PCBs and Human Health
PCBs are probable human carcinogens and can also cause non-cancer health effects, such as reduced ability to fight infections, low birth weights, and learning problems. The risks and hazards associated with PCBs in the Hudson River are a function of the toxicity of PCBs and an individual's exposure.
In December 1999, EPA released the Human Health Risk Assessment for the Mid-Hudson River. EPA found that the consumption of fish from the Mid-Hudson River (Federal Dam at Troy to just south of Poughkeepsie, NY) presents a cancer risk at the upper bound of the Superfund risk range and a non-cancer hazard that is above EPA's level of concern under the federal Superfund program.
In August 1999, EPA released the Human Health Risk Assessment for the Upper Hudson River. EPA found that the consumption of fish from the Upper Hudson River (Hudson Falls to the Federal Dam at Troy, NY) presents a cancer risk and non-cancer hazard that are above EPA's levels of concern under the federal Superfund program.
More detailed information can be found in the Executive Summaries. Links are provided below:
You can access the full reports from the Reports and Schedule page.
|USEPA Administrator Carol Browner, in testimony before the New York State Assembly Committee on Environmental Conservation, July 9, 1998, citing an EPA report on the carcinogenicity of PCBs, said "PCBs are a known animal carcinogen and a probable human carcinogen -- that the type of PCBs found in Hudson River fish are the most potent of all PCBs. Fifteen of the nation's top PCB experts reviewed the EPA report, and all agreed, including a GE scientist, that the EPA scientific review fairly interpreted the body of PCB science relative to ... carcinogenicity."|
A number of studies, including the
Mayes (General Electric) Rat Study, show that PCBs (polychlorinated
biphenyls) cause cancer in animals. They are probable human carcinogens.
In addition, they pose a number of serious non-cancer health hazards to
intellectual functions and the nervous, immune, and reproductive systems.
They pose special risks to pregnant women and have been linked to premature
births and lowered IQs in children. (See EPA Administrator
Carol Browner's testimony
before the Committee on Environmental Conservation of the New York State
Assembly, July 9, 1998.)
PCBs are a group of chemicals that contain 209 individual compounds (known as congeners) with varying harmful effects. EPA considers all PCB mixtures to be toxic. Information on specific congener toxicity is very limited; toxicity testing has been done on specific commercial mixtures, whereas PCBs found in the environment will include a mix of congeners because of biotransformation or bioaccumulation.
The greatest human risk from exposure to Hudson River PCBs is through the consumption of contaminated fish (see "Health Warning" above). PCB contamination is concentrated in fish because PCBs bioaccumulate.
What do other Agencies say about cancer and PCBs?
How is the toxicity of PCBs determined?
How does EPA evaluate toxicity information?
Do PCBs cause cancer?
How are non-cancer health effects evaluated?
What about recent studies of endocrine effects in humans?
What is risk assessment?
How is exposure to PCBs evaluated?
How are risks calculated?
How are hazards calculated?
How is risk assessment used by risk managers?
What is the Mayes (General Electric) Rat Study?
EPA's concern regarding the carcinogenicity of PCBs (the ability of PCBs to cause cancer) is shared by other agencies. The International Agency for Research on Cancer (IARC) has declared PCBs to be a probable carcinogen in humans based on sufficient evidence in animals and limited evidence in humans. IARC was established in 1965 by the World Health Organization to coordinate and conduct research on the causes of human cancer, and to develop scientific strategies for cancer control. In addition, the National Toxicology Program, a part of the National Institutes of Environmental Health Science (NIEHS), has concluded that PCBs are reasonably anticipated to be carcinogenic in humans based on sufficient evidence in animals. The National Institute for Occupational Safety and Health (NIOSH) has determined that PCBs are a potential occupational carcinogen.
To evaluate the potential toxicity of chemicals and the levels associated with the toxicity, EPA uses data from human epidemiological studies, laboratory animal toxicity studies and supporting information that may include structure activity analysis or tests on cells.
Epidemiology is the study of the causes of disease. One type of human epidemiological study looks at people who have been exposed to the chemical over a long period of time. These studies evaluate the occurrence of disease in the exposed population with the occurrence of disease in a non-exposed population. PCB epidemiology includes studies of workers exposed in factories that manufactured capacitors and people exposed by eating contaminated fish.
The advantage of human epidemiological studies in determining human health risk assessment is obvious since we are concerned with risk to humans. The disadvantages include the difficulties in determining exposures that may have occurred over 30 years ago (based on known cancer lag times), finding individuals who may have moved over this long time period, the potential for populations to be exposed to other chemicals in addition to PCBs, and the fact that exposures may be limited to healthy workers while children, pregnant women and others in the general population may be of special concern to EPA. Epidemiological evidence provides important information that can be refined in laboratory experiments where animal exposures can be controlled.
Animal toxicity studies are primarily conducted on mice, rats, and to a lesser extent in monkeys. These species share a similar evolutionary history to humans. The studies are conducted with appropriate animal safeguards including prior approval by institutional review boards on animal experimentation. Animal toxicity studies are designed to expose groups of laboratory-bred animals to 1) different levels of PCBs, 2) for varying portions of the animal's lifetime, and 3) through different routes of exposure (breathing, eating, etc.). These experiments provide information necessary to help determine short or longer term effects on the body, specific organ systems and biochemical processes (i.e., enzyme levels). The advantage of these studies is that the conditions of dose and exposure can be controlled and the specific effects of the PCBs evaluated. The disadvantage is that animals are not the primary species of concern for human toxicity. However, the value of animal studies has been well established.
EPA scientists evaluate data from published human epidemiological and animal toxicity studies. The main questions are: Do PCBs have the potential to cause cancer in humans? And if so, at what level? What other effects can PCBs cause in the body?
Through the Integrated Risk Information System (IRIS) process, EPA scientists evaluate the available scientific literature and develop a chemical file summarizing the available information and EPA's conclusions about the health effects of PCBs. The IRIS PCB files describe the non-cancer and potential cancer effects. These documents are reviewed by EPA scientists and scientists outside the Agency (external peer-reviewers).
As new information becomes available, EPA may re-evaluate the toxicity data to determine if a reassessment of health effects may be necessary. For example, in 1996, based on new scientific information, the Agency re-evaluated the potency of PCBs and updated the IRIS cancer assessment file. Currently, EPA is reevaluating the non-cancer health effects of PCBs, with a report anticipated in the year 2000.
The results of these analyses are presented in chemical files listed in the Integrated Risk Information System. The cancer assessment is presented under "Polychlorinated Biphenyls". The non-cancer assessments are presented as Aroclors 1016, 1248 and 1254.
EPA evaluates the ability of a chemical to cause cancer based on the weight of evidence of human epidemiological and animal toxicity studies. EPA also develops risk factors that indicate the relative potency of the chemical (the ability of a given quantity or dose to cause cancer).
Weight of Evidence: PCBs are classified as probable human carcinogens or likely to be carcinogenic in humans. As described in the IRIS file, the basis for this determination is a 1996 study in rats (sponsored by General Electric; reviewed by EPA and external peer reviewers) that found increased numbers of liver tumors in female rats exposed to Aroclors 1260, 1254, 1242 and 1016 and in male rats exposed to Aroclor 1260. These mixtures contain overlapping groups of congeners that, together span the range of congeners most often found in environmental mixtures. The findings of the 1996 GE study strengthened earlier studies which also demonstrated carcinogenicity in rats. Several epidemiological studies on human populations are being updated. EPA's evaluation of human epidemiological studies as summarized in IRIS identified limitations including the small number of individuals studied, short follow-up periods and confounding from exposures to other potential carcinogens. As a result, current human epidemiological evidence is inadequate to classify PCBs as known human carcinogens, but is suggestive that PCBs may cause cancer in humans.
Risk Factors: To quantify the potential for PCBs to cause cancer, EPA developed three cancer slope factors based on the 1996 GE rat study. The different cancer slope factors deal with different routes of exposure. A cancer slope factor is an upperbound estimate of excess lifetime cancer risks per unit dose or exposure to a carcinogen. It is presented in risk per (mg/kg)/day. The highest slope factor is for ingestion (i.e., food chain) exposure. The Cancer Slope Factor Chart provides a list of the cancer slope factors for ingestion, inhalation and dermal exposure to PCBs in units of milligrams of material ingested/bodyweight in kilograms per day.
EPA evaluates all animal studies of non-cancer health effects to identify the study (critical study) that is most representative of human PCB exposure and that meets rigid scientific criteria. The analysis identified the level where there were no observed adverse effects. Based on the literature, the Agency identified the critical studies for Aroclor 1254 and Aroclor 1016 (presented in tabular form) and described below.
Aroclor 1254: The critical study identified was a study of rhesus monkeys conducted by Dr. Arnold and others in 1994. The monkeys were exposed to varying doses of PCBs ingested in gelatin capsules for a period of five years. The critical effects identified were suppression of the immune system, inflammation of the Meibomian gland (a small gland in the inner portion of the eye), and distorted growth of fingernails and toenails. EPA developed a Reference Dose, the level below which adverse effects on the humans are not expected. EPA took the Lowest Observed Adverse Effect Level (LOAEL) found in the monkey study and divided it by a factor of 300 to protect sensitive humans.
The factor of 300 (reduction from animal to human exposure) was based on an evaluation of toxicity studies and the application of established factors for extrapolating from animals to humans. The Rhesus monkey has similar (to human) toxic responses and metabolism of PCBs in addition to sharing a general physiological similarity. Rhesus monkey studies predicted other changes noted in human studies such as chloracne, hepatic (liver) changes and effects on reproductive function. Where a NOAEL cannot be identified or where a less than lifetime animal study was conducted, individual factors of 10 are applied in all studies in extrapolating from animals to humans to protect sensitive humans (including children). These factors of 10 may be reduced to 3 by EPA scientists, based on the available information. For example, with Arochlor 1254, a full factor of 10 was used to protect sensitive humans. The other factors were reduced to approximately 3 based on the availability of studies in Rhesus monkeys. The factors are then multiplied together and rounded to the nearest integer, resulting in the factor of 300 for Aroclor 1254. IRIS Aroclor 1254 file
Aroclor 1016: The critical studies identified were monkey reproductive studies conducted by Drs. Barsotti and VanMiller in 1994, Dr. Levin and others in 1988 and Dr. Schantz and others in 1989 and 1991. These are a series of reports that evaluated toxicity around birth and long-term neurobehavioral effects of Aroclor 1016 in the same groups of infant monkeys. In the studies, groups of eight female monkeys were exposed through diet seven months before delivery and four months immediately following delivery. The critical effect identified at the No Observed Adverse Effect Level (NOAEL) was reduced birth weights. In developing the Reference Dose, the NOAEL was divided by a factor of 100 to protect sensitive humans, including children..
A procedure similar to that described (above) for Aroclor 1254 was applied to extrapolate from Rhesus monkeys to humans. The uncertainty factor for Aroclor 1016 was 100. Based on the monkey reproductive studies, a full factor of 10 was not deemed appropriate since infants exposed through the placenta represent a sensitive subpopulation. An additional factor of 3 was applied since information on male reproductive effects and second generation studies were not available. The other factors for less than chronic exposure, and from animals to humans, was the same for both Aroclors 1254 and 1016. These factors were multiplied together and rounded, yielding a factor of 100. IRIS Aroclor 1016 file
Since Reference Dose values were developed for Aroclor 1254 (in 1994) and Aroclor 1016 (in 1993), additional studies of human populations consuming fish have been reported. EPA scientists are evaluating this information to determine whether any modifications in the Reference Dose are appropriate. Federal Register Notice
Risk assessment is a process used by EPA to determine the potential health effects in humans (cancer and non-cancer) associated with exposure to chemicals. Risk assessment is used throughout EPA to evaluate chemical toxicity and potential health effects in humans.
Under Superfund law (Comprehensive Environmental Response, Compensation and Liability Act -- CERCLA), EPA is required to conduct a baseline risk assessment that evaluates current and future risks at all Superfund sites. Risk assessment was defined in 1983 by the U.S. National Academy of Sciences as involving one or more of the following four steps:
- Hazard identification - Do PCBs have the potential to cause cancer? What other health effects (such as changes in the immune system, reduced birth weight, etc.) are caused by PCBs?
- Dose response - What amount of PCBs in the human body causes these effects?
- Exposure assessment - How people are exposed to PCBs (i.e., eating, drinking, breathing, skin contact) and at what levels.
- Risk characterization - The answers to the above three questions are used to calculate what risk an individual having significant exposure runs of developing cancer or experiencing a non-cancer effect. The uncertainties connected with answering the three questions are also described.
The risk characterization is then used by risk managers in their decision making process.
To evaluate exposure, the Agency looks at the concentration of PCBs in fish, water, soil, sediment and air; the frequency with which an individual may come into contact with the media; the length of time the individual may be exposed, and the bodyweight of the individual. For carcinogens, the exposure is averaged over a lifetime. For non-carcinogenic effects, exposure is averaged over the portion of the lifetime during which the exposure occurs. Depending on the data available, separate analyses can be developed for children, adults and lifetime exposure.
The data used in the assessment may be based on actual concentrations in the fish, soil, etc. It may also be based on modeling that projects future concentrations. Information on exposure activities may be developed using national or local surveys of activities (i.e., fish consumption) (link to Exposure Factors Handbook). The result of the exposure evaluation is a calculated level of dose for each route of exposure.
Cancer risk calculates the increased probability of an individual developing cancer based on a number of assumptions concerning PCB exposure. The risks are calculated by multiplying the dose (from exposure) by the toxicity (cancer slope factor -- see above). The individual risks for each pathway are added together to reflect the total cancer risk. The risk characterization presents the calculated risks along with discussion of uncertainties.
Non-cancer hazards are calculated by comparing the dose (from exposure) with the Reference Dose. Exceeding the Reference Dose results in an increased potential of adverse health effects. The individual hazards from each pathway are added together to reflect the total hazard. The uncertainties associated with the exposure assumptions and Reference Doses are detailed in the risk characterization.
The results from the risk assessment (cancer risk and non-cancer hazards) are used by the risk manager during the Feasibility Study, Proposed Plan and Record of Decision to determine the need for future action at the site.
What is the Mayes (General Electric) Rat Study?
Comparative carcinogenicity in Sprague-Dawley rats of the polychlorinated biphenyl mixtures Aroclors 1016, 1242, 1254, and 1260. Toxicol Sci 1998 Jan;41(1):62-76
Mayes, BA, McConnell EE, Neal BH, Brunner MJ, Hamilton SB, Sullivan TM, Peters AC, Ryan MJ, Toft JD, Singer AW, Brown JF Jr, Menton RG, Moore JA
General Electric Corporate Research & Development, Schenectady, New York, USA.
A comprehensive chronic toxicity and carcinogenicity study was conducted on a series of Aroclors (1016, 1242, 1254, and 1260). Each Aroclor was assessed at multiple dietary concentrations, ranging from 25 to 200 ppm, for 24 months in male and female Sprague-Dawley rats. Liver toxicity was indicated by elevated serum enzyme activity (AST, ALT, and GGT), elevated serum cholesterol concentration, decreases in hematologic parameters (RBC, Hb, and Hct), hepatocellular hypertrophy, an increased incidence of altered hepatocellular foci, and an increased incidence of hepatocellular neoplasms (primarily adenomas). Liver toxicity was distinctly more severe in females than in males. The incidence of hepatocellular neoplasms was highly sex-dependent (females >> males), differed between Aroclor mixtures and, for females, increased with dose and followed the general incidence pattern of Aroclor 1254 > Aroclor 1260 approximately Aroclor 1242 > Aroclor 1016. A significant response (p < 0.05) in males was seen only for the high dose of Aroclor 1260. A small increase in the incidence of thyroid gland follicular cell adenomas was noted in males for Aroclors 1242, 1254, and 1260, with the incidence being uniform across dose groups and Aroclor mixtures. For females, increased survival relative to controls was observed for all Aroclor treatment groups. A significantly decreased trend in the incidence of mammary gland neoplasms compared to control was also noted for females receiving Aroclors 1242, 1254, and 1260.
PMID: 9520342, UI: 98199324
This report updates the cancer dose-response assessment for polychlorinated biphenyls (PCBs) and shows how information on toxicity, disposition, and environmental processes can be considered together to evaluate health risks from PCB mixtures in the environment. Processes that chemically change PCB mixtures after release into the environment need to be considered in assessing the mixtures. Thus, guidance is given on applying a range of dose-response parameters to different exposure routes, partial lifetime exposure, and mixtures of varying composition. The report focuses on analysis and interpretation rather than a compilation of results. [Office of Research and Development]
The Integrated Risk Information System (IRIS) is an electronic data base containing information on human health effects that may result from exposure to various chemicals in the environment. IRIS was initially developed for EPA staff in response to a growing demand for consistent information on chemical substances for use in risk assessments, decision-making and regulatory activities. The information in IRIS is intended for those without extensive training in toxicology, but with some knowledge of health sciences. PCB cancer information is found under polychlorinated biphenyls. PCB non-cancer information is found under the specific aroclors 1016 and 1254. [Office of Research and Development]
Part of the Drinking Water and Health pages, this fact sheet is about PCBs found in some public or private drinking water supplies. [Office of Ground Water and Drinking Water]
Information on the Federal program for regulating PCBs, with particular emphasis on regulatory activities. [Office of Pollution Prevention and Toxics]
Several human health studies have been conducted in the Great Lakes basin. The following review summarizes some of these studies and other studies concerning exposure to Great Lakes pollutants including PCBs. [EPA Region 5 Great Lakes Program]
Epidemiologic studies have been conducted on mothers exposed to toxic substances, similar to those identified in Great Lakes fish, whose children have exhibited either reproductive and developmental or neurobehavioral effects. [EPA Region 5 Great Lakes Program]
Disclaimer: The links in this section are connections to non-USEPA Web sites. USEPA cannot be responsible for the accuracy of any data nor for the appropriateness of content on these sites. Access to the sites is provided as a service to USEPA customers and does not indicate or imply endorsement by USEPA of any viewpoints, information, products, or services.
- ATSDR - ToxFAQs - Polychlorinated Biphenyls (PCBs)
- National Institute of Occupational Safety and Health
- NIH National Toxicology Program Bioassay of AroclorŪ for Possible Carcinogenicity
- International Agency for Research on Cancer (part of WHO)
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