3

Dimensions of the Problem: Exposure Assessment

EXPOSURE ASSESSMENT IS A crucial component of environmental epidemiology studies that seek to establish causal relationships between exposure to chemical and physical agents from hazardous-waste sites and adverse consequences to human health. The discipline of exposure assessment encompasses numerous techniques to measure or estimate the contaminant, its source, the environmental media of exposure, avenues of transport through each medium, chemical and physical transformations, routes of entry to the body, intensity and frequency of contact, and spatial and temporal concentration patterns. Exposure to a contaminant is defined as “an event that occurs when there is contact at a boundary between a human and the environment at a specific contaminant concentration for a specified period of time; the units to express exposure are concentration multiplied by time” (NRC, 1991, p. 3).

In environmental epidemiology, exposure assessment has proved difficult. Epidemiologic research typically involves retrospective studies. When data are gathered retrospectively, there is an enormous opportunity for exposure assessment to be influenced by apparent disease occurrence, and vice versa. Records of environmental pollution can sometimes provide a surrogate for exposure, but these surrogates are not always available, and direct measures of past exposures have not usually been recorded.



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ENVIRONMENTAL EPIDEMIOLOGY: Volume 1 3 Dimensions of the Problem: Exposure Assessment EXPOSURE ASSESSMENT IS A crucial component of environmental epidemiology studies that seek to establish causal relationships between exposure to chemical and physical agents from hazardous-waste sites and adverse consequences to human health. The discipline of exposure assessment encompasses numerous techniques to measure or estimate the contaminant, its source, the environmental media of exposure, avenues of transport through each medium, chemical and physical transformations, routes of entry to the body, intensity and frequency of contact, and spatial and temporal concentration patterns. Exposure to a contaminant is defined as “an event that occurs when there is contact at a boundary between a human and the environment at a specific contaminant concentration for a specified period of time; the units to express exposure are concentration multiplied by time” (NRC, 1991, p. 3). In environmental epidemiology, exposure assessment has proved difficult. Epidemiologic research typically involves retrospective studies. When data are gathered retrospectively, there is an enormous opportunity for exposure assessment to be influenced by apparent disease occurrence, and vice versa. Records of environmental pollution can sometimes provide a surrogate for exposure, but these surrogates are not always available, and direct measures of past exposures have not usually been recorded.

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ENVIRONMENTAL EPIDEMIOLOGY: Volume 1 Rothman (1990) noted estimates of exposure are very often heterogenious, poorly described, and involve low concentrations of toxicants. Although essential to well-designed epidemiologic investigations, exposure assessment has been and continues to be an inadequately developed component of environmental epidemiology, because the temporal characteristics of site discovery and investigation make it difficult; the conceptual framework and techniques for evaluation have only recently been established; epidemiologists often have not understood or given sufficient attention to exposure evaluation. This chapter has three sections. The first describes the potential for human exposure by identifying toxic chemicals found at hazardous-waste sites. This includes direct site contamination, contamination by unidentified or uncharacterized pollutants, and groundwater contamination from other sources. The second section discusses approaches to exposure assessment and their attendant problems. The third section examines reported exposure assessments associated with hazardous-waste sites and reviews the strengths and weaknesses of the reports. TOXIC-CHEMICAL EXPOSURE AT WASTE SITES Although much of the waste produced annually in the U.S. is not listed as hazardous, the U.S. Environmental Protection Agency (EPA) estimated in 1988 that the amount of hazardous waste managed by approximately 3000 licensed facilities was 275 million metric tons (EPA, 1988). In addition, there are a substantial number of uncontrolled disposal sites that contain hazardous wastes and that could present serious environmental or public health problems. For example, municipal waste sludge and incinerator ash can contain toxic materials such as lead, cadmium, mercury, and other toxic materials. In the late 1970s there was widespread publicity about the indiscriminate dumping of waste that was resulting in release of toxic agents into the environment. The national failure to address the many known and suspected hazards from uncontrolled hazardous waste sites led Congress to pass the Comprehensive Environmental Response, Compensation, and Liability Act of 1980 (CERCLA), generally known as the Superfund law. Under CERCLA's terms, more than 31,000 sites have been reported to EPA's CERCLA Information System (CERCLIS) inventory of sites that could require cleanup. EPA

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ENVIRONMENTAL EPIDEMIOLOGY: Volume 1 has completed more than 27,000 preliminary assessments, and more than 9000 sites have been investigated in detail (EPA, 1988). As of June 1988, EPA's National Priorities List (NPL), included 1236 sites, about 30 percent of which have had initial actions to reduce immediate threats. The number of identified sites represents a small proportion of the sites that are expected to be identified in the future (OTA, 1989). HAZARDOUS-WASTE SITES Within the past decade, estimates of the number of potential NPL sites have shifted dramatically. The Office of Technology Assessment (OTA, 1989) concludes that there could be as many as 439,000 candidate sites. This is more than 10 times that estimated earlier by EPA. These sites include Resource Conservation and Recovery Act (RCRA) Subtitle C and D facilities, mining waste sites, underground leaking storage tanks (nonpetroleum), pesticide-contaminated sites, federal facilities, radioactive release sites, underground injection wells, municipal gas facilities, and wood-preserving plants, among others. One recent EPA survey found that more than 40 million people live within four miles and about 4 million reside within one mile of a Superfund site. Residential proximity does not per se mean that exposures and health risks are occurring, but the potential for exposure is increased. As of December 1988, the Agency for Toxic Substances and Disease Registry (ATSDR) concluded that 109 NPL sites (11.5 percent) were associated with a risk to human health because of actual exposures (11 sites) or probable exposure (98 sites) to hazardous chemical agents that could cause harm to human health. These NPL sites were listed in the categories of “urgent public health concern” or “public health concern.” The states with the largest number of NPL sites are New Jersey, Pennsylvania, California, Michigan, and New York. They accounted for 464 of 1236 (37.5 percent) sites as of 1991 (Figure 3-1). The activities associated with these sites are shown in Table 3-1. Figure 3-2 depicts the observed contamination of various media as a percentage of 1189 final sites on the NPL as of February 1991. Note that a site can have more than one type of contamination. Data derived from the 951 ATSDR health assessments at hazardous-waste sites indicate the existence of more than 600 different chemical substances. Some of them are listed in Table 3-2. The documented migration of substances into water, soil, air, and food also is listed in Table 3-2. Most of the identified agents are toxic and represent potential threats to the public health, depending on the degree of expo-

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ENVIRONMENTAL EPIDEMIOLOGY: Volume 1 FIGURE 3-1 Few Superfund sites completely cleaned up. Source: Adapted from Viviano, 1991, with permission. sure. Of the compounds identified at more than 100 sites, lead, chromium, arsenic, cadmium, nickel, trichloroethylene (TCE), perchloroethylene (PCE), vinyl chloride, methylene chloride, chloroform, benzene, ethylene dichloride (EDC), and polychlorinated biphenyls (PCB) have been identified as either human or animal carcinogens and are classified in group 1 of the ATSDR-EPA list of the 100 most hazardous substances. A list of agents identified at more than 10 proposed and final NPL sites is listed in Appendix 3-A to this chapter, and the original ATSDR list of priority substances can be found in Appendix 3-B. Buffler et al. (1985) have reviewed the adverse health effects associated with specific toxicants identified at hazardous-waste sites. While discussing the types of chemicals found, the review addresses whether health effects could be detected in studies of populations exposed to these chemicals at waste-disposal sites. Skin and central nervous

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ENVIRONMENTAL EPIDEMIOLOGY: Volume 1 TABLE 3-1 Types of Activities at Hazardous-Waste Sites in the United States (Includes 1177 Final and Proposed Sites Placed on the National Priorities List as of June 1988) Activity Final Proposed Total Surface impoundments 295 137 432 Landfills, commercial/industrial 299 113 412 Containers/drums 229 64 293 Other manufacturing/industrial 102 137 237 Landfills, municipal 157 56 213 Spills 111 73 184 Chemical processing/manufacturing 82 78 160 Waste piles 73 46 119 Leaking containers 80 36 116 Tanks, above-ground 80 28 108 Tanks, below-ground 46 42 88 Groundwater plumes 63 12 75 Electroplating 36 27 63 Wood preserving 39 16 55 Waste oil processing 34 16 50 Ore processing/refining smelting 27 9 36 Open burning 24 12 36 Solvent recovery 24 11 35 Outfall, surface water 20 15 35 Military ordnance production/storage/disposal 19 14 33 Military testing & maintenance 16 10 26 Landfarm, land treatment/spreading 18 7 25 Battery recycling 17 6 23 Incinerators 17 1 18 Mining sites, surface 11 4 15 Underground injection 11 2 13 Drum recycling 8 4 12 Sand and gravel pits 7 3 10 Mining sites, subsurface 6 3 9 Road oiling 7 1 8 Laundries/dry cleaners 2 5 7 Sinkholes 6 1 7 Explosive disposal/detonation 2 1 3 Tire storage/recycling 2 0 2 Total sites a: 799 378 1177 a Since each site may have more than one activity, the number of activities is greater than the number of sites. Source: U.S. Environmental Protection Agency, Office of Emergency Response, Washington, D.C. 20460.

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ENVIRONMENTAL EPIDEMIOLOGY: Volume 1 FIGURE 3-2 NPL: Types of activities at 1189 final sites. Source: Environmental Protection Agency, Office of Solid Waste and Emergency Response, 1991. system (CNS) effects were the most likely effects to occur from direct contact with waste site chemicals. Hepatic, hematopoietic, renal, reproductive, and CNS effects were the most likely indicators of chronic, low-dose exposure through ingestion. UNIDENTIFIED OR UNCHARACTERIZED CONTAMINANTS To date, attention has focused on a relatively small number of chemical contaminants identified at hazardous-waste sites. Many identified or unidentified potential contaminants have received little scrutiny. These uncharacterized pollutants include substances that are not on the ATSDR-EPA list of 100 most hazardous substances, compounds that cannot be identified by standardized or accepted analytical methods, previously unidentified substances that result from in situ transformation processes, and by-products of treatment techniques. MacKay et al. (1989) suggest that large quantities of these potentially toxic compounds may be relatively mobile in the subsurface environment, and a potential exists for these compounds to contaminate groundwater.

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ENVIRONMENTAL EPIDEMIOLOGY: Volume 1 One EPA evaluation (Bramlett et al., 1987) of the composition of leachates from hazardous-waste sites documents the potential problem. The chemical composition of leachates from 13 sites located throughout the U.S. was analyzed. Only 4 percent of the total organic carbon (TOC) in the leachate was characterized by gas chromatography/mass spectroscopy according to their chemical structure. More than 200 separate compounds were identified in the 4 percent fraction. This included 42 organic acids, 43 oxygenated and heteroaromatic hydrocarbons, 39 halogenated hydrocarbons, 26 organic bases, 32 aromatic hydrocarbons, 8 alkanes, and 13 metals. The unidentified 96 percent of organic carbon is of unknown toxicity. Overall, the number of chemical agents found in the 4 percent of the leachate studied is large, and yet this represents only a fraction of the overall organic contribution. In addition to the toxicity of these chemical agents, whether the mobile compounds promote transport of chemical toxicants is an important subject for research. Research in California by MacKay et al. (1989) has documented the examples of uncharacterized compounds that could have important toxicologic properties or significance for transport. Chlorobenzenesulfonic acids have been identified at the Stringfellow Acid Pits in Glen Avon and at the BKK landfill in West Covina; arsenicals were found at a site in Rancho Cordova; and brominated alkanes were found at the Casmalia hazardous-waste disposal site, along with high melting explosive (HMX) (cyclotetramethylene tetramintriamine), research department explosive (RDX) (cyclonite), and mutagenic explosive by-products from the Lawrence Livermore National Laboratory, to name just a few. NONPOINT SOURCES As important as the NPL sites are, focusing attention solely on the chemicals identified at these sites understates the potential scope of the problem of groundwater contamination. Toxic contaminants in groundwater can be considered as “hazardous waste” in a public health or toxicologic context, in contrast to the regulatory framework for defining hazardous waste. Secondly, contaminated groundwater close to defined hazardous-waste sites may act as a confounder in environmental epidemiologic investigation. In California, for example, 70 percent of public drinking water comes from groundwater (Leeden et al., 1990). Moreover, recent surveys show that problems with ground-water are not unique to California. In 1986, EPA reported to Congress that groundwater contamination from organic chemicals had occurred or was occurring in 70 percent of the states; 65 percent and

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ENVIRONMENTAL EPIDEMIOLOGY: Volume 1 TABLE 3-2 Selected Hazardous Substances at 951 National Priorities List Sites: Number and Percentage of Sites and Documented Migration of Substances into Specific Media Substance ATSDR Priority Group No. % Sites with Migration Groundwater Surface Water Soil Air Food Sediment Metallic Elements   564 59 327 234 138 122 37 50 114 Lead 1 404 43 224 159 84 88 28 39 84 Chromium 1 329 35 142 93 55 48 12 15 46 Arsenic 1 262 28 36 92 46 54 16 19 50 Cadmium 1 232 24 112 72 49 45 18 21 44 Mercury 2 129 14 58 29 24 20 6 10 19 Nickel 1 126 13 55 30 24 15 3 8 21 Beryllium 1 21 2 9 2 3 1 0 0 3 Volatile Organic Compounds (VOCs)   518 54 268 236 88 81 71 31 58 Trichloroethylene 1 402 42 231 204 63 41 44 19 27 Benzene 1 323 34 139 115 41 27 29 9 24 Tetrachloroethylene 1 267 28 125 116 28 22 34 11 17 Toluene 2 256 27 101 78 26 29 26 6 20 Vinyl Chloride 1 187 20 87 80 16 14 18 7 9 Methylene Chloride 1 183 19 81 61 21 16 17 4 9 Chloroform 1 142 15 74 61 20 8 7 3 9 1,4-Dichlorobenzene 1 31 3 7 6 0 1 1 0 1 Polychlorinated Biphenyls (PCBs) 1 162 17 86 43 25 40 11 25 39

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ENVIRONMENTAL EPIDEMIOLOGY: Volume 1 Polycyclic Aromatic Hydrocarbons (PAH)   187 20 75 32 22 31 4 6 38 Benzo(a)pyrene 1 56 6 18 6 6 9 0 2 8 Benzo(a)anthracene 1 32 3 10 3 4 8 0 1 6 Benzo(a)fluoroanthene 1 25 3 10 1 3 5 0 0 4 Chrysene 1 23 2 6 2 1 3 0 1 4 Dibenzo(a,h)anthracene 1 4 <1 1 0 0 1 0 0 0 Phthalates   106 11 35 22 13 17 5 5 16 Bis(2-ethylhexyl)phthalate 1 88 9 35 22 13 16 3 5 16 Pesticides   82 9 25 13 8 17 6 7 12 Dieldrin/aldrin 1 29 3 13 8 2 6 3 2 3 Heptachlor/heptachlor epoxide 1 15 2 4 2 0 1 0 0 1 Dioxins   47 5 21 8 7 16 2 7 11 2,3,7,8-Tetrachlorodibenzo-p-dioxin 1 19 2 15 5 3 8 3 7 10 Other   Cyanide 1 74 8 23 13 9 7 3 2 8 N-Nitrosodiphenylamine 1 8 1 4 2 1 2 0 1 2 Source: Adapted from ATSDR, 1989.

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ENVIRONMENTAL EPIDEMIOLOGY: Volume 1 60 percent had groundwater contamination from metals and pesticides, respectively (EPA, 1987a). Contamination from nonpoint sources, such as agricultural runoff, may not derive from a specific hazardous-waste site, but is toxic waste and could pose significant health hazards unless recognized and controlled. For example, according to EPA (Appendix 3-A), the reproductive toxicant and carcinogen dibromochloropropane (DBCP) has been identified at only one NPL site. Although DBCP use was suspended in California in 1979, it persists in the environment and has been detected in more than one-fifth of drinking water wells in California not related to NPL sites. MacKay and Smith (1990) have reviewed the status of groundwater monitoring in California for “active” ingredients from pesticides, based on samplings from 1975 to 1988 of 10,929 wells. DBCP was detected in 2353 wells; in more than 1000 wells, it exceeded the state maximum contaminant level (MCL) of 0.2 parts per billion (ppb). About 100 of the wells that exceeded the limit were in public supply systems that serve large numbers of customers. One hundred were in smaller public supply systems, and others were private supply wells. It is estimated that approximately 500,000 Californians have DBCP in their drinking water supply. In addition to the active ingredients in pesticides, so-called “inert” ingredients also contaminate groundwater in California and elsewhere. Cohen and Bowes (1984) have estimated that 200 million pounds of inert ingredients were released to the land in pesticide use between 1971 and 1981. These are rough estimates because the composition of inert ingredients in a commercial pesticide formulation is proprietary. In some cases, materials that have been banned as active ingredients continued to be used as inert ingredients. Reports published by MacKay and co-workers (MacKay et al., 1987; Smith et al., 1990) note that inert ingredients can include TCE, PCE, formaldehyde, pentachlorophenol, ethylene dichloride, and 1,4-dichlorobenzene, all of which are known to be toxic. In 1987, EPA confirmed that these and other inert ingredients can have toxicologic significance (EPA, 1987b). Of the approximately 1200 substances used as inert ingredients in pesticide products, EPA (1987b) has determined that about 50 are of “significant toxicological concern” on the basis of their carcinogenicity, adverse reproductive effects, neurotoxicity, or other chronic effects. An additional 60 compounds were considered “potentially toxic.” These pollutants are not derived from hazardous-waste sites, but they illustrate the potential for groundwater contamination from agricultural chemical waste. They constitute a hazardous-waste hazard in themselves, whereas their impact on epidemiologic investigation of hazardous-waste sites would be that of a confounder.

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ENVIRONMENTAL EPIDEMIOLOGY: Volume 1 Since 1984, public drinking water supplies in California have been investigated by the California Department of Health Services (DHS) to determine the extent of groundwater contamination in the state (Smith et al., 1990). During the period 1984-1988, approximately 7000 large and small supply systems were evaluated, and about 1500 wells were found to be contaminated with organic chemicals. The chemicals identified in this monitoring included pesticides and solvents such as PCE, TCE, chloroform, EDC, TCA, and carbon tetrachloride. A total of 409 (5.6 percent) wells had one or more chemicals exceeding the state's action level or the Maximum Contaminant Level (MCL), and 18.3 percent of the wells had some contamination. Since early 1986, the state has sought to identify the sources of organic chemical pollution of contaminated supply wells identified by the monitoring program, but there is no comprehensive effort to identify new sources of groundwater contamination, and the evaluation of existing sources is slow. The MacKay and Smith study (1990) also documents groundwater contamination from a variety of solvents and toxic active ingredients in pesticides. These include 1,2-dichloropropane and ethylene dibromide (EDB), atrazine, simazine, bentazon, aldicarb, diuron, prometon, and bromacil, all of which have been linked with adverse human health effects. These data indicate the need for periodic screening of groundwater supplies in areas of high chemical use. Table 3-3 lists the major causes of groundwater contamination reported by states. NPL sites are included, but other sources of contamination are also important. The groundwater contamination from sources other than hazardous-waste sites is relevant to the conduct of exposure assessment in environmental epidemiology. For example, in the city of Santa Maria, California, which is adjacent to the operating Casmalia hazardous-waste site, numerous wells were closed because of contamination by organic solvents (Breslow et al., 1989). Possible sources of well water contamination include leaching from the Casmalia hazardous-waste disposal site (unlikely), use of such solvents as TCE and PCE to clean septic tanks (likely), and runoff of agricultural chemicals (likely). Groundwater contamination of this type from unrecognized nonpoint sources poses a twofold problem. Such contamination may provide important additional exposures that increase the overall health risk and can reduce the likelihood of finding effects in studies that fail to take these exposures into account. ASSESSMENT OF THE NATURE AND EXTENT OF EXPOSURE There is no question that large quantities of highly toxic chemicals are found at hazardous-waste sites. Even though it is not always

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ENVIRONMENTAL EPIDEMIOLOGY: Volume 1 exposures in connection with soil, including studies of ingested plants and fish from contaminated water, characterization of chemical transformation, and better measurements of residues. Weaknesses in data employed on exposure are common to most studies of hazardous-waste sites that the committee has reviewed. The flaws reflect historical tendencies to collect data to conform to environmental needs, rather than to meet the needs of public health assessment. Usually, exposure estimates are made with one medium—water—although others may be critical. Site assessments should use more realistic exposure measures, including direct studies of contaminants at the tap of incoming domestic water supplies, in order to improve their utility for epidemiologic research. In addition, where concerns have been raised, efforts should be made to include relevant soil and airborne measurements, so that integrated exposure assessment can be conducted. APPENDIX 3-A Frequency of Substances Reported at Final and Proposed NPL Sites * (3/91) 1,1,2-TRICHLOROETHYLENE (TCE) 401 LEAD (PB) 395 CHROMIUM AND COMPOUNDS, NOS (CR) 310 TOLUENE 281 BENZENE 249 TETRACHLOROETHENE 210 1,1,1-TRICHLOROETHANE 202 CHLOROFORM 196 ARSENIC 187 POLYCHLORINATED BIPHENYLS, NOS 185 CADMIUM (CD) 179 ZINC AND COMPOUNDS, NOS (ZN) 159 COPPER AND COMPOUNDS, NOS (CU) 150 XYLENE 136 1,2-TRANS-DICHLOROETHYLENE 134 ETHYLBENZENE 130 PHENOL 126 1,1-DICHLOROETHANE 124 METHYLENE CHLORIDE 107 1,1-DICHLOROETHENE 106 MERCURY 97 VINYL CHLORIDE 92 CYANIDES (SOLUBLE SALTS), NOS 90 NICKEL AND COMPOUNDS, NOS (NI) 83 CARBON TETRACHLORIDE 81 1,2-DICHLOROETHANE 77

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ENVIRONMENTAL EPIDEMIOLOGY: Volume 1 CHLOROBENZENE 65 PENTACHLOROPHENOL (PCP) 62 NAPHTHALENE 60 DDT 50 METHYL ETHYL KETONE 56 TRICHLOROETHANE, NOS 49 MORE THAN 15 SUBSTANCES LISTED 48 BARIUM 47 MANGANESE AND COMPOUNDS, NOS (MN) 44 PHENANTHRENE 41 HEAVY METALS, NOS 40 ACETONE 40 BENZO(A)PYRENE 37 IRON AND COMPOUNDS, NOS (FE) 33 CHLORDANE 33 VOLATILE ORGANICS, NOS 33 BENZO(J,K)FLUORENE 30 CHROMIUM, HEXAVALENT 30 PYRENE 29 CIS-1,2-DICHLOROETHYLENE 29 LINDANE 28 1,1,2-TRICHLOROETHANE 28 ARSENIC AND COMPOUNDS, NOS (AS) 27 BIS(2-ETHYLHEXYL)PHTHALATE 27 DICHLOROETHYLENE, NOS 26 ANTHRACENE 26 1,1,2,2-TETRACHLOROETHANE 26 STYRENE 23 URANIUM AND COMPOUNDS, NOS (U) 22 DDE 22 TETRACHLOROETHANE, NOS 21 CREOSOTE 19 FLUORENE, NOS 19 DIOXIN 18 SELENIUM 19 ETHYL CHLORIDE 18 CHRYSENE 18 RADON AND COMPOUNDS, NOS (RN) 18 ASBESTOS 17 TRINITROTOLUENE (TNT) 17 DDD 17 DICHLOROETHANE, NOS 17 DIELDRIN 17 SULFURIC ACID 17 WASTE OILS/SLUDGES 17 ACENAPHTHENE 16 RADIUM AND COMPOUNDS, NOS (RA) 16 ALDRIN 16 AROCLOR 1260 16 ENDRIN 16

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ENVIRONMENTAL EPIDEMIOLOGY: Volume 1 TRICHLOROFLUOROMETHANE 16 1,4-DICHLOROBENZENE 16 ACID, NOS 15 DI-N-BUTYL PHTHALATE 15 DICHLOROBENZENE, NOS 15 METHYL ISOBUTYL KETONE 15 M-XYLENE 14 1,2-DICHLOROBENZENE 14 ALUMINUM AND COMPOUNDS, NOS (AL) 14 CHLOROMETHANE 14 AMMONIA 13 TETRAHYDROFURAN 12 THORIUM AND COMPOUNDS, NOS (TH) 12 HEXACHLOROBENZENE 12 HEPTACHLOR 11 TOXAPHENE 11 TRIBROMOMETHANE 11 1,2-DICHLOROPROPANE 11 RDX (CYCLOTRIMETHYLENETRINITRAMINE) 10 ANTIMONY AND COMPOUNDS, NOS (SB) 10 BARIUM AND COMPOUNDS, NOS (BA) 10 BERYLLIUM AND COMPOUNDS, NOS (BE) 10 * This list is a frequency of substances documented during HRS score preparation, not a complete inventory of substances at all sites. “NOS”—Not otherwise specified, e.g., not identified as to specific isomer or congener. APPENDIX 3-B ATSDR Priority List of Substances for Toxicological Profiles (Listed in Federal Register 52(74), Friday April 17, 1987, p. 12869) CAS No. Substance Name Priority Group 1 50328 Benzo(a)pyrene 53703 Dibenzo(a,h)anthracene 56553 Benzo(a)anthracene 57125 Cyanide 60571 Dieldrin/aldrin 67663 Chloroform 71432 Benzene 75014 Vinyl chloride 75092 Methylene chloride 76448 Heptachlor/heptachlor epoxide 79016 Trichloroethene

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ENVIRONMENTAL EPIDEMIOLOGY: Volume 1 86306 N-Nitrosodiphenylamine 106467 1,4-Dichlorobenzene 117817 Bis(2-ethylhexyl)phthalate 127184 Tetrachloroethene 205992 Benzo(b)fluoranthene 218019 Chrysene 1745016 p-Dioxin 7439921 Lead 7440020 Nickel 7440382 Arsenic 7440417 Beryllium 7440439 Cadmium 7440473 Chromium 11196825 PCB-1260,54,48,42,32,21,1016 Priority Group 2 56235 Carbon tetrachloride 57749 Chlordane 62759 N-Nitrosodimethylamine 72559 4,4'DDE, DDT, DDD 75003 Chloroethane 75274 Bromodichloromethane 75354 1,1-Dichloroethene 78591 Isophorone 78875 1,2-Dichloropropane 79005 1,1,2,-Trichloroethane 79435 1,1,2,2-Tetrachloroethane 87865 Pentachlorophenol 91941 3,3'-Dichlorobenzidine 92875 Benzidine 107062 1,2-Dichloroethane 108883 Toluene 108952 Phenol 111444 Bis(2-chloroethyl)ether 121142 2,4,-Dinitrotoluene 319846 BHC-alpha, gamma, beta, delta 542881 Bis(chloromethyl)ether 621647 N-nitrosodi-n-propylamino 7439976 Mercury 7440666 Zinc 7782492 Selenium Priority Group 3 71556 1,1,1-Trichloroethane 74873 Chloromethane 75218 Oxirane 75252 Bromoform 75343 1,1-Dichloroethane 84742 Di-N-butyl phthalate

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ENVIRONMENTAL EPIDEMIOLOGY: Volume 1 88062 2,4,6-Trichlorophenol 91203 Naphthalene 98953 Nitrobenzene 100414 Ethylbenzene 107028 Acrolein 107131 Acrylonitrile 108907 Chlorobenzene 118741 Hexachlorobenzene 122667 1,2-Diphenylhydrazine 124481 Chlorodibromomethane 156606 1,2-Trans-dichloroethene 193395 Indeno(1,2,3-cd)pyrene 606202 2,6-Dinitrotoluene 1330207 Total xylenes 7221934 Endrin aldehyde/endrin 7440224 Silver 7440508 Copper 7664417 Ammonia 8001352 Toxaphene Priority Group 4 51285 2,4-Diitrophenol 59507 p-Chloro-m-cresol 62533 Aniline 65850 Benzoic acid 67721 Hexachloroethane 74839 Bromomethane 75150 Carbon disulfide 75694 Fluorotrichloromethane 75718 Dichlorodifluoromethane 78933 2-Butanone 84662 Diethyl phthalate 85018 Phenanthrene 87683 Hexachlorobutadiene 95487 Phenol,2-methyl 95501 1,2-Dichlorobenzene 105679 2,4-Dimethylphenol 108101 2-Pentanone,4-methyl 120821 1,2,4-Trichlorobenzene 120832 2,4-Dichlorophenol 123911 1,4-Dioxane 131113 Dimethyl phthalate 206440 Fluoranthene 534521 4,6-Dinitro-2-methylphenol 541731 1,3-Dichlorobenzene 7440280 Thallium

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ENVIRONMENTAL EPIDEMIOLOGY: Volume 1 REFERENCES Andelman, J.B. 1990. Exposure to volatile chemicals from indoor uses of water. Pp. 300-311 in Proceedings of the EPA/A & WMA specialty conference, Total Exposure Assessment Methodology Pittsburgh: Air & Waste Management Association. Andelman, J.B., A. Couch, and W.W. Thurston. 1986. Inhalation exposures in indoor air to trichlorethylene from shower water Pp. 201-211 in Environmental Epidemiology, F.C. Kopler and G.F. Craun, eds. Chelsea, Mich.: Lewis. Anderson, H.A. 1985. Evolution of environmental epidemiologic risk assessment. Environ. Health Perpect. 62: 389-392 ATSDR (U.S. Public Health Service, Agency for Toxic Substances and Disease Registry). 1989. ATSDR Biennial Report to Congress: October 17, 1986-September 30, 1988. Atlanta: Agency for Toxic Substances and Disease Registry. 2 vols. Bailar, J.C. 1989. Inhalation hazards: The interpretation of epidemiologic evidence. Pp. 39-48 in Assessment of Inhalation Hazards, D.V. Bates et al., eds. New York: Springer-Verlag. Baker, D.B., S. Greenland, J. Mendlein, and P. Harmon. 1988. A health study of two communities near the Stringfellow Waste Disposal Site. Arch. Environ. Health 43: 325-334 Bramlett, J., C. Furman, A. Johnson, W.D. Ellis, and N. Nelson. 1987. Composition of Leachates from Actual Hazardous Waste Sites. Project report prepared for U.S. Environmental Protection Agency. EPA/600/2-87/043; available from NTIS as PB87198743 Springfield: U.S. Department of Commerce, National Technical Information Service Breslow, L., Chairman of Commission on the health consequences of Casmalia resources facility operation, et al. 1989. Report of Santa Barbara Commission on Health Consequences of the Casmalia Resources Waste Disposal Facility. Report prepared for Santa Barbara Department of Health Services, California. Budnick, L.D., D.C. Sokal, H. Falk, J.N. Logue, and J.M. Fox. 1984. Cancer and birth defects near the Drake Superfund site, Pennsylvania Arch. Environ. Health 39: 409-413 Buffler, P.A., M. Crane, and M.M. Key. 1985. Possibilities of detecting health effects by studies of populations exposed to chemicals from waste disposal sites. Environ. Health Persp. 62: 423-456 Checkoway, H., N.E. Pearce, and D.J. Crawford-Brown. 1989. Research Methods in Occupational Epidemiology. New York: Oxford University Press. Clark, C.S., C.R. Meyer, P.S. Gartside, V.A. Majeti, B. Specker, W.F. Balistreri, and V.J. Elia. 1982. An environmental health survey of drinking water contamination by leachate from a pesticide waste dump in Hardeman County, Tennessee Arch. Environ. Health 37: 9-18 Cohen, D.B., and G.W. Bowes. 1984. Water Quality and Pesticides: A California Risk Assessment Program, Vol. 1. State Water Resources Control Board Report No. 84-6SP. Sacramento, Calif.: State Water Resources Control Board. Dawson, B.V., P.D. Johnson, S.J. Goldberg, and J.B. Ulreich. 1990. Cardiac Teratogenesis of trichloroethylene and dichloroethylene in a mammalian model. J. Am. Coll. Cardiol. 16: 1304-1309 Day, R., E.O. Talbott, G.M. Marsh, and B.W. Case. 1990. A Comparative Ecological Study of Selected Cancers in Kanawha County, West Virginia. Paper presented at the Second Annual Meeting of the International Society for Environmental Epidemiology, August 12-15, 1990, Berkeley, California Deane, M., S.H. Swan, J.A. Harris, D.M. Epstein, and R. Neutra. 1989. Adverse preg-

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ENVIRONMENTAL EPIDEMIOLOGY: Volume 1 nancy outcomes in relation to water contamination, Santa Clara County, California, 1980-1981 Am. J. Epidemiol. 129: 894-904 Droz, P.O., and M.M. Wu. 1991. Biological monitoring strategies. Pp. 251-270 in Exposure Assessment for Epidemiology and Hazard Control, S.M. Rappaport and T.J. Smith, eds. Boca Raton: CRC Press. Duffee, R.A., and L.R. Errera. 1982. Final Report on the Air Quality and Odor Portions of the Environmental Investigation Program of the McColl Site. East Hartford, Conn.: TRC Environmental Consultants. EHP (Environmental Health Perspectives). 1991. Lead in Bone: International Workshop on Lead in Bone: Implications for Dosimetry and Toxicology. Vol. 91, entire February issue EPA (U.S. Environmental Protection Agency). 1987a. National Water Quality Inventory: 1986 Report to Congress. EPA-440/4-87-008. Washington, D.C.: U.S. Government Printing Office. EPA (U.S. Environmental Protection Agency). 1987b. Inert ingredients in pesticide products: Policy statement. Notices, April 22. Fed. Reg. 52(77): 13305-13309 EPA (U.S. Environmental Protection Agency, Office of Policy Planning and Evaluation) 1988. Environmental Progress and Challenges: EPA's update. EPA-230-07-88-033. Washington, D.C.: U.S. Government Printing Office. Fagliano, J., M. Berry, F. Bove, and T. Burke. 1990. Drinking water contamination and the incidence of leukemia: An ecologic study. Am. J. Public Health 80: 1209-1212 Feldman, R.G., J. Chirico-Post, and S.P. Proctor. 1988. Blink reflex latency after exposure to trichloroethylene in well water. Arch. Environ. Health 43: 143-148 Froines, J.R. 1989. Worksite inspection and the control of occupational disease: The OSHA experience. Ann. N.Y. Acad. Sci. 572: 177-183 Froines, J.R., C.A. Dellenbaugh, and D.H. Wegman. 1986. Occupational health surveillance: A means to identify work-related risks. Am. J. Public Health 76: 1089-1096 Gann, P. 1986. Use and misuse of existing data bases in environmental epidemiology: The case of air pollution. Pp. 109-122 in Environmental Epidemiology, F. Kopfler and G.F. Craun, eds. Chelsea, Mich.: Lewis. Gillette, J.R. 1987. Dose, species, and route extrapolation: General aspects. Pp. 96-158 in National Research Council, Pharmacokinetics in Risk Assessment, Drinking Water and Health, Vol. 8. Washington, D.C.: National Academy Press. Goldberg, S.J., M.D. Lebowitz, E.J. Graver, and S. Hicks. 1990. An association of human congenital cardiac malformations and drinking water contaminants. J. Am. Coll. Cardiol. 16: 155-164 Goldman, L.R., B. Paigen, M.M. Magnant, and J.H. Highland. 1985. Low birth weight, prematurity and birth defects in children living near the hazardous waste site, Love Canal Haz. Waste Haz. Materials. 2: 209-223 Grisham, J.W., ed. 1986. Health Aspects of the Disposal of Waste Chemicals. New York: Pergamon Press. Hammond, S.K. 1991. The uses of markers to measure exposure to complex mixtures. Pp. 53-66 in Exposure Assessment for Epidemiology and Hazard Control, S.M. Rappaport and T.J. Smith, eds. Boca Raton: CRC Press. Harris, R.H., J.H. Highland, J.V. Rodricks, and S.S. Papadopulos. 1984. Adverse health effects at a Tennessee hazardous waste disposal site Hazardous Waste 1: 183-204 Hattis, D. 1987. A Pharmacokinetic/Mechanism-Based Analysis of the Carcinogenic Risk of Ethylene Oxide. CTIPD 87-1; available from NTIS as PB88-188784. Cambridge, Mass.: M.I.T. Center for Technology, Policy and Industrial Development. Hattis, D. 1990. Pharmacokinetic principles for dose-rate extrapolation of carcinogenic risk from genetically active agents. Risk Anal. 10: 306-316

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ENVIRONMENTAL EPIDEMIOLOGY: Volume 1 Hattis, D., and J.R. Froines. 1991. Uncertainties in Risk Assessment. Invited paper presented at the Conference on Chemical Risk Assessment in the DoD; Science, Policy and Practice. In press Hattis, D., and K. Shapiro. 1990. Analysis of dose/time/response relationships for chronic toxic effects: The case of acrylamide. Neurotoxicology 11: 219-236 Hattis, D., and J. Wasson. 1987. A Pharmacokinetic/Mechanism-Based Analysis of the Carcinogenic Risk of Butadiene. CTPID 87-3; available from NTIS as PB88-202817. Cambridge, Mass.: M.I.T. Center for Technology, Policy and Industrial Development. Heath, C.W., Jr. 1983. Field epidemiologic studies of populations exposed to waste dumps Environ. Health Perspect. 48: 3-7 Hertzman, C., M. Hayes, J. Singer, and J. Highland. 1987. Upper Ottawa Street Landfill Site health study. Environ. Health Perspect. 75: 173-195 Jo, W.K, C.P. Weisel, and P.J. Lioy. 1990a. Routes of chloroform exposure and body burden from showering with chlorinated tap water. Risk Anal. 10: 575-580 Jo, W.K, C.P. Weisel, and P.J. Lioy. 1990b. Chloroform exposure and the health risk associated with multiple uses of chlorinated tap water. Risk Anal. 10: 581-585 Lagakos, S.W., B.J. Wessen, and M. Zelen. 1986. An analysis of contaminated well water and health effects in Woburn, Massachusetts. J. Am. Stats. Assoc. 81: 583-596 Landrigan, P.J. 1983. Epidemiologic approaches to persons with exposures to waste chemicals Environ. Health Perspect. 48: 93-97 Landrigan, P.J., J.R. Froines, and K.R. Mahaffey. 1985. Body lead burden: Epidemiology data and its relation to environmental sources and toxic effects. In Dietary and Environmental Lead: Human Health Effects. Amsterdam: Elsevier. Leeden, F. van der, F.L. Troise, and D.K. Todd. 1990. The Water Encyclopedia. Chelsea, Mich.: Lewis. Lioy, P.J. 1990. Assessing total human exposure to contaminants: A multidisciplinary approach. Environ. Sci. Technol. 24: 938-945 Lioy, P.L., J.M. Waldman, A. Greenberg, R. Harkov, and C. Pietarinen. 1988. The Total Human Environmental Exposure Study (THEES) to benzo(a)pyrene: Comparison of the inhalation and food pathways Arch. Environ. Health 43: 304-312 Lipscomb, J.A., L.R. Goldman, K.P. Satin, D.F. Smith, W.A. Vance, and R.R. Neutra. In press. A follow-up study of the community near the McColl waste disposal site. Environ. Health Perspect. Logue, J.N., and J. Fox. 1986. Residential health study of families living near the Drake Chemical Superfund Site in Lock Haven, Pennsylvania, U.S.A. Arch. Environ. Health 40: 155-160 MacKay, D.M., and L.A. Smith. 1990. Agricultural chemicals in groundwater: Monitoring and management in California. J. Soil Water Conserv. 45: 253-255 MacKay, D., M. Gold, and G. Leson. 1987. Current and prospective quality of California's groundwater. Pp. 97-110 in the Proceedings of the 16th Biennial Conference on Groundwater, J.J. Devries, ed. University of California Water Research Center Report No. 66. MacKay, D.M., J.R. Froines, R.A. Mah, W. W.-G. Yeh, and W. Glaze. 1989. Nonconventional Pollutants in Raw and Treated Groundwater: Occurrence, Environmental Fate, Health Effects and Policy Implications Final project report to the Toxic Substances Research and Teaching Program, University of California, Davis. MacMahon, B. 1986. Comment. J. Am. Stats. Assoc. 81: 597-599 Marsh, G.M., and R.J. Caplan. 1987. Evaluating health effects of exposure at hazardous waste sites: A review of the state-of-the-art, with recommendations for future research Pp. 1-80 in Health Effects from Hazardous Waste Sites, J.B. Andelman and D.W. Underhill, eds. Chelsea, Mich.: Lewis.

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ENVIRONMENTAL EPIDEMIOLOGY: Volume 1 NRC (National Research Council). 1987. Pharmacokinetics in Risk Assessment. Drinking Water and Health, Vol. 8 Washington, D.C.: National Academy Press. NRC (National Research Council). 1988. Complex Mixtures: Methods for In Vivo Toxicity Testing. Washington, D.C.: National Academy Press. NRC (National Research Council). 1991. Human Exposure to Airborne Pollutants. Washington, D.C.: National Academy Press. OTA (U.S. Congress, Office of Technology Assessment). 1989. Coming Clean: Superfund's Problems Can Be Solved. OTA-ITE-433. Washington, D.C.: U.S. Government Printing Office. Ozonoff, D., M.E. Colten, A. Cupples, T. Heeren, A. Schatzkin, T. Mangione, M. Dresner, and T. Colton. 1987. Health problems reported by residents of a neighborhood contaminated by a hazardous waste facility. Am. J. Ind. Med. 11: 581-597 Paigen, B., L.R. Goldman, J.H. Highland, M.M. Magnant, and A.T. Steegman, Jr. 1985. Prevalence of health problems in children living near Love Canal. Haz. Waste Haz. Materials 2: 23-43 Paigen, B., L.R. Goldman, M.M. Magnant, J.H. Highland, and A.T. Steegman, Jr. 1987. Growth of children living near the hazardous waste site, Love Canal Hum. Biol. 59: 489-508 Pierce, T. 1985. The use of dermal absorption data in developing biological monitoring standards. Ann. Am. Conf. Gov. Ind. Hyg. 12: 331-337 Rothman, K.J. 1990. A sobering start for the Cluster Busters' Conference. Keynote Presentation. Am. J. Epidemiol. 132(Supp. 1): S6-S13 Satin, K.P., M. Deane, A. Leonard, R. Neutra, M. Harnly, and R.R. Green. 1983. The McColl Site Health Survey: An Epidemiologic and Toxicologic Assessment of the McColl Site in Fullerton, California Berkeley, Calif.: Special Epidemiological Studies Program, California Department of Health Services. Severn, D.J. 1987. Exposure assessment. Environ. Sci. Technol. 21(12): 1159-1163 Smith, T.J. 1988. Extrapolation of laboratory findings to risks from environmental exposures: Male reproductive effects of ethylene oxide. Birth Defects 24(5): 79-100 Smith, L.A., K.P. Green, and M.M. MacKay. 1990. Quality of ground water in California: Overview and implications. Pp. 93-107 in Proc. Seventeenth Biennial Conf. on Groundwater. Rpt. no. 72. Univ. Calif. Water Resources Center, Riverside. Swan, S.H., G. Shaw, J.A. Harris, and R.R. Neutra. 1989. Congenital cardiac anomalies in relation to water contamination, Santa Clara County, California, 1981-1983. Am. J. Epidemiol. 129: 885-893 Travis, C.C., and H.A. Hattemer-Frey. 1987. Human exposure to 2,3,7,8-TCDD. Chemosphere 16(10-12): 2331-2343 Upton, A.C., T. Kneip, and P. Toniolo. 1989. Public health aspects of toxic chemical disposal sites. Annu. Rev. Public Health 10: 1-25 U.S. Geological Survey. 1988. National Water Summary 1986: Hydrologic Events and Groundwater Quality U.S. Geological Survey Water Supply Paper 2325. Washington, D.C.: U.S. Government Printing Office Vianna, N.J., and A.K. Polan. 1984. Incidence of low birth weight among Love Canal residents. Science 226: 1217-1219 Viviano, F. 1991. U.S. toxics cleanup mired in lawsuits. San Francisco Chronicle (June 5): A1 Waldorf, H., and R. Cleary. 1983. Water Distribution System, Woburn Massachusetts, 1964-1979. Engineering Draft Report, Massachusetts Department of Environmental Quality. Wallace, L.A., E.D. Pellizzari, T.D. Hartwell, R. Whitmore, C. Sparacino, and H. Zelon. 1986. Total exposure assessment methodology (TEAM) study: Personal exposures,

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ENVIRONMENTAL EPIDEMIOLOGY: Volume 1 indoor-outdoor relationships, and breath levels of volatile organic compounds in New Jersey Environ. Int. 12: 369-387 Wallace, L.A., E.D. Pellizzari, T.D. Hartwell, C. Sparacino, R. Whitmore, L. Sheldon, H. Zelon, and R. Perritt. 1987. The TEAM (Total Exposure Assessment Methodology) Study: Personal exposures to toxic substances in air, drinking water, and breath of 400 residents of New Jersey, North Carolina, and North Dakota Environ. Res. 43: 290-307 Wallace, L.A., E.D. Pellizzari, T.D. Hartwell, R. Whitmore, H. Zelon, R. Perritt, and L. Sheldon. 1988. California TEAM study: Breath concentrations and personal air exposures to 26 volatile compounds in air and drinking water of 188 residents of Los Angeles, Antioch and Pittsburgh, California Atmos. Environ. 22: 2141-2163 Whorton, M.D., R.W. Morgan, O. Wong, S. Larson, and N. Gordon. 1988. Problems associated with collecting drinking water quality data for community studies: A case example, Fresno County, California Am. J. Public Health 78: 43-46 Wong, O., M.D. Whorton, N. Gordon, and R.W. Morgan. 1988. An epidemiologic investigation of the relationship between DBCP contamination in drinking water and birth rates in Fresno County, California Am. J. Public Health 78: 43-46 Wong, O., R.W. Morgan, M.D. Whorton, N. Gordon, and L. Kheifets. 1989. Ecological analyses and case-control studies of gastric cancer and leukemia in relation to DBCP in drinking water in Fresno County, California. 1989 Br. J. Indust. Med. 46: 521-528 Wrensch, M., S. Swan, P.J. Murphy, J. Lipscomb, K. Claxton, D. Epstein, and R. Neutra. 1990a. Hydrogeologic assessment of exposure to solvent-contaminated drinking water: Pregnancy outcomes in relation to exposure. Arch. Environ. Health 45: 21-216 Wrensch, M., S. Swan, J. Lipscomb, D. Epstein, L. Fenster, K. Claxton, P.J. Murphy, D. Shusterman, and R. Neutra. 1990b. Pregnancy outcomes in women potentially exposed to solvent-contaminated drinking water in San Jose, California Am. J. Epidemiol. 131: 283-300

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