PROCEEDINGS OF THE EXPERT PANEL WORKSHOP
TO EVALUATE THE PUBLIC HEALTH IMPLICATIONS
FOR THE TREATMENT AND DISPOSAL OF POLYCHLORINATED BIPHENYLS-
CONTAMINATED WASTE


Chapter 2 - Expert Panel Report
Health Effects Panel (Cont'd)

IX. Conclusions

  1. To date, a major focus of research and public health concerns about exposures to PCBs has been on cancer. There is sufficient evidence of the carcinogenicity of higher-chlorinated PCB mixtures in experimental animals. These animal data support the premise that PCBs are carcinogenic in humans. Human data are equivocal and inconclusive.

  2. There are few animal data that support the carcinogenicity and health effects of lower-chlorinated PCB mixtures. This data gap may be addressed by a study being conducted by General Electric that is expected to be completed by the end of 1995.

  3. With respect to human studies of cancer, two major limitations exist in addition to the typical limitations of cohort studies. Insufficient emphasis has been placed upon incidence data. Also, followup of existing cohort mortality studies, both occupational and nonoccupational (Yusho and Yu-Cheng), have been insufficient because approximately 80% or more of the cohort members were still alive at the end of the studies. This data gap is currently being partially addressed by General Electric and NIOSH, who are independently updating previous mortality studies. Second-generation effects have been overlooked as well. The offspring of the cohorts could be assessed for hormonally driven cancers (especially breast, ovarian, testicular, and prostate cancers).

  4. Public health concerns about reproductive and developmental outcomes are increasing relative to concerns about cancer outcomes resulting from PCB exposures. The enhanced ability to detect functional, in addition to structural, change has resulted in additional concerns about this area of potential health effects. More information is needed about the sensitivity of women of reproductive age to exposure to PCBs.

  5. There has been a tendency to think of PCB toxicity as being cumulative because PCBs are persistent and bioaccumulate. Recent data indicate that a group of PCB congeners exert their toxicity by reacting with estrogen receptors and also by influencing the endocrine system. It is not clear at this time how these effects are linked to health outcomes. However, until these relationships are adequately described, there should be greater concern about the lower-dose exposures that are experienced by larger percentages of the total population.

  6. It is important to distinguish between reproductive and developmental health issues. These two health effects may represent different exposure scenarios and biological mechanisms.

  7. Additional evaluations in animals and humans are needed on the association between PCB exposure and reproductive or developmental effects. For example, better documentation of clinical significance and better control of confounders are needed.

  8. Available scientific data for animals and humans suggest that PCBs cause developmental neurotoxicity. Neurodevelopmental and neurobehavioral effects are among the most sensitive indicators of PCB toxicity in animals. This may also be the case for humans.

  9. Neurologic effects of PCB exposure appear to be more important for children who are exposed as fetuses rather than as infants, or for adults who have been occupationally exposed.

  10. More definitive studies (toxicologic and epidemiologic) of neurologic effects need to be conducted. Efforts should be made to better document and estimate biochemical deficiencies or functional impairments that have clinical significance. Available data are insufficient to conclude whether the developmental neurotoxicity effects of various PCB congeners are similar or different. Also, existing data depend primarily on subjective measures of effect, and more objective data are needed to evaluate dose-response relationships.

  11. To fully understand the impact of PCBs on the immune system, it may be appropriate to evaluate how much of a reduction in IgG and IgM constitutes an adverse health effect. In addition, it may be appropriate to evaluate indicators of auto-immune dysfunction (for example, rheumatoid arthritis and systemic lupus erythematosus) in humans.

  12. There is a lack of information on the correlation between serum PCB levels and enzyme induction. In the future, reporting of serum PCB levels in basic research studies should be standardized for lipid weight. Investigations are needed to evaluate the merit of collecting planar PCB (congener-specific) data. For most occupational and many community epidemiologic studies, congener-specific PCB levels may not be of sufficient value to justify the expense.

  13. There is a lack of information pertaining to the functional toxicology of PCB mixtures and how they change gene expression and differentiation or interact with other chemicals. Because developmental neurotoxicologic effects are measured as loss of function, it is difficult to ascertain dose-response relationships.

  14. There is a need for a good inexpensive biomarker that can be used to characterize PCB exposures of large populations. This biomarker needs to be both sensitive (for example, enzyme induction) and specific. Currently, it is prohibitively expensive to determine serums levels of all PCBs, dioxins, and furans.

  15. Although current TEFs may overestimate the toxicity of dioxin-like PCBs, they are potentially helpful in evaluating the public health implications of potential or actual exposures. No TEFs have been developed for phenobarbital-like effects of PCBs.

  16. New study populations, such as women of reproductive age, are needed to evaluate the health effects of PCB exposures. Appropriate occupational cohorts may exist in Eastern Europe or in the former Soviet Union. Wildlife populations have been evaluated and should continue to be evaluated for health effects that may be applicable to humans.

  17. Evaluation of the health risks associated with remediation of PCBs should focus not only on the risks of PCBs, but on the risks of all substances present. Quantitative exposure analysis of all contaminants and evaluation of their fate and transport are needed.

  18. More information and followup are needed on exposures of and health effects among workers involved with PCB storage or disposal (for example, incinerator workers and capacitor/transformer retrofitters).

  19. Given the variety of PCB-related information that is currently available, an information repository is needed. This database should include summaries of ongoing research projects and copies of scientific articles and other information.

X. Recommendations

These recommendations are presented for consideration by ATSDR, other public health agencies, and research organizations. Unless specifically noted, they are not intended for any particular organization.

  1. Follow up existing cohorts for more complete evaluation of causes of mortality. Add morbidity evaluations when feasible.

  2. Continue animal studies that assess the specific health effects of lower-chlorinated congeners and mixtures.

  3. Analogous to follow up of persons exposed to dioxins at Seveso, Italy, evaluate the need to establish a registry of various groups (both occupational and non-occupational) that have been characterized in terms of PCB exposure. Evaluate the utility and feasibility of following the groups prospectively for multiple generations and focus on changes in and loss of function of immune, endocrine, and nervous system parameters.

  4. Assess the need for and feasibility of identifying and evaluating a second-generation population whose parents were exposed to PCBs. One approach might be to attempt to identify and follow children of parents in one or more of the larger occupational cohorts.

  5. Develop studies to assess the effects of PCBs on the reproductive experiences of women occupationally or environmentally exposed, controlling for known or suspected confounding factors.

  6. Conduct research to further evaluate the utility of TEFs for estimating environmental and public health risks of PCBs. Emphasis should be placed upon estrogen-like and phenobarbital-like PCBs. Evaluation should consider metabolic activity, additivity of toxic equivalents, interaction (or antagonistic) effects, and species and outcome specificity.

  7. Conduct comparative animal studies to determine whether the developmental or neurotoxic effects, or both, of various mixtures of PCB congeners are similar or different. Also include quantitative evaluation of dose-response relationships.

  8. Conduct studies to assess the neurologic and long-term public health consequences of occupational and pre-natal exposures.

  9. Use methods such as the reverse transcriptase polymerase chain reaction (PCR) to evaluate the correlation between serum PCB levels and enzyme induction.

  10. Conduct studies to further define the role of PCBs, either as individual congeners or as mixtures, in tumor promotion in experimental animals and cell cultures.

  11. Conduct clinical and epidemiologic studies in other human populations that have been significantly exposed to PCBs.

  12. Conduct baseline surveys of exposures and health status of workers at, and communities near, existing or new PCB incinerators before operation begins.

  13. ATSDR should establish a PCB database repository to collect, summarize, and store relevant data on the health effects of PCB congeners and mixtures and on ongoing research.

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Steele G, AB Smith, J Bernert, et al. 1990. Health Hazard Evaluation Report HETA 84-339-2052, Westinghouse Electric Company, Bloomington, Indiana. Cincinnati, OH: National Institute for Occupational Safety and Health, Hazard Evaluations and Technical Assistance Branch.

Steele G and BS Richter. 1992. Final Report: Community Exposure to Polychlorinated Biphenyls, Bloomington, Indiana. Indiana State Board of Health, Division of Chronic Disease. Atlanta, GA: Agency for Toxic Substances and Disease Registry.

Stehr-Green PA, E Welty, G Steele, et al. 1986. Evaluation of potential health effects associated with serum polychlorinated biphenyl levels. Environ Health Perspect 70: 255-259.

Steinberg KK, LW Freni-Titulaer, TN Rogers, et al. 1986. Effects of polychlorinated biphenyls and lipemia on serum analytes. J Toxicol Environ Health 19(3): 369-81.

Street JC and RP Sharma. 1975. Alteration of induced cellular and humoral immune responses by pesticides and chemicals of environmental concern: quantitative studies of immunosuppression by DDT, Aroclor 1254, carbaryl, carbofuran, and methyl parathion. Toxicol Appl Pharmacol 32: 587-602.

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XII. Appendices

Appendix A. Health Effects Panel Biosketches

The following persons were members of the Health Effects Panel. Although their participation included reviews of the individual draft reports pertaining to their panel, this does not imply their endorsement of the final written panel report or support for the conclusions derived in the report.

CHAIR: James M. Melius, M.D., Dr.P.H.
Director, Division of Occupational Health
and Environmental Epidemiology
New York State Department of Health

Graduated from University of Illinois, School of Medicine, 1974. Received board certification in family practice and occupational medicine. Received Doctorate of Public Health in Epidemiology from the University of Illinois, School of Public Health, 1984.

Worked for the National Institute for Occupational Safety and Health (NIOSH) in Cincinnati, Ohio, from January 1980 to June 1987. Directed the Division of Surveillance, Hazard Evaluations and Field Studies, a large research group that conducted occupational medical and epidemiologic studies, the last 2 years at NIOSH.

Worked as a medical consultant in the Division of Environmental Health Assessment, New York State Department of Health, June 1987. Appointed Director of the Division of Occupational Health and Environmental Epidemiology, January 1988. Appointed Professor of Environmental Health and Toxicology, School of Public Health of the State University of New York at Albany, May 1990. Currently serves on the Study Section for Occupational Health for the National Institutes of Health and has recently been a member of three National Academy of Sciences committees.


RAPPORTEUR: Greg Steele, Dr.P.H., M.P.H.
Environmental Epidemiologist
Indiana State Department of Health

Doctor of Public Health, University of Alabama-Birmingham, School of Public Health, Epidemiology, 1991. Environmental Epidemiologist, Epidemiology Resource Center, Indiana State Department of Health, Indianapolis, Indiana, 1983 to present. Association of State and Territorial Health Officials, Consultant to the Environmental Committee, 1987-1992.


Henry A. Anderson, M.D.
Chief Medical Officer, Occupational & Environmental Health
Wisconsin Division of Health

Chief Medical Officer from October 1991 to present. State Epidemiologist for Occupational and Environmental Disease, Wisconsin Division of Health, Madison, June 1980 to present. M.D., University of Wisconsin Medical School, Madison, 1972. American Board of Preventive Medicine, Subspecialty: occupational and environmental medicine, 1977. Chairperson, Council of State and Territorial Epidemiologists (CSTE)-Section of Occupational, Environmental Health, 1982-1988. President, Wisconsin Preventive Medicine Society, 1986 to present. Associate Editor, American Journal of Industrial Medicine.


Jean D. Brender, R.N., Ph.D.
Director, Noncommunicable Disease Epidemiology and Toxicology Division
Texas Department of Health

University of Washington School of Public Health, Ph.D., Epidemiology (Noninfectious disease epidemiology), 1983. Director, Environmental Epidemiology Program, Texas Department of Health, Austin, Texas, 1987-1993. Presently Director, Noncommunicable Disease Epidemiology and Toxicology Division, Texas Department of Health, and State Environmental Epidemiologist.

Dorothy A. Canter, Ph.D.
Science Advisor, Office of Solid Waste and Emergency Response
U.S. Environmental Protection Agency

George Washington University, Ph.D., Biophysics, May 1974. Assistant to the Director, National Toxicology Program, 1980-1990. Science Advisor, Office of Solid Waste and Emergency Response, Environmental Protection Agency, March 1990 to present.


Theodora Emily Colborn, Ph.D.
Senior Fellow, World Wildlife Fund, Inc.

Senior Fellow, World Wildlife Fund, 1989-1993. Senior Fellow, The Conservation Foundation, Washington, D.C., 1987-1988. Congressional Fellow, Office of Technology Assessment, 1985-1987. University of Wisconsin-Madison, Ph.D. Zoology (distributed minor in epidemiology, toxicology, and water chemistry), 1985.


Joe G.N. Garcia, M.D.
Professor of Medicine, Physiology, Biophysics
Director, Indiana University Occupational Lung Center
Indiana University School of Medicine

Graduated University of Texas Southwestern Medical School, M.D., Dallas, Texas. Residency in Internal Medicine, University of Iowa. Board Certification in Internal Medicine, Pulmonary Medicine, and Critical Care Medicine. Director of Occupational Medicine, University of Texas at Tyler, 1985-1988. Director of the Occupational Lung Center, Indiana School of Medicine, 1988-1993. Calvin H. English Investigator in Medicine, 1989 to present. Presently at Wishard Memorial Hospital, Division of Pulmonary and Critical Care Medicine.


Stephen B. Hamilton, Jr., Ph.D.
Manager, Environmental Science and Technology
General Electric Corporation

Doctor of Philosophy (Ph.D.) degree-Organic Chemistry, Northwestern University, 1959. Manager of Environmental Science and Technology, GE Corporate Environmental Programs, 1981 to present. Honors, Fulbright Fellow, 1959-1960. Special interests and competence: synthesis of organic compounds and intermediates, organic chemistry mechanisms, human health effects and toxicology of PCBs, especially individual PCB congeners, environmental fate of PCBs, PCB destruction research.

George W. Lucier, Ph.D.
Chief, Laboratory of Biochemical Risk Analysis
National Institute of Environmental Health Sciences

Ph.D. (Entomology), University of Maryland, June 1970. National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, 1970 to present. Chief, Laboratory of Biochemical Risk Analysis, Division of Biometry and Risk Assessment, 1984 to present. Co-Editor, Environmental Health Perspectives, National Institute of Environmental Health Sciences, 1973 to present.


Mitchell Singal, M.D., M.P.H.
Medical Officer
National Institute for Occupational Safety and Health

M.D., Wayne State University, Detroit, Michigan, May 1969. M.P.H. (major in Environmental Health Sciences), University of California, Berkeley, June 1974. Medical Officer, Hazard Evaluations and Technical Assistance Branch, National Institute for Occupational Safety and Health, Cincinnati, Ohio, July 1977 to present. Senior Medial Officer, April 1991 to present. Specialty Board Certification (American Board of Preventive Medicine), General Preventive Medicine, 1976. Occupational Medicine, 1980.


CO-CHAIR: Lee M. Sanderson, Ph.D.
Division of Health Assessment and Consultation
Agency for Toxic Substances and Disease Registry

Currently Senior Epidemiologist, Division of Health Assessment and Consultation, Agency for Toxic Substances and Disease Registry. Epidemiology, Ph.D., University of Texas School of Public Health, Houston, Texas, 1981.


CO-CHAIR: Obaid M. Faroon, Ph.D., D.V.M.
Division of Toxicology
Agency for Toxic Substances and Disease Registry

Environmental Health Scientist, Agency for Toxic Substances and Disease Registry, 1991 to present. Ph.D., Histology and Pathology, College of Veterinary Medicine, The University of Tennessee, Knoxville, Tennessee. D.V.M., School of Veterinary Medicine, The University of Baghdad, 1976.


Appendix B. The Bloomington Polychlorinated Biphenyls (PCB) Project:
Questions and Issues for the PCB Health Effects Panel

I. Introduction

The Agency for Toxic Substances and Disease Registry will convene three expert panels at a workshop to address PCB-related health issues. As one of the three, the Health Effects Panel will discuss the current knowledge of health effects associated with exposures to PCBs and make recommendations to better determine the public health implications associated with the remediation of PCB-contaminated soils and other waste materials. The Health Effects Panel is a multidisciplinary group of scientists who have expertise in toxicology, medicine, epidemiology, and environmental science.

The purpose of this document is to identify current issues and questions that will serve as an outline for the discussions of the Health Effects Panel and as a catalyst for formulating appropriate recommendations. These questions and issues were identified by the Chair, Rapporteur, and Co-chairs of the Health Effects Panel. The background and foundation for these specific questions and issues are included in a separate draft document entitled "Background Discussion Paper for the PCB Health Effects Panel: Summary of Health Effects associated with PCBs."

II. General Overview

  1. Structural activity relationships: PCBs have been classified into coplanar (dioxin-like activity) and non-coplanar (non-dioxin-like activity).

    1. What is the toxicity of non-coplanar PCBs and what is the mechanism?

    2. What are the kinds of chemical interactions (additive, potentiation, etc.) between coplanar and non-coplanar PCBs?

  2. Mixture toxicity and interactions: Commercial PCB formulations, such as Aroclors and Kanechlors, are complex mixtures containing about 209 congeners. These congeners have different absorption, distribution, and metabolism rates in addition to different environmental fates.

    1. The general population may be exposed to mixtures that are different from those of occupational exposure. In food and the environment, only highly chlorinated congeners persist for longer times. Should concerns about public health implications focus primarily on the highly chlorinated biphenyls?

  3. Numerous exposure assessments have been conducted for occupationally or non-occupationally PCB-exposed populations and for general populations not known to be exposed to PCBs. These assessments have provided reference ranges for serum PCB levels.

    1. Serum PCB levels are often expressed as total PCBs and do not specify the level of highly chlorinated PCBs. Are total serum PCB levels a good predictor of the biological effects of PCB exposure?

    2. From a public health perspective, should an action level for serum PCBs be established by ATSDR? If yes, what should that level be?

  4. Human exposures to PCBs often involve exposure to PCB mixtures containing contaminants such as polychlorinated dibenzofurans (PCDFs) and polychlorinated dibenzodioxins (PCDDs).

    1. What are the issues related to PCB interaction with these and possible other contaminants?

  5. Most of the scientific data pertaining to human health effects comes from the study of occupational exposures while the majority of human exposures occur in non-occupational settings.

    1. With consideration of potential healthy worker effects and potential greater susceptibility of sensitive subgroups of the general population, what inferences should be made in considering the public health implications of PCB exposures?

III. Cancer Outcomes

  1. PCBs induce nodular hyperplasia, preneoplastic nodules, adenomas, and trabecular carcinomas in the livers of animals. The development of cancer depends upon dose, chlorination of the congeners, and the length of exposure. PCBs also may affect the inhibitory or promotional effects of other chemicals.

    1. Animal studies suggest that PCBs promote the development of neoplastic lesions in the livers of animals with prior exposure to chemicals such as N-nitrosodiethylamine. What public health implications and impacts upon remediation strategies should this observation have?

    2. Animal studies suggest that low-chlorinated (30% chlorine) PCBs require longer latency periods for the development of neoplastic nodules in rats. Why?

  2. Eleven different human mortality studies of occupational and non-occupational exposures to PCBs have been identified and summarized. The results of these studies show inconsistencies and differences in association between PCB exposures and specific types of cancer.

    1. What specific cancer risks have been substantiated?

    2. Which cancer risks are inconclusive?

    3. What are the data gaps associated with these inconclusive risks and how might they be resolved?

IV. Reproductive/Developmental Effects

  1. With respect to developmental toxicity, animal studies have shown that PCB exposures caused decreases in fetal survival and increases in fetal hydronephrosis. Perinatal exposures induced neurobehavioral changes that included spinning behavior, cognitive dysfunction, spatial learning memory deficits, and axonal degeneration in the ventral white matter in animals. In humans, lower birth weights have been shown and are related to shorter periods of gestation.

    1. PCBs are capable of passing through the placental barrier and being secreted in the milk of exposed mothers. In terms of public health implications, what PCB burden level in mothers has the potential to induce embryonic or fetal toxicity in humans? What is the concentration in umbilical cord blood that may cause health effects in the fetus?

  2. Many of the epidemiologic studies have shown observed effects that may either not be clinically significant or may be relatively minimal compared to other factors that may affect growth and development.

    1. What effects have been demonstrated that should be regarded as having public health implications?

V. Neurologic Effects

  1. Observed alterations in neurobehavioral parameters (reduction in response to pain stimuli), and neurochemical levels in specific brain areas (dopamine in the caudate nucleus, epinephrine in the frontal cortex) in mammals are highly suggestive of neurotoxic effects of PCB mixtures, particularly in developing brains.

    1. How much reduction (% reduction) in neurochemical levels in brain should be considered an adverse health effect? Can we establish a NOAEL, LOAEL, or serious LOAEL for this effect?

    2. What neurobehavioral test batteries used in animals are valid for humans?

    3. In animals, the lightly chlorinated PCB congeners are more effective in reducing central dopamine concentrations. Are these effects of concern for humans?

  2. Neurodevelopmental and neurobehavioral changes may be among the most sensitive endpoints of PCB toxicity for animals.

    1. If neurodevelopmental and neurobehavioral effects are among the most sensitive parameters of PCB toxicity in animals, what analogies from animal studies can be made for humans?

VI. Other Effects

  1. Enzyme inductions: It has been documented that different PCB congeners have different potencies for enzyme inductions.

    1. When evaluating the toxicity of a congener, is the enzyme induction potency an indication of the toxicity of the congener?

    2. Where enzyme induction can be observed without clinical symptoms, as occurs in low-level exposures to PCBs, should the enzyme changes be considered an adverse health effect? Should such enzyme changes be classified in terms of LOAELs, NOAELs, or adaptive changes?

    3. For enzyme induction produced by PCBs, the position of the chlorine atoms on the molecule (both para and two meta positions) may be more important than the degree of chlorination. Is this also true for the toxicity and carcinogenicity of various PCB congeners? If so, what are the public health implications?

    4. It has been suggested that TEFs proposed for "dioxin-like" PCBs overestimate the potency of these compounds by a factor of 10 to 1,000. Is there any work in progress either to improve upon the TEFs method or to identify a better approach than the TEFs? What are the limitations of using TEFs to evaluate public health implications of PCBs at hazardous waste sites?

  2. Animal studies indicate that PCBs induce MFOs which can influence the toxicity of individual PCB congeners and other contaminants.

    1. What interactions between PCBs and dioxins/furans have been noted or can be anticipated?

    2. What interactions between PCBs and other common contaminants, particularly solvents, have been noted or can be anticipated?

    3. What interactions among PCB congeners have been noted or can be anticipated?

    4. What is the best way for health assessors to deal with potential public health implications of interactions?

  3. Dermatological effects are among the most commonly reported clinical endpoints of PCB toxicity in humans.

    1. What, if any, conclusions can be made about a relationship between human dermal morbid conditions and the observation of malignant melanomas in human populations exposed to PCBs?

  4. With reference to the immune system, the results of animal studies suggest that PCBs are immunosuppressive. Reductions of spleen and thymus weights, IgG and IgM serum levels, lymphocyte count, natural killer cells, and resistance to infection have been reported. Human studies show reversible suppressed immune function.

    1. How much decrease in IgG or IgM is considered an adverse health effect of PCB exposure?

    2. What are the best methods for evaluating changes in the immune system?

  5. Animal studies have shown a variety of hepatic effects from PCB exposure. Human exposure studies have shown liver enzyme induction and elevation of various liver enzymes in the serum (particularly GGTP and SGOT). Human mortality studies have been inconsistent in showing excess deaths from liver cancer.

    1. What can be concluded about hepatic public health implications of PCB exposure?

VII. Conclusions, Data Gaps, and Recommendations

  1. PCB-related exposure or morbidity assessments of human populations have usually been done at a point in time rather than longitudinally and are limited in their ability to assess concomitant risk factors.

    1. Is there a need to monitor and follow a defined exposed population (occupational or non-occupational) for an increased incidence of cancer or other diseases?

    2. Is further human research needed to evaluate the chronic toxicity of PCB exposures? If yes, what are the data gaps and what are the corresponding activities needed to fill those gaps?

  2. Epidemiologic evaluations of public health risks associated with exposures to PCBs have focused more upon morbidity than mortality.

    1. Is mortality an appropriate or sensitive enough index or endpoint for evaluating public health implications of human exposures to PCBs?

  3. Existing mortality studies of exposures to PCBs were limited in their ability to address public health risks associated with either PCB-related contaminants or exposures to other chemicals or substances that were occurring concurrently.

    1. How can exposure issues and health impacts related to PCB contaminants and concurrent exposures be better addressed?

    2. How might these answers address public health issues associated with the remediation of PCB-contaminated soils or waste materials?

  4. Review of existing mortality studies of exposures to PCBs has identified limitations pertaining to the magnitude of study population sizes and person-years at risk. Historical cohort studies represent the vast majority of study designs.

    1. Should additional analyses and studies be done?

    2. If yes, how should they be done?

    3. Should different types of studies and evaluations be undertaken?

  5. Remediation approaches (incineration and other technologies) for PCB-contaminated soils and waste materials might involve concurrent human exposures to PCBs, PCB-related contaminants, and other hazardous chemicals and substances (specific identities may often be unknown).

    1. Is additional exposure or health information needed? If yes, what is that information and how can it be obtained?

    2. If information is lacking concerning the presence of substances in addition to PCBs, what public health implications can be determined and what are the limitations upon determining them?

Appendix C. Glossary

Acute Exposure -- Exposure to a chemical for a duration of 14 days or less, as specified in the Toxicological Profiles.

Adjustment -- A summarizing procedure for rates or measures of association in which the effects of differences in composition for variable(s) among populations being compared have been removed by mathematical procedures. Age is the variable for which adjustment is most often carried out.

Adsorption Coefficient (Koc) -- The ratio of the amount of a chemical adsorbed per unit weight of organic carbon in the soil or sediment to the concentration of the chemical in solution at equilibrium.

Adsorption Ratio (Kd) -- The amount of a chemical adsorbed by a sediment or soil (i.e., the solid phase) divided by the amount of chemical in the solution phase, which is in equilibrium with the solid phase, at a fixed solid/solution ratio. It is generally expressed in micrograms of chemical absorbed per gram of soil or sediment.

Age-Specific Rate -- A rate for a specified age group. The numerator (number of cases or persons with disease) and denominator (number of persons) refer to the same age group.

Association -- The degree of statistical dependence between two or more events or variables. Events are said to be associated when they occur more frequently together than one would expect by chance. Association does not necessarily imply a causal relationship. Statistical significance testing enables us to determine how unlikely it would be to observe the sample relationship by chance if in fact no association exists in the population that was sampled.

Bias -- Any effect at any stage of investigation or inference tending to produce results that depart systematically from the true values (to be distinguished from "random error").

Bioconcentration Factor (BCF) -- The quotient of the concentration of a chemical in aquatic organisms at a specific time or during a discrete time period of exposure divided by the concentration in the surrounding water at the same time or during the same period.

Birth Certificate -- Official, legal document recording details of a live birth, usually comprising name, date, place, identity of parents, and sometimes additional information such as birth weight. It provides the basis for vital statistics of birth and birth rates in a political or administrative jurisdiction, and is the denominator for infant mortality and certain other vital rates.

Cancer Effect Level -- The lowest dose of chemical in a study, or group of studies, that produces significant increases in the incidence of cancer (or tumors) between the exposed population and its appropriate control.

Carcinogen -- A chemical capable of inducing cancer.

Case -- In epidemiology, a person in the population or study group identified as having the particular disease, health disorder, or condition under investigation. A variety of criteria may be used to identify cases, e.g., individual physician diagnoses, registries and notifications, abstracts of clinical records, surveys of the general population, population screening, and reporting of defects such as in a dental record. The epidemiological definition of a case is not necessarily the same as the ordinary clinical definition.

Case-control Study -- Persons with a specific disease (cases) are compared to persons without that disease (controls or comparisons) to evaluate differences in potential risk factors or determinants of disease. When a case-control study demonstrates that cases have been exposed to a presumed risk factor significantly more often than controls, it is possible to estimate the approximate relative risk associated with exposure.

Cause-specific Rate -- A rate that specifies events, such as deaths, according to their cause.

Ceiling Value -- A concentration of a substance that should not be exceeded, even instantaneously.

Chronic Exposure -- Exposure to a chemical for 365 days or more, as specified in the Toxicological Profiles.

Cohort study -- A defined group of peoples with varying levels of exposure are followed over a period of time sufficient to allow health outcomes of interest to occur. Numbers or rates of cause-specific disease or death are calculated for members of the cohort and compared to what would be expected based upon a pre-determined "standard" population.

Confounding [from the Latin "confundere," to mix together] -- A situation in which the effects? of two processes are not separated. In other words, it is the distortion of an apparent effect of an exposure on risk brought about by the association with other factors that can influence the outcome.

Confounding variable (or confounder ) -- A factor that distorts the apparent magnitude of the effect of a study factor on risk. Such a factor is a determinant of the outcome of interest and is unequally distributed among the exposed and the unexposed.

Congener -- A chemical compound closely related to another in composition and exerting similar or antagonistic effects, or something derived from the same source or stock.

Death Certificate -- A vital record signed by a licensed physician or, in some nations, by another designated health worker, that includes cause of death, decedent's name, sex, birth date and place of residence and of death. Occupation, birthplace, and other information may be included. Immediate cause of death is recorded on the first line, followed by conditions giving rise to the immediate cause; the underlying cause is entered last.

Denominator -- The population (or population experience, as in person-years, passenger-miles, etc.) at risk in the calculation of a rate or ratio. The lower portion of a fraction used to calculate a rate or ratio.

Developmental Toxicity -- The occurrence of adverse effects on the developing organism that may result from exposure to a chemical before conception (either parent), during prenatal development, or postnatally to the time of sexual maturation. Adverse developmental effects may be detected at any point in the life span of the organism.

Embryotoxicity and Fetotoxicity -- Any toxic effect on the conceptus as a result of prenatal exposure to a chemical; the distinguishing feature between the two terms is the stage of development during which the insult occurred. The terms, as used here, include malformations and variations, altered growth, and in utero death.

EPA Health Advisory -- An estimate of acceptable drinking water levels for a chemical substance based on health effects information. A health advisory is not a legally enforceable federal standard, but serves as technical guidance to assist federal, state, and local officials.

Epidemiology -- The study of the distribution and determinants of health-related states and events in populations, and the application of this study to control of health problems.

Immediately Dangerous to Life or Health (IDLH) -- The maximum environmental concentration of a contaminant from which one could escape within 30 minutes without any escape-impairing symptoms or irreversible health effects.

Immunologic Toxicity -- The occurrence of adverse effects on the immune system that may result from exposure to environmental agents such as chemicals.

Incidence -- The number of instances of illness commencing, or of persons falling ill, during a given period in a specified population. More generally, the number of new events, e.g., new cases of a disease in a defined population, within a specified period of time. The term incidence is sometimes used to denote INCIDENCE RATE.

Incidence Rate -- A measure of the rate at which new events occur in the population. The number of new events, e.g., new cases of a specified disease diagnosed or reported during a defined period of time, is the numerator, and the number of persons in the stated population in which cases occurred is the denominator.

Intermediate Exposure -- Exposure to a chemical for a duration of 15-364 days, as specified in the Toxicological Profiles.

International Classification of Diseases (ICD) -- The classification of specific conditions and groups of conditions determined by an internationally representative group of experts who advise the World Health Organization, which publishes the complete list in a periodically revised book, the Manual of the International Statistical Classification of Diseases, Injuries and Causes of Death. Every disease entity is assigned a number. There are 17 major divisions (chapters) and a hierarchical arrangement of subdivisions (rubrics) within each. The Ninth Revision of the Manual (ICD-9) was published by WHO in 1977, after ratification in 1976.

In Vitro -- Isolated from the living organism and artificially maintained, as in a test tube.

In Vivo -- Occurring within the living organism.

Isomerism -- The relationship that exists between two or more different chemical compounds that have the same molecular formula; the compounds are isomers of each other.

Latent Period (or latency) -- Delay between exposure to a disease-causing agent and the appearance of manifestations of the disease. After exposure to ionizing radiation, for instance, there is a latent period of 5 years, on average, before development of leukemia, and a latent period of more than 20 years before development of certain malignant conditions. The term "latent period" is often used synonymously with "induction period," that is, the period between exposure to a disease-causing agent and the appearance of manifestations of the disease. It has also been defined as the period from disease initiation to disease detection.

Lethal Concentration(LO) (LCLO) -- The lowest concentration of a chemical in air that has been reported to have caused death in humans or animals.

Lethal Concentration(50) (LC50) -- A calculated concentration of a chemical in air to which exposure for a specific length of time is expected to cause death in 50% of a defined experimental animal population.

Lethal Dose(LO) (LDLO) -- The lowest dose of a chemical introduced by a route other than inhalation that is expected to have caused death in humans or animals.

Lethal Dose(50) (LD50) -- The dose of a chemical that has been calculated to cause death in 50% of a defined experimental animal population.

Lethal Time(50) (LT50) -- A calculated period of time within which a specific concentration of a chemical is expected to cause death in 50% of a defined experimental animal population.

Lowest-Observed-Adverse-Effect Level (LOAEL) -- The lowest dose of chemical in a study, or group of studies, that produces statistically or biologically significant increases in frequency or severity of adverse effects between the exposed population and its appropriate control.

Malformations -- Permanent structural changes that may adversely affect survival, development, or function.

Minimal Risk Level -- An estimate of daily human exposure to a dose of a chemical that is likely to be without an appreciable risk of adverse non-cancer effects over a specified duration of exposure.

Morbidity -- Any departure, subjective or objective, from a state of physiological or psychological well-being. In this sense, sickness, illness, and morbid condition are similarly defined and synonymous.

Morbidity Rate -- A term used indiscriminately to refer to incidence or prevalence rates of disease.

Mortality Rate -- A rate expressing the proportion of a population who die of disease, or of all causes. The numerator is the number of persons dying; the denominator is the total population (usually mid-year population) in which the deaths occurred. The unit of time is usually a calendar year. To produce a rate that is a manageable whole number, the fraction is usually multiplied by 1,000 to produce a rate per 1,000. The rate is also called the "crude death rate."

Mortality Statistics -- Statistical tables compiled from the information contained in DEATH CERTIFICATES. Most administrative jurisdictions in all nations produce tables of mortality statistics. These may be published at regular intervals; they usually show numbers of deaths or rates of death, or both, by age, sex, cause, and sometimes other variables.

Mutagen -- A substance that causes mutations. A mutation is a change in the genetic material in a body cell. Mutations can lead to birth defects, miscarriages, or cancer.

Neurotoxicity -- The occurrence of adverse effects on the nervous system following exposure to a chemical.

No-Observed-Adverse-Effect Level (NOAEL) -- The dose of chemical at which there were no statistically or biologically significant increases in frequency or severity of adverse effects seen between the exposed population and its appropriate control. Effects may be produced at this dose, but they are not considered adverse.

Octanol-Water Partition Coefficient (Kow) -- The equilibrium ratio of the concentrations of a chemical in n-octanol and water, in dilute solution.

Permissible Exposure Limit (PEL) -- An allowable exposure level in workplace air averaged over an 8-hour workday.

Prevalence -- The number of instances of a given disease or other condition in a given population at a designated time; sometimes used to mean PREVALENCE RATE. When used without qualification, the term usually refers to the situation at a specified point in time (point prevalence).

Prevalence Rate (Ratio) -- The total number of all individuals who have an attribute or disease at a particular time (or during a particular period) divided by the population at risk of having the attribute or disease at this point in time or midway through the period. A problem may arise with calculating period prevalence rates because of the difficulty of defining the most appropriate denominator.

q1* -- The upper-bound estimate of the low-dose slope of the dose-response curve as determined by the multistage procedure. The q1* can be used to calculate an estimate of carcinogenic potency, the incremental excess cancer risk per unit of exposure (usually µg/L for water, mg/kg/day for food, and µg/m3 for air).

Reference Dose (RfD) -- An estimate (with uncertainty spanning perhaps an order of magnitude) of the daily exposure of the human population to a potential hazard that is likely to be without risk of deleterious effects during a lifetime. The RfD is operationally derived from the NOAEL (from animal and human studies) by a consistent application of uncertainty factors that reflect various types of data used to estimate RfDs and an additional modifying factor, which is based on a professional judgment of the entire database on the chemical. The RfDs are not applicable to non-threshold effects such as cancer.

Reportable Quantity (RQ) -- The quantity of a hazardous substance that is considered reportable under CERCLA. Reportable quantities are (1) 1 pound or greater or (2) for selected substances, an amount established by regulation either under CERCLA or under Section 311 of the Clean Water Act. Quantities are measured over a 24-hour period.

Reproductive Toxicity -- The occurrence of adverse effects on the reproductive system that may result from exposure to a chemical. The toxicity may be directed to the reproductive organs or the related endocrine system or both. The manifestation of such toxicity may be noted as alterations in sexual behavior, fertility, pregnancy outcomes, or modifications in other functions that depend on the integrity of this system.

Risk -- A probability that an event will occur, e.g., that an individual will become ill or die within a stated period of time or at a particular age. Also, a nontechnical term encompassing a variety of measures of the probability of a (generally) unfavorable outcome.

Short-Term Exposure Limit (STEL) -- The maximum concentration to which workers can be exposed for up to 15 minutes continually. No more than four excursions are allowed per day, and there must be at least 60 minutes between exposure periods. The daily TLV-TWA may not be exceeded.

Standardized Mortality Ratio (SMR) -- The ratio of the number of deaths observed in the study population to the number of deaths expected if it had the same rate structure as the standard population.

Statistical Significance -- Statistical methods allow an estimate to be made of the probability of the observed or greater degree of association between independent and dependent variables under the null hypothesis. From this estimate, in a sample of given size, the statistical "significance" of a result can be stated. Usually the level of statistical significance is stated in the P value.

Stratification -- The process of or result of separating a sample into several subsamples according to specified criteria such as age groups, socioeconomic status, etc. The effect of confounding variables may be controlled by stratifying the analysis of results. For example, lung cancer is known to be associated with smoking. To examine the possible association between urban atmospheric pollution and lung cancer, controlling for smoking, the population may be divided into strata according to smoking status.

Target Organ Toxicity -- This term covers a broad range of adverse effects on target organs or physiologic systems (e.g., renal, cardiovascular) extending from those arising through a single limited exposure to those assumed over a lifetime of exposure to a chemical.

Teratogen -- A chemical that causes structural defects that affect the development of an organism.

Threshold Limit Value (TLV) -- A concentration of a substance to which most workers can be exposed without adverse effect. The TLV may be expressed as a TWA, as an STEL, or as a CL.

Time-Weighted Average (TWA) -- An allowable exposure concentration averaged over a normal 8-hour workday or 40-hour workweek.

Toxic Dose (TD50) -- A calculated dose of a chemical, introduced by a route other than inhalation, which is expected to cause a specific toxic effect in 50% of a defined experimental animal population.

Uncertainty Factor (UF) -- A factor used in operationally deriving the RfD from experimental data. UFs are intended to account for (1) the variation in sensitivity among the members of the human population, (2) the uncertainty in extrapolating animal data to the case of humans, (3) the uncertainty in extrapolating from data obtained in a study that is of less than lifetime exposure, and (4) the uncertainty in using LOAEL data rather than NOAEL data. Usually each of these factors is set equal to 10.

Sources

ATSDR. 1993. Toxicological Profile for Selected PCBs (update). Atlanta: ATSDR/TP-92/16.

Last J, ed. 1983. A Dictionary of Epidemiology. New York: Oxford University Press.

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