, copper concentration in tap water may exceed the EPA copper water limit of 1.3 ppm. Levels greater than 10 ppm can develop depending on the plumbing system, pH and hardness of water (U .S. Department of Health and Human Services, 19903). Copper is released to water as a result of natural weathering of soil and emissions fi'om industries and sewage treatment plants. Most of this copper is attached to particulate matter (Nriagu, 1979b). _ A” -L—d-a-f 14 Soil Pollution The EPA ( 1990a) estimated that 97% of copper released into the environment is applied to soil. The forms are primarily tailings and overburden from copper mines and tailings from mills. Other releases to land consist of municipal refuse and sludge fiom publicly owned treatment works (POTWs). The copper content of municipal solid waste is 0.16 percent. Much of the sludge is landfilled directly or as a residue from incineration. The addition of sewage sludge to agricultural soil improves physical aspects and acts as a valuable source of nutrients to growing crops. However, there is increasing concern over the use of sewage sludge which has been polluted by heavy metals. Until recently, studies have concentrated on the uptake and transport of heavy metals into the food chain via crops. Now, however, there is growing evidence of an adverse effect on microbial processes related to nutrient cycling in these types of soils (Donker et al., 1994). Most of the copper in soil is apparently tightly bound to soil components and may not be accessible for uptake. While investigations show that copper does not leach significantly from soil, levels of copper as high as 2.8 ppm have been found in some groundwater (U .S. Department of Health and Human Services, 1990a ). Air Pollution Copper is discharged into the air naturally fiom windblown dust and volcanoes, and from anthropogenic sources. The mean concentration of copper in the atmosphere is 5-200 ng/m3 . The amount of copper and other pollutants in wind blown dust from a waste site is of some concern. In one study, the amount of airborne copper and other heavy metals accumulated near a large refiise dump that received municipal and industrial 15 waste and sewage sludge was determined. First measuring the amount of the metal accumulated was measured. The deposition rate was then determined and compared with that for an agricultural control area. The mean copper deposition rate was twice as high near the dump as in the control area (US. Department of Health and Human Services, 1990 a). Effect of Copper Pollution on Terrestrial Animal Life According to Nriagu (1979b), excessive intake of copper can have significant effects on animals. Depending on the species involved, grth rates and food intake may be cut down, anemia can develop, and considerable damage may be done to the liver, kidneys, brain, and muscle, ofien resulting in death. Luckily the tolerance to copper of most domestic and laboratory animals is relatively high. Copper poisoning is a much less serious problem in animal husbandry than is copper deficiency. It is often necessary to increase dietary intakes of copper by 20- to 50-fold over normal levels before any damages caused by copper toxicity develop. However, this is not invariably the case. With some species, copper poisoning may occur quite readily, even under natural conditions. Up to 15 ppm of copper is generally recognized as safe (GRAS) by the FDA in livestock feed. Cattle can tolerate mineral mixtures and feeds with added copper . In contrast, sheep are susceptible to the toxic effects of added copper. Adding excess copper to sheep, swine, and poultry feeds may create a hazard for the consuming public because the metal accumulates in the animal's liver (National Research Council, 1977). Pigs are much more tolerant of copper than are ruminant animals and under normal situations would be considered unlikely to suffer from copper poisoning (Nriagu, 1979b). 16 Effects of Copper Pollution on Aquatic Life Baatrup (1991) explained that the increasing discharge of wastes from industrial and agricultural activities has dramatically changed the conditions of aquatic life. The dissolved toxicants act directly and continuously on aquatic animals. This continuous exposure to chemical pollution, even at low sublethal doses, may cause serious damage to aquatic life processes. Copper in water is exceedingly toxic to aquatic biota, in contrast to its low toxicity to mammalian consumers of water. Concentrations as low as 5 to 25 ug/l are lethal within 4 days to some invertebrate and fish species. The suggested standard for public water supplies, based on palatability, is 1,000 ug/l. The extreme sensitivity is a consequence of high surface-volume ratios of algae. High respiratory water flows, plus an extensive, highly permeable gill surface area that facilitates rapid uptake of large amounts of copper, makes invertebrates and fish sensitive. The sensitivity to waterborne metals is analogous to mammalian sensitivity to airborne metals as a result of the rapid and continuous respiratory uptake. Ingested copper is available only in limited amounts since fi'eshwater biota generally do not drink water, and fecal material vies with the stomach and intestinal tract for absorption of ingested copper (Nriagu, 1979 b). Copper Toxicity to Aquatic Invertebrates Some concentrations of copper have been found to be acutely toxic to invertebrates. Sensitivity to copper differs greatly fi'om species to species. A portion of the variation in toxicity among species is related to the nature of the body covering. In general, larvae or younger stages are more sensitive to copper than are adults. Adaptation to high copper concentrations in water or sediment appears to occur but is probably due to genetic selection of hardy individuals rather than acclimation. In addition to reduction 17 in survival rate, growth, and reproduction, copper also causes histopathologically observable tissue damage, decreased oxygen consumption, or distress conduct in invertebrates. The mode of operation of copper in invertebrates is not well known, although impairment of osmotic and ionic regulation may be one possible cause of death (Nriagu, 1979 b). Copper Toxicity to Fish Ashraf et al. (1992) declared that fish are known for their ability to gather trace metals from seawater and sediment. The processes leading to trace metal mobilization and resorption by sediments are known specifically to influence the persistence, toxicity, . uptake and transport in fish. Relationships between tissue concentrations and the mechanisms involved in the bioaccumulation of trace metals in fish have evidenced a strong dependency between trace metal and characteristic of each type of species. Copper is an essential metal, an integral part of several enzymes. However, at elevated levels, copper is highly toxic to fish, especially in fiesh water because of the higher contents of ionic copper (Baatrup, 1991). According to Nriagu (1979b), many factors affect lethal copper toxicity to fish through changes in the availability of copper to the fish, and the sensitivity of the fish to a given amount of copper taken up. Lethal efi‘ects may be observed over a wide range of concentrations (23 to 10,200 ug/l); the variations are primarily a result of the efi‘ects of water hardness, organic complexing capacity, and species sensitivity. Numerous histological, physiological, and enzymatic responses of fish to near-lethal copper exposures suggest that osmoregulatory failure during exposure to the metal is the probable cause of death. Sublethal efi‘ects of copper in fish occur at concentrations up to the lethal level. The initial signs of toxicity, however, can be observed at concentrations less than 160 ug/l. The behavior and growth 18 of salmonids (fish of the family Salmonidae) are the most sensitive parameters. Avoidance, activity, appetite, growth, and migration are affected by copper concentrations between 4 and 10 ug/l. Physiological responses, including inhibition of gill ATPase (adenosine triphosphatease), plus short term corticosteroid elevation, were also observed between 5 and 10 ug/l. Threshold effects on reproduction, growth, and mortality, and hence fish production, were observed between 10 and 20 ug/l for salmonids, catfish, and walleyes, between 18 and 40 ug/l for fathead minnows, and between 40 and 160 ug/l for bluegills. Finally, disease was induced in eels, salmonids, suckers, and cyprinids at 30 to 60 ug Cu/l. These data indicate that fish populations are adversely affected at copper concentrations well below the lethal level, so that some species could disappear without direct observable mortality (Nriagu, 1979b). According to Baatrup (1991), the toxicity of copper seems to result from its interaction with cellular membranes. Increased free radical formation and lipid peroxidation may lead to severe cellular stress. Fish depend on their external and internal senses for mediating behavior such as food search, predator recognition, communication, orientation, and migration. Stimuli are perceived by specialized sensory structures and converted into electrical signals, which are conducted to the central nervous system. Here, neural information is integrated and appropriate behavioral responses are generated. Unfortunately, the nervous system is one of the most vulnerable parts of the animal body, and injuries to its elements may strongly influence the behavior and survival of the organism. In fish, both acute and chronic injuries to the nervous system can occur. Dissolved toxicants, including copper, act directly on superficial sense organs, including olfactory and taste organs, which are not protected by "external barriers" or internal detoxifying systems. Pollutants may disrupt normal chemosensory firnction by masking or counteracting biologically relevant chemical signals, or they may cause direct morphological and physiological damage to the receptors. In addition, pollutants absorbed across the skin or the gills may enter the blood l9 stream and thereby reach internal sense organs and other nervous tissues, including the brain OBaatrup, 1991). A study by Curby et al. (1976) showed that freshwater adapted fish used in copper pollutant tests were less able to adjust to new experimental situations than test fish taken from a saltwater tank. The freshwater adapted fish appeared to be the most affected by the metal insult. They were the most sluggish, did not eat when fed or seem to sense the food in the water; they were the first to die in the adverse conditions. This may mean, in a larger sense, that even fish in the wild that appear to be adapted to slightly deleterious conditions are less able to withstand any subsequent change in the environment. Such fish would be more susceptible to a lower level of pollutants in the water than would fish in a "healthy" environment. Effects of Copper Pollution in Plants A study by Madry (1978) shows that suppression of growth and reduced productivity of plants by air pollution are due to the way in which contaminants affect the physiology of the plant itself. These injuries interfere unfavorably with some or all of the normal plant processes such as photosynthesis, respiration, transpiration, cell permeability, root development, etc. , all of which are essential for plant growth. Copper and its various salts are highly toxic to lower forms of life such as algae, bacteria, etc. In protein synthesis and photosynthesis, excesses of copper, zinc, and other metals may be substituted in these processes, replacing iron, magnesium, manganese, or other desirable metals. Excesses of the element in higher plants have also become toxic. It is apparent that uncontrolled use and undesirable accumulation of copper must be avoided. 20 Donker et al. (1994) concluded in their study that contaminants were accumulating on the leaf surfaces and entering the plants through the stomates. At the same time, some of the metals were entering the plant through a root system that had been damaged by the metals or a myriad of other factors. Both sources contributed to the excess in plant accumulation of the metals and suppression of growth. At increasing metal concentrations in the environment, heavy metal-sensitive species disappear. However, a few angiosperrns can still be found on soils with toxic heavy metal concentrations (Zn up to 60,000 mg/kg, and Cu 7,000 mg/kg). CHAPTER 3 HEALTH EFFECTS ASSOCIATED WITH COPPER IN HUMANS Introduction In 1977, the National Academy of Sciences stated that the shortage of literature on ill effects caused by exposure to copper and its compounds in industry suggests that copper is not a particularly hazardous industrial substance. However, if workers are subjected to excess concentrations of the metal in any of its forms, unwanted health effects can result. According to Venugopal and Luckey (1983), the range between deficiency and toxicity of Cu is ample for mammals. In humans, manifestations of copper toxicosis do not occur until much higher levels have been reached than in other animals. The copper content of a 70 kg (154 lb) human adult is between 80 and 150 mg, and the average daily dietary intake by a normal adult is about 4-5 mg. The range of requirement of copper by human beings is 1.0-3.8 mg/day (Lee, 1972). The Copper and Brass Research Association (1947) pointed out that several factors determine whether damaging health effects will occur and what the type and severity of those health effects will be, if a person is exposed to c0pper. These factors include the dose, the duration, the route or pathway of exposure ( breathing, eating, 21 drinking, or skin contact), other chemical exposure, and individual features such as age, sex, nutritional status, family traits, life style, and state of health. The following section analyzes two factors: large dose ingestion, and fumes and dust exposure . Large Quantities of Copper Ingested Accidental ingestion of large amounts of copper salts has been discussed by Friberg (1977), the National Academy of Sciences (1977), Carson and Ellis (1986), and Dillon (1991). They defined the consequences of overdoses of copper ingested by humans. The chain of effects is as follows: 1. An instantaneous metal taste. 2. Gastrointestinal disturbances such as epigastric burning, nausea, vomiting and diarrhea. These manifestations generally protect the patient from serious systemic effects such as hemolysis, liver and renal damage, oliguria, azotemia, hemoglobinuria, hematuria, proteinuria, hypotension, tachycardia, convulsions, coma, or death. After suicidal ingestion of a large quantity of copper sulfate, jaundice and renal harm have occurred at average copper concentrations in blood of about 8,000 mg/l, whereas at a copper level of about 3,000 mg/l only gastrointestinal disturbances were seen (F riberg, 197 7). 23 Copper Fumes and Dust Toxicity Industrial exposure to copper dust or fumes has been frequent, but health surveys of workers engaged in the processing of copper have not revealed signs of chronic illness (F riberg, 197 7). Dusts and fumes fiom copper and its compounds usually have an intolerable taste, a warning that tends to cause humans to limit exposure before serious toxic intake can occur. However, metal fume fever from exposure to copper can happen (National Academy of Sciences, 1977). The Occupational Safety and Health Administration (OSHA) has assigned a limit to protect workers of 0.2 mg/m3 of copper times and 1 mg/m3 copper dusts and mists in occupational air during an 8-hour work shift. The National Institute for Occupational Safety and Health (NIOSH) suggests that the concentration in workroom air be limited to 0.1 mg/m3 for copper firmes and 1 mg/m3 for copper mist, averaged over an 8 hr work shift (U .S. Department of Health and Human Services, 1990 a). The US. Department of Health and Human Services (1990a), discussing several reports of human exposure to airborne copper, stated that three reports addressed effects difi‘erent fi'om metal firme fever. One study examined 100 factory workers over a period of 4 years. The workers sieved copper dust, the purity of which was 99.9%. The reported copper levels in the air were 464 mg Cu/m3 in the first year, 132 mg Cu/m3 in the second, and 111 mg Cu/m3 during the third. The concentration of copper in the air was not reported for the fourth year, but was assumed to be less than 111 mg Cu/m3. Efi‘ects of exposure were found on the respiratory system, liver, gastrointestinal system, reproductive system, nervous system, and sella turcica. 24 Exposure to copper dust can produce several reactions in the human body: 1. Metal Fume Fever Respiratory Effects Anemia and Hemolytical Effects Dermal / Ocular Effects Gastrointestinal Effects Neurological Effects Reproductive Effects Other Systemic Effects 509°>’P‘$":‘>P’.N Heart Disease Metal Fume Fever Inhalation of c0pper fumes or fine copper dust may cause so called metal firme fever. Boyce (1961) found that metal firme fever is caused by inhaling rather heavy concentrations of dust or fumes. The most potent particle size range appears to be less than 0.6 microns. According to Carson and Ellis (1986) and Friberg (1977), metal fume fever is an influenza like syndrome with symptoms which dissipate after 24 hours. Fume fever symptoms of respiratory irritation, chills and aching muscles were discussed by Baselt (1988). Chronic copper poisoning in industry was related to anorexia, nausea, vomiting, nervous manifestations and hepatomegaly (enlargement of the liver). Serum copper concentrations ranged fi'om 0.8 to over 2 mg/l in such cases. Boyce (1961) stated that a worker recuperating from fume fever is fairly immune and generally can experience another inhalation without experiencing a second attack. Gleason (1968) reported that metal fume fever appeared after exposure to about 0.1 mg/m3 of fine copper dust. A number of workers who acquired copper fume fever had serum copper levels that averaged 1.26 mg/l. Copper fever has been found among men handling copper oxide powder in a paint factory, and copper acetate dusts have caused complaints of sneezing, coughing, digestive disorders, and fever. Visible metal firme fever has also been reported in three men who were exposed to dust produced during the polishing of copper plates (National Academy of Sciences, 1977). Respiratory Effects In humans, copper is a respiratory irritant. Plant employees exposed to copper dust experienced mucosa] irritation of the mouth, eyes, and nose (U .S. Department of Health and Human Services, 1990a). Venugal and Luckey (1983) showed that inhalation of dusts and fumes of metallic Cu and its salts produces congestion of nasal mucous membranes, ulceration and perforation of the nasal septum, and pharyngeal congestion. The National Academy of Sciences (197 7) and Friberg ( 1977) reported that pulmonary copper deposition and fibrosis happened in the lungs of some vineyard workers after years of exposure to a pesticide with a high content of copper. Later granulomas and malignant tumors appeared in these laborers' livers and lungs. Anemia and Hemolytic Effects Decreased hemoglobin and erythrocyte levels have been observed in workers exposed to airborne copper levels of 0.64-1.05 mg/m3. Results of hair analysis showed that the workers were also exposed to iron, lead and cadmium (U. S. Department of Health and Human Services, 1990a). Mild, possibly hemolytic, anemia has been observed in workers exposed to copper in the air at levels at or below the TLV (Carson and Ellis, 1986) 26 Hepatic Effects Hepatomegaly (big liver) was observed in factory workmen exposed to copper dust (U .S. Department of Health and Human Services, 1990a). In two autopsied cases of so called ”vineyard sprayers lung", hepatic granulomas were found (U .S. Department of Health, 1990). Denna] / Ocular Effects Gafaber (1967) found that brass dust and slivers may cause dermatitis by mechanical irritation, and Boyce (1961) added that skin conditions due to handling copper powder can make trouble during hot humid weather. Some individuals seem to be more sensitive than others and raw copper powder seems to cause considerably more trouble than after it has been blended with a stearate lubricant. Mucosal irritation of the eyes has been seen in factory workers exposed to copper dust (U .S. Department of Health and Human Services, 1990a). The National Academy of Science (1977) aflirmed that presence of a particle of metallic copper in the eye may result in loss of the eye, sunflower cataracts, or visible deposits of copper in the cornea known as Kayser—Fleischer rings. Gastrointestinal Effects Anorexia, nausea, and occasional diarrhea were described in factory workers exposed to copper dust. A portion of the copper in the air was probably ingested; thus, the gastrointestinal efl‘ects were probably the result of oral exposure to copper (U. S. Department of Health and Human Services, 1990a). 27 Neurological Efl‘ects Headache, vertigo, and drowsiness were reported in factory workers exposed to copper dusts (US. Department of Health and Human Services, 1990a). Reproductive Effects Sexual impotence was reported in 16% of inspected factory workers exposed to copper (US. Department of Health and Human Services, 1990a). Other Systemic Effects Seven cases of enlargement of the sella turcica, nonsecretive hypophyseal adenoma, accompanied by obesity, arterial hypertension, ”and red faces" in factory workers exposed to copper dust were reported (US. Department of Health and Human Services, 1990a) . Heart Disease A high concentration of copper in the blood may be a risk component for coronary disease, along with raised blood cholesterol and cigarette smoking. According to Webb (1991), Frei and Gaziano (1993), Chiu, Jeng and Shieh (1994), and Lamb and Leake (1994), the copper appears to work in combination with cholesterol to firrther atherosclerosis, the thickening of the arterial wall, a high level of low-density lipoprotein (LDL) cholesterol in the blood, a high level of copper, and a low concentration of selenium. CHAPTER 4 ENVIRONMENTAL AND HEALTH EFFECTS ASSOCIATED WITH ZINC Environmental Effects Associated with Zinc Animal Toxicity Inhalation Lam et al. (1985) found firnctional, morphologic, and biochemical changes in the respiratory tract of guinea pigs exposed to 5 mg/m3 zinc oxide for 3 hours/day for 6 days. Amdur et al. (1982) reported on the pulmonary response of guinea pigs to zinc oxide fumes. The animals were exposed to approximately 1 mg/m3 of freshly formed zinc oxide. Conner et al. (1982,1985) studied the irritancy potential of a combination of zinc oxide and sulfur dioxide. Guinea pigs were exposed to 6 mg/m3 zinc oxide mixed with 1 ppm sulfur dioxide, for 3 hours a day for 6 days. Total lung capacity, vital capacity, functional residual volume, alveolar volume and diffusing capacity were decreased following exposure and had not returned to normal 72 hours afier exposure. Similar but more severe changes were seen after a single 3-hour exposure of 25 mg/m3 zinc oxide and sulfur dioxide. Hilderman and Taylor (1974) reported a case of acute emphysema in cattle exposed to zinc oxide fumes emitted during oxyacetylene cutting and welding of 28 29 galvanized pipe. Three heifers were severely affected, and died within a short time. The animal autopsy showed severe changes in lungs with edema, emphysema, and hemorrhages. In this case, a galvanized material was implicated, but the extremely severe condition caused by the firmes indicated either that cattle are highly sensitive to zinc oxide times, or that other metals, such as cadmium, may have been involved. Harding (195 7) administered, 50 mg of zinc stearate to rats by intratracheal instillation. Approximately 50 percent were dead after dosing. Beeckmans et al. (1963) described the effects of zinc oxide fumes on rats. 132 rats were exposed to 400 to 600 mg/m 3 of zinc oxide firmes for 10 to 20 nrinutes. 16 rats died during the experiment. Other rats showed a marked fall in body temperature, which was increased when zinc oxide was irradiated by ultraviolet light for 50 seconds. In sacrificed animals, 1,100 - 5,500 mg of zinc for each gram of lung tissue was found. Oral Sampson et al. (1942) reported the effect of ingestion of zinc lactate in pigs. Pigs were fed 17.5 g of zinc lactate for 9.5 months. They began losing their appetite after only a few weeks on the diet. Symptoms of stiffness and lameness were also found. Autopsy findings revealed pathologic lesions in the joints and an increased liver zinc content. Brink et al. (1959) and Hill et al. (1983) also studied the arthritic condition by feeding pigs with 500 to 8000 mg/kg zinc. In addition to the arthritic condition characterized by swollen joints, at feeding levels of 2000 mg/kg and above, test animals exhibited depressed weight gain and food consumption. Brink et al. (1959) also found dosage - related increase in deaths. Postmortem examination revealed extensive hemorrhaging in axillary spaces and intestine and marked gastritis with some ulceration. Smith and Embling (1984) reported the effect of zinc ingestion in sheep. Animals were administered 240 mg zinc/kg as zinc oxide or zinc sulfate, three times a week for 4 30 weeks. This produced pancreatic damage in all exposed animals. Animals ingesting zinc sulfate also experienced severe diarrhea which commenced after a week of dosing and persisted throughout the experiment. All animals in the zinc sulfate group died after 13 days. Postmortem examination revealed a reduction of the papillation of the rumen wall and edema of the fundic folds of the abomasum. The liver had a finely mottled surface and an orange brown color. Dewar et al. (1983) studied the effects of excessive dietary zinc oxide in chicks and hens. Chicks were maintained on a diet containing 2,000, 4,000, or 6,000 mg/kg for 42 days or 1,000, 2,000, or 4,000 mg/kg for 28 days while hens received 10,000 or 20,000 mg/kg for 4 days. Mortality was high in chicks receiving 4,000 and 6,000 mg zinc/kg. Postmortem examination revealed macrosc0pic abnormalities of the alimentary tract. In five chicks in the 6,000 mg/kg group, there was internal hemorrhaging fiom the descending aorta or the thoracic aorta. Histological examination revealed gizzard and pancreatic lesions in all exposed groups. There was no mortality reported for the exposed hens; however gizzard and pancreatic lesions were found in both exposed groups. Carcinogenicity Leonard and Gerber (1989) studied small mammals and showed that zinc is cocarcinogenic with 4-mitroquinoline-N-oxide on oral cancer and with N-ethyl-N- nitrosourea on brain cancer. There is conclusive evidence that repeated intratesticular injections of zinc salts can induce testicular sarcomas in birds and rats. Zinc and zinc compounds are not conclusively carcinogenic except when injected directly into the testes; no field or experimental evidence exists showing zinc to be tumorigenic through any other route. Zinc is essential for the growth of rapidly proliferating cells such as tumors. 31 Accordingly, growth of animal tumors is stimulated by zinc and retarded by zinc deficiency. Under conditions of high gonadal activity, the injection of zinc salts into testes of fowl has induced testicular tumors. Nriagu (1980) also reported that seminomas, interstitial cell tumors, and teratomas occurred in rats after testicular injection of zinc salts. Teratogenicity No conclusive evidence has shown that excessive zinc produces any teratogenic effect in mammals (National Association of Sciences, 1979; Dawson et al., 1988; Leonard and Gerber, 1989). However, Dawson et al. (1988) showed that excess zinc is teratogenic to frog and fish embryos, possibly by inhibition of DNA synthesis. Reproduction Samanta and Pal (1986) and White (1955) reported that excessive dietary zinc may adversely affect fertility in humans and lower animal forms. Zinc Hazards to Fishes Most of the zinc introduced into aquatic environments is eventually partitioned into the sediments. According to Skidmore (1967), zinc bioavailability fi'om sediments is enhanced under conditions of high dissolved oxygen, low salinity, low pH, and high levels of inorganic oxides and humic substances. 32 Several documents report the toxic effects of zinc salts on the gills of experimental fishes. Skidmore (1967) reported on epithelial damage of gills which decreased the permeability of the gills to oxygen. Skidmore and Tovell (1972) reported on the effect of acute exposure of rainbow trout to 40 mg/l of zinc sulfate. This caused an acute inflammatory reaction in the gill with a separation of the epithelium outward fiom the pillar cells. This was followed by circulatory breakdown, tissue destruction, respiratory collapse, and death. Matthiessen and Brafield ( 1973) demonstrated the effects of dissolved zinc on the gills of the stickleback. Detachment of the epithelial cell upon exposure to zinc was found. Burton et al. (1972) confirmed an earlier hypothesis that the major physiological change preceding death in acute toxicity studies with zinc was tissue hypoxia. The hypoxia was directly related to gill tissue damage which disrupts normal gas exchange at the gill surface Other experiments also showed that fish eggs and fly are extremely sensitive to zinc poisoning. Pickering and Vigor (1965) indicated very great sensitivity to zinc of eggs and fly of the fathead minnow. He found median tolerance limits (TL 50) of 3.92 to 3.98 mg/l for 1 day old eggs. The TL 50 values continued to drop until on the 12th day the level had fallen to 1.97 to 1.69 mg/l. Newly hatched fry exposed for 2 days to zinc sulfate had a TL 50 of 0.95 mg/cc. Skidmore (1966, 1967) studied the effects of zinc sulfate on zebra fish eggs. The result showed that sensitivity to zinc sulfate increased during the course of embryonic development. Later embryonic stages of 2 to 4 days and newly hatched fly 4 to 13 days old were highly susceptible to the toxic effects of zinc. Birge and Just (1975) reported that zinc appeared to be more toxic to late embryonic stages and newly hatched fiy. ' Lloyd (1960) studied the cause of death of fish in solutions of zinc sulfate. The reason was not fiom the precipitation of mucus on the gills but probably fi'om zinc- induced damage to gill epithelium. Crandall and Goodnight (1962) found that guppies reared in zinc solutions experienced stunted growth, had a higher mortality rate, and 33 showed less sexual dimorphism. The report also showed many abnormalities among the internal organs. The liver had degenerated, the pancreas was undersized, the kidneys were distorted and hemorrhaged, and the skeletal muscles were underdeveloped. Bengeri and Patil (1986) showed that signs of zinc poisoning in fish included hyperactivity followed by sluggishness; before death, fish swam at the surface. They were lethargic and uncoordinated, showed hemorrhaging at gills and base of fins, shed scales, and had extensive body and gill mucus. Eisler and Gardner (1973) indicated that acute exposures to high lethal concentrations of zinc caused tissue damage of epithelia lining the oral cavity. Reed et al. (197 8) studied the acute toxicity effects of varying concentrations of zinc on certain fishes native to Illinois. Fourteen-day bioassays were performed with bluegill fry, channel catfish fingerlings, and largemouth bass fingerlings in waters relatively high in alkalinity and the salts of calcium and magnesium. The result indicated that the 14- day median tolerance limit at 20°C was 11.0 mg/l soluble zinc for blue gill, 8.2 mg/l soluble zinc for the channel catfish, and 8.0 mg/l soluble zinc for the largemouth bass. Plant Toxicity Brenchley (1941) reported that the normal levels of zinc range fiom 10 to 100 mg/kg in most crops and pasture plants. Zinc was early established as essential for the grth of higher plants. However, there are some reports indicating the toxicity of zinc in plants. That is mostly seen in the areas close to some emission source. Sensitive terrestrial plants died when soil zinc concentrations were more than 100 mg/kg. 34 Toxicity of Mixtures of Zinc and C0pper Several reports indicate the toxicity of mixtures of zinc and copper. Sprague (1986) suggested that mixtures of zinc and copper are generally acknowledged to be more-than-additive in toxicity to a wide variety of aquatic organisms. Venugopal and Luckey (1973,1975) reported that zinc toxicity can be alleviated by Cu and Fe. Klevay (1973) reported that an imbalance between zinc and copper is an important factor in the production of hypercholesterolemia in rats. He also suggested that animal fat ingestion and the zinc: copper ratio in milk may be important in the etiology of cardiovascular disorders in man. These hypotheses have not yet been firlly tested and are not generally accepted. Samman and Roberts (1988) reported that high levels of administered zinc limits c0pper uptake in humans and certain animals. Saxena et al. (1989) suggested that excessive zinc in humans interferes with copper absorption from the intestine, resulting in copper deficiency and eventually in cardiovascular diseases; high zinc intakes also decrease iron bioavailability, leading to a reduction of erythrocyte life span by 67%. 35 Health Effects Associated with Zinc in Humans Exposure According to the EPA (1987b), humans are exposed to zinc through the inhalation of air and the ingestion of food and water. Zinc levels in air are generally less than 1 mg/m3. Assuming that an individual inhales 20 m3 of air per day with an average zinc concentration of 1 mg/m 3, the daily zinc contribution from this source would be 20 mg. The EPA (1980b) reported that zinc dietary intake is 18 to 18.6 mg/day for males age 15 to 20 years old , whereas the dietary intake by girls 12 to 14 years old was 10 mg. Nriagu (1980) reported daily zinc dietary intakes of 14 to 80 mg. Inhalation Toxicity According to EPA (1987b), Prasad (1993) and Baselt (1988), in certain occupational settings, the inhalation of zinc oxide fumes as well copper fumes, as mentioned before, produces a disease known as metal fume fever. The disease is initiated by inhalation of zinc oxide firmes. Venugopal and Luck (1978) stated that zinc oxide fumes will accumulate in the lungs before being absorbed into the blood. Zinc is found in high concentrations in bone, skin, prostate gland, choroid of the eye, and serum. It is distributed to all organs and tissue of mammals. Metal firme fever usually occurs within a few hours after inhalation and has a short duration, about 6—48 hours. Fume fever symptoms from zinc oxide fume inhalation difl'ered fi'om copper fume inhalation. 36 Distinctive manifestations of zinc oxide firme fever are headache, leukocytosis and sweating and of copper fume fever are chills, anorexia, vomiting, nervous manifestations and enlargement of the liver. Metal fume fever generally strikes at the beginning of the work week when the worker has not been exposed for two days, and so it has been called "Monday Fever”. Further repeated exposure does not cause any new symptoms, suggesting some type of adaptation. Carcinogenic and teratogenic effects Excess zinc may have carcinogenic effects. Kok et al. (1988) reported data on mortality from cancer and cardiovascular disease correlated with zinc and copper status, in a population from the Netherlands. The EPA (1987b) concluded that many human studies have documented the level of zinc in both cancerous and noncancerous tissues, and the zinc content has been found to be both high and low with no definite pattern. Carson and Ellis (1986) tested laboratory animals which were injected with zinc salt, inducing testicular tumors. However, zinc appears to be indirectly involved, since zinc is required for tumor growth. Pounds (1985) has described metal carcinogens causing genetic damage in short term tests for mutagenicity in bacteria, yeast or mammalian cell-culture. The evidence showed the types of tumors caused by zinc excess include leydigioma, seminoma, chorionepithelioma and teratoma. Recent research on the effects of zinc excess in animals has shown positive teratogenic effects. A report, by Luo et al. (1993), demonstrates that Zn2+ is strongly teratogenic for Xenopus embryos, south African frog. 37 Risk of progression to AIDS High intakes of zinc may be monotonically and significantly associated with an increased rate of progression to acquired immunodeficiency syndrome (AIDS). Tang et al. (1993) investigated the different levels of dietary intake of micronutrients by a group of 281 HIV-1 seropositive homosexual/bisexual men. Participants completed a self- administered senriquantitative food frequency questionnaire as baseline. The data shows increased intake of zinc associated with risk of developing AIDS. CHAPTER 5 ENVIRONMENTAL EFFECTS ASSOCIATED WITH HEXAVALENT CHROMIUM According to the Environmental Criteria and Assessment Office (1984), the industries that employ chromium are metallurgy (3 29,000 metric tons/year), manufacture of refractories (97,000 metric tons/year), and the chemical industry (114,000 metric tons/year). The primary chromium chemicals are sodium chromate and sodium dichromate, which are converted to other compounds including pigments and catalysts. Pigments consume approximately 29,000 metric tons/year and chromate catalysts less than 2,000 metric tons/year of chromium. Nriagu and Nieboer (1988) and Elias et al. (1989) classified chromate pigments in two categories: corrosion inhibition and color pigments. Corrosion inhibition pigments based on zinc chromates, strontium chromates and barium chromates, are used in coatings to prevent the corrosion of metals. Chromate color pigments are mostly lead chromates, which include the yellows (lemon, primrose, and medium yellows), chrome oranges, molybdate orange, chrome green, and Guinet's green. They are used in printing inks, rubber, paper, etc. 38 39 The Lead Chromate Committee (198 7) described chrome yellow and molybdate orange as valuable color pigments with technical and economic benefits over most alternative pigment types. They impart bright and stable colors to printing inks, as well as surface coatings and plastics. Their bright colors, opacity, light-fastness, good heat resistance, and complete freedom from bleed make replacement with other colors difficult and costly. According to Sullivan (1969), chromic phosphate is utilized for green pigments, chromic potassium sulfate is used in the manufacture of inks, chromic sulfate is used in the manufacture of green inks, lead chromate (V1) is used as a pigment in oil and water colors; basic lead chromates are used as pigments (colors fi'om brown-yellow to red); potassium dichromate (V1) is used in printing photolithography and pigment prints; sodium dichromate (V1) is used in the manufacture of chrome pigments and dyes; and ammonium dichromate (V1) is used in lithography and photoengraving. OSHA (1979) stated that chromate pigments are used in colored plastics (polyesters, vinyls, thermosets, polystyrenes) employing chrome yellow, chrome orange, chrome green (lead chromate), molybdate orange and zinc chromate. Chromate pigments are also employed, in a limited amount, for colored elastomers (urethanes and nonsulfirr vulcanized elastomers) using chrome yellow and chrome green. Landfill According to the US. Department of Health and Human Services (1993), a higher level than normal of chromium can be expected near landfill sites with chromium- containing wastes, and near industrial facilities that manufacture or use chromium and chromium-containing compounds. 4O Kapil and Keogh (1990) cite a case in Hudson County, New Jersey in the 1960's and 1970’s where slag containing chromium in carcinogenic forms and in acutely toxic concentrations was used as landfill in residential, commercial, and recreational settings in over 100 locations. Community exposure from this fill occurred in a variety of ways: wind, soil erosion, chromium compounds leached by rainwater, and children playing in areas where slag was used as fill. Nriagu and Nieboer (1988) discussed groundwater contamination by chromium in industrialized areas. Typically, chromium-containing wastes have been disposed of by discharge to surface impoundments or lagoons. Leakage from these lagoons into groundwater has been relatively common. Almost all reported incidence of chromium- related groundwater contamination are of industrial origin. Air According to Towill et al. (1977), the total chromium atmospheric emissions are approximately 11,000 to 16,000 tons/year in the United States. Nriagu and Nieboer (1988) estimated that emissions from anthropogenic sources were about 5,000 tn/year in 1978. According to the US. Department of Health and Human Services (1993), anthropogenic emissions decreased to 2,700-2,900 tn/year by 1993. The US. Department of Health and Human Services (1993) estimated US. atmospheric chromium emissions from anthropogenic sources as : combustion of coal and oil 1,723 tn/year (0.2% Cr(IV)), chromeplating 700 tn/year (100% Cr (IV )), sewage sludge incineration 133 tn/year (less than 0.1%Cr (VI)), municipal refuse incineration 2.5 tn/year (0.3% Cr (VI)) and chromium chemical manufacturing 18 tn/year (67% Cr (V0). The Environmental Criteria and Assessment Office (1984) reported an air concentration of total chromium of 0.005 ng/m3 at the South Pole. In the United States, 41 reported values were between 0.005 and 0.157 ug/m3. The total yearly deposition of chromium in urban areas may vary fiom 0.12 ug/m2 to 3 ug/m2 . In general, urban areas have higher total deposition than rural areas. No federal or state ambient air chromium standards have been proposed. Water Shepherd and Jones (1971) reported concentrations of chromium in seawater of 0.05 ug/ 1. In one survey, the chromium content of 24 municipal water supplies was found to be fiom 1 to 40 ug/l. The chromium content of marine animals generally falls between 200 and 1,000 ug/l. The Environmental Criteria and Assessment Office (1984) described the origin of chromium in surface waters as surface runoff, deposition from air, and release of municipal and industrial wastewaters. Most of the chromium present in surface water was hexavalent The US. Department of Health and Human Services (1993b) has assigned the maximum level of Cr (III) and Cr (VI) allowed in drinking water that is not expected to cause effects that are harmful to health: 1,400 ug chromium/l for 10 days of exposure for children, 240 ug chromium/l for longer-term exposure for children, 840 ug chromium/1 for longer-term exposure for adults, and 120 ug chromium/l for lifetime exposure of adults. In contrast, Kapil and Keogh (1990) mentioned a EPA recommended concentration for drinking water of SOug/l Cr (VI) because of the toxic effects of Cr (VI) and possibility of oxidation of Cr (III) to toxic Cr (VI). ‘6 Soil Chromium in the soil exists predominantly in the trivalent oxidation state. The main origin of chromium that contaminates the soil is fallout and washout from the atmosphere. Another source is sewage sludge when it is used as a fertilizer (Towill et al., 1977). Eisler (1986) observed that extremely high levels of Cr (VI) in sludge components may have serious effects on wildlife when the sludge is applied to croplands. The chromium quantity in the soil, according to the Environmental Criteria and Assessment Office (1984), varies with soil origin and degree of contamination from anthropogenic sources. Tests on domestic soil have shown chromium concentrations ranging from an average of 14-70 ppm. Because the amount of chromium in food and food plants is relatively low, and because chromium does not appear to accumulate in mammalian systems, bioaccumulation in the soil-plant-animal system does not appear to be a significant exposure source. Effects of Chromium on Vegetation According to Krupa et al. (1982), plants, in general, tolerate soluble chromium in amounts of 006-50 ppm on average. The most sensitive plants are tobacco, maize and oats. The highest accumulation of chromium in plant organs appeared in the roots. Chromate taken up into leaves caused changes in the content of plastid pigments and lipoquinones similar, in general, to those in senescent plants. 43 Sullivan (1969) related dependency of chromium effects on plant type, chromium concentration in the soil, and availability of the chromium to plants. In soils less acidic than pH 4, very little chromium is available to plants. When small amounts of chromium are available, the growth of cats and barley is stimulated. However, even a smaller amount is toxic to wheat. Toxic effects may be expected in plants when the levels of available chromium in the soil exceed 7-10 ug Cr (VI) /g of soil. Nevertheless, some plants may tolerate as much as 100,000 ug Cr (VD/g. Anderson (1982) associated effects of chromium with alterations in the plant roots and symbiotic soil microorganisms. Such impairment irnpedes the transport of nutrients to plant tissues and therefore reduces plant growth and viability. Inhibition can occur at concentrations as low as 10 ppm. The National Academy of Sciences (1974) gave examples for water plants where hexavalent chromium at 003-64 ppm inhibited the growth of algae, whereas lower concentrations stimulated growth in some cases. Hexavalent chromium at 1-5 ppm in seawater reduced photosynthesis of giant kelp macrocystic pyrifera by 20 to 30 percent after 7 to 9 days, 5 ppm produced 50 percent inactivation of photosynthesis within 4 days and in the case of land plants, the effects on growth of adding chromium to the soil depended on the amount of chromium naturally present in the soil. The National Research Council (1974) provided more examples. Although chromium at 75 ppm in soil was not hannful to orange seedlings, the addition of Cr at 150 ppm was toxic. Chromic sulfate stimulated the grth of corn seedlings in culture solutions containing chromium at 0.5 ppm, but at 5 ppm and above it inhibited growth. The growth of tomatoes, oats, kale, and potatoes was reduced by chromium (as chromate) at 16 ppm. Chromium at 5 and 10 ppm in nutrient solutions produced iron chlorosis in cat plants, and at 15-50 ppm it was toxic. Chromium at 8 and 16 ppm produced iron chlorosis in sugar beets, and at 5 ppm (as chromate) it was toxic to tobacco and at 10 ppm toxic to corn. In some instances, toxicity has been associated with the chromium concentration in 44 plant tissues. For example, tobacco leaves grown on serpentine soil, which normally has a high chromium concentration (possibly several percent), may contain chromium at 14 ppm (dry weight) without toxic signs; but at 18-34 ppm, toxic effects were visible. Concentrations of 175 ppm (dry wt) in the roots were without harm; but at 375-410 ppm, toxic symptoms were present. In fruits, vegetables, and grain, no harmful evidence was found with concentrations from traces to about 14 ppm (dry tissues); but toxic symptoms appeared in corn when the leaves contained 4-8 ppm and in oats when the leaves contained 252 ppm. Witter (1989) stated that chromium in sludge is present as Cr (III) in which form it is non-mobile, and in which it remains in the soil. Toxic effects of chromium on plants of chromium have only been noted when added as Cr (VI). Chromium is relatively non- zootoxic and no negative food chain effects can be expected because of the extremely low plant uptake of Cr. Field and pot experiments show no negative efl‘ects on plant growth and non-significant or minimal (less than 1%) Cr uptake when sludge containing chromium was applied at rates of 110 kg Cr/Ha. Terrestrial Animals The US. Department of Health and Human Services (1993b) noted harmful effects on the respiratory system and a lower capability to fight disease, if animals breath high levels of chromium. Eisler (1986) reviewed the effects of Cr (VI) in dogs and chickens. Cr (VI) was deadly to dogs when exposed for 3 months to food with 100 ppm of Cr (VI). Tissue accumulations (especially in the brain) were significant in dogs exposed to drinking water concentrations of 11.2 ppm Cr. Male domestic chickens fed diets containing up to 100 ppm of Cr (V1) for 32 days showed no adverse effects in survival, growth, or food utilization eficiency. However, teratogenic effects were documented in chicken embryos 45 after eggs had been injected with Cr (VI). Chromium is an animal carcinogen. In the only animal study demonstrating a carcinogenic effect of an inhaled chromate, adenocarcinomas were reported in lungs of mice exposed throughout life to CaCrO4 dust at 13 mg/m3 for 35 hours weekly. Aquatic Organisms Towill et al. (1977) stated that chromium is considerably toxic to fish and many other aquatic organisms, especially in its hexavalent form. This toxicity varies depending on their sensitivity to the element. The lethal level for some invertebrates is 0.05 ppm, while tests on other organisms, including fish, indicate that several tens of ppm can be tolerated. Maximum permissible concentrations must be set based on the more sensitive organisms. Eisler (1986) compared different factors that determine sensitivity to chromium (VI). Younger life stages are more sensitive than older organisms. The organisms most sensitive to Cr (IV) were freshwater crustaceans, rotifers and marine crustaceans. Invertebrates Invertebrate species are generally more sensitive to Cr (VI) than fish species. Eisler (1986) reported acute levels of Cr (V1) for six freshwater invertebrate species fi'om five families. These ranged fiom 67 ug/l for a scud to 59,900 ug/l for a midge. Shepherd and Jones (1971) and Eisler (1984) associated Cr (V1) with unfavorable effects in invertebrates of amply separated taxa: reduced survival and fecundity of the cladoceran D_a_ph_nia mgna at a concentration of 10 ppb and exposure for 32 days; growth inhibition of the protozoan Chilomong W at 1,100-3,000 ppb during exposures 46 of 19-163 hours at temperatures of 10- 30 degree celsius; abnormal movement patterns of larvae of the midge Chironomus tentans at 100 ppb for 49 hours; and a temporary decrease in hemolyrnph glucose levels in the fieshwater prawn Macrobrachium larnarrei surviving 1,840 ppb Cr (IV) for 96 hours. The acute toxicity of Cr (VI) in 20 saltwater vertebrate and invertebrate species ranges from 2,000 ug/l for polychaete annelids and a mysid shrimp, to 105,000 ug/l for the mud snail. Polychaetes and microcrustaceans are the most acutely sensitive taxa. Chronic toxicity was observed at Cr (VI) concentrations of 25 and 123 ug/l for polychaetes and amysid shrimp, respectively. Shepherd and Jones (1971) found, in a 2-year study of oyster mortalities in water containing 0.01 ppm chromium, that toxicologic effects may be cumulative even at these low concentrations. Fish Anderson (1982) revealed that the grth and reproductive capacity of fish can be adversely afl‘ected at concentrations of Cr(VI) as low as 10 ppb. Nriagu and Nieboer (1988) said that Cr (IH) seems to be more poisonous to fish than Cr(VI). The mean 96-hour LC 50 for Cr(III), pooling data for all species and water conditions, was 22.0 mg/L, significantly lower than the 100.7 mg/l for Cr (VI). The chronic and/or sublethal effects of Cr(VI) and Cr(IH) to fish include histophatological damage, altered blood parameters such as hematocrit, serum protein levels, and blood glucose levels, decreased enzyme activity, and impaired respiratory and locomotory activities. Generally, reproduction and larval survival seem to be the most sensitive indicators of chronic toxicity. As well, the coldwater salmonids appear to be the most sensitive family of fish to chromium toxicity; while the warmwater minnows, carps, and livebearers appear to be the most tolerant families of fish to chromium toxicity, both acute and chronic. 47 Shepherd and Jones (1971) referred to a toxic concentration of about 20 ppm Cr (V1) for minnows and rainbow trout. The growth of chinook salmon was reduced at a measured concentration of 16 ppb of Cr (VI). Eisler (1986) stated that Cr (VI) concentrations of 16 to 21 ppb in the medium resulted in reduced growth of rainbow trout during exposure of 14 to 16 weeks and altered plasma cortisol metabolism after 7 days. Anderson (1982) reported the result of long-term tests with brook trout and rainbow trout. Both presented chronic effects at 265 ug /l, which is much lower than the 1,990 ug/l for the fathead minnow. In chronic tests with brook trout, rainbow trout, and fathead minnows, a temporary adverse affect on growth occurred at low concentrations. Eisler (1986) stated that Cr (VI) concentrations of 16 to 21 ppb in the medium resulted in reduced growth of chinook fingerlings during exposure of 14 to 16 weeks. Anderson (1982) indicated a tolerance level of 45 ppm for blue gills exposed 20 days in hard water, and of 200 ppm (using K2Cr207) for mummichogs exposed in seawater for 1 week. The toxicity of chromium to Channa punctatus was described by Sastry and Tyagi (1981). Exposure of Channa punctatus for 30 days to a sublethal concentration of chromium produced some marked changes in blood and tissues. The blood glucose and lactic acid levels were elevated. Liver glycogen was depleted. Regulations According to the Lead Chromate Committee (1987), wastes are judged hazardous by the Resource Conservation and Recovery Act (RCRA) only if they do not pass the tests for ignitability, corrosivity, reactivity, or Toxic Characteristic Leaching Procedure (TCLP formerly EP) toxicity outlined in the regulation. For this purpOse, lead chromate pigments were tested. Results indicated that, with few exceptions, the toxic characteristic leaching toxicity exceeds the 5 mg/l maximum for lead, and encapsulated lead chromates 48 as currently produced are closer to the 5 mg/l limit but still above it. However, all of the colored lead chromate pigments tested were well below the 5 mg/l maximum for chromium. In conclusion, any offgrade or contaminated chrome yellows or molybdate oranges must be treated as a hazardous waste. Waste sludge containing pigment would not necessarily be hazardous based on lead chromate content unless leaching tests indicated 5 mg/l of lead or chromium could be extracted. Handling properties of lead chromate pigments are improved by granulation, resin encasement, surface treatment with materials such as teflon fibers, and electrostatic charge neutralization. Finley et al. (1992) point out that the EPA is developing an inhalation reference concentration (MC) for Cr (IV) and 0011). Inhalation reference concentration (MI?) is an estimate of continuous exposure to the human population (including sensitive subgroups) that is likely to be without an appreciable risk of deleterious effects during a lifetime. Cr (V1) is considered by the EPA to be a known inhalation carcinogen. For that reason the EPA in 1991 proposed to promulgate an inhalation RfC of 0.002 ug/m3 for both Cr(VI) and Cr (III). The proposed Rsz are several orders of magnitude less than threshold limit values and other occupational exposure limits. q _—‘_ CHAPTER 6 HEALTH EFFECTS ASSOCIATED WITH HEXAVALENT CHROMIU M Introduction According to the Environmental Criteria and Assessment Oflice (1984), depending on the oxidation state and type of chromium compounds, we can determine the risks and benefits to human health. In the natural environment, chromium appears in two oxidation states, hexavalent [Cr(VI)] and trivalent [Cr(III)]. Chromium (V1) is toxic to animals and plants, whereas Cr (ID) is considered to be less toxic (Nriagu and Nieboer, 1988). Cr (VI) has a high penetration power. According to OSHA (1979), hexavalent chromium can be absorbed through the skin, lungs, or intestinal tract by sorption through the membranes and tissues. Then, Cr (V1) is able to attach itself to protein, nucleic acids, and hemoglobin. The new complexes which are formed may interfere with the regulation of cellular activity, and may exert a carcinogenic action on the cells (Sullivan, 1969). Towill (1977) recommended that exposure to Cr(VI) compounds be controlled, especially in the occupational environment. Among the three standards recommended by NIOSH for the control of worker exposure to chromium, there are two standards tlmt pertain to Cr (VI). One standard pertains to occupations and workplace where there is 49 50 exposure to Cr (VI) material associated with an increased incidence of lung cancer. This standard allows concentration of Cr (VI) in the airborne workplace not greater than 25 ug/m3 (determined as a time-weighted average (TWA) exposure for up to a 10 hr- workday, 40 hr workweek) and not greater than 50 ug Cr (VI)/m3 of breathing zone air (determined by any 15-min sample). Two years ago OSHA issued a new standard which reduced the permissible exposure limit even firrther. The level of chromic acid and chromic (VI) compounds in the workplace air should not be higher than 100 ug Cr/m3 for any period of time (US. Department of Health and Human Services, 1993b). Cancer Chromium compounds are among the few established causes of work or environment-related cancer that have been known for more than 100 years. Levy and Venitt (1986) stated that no one has determined which kinds of hexavalent chromic salts (chromates or dichromates) are responsible for the increased risk of lung cancer. As stated before, Cr (VI) induces cancer because of its wide solubility. Therefore, chromates with aqueous solubility are more active in inducing tumors. The potential carcinogenicity of Cr (VI) compounds will depend to a large extent on chemical composition and those physical properties which determine the absorption, distribution and retention of a sufficient concentration of chromate ions at the target location. Only certain Cr(VI) compounds are chemical carcinogens. Anderson (1982) identified some potential chromium carcinogens as chromates of calcium, lead, and zinc. The US. Department of Health and Human Services (1993b) mentioned calcium chromate, chromium trioxide, lead chromate, sodium dichromate, strontium chromate, and zinc chromate as known carcinogens. 51 The Lead Chromate Committee (1987) discussed an animal study conducted at the University of Aston, England in which calcium chromate and strontium chromate produced a high incidence of tumors, while zinc chromate, which is somewhat less soluble, produced a lower number of bronchial carcinomas. Among the seven lead chromate-type pigments tested, Lead chromate, Primrose chrome Yellow, LD Chromate Yellow, and Medium Chrome Yellow, each produced one case of carcinoma out of a population of 100 rats. The remaining pigments (Molybdate Chrome Orange, Light chrome Yellow, and Silica-encapsulated Medium Chrome Yellow) did not produce any cases of carcinoma. In addition, no tumors were found in the barium chromate group. Neither the highly soluble (chromic acid or sodium dichromate), nor the insoluble compounds (barium chromate) can be considered to be carcinogenic. Only chromates of medium solubility (strontium, calcium and zinc chromate) are carcinogenic. In humans, chromium compounds produce cancers only in the respiratory system and only via respiration. Sullivan (1969) defined the average duration of exposure to chromium before death fi'om respiratory tract cancer as 18 years. The US. Department of Health and Human Services (1993) believes that chromium (V1) is primarily responsible for the increased lung cancer rates observed in workers who were exposed to high levels of chromium in workroom air. According to NIOSH (1975), Gross and Kolsh in 1943 reported the first study of cancer in the chromate pigments industry in Germany. Three firms which manufactured lead chromate (chrome yellow) and zinc chromate (zinc yellow) pigments participated in this study . 8 deaths from lung cancer were reported. Five of these deaths occurred among workers producing zinc chromate; the other three deaths occurred among workers in plants producing chromates of both zinc and lead. Four of the deceased were only 33- 37 years of age . Seven of the deceased had worked in the industry 5-17 years. The authors suggested that zinc chromate was the prime causative agent and should be considered to be a potent carcinogen. 52 Langard (1993) mentioned a reported issued by Letterer et al. which reported two cases of lung cancer in workers 36 years old, after 7 and 20 years of work in a chromium pigment plant. One had been exposed to zinc chromate only. NIOSH (1975) and Langard (1993) referred to a very famous report published by Langard and Norseth in 1975. This study examined a Norwegian zinc chromate company. 133 male workers were observed from 1953 to 1972. Zinc chromate was the main exposure, but a small number of the workers were exposed to lead chromate between 1948 and 1952. Of these a cohort of 24 were derived comprising those who were employed for more than 3 years before December, 1972. Three cases of lung cancer occured in this group between 1951 and 1972. The Lead Chromate Committee of the American Dry Color Manufacturers' Association (1987) in 1974 sponsored a study of three typical United States chromate pigment production plants. The final report showed a level of lung cancer slightly higher than expected, and a lower level than was seen in the Norwegian population. The authors concluded that lead chromate is a carcinogen. A five year follow-up study through the end of 1979 found no evidence to support an association between lead chromate and lung cancer, but did find evidence to tie increased lung cancer to exposure to zinc chromate. According to Nriagu and Nieboer (1988), three chromate pigment plants in Great Britain were studied in 1984. An elevated risk of lung cancer was found only in the plants that produced both zinc and lead chromate, and was absent in workers who were employed only in the manufacture of lead chromate. Langard (1993) also referred to the same study stating that a nonsignificant excess of lung cancer deaths was seen in a small subgroup of workers exposed to lead chromate only, as well as in a small group of lead chromate workers who had previously suffered fi'om lead poisoning. These findings remained consistent with the hypothesis that lead chromate might be noncarcinogenic. Zinc chromate is a more potent human carcinogen by inhalation than are other Cr (VI) compounds. 53 Dermal Diseases Stern et al. (1993) referred to Cr (VI) as a potent source of allergic contact dermatitis. Chromium is the second most common skin allergen, the most common sensitizer, and the most important cause of occupational dermatitis. An EPA inhalation reference concentration (RE) based on noncancer toxicity is pending. The National Academy of Sciences (1974) classified chromium skin exposure as a corrosive reaction, including ulcers and stigmata (scars), and sensitization reaction, including eczematous contact dermatitis (allergic reaction). Anderson (1982) and Stern et al. (1993) stated that short-term exposure can cause allergic contact dermatitis (skin ulceration or eczema). Allergic dermatoses are associated with the handling of chronrium-containing materials. These ulcerations result from contact with chromium acid, sodium or potassium chromate or dichromate, and ammonium dichromate at levels high enough to provoke an immediate response in normal healthy workers. The dermatoses can continue for long periods of time. This dermatitis is described as localized swelling and inflammation, wrythema , papules and vesicles, followed by dryness, scaling, and fissuring, on breaks in the skin or where abrasion of the workers' bodies in contact with chromium compounds exists, but exposure of the skin to chromic vapors, firmes and/or dusts may contribute to these effects. Sullivan (1969) described the location of these ulcerous dermatoses in the skin, usually on the hands and forearms, and occasionally on the feet, ankles, face, and back. Other specific sites like roots of the fingernails, knuckles, eyelids, edges of the nostrils and throat were mentioned by the National Academy of Sciences (1974). The US. Department of Health and Human Services (1993b) pointed out that corneal vesication result fi'om a crystal of potassium dichromate or a drop of potassium dichromate in the 54 eyes. Sullivan (1969) stated that these ulcers in some cases have perforated to the bone. Over 50% of a group of chromate workers showed signs of either active or healed chrome ulcers. On a few workers who are apparently hypersensitive to chromates, the dermatitis is an immune system response to an allergen absorbed into the skin and appears as an allergy. Sensitization may develop, resulting in typical asthmatic attacks, which recur on later exposure even when exposure is to much lower concentrations. Nriagu and Nieboer (1988) alluded to the report of Parkhurst in 1925 where a risk of chromate dermatitis was identified in the printing industry. Pirila and Kilpio in 1954 reported chromate sensitivity in 27% of 149 cases of dermatitis among printing workers. Of 76 cases of dermatitis reported among lithographers, 17 patch-tested positively to potassium dichromate. Spruit and Malton in 1975 demonstrated high chromium levels in the materials handled by three men working in an offset printing factory who developed dermatitis and chromate sensitivity. The use of potassium dichromate in the printing industry has declined following suitable substitution by other agents. OSHA (1979) recommended that during production operations, where splashes of liquid pigment can occur or dry powders can be inhaled, workers must be protected. Drying, grinding, blending, and packaging are operations where chromate exposure is likely to occur because chrome dust is very fine, and once it gets into the workplace air it remains a long time. Respiratory Effects Bencko (1985) reported a concentration of chromium in lungs of individuals living in industrialized areas of 70 ug, the liver 270 ug and the kidneys 90 ug per 1 kg fresh tissue. Considerably lower levels were found in persons residing in non-industrialized areas of the country. 55 According to the US. Department of Health and Human Services (1993b) and Anderson (1982), long-term breathing of concentrations of chromium (VI) greater than 2 ug/m3 can induce inflammation of the thin mucous membrane layer covering the nasal septum producing irritation to the nose, such as runny nose, sneezing, itching, and nosebleeds. Longer exposure can cause ulcers and perforation or holes in the nasal septum. Kartz and Salem (1993) and Anderson (1982) pointed out that this perforation can be present without any awareness by the workers. If the exposure continues, the perforations get deeper and become very painful. The National Academy of Sciences (1974) remarked about additional effects due to exposure to high concentrations of chromium: cough, headache, dyspnea, substemal pain, and bronchospasm. The bronchospasm is likely to be due to chemical irritation of the air passages, and not to "bronchitis", although it is commonly so diagnosed. A long-term inhalation of chromate dust causes chronic irritation of the respiratory tract and results in such symptoms as congestion and hyperemia, chronic catarrh, congestion of the larynx, polyps of the upper respiratory tract, chronic inflammation of the lungs, emphysema, tracheitis, chronic bronchitis, chronic pharyngitis, and bronchopneumonia. Some German doctors affirmed that a typical pneumonoconiosis resulted from exposure to some chromates. Two incidents of acute puhnonary complications involving the deeper pulmonary structures after inhalation of massive amounts of chromic acid mist have been delineated. The estimated chromic acid concentration in the mist was 20—30 mg/m3. The manifestations included cough, chest pain, some dyspnea, pleural eflirsion, and loss of weight. In another study, atrophic rhinitis was reported in 5-10% of a group of workmen exposed to the mist of a 5% chromic acid solution. Hyperemia, swelling, congestion, and nasal catarrh occurred in some of these persons. 56 Mutation According to Bianchi (1980), evidence has accumulated to show that compounds of chromium possess the ability to cause transformation and mutation. Cr (VI) increases the frequency of sister chromatid exchanges (SCEs) and increases the frequency of chromosome aberrations, in mammalian cells, only at extremely high concentrations. Gennart (1993) reported an increased fi'equency of chromosomal aberrations and/or sister- chromatid exchanges (SCE) in lymphocytes of workers exposed to Chromium (VI) compounds. CHAPTER 7 ENVIRONMENTAL EFFECTS ASSOCIATED WITH CADMIUM Introduction According to Dorn (1979) and Dobson (1992), cadmium is used mainly in the production of electroplating for protective plating on steel, pigments and chemicals in plastics and glass, plastic stabilizers for polyvinyl chloride, alloys and solders, electrode material in nickel-cadmium batteries, semi-conductors and photocells, and pesticides. Stansley et al. (1991) included smelter emissions, wastewater discharges, landfill application of sewage sludge fertilizers, and fossil fuel combustion as anthropogenic sources of cadmium. If these sources of emission continue, cadmium in the environment will reach a dangerous level. Osuna and Edds (1982) state that the concentration of this metal in humans has already increased, with the kidney the main organ affected. 57 58 Plastics Cadmium is used as a pigment and a stabilizer in the polymer industry. According to Dobson (1992), these materials held 22% and 12%, respectively, of the consumption of cadmium around the world in 1985. Cadmium pigments' share of the market remains constant. In contrast, the use in stabilizers for plastics is decreasing, due to manufacturers replacing cadmium by other cheaper compounds. For instance, liquid barium-zinc compounds are used in PVC instead of cadmium. This compound costs less and performs better. Monks (1990) stated that ABS is the plastic that most commonly use cadmium as a pigment. ABS accounts for 35% (200 tons) of the total cadmium use in plastics, followed by HDPE (25%), polypropylene (15%), polystyrene (10%) and LLDPE (10%). 45% (90 tons) of cadmium used in ABS finds its way into municipal landfills and garbage incinerators. Plastics are an important source of cadmium in solid waste. Monks (1990) ranked cadmium in plastics as the second largest contributor of this metal to the total waste in 1986. The amount discharged in 1986 in the US. was 564 tons. This represents 28% of the total cadmium released. Monks (1990) discussed the increasing concern of additives makers and users about pigments and PVC heat stabilizers based on cadmium. This concern is a result of the surge of regulations proposed by CONEG, OSHA, and the Clean Air Act for the metals use in plastics. These regulations have emerged due to cadmium contamination of air and groundwater resulting from the incineration of cadmium-containing plastics. Cadmium containing pigment makers are planning to phase out their use because they are pushed to 59 replace cadmium by the pigment users. However, the replacements for cadmium pigments do not provide the same palette diversity as pigments made with cadmium. Plasticizers The British Department of the Environment (1980) described cadmium plasticizers as inhibitors of degradation by heat or light in PVC. This degradation causes darkening, toughening and embrittlement. Plasticizers that contain cadmium in amounts of l to 20% are used. These plasticizers are used in small quantities in the polymer (1 to 3%). Pigments The Department of the Environment (1980) reported the total amount of cadmium used in Great Britain as a pigment as 550 tonnes in 1978. A great percent (70%) of cadmium pigment was employed in the coloring of plastics such as polyvinyl chloride (PVC), polystyrene (PS) and polypropylene (PP). The rest of the cadmium pigment was used in the coloring of rubber and, to a lesser extent, industrial and car paints, ceramic decorative materials, iridescent and colored glasses, enamel, and printing inks. Cadmium pigments can provide us with a whole diversity of colors fi'om lemon- yellow, through orange, to deep maroon. In addition, cadmium pigments deliver colors such as khakis, browns and even greys (Department of the Environment , 1980). The kind of cadmium compounds used as pigments were described by the Commission of the European Communities (1981) and the Department of the Environment (1980). Cadmium sulfide and selenide are used especially for printing ink, rubber, plastics, coated fabrics and leather. Properties of these two compounds include brightness, opacity, heat resistance up to 1200 Celsius, light stability, good covering power, insolubility in organic solvents and insolubility in water. However, these 60 compounds are expensive, are darkened by atmospheric sulfirr, and are toxic when are used in toys or food containers. Cadmium oxide or carbonate are used for coloring enamels, glazes and glass. According to Monks (1990), the closest alternatives for cadmium pigment substitutions are organic compounds and inorganic compounds such as iron oxide and a host of nickel titanates blended with antimony. However, it is difficult to get the same shades of color as cadmium provides. Iron oxide mutes to a reddish-brown color and nickel titanates with antimony have poor color dispersion. In cheap plastics and paints, cadmium pigments have already been replaced. Due to the heat resistance property of cadmium pigment, it is difficult to find replacements with the same color shades as cadmium when the pigment is exposed to high temperatures. Polyethylenes, PVC and polystyrene wraps, containers and household objects include in their manufacturing pigments derived from cadmium compounds. Preda et al. (1983) studied the release of this metal fi'om the plastic. They observed pathological changes in the tissues of white rats exposed to extracts of such plastics. Water Concentrations of cadmium in water are low and constant. Such concentration is below the drinking water standard (0.01 mg/l). The World Health Organization recommended that the concentration in drinking water needs to be kept below 0.005 mg Cd/l (Dom, 1979). Soluble cadmium is persistent and highly toxic. Taylor (1983) found lethal effects of soluble cadmium at levels greater than 0.002 mg/l. in fresh water and greater than 0.095 mg/l in marine water. The EPA established in 1980 an allowable concentration of 61 cadmium in water equivalent to 0.0063 mg/l in fresh water and 0.059 mg/l in marine waters. Webb (1975) mentioned smelting and refining of zinc and lead ores, and the dumping of sewage sludge and of waste plastics as the major industrial contaminants. Major packaging-related industries that dump great amounts of sewage sludge and waste are pulp and paper mills, rubber processing, and paint and ink plants. The recovery of cadmium fiom industrial wastes is uneconomic due to low levels of cadmium. Air Nriagu (1990) estimated the emissions around the world of cadmium as 7570 tonnes. 90% of this number is accounted for by anthropogenic sources. Smelting of base metal ores is the main source of cadmium, with a amount of 5,299 tonnes/year, followed by refuse incineration (about 750 tonnes/year), coal combustion (about 530 tonnes/year), cement production (about 270 tonnes/year), and fertilizer production (about 170 tonnes/year). Atmospheric concentrations of cadmium in urban locations are below 10 ng/m3. Cadmium released anthropogenically is transmitted to the food chain. Incineration of wastes containing cadmium, such as plastics, increases the level of cadmium in the air. Exposure to this level is predicted to increase human cancer risk in urban or industrial areas (EPA, 1985). 62 Soil Nriagu (1990) listed the main cadmium pollutant sources in soil as atmospheric fallout, urban refirse disposal, dumping of fly ash, use of sewage sludge as a source of nutrients or organic amendments for improving soil physical properties, disposal of agricultural and animal wastes, and the application of fertilizers. The Commission of the European Communities (1981) estimated a range of concentration of cadmium in the soil of 0.01- 2.5 mg/kg. Commonly the level is less than 1mg/kg. According to Hattori (1989), when these levels are exceeded, the effects are decrease of vegetation due to plant toxicity. Sewage Sludge and Land Disposal Soils improved by sewage sludge contain a high concentration of cadmium. The Commission of the European Communities (1981) described the treatment of sewage sludge before it is included in the soil. 30% of the cadmium in the raw sewage is separated by sedimentation. Then, 60 to 70% of the cadmium is separated by activated sludge treatment. In total, 90% of the cadmium in raw sludge is removed. However, the remaining 10% is added to the soil. This amount will increase the level of cadmium in agricultural soil. Dom (1979) mentioned a fertilizer called "Milorganite" which is a result of municipal sewage converted to organic fertilizer. The use of this fertilizer may increase the content of cadmium in soil. Jones et al. (1987) pointed out that the increase in this metal may have an adverse effect on human health. Food based on plants is one of the major source of dietary cadmium. The World Health Organization's (WHO) allowable intake of cadmium by an adult is 51-71 ug/day, except for beef, canned fish and canned tomato sauce, which should 63 be limited to 100 ug/kg, and kidney and canned kidneys, which would be limited to 500 ug/kg. The present average daily intake of cadmium in Europe is 20-40 ug/day. This amount will increase in the long term, reaching WHO'S allowable limits of 51-71 ug/day. Most of the increase in dietary cadmium results from grain and cereal intake. Wolf and Baker (1979) emphasized the limitation of cadmium in soil to no more than 3 pounds/ acre as what they considered safe. Sewage containing more than 50 ppm is not beneficial to plants due to cadmium accumulation in the soil. Considerable leaching of cadmium from soil to ground water can occur only in extreme contamination, low pH or both. This contaminated ground water can contaminate aquatic systems. Cadmium concentration in soil solutions may be 0.1-1 ug/l (Nriagu and Sprague, 1987). Animal Toxicity According to Webb ( 1975), concentrations of cadmium present in the environment may be a great hazard for sensitive animals. Such low levels can produce adverse effects in domestic animals. Stansley et al. (1991) reported a case of accumulation of high amounts of cadmium in the liver and kidneys of wild moose and deer. Birds Eisler (1985) noted that aquatic birds are highly tolerant to cadmium. He mentioned adult drake mallards have survived a dose of 200 ppm of cadmium given for 90 days. Terrestrial birds are more tolerant than aquatic birds. Efi‘ects on terrestrial bird toxicity include growth retardation, anemia, and testicular damage. ‘. _ _ :33 —_._’=w 64 Aquatic Organisms According to Taylor (1983), international covenants (Oslo, London, Paris, Rhine, and Barcelona Conventions and the EEC Directive on the Discharge of Dangerous Substances) include cadmium and its compounds on their black lists. The reason behind this decision was to prevent aquatic pollution. Cadmium presents all the selective factors: persistence, toxicity and bioaccumulation. Eisler (1985) found a decrease in growth, respiratory disruption, molt inhibition, shortened life span of next generation crustaceans, altered enzyme levels, and abnormal muscular contractions in marine organisms exposed to cadmium in a range from 0.5 to 10 ppm. Sea water organisms can resist higher levels of cadmium than fi'eshwater organisms. In freshwater biota, high mortality rates, reduced growth and inhibited reproduction were present at concentrations exceeding 10 ppb. Mortality increased as time of exposure increased, water hardness decreased, and the organism's age decreased. Concentration of cadmium in marine organisms (particularly zooplankton, mollusks and other filter-feeders) was 10 3 or 10 4. Shellfish also accumulate Cd; the brown meat of the edible crab, for example, consistently contains around 5-15 mg/kg of Cd. Fish The Commission of the European Communities (1981) classified fishes according to their sensitivity. Salmonid fish and some species of invertebrates, such as gamma magna and W were the most sensitive. In fish species that are particularly sensitive to cadmium, it accumulates mainly in the liver, gills, and kidney. Webb (197 5) pointed out that cadmium accumulates in gills as water passes through, and in the body when water is ingested. 65 Lowe-Jinde and Niimi (1984) stated cadmium toxicity signs in fish are growth reduction, testicular injury, impaired gill function, hematological changes, and disturbances in osmotic-ionic balance and carbohydrate metabolism. Lower concentrations of Cd than those that are toxic to adult fish affect reproduction and are toxic for the larvae. According to Dobson (1992), toxicity decreases as salinity increases, temperature decreases, and oxygen content increases. The Commission of the European Communities (1981) noted that accumulation of cadmium in muscle fish tissue varies to levels 1000 times higher than in the seawater (less than 0.1 ug of cadmium in a liter of seawater). Metallothionin (MT) is a protein that regulates the detoxification of heavy metals. Gagne et al. (1989) mentioned that cadmium reduces the synthesis of this compound, decreasing the detoxification ability of fish. Studies of 30 to 60 days duration with three comparatively sensitive species of freshwater fishes demonstrated that cadmium, in a range of concentration fi'om l to 3 ppb in water of low alkalinity caused reductions in growth, survival, and fecundity of brook trout, the most sensitive species tested. Under conditions of increasing alkalinity, the maximum allowable cadmium concentration range for brook trout is 7 to 12 ppb (Eisler 1985) Invertebrates Nriagu and Sprague (1987) described cadmium toxicity in three groups of freshwater invertebrates. The most sensitive group was crustaceans, which manifested effects at an average of 62 ug/l. Within this group, the cladocerans were the most affected (19 ug/l), copepods the most tolerant (250 ug/l), and the amprious intermediate (62 ug/l Cd). Insect larvae were the most tolerant, exhibiting a broad range of tolerance fiom 840 to 233,000 ug/l. The gastropod mollusks were intermediate, ranging between 300 and 66 8,400 ug/l. According to Dobson (1992), toxicity increases as temperature and salinity increase. Plant Toxicity The content of cadmium in plants fluctuates depending on differing growing conditions and on natural variations in other factors (Commission of the European Communities, 1981). Eisler (1985) mentioned cadmium toxicity in freshwater biota, in general, at a range of cadmium concentration fiom 0.47 to 5.0 ppb. The effects of this exposure were decreases in standing crop, decreases in growth, inhibition of reproduction, immobilization, and population alterations. Dobson (1992) and EPA (1980) pointed out growth reduction as the main toxic effect in plants. Cadmium reduced the length of shoots and roots, depending on the concentration. Cadmium in soil is bound; therefore, this cadmium is not available to the plant. However, cadmium applied to the soil in nutrient solutions is more available to plant absorption. Cadmium solutions are applied to the soil frequently as fertilizer. Due to the accumulation property of cadmium, cadmium soil content increases. Effects on plant growth were seen only when cadmium concentration reached a high level. Webb (1975) mentioned roots as the part of the plant that contains the greatest concentration of cadmium. Cadmium, among all the toxic metals released in the environment, is the only one that can be stored in the human food chain in considerable quantities. Cadmium accumulates mainly in certain kinds of plants such as food crops, root crops, leafy vegetables and tobacco plants (N riagu, 1990). 67 Hallenbeck (1979) mentioned the long biological half-life of cadmium, which is about 16 to 33 years, its mobility, and efliciency of deposition as the main causes of cadmium accumulation. The accumulation of cadmium in human bodies reaches a peak at about age 50 and then remains constant. CHAPTER 8 HEALTH EFFECTS ASSOCIATED WITH CADMIUM Introduction According to Thun et al. (1989), approximately 100,000 employees in the United States are exposed occupationally to cadmium. Waalkes et al. (1992) mentioned that cadmium is a very widely known potent occupational metallic toxicant for an ample range of tissues and organ systems, whose toxicity depends on the concentration in the organ, although this varies widely with the tissue in question. Zettergren et al. (1991) and Mueller (1993) added that cadmium's effects on different organ systems include damage to the tissues of the reproductive system; induction of testicular interstitial cell cancer; structural and functional damage to liver, kidney, lung and nervous system; and disturbance of calcium metabolism, which can lead to conditions such as osteoporosis and osteomalacia. Mueller (1993) and Shaikh et al. (1987) pointed out that cadmium stays in the body for a long period, having a half-life of 10 to 30 years. This metal is stored in the liver and kidneys bound to metallothionein (MT). For this reason, if the exposure is 68 69 chronic, the accumulation of cadmium increases the body burden, causing nephrotoxicity years later even when exposure has ceased. Acute Effects Harnmens et al. (1978) described the symptoms of acute inhalation of cadmium as a metallic taste in the mouth; headache; shortness of breath, chest pain, cough with foamy or bloody sputum, abnormal pulmonary rales, and physical signs which mimic the flu; weakness and leg pains; pulmonary edema, which may lead to death or may gradually improve over several days; pneumonic consolidation; and later liver damage. Murray et al. (1981) and Waalkes et al. (1992) mentioned that in a case of brief exposure to a high dose of cadmium, the organs afi‘ected are the lungs in the case of inhalation, and the gastrointestinal tract in the case of oral exposure. The lung is the initial site of damage in high level inhalation exposure. The EPA (1989) observed that lung irritation results fi'om inhalation of air with a concentration of 1 mg/m 3 of cadmium. Bamhart and Rosenstock (1984) mentioned that acute inhalation of cadmium firmes may cause metal firme fever and chemical pneumonitis in workers only if the workplace is poorly ventilated. The symptoms of metal fume fever are fever, general malaise, and chest tightness. Chemical pneumonitis can result in death if ventilation is not improved. 70 Chronic Effects Bamhart and Rosenstock (1984) stated that long-term exposure to low levels of inhaled cadmium may cause emphysema, pulmonary fibrosis, renal insufficiency, and maybe cancer. According to Waalkes et al. (1992) and Mueller (1993), the kidneys and lungs are the critical organs afl'ected. The manifestations of lung damage are pulmonary emphysema and bronchitis. De Silva and Donnan (1981) and EPA (1989) mentioned that long term exposure at 0.02 mg/m 3 of cadmium in the air, posed a relatively small risk of lung or kidney damage but at 0.1 mg/m 3 of cadmium in the air the risk of emphysema formation and kidney damage (proteinuria) increased. The signs of damage may not appear until many years after the last exposure to cadmium. Peereboom and C0pius (1981) reported early efl‘ects of chronic exposure to cadmium as emphysema, renal lesions and proteinuria and also anemia, anosmia and yellow coloring of the teeth, at cadmium concentrations of 0.5-5 mg/m 3 in air during 10 years or longer for 8 h/day, which were found in several factories. Exposure Limits Peereboom and Copius (1981) stated exposure to 40-48 mg/m3/hr of cadmium in air causes adverse efl‘ects in humans. According to their data the lethal dose of cadmium for man is 5 mg/m 3 for 8 hours exposure. The American Conference of Governmental Industrial Hygienists set a Threshold Limit Value (TLV) at 200 ug/m 3 for Cd dusts and 100 ug/m3 for Cd fume (Peereboom and Copius, 1981; Lauweys et al., 1974; EPA, 1993). Because breathing 71 cadmium may cause lung cancer, the National Institute for Occupational Safety and Health (NIOSH) wants workers to breathe as little cadmium as possible. OSHA (1992) established three limits of exposure in the workplace. The permissible exposure limit (PEL) is a Threshold Limit Value of s ug/m 3 of all cadmium compounds (dust or fumes), which must not be exceeded in the air during any 8-hour work shift of a 40-hour work week. The action level is half of the PEL, 2.5 ug Cd/m 3, and the separate engineering control air limit (SECAL) is 15 or 50 ug/m 3. The higher value is used where it is not possible to achieve the PEL limit through engineering and work practices alone. Exposure Effects Death The US. Department of Health and Human Services (1993a) reported inhalation exposure to cadmium as a possible cause of death in humans. Pulmonary edema and chemical pneumonitis resulting from exposure to cadmium can lead to death from respiratory failure. The lowest measured concentration of cadmium in the lungs of men dying from cadmium inhalation is 1.5 ug/g wet weight. The exposure to 1-5 mg/m 3 for 8 hours could cause some deaths among exposed humans. Musculoskeletal Effects The US. Department of Health and Human Services (1993a) reported the possibility of developing calcium deficiency, osteoporosis or osteomalacia in workers after long-term occupational exposure to high levels of cadmium. According to 72 Fleisher et al. (1975), osteoporotic disease ("Itai-Itai”) developed among Japanese who ingested cadmium fi'om contaminated drinking water. Immunological Effects According to the US. Department of Health and Human Services (1993), cadmium inhalation causes a decrease in the generation of reactive oxygen species by leukocytes compared to unexposed controls. Developmental Effects The US. Department of Health and Human Services (1993) reported a decrease in birth weight of Russian babies whose mothers were occupationally exposed to cadmium at concentrations ranging from 0.02 to 35 mg/m 3. Genotoxic Efl‘ects Tang et al. (1990) reported studies that proved the existence of chromosomal aberrations in peripheral lymphocytes, resulting fiom cadmium exposure. Reproductive Efl‘ects Mason (1990) discussed a study which observed high tissue cadmium levels and some histological changes in testicular autopsy samples from men who had suffered severe cadmium fume poisoning. 73 Respiratory Effects The US. Department of Health and Human Services (1993a) and Waalkes et al. (1992) reported typical symptoms presented due to inhalation of long- term high levels of Cadmium oxide firmes or dust exposure as severe tracheobronchitis, pneumonitis, and puhnonary edema. These can lead to death if the exposure continues, and those who survive may have impaired lung function several years later. According to Waalkes et al. (1992) and the US. Department of Health and Human Services (1993a), low-level long-term exposure to cadmium fumes or dust produces chronic bronchitis, progressive fibrosis of the lower airways, alveolar damage resulting in dyspnea and emphysema, chronic rhinitis and impairment or loss of the sense of smell due to chronic irritation or necrosis of the nasal membranes. Exposure duration and level will define the severity of the disease. To evaluate respiratory effects due to cadmium exposure, Piscator (1981) considered concentration in the workplace, particle size and type of compound. Small particles such as cadmium oxide deposit mainly in the lower part of the respiratory tract and the alveoli and are relatively easily absorbed. Large particles, e. g. cadmium sulfide, deposit in the upper respiratory tract and have a relatively low solubility and absorption. Cardiovascular Efl‘ects Spieker et al. (1987) defined cadmium as a substance that significantly alters the vasopresor-induced reactivity and the stress strain characteristics of the blood vessel wall. This suggests that long-term exposure to cadmium might be associated with hypertension. Bhattacharyya and Chaudhuri (1988) studied the role of cadmium in the genesis of hypertension. They found that 34.1% of hypertension patients had 74 increased levels of cadmium in blood, urine or kidney tissues, causing cardiomegaly and neurological disturbances. They reported more cases of positive cadmium in male patients and persons residing in urban areas. Renal Effects Waalkes et al. (1992) and Piscator (1981) classified the kidney as the main organ affected by chronic exposure to cadmium. Piscator (1981) and Shaikh et al. (1987) estimated that a long-term exposure at the critical concentration of 200 ug of cadmium / kg of wet weight in the human kidney might cause damage in renal tubes. According to Waalkes et al. (1992), Peerebom and Copius (1981), Murray et al. (1981) and Thun et al. (1989), tubular disfirnction is shown as proximal tubule necrosis and chronic nephritis. Nephropathy causes an acquired Fanconi syndrome, an increase in low molecular weight proteinuria, arninoaciduria, glucosuria, azotemia (secondary to chronic interstitial scaring), and changes in calcium metabolism (hypercalciuria). This altered calcium metabolism results in an increase in calcium excretion and the formation of renal calculi. Peereboom and Copius ( 1981) mentioned an elevated level of renal stones among industrial cadmium workers. Waalkes et al. (1992) reported women suffering with Itai-Itai disease who developed severe osteomalacia and osteoporosis. De Silva and Donnan (1981) described a company that manufactures cadmium selenosulphide and cadmium sulphide pigments in England. They studied only the cadmium in the color production section, in which exposure was high in many locations. Cadmium carbonate and cadmium sulphide were produced by precipitation, then filtered and dried. After drying, the carbonate and sulphide were crushed, milled, blended with selenium and sulphur, and calcined to produce red and yellow pigments, respectively. The drying stage is the one which produced the highest amount of dust. 75 The cadmium concentration was ten times higher than 0.05 mg/m3 which is the hygiene standard recommended by the British Occupational Hygiene Society. They observed signs of renal damage in the 6 workers who had worked in the production plant for 7 years or more. In addition, two of these men exhibited exertional dyspnea, and respiratory obstruction with mild symptoms. Cancer The US. Department of Health and Human Services (1993) and Waalkes (1992) described experimental results that relate cadmium exposure to risk of lung cancer as conflicting. Confounding factors such as exposure to other metals and smoking may explain observed increases in cancer rates. The data did not show enough evidence to confirm that an increased risk of lung cancer in humans followed prolonged inhalation exposure to cadmium. According to Kjellstrom et al. (1979), four prostatic cancers were observed among 248 workers with a minimum of 1 years exposure to cadmium oxide. The expected rate was 0.58 prostatic cancers. The IARC concluded that occupational exposure to cadmium in some form increases the risk of prostate cancer in man. Heavy exposure to cadmium therefore causes an excessive death rate from prostatic cancer (Piscator, 1981). Sarcomata at injection sites in rats have been found after subcutaneous or intramuscular injections of low doses of cadmium in the form of metal powder and sulfide. Higher doses produced testicular tumors (Piscator, 1981). CHAPTER 9 ENVIRONMENTAL EFFECTS ASSOCIATED WITH MERCURY Introduction The Agency for Toxic Substances and Disease Registry (1992) classified mercury in three groups: elemental mercury, inorganic mercury salts, and organic mercury. Elemental mercury is volatile when it is heated. The EPA (1987) considers mercury as a hazardous air pollutant. According to Leonard et al. (1983), the electrical apparatus industry uses 25% of the mercury produced; the chlorine-alkali industry uses 20%; the ship-bottom paints industry uses 15%; the industrial and control instruments industry uses 10%; the dental preparations industry uses 5%; and laboratories, pharmaceuticals, amalgams and catalysts use 15%. 76 77 Catalysts Kew (1980) and Nriagu (1979a) emphasize the importance of mercury as a catalyst used in the synthesis of vinyl chloride and vat dyes. These catalysts are employed for converting acetylene into acetaldehyde, vinyl chloride and vinyl acetate; the last two being the starting materials for the production of polyvinyl chloride (PVC) and polyvinyl acetate (PVA). The catalysts are commonly mercuric chloride (vinyl chloride) and mercuric sulfate (vinyl acetate). Carbon pellets impregnated with mercuric chloride are the major source of contamination. In the dyestuff industry, mercuric sulfate is used as a catalyst in the production of anthroquinone derivatives of dyes. Organomercurial salts have also been used as catalysts in the production of urethane and urethane resins. The disposal of spent catalysts to the land is the major source of release of mercury in this category. Only 100 kg/year is released to air and 200 kg/year to water. Because recovery of mercury from mercurial catalysts is not economical, mercury is being effectively replaced by other materials. Air The Agency for Toxic Substances and Disease Registry (1989) reported a concentration of mercury in the atmosphere of 20 ng Hg/m3. The anthropogenic releases of mercury to the atmosphere have been estimated to be 2,000-3,000 metric tons/year, mostly fi'om the mining and smelting of mercury ores, industrial processes involving the use of mercury, and combustion of fossil fuel. 78 Water The Agency for Toxic Substances and Disease Registry (1989) estimated a concentration of mercury in fresh water of 0.025 ug Hg/l. The level of inorganic mercury in rivers, lakes, and streams is limited to 144 ug/l of water, and all releases of more than one pound of mercury metal need to be reported. The FDA level of mercury in bottled water is no more than 2 ug/l, and the EPA's limit is 0.021 milligrams of inorganic or organic mercury per day in food or in water. Mercury may also be released to surface waters in effluents fiom a number of industrial processes including ink manufacturing. Kew (1980) mentioned levels of 0.2-85 ug/l of mercury in urban runoff, and 0.2 ug/l to 0.6 ug/l in storrnwater and combined sewer runofl‘ in 11 cities across the US. The Agency for Toxic Substances and Disease Registry (1992) noted an elevated mercury level in 25% of groundwater and surface-water samples fiom 2,785 hazardous waste sites tested. Industrial processes that may result in mercury-containing effluent include chloride and caustic soda production , mining and ore processing, metallurgy and electrOplating, chemical and ink manufacturing, paper milling, leather tanning, textile manufacturing, and pharmaceutical production. Soil and water microorganisms methylate mercury. The resulting substance is methyl mercury, which accumulates rapidly in fish and other aquatic organisms. This compound accounts for 70 to 90% of the total mercury detected in fish. The mercury concentration in fish at the top of the food chain is typically biomagnified up to 100,000 times the concentration in surrounding waters. Predacious fish can have more than 50 times the average mercury concentration found in most other fish. Fish and fish products have concentrations of mercury from 0.1 to 0.22 mg Hg/kg fish. This amount is below the 79 FDA limit for edible fish of 0.5 mg/kg (Agency for Toxic Substances and Disease Registry, 1992) . Minamata Bay in Japan was contaminated with mercury in the 1950‘s by eflluent discharged from a factory that used a mercury catalyst. Fish consumed from this bay poisoned hundreds of people, causing 41 deaths. Studies of methyhnercury concentrations in the blood of newborns showed a significant correlation with maternal blood levels. Damage to the fetal nervous system and derangement of developmental processes such as neuronal migration and neuronal cell division were seen in newborns whose mothers were exposed to contaminated fish (Agency for Toxic Substances and Disease Registry, 1992) . Landfills and Soil According to Kew (1980), the sources of release of mercury in land areas are landfilling and lagooning of industrial and municipal sludge, flyash disposal, and agricultural applications. Mercury migration to groundwater probably happens only in poorly operated landfill sites. However, we need to consider that over one-half of the US. landfill sites did not comply with regulatory requirements. Little information is available concerning mercury contamination through sludge and fertilizer application to agricultural sites. Mercury in the sludge is assumed to be less available for biological uptake and leaching. Accumulation in the soil surface is likely for mercury applied in this form. 80 Animals Taylor (1979) mentioned that since mercury is a well-known aquatic pollutant, it is included in the black list of all the international conventions such as the Oslo, Paris and Barcelona Conventions and the EEC Directive on the discharge of dangerous substances. Eisler (1987) listed early developmental stages as the most sensitive in all organisms tested, and methylrnercury as more toxic than inorganic forms. Lethal concentrations of total mercury to sensitive organisms varied fiom 0.1 to 2.0 ug/l of medium for aquatic fauna; from 2.2 to 31 mg/kg body weight (acute oral) and 4 to 40 mg/kg (dietary) body weight for birds; and fiom 0.1 to 0.5 mg/kg body weight and l to 5 mg/kg body weight for mammals. Mercury is a known mutagen, teratogen, and carcinogen. At comparatively low concentrations in birds and mammals, it adversely affects reproduction, grth and development, behavior, blood and serum chemistry, motor coordination, vision, hearing, histology, and metabolism. It has a high potential for bioaccumulation and biomagnification, and is slow to be metabolized by the body (Eisler, 1987). Aquatic Organisms According to Eisler (1987), toxic concentrations of mercury salts ranged from less than 0.1 ug/l to more than 200 ug/l for representative species of marine and freshwater organisms. Concentrations lower than 2.0 ug/l were usually associated with early developmental stages, long exposures, and flow through tests. Among metals tested, mercury was the most toxic to aquatic organisms. Signs of acute mercury poisoning in fish included flaring of gill covers, increased fiequency of respiratory movements, loss of 81 equilibrium, sluggishness, and effects on the reproduction, growth, behavior, metabolism, blood chemistry, osmoregulation, and oxygen exchange. Reproduction was inhibited among sensitive species of aquatic organisms at water concentrations of 0.03 to 1.6 ug Hg/l. Reduced growth of sensitive species of aquatic organisms has been recorded at water concentrations of 0.04 to 1 ug Hg/l. Signs of chronic mercury poisoning included emaciation, brain lesions, cataracts, diminished response to change in light intensity, inability to capture food, abnormal motor coordination, and various erratic behaviors. In general, the accumulation of mercury by aquatic biota is rapid, and depuration is slow. Kew (1980) reported on chronic or sublethal toxicity for freshwater invertebrates. Minimum chronic effects levels for Dahnia magria were 0.9 ug/l and less than 0.01 ug/l for HgC12 and CH3HgCl, respectively. The lowest concentration of mercury resulting in sublethal effects in marine finfish was 10 ug/I HgClz, causing abnormal deve10pment in the mummichog Fundulus Heteroclitus and decreased respiration in the winter flounder, PseudofpleuronecieS americanus. The mean number of broods of brine shrimp decreased with concentrations of 1 ug/l and 10 ug/l HgClz and of 1 ug/l CH3HgCl, and adult reproductive lifespans were reduced at concentrations of 10 ug/l HgClz and 5 ug/l CH3HgCl. However, 10 ug/l HgC12 had no effect on the average number of offspring produced in each brood, while 1 ug/l CH3HgCl significantly reduced the fecundity of the shrimp. The fiddler crab exhibited an increased metabolic rate when exposed to 1.8 ug/l HgClz. Sublethal efl‘ects in other invertebrates included decreased egg production, reduced shell growth, and inhibition of limb regeneration. 82 Terrestrial Organisms According to Eisler (1987), mercury causes teratogenic, mutagenic, and carcinogenic effects in mammals; the fetus is the most sensitive life stage. Methylmercury irreversibly destroys the neurons of the central nervous system. Dietary concentrations of 3 mg/kg CH3HgCl produced adverse reproductive effects in mallards and black ducks; oral doses of 13 mg/kg and 60 mg/kg were lethal to goshawks and ducklings, respectively. Birds Eisler (1987) depicted the signs of mercury poisoning in birds as muscular incoordination, falling, slowness, fluffed feathers, calmness, withdrawal, hyporeactivity, hypoactivity, and eyelid drooping. Sublethal effects of mercury, administered by a variety of routes on birds, included adverse effects on growth, development, reproduction, blood and tissue chemistry, metabolism, and behavior; histopathology and bioaccumulation were also noted. Plants Kew (1980) reviewed the effects of residues of 0.6 mg/kg and 10 mg/kg of mercury on maize seedlings. This concentration inhibited growth in the shoots and roots respectively. Methylmercury can act directly upon the genetic material of plants, producing chromosome fiagmentation, somatic mutations and pollen sterility According 83 to Siegel et al. (1984), mercury vapor, primarily elemental mercury, can accelerate senescence-related processes due to accelerating the production of ethylene. CHAPTER 10 HEALTH EFFECTS ASSOCIATED WITH MERCURY Introduction Because mercury evaporates at room temperature and quickly builds up in the air as an odorless vapor, it needs to be handled carefully. This vapor is monatomic and lipid soluble. Therefore, 80% of mercury vapor inhaled will be absorbed through the alveoli upon inhalation (McCarthy, 1993 and Cragle et al., 1984). Mercury Concentration Limits Cragle et al. (1984) reported nonspecific symptoms such as shyness and loss of appetite in men exposed to less than 0.1 mg/m3 time-weighted average (TWA) air concentrations of elemental mercury. Many organizations report their limits of mercury in the workplace as the threshold limit value that is the Time Weighted Average (TWA) for an eight-hour day or 40-hour week. The Occupational Safety and Health Administration (OSHA) TWA for organic mercury is 0.1 mg/m3, and for inorganic vapor is 0.05 mg/m3. The National 84 85 Institute for Occupational Safety and Health and the American Conference of Governmental Industrial Hygienists TWA for inorganic mercury is 0.050 mg/m3 (Burt, 1986; McCarth, 1993; Kew, 1980; Agency for Toxic Substances and Disease Registry, 1989 and Tierney et al., 1979) . Mercury Exposure Indicators Cragle et al. (1984) and Burt (1986) found urine mercury levels as a good indicator of personal exposure to inorganic mercury but not predictors of symptoms. The World Health Organization (WHO) uses a 1:2 ratio to relate air concentration of inorganic mercury in ug/m3 and urine mercury levels in mg/l. According to Susuki et al. (1991), slight effects on the central nervous system may occur in groups of workers with average urinary mercury levels of about 5 ug/g creatinine and possibly lower. Acute Effects Nriagu (1979a) pointed out that inorganic mercury is rapidly lost from the body. Therefore, exposure effects may disappear if the worker is removed from exposure for a period of time. Only in the case of recurrent exposures and toxicity, do manifestations of mercurialism become chronic. Nriagu (1979a) and Cragle et al. (1984) indicated that acute toxicity due to inhalation of miligrams of mercury can cause, after a delay of a few hours, a metal firme fever with symptoms of nausea, abdominal cramps, diarrhea, muscle aches, fever and an 86 elevated white blood cell count and, within a few days, a metallic taste as well as further inflammation of the gums, loosening of the teeth, ulcers of the mouth and a blue line at the gum margins. In extreme instances, the exposure victim may die of acute chemical pneumonitis. Roels et al. (1982), Nriagu (1979a) and Kew (1980) noted that the central nervous system and the kidney are the two major organs affected by mercury exposure. In low doses, mercury may induce renal and liver disease, and occasionally a tremor is noted. The Agency for Toxic Substances and Disease Registry (1992) pointed out that in a survey performed by NIOSH, 70,000 workers were estimated to be potentially exposed to mercury in the workplace. In this number were included ink manufacturing workers. Chronic Effects Kew (1980) noted that the beginning of chronic mercury poisoning is often slow and insidious. The effects of mercury exposure appear in sequences. It begins with progressive numbness of the distal parts of the extremities and often of the lips and tongue, and is followed by an ataxic gait, clumsiness of the hands, dysarthria, dysphagia, deafiiess, and blurring of vision. The EPA (1987a) pointed out that exposure to levels below 0.1 mg Hg/m3 causes non-specific symptoms such as introversion, insomnia, and anxiety. Kew (1980) reported that inhalation of 0.1 to 0.6 mg/m3 of mercuric chloride may cause non-specific signs such as insomnia, loss of appetite and weight loss. According to the EPA (1984, 1987a) and Kew (1980), in the workplace, chronic mercury vapor intoxication has resulted in mental disturbances (short term memory loss and changes in personality characteristics), objective tremors, and gingivitis, at average air 87 concentrations less than 0.1-0.2 mg Hg/m3. Tremor is caused by the motor disfunctioning of the central nervous system. Systemic Effects Gingivitis Gingivitis was defined by McCarthy (1993) as a disease caused by poor dental hygiene, and is seen initially as sore gums. According to McCarthy (1993) and Nriagu (1979a), atrophic changes appearing in the gums, known as gum disease, is a common sign of chronic high level mercury vapor exposure. The gums initially become swollen and boggy and later retract. In individuals who have pre-existing pyorrhea, evidence of infection can be aggravated. In severe cases, there can be loosening of the teeth with bony re-absorption of the jaw. With severe chronic exposure, one can even note necrosis of the lower jaw like the oral pathology noted in acute vapor toxicity. Gastrointestinal Effects The Agency for Toxic Substances and Disease Registry (1989) lists common symptoms from acute exposure to mercury vapor as nausea, vomiting, gingivitis, and mercurial stomatitis. 88 Cardiovascular Effects The Agency for Toxic Substances and Disease Registry (1989) reported that acute inhalation of metallic mercury vapor can result in increased blood pressure. Renal Effects McCarthy (1993), the Agency for Toxic Substances and Disease Registry (1989) and Nriagu (1979a) remarked on the effects of mercury exposure on the renal system. The kidney has a remarkable capacity to concentrate mercury, due to its ability to eliminate mercury from the body, and is a target organ when inhalation exposure to metallic mercury occurs. The first sign of kidney damage is increased creatinine excretion, which means renal insufliciency, followed by damage of the proximal tubules. Dermal/ocular Effects The Agency for Toxic Substances and Disease Registry (1989) pointed out that acute exposure for 2 weeks to mercury concentrations less than 1 mg/m3, and intermediate exposure for 2 months at unspecified concentrations, resulted in the beginning of erythematous and pruritic skin rashes. Ocular effects observed from this same acute exposure included red, burning eyes and conjunctivitis. Nriagu (1979) and the Agency for Toxic Substances and Disease Registry (1989) stated that workers chronically exposed to low concentrations of mercury exhibited mercurialentis, which is a peculiar grayish-brown or yellow haze on the outer surface of their lenses, decreasing visual acuity. 89 Musculoskeletal Effects Kew (1980) mentioned the existence of spasticity and rigidity due to exposure to mercury. Muscle stretch reflexes are usually maintained or become hyperactive, and extensor plantar responses are occasionally presented during the later stages. Insomnia, agitation, hypomania, and the loss of emotional control are frequently noted, and most individuals have abnormal involuntary movements, including choreoathetosis, myoclonus, and coarse resting and action tremors. McCarthy (1993) reported that employees subjected to exposure to high concentrations of mercury oxide particles and vapor for 60-80 hours a week, 7 days a week, presented incapacitating muscular pains of the lower back and extremities, severe burning sensations of the feet and lower legs, muscle cramps, and muscle fasciculations. Neurological Effects According to Burt (1986) and Williamson et al. (1982), the central nervous system is the part of the body most severely affected by chronic high-level mercury exposure. This causes long-lasting and deep neurological damage. The initial outcomes of toxicity consist of fine tremor and erethism. Tremor McCarthy (1993) and Nriagu (1979) stated that tremors are the earliest and most notable mark of chronic exposure to moderate levels of inorganic mercury. It is seen at the beginning as a fine tremor in the hands; then it develops to a fine postural tremor. This is associated with trouble in accomplishing fine movements, in coordination, difficulty with gait (ataxia) and even hoarseness due to ataxia of the vocal cords. With greater or longer- 90 period exposures, the tremor multiplies in amplitude and becomes coarse, which is aggravated by voluntary movements. As the severity of the tremor increases, it can be interrupted by clonic-like jerks of one or more extremities. This progresses to involve the entire body as well. Erethism McCarthy ( 1993) and Nriagu (1979) defined erethism as a form of psychic disturbance. Workers affected experience nervousness, irritability and change of temperament. They become easily upset and embarrassed and lose self-confidence, and often have a feeling as if they are being watched. They usually have headaches, drowsiness, insomnia, fatigue or flushing. Williamson et al. (1982) compared a group of 12 chronically mercury-exposed workers with a matched control group. The mercury-exposed group showed poorer psychomotor co-ordination and premature fatigue, although simple motor responses were not affected. General arousal levels also remained unaffected, but mercury-exposed workers were superior in sustaining attention. In spite of this, mercury-exposed groups showed clear deficits in short-terrn memory. Respiratory effects The Agency for Toxic Substances and Disease Registry (1989), Milne at al. (1973) and Nriagu (1979a) discuss respiratory effects as a result of mercury vapor intoxication. Due to inhalation of metallic mercury vapor through the lungs, the metal is absorbed, causing pulmonary irritation with chest tightness, a cough and shortness of breath followed by pulmonary edema, lobar pneumonia, desquamation of the bronchiolar epithelium, and death. The resulting obstruction (bronchiolar blockage by mucus and fluid) 91 results in alveolar dilation, emphysema, and pneumothorax. Death can occur due to these puhnonary effects. Survivors can acquire chronic shortness of breath as well as interstitial fibrosis of the lungs. The Agency for Toxic Substances and Disease Registry (1989) separated human health effects fi'om breathing metallic mercury into short-term and long-term exposure. At levels in air of O. 13 ppm for 3 hours, workers experienced chest pains, shortness of breath and cough. At levels in air of 5.4 ppm for 8 hrs, workers experienced persistent irritability, lack of ambition and lack of sexual desire. At levels in the air of 1.1 to 44 mg/m3 for 4-8 hours workers exhibited chest pains, dyspnea, cough, hemoptysis, impairment of pulmonary firnction (reduced vital capacity), diffirse pulmonary infiltrates, and evidence of interstitial pneumonitis. At levels in air of 0.0032 ppm for 15 years, the workers experienced shakiness. Developmental Effects The Agency for Toxic Substances and Disease Registry (1989) and Clarkson (1993) stated that women exposed to methylrnercury in fish may give birth to babies with severe brain damage. This happened in the Minamata Bay case, where 30 cases were reported. The mothers experienced no symptoms or only mild effects such as transient paresthesia. The prenatal brain damage was diffuse and widespread, due to interference with neuronal migration. The occurrence of microcephaly suggested that cell division had been suppressed. In women chronically exposed to metallic mercury vapor, increased fi'equencies of menstrual disturbances and spontaneous abortions were seen. 92 Mutation According to the EPA ( 1984) and the Agency for Toxic Substances and Disease Registry (1989), chromosomal anomalies such as aneuploidy have been reported in lymphocytes from whole blood cultures of workers occupationally exposed to organic or inorganic mercury compounds, mainly by inhalation. Also, chromosome aberrations were reported in workers exposed to metallic mercury vapor. CHAPTER 11 ENVIRONMENTAL EFFECTS ASSOCIATED WITH LEAD Introduction Lead is not essential nor beneficial to any living organisms (Eisler, 1988). Lead is incorporated in animals and humans by inhalation, ingestion, dermal absorption, and placental transfer to the fetus. Uses Lansdown and Yule (1986) estimated the world production of lead in 1986 as 5 million metric tons. Since 1981 the consumption of lead by industry has decreased in the USA and UK. Winder (1984) discusses the use of lead 11 carbonate as a pigment. In the manufacturing of this material, sheets of lead undergo slow decomposition under the action of acetic acid vapor, moist air and carbon dioxide. Other lead compounds used as pigments are Lead H chromate (chrome yellow) and basic chromate (chrome red). Pigments used in paints have been replaced due to their toxicity. The substitute for lead 93 94 pigments in paints is titanium dioxide due to its opacity, covering power, cheapness, stability, and of course, safety. Lansdown and Yule (1986) discuss use of lead as a stabilizer in the manufacturing of certain plastics. Polyvinyl chloride is stable over a broad temperature range due to the use of lead carbonate or lead silicate during processing. Lead dithiocarbonate is used also as an accelerator in the manufacture of rubber. Packaging Inks Lavelle and Fetsko (1977) listed pigments based on lead as white lead, basic lead sulfate, chrome yellows, phloxine toner, molybdate orange and chrome green. Among these pigments, white lead and chrome yellow cause concern among manufacturer. White lead causes poisoning in cases of ingestion of paint chips. Chrome yellow used in printing ink is the one which increases the content of lead in printed materials. Lead-based pigments are no longer used in printing inks and have been replaced by cobalt or manganese compounds. Lead-based pigments are part of different kinds of industrial coatings. Their low cost, good dispensability and opacity make them popular. Lead-based coatings are not considered hazardous because they are insoluble . 20 years ago lead content in paper used in the food industry ranged from 2 to 10,000 ppm depending on the quantity of printing and color of ink. Printed paper packages contained more lead than unprinted material, although some unprinted ones contained up to 58 ppm due to the use of recycled paper or virgin mixed with recycled paper (Heichel et al., 1976). The amount of lead in paper, both recycled and virgin, has decreased because of the decrease of heavy metal pigment used. Lavelle and F etsko (1977) referred to the British Printing Ink Manufacturer’s clause b (ii) that limited lead content in immediate food wrappers for ice cream and ice lollies, and marking inks for pencils. The Society of British Printing Ink Manufacturers 95 recommended the elimination of lead and lead chromates from all printing inks in UK. Hankin et al. (1974) mentioned the FDA regulation issued around 1950 which limits the use of lead by food packaging industries. According to such regulations, lead cannot exceed 0.06% (600 ppm) of the total weight of dried paint film on the package. The Hazardous Substances Act bans any paint or surface coating material intended for use in or around the house that contains more than 0.5 % (5000 ppm) lead in the coating. Hutchinson (1979) stated that the European Economic Community Directive mandates the labeling of printing inks with a harmful symbol where the soluble lead content is equal to or exceeds 1%. Disposal of printing ink refuse can be simplified by the elimination of lead containing materials. The increase of lead content in recycled packaging material, potentially contaminating food products, can be avoided by reducing the content of lead- based ink used in the package, such as in corrugated cases where contamination of the content can be reduced by using flexographic inks formulated with lead-free pigments (Hutchinson, 1979) . Organic pigments are replacing pigments such as Primrose chromate, Lemon chrome, Mid chrome and scarlet chrome shades. Difficulties arise in the matches for flexo inks for black colored grounds, films and foil, scarlet chrome and mid-chrome shades. Lead chromate give a broad variety of shades that in many cases is difficult to substitute. In addition, the new organic pigments used to replace lead-based pigments are relatively high in cost (Hutchinson, 1979). Air Lansdown and Yule (1986) estimated anthropogenic emissions of lead from mining as 8.2 tonnes/year , from primary lead production as 31 tonnes/year, from primary non-ferrous production as 45.5 tonnes/year, from secondary smelting as 0.8 tonnes/year , from iron and steel production as 50 tonnes/year, from industrial uses as 7.4 tonnes/year, from coal combustion as 14 tonnes/year, from petrol combustion as 273 tonnes/year and from waste incineration as 10.4 tonnes/year . The total anthropogenic emission of lead was estimated as 449 tonnes/year in 1980 . According to Needleman (1991), lead in the atmosphere derived from human activities, especially combustion of oil and its derivatives, has changed the natural cycle of lead. The concentration of lead in urban areas is greater than the concentration in rural and sub rural areas. These concentrations average 1 ug/m 3 to 3 ug/m3 in urban areas, 0.1 ug/m3 in suburban areas, and less than 0.05 ug/m3 in rural areas (Tierney at al., 1979). Soil According to Lansdown and Yule (1986) and Needleman (1991), due to its long half-life in soil, lead is in general immobile. Lead can persist in soil for many years after deposition has stopped. Needleman (1991) pointed out that lead associates with dust (small particles) in soil. If these particles are resuspended in air, they can stay suspended for a long time. Dust with high lead content, therefore, is hazardous because it is not visible and can remain 97 trapped in carpet and upholstery. The concentration of lead in soil ranges from 10 to 50 ug/g in rural areas, and from 100 to 10,000 ug/g in urban areas. Water Needleman (1991) mentioned the presence of lead in small quantities in ground and natural surface water. Due to the insolubility of lead compounds, the concentration of lead in water supplies is low, with concentrations averaging less than 5 ug/l. Aquatic Organisms Eisler (1988) stated that lead is toxic to all aquatic biota. Waterbome lead is the most toxic. Lead concentrations of more than 10 ug/l in water produce spinal curvature; anemia; darkening of the dorsal tail region, producing a black-tail effect due to selective destruction of spinal neurons; ALAD inhibition in erythrocytes, spleen, liver, and renal tissues; reduced ability to swim against a current; destruction of the respiratory epithelium; basophilic stippling of erythrocytes; elevated lead concentrations in blood, bone, gill, liver, and kidney; muscular atrophy; paralysis; renal pathology; growth inhibition; retardation of sexual maturity; altered blood chemistry; testicular and ovarian histopathology; and death in fish. Although lead is concentrated by biota from water, there is no convincing evidence that it is transferred through food chains. 98 Birds Eisler (1988) discussed mortality in waterfowl and other birds due to ingestion of spent lead shot. In sensitive birds, a reduction in survival rate was seen at doses of 75 to 150 mg Pb+2/ kg or 28 mg alkyl lead/kg. Signs of toxicity in birds are loss of appetite, lethargy, weakness, emaciation, tremors, drooped wings, green liquid feces, and impairment of locomotion, balance, and depth perception. Plants Eisler (1988) referred to lead as a non-essential element for plants. On the contrary, high amounts of lead cause growth, photosynthesis, mitosis and water absorption reduction. Due to the long half-life of lead in soil, several hundred mg lead/kg in soil are needed to result in any adverse efl‘ects. Lansdown and Yule (1986) studied the uptake of lead by plants. They stated that lead in edible plants is unaffected by increasing lead content in soil. Therefore, lead content in foodstuffs is limited. CHAPTER 12 HEALTH EFFECTS ASSOCIATED WITH LEAD Introduction Hutchinson (1979) mentioned inhalation and ingestion as the only sources of lead poisoning in the printing industry, and small quantity exposure at regular periods of time as the most prevalent cause of poisoning. Inhalation of dust and fine powder is the major occupational risk. For these reasons, dust in workplaces needs to be kept to an absolute minimum. Needleman (1991) estimated that 40 - 50% of the lead inhaled is absorbed. Small particles (1 to 2 um) are trapped in the upper respiratory tract and passed to the digestive tract to be ingested. The remaining particles pass to the lower lung. Eisler (1988) described progressive development of lead poisoning as mild or severe dysfirnction of the alimentary tract as shown by loss of appetite, constipation, abdominal cramps, headaches, general weakness, fatigue, atrophy of forearm extensor muscles, or paralysis of these muscles and more striking atrophy. Lead encephalopathy occurs frequently in lead-poisoned infants and young children. According to OSHA (1975), the threshold limit value for lead for an 8 hour-day in the workplace is 50 ug/m3. OSHA suggests care in the handling of lead and its compounds. Workers who do not practice personal hygiene are at big risk. It is necessary 99 100 to wash any clothes used at work and shower before returning home. Alexander (1989) reported elevated blood lead levels among children of lead-exposed workers due to high levels of lead in the parents' clothing. Eisler (1988) and Winder (1984) considered the hazardous increase of lead contamination in the environment. Exposure to environmental lead concentrations can put human health at risk. 7 ug of lead/1 in human blood is enough to produce chronic symptoms in humans. Such concentration is close to the 2.3 ug/l that is the present average concentration of lead in human blood. Therefore, it is necessary to keep environmental lead levels to minimum. N eurotoxicity According to Winder (1984), exposure to lead for a long period of time may cause hyperactivity, mental retardation, intellectual and psychological impairment, and other behavioral changes. Urban air may contain enough lead to cause impairment of brain firnction in children. Needleman (1991) and Singhal and Thomas (1980) recognized that children ingest lead existing in the environment in forms such as dirt and dust. They referenced studies of children living in urban areas who had difficulties in completing intelligence, perceptual motor, and memory tests. Singhal and Thomas (1980) pointed out behavioral changes as the most permanent and dimcult effects to diagnose. The initial symptoms of behavioral changes are depression, insomnia, irritability, memory impairment, and clumsiness, which are diflicult to recognize as low-level lead exposure symptoms. The disease develops to encephalopathy, beginning with intractable seizures, and leads to coma and death within a short period of time. In some cases, incidents of vomiting, drowsiness, altered consciousness (stupor), deep ataxia, muscle weakness or tremor, numbness, paralysis, or 101 persistent headache, or depression may be observed, after which the patient becomes comatose. Singhal and Thomas (1980) and Winder (1984) described peripheral nerve damage as the most insidious abnormality in workers exposed to lead. Damage to peripheral nerves causes motor disorders such as atrophy of muscles in the forearm and upper arm. Needleman (1991) mentioned some central nervous system related symptoms as visuomotor abnormalities and uncontrolled fine movements at a lead exposure level of 0.4 mg/ cc in blood. Chronic lead exposure caused. deficits in short-term memory, and visual acuity was affected. Reproductive Effects Singhal and Thomas (1980) reported abortions in women and sterility in men exposed to lead in printing operations. According to the World Health Organization ( 197 7), lead poisoning and moderately increased lead absorption decreased male fertility due to lead's effects on gonad function. Lead not only affects the viability of the fetus, but development as well. Developmental consequences of prenatal exposure to low-levels of lead include reduced birth weight, reduced brain development, and premature birth. 102 Renal Effects Singhal and Thomas (1980) considered acute and chronic renal damage as lead toxicity effects. Acute renal damage signs are situated in the proximal tubular epithelium, involving changes in membrane functions and in energy metabolism, structural aberrations of mitochondria, and the appearance of pathognomonic morphological features in nuclei and cytoplasm of proximal tubular epithelial cells. Singhal and Thomas (1980), the US. Department of Health & Human Services (1990), and the World Health Organization (1977) mentioned severe acute neophropathy symptoms such as arniniaciduria, glycosuria, and hypophosphatenria , which result from depressed tubular reabsorption. Prolongation of the acute exposure leads to chronic lead neophropathy, which is usually associated with gout and hypertension. Hypertension is directly associated with atherosclerosis, coronary artery disease, heart disease, stroke, and end-stage renal disease. Renal disease, hypertension, and cerebrovascular disease are frequently reported as significant causes of excess mortality in lead workers. Gout may develop as a result of lead- induced hyperuricemia. Cancer Singhal and Thomas (1980) stated that lead exposure can cause the development of tumors (adenomas or adenocarcinomas) in the renal cortex. This development is induced by large doses of lead in the kidney in a short period of time. 103 Gastrointestinal Effects The World Health Organization (1977) mentioned that in low-level lead exposure, acute pain in the abdomen can result. Such a symptom is consider a warning to avoid prolonged periods of exposure that can result in severe effects. Cardiovascular Effects The World Health Organization (1977) mentioned toxicity in the heart due to lead exposure. The toxicity manifestations were increased capillary permeability, and atherosclerosis. Mutagenic Effects The World Health Organization (1977) reported chromosomal aberrations in workers exposed to zinc, cadmium and lead. It was concluded that lead was responsible for the aberrations. Eisler (1988) pointed out that aberrations occurred in human blood lymphocytes . 104 Hematological Effects The US. Department of Health & Human Services (1990b). stated that lead enters the human body and inhibits the production of hemoglobin in blood, causing two types of anemia. Hemolytic anemia results when the body is exposed to acute high levels of lead. CHAPTER 13 THE DESIGN OF THE INVESTIGATION AND ANALYSIS OF DATA The Study Population This study was limited to companies which manufacture inks for the packaging industry. Individuals in charge of manufacturing, development or research operation ill their company were asked to respond to the questionnaire. The population for this investigation was selected from ink manufacturing companies classified by the National Association of Ink Manufacturers. Two hundred twenty-four companies were identified, each one receiving one questionnaire for a total of 224 possible respondents. The Instrument The format used for the instrument was as follows (see appendix B). The first page included the purpose of the study and general return instructions. The statement of the problem spelled out twenty-five questions to be answered. Three of the questions requested specific responses indicating the interest in the CONEG Model Toxics in Packaging legislation. Six questions requested information pertaining to limitations of heavy metal in inks and to written certificates of compliance required by the packaging 105 106 industry. Four of the questions required specific responses which indicated the increase of cost and/or price as a result of heavy metal content reduction. Five questions requested information pertaining to substitution of inks that contain heavy metals. The next two questions involved substitution for petroleum oil inks. The last questions in the questionnaire indicated the awareness of any tests and regulations related to use of heavy metals. The Mailed Questionnaire Survey The questionnaires were mailed to 224 individuals representing the different ink manufacturing companies. Three and one-half weeks later, 51 questionnaires had been returned. The returned instruments included 2 that had no forwarding address and 17 that indicated the respondent was no longer responsible for the activities described in this investigation. The net result at this point was 32 completed questionnaires, or 14%, a very good response rate for a survey of this type. The percentage of replies to the survey was considered adequate to draw conclusions for this investigation. The survey provided a good number and distribution of responses. The number of personal comments returned with the survey instrument indicated that those individuals who did respond were doing so out of genuine interest in the problem. 107 Describing the Data The data accumulated through the survey instrument will be summarized through statistical means, so that the results will indicate the most frequent option chosen. The descriptive survey method was used to design and carry out the data collection process for this investigation. The data were arranged on an ordinal scale and thus will be described using descriptive statistics. Descriptive statistics is based upon central tendencies, a means of describing the typical or average values and variability, the spread or extent of the values (Hays, 1994). Measures of central tendency are the mean and median. The arithmetic mean is calculated by adding the observations and dividing by the number of observations. The median is the point at or below which precisely 50% of the cases fall. The mean is the most serviceable measure for purely descriptive statistics and for distributions which lack a clearly dominant single peak (Hays, 1994 and Juran et al. 1974). Therefore, it will be used for this investigation. The literature did not record any general rules to follow in setting numeric values for the responses presented in the instrument. We selected the following numbers to describe the data: ' Never ............................................... l Sometime .......................................... 2 Usually .............................................. 3 Frequently ......................................... 4 Always .............................................. 5 or None of them ...................................... l 108 Some of them ...................................... 2 Most of them ....................................... 3 All of them ........................................... 4 The mathematical formula for calculating the mean is (Edward, 1967) : Mean= sumf X/sumf Where: X= Level of importance or midpoint of range percent sum f X = the sum of the product of frequencies and X per range sum f = the total number of fiequencies Profile of the Responses The questionnaire asked the respondents to provide information concerning heavy metals used in ink formulation. Table I provides a summary of the responces. Of those companies responding, 94 percent (30 of 32) use copper in their inks, followed by zinc and lead with 53 percent and 44 percent respectively. Respondents were asked about the Model Toxics in Packaging legislation as developed by the Coalition of Northeastern Governors (CONEG) Source Reduction Council. It was found that all the companies surveyed were familiar with this legislation. However, only three companies in New Jersey, two in Massachusetts, and one in Pennsylvania are in states which have enacted this legislation, limiting the total quantity of lead, cadmium, chromium (VI) and mercury to 100 ppm. 22 percent of the respondents did not know if their states had passed this regulation. 109 TABLE I WHICH OF THESE HAS YOUR COMPANY USED IN INK FORMULATION? hks Frequency Percent Copper 30 93.8% Zinc 17 53.1% Lead 14 43.8% Cadmiun 8 25.0% Chromilm (VI) 9 28.1% Mercuy 3 9.4% Net Respondents 32 100.0% 110 Twenty-eight of thirty-two companies surveyed limit the amount of heavy metals in their inks. Table II shows reported limits on heavy metals and the source of limitation. As we can see, there were only two major sources of limitation that the industries took into account : CONEG and customers. We can see that 32 percent of the respondents limit their inks due to CONEG types of regulation. Most of the companies that limit heavy metals to below 100 ppm are regulated by CONEG types of regulations. Table HI and Figure 1 provide information about written certificates of compliance. Customers in the packaging industry usually ask for certificates of compliance. Table IV and Figure 2 illustrate the less frequent request for a certificate of compliance among non-packaging industries. Control of heavy metal content in packages is of greater concern among packaging manufacturers due to the existence of CONEG types of legislation in many states. Respondents were asked about major non-packaging industries. Responses indicate misunderstanding of the question, with printers of packaging and labels, food packaging and corrugate cardboard industry listed as non-packaging industries. As shown in Table V, toy makers were listed most fi'equently as the major non-packaging industry that ask for compliance certification. To comply with legislation, the ink industry uses mostly random sampling (53 percent). 28 percent of the respondents calculate the level of contamination of their products. 12.5 percent of the respondents don't test or use supplier certification (see Table VI). When the industry was asked if an ASTM testing method for heavy metal content for use by the ink industry is needed, 41 percent responded that it is not necessary and 22% that it is necessary. Among the respondents, 59 percent stated the reduction of heavy metal content affected costs, and 38 percent their prices. Tables VII and VIII show the average increase of cost and price of products due to reduction of heavy metal content as 9% and 5% respectively, in cases where costs or price rose. 111 TABLE II QUANTITY OF HEAVY METALS ALLOWED IN INKS AND SOURCES OF LINIITATION in of limitation 100 CONEG 100 000 Customers Customers 20 ais Waste control districts a.r.s Unitation 100 CONEG 5 limitation 50 Customers 100 CONEG CONEG CONEG 1 1 l l 6 2 l 4 2 2 l l l l m—NNNHNNWNN s—s N tun 112 TABLE III HOW OFTEN DO YOUR CUSTOMERS IN THE PACKAGING INDUSTRY ASK YOUR COMPANY FOR A WRITTEN CERTIFICATION OF COMPLIANCE WITH TOXICS LEGISLATION? 9 Frequency (1) FIGURE 1 FREQUENCY OF USE OF WRITTEN CERTIFICATION OF COMPLIANCE WITH TOXICS LEGISLATION IN THE PACKAGING INDUSTRY 113 TABLE IV HOW OFTEN DO YOUR CUSTOMERS IN OTHER INDUSTRIES ASK YOUR COMPANY FOR A WRITTEN CERTIFICATE OF COMPLIANCE WITH TOXICS LEGISLATION? 30 .-. :1 l . 101/*1 fl .5! , 1 2 3 4 5 Frequency (1) FIGURE 2 FREQUENCY OF USE OF WRITTEN CERTWICATE OF COMPLIANCE WITH TOXICS LEGISLATION IN NON-PACKAGING INDUSTRIES 114 TABLE V MAJOR INDUSTRIES WHICH ASK FOR CERTIFICATION omrnercial 32 TABLE VI WHICH ANALYTICAL METHODS DO YOU GENERALLY USE TO DETERMINE METAL CONTENT IN YOUR INKS? Batch-to—batch T ° of random Calculation contamination levels Commercial laboratories ASTM-63 Certification Don't test Net 115 TABLE VII BY ABOUT WHAT PERCENT HAVE YOUR COSTS INCREASED DUE TO REDUCTION OF HEAVY METAL CONTENT? Y 8 '13 ‘18 :3 Frequency (1) FIGURE 3 PERCENTAGE COST INCREASED DUE TO REDUCTION OF HEAVY METAL CONTENT 116 TABLE VIII BY ABOUT WHAT PERCENT HAVE YOUR PRICES INCREASED DUE TO REDUCTION OF HEAVY METAL CONTENT? E3 Frequency (0 FIGURE 4 PERCENTAGE PRICE INCREASED DUE TO REDUCTION OF HEAVY METAL CONTENT 117 Tables IX and X provide information concerning reformulation of inks for the packaging and non-packaging industry. We found that 78% of manufacturers have reformulated at least some of their inks for the packaging industry, and 72% for the non- packaging industry, to reduce or eliminate their heavy metal content. As shown in Tables XI and X11, Napthol and AZO reds are the main substitues for cadmium red. Tables XIII and XIV show diarylide yellow, benzimidazolone and hansa yellow are the major substitutes for cadmium yellow. Tables XV and XIV present dianisidine orange and DNA orange substitutes for cadmium orange. Tables XVII, XVIII, XIX and XX show diarylide yellow and hansa yellow as the main substitute for lead based yellow and chromate yellow. Tables XXI and XXII present diarylide orange as the main replacement for lead orange. Tables XXIII and XXIV show dianisidine orange and DNA exotic as the substitutes for lead molybdate. Tables XXV and XXVI present copper free phtalo blue as the main substitute for copper. Table XXVI] show MetalStar Alugold and Toned Aluminum as the main substitutes for bronze based inks. Respondents did not expect firture substitutes for bronze based inks. Appendix C includes a table which indicates the difl‘erent possible substitutes for each heavy metal studied. The majority of companies surveyed stated that they are almost certain that heavy metals will be replaced in 5, 10 or 20 years. There were seven companies that already have totally replaced heavy metals (Table XXVHI). From Table XXIX, we can conclude that the quantity of ink produced in each company is kept as a corporation secret. When we asked about such quantity, the majority of companies did not respond. Few companies have switched or plan to switch to soybean oil inks (see Tables XXX and XXXI). Table XXXII illustrates that the most influential regulations or tests related to use of heavy metals in the ink industry are the Resources Conservation and Recovery Act, Clean Water Act, and Toxic Characteristic Leaching Procedure, in addition to CONEG types of regulation. 118 TABLE IX HAVE YOU REFORMULATED ANY OF YOUR INKS FOR THE PACKAGING INDUSTRY TO REDUCE OR ELIMINATE THEIR HEAVY METAL CONTENT? Frequency (0 FIGURE 5 REFORMULATION INKS FOR THE PACKAGING TO REDUCE OR ELMNATE HEAVY METAL CONTENT 119 TABLE X HAVE YOU REF ORMULATED ANY OF YOUR INKS FOR THE NON-PACKAGING INDUSTRY TO REDUCE OR ELIMINATE THEIR HEAVY METAL CONTENT? FIGURE 6 REFORMULATION OF INKS FOR THE NON-PACKAGING TO REDUCE OR ELIMINATE HEAVY METAL CONTENT 120 TABLE XI CADMIUM RED REFORMULATION Disazo (7.5%) Quinacridone (17.5%) , . Napthol (45.0%) ”ts-h, - :‘vt, ' Azo Reds (30.0%) FIGURE 7 CADMIUM RED REFORMULATION IN THE PAST TABLE XII CADMIUM RED REFORMULATION Disazo (17.4%) AZO Reds (17.4%) y. .. Quinacn'done (21 1%) Napthol (43.5%) FIGURE 8 CADMIUM RED REFORMULATION IN THE FUTURE 121 TABLE XIII CADMIUM YELLOW REFORMULATION IN THE PAST Titanium Dioxide (7.5%) . . . Ben2lmldazolone (30.0%) Diarylide Yellow (45.0%) a Hansa Yellow (17.5%) FIGURE 9 CADMIUM YELLOW REF ORMULATION IN THE PAST TABLE XIV CADMIUM YELLOW REFORMULATION IN THE FUTURE Benzimidazolone (1 1 .1%) Dialylide Yellow (500%) ‘ Hansa Yellow (38.9%) FIGURE 10 CADMIUM YELLOW REFORMULATION IN THE FUTURE 122 TABLE XV CADMIUM ORANGE REFORMULATION IN THE PAST requency 'Percent of Responses 12 63.2_°/2 7 36.8% 1 9 100.0% DNA Orange (36.8%) - 3" Dianisidine Orange (63.2%) FIGURE 11 CADMIUM ORANGE REFORMULATION IN THE PAST IN THE PAST TABLE XVI CADMIUM ORANGE REFORMULATION IN THE FUTURE AAOT Yellow (8.3%) Exotic Oranges (8.3%) DNA Orange (25.0%) Dianisidine Orange (58.3%) FIGURE 12 CADMIU M ORANGE REFORMULATION IN THE FUTURE IN THE FUTURE 123 TABLE XVII LEAD BASED YELLOW REFORMULATION IN THE PAST Monoaly-l-nldm e yue qulgg/OSB 3%) 7 A Hansa Yellow (25.0%) Dialylide Yellow (41.7%) AAOT (16.7%) FIGURE 13 LEAD BASED YELLOW REFORMULATION IN THE PAST TABLE XVIII LEAD BASED YELLOW REFORMULATION IN THE FUTURE Tltanium Dioxide (20.0%) Monoalylide (20.0%) '1‘ . Dialylide Yellow (60.0%) FIGURE 14 LEAD BASED YELLOW REFORMULATION IN THE FUTURE 124 TABLE XIX CHROMATE YELLOW REFORMULATION IN THE PAST Benzimidazolone (3.1%) Hansa Yellow (34.4%) Dialylide Yellow (59.4%) ' " ‘ Exotic Yellow (3.1%) FIGURE 15 CHROMATE YELLOW REFORMULATION IN THE PAST TABLE XX CHROMATE YELLOW REFORMULATION IN THE FUTURE Benlftfi‘fiuag‘ogfié’lffiig") Hansa Yellow (33.3%) Diarylide Yellow (53.3%) 1 FIGURE 16 CHROMATE YELLOW REFORMULATION IN THE FUTURE TABLE XXI LEAD ORANGE REF ORMULATION Tltanium Dioxide (14.3%) DNA Orange (14.3%) Azo Red (14.3%) Dialylide Orange (28.6%) Napthol (14.3%) Dianisidine Oran. (14.3%) FIGURE 17 LEAD ORANGE REF ORMULATION IN THE PAST TABLE XXII LEAD ORANGE REFORMULATION Tltanium Dioxide (25.0%) Dialylide Red (25.0%) // Dialylide Orange (25.0%) FIGURE 18 LEAD ORANGE REFORMULATION IN THE FUTURE AZO Red (25.0%) 126 TABLE XXIII LEAD MOLYBDATE REF ORMULATION IN THE PAST Benzimidazolone (4.5%) DNA Exotic (40.9%) ’ ‘ r. Dianisidine Oran. (54.5%) FIGURE 19 LEAD MOLYBDATE REFORMULATION IN THE PAST TABLE XXIV LEAD MOLYBDATE REF ORMULATION IN THE FUTURE 127 TABLE XXVI COPPER REFORMULATION IN THE PAST Cobalt Blue (14.3%) Ultramarine Blue (14.3%) Cu flee phtalo blue (57.1%) Peacock Blue (14.3%) FIGURE 20 COPPER REFORMULATION IN THE PAST TABLE XXVI COPPER REFORMULATION IN THE FUTURE Cobalt Blue (20.0%) Cu flee phtalo blue (40.0%) Ultramarine Blue (20.0%) Peacock Blue (20.0%) FIGURE 21 COPPER REFORMULATION IN THE FUTURE 128 TABLE XXVH BRONZE REFORMULATION IN THE PAST Toned Aluminum (37.5%)//l~\ MetalStarAlugold (37.5% Acrylac gold (12.5%) Cloda ink (12.5%) FIGURE 22 BRONZE REFORMULATION IN THE PAST 129 TABLE XXVHI REPLACEMENT OF HEAVY METAL INKS IN THE FUTURE 0 w. . . ._ , Almost Certain Probably will Notsme Probably went .1 .5 .10 E320 FIGURE23 REPLACEMENT OF HEAVY METAL INKS IN THE FUTURE 130 TABLE XXIX ESTIIVIATION OF SALES OF HEAVY METALS Copper Zinc Lead Chromium B 1-5% I e10% I 11-15% [:1 16-20% FIGURE 24 ESTIMATION OF SALES OF HEAVY METALS 131 TABLE XXX REPLACEMENT OF PETROLEUM OE INKS BY SOYBEAN OIL INKS IN THE PRESENT FIGURE 25 REPLACEMENT OF PETROLEUM OIL INKS BY SOYBEAN OIL INKS IN THE PRESENT 132 TABLE XXXI REPLACEMENT OF PETROLEUM OIL INKS BY SOYBEAN OIL INKS IN THE FUTURE FIGURE 26 REPLACEMENT OF PETROLEUM OIL INKS BY SOYBEAN OH; INKS IN THE FUTURE 133 TABLE XXXII AWARENESS OF TESTS AND REGULATIONS RELATED TO USE OF HEAVY METAL IN THE INK INDUSTRY onservation Act lean Water Act oxrc lmracteristic Procedure tate National tandards Institute ° ' for and Materials C " Paint et CHAPTER 13 SUMMARY AND CONCLUSIONS The Model Toxics in Packaging Legislation as developed by the Coalition of Northeastern Governors (CONEG) found and declared that: 1. " The management of solid waste can pose a wide range of hazards to public health and safety and to the environment. " 2. " Packaging comprises a significant percentage of the overall solid waste stream." 3. Heavy metals included in packaging are likely to be present in emissions or ash when packaging is incinerated, or in leachate when packaging is landfilled. 4. " Lead, mercury, cadmium and hexavalent chromium, on the basis of available scientific and medical evidence, are of particular concern. ” 5. " It is desirable as a first step in reducing the toxicity of packaging waste to eliminate the addition of these heavy metals to packaging. " The following summary and conclusions have been made, based upon the five declarations in the Model Toxics in Packaging Legislation as develop by CONEG. Each declaration will be analyzed to corroborate the veracity of the statements. 134 135 Declaration 1. Solid Waste as a Hazard to Health and Environment Heavy metals in solid waste represent a hazard to health and environment for two reasons. First, solid waste containing heavy metals disposed in landfills represents an important threat to groundwater resources if landfills are improperly operated. Unfortunately, many landfills were (are) used improperly; illegal dumps of hazardous waste or insufficient disposal facilities are not unusual. Second, rapid urban and suburban development in the United States has caused many once remote dumping grounds to be close to developed areas which can pose a hazard to public health and environment. Declaration 2. Packaging as a Significant Percent of Solid Waste Stream Packaging comprises 33% percent of total sources of landfilled municipal solid waste. Two-thirds of the total municipal waste is metals (8.7 %); glass (8.2%); plastic (6.6%); and paper and paperboard (41%). Declaration 3. Environmental Hazards of Heavy Metal Disposal Capper Sewage sludge contains an elevated level of copper, the majority coming from industrial discharges. This sludge is fiequently applied to land or landfilled. Most of the copper in soil is apparently tightly bound to soil components and may not be accessible for uptake by plants when sludge is applied to soil and it does not leach significantly fiom soil to groundwater when sludge is landfilled. However, generation of airborne copper from 136 waste sites is twice as high as from agricultural control areas. Sludge dumped in waste sites is increasing the level of copper in air that may reach excessive levels. Chromium Chromium-containing wastes have been disposed by discharging them to surface impoundments or lagoons. Leakage from these lagoons into groundwater has been relatively common. Almost all reported incidences of chromium related groundwater contamination are of industrial origin. When sludge containing chromium (VI) was applied to land, it was found relatively low amounts of chromium (VI) were found in food plants. Cr (VI) does not appear to accumulate in mammalian systems. Therefore, bioaccumulation in the soil-plant- animal system does not appear to be a significant exposure source. Cadmium Cadmium based inks in packaging application are a concern due to the major packaging related industries that dump large amounts of sewage sludge and wastes containing cadmium. These include pulp and paper mills, rubber processing, and paint and ink plants. Cadmium is used as a pigment and a stabilizer in the polymeric industry. When cadmium containing plastics are incinerated, the levels of cadmium in air are increased. Exposure to this level in air is predicted to increase human cancer risk in urban or industrial areas. Cadmium fiom sludge applied to land is transmitted to the food chain in considerable quantities. Cadmium accumulates mainly in certain kinds of plants such as food crops, root crops, leafy vegetables and tobacco plants. Food containing elevated 137 levels of cadmium is expected to increase in the long-term the daily intake of cadmium from 20-40 ug/day to the World Health Organization's allowable range limit of 51-71 ug/day. When waste containing cadmium is landfilled, considerable leaching of cadmium fiom soil to groundwater can occur only in cases of extreme contamination, low pH or both. Mercury Mercury is used as a catalyst in the synthesis of vinyl chloride and vinyl acetate, and is used in the production of urethane and urethane resins. Recover of mercury fi'om mercurial catalysts is not economical; mercury is being effectively replaced by other materials. Mercury migration fiom landfills to groundwater happens only in poorly operated landfill sites. However, it was found that ground water and surface-water from 25% of waste sites in the United States have an elevated mercury level. Due to its long half-life in soil, lead is, in general, immobile. As a result, the concentration of lead in water supplies is low. Lead in edible plants is unaffected by increasing lead content in soil. Therefore, lead content in foodstufi‘s is limited. Exposure to environmental lead concentration can put human health at risk. 7 ug of lead/l in human blood is enough to produce chronic symptoms in humans. Such concentration is close to the 2.3 ug/l that is the present average concentration of lead in human blood. Therefore, it is necessary to keep environmental lead levels to a minimum. I38 Declaration 4. Heavy Metal Exposure as a Health Hazard Copper If workers are subjected to excess concentrations of the metal in any of its forms, unwanted health effects can result. Industrial exposure to copper dust or fumes has been frequent, but health surveys of workers engaged in the processing of copper have not revealed signs of chronic illness. Exposure to copper dust can produce metal fume fever, respiratory effects, anemia and hemolytic efl‘ects, hepatic effects, dermal/ocular effects, gastrointestinal effects, neurological effects, reproductive effects and cardiovascular efi‘ects. Chromium Cr (VI) has a high penetration power and can be absorbed through the skin, lungs, or intestinal tract. Due to Cr (VI) wide solubility, chromates of calcium, strontium, and zinc; chromium trioxide; and sodium dichromate are responsible for a wide variety of types of cancers, primarily lung cancer in workers who were exposed to high levels of zinc chromate in workroom air, such as in pigment production plants. Zinc chromate is a more potent human carcinogen by inhalation than are other Cr (VI) compounds. Chromium is the second most common skin allergen, the most common sensitizer, and the most important cause of occupational dermatitis. Chromosomal aberrations and sister chromatid exchanges in lymphocytes of workers exposed to Cr (VI) occur. 139 Cadmium Cadmium is a very widely known potent occupational metallic toxicant for an ample range of tissues and organ systems, whose toxicity depends on the concentration in the organ. Cadmium effects on different organ system include damage to the tissues of the reproductive system, induction of testicular interstitial cell cancer, structural and functional damage to the liver, kidney, lung and nervous system and osteoporosis and osteomalacia. Cadmium once entering the human body stays in the body for a long period, having a half-er of 10 to 30 years. For such reason, concentration of this metal in humans has already increased resulting from accumulation of cadmium from daily intake. If cadmium emissions continue, cadmium in the environment will reach a dangerous level. Mercury Inorganic mercury is rapidly lost fiom the body. Therefore, only in the case of recurrent exposures and toxicity, do manifestations of mercurialism become chronic. Exposure effects may disappear if the worker is removed from exposure for a period of time. The central nervous system and the kidney are the two major organs affected by mercury exposure. In low doses, mercury may induce renal and liver disease and occasionally a tremor is noted. In the workplace, chronic mercury vapor intoxication has resulted in mental disturbances, objective tremors, and gum diseases at average air concentrations less than 100-200 ug/m3. 140 Inhalation of dust and fine powder is the major occupational risk of lead. Direct contact with such powder should be avoided and it is also necessary to wash any clothes used at work and shower before returning home to avoid exposure of children to high levels of lead. Exposure to lead can cause neurotoxicity, reproductive effects, renal effects, cancer, gastrointestinal efi‘ects, cardiovascular efl‘ects, mutagenic effects, and hematological effects. Declaration 5. Heavy Metal Reduction From the profile of the responses we can conclude the following: - 28 out of 32 ink industries limit heavy metal (cadmium, chromium (VI), mercury and lead) based ink, and 12 out of 32 limit to less than 100 ppm due to CONEG types of regulations. ° The major sources of limitation for heavy metals are the CONEG regulation and customers. ° Customers in the packaging industry ask more fi'equently for certificates of compliance with CONEG types of regulations than non- packaging industries. - 59% of the respondents said cost were affected by the reduction of heavy metal content in their inks. These industries increased their costs by an average of 9 %. - 38% of the respondents prices were affected by the reduction of heavy metal content in their inks. These industries increased their prices by an average of 5 %. 141 a Only seven companies (22%) were increased their costs due to reduction of heavy metal content, but, their prices were not affected. Twelve companies (3 8%) mentioned that their costs were increased, as a consequence, their prices were increased but not in the same proportion. - One response to CONEG regulations was replacement of heavy metal based pigments used in the packaging industries. Many ink companies have almost eliminated the use of such pigments in their inks, or will eliminate them in 5 to 20 years. a Substitutes such as hansa yellow, DNA orange, diarylide, benzimidazolone, titanium dioxide, dianisidine and A20 reds are used widely because they comply with current legislation. - In the industry, the use of phthalocyanine ink, blue and green is in question. Non- copper based phthalo blue is used as a substitute for phthalo blue. Recommendations for Future Work I have three recommendations for firture work. First, conduct a research to evaluate the content of heavy metals in post-consumer materials using analytical methods that measure soluble or leachable metals. The increase of heavy metal in recycled packaging material might increase the concentration of heavy metal in landfills and increase the risk of contamination of the contents. A second recommendation will be to record heavy metal air content in different ink manufacturing industries and relate these to workers health conditions and ink powder manipulation procedures. 142 Finally, a specific analytical method for testing was not specified by the CONEG regulation, causing confusion between the ink industry and its suppliers. For this reason I recommend to evaluate the different types of tests used, and propose a standard heavy metal test to be used. ("WV . film . ‘ if ”‘1’,“ ‘ ' unit.» at ‘ GLOSSARY Abomasum: Adenocarcinoma: Adenoma: Adenosine tliphospahteasa: Alveolus: Aminoaciduria: Angiosperms: Anorexia: Anosmia: Aorta: Atherosclerosis: Athetosis: GLOSSARY The fourth or true digestive stomach of a ruminant Carcinoma derived fiom glandular tissue or in which the tumor cells form recognizable glandular structures. Benign epithelial tumor in which the cells are clearly derived fiom grandular ephitelium. Nucleotide compound, occurring in all cells, where it represents energy storage in form of high-energy phosphate bonds. A general term used in anatomical nomenclature to designate a small saclike dilatation. An excess of amino acids in the urine. A plant of the class angiosperrnae. Plant that produce seeds enclosed in an ovary. Loss of appetite. Absence of the sense of smell. The main trunk from which the systematic arterial system proceeds. An extremely common form of arteriosclerosis in which deposits of yellowish plaques (atheromas) containing cholesterol, lipoid material, and lipophages are formed within the intirna and inner media of large and medium-sized arteries. Atherosclerosis ° The source of the medical terms is Resell, E. (1989). Human Medicine Dictionary. Orchard Publishers. New York. 143 Azotemia: Basophilic: Bronchospasm: Cardiomegaly: Coronary: Corticosteroid : Cortisol: Chemosensory: Chlorosis: Chorionepithelioma: Choroid : Chorea: Choreoathetosis: Dermatitis: Derrnatosis: Dirnorphism: Dysrrhagia: 144 An excess of urea or other nitrogenous bodies in the blood. Staining readily with basic dyes. Spasmodic contraction of the smooth muscle of the bronchi, as occurs in asthma. Cardiac hypertrophy The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. Steroids produced by the adrenal cortex in response to the release of corticotropin by the pituitary gland. Influence carbohydrate, fat and protein metabolism and regulate electrolyte and water balance. The major natural glucocorticoid produced by the human adrenal cortex. Relating to the perception of chemical substances, as in odor detection. Disorder generally affecting adolescent females, believed to be associated with iron deficiency anemia. An epithelial malignancy of trophoblastic cells. The thin, pigmented, vascular coat of the eye extending fiom the ora serrata to the Optic nerve. The ceaseless occurrence of a wide variety of rapid, highly complex, jerky movements that appear to be well coordinated but are performed involuntarily. A condition marked by choreic and athetoid movements. Inflammation of the skin. Any skin disease, especially one not characterized by inflammation. The property of having or existing in two forms, as fungi that can grow as molds or yeasts. Difficulty in swallowing. Dyspnea: Edema: Emphysema: EPA: Epithelium: Erythrocyte: Etiology: Fasciculation: Glucosuria: Granuloma: Histopathology: Hematocrit: Hematuria: Hemoglobinuria: Hemoglobin: Hernolysis: Hemolytic: Hernoptysis: 145 Difficult or labored breathing. The presence of abnormally large amounts of fluid in the intercellular tissue spaces of the body. A pathological accumulation of air in tissues or organs; applied especially to such a condition of the lungs. US. Environmental Protection Agency . The covering of internal and external surfaces of the body. One of the elements found in peripheral blood; called also red blood cell. All the factors that contribute to the occurrence of a disease or abnormal condition. A small local contraction of muscles, visible through the skin, representing a spontaneous discharge of a number of fibers innervated by a single motor nerve filament. An excess of glucose in the urine A tumor-like mass or nodule of granulation tissue, with actively growing fibroblast capillary buds. A branch of pathology concerned with the tissue changes characteristic of disease. The tissue changes that afi'ect a part or accompany a disease. The volume percentage of erythrocytes in whole blood Blood in the urine The presence of free hemoglobin in the urine The oxygen-carrying pigment of the erythrocytes, formed by the developing erythrocyte in bone marrow. The liberation of hemoglobin. Producing hemolysis The expectoration of blood or of blood-stained sputum. Hypercholesterolemia: Hyperemia: Hyperuricemia: Hypomania: Hypophosphatemia: Hypophyseal: Hypophysis: Leukocytosis: Lymphocyte: Macrophage: Mucous: Myoclonus: Hypoxia: Nasal septum: Necrosis: Nephritis: Nephropathy: NIOSH: Oliguria: 146 Excess of cholesterol in the blood. An excess of blood in a part; engorgement. Excess of uric acid in the blood. Mania of a moderate type. An abnormally decreased amount of phosphates in the blood. Pertaining to a hypophysis, especially to the hypophysis cerebli, or pituitary gland. The pituitary gland. An epithelial body located at the base of the brain in the sella turcica. A transient increase in the number of leukocytes in the blood. A mononuclear leukocyte. Any of the large, mononuclear highly phagocytic cells in the human blood. Pertaining to mucus. Shock like contractions of a portion of a muscle, an entire muscle, or a group of muscles. Reduction of oxygen supply to tissue below physiological levels despite adequate perfirsion of the tissue by blood. The partition separating the two nasal cavities in the midplane. Morphological changes indicative of cell death. Inflammation of the kidney Disease of the kidneys National Institute for Occupational Safety and Health Secretion of a diminished amount of urine in relation to the fluid intake. OSHA‘ Osmotic: Osmoregulation: Osteomalacia: Osteoporosis: Papule: Paresthesia: Pathognomonic: Pillar cells: Plastid: Pneumoconiosis: Pneumonitis: Pneumothorax: Proteinuria: Pleura: Polyp: RCRA: Receptor: Teratogenic: Teratoma: 147 Occupational Safety and Health Administration The flow or diffusion that takes place through a membrane of a living cell. Regulation of osmotic pressure in the body of a living organism. A condition marked by softening of the bones. Abnormal rarefraction of bone. A small circumscribed, superficial, solid elevation of the skin. Sensibility for weight or pressure; pressure sense. Specially distinctive or characteristic of a disease or pathologic condition. Elongated supporting cells in a double row. Any of the specialized organelles of plant cells that contain pigments. A condition characterized by permanent deposition of substantial amounts of particulate matter in the lungs. Inflammation of the lungs. An accumulation of air or gas in the pleural space. An excess of serum proteins in the urine. The serous membrane investing the lungs. A morbid excrescence fi'om mucous membrane. Resource Conservation and Recovery Act. Specific molecule on the surface of a cell that responds in a specific way Tending to produce anomalies of formation. A true neoplasma made up of a number of different types of tissue. APPENDIX A 148 11200, App. A ‘5 State Regulations Appendix A: Model Toxics Legislation " as developed by The Source Reduction Council of The Coalition of Northeastern Governors (CONEG) December 14, 1989 Summary* The legislation calls for the reduction of lead, m'eréury, cadmium and hexavalent chromium in packaging or packaging materials used or sold within the state. Manufacturers and distributors would have two years to clear inventory and make necessary adjustments to their operations in order to comply with the law. Manufacturers and distributors of packaging or packaging materials would be required to reduce the sum of the concentration levels of incidentally introduced lead, cadmium, mercury and hexavalent chromium to 600 parts per million two years after the legislation is signed into law; 250 parts per: million three years after it is signed into law; and 100 parts per million four years after it is signed into law. The legislation prohibits the intentional introduction of the four heavy metals during manufacturing or distribution. The legislation provides an exemption for packaging made from post-consumer materials; packages and packaging components manufactured prior to the effective date of the legislation; packaging that is essential to the protection, safe handling or function of the package’s contents—for example, medical products related to radiation therapy, x-rays, etc; packages and packaging components for which there is no feasible alternative; reusable packaging for products that are subject to other federal or state health, safety, transportation or disposal requirements (i.e., hazardous waste); and packaging having a controlled distribution and reuse (i.e., beverage containers subject to mandatory deposit requirements). Manufacturers and suppliers of packaging and packaging components are required to furnish a certificate of compliance to the purchasers of packaging. (This applies to companies that actually put their products in the package and does not apply to the retailer or the individual consumer.) The public and the state have access to these certificates. The legislation also provides for a review process by the state to determine the effectiveness of the act. More specifically, that review will address the need to continue the recycling exemption and Will determine if other toxic substances contained in packaging should be subject to reduction. " Revised January 1995. The Source Reduction Council of The Coalition of Northeastern Governors (CONEG) 400 North Capitol St.. N. W. Suite 382 Washington, 0.0. 20001 (202) 624-8450 Tab 200 Page I January 1995 7 wrcnmenfa/ Packaging 149 State Regulations 11200, App. A Section 1. (Title) Section 2. The legislature finds and declares that: a. The management of solid waste can pose a wide range of hazards to public health and safety and to the environment; b. Packaging comprises a significant percentage of the overall solid waste stream; c. The presence of heavy metals in packaging is a part of the total concern in light of their likely presence in emissions or ash when packaging is incinerated, or in leachate when packaging is landfilled; d.Lead, mercury, cadmium and hexavalent chromium, on the basis of available scientific and medical evidence, are of particular concern; e. It is desirable, as a first step in reducing the toxicity of packaging waste, to eliminate the addition of these heavy metals to packaging; and f. The intent of this act is to achieve this reduction in toxicity without impeding or discourag- ing the expanded use of post-consumer materials in the production of packaging and its components. Section 3. Definitions* ”Package": means a container providing a means of marketing, protecting or handling a product and shall include a unit package, an intermediate package and a shipping container as defined in ASTM D996. ”Package" shall also mean and include such unsealed receptacles as carrying cases, crates, cups, pails, rigid foil and other trays, wrappers and wrapping films, bags and tubs. ”Distributor”: means any person, firm or corporation who takes title to goods purchased for resale. ”Packaging Component”: means any individual assembled part of a package such as, but not limited to, any interior or exterior blocking, bracing, cushioning, weatherproofing, exterior strapping, coatings, closures, inks and labels. Tin-plated steel that meets the American Society for Testing and Materials (ASTM) specification A- 623 shall be considered as a single package component.“ Electra-galvanized coated steel and hot dipped coated galvanized steel that meet the American Society for Testing and Materials (ASTM) specifications A-SZS and .4-879 shall be treated in the same manner as tin-plated steel. ”Manufacturing”: means physical or chemical modification of (a) material(s) to produce packaging or packaging components. ”Dr'stn'butz'on ”: means the practice of taking title to (a) package(s) or packaging component(s) for promotional purposes or resale. Persons involved solely in delivering (a) package(s) or packaging Componen t(s) on behalf of third parties are not considered distributors. ”Manufacturer”: means any person, firm, association, partnership or corporation producing (a) PaCkage(s) or packaging components(s) as defined in this act. ‘ Revised January 1995. 3 Tl'n.pjated steel. electro-gajvanized steel and hot dipped coated galvanized steel language was inadvertently omitted from . December 14, 1989. adoption of the model legislation. lt was later adopted and added ‘0 “‘9 model legislation by the 'fnber states of the Toxics in Packaging Clearinghouse (TPCH) on April 21, 1993. 200 January 1995 OThompson Publishing Group lnc. 1995 all 150 11200, App. A State Regulations ”Supplier”: means any person, firm, association, partnership or corporation who sells, offers for sale, or offers for promotional purposes packages or packaging components which shall be used by any other person, firm, association, partnership or corporation to package (a) product(s). ”Intentional Introduction”: means the act of deliberately utilizing a regulated metal in the formation of a package pr packaging component where its continued presence is desired in the final package or packaging component to provide a specific characteristic, appearance or quality. The use of a regulated metal as a processing agent or intermediate to impart certain chemical or physical changes during manufacturing, whereupon the incidental retention of a residue of said metal in the final package or packaging component is neither desired nor deliberate, is not considered intentional introduction for the purposes of this act where said final package or packaging component is in compliance with subsection c of section 4 of this act. The use of recycled material as feedstock for the manufacture of new packaging materials, where some portion of the recycled materials may contain amounts of the regulated metals, is not considered intentional introduction for the purposes of this act where the new package or packag- ing component is in compliance with subsection c of section 4 of this act. ”Intentional Presence”: means the presence of a regulated metal as an unintended or undesired ingredient of a package or packaging component. Section 4. Prohibition/Schedule for Removal of Incidental Amounts a. As soon as feasible but not later than two years after the adoption of this act, no package or packaging component shall be offered for sale or for promotional purposes by its manufac- which includes, in the package itself or in turer or distributor in the state of any packaging component, inks, dyes, pigments, adhesives, stabilizers or any other additives, any lead, cadmium, mercury or hexavalent chromium which has been intention- ally introduced as an element during manufacturing or distribution as opposed to the incidental presence of any of these elements. b. As soon as feasible but not later than two years after the adoption of this act, no product shall be offered for sale or for promotional purposes by its manufacturer or distributor in in a package which includes, in the package itself or in any of its the state of packaging components, inks, dyes, pigments, adhesives, stabilizers or any other additives, any lead, cadmium, mercury or hexavalent chromium which has been intentionally introduced as an element during manufacturing or distribution as opposed to the incidental presence of any of these elements c. The sum of the concentration levels of lead, cadmium, mercury and hexa valent chromium present in any package or packaging component shall not exceed the following: 0 600 parts per million by weight (0.06 percent) effective two years after adoption of this statute; 0 250 parts per million by weight (0.025 percent) effective three years after adoption of this statute; and 0 100 parts per million by weight (0.01 percent) effective four years after adoption of this statute. Tab 200 Page ill 5?? w‘ronmenra/ Packagmg January 1995 11200, App. A 151 State Regulations ‘ 0 Section 5. Exemptions" All packages and packaging components shall be subject to this act except the following: a. those packages or package components with a code indicating date of manufacture that were manufactured prior to the effective date of this statute; . those packages or packaging components to which lead, cadmium, mercury or hexavalent chromium have been added in the manufacturing, forming, printing or distribution process in order to comply with health or safety requirements of federal law, provided that the manufacturer of a package or packaging component must petition the [state administrative agency] for any exemption from the provisions of this subsection for a particular package or packaging component based upon either criterion; and provided further that the [state administrative agency] may grant an exemption for up to two years if warranted by the circumstances; and provided further that such an exemption may, upon reapplication for exemption and meeting the criteria of this subsection, be renewed at two year intervals; or . packages and packaging components that would not exceed the maximum contaminant levels set forth in subsection c of section 4 of this act but for the addition of post—consumer materials; and provided that the exemption for this subparagraph shall expire January 1, 2000; or . those packages or packaging components to which lead, cadmium, mercury or hexavalent chromium have been added in the manufacturing, forming, printing or distribution process for which there is no feasible alternative, provided that the manufacturer of a package or packaging component must petition the [state administrative agency] for any exemption from the provisions of this subsection for a particular package or packaging component based upon the criterion; and provided further that the [state administrative agency] may grant an exemption for up to two years if warranted by the circumstances; and provided further that such an exemption may, upon reapplication for exemption and meeting the criterion of this subsection, be renewed at two-year intervals. For purposes of this subsection, a use for which there is no feasible alternative is one in which the regulated substance is essential to the protection, safe handling or function of the package’s contents; or . packages and packaging components that are reused but exceed contaminant levels set forth in subsection c of section 4 of this act, provided that the product being conveyed by such package and/ or the package / packaging component is (are) regulated under federal and/ or state health or safety requirements; and provided that transportation of such packaged product is regulated under federal and / or state transportation requirements; and provided that disposal of such package is performed according to federal and/ or state radioactive or hazardous waste disposal requirements, and provided that an exemption under this subparagraph shall expire on January 1, 2000; or . packages and packaging components having a controlled distribution and reuse that exceed the contaminant levels set forth in subsection c of section 4 of this act, provided that the manufacturer or distributor of such packages or packaging components must petition the [state administrative agency] for exemption and receive approval from the [state administrative agency], working with the CONEG Toxics in Packaging Clearinghouse, according to standards in subsection f.l below set by such agency and based upon satisfactory demonstrations that the environmental benefit of the controlled distribution and reuse is significantly greater as compared to the same package manufactured in compliance with the contaminant levels set forth in subsection c of section 4; and provided that an exemption under this subparagraph shall expire on January 1, 2000. "' Revised January 1995. Tab 200 Page iv January 1995 ©Thompson Publishing Group Inc. 1995 l 52 State Regulations 13200, App. A 1. Standards A plan, to be proposed by the manufacturer seeking the exemption or his designee, shall include each of the following elements: i. a means of identifying in a permanent and visible manner those reusable entities containing regulated metals for which an exemption is sought; ii. a method of regulatory and financial accountability so that a specified percentage of such reusable entities manufactured and distributed to other persons are not discarded by those persons after use, but are returned to the manufacturer or his/her designee; iii. a system of inventory and record maintenance to account for reusable entities placed in, and removed from, service; iv. a means of transforming returned entities that are no longer reusable into recycled materials for manufacturing or into manufacturing wastes that are subject to existing federal and / or state laws or regulations governing such manufacturing waste to ensure that these wastes do not enter the commercial or municipal waste stream; and v. a system of annually reporting to the [appropriate state administrative agency] changes to the system and changes in designees. Section 6. Certificate of Compliance As soon as feasible but not later than two years after the adOption of this act, a certificate of compliance stating that a package or packaging component is in compliance with the requirements of this act shall be furnished by is manufacturer or supplier to is purchaser, provided, however, where compliance is achieved under the exemption(s) provided in subsection 3 b or c, the certificate shall state the specific basis upon which the exemption is claimed. The certificate of compliance shall be signed by an authorized official of the manufacturing or supplying company. The purchaser shall retain the certificate of compliance for as long as the package or packaging component is in use. A copy of the certificate of compliance shall be kept on file by the manufacturer or supplier of the package or packaging component. Certificates of compliance, or c0pies thereof, shall be furnished to the [state administrative agency] upon its request and to members of the public in accordance with section 9. If the manufacturer or supplier of the package or packaging component reformulates or creates a new package or packaging component, the manufacturer or supplier shall provide an amended or new certificate of compliance for the reformulated or new package or packaging component. Section 7. Enforcement [Each state to add its own enforcement provisions] Section 8. State Review* [The state administrative agency] shall, in consultation with the Source Reduction Council of CONEG, review the effectiveness of this act no later than 42 months after its adoption and shall provide a report based upon that review to the governor and legislature. The report may contain recommendations to add other toxic substances contained in packaging to the list set forth in this act in order to further reduce the toxicity of packaging waste, and a description of the nature of the Silastitutes used in lieu of lead, mercury, cadmium and hexavalent chromium. "' Revised January 1995. Tab 200 Environmental Packaging January 1995 ”9‘ “Li 3200,. ’ ' 153 11200, App. A State Regulations [The state administrative agency] shall, in consultation wth the Source Reduction Task Force of CONEG, review the extension of the recycling exemption as it is provided for in subsection c of section 5 of this act. This review shall commence no later than January 1, 1997. A report based upon that review shall be provided to the governor and legislature by January 1, 1999. Section 9. Public Access Any request from a member of the public for any certificate of compliance from the manufacturer or supplier of a package or packaging component shall be: a. Made in writing with a copy provided to the [state administrative agency]; b. Made specific as to package or packaging component information requested; and c. Responded to by the manufacturer or supplier within 60 days. Section 10. Effective Date This act shall become effective immediately upon adoption. Section 11. Severability and Construction* The provisions of this act shall be severable, and if any court declares any phrase, clause, sentence or provision of this act to be invalid, or its applicability to any government, agency, person or circumstance is declared invalid, the remainder of the act and its relevant applicability shall not be affected. The provisions of this act shall be liberally construed to give effect to the purposes thereof. Source: Thompson Publishing Group. Environmental Packaging. U.S. Guide to Green Labeling, Packaging and Recycling. Whashington, D.C. ‘ Added January 1995, ‘ Tabzoo P190 iv.il January 1995 ©Thompson Publishing Group Inc. 1995 APPENDIX B Survey Questionnaire Heavy Mbtals in the Ink Industry Carla M. Vidal School of Packaging Michigan State university East Lansing, MI 48823 1. Name 2. Company Name 3. Street No. , ( ) City State Zip Code 4. Telephone Number - area number 5. Date tho: If you have any questions please call me at (517) 353-5143. 154 155 Questionnaire This questionnaire is intended for people working in the development, manufacturing or research division of companies that manufacture inks for the packaging industry. It is completely voluntary and confidential. No company or individual names will be identified in survey reports. If you don’t want to answer a question , just skip over it. Instructions: Place a X in the block provided that best describes your operation. l.— Does your company use or manufacture inks for the packaging industry? Yes NO Continue Stop - Your company is not in the scope of my study. Thank you for your“ time. Please r e t u r n t h e questionnaire in the envelope provided. 2.- Are you knowledgeable about the .manufacturing, development or research operation of your company? Yes No Continue Stop - Please direct the questionnaire to the appropriate person in your company. 3.— Which of these has your company used in ink formulation? (Mark all which apply) r II n r 11 r Co ' L d dm' h ' pper llzlnc lI lLea Jl Ll Ca lumILIC romlum (VI) JI Mercury A B C D E F 156 4.- We are interested in how the model toxics in packaging legislation as developed by the Coalition of Nbrtheastern Governors (CONEG) Source Reduction Council is affecting the ink industry. Are you familiar with this legislation? l.Yes 2.No Go to question 7. 5.- Fourteen states in the U.S. have already passed this law. Has your state passed this legislation? If yes, when? 1. Yes 2. No 3. Don’t know I Year -—-—-——- Go to question 7. 6.- Does your company limit the total quantity of Lead, Cadmium, Chromium (VI) and Mercury, in your inks because of toxics in packaging legislation ? Yes,< 600 ppm Yes,< 250 ppm Yes,< 100ppm No don’t Know 1 2 3 4 7.- Does your company limit the amount of heavy metal in your inks? 1. Yes 2. No 3. Don’t know I Go to question 9. 157 8.- Please indicate the quantity of the following heavy metals you allow in your inks and the source of the limitation (internal, CONEG, state legislation, ANSI, ASTM, consumer standard, etc) ? Metal Quantity in ppm Source of No limitation Limitation Copper Zinc Lead Cadmium Chromium U (IV) Mercury Total heavy metals (Lead + Cadmium+ Chromium (IV)+ Mercury) 9.— How often do your customers in the packaging industry ask.your company for a written certificate of compliance with toxics legislation? 1. Never 2. Sometimes 3. Usually 4. Frequently 5. Always 158 10.- How often do your customers in other industries (non-packaging), ask your company for a written certificate of compliance with the toxics legislation? 1. Never - Go to question 11. 2. Sometimes 3. Usually 4. Frequently 5. Always Please list the major industries which ask for such certification. ll.- Which types of analytical methods do you generally use to determine heavy metal content in your inks? (Mark all which apply) 1. Batch-to-batch testing 2. Testing of random samples 3. Calculation of contamination levels 4. Don’t test 5. Don’t know 6. Other methods (list): 12. 13. 14. 15. 16. 17. 159 Do you feel that an ASTM standard is needed to provide a unique testing method for heavy metal content for use by the ink industry? YES No Don’t Know‘ Generally speaking, do you think that reduction of heavy metal content has increased your costs? ‘2. NOT {3. 1. Yes I I Don’t knowl l I Go to question 17. By about what percent have your costs increased ? 1. <1% 2 1—5% 3. 6-10% 4. ll-lS% 5. > 15 6. Don’t Know — Has the price of your products increased in response to that cost increase? 1. Yes 2. No 3. Don’t know l L———————-Go to question 17. - By about what percent have your prices increased ? 1. <1% 2. 3. 6 10 O ‘6 4. 11-15% S. > 15 6. Don’t Know Have you reformulated any of your inks for the packaging industry to reduce or eliminate their heavy metal content? None of them Some of them Most of them All of them 160 18.— Have you reformulated any of your inks for other 19. industries (non-packaging) to reduce or eliminate their heavy metal content? None of them Some of them Most of them All of them Please provide below as much detail as you can about ink reformulations and the reasons for reformulation. We have selected some major pigments and alternatives to simplify your task. Please check all which apply. A-Cadmium.red Substitutes: Please check: all which, your company is using ___ AZO reds ___ Quinacridone perylene ___ Napthol ___ Disazo Other(please specify ) Reason for reformulation: Please check all which apply Legislation Environmental concern Health concern Customer request Other (please specify ) B-Cadmium.yellow Substitutes: Please check all which your company is using Benzimidazolone Hansa yellow Diarylide yellow Other(please specify ) Continue on the next page 161 Reason for reformulation: Please check all which apply Legislation Environmental concern Health concern Customer request Other (please specify Substitutes: Please check all which. your Exotic Oranges Dianisidine Orange DNA Orange Other(please specify ) Reason for reformulation: Please check all which apply Legislation Environmental concern Health concern Customer request Other (please specify ) D-Lead-based yellows Substitutes: Please specify below Reason for reformulation: Please check all which apply Legislation Environmental concern Health concern Customer request Other (please specify ) ||||| E-Chromate yellow Substitutes: Please check all which. your company is using Hansa yellow Diarylide yellow Benzimidazolone Exotic yellow Other (please specify ) Continue on the next page ||||| 162 Reason for reformulation: Please check all which apply Legislation Environmental concern Health concern Customer request Other (please specify ) F-Zinc chromate Substitutes: Please specify below Reason for reformulation: Please check all which apply Legislation Environmental concern Health concern Customer request Other (please specify ) G-Lead- Orange Substitutes: Please specify below Reason for reformulation: Please check all which apply ___ Legislation Environmental concern Health concern Customer request Other (please specify ) Substitutes: Please check: all which. your Dianisidine orange DNA exotic Benzimidazolone (VAT orange) Other (please specify ) Reason for reformulation: Please check all which apply Legislation Environmental concern Health concern Customer request Other (please specify ) Continue on the next page 163 I-Zinc Substitutes: Please specify below Reason for reformulation: Please check all which apply Legislation Environmental concern Health concern Customer request Other (please specify ) J-Copper Substitutes: Please specify below Reason for reformulation: Please check all which apply Legislation Environmental concern Health concern Customer request Other (please specify ) K-Bronze (zinc+copper) Substitutes: Please check all which. your company is using Acrylac gold Croda ink MetalStar Alugold Other (please specify ) |||| Reason for reformulation: Please check all which apply Legislation Environmental concern Health concern Customer request Other (please specify ) Continue on the next page I I 164 L-Mercury Substitutes: Please specify below Reason for reformulation: Please check all which apply Legislation Environmental concern Health concern Customer request Other (please specify ) M-Others (please specify below; attach an extra page if needed) Substitutes: Reason for reformulation: (Please check all which apply) Legislation ___Legislation ___Legislation —_—Environmental Environmental ___Environmental __—concern -_—'concern concern Health concern ___Health concern ___Health concern __— Customer ___Customer ___Customer __—request request request Other ___Other ___Other . (please specify' (please specify' (please speCify ) 20.- Do you anticipate having to replace heavy metal inks in the next 1, 5, 10 or 20 years? Option\Year 1 5 10 20 Almost certain Probably will Not sure Probably won’t Will not — Go to question 22 165 21.- Please provide as much detail as you can about the ink reformulations you foresee and the reasons for reformulation. We have selected some major pigments and alternatives to simplify your task. Please check all which apply. A-Cadmium.red Substitutes: Please check. all which. your company is likely to use ___ AZO reds ___ Quinacridone perylene ___ Napthol ___ Disazo Other(please specify ) Reason for reformulation: Please check all which apply Legislation Environmental concern Health concern Customer request Other (please specify ) B-Cadmium.yellow Substitutes: Please check. all which. your company is likely to use Benzimidazolone Hansa yellow Diarylide yellow Other(please specify ) Reason for reformulation: Please check all which apply Legislation Environmental concern Health concern Customer request Other (please specify ) ||||| C-Cadmium.orange Substitutes: Please check all which. your company is likely to use Exotic Oranges Dianisidine Orange DNA Orange Other(please specify ) Continue on the next page |||| 166 Reason for reformulation: Please check all which apply Legislation Environmental concern Health concern Customer request Other (please specify ) D-Lead-based yellows Substitutes: Please specify below Reason for reformulation: Please check all which apply Legislation Environmental concern Health concern Customer request Other (please specify ) E-Chromate yellow Substitutes: Please check all which. your company is likely to use Hansa yellow Diarylide yellow Benzimidazolone Exotic yellow Other (please specify Reason for reformulation: Please check all which apply Legislation Environmental concern Health concern Customer request Other (please specify ) ||||| F-Zinc chromate Substitutes: Please specify below Continue on the next page 167 Reason for reformulation: Please check all which apply Legislation Environmental concern Health concern Customer request Other (please specify ) G-Lead- Orange Substitutes: Please specify below Reason for reformulation: Please check all which apply Legislation Environmental concern Health concern Customer request Other (please specify Substitutes: Please check all which your Dianisidine orange DNA exotic Benzimidazolone (VAT orange) Other (please specify ) Reason for reformulation: Please check all which apply Legislation Environmental concern Health concern Customer request Other (please specify ) I-Zinc Substitutes: Please specify below Continue on the next page 168 Reason for reformulation: Please check all which apply Legislation Environmental concern Health concern Customer request Other (please specify ) J-Copper Substitutes: Please specify below Reason for reformulation: Please check all which apply Legislation Environmental concern Health concern Customer request Other (please specify ) K-Bronze (zinc+copper) Substitutes: Please check all which your company is likely to use Acrylac gold Croda ink MetalStar Alugold Other (please specify ) Reason for reformulation: Please check all which apply Legislation Environmental concern Health concern Customer request Other (please specify ) ||||| L-Mercury Substitutes: Please specify below Reason for reformulation: Please check all which apply Legislation Environmental concern Health concern Customer request Other (please specify ) |||l| Continue on the next page 169 M-Others (please specify below; attach an extra page if needed) Substitutes: Reason for reformulation: (Please check all which apply) .___Legislation ___Legislation ___Legislation ___Environmental ___Environmental____Environmental concern concern concern ___Health concern ___Health concern ___Health concern .___Customer ___Customer ___Customer request request request ___Other ___Other ___Other (please specify’ (please specify' (please specify ) ) ) 22.- Please estimate in tonnage, dollar amount and/or percent of sales the quantity of your total production which is copper, zinc , lead, cadmium, mercury or hexavalent chromium related pigments/inks. I . 1| ll . ll . Copper (tZ1nc ||Lead ||Cadm1um||Chrom1um. Mercury Jl 1| Jl A B C D E F Tonnage Dollars % sales 23. 170 Do you use soybean oil as the vehicle to replace petroleum oil inks? Already Have converted Have converted some Not sure No Do you plan to use soybean oil as the vehicle to replace petroleum oil inks? Will convert all Will convert some Not sure No 171 25.- Are you aware of any other regulations that limit the use of heavy metals in the ink industry? (mark all that are relevant) 1.Resources Conservation and Recovery Act (RCRA) 2. Clean water Act (EPA) 3. Toxic characteristic Leaching procedure (TCLP) (EPA) 4. State Legislation 5. American National Standards Institute (ANSI) 6.American Society for Testing and Materials (ASTM) 7. Lead Containing Paint Other NOTE: When you have completed the questionnaire please return it in the enclosed envelope. Your early response by February 03, 1995 will be appreciated. I appreciate your professional assistance. Thank you for your valuable help. APPENDIX C 172 Essa-.2 ESP ><><><>< .2. 320 flail-ll «sass: ><><>< 02m gmoo can xuouaod 03.0 Earn. 08“. :0 a6=o> ozoxm 5:; 3.8.38.2 XX 3o=o> ._.O<< 0320 o_8xm «ago <20 ><><><>< OEQU Fl 02.6.0 E:.:2F ><><><>< gall ><><><>< XXX ><><><>< Bo=o> coca: wagons—28.23 l Ensure 335 _Eflazll, oucotm |— scoocoaocsw atom QN< “XXXXX Soon oEnh o Eonn. 26:0 .5 26:0 sh. o 208 26:0»8 3| assassins: >¢hmnoz. :2. m2... 2. 92.52 >>¢<52=u LIST OF REFERENCES LIST OF REFERENCES Abel, A (1992). The Cgloration of Advanced Coatings. Paint Research Association. Agency for Toxic Substances and Disease Registry (1989). Toxigalogicg Profile fgr Mam . U.S. Public Health and Human Services. U. S. Environmental Protection Agency. Atlanta, Ga. Agency for Toxic Substances and Disease Registry (1992). Maggy Toxigity. U. S. Department of Health and Human Services. Public Health Services. Atlanta, Ga. Alexander, D. (1989). "Chronic lead exposure: a problem for minority workers.” AAQHN Journal. 37 (3): 105-108. Amdur, M.; McCarthy, 1.; and Gill, M. (1982). ”Respiratory response of guinea pigs to zinc oxide fitme.” &. Ind, Hyg. A_s_sg&. J. 43:887-889. Anderson, N. (1982). The Environmental Impag of Qhrgmium. Department of Environmental Protection. Ashraf, M.; Tariq, J.; and Jafl‘ar, M. (1992). "Trace metals in fish, sediment and water fi'om the southwest coast of the Arabian sea, Pakistan" Tgximlggical and Environmml Chm’stry 34 (2/4) : 99. Baatrup. E. (1991).'Structural and Functional Efl‘ects of Heavy Metal on the Nervous System.” m arative Biochemi ° - Pmmggy Ed Toxigglogy 100 : 253. Baselt, R. (1988). Biglggig Mgniton'ng Methods for Industrifl th’gfls 2nd edition. PSG Pub. Co., Massachusetts. Bamhart, S.; and Rosenstock, L. (1984). "Cadmium Chemical Pneumonitis.” Chest. 86:5. Beeckmans, J., et al. (1963). ”Toxicity of Catalytically Active Zinc Oxides." Arch. Envirgn. Hgnh . 7:346. Bencko, V. (1985). ”Chromium: a review of environmental and occupational toxicology. ”1mm! of Hygige, Epidemiology, Microbiolggy, Md Immgnglggy. 29(1):37-46. 173 174 Benemelis, R (1991) . "Trends in the U.S. Ink Market." I_n_k Print. p. 18,14. Bengeri, K.; and Patil, H. (1986). "Respiration, liver glycogen and bioaccumulation in Labeo rohita exposed to zinc.” Indian Journal of Comparative Animal Physiology 4:79-84. Bhattacharyya, S.; and Chaudhuri, A. (1988). "Role of Cadmium in Essential Hypertension." JAPI. 36 (7). Bianchi, V. et al. (1980). "Mechanisms of Chromium Toxicity in Mammalian Cell Cultures. Toxicolggy." 17: 219-224. Birge, W.; and Just, J. (1975). Sensitivity of vertebrate embryos to heayy metals as a criterion of water quality, Phase 11. Research Report No. 84. University of Kentucky, Water Resources Research Institute. Leington, KY. Boyce, A (1961) . The Handling of Mgal Powders for Powder Metallurgical Applications. American Powder Metallurgy Institute. Princeton. Brenchley, W. (1941). Inorganic Plant Poisons and Stimulants. Cambridge University Press. London. p. 110. Brink, M.; Becker, 0.; Terrill, S.; and Jensen, A. (1959). "Zinc toxicity in the weanling pig.” J. Anim. Sci. 18:836-842. Burton, D.; Jones, A.; and Cairns, J. (1972). "Acute zinc toxicity to rainbow trout (Salmo gairdneri): confirmation of the hypothesis that death is related to tissue hyposia." JourngaLof the Fisheries Re_s_ear§h Board of Canada. 29: 1463-1466. Burt, S. (1986). "Mercury toxicity- an overview.” AAOHN joumal. 34(11): 543-546. Carson, B.; and Ellis, H. (1986) . Toxicology and Biological Monitoring of Metals in Humans. Lewis Publishers, Chestsea, MI. p.93-99. Chiu, H.; Jeng, J.; and Shieh, S. (1994). ”Increased oxidizability of plasma low density lipoprotein from patient with coronary artery disease." Biochimica et Biophysiga Acta 1225 (2): ZOO-208. Clarkson T. (1993). "Mercury: Major Issues in Environmental Health.” Ezriz H_ealth Perspectives. 100: 31-38. Commission of the European Communities (1981). Ecotoxicology of Cadmium. Luxemburg. 175 Conner, M.; Rogers, A.; and Amdur, M. (1982). "Response of guinea pig respiratory tract to inhalation of submicron zinc oxide particles generated in the presence of sulfur dioxide and water vapor." T oxicol. Appl. Pharmacol. 66:434-442. Conner, M.; Lam, H.; Rogers, A; Fitzgerald, 8.; and Amdur, M. (1985). "Lung injury in guinea pigs caused by multiple exposures to submicron zinc oxide mixed with sulfirr dioxide in a humidified fiimace.” J. Toxicol. Environ. Hgth 16:101-114. Copper and Brass Research Association (1947). Copper and Health. New York. Crandall, C.; and Goodnight, C. (1962). "Effects of sublethal concentrations of several toxicants on growth of the common guppy, Lebistes reticulatus. " Limnology and Oceanography . 7(2):233-239. Cragle, D.; Hollis, D.; Qualters, J.; Tankersley, W.; and Fry, S. (1984). ”A Mortality Study of Men Exposed to Elemental Mercury.” Journal of Occupational Medipine. 26(11):817-821. Czarnecki, R.(1992). ”Formulating Inks to Meet the Challenge of the Regulatory Age." Flexo. 17(2). Curby, W.; Winick, R. ; and May, E. (1976). Assays of Toxic Pollutants by Fish Blood. Ecological Research Series (Narragansett: Rhode Island, US Environmental Protection Agency). Dawson, D.; Stebber, E.; Burks,S.; and Bantle, J. (1988). "Evaluation of the developmental toxicity of metal-contaminated sediments using short-term fathead minnow and frog embryo-larval assays. ” Environmental Toxicology and Chemistgz. 7:27-34. Department of the Environment (1980). Cadmium in the Environment and Its Sigmtj' cance to Man. London. Her Majesty's Stationery Office. London. De Silva, P.; and Donnan, M. (1981). ”Chronic cadmium poisoning in a pigment manufacturing plant. " Britis_h Journal of Industrial Medicine. 38 (I): 76-86. Dewar, W.; Wight, P.; Pearson, R.; and Gentle, M. (1983) "Toxic effects of high concentrations of zinc oxide in the diet of the chick and laying hen.” Br. Ppult. Sci. 24:397-404. Dillon, H. (1991) . Biological Monitoring of Exposure to Chemicals: Metals. Wiley, New York. Dobson, S. (1992). Cadmium- Epvirorimental Aspects. Environmental Health Criteria l3 5. World Health Organization. Geneva. 176 Donker, M.; Eijsackers, H.; and Heirnbach, F. (1994). Ecotoxicolquof Soil gm. Lewis Publishers. Ann Arbor, MI. Dom, R (1979). "Cadmium and the Food Chain." Cornell Veterinarian (LJSA). 69:4 (323- 344). Edward, A. (1967). _Sgttistica‘L Methods. Second Edition. Holt, Rinehart and Winston, Inc. New York. Eisler, R; and G. Gardner (1973). "Acute toxicology to an estuarine teleost of mixtures of cadmium, copper and zinc salts." Journal of Fish Biology 5: 131-142. Eisler, R. (1985). Cadmium Hazards to Fish, Wildlife. 1nd Invertebrates: A Smoptic m. U.S. Fish and Wildlife Service. Laurel, MD. Eisler R. (1986). Chromium Hazard to F isl_r, Wildlife, and Invertebrates: A ngoptic Review. U.S. Fish and Wildlife Service. Laurel, MD. Eisler R. (1987). Mercury Hazards to FishL Wildlife, and Invertebrates: A Smopfic lie—view, U.S. Fish and Wildlife Service. Laurel, MD. Eisler, R. (1988). Lead Hazard to Fis_h. Wildlife. Ed Invertebrates: A Smoptic review. U.S. Fish and Wildlife Service. Laurel, MD. Elias, Z., et al. (1989). "Cytotoxic and neoplastic transforming effects of industrial hexavalent chromium pigments in Syrian hamster embryo cells. " Carcinogenesis. 10 (11): 2043-2052. Blinder, C. (1986). "Zinc." Handbook on the Toxicology of Metals, Second Edition. Volume II: Specific Metals. Elsevier, New York, pp. 664-679. Environmental Criteria and Assessment Oflice (1984). Health Assessment Document for Chromium. U.S. Environmental Protection Agency. Research Triangle Park, North Caroline. Environmental Data Services (1980). Report 63. Orchard House. London. EPA (1980a ). Ambient Water My’ Criteria for Cadmium.Cincinnati, Ohio. Ofice of Health and Environmental Assessment, Environmental Criteria and Assessment Office. EPA (1980b ) Ambient Water M'ty Criteria for Zinc. Cincinnati, Ohio. Office of Health and Environmental Assessment, Environmental Criteria and Assessment Office. Research Triangle Park, NC. 177 EPA (1984). Health Effects Assessment for Mercury Environmental Criteria and Assessment Office. Research Triangle Park, NC. EPA (1985). Environmental Profiles and Hazard Indices for Constituents of Municipal Sludge: CedmiumEnvironmental Criteria and Msessment Ofiice. Research Triangle Park, NC. EPA (1986). Toxicology of Metals. Vol 2: Zinc. Washington, DC. EPA report. EPA (1987a). Merch Health Effects Update: Health Issue Assessment. Environmental Criteria and Assessment Office. Research Triangle Park, NC. EPA (1987b). Sum Review of the Health Effects Assecjeted with Zinc and Zine page. Washington, DC. EPA (1989). Toxicological Profile for Cadmium. Agency for Toxic Substances and Disease Registry. Atlanta, Ga. F eamcombe, J. (1995). ”Design Strategies Help Packagers Overcome Environmental Hurdles. ” Packaging Technology & Engjpeering. 22:22-27. Finley, B. ; Proctor, D.; and Paustenbach, D. (1992). "An Alternative to the US EPA's Proposed Inhalation Reference Concentrations for Hexavalent and Trivalent Chromium. " Regplatog Toxicology and Pharmacology. 16: 161-176. Fishman, D.; and Adelsky, J. (1992). ”Heavy Metals Regulations for Printing Ink Users." American Ink Maker. 70: 3. Fleisher, L.; Yorio, T.; and Bentley, P. (1975)." Effect of Cadmium on Epithelial Membranes. Toxinogy and Applied Pharmacology." 33: 384-387. Flower, F. ; Leone, 1.; Gilman, E.; and Arthur, J. (1978).Study of Vegetation Problems Asm’ated with Refirse Landfills. EPA. Frei, B.; and Gaziano, M. (1993) . ”Content of antioxidants, preformed lipid hydroperoxides, and cholesterol as factors of the susceptibility of human LDL to metal ion-dependent and-independent oxidation. " Journal of Lipid Research 34 (12): 2135-2145. Friberg, L (1977). Toxicology of Metals. Volume 2. EPA/600/ 1-77/022. Permanent Commission and International Association of Occupational Health. Rearch Triangle Park, N. C. 178 Gafaber, W. (1967) . Occupational Diseases. US Department of Health, Education, and Welfare. Gagne, F.; Marion, M.; and Denizeau, F. (1989). "Metal Homeostasis and Metallothionein induction in Rainbow Trout Hepatocytes Exposed to Cadmium.” Fundamental and Applied Toxicology. 14: 429-437. Gennart, J. et al. (1993). "Increased sister chromatid exchanges and tumor markers in workers exposed to elemental chromium, cobalt and nickel containing dusts." Mutation Research. 299: 55-61. Gols, A. (1990). "Metals in Sewage Must be Reduced." New YoLk Times, Sec 1. p. 35. Hallenbeck, W. (1979). "Municipal Sludge Management: Health Aspects of Crop Uptake of Cadmium from Sludge-Amended Soil and Recommendations for Regulation.” Environmental Management. 3 (2): 155-158. Hammens, A. et al. (1978). Reviews of the Environmentafifi‘ects of Pollutapts : IV. Cadmium. Health Efi‘ect Research Laboratory. Cincinnati. Hankin, L.; Heichel, G.; and Borsford, R (1974). ”Lead Content of Printed Polyethylene Food Bags. " Bulletin of Environmental Contamination & Toxicology. 12 (6) :. 645-648. Harding, H. (1957). " Some enquiries into the toxicology of zinc stearate.” Br. J. In_d._Med. 15: 130-132. Hattori, H. (1989). "Influence of Cadmium on Decomposition of Sewage Sludge and Microbial Activities in Soils." Soil Sci. Plant Nutr. 35 (2): 289-299. Hays, W. (1994). Statistics. F ifth Edition. Harcourt Brace College Publishers. Texas. Heichel, G.; Hankin, L.; and Botsford, R (1976). " Lead in Paper: a Potential Source of Food Contamination. ” Milk Food Technology (USA). 37(10) : 499, 505. Hickman, E. (1 98 7). ”Raw Materials- the trend towards a safer environment. " Polymeric Paint Colour Jogmal. 177: 4192. Hildennan, E; and Taylor, P. (1974). "Acute pulmonary emphysema in cattle exposed to zinc oxide firrnes. " Can. Vet. J. 15:173-175. Hill, E. (1 979). "Co-precipitation: a new approach to production of pigments. " American Ink Makers. 5 7: 9. 179 Hill, G.; Miller, E.; and Stowe, H. (1983). "Effect of dietary zinc levels on health and productivity of gills and sows through two parities”. J. Anim. Sci. 57:114-122. Hyland, T. (1990). "Ink Makers Take on Heavy Metals." Paperboard Packegrp' g. 75:10,pp.28,30,32. Hutchinson, G. (1979). ”The move away fiom lead." British Ink Maker. 21 :3: 98-100. Johnston, G. (1992). " Swimming in the Sea of Regulation." Flexo. 17: 4. Jones, K.; Symon, C.; and Johnston, A. (1987). "Retrospective Analysis of an Archived Soil Collection. II. Cadmium." The Science of the Total Environment. 67: 75-89. Juran, J. (1974). Mity Control Handbook. McGraw-Hill Book Company. New York. Kapil, V.; and Keogh, J. (1990). Chromium Toxici_ty. Agency for Toxic Substances and Disease Registry. U.S. Dept. of Health and Human Services. Atlanta,Ga. Kartz, S.; and Salem, H. (1993). ”The Toxicology of Chromium with Respect to its Chemical Speciation : Review.” Jouml of Applied Toxicology. l3 (3) : 217-224. Kew, G. (1980). An Exposure and Risk Assessment for Mercug. U.S. Environmental Protection Agency. Washington DC. Kjellstrom, T.; Friberg, L.; and Rahnster, B. (1979). "Mortality and Cancer Morbibity among Cadmium-Exposed Workers. " Environmental Health Perspectives. 28: 199-204. Klevay, L. (1973). "Hypercholesterolemia in rats produced by an increase in the ratio of zinc to copper ingested.” Amer. J. Clin. Nutr. 26:1060-1068. Kobusch, A; and Bock, K. (1990). ”Zinc Increases EEG-stimulated DNA Synthesis in Primary Mouse Nepatocytes." Biochemical Pharmacology. 39(3):555-8. Kok, F.; Van Duijn, C.; Hofrnan, A; Vander Voet, G.; and De Wolfi‘, F. (1988) " Serum Copper and Zinc and the Risk of Death from Cancer and Cardiovascular Disease.” American Journal Epidemiology. 128:352-9. Kritharides, L.; Jessup, W.; Gifford, J.; and Dean, R (1993) ."A Method for Defining the Stages of Low-Density Lipoprotein Oxidation by the Separation of Cholesterol and Cholesteryl Ester- Oxidation Products Using HPLC. " Anebgical Bieehemimy 213:1,p.79—89. 180 Krupa, Z.; Ruszkowski, M.; and Gilowska-Jung, E. (1982). "The effect of chromate on the synthesis of plastid pigments and lipoquinones in Zea mays L. seedlings". Acta Societatis Botanicorum Poloniae. 51 (2): 275-281. Lam, H.; Conner, M.; Rogers, A; Fitzgeraldand, S.; and Amdur, M. (1985). "Functional and morphologic changes in the lungs of guinea pigs exposed to fi'eshly generated ultrafine zinc oxide." Toxicol. Appl. Pharmacol. 78:29-38. Lamb, D.; and Leake, M. (1994). "Acidic Ph enables caeruplasmin to catalyze the modification of low-density lipoprotein." Febs Letters . 338 (2) : 122-126. Langard, S. (1993). "Role of chemical species and exposure characteristics in cancer among persons occupationally exposed to chromium compounds." Scand. J. Work Environ. Health. 19 / Suppl 1, pp. 81-89. Lansdown , R.; and Yule, W. (1986). Lead Toxicity. The John HOpkins University Press. Washington DC. Larson, M. (1992). "Dress up that Bottle." Packaging (U .S.). 37 : 3. Lauweys, R.; Buchet, J .; Roels, H.; Brouwers, J .; and Stanescu, D. (1974). ”Epidemiological Survey of Workers Exposed to Cadnrium." Arch. EnvironHealth. 28( 3): 145-148. Lavelle, J.; and F etsko, J. (197 7). Lead in the Consumer Environment. National Association of Printing Ink Manufacturers. Indiana. Lead Chromate Committee (1987). "A new look at lead chromate pigments." American Ink Maker. 65 (3): 36,38,40,94-95. Lee, D.(1972). Metallic contaminants and human health. John E. Fogarty International Center for Advanced Study in Health Sciences. Proceedings, No. 9. Environmental Sciences. Academic Press, New York. Leh, F .; and Lak, R. (1974). Environment and Pollution Sources Health Efi‘ects, Monitoring and Control. Charles C Thomas Publisher, Springfield Illinois. Leonard, A; and Gerber, G. (1989)."Zinc toxicity; does it exist?". Journal of the American College of Toxicolqu. 8: 1285-1290. Leonard A; Jacquet, P.; and Lauwerys, R. (1983). "Mutagenicity and teratogenicity of mercury compounds." Mutgtion Research 114 (1): 1-18. 181 Levy, L.; and Venitt, S. (1986). "Carcinogenicity and mutagenicity of chromium compounds: the association between bronchial metaplasia and neoplasia." Carcinogenesis. 7 (5): 831-835. Lloyd, R. (1960)." The toxicity of zinc sulphate to rainbow trout." Annals of Applied Biology. 48(1):84-94. Lowe-Jinde, L.; and Niimi, A (1984). "Short-term and Long-term Effects of Cadmium on Glycogen Reserves and Liver Size in Rainbow Trout." Arch. Environ. Contam. Toxicol. 13: 759-764. Luo, S.; Plownan, M.; Hopfer, S.; and Sunderrnan Jr., P. (1993) ”Embryotoxicity and Teratogenicity of Cu2+ and Zn2+ for Xenopus Iaevr's, Assayed by the FETAX Procedure." Annals of Clinical and Laboratory Science. 23(2):]10-20. Lusting, T. (1990). "Inks and Heavy Metals Don't Mix." Graphics and Arts Mon. 62:8. Madry, A. (1978). Bioassay of Soils Contaminated by Secondm Brass and Coppg Company. Ofice of Air Pollution Control.Technical Support Operations. Connecticut. Matthiessen, P.; and Brafield, A. (1973). "The effects of dissolved zinc on the gills of the stickleback Gasterosteus aculeatus (L)." Journal of Fish Biology. 52607-613. McCarthy, J. (1993). "Exposure to mercury vapor. " Occupational Health. 35(6): 256-262. Minear, R; Ball, 0.; and Church, R. (1981). Data Base for InfluentLHeayy Metals in Publicly Owned Treatment Works. U. 8. Environmental Protection Agency. Municipal Envionmental Research Lab. Cincinnati, OH. Monks, R. (1990). Worries Growing Over Use of Cadmium. Plastics Technology. 36 (3): 113-115. Mueller, P. (1993). "Detecting the Renal Effects of Cadmium Toxicity.” Clin. Chem. 39(5): 743-745. Murray T.; Walker, 3.; Spratt, D.; and Chappelka, R (1981). "Cadmium Nephropathy: Monitoring for Early Evidence of Renal Dysfirnction. " Arch. Environ. Heal_t__h. 36 (4): 165-171. National Academy of Sciences (1974). Chromium: Its Medical and Biological Effects of Environmeptel Palms. National Research Council. Washington, DC. National Academy of Sciences (1977). Cappg: Its Medical and Biologic Effects of Enviremne_n_t§l Ppllugrts. National Research Council. Washington, DC. 182 National Academy of Sciences (1979). Zinc. United States National Academy of Sciences, National Research Council, Subcommittee on Zinc. University Park Press, Baltimore, Md. National Research Council (U .S.)(l974). Chromium. National Academy of Sciences. Washington DC. National Research Council. Copper. (1977). Committee on Medical and Biologic Efl‘ects of Environmental Pollutants. Environmental Protection Agency, Washington, DC. NIOSH (1975). Occupational Exposure to Chromium (yr). National Institute for Occupational Safety and Health . U.S. Dept. of Health Education and Welfare, Cincinnati. Nriagu, J. (1979a). The Biogeochemistgg of Mercug in the Environment. Elsevier/ North- Holland Biomedical Press. Amsterdam, New York. Nriagu, J. (1979b) Comm in the Environment. Part I: Ecological Cycling and Part H: Health Effects. John Wiley and Sons, New York. Nriagu, J .; and Sprague, J. (1987). Cadmium in the Aquatic Environment. John Wiley & Sons. New York. Nriagu, J .; and Nieboer, E. (1988).Advances in Environmental Science and Technology. Vol. 20. John Wiley & Sons. New York. Nriagu, J. (1980) Zinc in the Environment Part 11: Health Effects. John Wiley & Sons. New York. Nriagu, J. (1990). "Food Contamination with Cadmium in the Environment." Advances in Environmental Science and Technology. 23: 59-84. Needleman, H. (1991). Human Lead Exposure. CRC Press. Washington, DC. OSHA (1975). Lead. U.S. Dept. of Labor, Occupational Safety and Health Administration. Washington, DC. OSHA (1979). Health Hazards f Chromate Pi ents Paints: H valent Chromium. Dept. of Labor, Occupational Safety and Health Administration. OSHA (1992). Mpatipnal Emsure to Cadmium. U.S. Dept. of Labor. Occupational Safety and Health Administration.Washington, D.C. 183 Osuna, 0.; and Edds, G. (1982). ”Toxicology of aflotoxin B1, warfarin, and cadmium in young pigs: Performance and hematology." Am. J. Vet. Res 43 (8): 1380-1386. Peereboom J.; and Copius, J. (1981). "Exposure and Health Effects of Cadmium. Part 2: Toxic Effects of Cadmium to Animals and Man." Toxicological and Environmental Chemistry Reviews. 4 (1/2): 67-178. Pickering, Q.; and Vigor, W. (1965). "The acute toxicity of zinc to eggs and fly of the fathead minnow." Proggessive Fish Culturist. 27: 153-157. Piscator, M. (1981). "Role of Cadmium in Carcinogenesis with Special Reference to Cancer of the Prostate." Environmental Health Perspectives. 40: 107-120. Pounds, J. (1985). The Toxic Effects of Metals in Industrial Toxicolagy. LifeTirne Learning publications, New York. p. 195-209. Preda, N.; Popa, E.; and Ariesan, M. (1983). "The Possibility of Food Contamination with Cadmium by means of Colored Plastics." Journal of Applied Toxicology. 3 (3): 139-142. Prasad, S. (1993). "Essentiality and Toxicity of Zinc." Scandinavia__n Jam pf work, environment&health 19: 134-6 Reed , A; Richey, B.; and Roseboom, C. (1980). Acute Toxicity of ZinLcto Some Fishes in High Alkalinigy Water. Illinois State Water Survey Div., Charnpaign. Renson, J. (1992). "Environmental Regulations Affecting the Printing Ink Industry." American Ink Maker. 70: 3. Roels, H.; Lauwerys, R; Buchet, J .; Bernard, A; Barthels, A.; Oversteyns, M.; and Gaussin, J. ( 1982). "Comparison of Renal Function and Psychomotor Performance in Workers Exposed to Elemental Mercury." Int. Arch. OccuL Environ. Health. 50:77-93. Rusterholtz, W. (1987). "Inks and the Environment: An Update for Boxrnakers." Boxboard Containers. 95(2): 27-28. Rusterholtz, W. (1989). "Heavy Metal Paranoia." American Ink Makers. 67 : ll. Rusterholtz, W. (1992). "Metals, Pigments, and Printing Ink." American Ink Mger. 70: 6. Salonen, J. et a1. (1992) . "Autoantibody against Oxidised LDL and Progression of Carotid Atherosclerosis." The Lancet. 339(8798)p.883-888. 184 Samanta, K.; and Pal, B. (1986). "Zinc feeding and fertility of male rats." Int. J. Vim Nutr. Res. 56:105-107. Samman, S.; and Roberts, D. (1988). "Zinc and cholesterol metabolism." Nutrition Research. 82559-570. Sampson, J .; Graham, R; and Hester, H. (1942)."Studies on feeding zinc to pigs." Cornell V_et. 32:225-236. Sastry, K.; and Tyagi, S. (1981). "Toxic effects of Chromium in a Freshwater Teleost Fish, Channa Punctatus." Tofiwlowers. 11(1): 17-21. Saxena, R; Bedwal, R; and Mathur, R (1989). "Zinc toxicity and male reproduction in rats: a histological and biochemical study." Trace Elements in Medicine. 6:119- 133. Shaikh, Z.; Tohyarna, C.; and Nolan, C. (1987). "Occupational exposure to cadmium: Effect on metallothionein and other biological indices of exposure and renal firnction." Archives of ToxicoLogy. 59(5): 360-364. Shepherd, C.; and Jones, R (1971). Hexavalent chromiam: Toxicological effects and means for removalfi from aqueous solution. Naval Research Laboratory. Washington, DC. Singhal, R; and Thomas, J. (1980). Lead Toxicig. Urban & Schwarzenberg. Maine. Skidmore, J. (1967). "Oxygen uptake by zebrafish (Brachydanio rerio) of different ages in relation to zinc sulphate resistance." Journal; of the Fisheries Research Board of Canada. 24(6): 1253-1267. Skidmore, J.; and Tovell, P. (1972). "Toxic effects of zinc sulphate on the gills of rainbow trout." Water Research. 6:217-230. Skidmore, J. (1966). "Resistance to zinc sulphate of zebrafish (Brachydanio rerio) embryos after removal or rupture of the outer egg membrane. " J oumal of the Fisheries Research Board of Canada. 23(7): 103 7-1041. Smith, 8.; and Embling, P. (1984). "The influence of chemical form of zinc on the effects of toxic intraruminal doses of zinc to sheep." JAT J. Appl. Toxicol. 4:92-96. Spieker C.; Zidek, W.; and Zumkley, H. (1987). ”Cadmium and Hypertension." Nephron. 47, (suppl. 1): 34-36. 185 Sprague, J. (1986). TaxiaigLand tissue concentrations of lead zinc and cadmium for W. International Lead Zinc Research Organization, Research Triangle Park, NC. 215 pp. Stansley W.; Roscoe, D.; and Hazen, R (1991). "Cadmium contamination of deer livers in New Jersey; human health risk assessment." The Science of the Totg Environment. 107: 71-82. Stern, A; Bagdon, R; Hazen, R; and Marzullin, F. (1993). "Risk Assessment of the allergic dermatitis potential of environmental exposure to hexavalent chromium." Journal of Toxicology and Environmental Health. 40(4): 613-641. Sullivan, J. (1969). Air Pollution Aspects of Chromium apd its Communds. National Air Pollution Control Administration. Bethesda, Maryland. Susuki, T.; Imura, N.; and Clarkson, T. (1991). Admces in Mercury Toxicolagy. Plenum Press, Rochester series. New Jersey. Tang, A; Graham, M.; Kirby, A; McCall, L.; erlett, W.; and Saab, J. (1993). "Dietary Micronutrition Intake and Risk of Progression to Acquired Immunodeficiency Syndrome (AIDS) in Human Immunodeficiency Virus Type 1 (HIV -1)-infected Homosexual Men.” The American Journal of Clinical Nutrition. 138(11):937-951. Tang, X.; Chen, X.; Zhang, J.; and Qin, W. (1990). "Cytogenetic Investigation in Lymphocytes of People Living in Cadmium-polluted Areas. " Mugtion Research. 241: 243-249. Taylor, D. (1979). "A review of the lethal and sub-lethal effects of mercury on aquatic life." Residue Reviews. 72: 33-69. Taylor, D. (1983). "The significance of the accumulation of cadmium by aquatic organisms." Ecotoxicology and Environmental Safety. 7(1): 33-42. Thompson Publishing Group (1995). Environmental Packaging. U.S. Guide to Green Labeling, Packagrp' g and Regycling. Washington, DC. Thun, M.; Osorio, A; Schober, S.; Harmon, W.; Lewis, B.; and Halperin, W. (1989). "Nephropathy in cadmium workers: assessment of risk from airbone occupational exposure to cadmium." British Journal of Industrial Marine. 46: 689-697. Tierney, D.; Blackwood, T.; and Briggs, T. (1979). Status Assessment of Toxic Chemicals. Industrial Environmental Research Laboratory. Cincinnati, Ohio. 186 Towill, L.; Shriner, C.; Drury, J .; Hammons, A; and Holleman, J. (1977). Reviews of the Environmental Efl‘ects of Pollu_tants: III. Chromium. Health Effects Research Laboratory. U.S. Environmental Protection Agency. U. S. Department of Health and Human Services (1990a). Toxicological Profile for Copper. Public Health Services. Atlanta, Ga. U.S. Department of Health & Human Services (1990b). Lead Toxiciry. Public Health Services. Atlanta, Ga. U.S. Department of Health and Human Services (1993a). Toxicological Profile for Cadmium. Public Health Services. U.S. Department of Health and Human Services (1993b). Update: Toxicological Profile of ChromiumSyracuse Research Corporation. Atlanta, Ga. Venugopal, B.; and Luckey, T. (1983) . Mpepal Toxicimj in Mammals. Vol. 2. Plenum Press, New York. Venugopal, B.; and Luckey, T. (1977-1978) MetaLToxicifitLin Mammals. Vol. 2. Plenum Press, New York. pp. 69-76. Waalkes M.; Coogan, T.; and Barter, R. (1992). "Toxicological Principles of Metal Carcinogenesis with Special Emphasis on Cadmium." Critical Reviews in Toxicology. 22: (3,4): 17 5-201 . Webb, J. (1991). "Copper and Cholesterol Make a Lethal Cocktail." New Scientist 130(1764): 20. Webb, M. (1975). "Cadmium." British Med. Bull. 31(3): 246-250. White, I. (1955). "The toxicity of heavy metals to mammalian spermatozoa." Austr. J. Exp. Biol. 33:359-366. Winder, C. (1984). The Developmental Neurotoxicigr of Lead. MIT Press LimitedNew York. Williamson A; Teo, R; and Sanderson, J. (1982). "Occupational Mercury Exposure and its Consequences for Behavior." Int. Arch. Occup. Environ. Health. 50:273-286. \Vrtter, E. (1989). Agp'cultural Use of Sewage Sludge. Naturvardsverket Rapport: 3620. Wolf, A; and Baker, D. (1979). "Cadmium limits for cropland indicated in sewage sludge." Science in Agriculture. 26(3): 10-11. 187 World Health Organization. (1977). EnvironmentaL Health Criteria3: Lea_d.Washinton, D.C. Zettergren, L.; Boldt, B.; Petering, D.; Goodrich, M.; Weber, D.; and Zettergren, J. (1991). "Effects of prolonged low-level cadmium exposure on the tadpole immune system.” ToxicologyLetters. 55: 11-19.