Authors
Brouwer A, Longnecker MP, Birnbaum LS, Cogliano J, Kostyniak P, Moore J, Schantz S, Winneke G.

Title
Characterization of potential endocrine-related health effects at low-dose levels of exposure to PCBs.

Journal
Environmental Health Perspectives 107 Suppl 4:639-49. 1999.

Exposure to polychlorinated biphenyls (PCBs) produces a variety of toxic effects both in wildlife and humans. Assessment of the risks imposed by PCBs is challenging for several reasons. PCBs are actually a mixture of up to 209 congeners with the resulting toxicity dependent on the number and position of chlorine atoms located on the biphenyl rings. Both parent PCBs and their metabolites have been associated with toxic effects; with PCB metabolites mainly associated with endocrine-disruption.

The authors speculate that there are several key strategies to best investigate the risks of low-dose PCB exposure on humans. Models should be designed to determine the mechanism of action of these chemicals on the endocrine system. Studies should focus on PCB competition at endocrine receptors, the effects of PCBs on hormone metabolism and synthesis, and PCB interference with hormone transport proteins. PCBs and PCB metabolites show variable affinity for the estrogen receptor and can exhibit both estrogenic and antiestrogenic activity. There is little evidence that PCBs compete for thyroid hormone receptors. PCB disruption of normal hormone synthesis or metabolism is another possible mechanism of action for PCBs. PCBs have been shown to induce thyroid hormone glucuronidation and to inhibit hormone sulfation, thereby compromising the availability of intracellular T3. There is some evidence to suggest that dioxin-like PCBs affect the enzyme aromatase, thereby disrupting the normal production of estradiol from testosterone. Interference with the transport or carrier proteins by PCBs can affect the availability of free hormones for biological activity. PCBs have been shown to competitively displace T4 from its carrier protein, consequently limiting T4 bioavailability.

Animal models of PCB exposure are important for the evaluation of toxic effects under controlled conditions. Exposure to PCBs, like so many toxicants, can have devastating effects during gestation and in exposed offspring while adults may be asymptomatic. Identification of the PCB-sensitive periods of development is important for human risk assessment. A wide dose range should be examined with different populations of PCB congeners to ascertain the effects of various mixtures. The use of different mixtures of PCB congeners makes it difficult to compare results from different studies. Investigations using individual PCB congeners or high dose mixtures are not relevant for human risk assessment as both humans and wildlife are typically exposed to low dose mixtures of PCB congeners. Areas of focus for future research should include neurodevelopment, reproductive, thyroid and immunologic effects with defined endpoints (auditory impairment, fertility, serum hormone levels). Finally, measurements of PCB contamination are not standardized, again making comparisons between studies difficult. Efforts should be made to develop PCB congener mixtures, at dosages relevant to the contamination seen in humans and wildlife, to further investigate the actions of PCBs as endocrine disruptors.

The authors have provided a concise review of the effects of PCB exposure on laboratory animals, wildlife and humans. The major effects of PCB exposure include disruption to the thyroid hormone system (T4 depletion, increased TSH, effects on neurodevelopment) and the reproductive system (uterotrophic effects, sex differentiation, sex behaviour, fertility and endometriosis). Carcinogenic effects due to PCB exposure are more pronounced at higher exposure levels and include tumours of the breast, prostate, ovary and thyroid gland. As with the data on many other toxicants, it will be difficult to determine the true risk posed to humans until studies are standardized with respect to dose, PCB congener mixture, design, exposure period (i.e., adult vs. neonate) and measurement of PCB contamination.