EHP 105(1) Correspondence

Comments on "A Reevaluation of Cancer Incidence near the Three Mile Island Nuclear Plant"

This issue of the journal includes a critical review and reanalysis by Wing et al. (1) of a cancer study we conducted in the aftermath of the 1979 accident at the Three Mile Island (TMI) nuclear plant (2,3). We find the lengthy piece tendentious and unbalanced. No notice is taken of any of the innovations of the original study, such as the exposure model that took detailed account of prevailing winds and topography. As the findings from the reanalysis differ little from the original study, we will focus our comments on four brief points.

First, both our initial views and subsequent conclusions about the possibility of an accident-related cancer increase have been misrepresented. At the time we undertook the study, we were doubtful about effects of exposure, and appropriately so, given both the very low official estimates of the TMI releases and the short latency period. Nonetheless, we did think it was possible that unmonitored releases might have been greater than those estimated and thus might have produced levels of radiation exposure greater than background levels. Analysis of the off-site thermoluminescent dosimeter data available to us toward the end of our study led us to rule this out, however, and to conclude that the releases were in fact within range of official dose estimates. If the dosimeter data had yielded a different result, our interpretation of the findings would have reflected this. The conclusions we did reach have also been misrepresented. Wing et al. (1) claim we "concluded that observed associations did not reflect an accident effect." We actually said the following: "Overall, the pattern of results does not provide convincing evidence that radiation releases from the Three Mile Island nuclear facility influenced cancer risk during the limited period of follow-up" (2).

Second, contrary to what Wing et al. (1) claim, we did in fact specifically recommend follow-up of the TMI area population, both in the author's reply (4) to the commentary accompanying initial publication of the paper on cancer and radiation emissions at TMI (2) and also in official communications with the Three Mile Island Public Health Fund. Indeed, the fund accepted the recommendation for follow-up, and such studies are currently under way at the University of Pittsburgh under the direction of Evelyn Talbott.

Third, the initial assumptions of Wing et al. (1), and the context in which they interpret their results, are based on strictly anecdotal reports of symptoms. These reports are consistent with radiation poisoning, but inconsistent with even the worst-case scenarios concerning radiation releases from TMI. The sole supporting evidence Wing et al. cite for assuming levels of radiation emissions that could lead to vomiting and hair loss comes from cytogenetic analysis by Russian scientists of 29 symptomatic individuals from TMI. These data, which we have not seen, are reported in a 1996 Russian publication, which was certainly not available to us at the time of our study. It seems odd that these data, if meaningful for the United States and the people of Three Mile Island, should appear in such an out-of-the-way place.

Fourth, the principal difference between our work and that of Wing's team is in the interpretation of results and not in the results themselves. Their replication of our original analysis produced figures identical to ours "within rounding error" [see Table 1 of Wing et al. (1)]. In addition, the analysis based on their model gave results for all cancers that were quite similar to the result found with our approach. Like us [see Tables 2 and 3 in Hatch et al. (2)], Wing et al. find positive associations of accident dose with all cancers, lung cancer, and adult leukemia. There are no new findings here, only a new interpretation--partly for the reasons mentioned above and partly, we suspect, because of a change in the zeitgeist. Due to the concerns of the time about radiation risks to children living near nuclear plants, childhood cancer was a focus of our analyses, but children have been omitted from the reanalysis published here.

In addition to these four major points, we wish to make some additional corrections or clarifications (that are by no means exhaustive).

Wing et al. (1) mischaracterize the history of our dosimetric model. There were no court-imposed limitations on our exposure models. The only limitation involved our agreement to use an exposure model rather than upper limit dose calculations, which are not suitable for an epidemiological study in the first place.
Wing et al. also fail to acknowledge that our use of relative rather than absolute doses is an approach designed to overcome the very uncertainties in radiation dosimetry that they cite as concerns.
Pool (5) did not attribute the statement "... already believed that the low levels of radioactivity released by the accident were unlikely to have a measurable effect on cancer rates" to Hatch et al., as Wing and his coauthors claim, but rather to unnamed scientists.
In spite of a possible undercount of 1975 cancers, there was no evidence that this was geographically biased rather than randomly distributed throughout the study area. Because we defined exposure to radiation in geographic terms, we saw no need to exclude the 1975 data.
We considered but rejected a post- versus preaccident analysis such as Wing et al. have conducted because the TMI plant was operational in the preaccident period and we had also undertaken the evaluation of effects of emissions during routine operations.
Surprisingly, Wing et al. (1) do not seem to have adjusted their standard errors to reflect the a posteriori nature of their hypotheses.

What leads two groups of epidemiologists to attach different meaning or give different emphasis to essentially the same data is a puzzle that is likely to remain with us for as long as subjectivity plays a role in epidemiology (6). The best we can do is to state clearly and completely the assumptions we begin with and the reasons for the conclusions we reach. After that, it is up to the reader. Indeed, we urge readers of the critique by Wing et al. (1) and our response to refer to our original publications before reaching a judgment.

Maureen Hatch
Mt. Sinai School of Medicine
New York, New York

Mervyn Susser
Columbia School of Public Health
New York, New York

Jan Beyea
Consulting in the Public Interest
New York, New York

References

1. Wing S, Richardson D, Armstrong D, Crawford-Brown D. A reevaluation of cancer incidence near the Three Mile Island nuclear plant: the collision of evidence and assumptions. Environ Health Perspect 105:52-27(1997).

2. Hatch MC, Beyea J, Nieves JW, Susser M. Cancer near the Three Mile Island nuclear plant: radiation emissions. Am J Epidemiol 132:392-412 (1990).

3. Hatch MC, Wallenstein S, Beyea J, Nieves JW, Susser M. Cancer rates after the Three Mile Island nuclear accident and proximity of residence to the plant. Am J Public Health 81: 719-724 (1991).

4. Hatch M, Susser M. Authors' response to "Cancer near Nuclear Installations." Am J Epidemiol 132:416-417 (1990).

5. Pool R. Three Mile Island. A stress-cancer link following the accident? [news]. Nature 351:429 (1991).

6. Susser M. Judgment and causal inference: criteria in epidemiological studies. Am J Epidemiol 141:701-715 (1995). [Reprint, historical paper for 75th anniversary volume; first published in Am J Epidemiol 105:1-15 (1977).]

Proposed PCB Congener Groupings for Epidemiological Studies

Figure 1. Polychlorinated biphenyl. Positions 2,3,4,5,6 and 2',3',4',5',6' are substituted with H^- or Cl^-. Positions 2, 2', 6, and 6' bear ortho-substituents.

Health effects related to polychlorinated biphenyls (PCBs), which include 209 possible congeners exhibiting a variety of chlorine substitution patterns (Fig. 1), are the subject of numerous research investigations. Individual members of this family evoke diverse responses in experimental models and in humans. Certain PCB congeners mimic hormones and are neurotoxic (1-3). Others produce a dioxinlike response, which has been attributed to steric homology with 2,3,7,8-tetrachlorodibenzodioxin (TCDD) (4,5). Epidemiologic studies have tended to report health effects expressed as the total of individual PCB congener levels or as the concentration relative to a commericial PCB mixture (e.g., Aroclor 1248, 1254, or 1260). However, as congener-specific analyses of serum, adipose tissue, and other media become routinely available, it is highly desirable to organize risk analysis along biologically plausible lines, thereby avoiding misclassification of exposure and strengthening the toxicologic associations.

One approach to interpreting PCBs in environmental materials is to group the dioxinlike PCB congeners together. With this method, a single index is computed as the sum of the congener concentrations weighted by their toxic equivalents relative to TCDD (4,6). However, analagous schema for estrogenic, neurotoxic, and cytochrome P450-inducing PCBs are not available at this time.

As a means of evaluating hormonal effects, Wolff and Toniolo (7) proposed a classification system based on structural, biological, and pharmacokinetic considerations. They assigned PCB congeners to three groups: estrogenic/neurotoxic, antiestrogenic (dioxinlike), and enzyme-inducing [phenobarbital (PB)-type cytochrome P450]. The desirability of developing such a system has been raised recently with respect to a number of ongoing research investigations that are attempting to relate exposure to organochlorines, including PCBs, with breast cancer risk (8). One of these studies, in which we are co-investigators, is determining levels of PCBs in house dust as well as blood, providing an opportunity to assess exposure using internal and external measurements. As a starting point for discussion and initial classification, we suggest one possible set of PCB functional groupings (see Table 1) based on existing literature (1-8,11-13) and structure-activity considerations.

Mary S. Wolff
Mount Sinai School of Medicine
New York, New York

David Camann
Southwest Research Institute
San Antonio, Texas

Marilie Gammon
Columbia School of Public Health
New York, New York

Steven D. Stellman
American Health Foundation
New York, New York

The authors acknowledge support from NIH, grant CA/ES66572.

References

1. Korach KS, Sarver P, Chae K, McLachlan JA, McKinney JD. Estrogen receptor-binding activity of polychlorinated biphenyls: conformationally restricted structural probes. Mol Pharmacol 33:120-126 (1988).

2. Safe SH. Polychlorinated biphenyls, dibenzo-p-dioxins, dibenzofurans, and related compounds: environmental mechanistic considerations which support the development of toxic equivalency factors. Crit Rev Toxicol 21:51-88 (1990).

3. Seegel RF, Schantz SL. Neurochemical and behavioral sequelae of exposure to dioxins and PCBs. In: Dioxins and health (Schecter A, ed). New York:Plenum Press, 1994;409-434.

4. Safe SH. Toxicology, structure-function relationship, and human and environmental health impacts of polychlorinated biphenyls: progress and problems. Environ Health Perspect 100:259-268 (1993).

5. Kutz FW, Barnes DG, Bottimore DP, Greim H, Bretthauer EW. The international toxicity equivalency factor (I-TEF) methods of risk assessment for complex mixtures of dioxins and related compounds. Chemosphere 20:751-757 (1990).

6. Ahlborg UG, Becking GC, Birnbaum LS, Brouwer A, Derks HJGM, Feeley M, Golor G, Hanber A, Larsen JC, Liem AKD. Toxic equivalency factors for dioxin-like PCBs. Chemosphere 28:1049-1067 (1994).

7. Wolff MS, Toniolo PG. Environmental organochlorine exposure as a potential etiologic factor in breast cancer. Environ Health Perspect 103(suppl 7):141-145 (1995).

8. Timing of environmental exposures in breast cancer and northeast/mid-Atlantic breast cancer programs, NIEHS, 25-26 September 1996.

9. Vorhees DJ. Multimedia human exposure to polychlorinated biphenyls [PhD dissertation]. Harvard School of Public Health, Boston, MA, 1996.

10. Ballschmitter K. Zell M. Analysis of polychlorinated biphenyls by glass capillary gas chromatography. Fresenius Z Anal Chem 302: 20-31 (1980).

11. McFarland VA, Clarke JU. Environmental occurrence, abundance, and potential toxicity of polychlorinated biphenyl congeners: considerations for a congener-specific analysis. Environ Health Perspect 81:225-239 (1989).

12. Connor K, Safe S, Jefcoate CR, Larsen M. Structure dependent induction of CPYP2B by polychlorinated biphenyl congeners in female Sprague-Dawley rats. Biochem Pharmacol 50:1913-1920 (1995).

13. Harper N, Connor K, Steinberg M, Safe S. Immunosuppressive activity of polychlorinated biphenyl mixtures and congeners: nonadditive (antagonistic) interactions. Fundam Appl Toxicol 27:131-139 (1995).

DDT/DDE and Infant Exposure

The article by López-Carrillo et al. (1), which discusses the public health implications of using DDT in Mexico, is a welcome contribution to the literature. DDT is a public health concern not only in the countries still using the chemical but also in those countries that have restricted, phased out, or banned use of the chemical. Presently, it is difficult to conclude if DDT contributes to breast cancer incidence, and the lack of complete confidence in our understanding of the relationship between this xenoestrogen and breast cancer should not prevent us from finding alternatives to DDT that have less public health impact. López-Carrillo et al. (1) base their concern for DDT primarily on the possible increase of breast cancer with exposure. Although this endpoint is of concern, toxicological endpoints that deserve equal attention pertain to infant exposure.

Teratology studies by Eriksson et al. (2-4) have investigated neurological and developmental endpoints in neonatal mice. Although work is still required to elicit the nature of low-dose DDT damage to the central nervous system in neonates, the results of their work suggest that 1) the neonatal period of brain development may be similar to other perinatal periods in which the brain is susceptible to xenobiotic compounds and 2) susceptibility to damage by DDT and similar-acting compounds may be greatest during the height of rapid brain growth and during the rapid development of muscarinic acetylcholine receptors in the cerebral cortex (2-5).

Although a direct comparison between the 10-day-old mice used in these studies and 10-day-old humans cannot be made, the sequence of events of brain development between humans and rodents is quite similar (6,7) That is, nerve production, myelin formation, receptor development, etc., are events that occur in the same order in rodents and humans (7). At day 10, mice are in their last stages of neuron production for the hippocampus and cerebellum (8). Antimitotic drugs are much more toxic if exposure occurs earlier in development when more neurons are being produced (9,10). However, the first 2 weeks of postnatal life in the rodent are a period of rapid development of synaptic connections, transmitter systems, and myelination. During this stage of brain development, exposure to teratogens leads to disruption of some or all of these events, resulting in permanent injury. For example, metals such as lead, cadmium, and organotin can injure the brain at this stage, as can hypothyroidism (11). The applicability of these teratology study results to the human situation will continue to become clearer as future findings delineate effects at developmental time points when mice are more sensitive and when the development of rodent and human neurosystems are similar.

It was with the consideration of this previously described experimental work that a breast milk study was initiated in the state of Washington to access a population of concern consisting primarily of low-income Hispanics. We conducted this study to 1) determine actual levels of DDT and DDE in breast milk of mothers residing in the Yakima River basin; 2) assess the relative impact of fish consumption on the total DDT/DDE body burden; and 3) determine if total DDT and DDE levels received by breast-feeding infants were elevated to potentially deleterious levels. Fish collected from the Yakima River between 1989 and 1991 had DDT and DDE levels among the highest recorded in the United States (12). We were concerned that mothers who frequently consumed Yakima River bottom-feeding fish could have breast milk DDT and DDE concentrations sufficiently high to expose their infants to potentially deleterious levels of these compounds. Among the 36 individuals sampled (12 individuals for each of three cohorts: fish consumers, Mexico-born nonconsumers, and U.S.-born nonconsumers); results indicated that fish consumption did not significantly increase DDT/ DDE breast milk concentrations. However, as has been reported elsewhere, subjects born in Mexico had significantly elevated levels of DDT and DDE (p < 0.01) in breast milk compared to levels found in subjects born in the United States (1,13,14).

For each cohort sampled, an infant DDT intake level was determined using the breast milk value that included two-thirds of that particular cohort. For a 5-kg infant consuming 1 kg breast milk daily, infant DDT intake levels for the cohorts were in the range of 0.7-3.5 X 10^-3 mg/kg/day. These results do not include two outliers from the Mexico-born nonconsumer cohort who had DDT/DDE levels greater than two standard deviations from the mean. Our infant exposure values derived from the cohort data (excluding outliers) were more than two orders of magnitude below the administered dose used by Eriksson et al. (2-4). The two women (considered outliers) had DDT breast milk levels that correspond to the elevated levels observed in women living in Mexico. These DDT breast milk levels would expose breast-feeding infants each day to levels that are less than two orders of magnitude from the one-time administered dose given to neonatal mice.

Although DDT may contribute to an increase in breast cancer, exposure to DDT may also produce neurological and developmental endpoints of significance that require consideration. The study conducted in Washington State and data on breast milk DDT levels obtained from women in Mexico indicate that infants may be exposed to potentially deleterious levels of these compounds through breast milk. With DDT in our environment, various populations can still be exposed to sufficiently elevated DDT levels in the United States that warrant concern. Also, due to the influx of Mexico-born women into the United States, their U.S.-born infants may be a population of concern. Future research in this area should consider the feasibillty of detecting these neurological and developmental outcomes in individuals that have been previously exposed as infants, and not just for those living in areas where DDT is still in use but also in countries or areas where use has been banned or severly restricted.

Koenraad Mariën
Office of Environmental Health Assessment Services
State of Washington Department of Health
Olympia, Washington

References

1. López-Carrillio L, Torres-Arreola L, Torres-Sánchez L, Espinosa-Torres F, Jiménez C, Cebrián M, Waliszewski S, Saldate O. Is DDT use a public health problem in Mexico? Environ Health Perspect 104:584-588 (1996).

2. Eriiksson P, Archer T, Fredriksson A. Altered behaviour in adult mice exposed to a single low dose of DDT and its fatty acid conjugate as neonates. Brain Res 514:141-142 (1990).

3. Eriksson P, Nilsson-Hakansson L, Nordberg A, Aspberg A, Fredriksson A. Neonatal exposure to DDT and its fatty acid conjugate: effects on cholinergic behavioural variables in the adult mouse. Neurotoxicol 11:345-354 (1990).

4. Eriksson P, Ahlbom J, Fredriksson A. Exposure to DDT during a defined period in neonatal life induces permanent changes in brain muscarinic receptors and behaviour in adult mice. Brain Res 582:277-281 (1992).

5. ATSDR. Toxicological Profile for 4,4'-DDT, 4,4'-DDE and 4,4'-DDD. (U.S. H.H.S.- A.T.S.D.R. Draft, 1993). Atlanta, GA:Agency for Toxic Substances and Disease Registry, 1993.

6. Koëter HBWM. Behavioural teratology of exogenous substances: regulation aspects. Prog Brain Res 73:59-67 (1988).

7. Rodier PM. Comparitive postnatal neurological development. In: Prenatal exposure to toxicants (Needleman HL, Billinger D, eds). Baltimore, MD:Johns Hopkins University, 1994; 3-23.

8. Rodier PM. Critical periods for behavioral anomalies in mice. Environ Health Perspect 18: 79-93 (1976).

9. Rodier PM. Time of exposure and time of testing in developmental neurotoxicology. Neurotoxi-cology 7:69-76 (1986).

10. Rodier P. Chronology of neuron development: animal studies and their clinical implications. Dev Med Child Neurol 22:525-545 (1980).

11. Ruppert PH. Postnatal exposure. In: Neuro-behavioral toxicology (Annau Z, ed). Baltimore, MD:Johns Hopkins University Press, 1986; 170-189.

12. U.S. Geological Survey. Surface-water-quality assessment of the Yakima River basin, Washington: pesticide and other trace-organic-compound data for water, sediment, soil, and aquatic biota, 1987-91. USGS Report 92-644. Portland, OR:U.S. Geological Survey, 1992.

13. Waliszewski SM, Pardio Sedas VT, Infanzon RM, Rivera J. Determination of organochlorine pesticide residues in human adipose tissue: 1992 study in Mexico. Bull Environ Contam Toxicol 55:43-49 (1995).

14. Waliszewski SM, Pardio Sedas VT, Infanzon RM, Rivera J. Organochlorine pesticide residues in human breast milk from tropical areas in Mexico. Bull Environ Contam Toxicol 57:22-28 (1996).

Lead in Drinking Water: A Preventive Solution

Many children are at risk from lead (Pb) poisoning. One study found that one in five children in North Carolina had tested positive for elevated levels of Pb in their blood (1). In a separate study in Missouri, it was reported that 5.7% of 528 schools and 2.4% of 1,123 day care centers exceeded the EPA's action level of Pb in drinking water (2). These numbers and conclusions justify major concern, and efforts to curtail Pb consumption should be rigorously investigated.

One source that certainly contributes to this widespread problem is permanently installed drinking water fountains (3); of notable concern are water fountains found in elementary schools (1,2,4). Many old school buildings probably contain Pb-contaminated supply pipes or Pb solder from which the Pb leaches into drinking water and is then passed into human tissues, causing various physiological and neurological damage. As water in these buildings rests in Pb-contaminated plumbing overnight, throughout the summer months, and during school vacations when there is little movement of water, Pb accumulates and levels increase, causing a potential health threat. However, leaching of Pb is unpredictable, and strategies for the elimination of it from drinking water have been difficult to develop and evaluate. Although various approaches have been devised to reduce Pb in water to safe levels, i.e., adding calcium carbonate and legislating stringent Pb piping standards, these endeavors are not sufficient for complete safety (3)Temporary efforts to reduce Pb concentration in drinking water include morning flushing of the water source or permanently installed water coolers (1), use of Pb filters, or switching to bottled water dispensed in free-standing coolers. It has been reported that one-time morning flushing of drinking water coolers in elementary schools may not provide day-long Pb exposure protection for children (4). Flushing is tedious and time consuming and offers only temporary reduction of Pb because, in many cases, the Pb leaches back into the water from Pb-contaminated plumbing; therefore, many people have switched to bottled water dispensed in free-standing coolers. Until recently, it was not known whether chemical contaminants such as Pb would accumulate in bottled water dispensed in free-standing coolers.

We have examined bottled water dispensed from free-standing coolers and found Pb levels to be less than 5 ppb without any evidence of Pb accumulation in water remaining in contact with the plastic plumbing materials and the stainless steel water reservoir cooling tank during periods of non-use up to 28 days (unpublished observations). These free-standing water coolers with plastic plumbing and a stainless steel cooling tank may be one way to provide school children with Pb-free drinking water.

Bill Jirles
Julius Thigpen
Diane Forsythe
National Institute of Environmental Health Sciences
Research Triangle Park, North Carolina

References

1. Mass RP, Patch SC, Gagnon AM. The dynamics of lead in drinking water in U.S. workplaces and schools. Am Ind Hygiene Assoc J 55: 829-832 (1994).

2. Gnaedinger RH. Lead in school drinking water. J Environ Health 55(6):15-18 (1993).

3. Davis WF. A case study of lead in drinking water: protocol, methods, and investigative techniques. Am Ind Hyg Assoc J 51:620-624 (1990).

4. Murphy EA. Effectiveness of flushing on reducing lead and copper levels in school drinking water. Environ Health Perspect 101:240-241 (1993).

Calculation of Cancer Risk

Recently the EPA proposed changes in how it determines which chemicals and pollutants cause cancers, relying less on animal tests and more on new techniques of molecular biology. Acknowledging recent advances in molecular biology and other fields, EPA's new proposal would give more weight to a broad range of evidence, including details about precisely how toxic agents wreak their harm on human cells and on genetic material that control cells' reproduction. By taking the mechanics of cancer into account, the new approach will more precisely measure a chemical's cancer potential. At the same time, the new proposal opens the way for new statistical analyses about the effects that chemicals might have at very small doses that people are exposed to, rather than at very large doses given to animals to test their effects.

In summary, the EPA will rightly draw more on improved understanding of the mechanism by which toxic effects are produced. Over the years it has been recognized that the ultimate value of toxicological information relates to its use in the development of formal risk or safety assessments. Thus, a broad array of research is focused on the development of mechanistic information that will have value in assessing the potential human health risk of environmental pollutants and consumer products and assessing the safety of pharmaceuticals.

From this research have emerged significant advances in our understanding of the mechanism of carcinogenesis, which justifies EPA's effort to rethink cancer calculations. Among these advances are the following:

Significant developments in science of how humans metabolize cancer-causing substances. Most molecules identified as carcinogenic do not produce their detrimental effects themselves. They have to be metabolized, usually into a form that can react irreversibly with sites on DNA, altering gene expression. The role of two important sets of enzymes--the cytochrome P450 family and the glutathione S-transferase--are now well known from both human and animal studies to play an important role in the metabolism of carcinogens.
A better understanding of the potential differences in a tumor suppressor gene pathway in chemically induced and spontaneous kidney cancer.
An understanding of the different capacities of cells for DNA repair. Two types of DNA repair exist: repair pathways and a tolerance mechanism. In repair mechanism, the DNA damage is removed, while tolerance mechanism circumvents the damage without fixing it.
Increased information on the role of viruses in caricinogenesis. For example, recent reports describe how an adenovirus that has a key gene deleted can no longer reproduce itself in normal cells, but does just fine in cancer cells lacking the p53 tumor suppressor gene. As a result, the virus kills the cancer cell, apparently without harming the normal cells.
Advances in our knowledge of signal transduction that have led to major insights into the fundamental pathway that govern growth regulation of cells. These discoveries fulfill the long-sought ability to delineate a sequence of events from extracellular signals to nuclear responses. Additionally, key molecules in the pathway are evolutionarily conserved and mediated in an eclectic array of signals. Alterations in the pathway are important in tumorigenesis and tumor progression.
Discovery that apoptosis--programmed cell death--is highly regulated at the molecular level by oncogenes and anti-oncogenes. Understanding the biochemical and molecular pathway that controls apoptosis is central to the cancer problem.
The characterization of the relationship between peroxisome proliferators and cancer, including the role of cell receptors, DNA oxidation, and gene expression.
A better understanding of the mechanism through which the leukemogen benzene affects bone marrow. Metabolites of benzene are found to be highly concentrated in bone marrow of exposed animals.
The elucidation of generic mechanisms of action common to multiple chemicals. These studies have included nitroaromatic compounds, automotive fuels, dioxin, butadiene, chloroform and chlorine, dimethylamine, ethylene oxide, and furans.
Increased expertise in the development of methods for conducting carcinogenic studies, including numerous assays and techniques in a range of disciplines.

In 1996, there was evidence of high momentum in both privately funded and government supported research aimed at better understanding risks to human health from exposure to environmental agents.

Clearly, environmental health research including risk assessment science is at a remarkable point in time. There is a wonderful record of accomplishments, and this accounting is only a partial list. There has been enormous progress against cancer, yet so much more remains to be done in improving the basis for understanding and assessing potential adverse effects of chemicals and consumer products on human health.

The more we know about the mechanisms involved in environmental chemical interactions with complex mammalian organisms, including both laboratory animals and humans, the more confident the public will become in estimates of human health risks, and the firmer the scientific foundation for environmental health policy formulation will become for the prevention and control of cancer and related diseases, dysfunction, and premature death. This policy and the related regulations and intervention programs shape our society and suggest priorities for investment of public health resources. The importance of these issues cannot be overstated, and the EPA appears to be moving in the right direction.

Bailus Walker
Howard University Cancer Center
Washington, D.C.

Responsible Care and the Third World

As you point out, many environmental health scientists remain skeptical that the chemical industry's Responsible Care initiative is mainly a public relations ploy to improve the industry's dismal public image [EHP 104:1138(1996)]. Nowhere is the challenge greater than in the rapidly industrializing countries of the Third World, where corporate responsibility is not compelled by public awareness, regulation, and compensation laws.

The double standards of global corporations that operate more polluting and dangerous plants in Third World countries were described not only by industry critics but also the International Labor Office and the United Nations Center on Transnational Corporations (1,2). After the disaster at Union Carbide's plant in Bhopal, India, giant chemical producers based in the United States and Europe have been obliged to issue policy statements to the effect that they do not have lower standards for the protection of human health and safety and the environment in their Third World operations.

When pressed, however, leading firms have been reluctant to disclose toxic release inventory data for pollution from their foreign plants as they have had to do by law in the United States since 1988. Similarly, U.S. law requires a process hazards analysis in the event of failure of safety systems, including worst-case accident scenarios--are the big companies willing to release similar analyses for their affiliates' plants in Africa, Asia, and Latin America? What about meeting modern standards for disposal of hazardous wastes from plants located in countries with no facilities available for disposing of these wastes in a manner that would meet the standards the companies face in Europe and North America? Where a control limit is opposed by a corporation as unnecessarily strict, does the company comply with the limit outside the country where the limit is in effect but being challenged in court? If a pesticide is banned for certain uses or voluntarily withdrawn from markets in the United States, does that mean it will be similarly withdrawn elsewhere? If teratogenic glycol ether solvents are withdrawn from uses in the United States because of liability considerations, will they be withdrawn from sale in other countries where no such liability exists?

Product stewardship is the most challenging area that the chemical corporations have tried to address through the Responsible Care initiative. But closer examination has shown that, in 1991, DuPont's putative product stewards were none other than the company's sales representatives. Obviously salespeople have neither the incentive nor the training to critically evaluate the industrial hygiene and pollution control measures of their customers.

To some extent, industry is being forced to develop cleaner and safer processes and products in North America and Europe. Will the companies who are making these advances in some countries rapidly transfer them around the world? Or will the companies take many years to reformulate adhesives, sealants, and paints made with toxic solvents and heavy metal pigments in Third World countries?

Responsible Care does not deal with the very sensitive subject of compensation. Bayer has operated highly hazardous chromate facilities in Mexico and South Africa and many workers and members of the surrounding communities have been harmed. Lung cancer has been recognized as a compensable occupational disease in chromate workers in Germany since 1936, but this was not entered in the schedule of occupational diseases in South Africa until 1994. When a Natal doctor attributed some workers' lung cancer deaths to their occupation, Bayer steadfastly refused to pay any compensation. Perhaps the best way of getting global corporations to eliminate double standards is to have them held liable in their home countries, as U.S. companies are for the creation of toxic waste sites under the Comprehensive Environmental Response, Compensation, and Liability Act.

The subjects of this letter are dealt with in more detail elsewhere (3). However, it is clear that the greatest testing ground for corporate policies on health, safety, and the environment, and industry initiatives like Responsible Care is the rapidly industrializing countries. Public health workers should subject the big companies' claims to careful international scrutiny. Curbing double standards represents both a formidable challenge and a great opportunity in environmental health.

Barry I. Castleman
Environmental Consultant
Baltimore, Maryland

References

1. International Labor Office. Safety and Health Practices of Multinational Enterprises. Geneva:International Labor Office, 1984.

2. United Nations. Environmental Aspects of the Activities of Transnational Corporations: A Survey. New York:United Nations, 1985.

3. Castleman BI. The migration of industrial hazards. Int J Occup Environ Health 1:85-96 (1995).

Last Update: Febuary 25, 1997