Weight of Evidence Evaluation of Potential Human Cancer Risks from Exposure to Polychlorinated Biphenyls: An Update Based on Studies Published Since 2003

Abstract

Drawing on all data available in 2003, the WoE of the human epidemiological data for polychlorinated biphenyls (PCBs) demonstrates that exposure to a mixture of PCBs (i.e. Aroclors) did not pose a cancer risk to humans (. This evaluation was based on criteria established by the US Environmental Protection Agency (EPA) as well as on a different methodology used by the Agency for Toxic Substances and Disease Registry (ATSDR). Subsequently, at least 15 more studies on the potential cancer risks (both incidence and mortality) of PCBs have been published. All studies published since 2003 are critically reviewed using the criteria established by the and . None of the studies published since 2003 change the conclusions drawn by : “that the weight of evidence does not support a causal association for PCBs and human cancer”. This conclusion pertains to all cancers combined, as well as to the various cancers that have been sporadically reported in the occupational cohort mortality studies. With respect to breast cancer risk, the WoE is compelling that environmental exposure to PCBs is not etiologically implicated in breast-cancer risk. This conclusion is supported by the consistently negative findings for increased breast-cancer mortality in occupational studies, which now involve almost 9,000 women occupationally exposed to PCBs. Similarly, the incidence studies in which PCB background levels are reported to be associated with increased risk of non-Hodgkin's lymphoma or prostate, testicular, and intestinal cancer are not corroborated by occupational cohort studies with PCB exposures far in excess of environmental exposures. The most likely explanation for these discordant findings is discussed in this review. Finally, the recent elucidation of the mode of action by which PCBs promote liver tumors in rats, combined with the demonstration that none of the key events in the mode of action occurred until substantial tissue accumulation of total PCBs had occurred, casts further doubt that PCB exposure at environmental or occupational levels poses a carcinogenic risk to humans. The dramatic differences between rodents and humans in sensitivity to PCB-mediated induction of CYP1A1 suggests that even occupational exposures to PCBs have never resulted in PCB body burdens approaching the levels required to initiate the sequence of events involved in the promotion of liver tumors in rodents.

Keywords::

• Cancer
• humans
• polychlorinated biphenyls (PCBs)
• polymorphisms
• weight of evidence

Acknowledgements

Declaration of interest: The authors of this article were compensated by General Electric for the preparation of this review. The interpretation of the data presented, as well as the conclusions reached, is the sole responsibility of the authors. The authors alone are responsible for the content and writing of the paper.

End notes

Notes

¹Although PCBs are on the list of substances the EPA intends to reevaluate as part of the Integrated Risk Information System, there is no indication that this will be done anytime soon. The most recent Integrated Risk Information System evaluation of PCB carcinogenicity is current to 1996, reviews only three studies (Bertazzi et al., 1987; Brown, 1987; Sinks, 1992) and also cites (with no review) NIOSH (1977), Gustavsson et al. (1986), and Shalat et al. (1989). Clearly, this does not qualify as a WoE assessment. Similarly, PCBs are not on the National Toxicology Program candidate list of chemicals for consideration in the 12th Annual Report on Carcinogens. With respect to international bodies, the International Agency for Research on Cancer (IARC) updated its PCB evaluation in 1987, citing a total of five studies (Brown and Jones, 1981; Brown, 1987; Bertazzi et al., 1981, 1987; Gustafasson et al., 1986). This also cannot be considered a WoE assessment and, indeed, the IARC typically does not conduct these types of assessments. The evaluation by the WHO through the International Programme on Chemical Safety (IPCS) is current as of 1993 and cites the same studies as the IARC (1987). Finally, the IPCS, in its Concise International Chemical Assessment Document series (2003), also reviewed the potential human carcinogenicity of PCBs, concluding that “Epidemiological studies suggest exposure-related increases in cancers of the digestive system, especially liver cancer, and malignant melanoma. However, the limitations of exposure information, the inconsistency of the results, and, in some cases, the presence of confounding exposures preclude a clear identification of an exposure–response relationship”. While some 50 studies were considered in the IPCS evaluation, and although the conclusions seem correct, they were not based on a formal WoE process. This is true despite the existence of explicit IPCS guidelines for evaluating bodies of epidemiological data using a WoE processes (IPCS, 1999).