Uses of Environmental Testing in Human Health ... - ACS Publications

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Uses o f E n v i r o n m e n t a l Testing i n H u m a n H e a l t h R i s k Assessment 1

Downloaded by NORTH CAROLINA STATE UNIV on October 28, 2012 | http://pubs.acs.org Publication Date: October 31, 1984 | doi: 10.1021/bk-1984-0267.ch002

CLARK W. HEATH, JR.

Centers for Disease Control, Atlanta, GA 30333 The process for assessing environmental health risks is complex. Information regarding 1) the environmental agent, 2) the pathways by which exposure occurs, and 3) the biologic effects observed after exposure must be assembled and simultaneously evaluated. Incomplete knowledge or inadequate methodology in any of these three areas can severely inhibit accurate or useful estimates of health risk. Environmental testing is a critical element in this process since it enables the qualitative and quantitative determination of toxic chemicals in the environment and the definition of environmental pathways which may lead to human exposure. This paper briefly reviews the overall process of health risk assessments and the particular role which environmental testing plays. Recent efforts to assess environmental health risks in relation to Love Canal illustrate both the usefulness and the limitations of environmental testing in risk assessment. The Risk Assessment Process The process of performing risk assessment is outlined in Table I. Factors contributing to the nature and degree of exposure are examined first. They include characteristics of the toxic material, environmental pathways, and mechanisms operating in absorption and metabolism in the host. Next, the biologic effects resulting from such exposure are defined in relation to the amount of exposure, to humans and in animal models. Finally, information about exposure and biologic effect characteristics is interpreted in relation to predetermined definitions of biologic safety to establish benchmarks for acceptable exposure risk levels O ) . The toxic chemical(s) of concern must be identified and their physical and chemical characteristics evaluated. The concentrations of each of the chemicals must be measured, ideally in both the environment and in the tissues of exposed humans. Depending on the nature and distribution of toxic material, environmental measurements may be required in air, water, soil, or food, or in combinations of these media. The critical limiting factor at this stage of assessment relates to the degree to which particular chemicals can be identified 'Mailing address: Emory University School of Medicine, Atlanta, GA 30322 This chapter not subject to U.S. copyright. Published 1984, American Chemical Society

In Environmental Sampling for Hazardous Wastes; Schweitzer, G., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1984.

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ENVIRONMENTAL SAMPLING FOR HAZARDOUS WASTES Table I . The Process of Environmental Risk Assessment


I.

ASSESSMENT OF EXPOSURE A. I d e n t i f i c a t i o n of toxins and measurement of t h e i r levels or concentrations i n the exposure s e t t i n g . 1. In the environment: a i r , water, s o i l , food. a) Laboratory technology: quality assurance, precision, s e n s i t i v i t y , accuracy. b) Interaction of chemicals producing p o t e n t i a l l y toxic byproducts. 2. In the host: l e v e l s of toxin i n serum or t i s s u e . a) Persistence i n tissue: excretion, tissue/organ specificity. b) Metabolic a l t e r a t i o n s : p o t e n t i a l l y toxic byproducts. B. Environmental pathways for exposure. 1. Mechanisms for transmitting toxin to host: ingestion, inhalation, dermal contact, physical and b i o l o g i c vectors. 2. Degree and mode of exposure: contact through human activities. 3. Degree and mode of absorption into host: E f f e c t i v e dose at t i s s u e / c e l l l e v e l depends on nature of toxin, route of exposure, and interaction of target tissue with absorbed metabolized toxin. I I . ASSESSMENT OF BIOLOGIC EFFECT A. Human e f f e c t s : epidemiologic and c l i n i c a l observations. 1. Acute c l i n i c a l e f f e c t s : organ system s p e c i f i c i t y , short latency, high dose exposure. 2. Delayed (chronic) c l i n i c a l e f f e c t s : long and variable latency, lower dose exposure. 3. S u b c l i n i c a l e f f e c t s : c l i n i c a l laboratory test a l t e r ation ( l i v e r function, nerve conduction v e l o c i t y ) , mutagenicity testing, cytogenetic t e s t i n g . Requires estimation of eventual l i k e l i h o o d of c l i n i c a l disease predicted by s u b c l i n i c a l abnormalities. B. Non-human e f f e c t s : experimental observations i n toxicologic testing i n animals or i n b a c t e r i a l or c e l l culture test eyeterns. C. Low dose e f f e c t s : usually not measurable d i r e c t l y i n human or animal observations. Need to extrapolate observed high dose effects to low or zero dose range by theoretical doseresponse models. I I I . SELECTION OF SAFETY STANDARDS Choice of c r i t e r i a f o r defining a "safe" l e v e l of toxin i n the environment based on animal and human observations. a) Potential carcinogenic e f f e c t s : 1/1,000,000 l i f e t i m e cumulative r i s k . b) Non-carcinogenic e f f e c t s : Highest l e v e l of toxin at which no effect i s observed (NOEL), lowered by safety margin of 100 to 1000 f o l d to allow f o r interspecies biologic variation.



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and measured In each of the media. Testing methodology must be capable of y i e l d i n g reproducible results of known and acceptable p r e c i s i o n and s e n s i t i v i t y . This requirement i s especially important when testing i s undertaken i n more than one laboratory. Although analytic standards and reference materials exist for a wide range of Individual chemicals i n d i f f e r e n t environmental media, interactions among multiple chemicals coexisting i n the environment pose d i f f i c u l t i e s for many testing procedures. Measurement of exposure can be made by determining levels of toxic chemicals i n human serum or tissue i f the chemicals of concern p e r s i s t i n tissue or i f the exposure i s recent. For most s i t u a t i o n s , neither of these conditions i s met. As a r e s u l t , most assessments of exposure depend primarily on chemical measurements i n environmental media coupled with semi-quantitative assessments of environmental pathway8. However, when measurements i n human tissue are possible, valuable exposure information can be obtained, subject to the same l i m i t a t i o n s c i t e d above f o r environmental measurement methodology. Interpretation of tissue concentration data i s dependent on knowledge of the absorption, excretion, metabolism, and tissue specificity c h a r a c t e r i s t i c s for the chemical under study. The toxic hazard posed by a p a r t i c u l a r chemical w i l l depend c r i t i c a l l y upon the concentration achieved at p a r t i c u l a r target organ s i t e s . This, i n turn, depends upon rates of absorption, transport, and metabolic a l t e r a t i o n . Metabolic alterations can involve either p a r t i a l i n a c t i v a t i o n of toxic material or conversion to chemicals with increased or d i f f e r i n g toxic properties. Toxic chemicals can be transported with d i f f e r i n g levels of e f f i c i e n c y to the target host depending upon the transport pathways. Exposure may occur d i r e c t l y by ingestion, inhalation, or dermal contact or through some form of Intermediate vector such as insects or clothing contamination. The r e l a t i v e contribution of d i f f e r e n t pathways must be assessed by examining the nature of human a c t i v i t i e s which may be expected i n p a r t i c u l a r exposure settings. This evaluation w i l l i d e n t i f y both the situations f o r which the greatest exposure may be anticipated (young children Ingesting s o i l while at play, f o r instance) and the safety standards that w i l l eventually be needed. Again, the actual concentration of toxic chemical i n the host c e l l depends partly on assessments of host-environment contact and p a r t l y on knowledge of absorption and metabolism of the p a r t i c u l a r chemicals. B i o l o g i c E f f e c t . Ideally, r i s k assessment i s based on quantitative knowledge of b i o l o g i c effects i n humans. Unfortunately, such d i r e c t human information does not exist for most toxic chemicals. Therefore, prediction of human effects usually depends upon extrapolating the r e s u l t s of experimentally exposed laboratory animals (usually r o dents). Such extrapolations must be performed not only between species, but between observed high dose effects and predicted low dose e f f e c t s . Most animal toxicologic testing and v i r t u a l l y a l l observed human health effects involve r e l a t i v e l y high dosages. Since safety standards are commonly aimed at preventing the potential e f f e c t s of low dose exposure (especially cancer), low dose extrapolations from e x i s t i n g high dose data are a c r i t i c a l phase i n r i s k assessment. S t a t i s t i c a l models f o r predicting low dose effects



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e x i s t . Some are based on the assumption that a no-threshold l i n e a r relationship exists between dose and b i o l o g i c response. Others encompass various concepts of threshold effect and curved dose response relationships which predict d i f f e r i n g degrees of dose r e sponse depending upon the influence of host tissue repair or excret i o n mechanisms. The eventual safety standards developed can vary quite widely according to the theoretical model selected i n a p a r t i c ular r i s k assessment. Biologic e f f e c t s should be assessed for both c l i n i c a l and subc l i n i c a l changes. Either can be acute or delayed, with delayed effects often associated with lower exposures. Clinical illness occurs infrequently following chemical exposures, especially at moderate or low dose l e v e l s . To increase the probability of detecting c l i n i c a l endpoints at lower dose levels i n experimental animals or human epidemiologic studies, i t i s desirable to maximize the size of populations examined. Sample s i z e , therefore, rapidly becomes a l i m i t i n g factor for making c l i n i c a l observations. When population size i s l i m i t e d , i t becomes necessary either to measure s u b c l i n i c a l effects which may occur with greater frequency than c l i n i c a l effects at given dose levels ( l i v e r function abnormalities, cytogenetic changes) or to accept theoretical extrapolations downward from high dose c l i n i c a l e f f e c t s . Increasingly, r i s k assessment e f f o r t s have begun to focus more on s u b c l i n i c a l e f f e c t s , both i n humans and i n test animals. Although this trend holds promise f o r greater testing s e n s i t i v i t y , i t w i l l require Improved understanding of the r e l a t i o n ship between s u b c l i n i c a l endpoints and eventual c l i n i c a l i l l n e s s . Such s u b c l i n i c a l - c l i n i c a l extrapolation i s of c r i t i c a l importance f o r r i s k assessment. It i s not at a l l clear at present, for example, that cytogenetic changes observed i n exposed populations necessarily fore-shadow l a t e r increases i n incidence of cancer or genetic disease. Acceptable Risk. Once information i s assembled concerning the c h a r a c t e r i s t i c s of exposure and biologic e f f e c t s , that information must be interpreted i n terms of human safety standards. That i n t e r pretation requires that one establish a set of c r i t e r i a representing acceptably safe conditions for human existence, bearing i n mind that zero concentrations of environmental chemicals are u n r e a l i s t i c . This process of standard-setting i s by nature q u a l i t a t i v e and somewhat a r b i t r a r y . Nevertheless, certain conventions have evolved for setting safety l e v e l targets. In case of carcinogenic or potent i a l l y carcinogenic substances, with the assumption that no dose threshold exists for cancer r i s k , that target has conventionally been set as a l i f e t i m e increased r i s k of one case of cancer i n a population of one m i l l i o n persons. For chemicals presumed to be noncarcinogenic, acceptable r i s k has been conventionally set at the highest dose l e v e l at which no observed b i o l o g i c effect i s observed i n experimental animals (NOEL or "no observed effects l e v e l " ) . The l a t t e r standard i s then adjusted downward by applying a safety factor of 100 to 1000 f o l d to make allowance for uncertainties of extrapol a t i o n s f o r differences between species and dosages.


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Environmental Testing Once an acceptable "safe" l e v e l of chemicals has been determined for p a r t i c u l a r environmental media based on existing toxicologic and epidemiologic data and on appropriate safety model c r i t e r i a , accurate, reproducible, and economically feasible programs for measurement of environmental chemicals must be implemented. Since most toxic chemi c a l exposure situations involve multiple chemicals, the task i s f a r from simple. Aside from the economic f e a s i b i l t y of testing programs which often involve large numbers of samples, two other considerations are of central concern. These are 1) sampling design and framework, and 2) technical laboratory procedures. With respect to sampling, s u f f i c i e n t numbers of environmental samples should be obtained to permit r e l i a b l e s t a t i s t i c a l and b i o l o g i c interpretation of r e s u l t s . At the same time, the samples c o l lected should be from environmental locations where human exposure i s most l i k e l y to occur (or did occur, i f questions of past exposures require assessment). They should also be targeted f o r those environmental media which can be expected to have the greatest potential f o r human exposure and absorption. F i n a l l y , the samples must be obtained and preserved so that the chemicals which pose the greatest threat for human health i n terms of t o x i c i t y and tissue persistence can be accurately measured. Laboratory quality assurance procedures must be b u i l t into the sampling plan so that reproducibility and precision of test results can be c l e a r l y demonstrated when testing i s complete. This includes defining the precision of the measurement system and sample c o l l e c t i o n procedures and providing f o r adequate numbers of repeat or s p l i t samples, as well as b l i n d l y inserted positive and negative control specimens. If r i s k assessment i s dependent upon assessing potential environmental exposure, overtime arrangements must be made at the s t a r t f o r laboratory consistency for as long as testing i s expected to continue. Because of the complexity and expense involved, even f o r limited environmental testing programs involving few chemical toxins, specimen c o l l e c t i o n and laboratory testing should not be h a s t i l y undertaken. Careful advance planning i s necessary, complete with outside peer review and approval of proposed testing plans. This i s e s p e c i a l l y true for chemicals f o r which laboratory technology and sampling procedures are not yet f u l l y developed. Environmental Testing at the Love Canal When the Love Canal problem came to active public attention, i t was necessary to reconstruct the nature and extent of past exposure as well as address current and future human exposure. Multiple chemicals of uncertain amounts and d i s t r i b u t i o n patterns within the Canal s i t e required varied laboratory technologies, multi-media sampling, and large numbers of samples drawn from a wide and diverse neighborhood s e t t i n g . The problem was of concern to public health agencies at various levels of Government, and several d i f f e r e n t test programs were undertaken by different organizations, p r i n c i p a l l y the State of New York i n the i n i t i a l phases of remedial work and the U.S. Environmental Protection Agency (EPA) during l a t e r phases.



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At the s t a r t , the focus was on environmental chemical levels at the Canal s i t e i t s e l f and i n homes Immediately adjoining i t * An extensive multi-media testing program was conducted over several months i n 1978 and 1979 by the New York State Department of Health (2). This work concentrated on the f i r s t two rings of homes adjacent to the Canal i n i t s early phases but l a t e r was extended to include larger neighborhoods* Community concern was focused especially to the east, where Canal chemicals might p o t e n t i a l l y spread through the remaining traces of pre-existing natural drainage channels i n surface s o i l . Although a long l i s t of Canal chemicals was targeted f o r analysis, a select number of chemicals received p a r t i c u l a r attention on the basis of t h e i r r e l a t i v e l y unique presence i n the Canal. For example, chlorobenzene and chlorotoluene had value as marker contaminants. Water, s o i l , and a i r were sampled, with special emphasis given to water and a i r within homes where people might be expected to have had the highest and most sustained exposure. In l a t e r phases of t e s t i n g , chemical levels i n storm sewers and streams draining the Love Canal neighborhood also received attention. When remedial drainage construction work began, environmental sampling was also required to guide the location of underground drainage pipes and to monitor worker exposure conditions. Since simultaneous health effect surveys were conducted i n the Love Canal area, environmental test results i n the homes adjoining the Canal were examined i n an e f f o r t to demonstrate the presence or absence of correlations between environmental chemical levels and frequencies of p a r t i c u l a r health abnormalities. This e f f o r t was l a r g e l y unsuccessful, since the t o t a l exposed population proved to be too small f o r meaningful interpretation of most health endpoints of interest and since d i f f i c u l t i e s i n c o n t r o l l i n g f o r subjective reporting of health symptoms made i t d i f f i c u l t to interpret health survey results OA). The results of environmental testing i n Love Canal homes conducted p r i o r to remedial drainage construction were used as a basis for testing the hypothesis that persistent cytogenetic abnormalities might have resulted from Canal exposure i n persons who had been l i v i n g adjacent to the Canal i n 1978 (5)· For this study, 12 households with the highest concentrations of marker organic chemicals i n basement a i r i n 1978 were selected. Persons who had l i v e d i n several of these homes were then studied f o r frequencies of d i f f e r e n t forms of chromosomal aberration i n comparison with frequencies found i n simultaneous testing of matched households elsewhere i n the Niagara F a l l s urban/suburban area. No s i g n i f i c a n t differences i n frequencies were seen i n this comparison. Whether cytogenetic changes were never Induced by chemical exposure i n homes near the Canal, or i f they had been Induced but did not p e r s i s t , could not be resolved by this study. Extensive t e s t i n g was also carried out to assess future hazards for human habitation and r e s i d e n t i a l use of the area. This testing was carried out i n an extensive program funded by EPA i n 1980-81 a f t e r remedial drainage construction work at the Canal was complete (6). A l l of the survey design and technical laboratory problems described above were encountered i n this program. Despite extensive e f f o r t s to meet requirements f o r sample size and d i s t r i b u t i o n , to provide f o r adequate control sampling away from the Canal area, and



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to allow for s a t i s f a c t o r y sample c o l l e c t i o n procedures and laboratory testing protocols, time and resource constraints limited the scope of the program. Questions were raised regarding the interpretation of results i n the face of sustained public concern and l i t i g a t i o n over the entire s o c i o - s c i e n t i f i c s i t u a t i o n . From the viewpoint of scien t i f i c assessment, however, review of EPA test results by the U.S. Department of Health and Human Services concluded that, despite l i m i t a t i o n i n sample size and questions regarding certain technical laboratory procedures, the data were s u f f i c i e n t to judge the Love Canal r e s i d e n t i a l area safe f o r human r e s i d e n t i a l use. This r i s k assessment, using the environmental test data i n hand, was based on the absence of chemical levels above the low parts per b i l l i o n range. The conclusion was reached with the s t i p u l a t i o n that storm sewer drainage tracks known to contain excess levels of dloxln and other persistent organic chemicals be cleaned, that the Canal s i t e i t s e l f not be used f o r home s i t e s , and that an adequate program f o r monitor ing chemical contaminant within the Canal s i t e be established and maintained into the Indefinite future. These recommendations regard ing future h a b i t a b i l i t y have not been adopted pending review of the data on which they were based and consideration of the possible need for further evaluative environmental t e s t i n g .

Literature Cited 1. 2. 3. 4. 5. 6.

"Health Risk Estimates for 2,3,7,8-Tetrachlorodibenzodioxin in Soil," Centers for Disease Control, Morbidity and Mortality, Weekly Report, 1984. Kim, C. S.; Narang, R.; Richards, A. et al. Proc. Environmental Protection Agency National Conference on Management of Uncon trolled Hazardous Waste Sites, 1980, p. 212. Vianna, N. J . Proc. 10th Ann. NY State Dept. of Health Birth Defects Symp., 1980, p. 165. Heath, C. W., Jr. Envlr. Health Perspect. 1983, 48, 3-7. Heath, C. W., Jr.; Nadel, M. R.; Zack, Μ. Μ., J r . , et al. J . Amer. Med. Assoc. 1984, 251, 1437-40. "Environmental Monitoring at Love Canal," Environmental Protec tion Agency, EPA 600/4-82-030a, 1982.

RECEIVED August 6, 1984


Uses of Environmental Testing in Human Health ... - ACS Publications

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