Fate and Transport in the Environment
Methods for Monitoring in the Environment
Methods for Measuring Human Exposure
Strategies for Preventing or Controlling Exposure
PCBs - Harmful Effects
PCBs - Dose Response
Sites of Toxicity
Mechanisms of Toxicity
Links for More Information
Links for More Information
PCBs Sites of Toxicity Within the Endocrine System
While PCBs have been found to be toxic to several organs and organ systems, this discussion of toxicity will be restricted to toxicities to the endocrine system.
Information gathered from epidemiologic studies, animal studies, in-vitro and in-vivo studies and studies of the Yusho and Yu Cheng cohorts (two populations that experienced unusually high exposure to PCBs after accidents) have provided varying degrees of evidence of PCBs toxicity to the endocrine system.
Sites of PCB toxicity within the endocrine system include:
Observational Human studies
- Results from an occupational study of employees at a PCB production facility found increased thyroid gland volume among workers as well as the nearby residents (1)
- Observational studies involving the Yu-Cheng cohort suggest an increased risk for goiter among this special cohort (2).
- Depending on the age of the cohort, the methods used to measure PCB exposure, and the conditions of exposure, several epidemiologic studies have found both positive and negative correlations between PCB exposure and circulating thyroid hormone levels of TSH, T4 and T3.
- Evidence of thyroid toxicity due to PCB exposure produced from human epidemiologic studies is supported by even stronger evidence for thyroid toxicity from animal studies.
- Depending on the dose, duration, and type of PCB, some characteristic findings in rat studies are hyperplasia, hypertrophy, increased vacuolization of follicular cells, depletion of follicular colloid, reduced follicular size, and thyroid enlargement.
- General findings from animal studies suggest that PCBs alter the manufacturing and levels of thyroid hormones that lead to disruption of their ability to reach peripheral tissues. PCBs may also accelerate the metabolic clearance of thyroid hormones.
- Two studies in rats provide convincing evidence that PCBs affect the thyroid hormone system. In one study, neurobehavioral deficits found in rat pups due to PCB exposure in utero were weakened by injections of the thyroid hormone T4. In another study T4 injections given to male rats reduced toxic effects from PCB exposure in the testes and in sperm production (3,4).
- Higher PCB levels were found in women with history of miscarriage than control patients (5).
- Women exposed to PCBs in the Yusho incident displayed menstrual irregularities. However, these effects are difficult to attribute to PCBs alone due to other chemicals of concern that this cohort may have also been exposed to (6).
- Epidemiologic studies that assessed fish consumption as a surrogate for PCB exposure have found evidence of shorter length of menstrual cycles, reduced probability of conception during a given menstrual cycle, and reduced number of months of lifetime lactation in women with high fish consumption. This data needs to be interpreted cautiously because many of the studies were not able to control for many known confounders (7-9).
- Human epidemiologic studies including occupational studies and studies of fish consumption have provided only very weak and inconsistent evidence of PCB toxicity to the male reproductive system. However, evidence of PCBs toxic effects in females and data from animal studies provide a foundation of concern that PCBs may also have toxic effects on the male reproductive system.
- Potential estrogenic and anti-estrogenic effects in the offspring of animals exposed to noncommercial mixtures of PCBs have been reported. Some of these effects include increased relative uterine weight in immature females and reduced testes weights and serum testosterone levels in adult males.
- Data on the reproductive effects in male animals is limited. Weanling rats treated by gavage for 15 weeks showed reductions in seminal vesicle and cauda epididymal weights, caudal epididymal sperm counts, and body weight gain. However, treatment with lower doses did not produce any effects. These differences may have been due to the age of the rats during the exposure period in relation to vulnerable periods of testicular development.
- Although evidence of reproductive toxicity in adult male animals is not strong, stronger evidence exists to suggest reproductive toxicity in male offspring of rats that were lactationally exposed to PCBs. Fertility of male offspring of rats exposed to PCBs was reduced compared to controls.
- Studies in male mice suggest negative effects on the morphology and production of sperm and fertility due to gestational, lactational, or adult exposures to PCBs.
- In studies of rats and mice reproductive effects such as prolonged estrus, decreased sexual receptivity, reduced implantation rate in adults and/or their offspring exposed via gestation and lactation, and decreased conception have been observed in animals orally exposed to commercial PCB mixtures.
- Studies of minks and monkeys have demonstrated these to be especially sensitive species with reproductive effects occurring after low doses of exposure. Some of the reproductive effects observed include reproductive inhibition, prolonged menstruation, and decreased fertility (impaired ability to conceive and decreased fetal survival).
Studies in experimental animals have demonstrated potentially toxic effects in the adrenal glands and serum adrenal steroid levels from PCB exposure. Findings of decreased adrenal steroid levels in animals exposed to PCBs correlates with the findings that decreased levels of adrenal steroids have also been associated with hypothyrodism in human studies. It is hypothesized that these effects are due to a decrease in the secretion and metabolism of adrenal steroids.
The majority of information in this site came from the ATSDRs toxicological profile for PCBs. The studies referenced in the content of this web page are some of the specific studies referenced in the ATSDR article. Other sources of information came from the EPA and ATSDR websites listed under useful links below.
1. Langer P, Tajtakova M, Fodor G, et al. 1998. Increased thyroid volume and prevalence of thyroid disorders in an area heavily polluted by polychlorinated biphenyls. Eur J Endocrinol 139:402-409.
2. Guo YL, Yu M-L, Hsu C-C, et al. 1999. Chloracne, goiter, arthritis, and anemia after polychlorinated biphenyl poisoning: 14-year follow-up of the Taiwan Yucheng cohort. Environ Health Perspect 107(9):715-719.
3. Cooke PS, Zhao Y-D, Hansen LG. 1996. Neonatal polychlorinated biphenyl treatment increases adult testis size and sperm production in the rat. Toxicol Appl Pharmacol 136:112-117. Goldey & Crofton 1998.
4. Gerhard I, Daniel B, Link S, et al. 1998. Chlorinated hydrocarbons in women with repeated miscarriages. Environ Health Perspect 106:675-681.
5. Kusuda M. 1971. A study on the sexual functions of women suffering from rice-bran oil poisoning. Sanka to Fujinka 38:1062-1072.
6. Mendola P, Buck GM, Sever LE, et al. 1997. Consumption of PCB-contaminated freshwater fish and shortened menstrual cycle length. Am J Epidemiol 146(11):955-960.
7. Buck GM, Vena JE, Schisterman EF, et al. 2000. Parental consumption of contaminated sport fish from Lake Ontario and predicted fecundability. Epidemiology 11:388-393.
8. Kostyniak PJ, Stinson C, Greizerstein HB, et al. 1999. Relation of Lake Ontario fish consumption, lifetime lactation, and parity to breast milk polychlorobiphenyl and pesticide concentrations. Environ Res 80:S166-S174.