Grouping of PFAS for human health risk assessment: Findings from an independent panel of experts.

An expert panel was convened to provide insight and guidance on per- and polyfluoroalkyl substances (PFAS) grouping for the purposes of protecting human health from drinking water exposures, and how risks to PFAS mixtures should be assessed. These questions were addressed through multiple rounds of blind, independent responses to charge questions, and review and comments on co-panelists responses. The experts agreed that the lack of consistent interpretations of human health risk for well-studied PFAS and the lack of information for the vast majority of PFAS present significant challenges for any mixtures risk assessment approach. Most experts agreed that "all PFAS" should not be grouped together, persistence alone is not sufficient for grouping PFAS for the purposes of assessing human health risk, and that the definition of appropriate subgroups can only be defined on a case-by-case manner. Most panelists agreed that it is inappropriate to assume equal toxicity/potency across the diverse class of PFAS. A tiered approach combining multiple lines of evidence was presented as a possible viable means for addressing PFAS that lack analytical and/or toxicological studies. Most PFAS risk assessments will need to employ assumptions that are more likely to overestimate risk than to underestimate risk, given the choice of assumptions regarding dose-response model, uncertainty factors, and exposure information.

Development of a dermal cancer slope factor for benzo[a]pyrene.

Polycyclic aromatic hydrocarbons (PAHs) are commonly found at environmentally impacted sites in both Canada and the United States, and also occur naturally. Typically, benzo[a]pyrene (B[a]P) is selected as a standard to which the cancer potencies of other carcinogenic PAHs are compared. Cancer potency estimates for B[a]P have been published for the oral and inhalation routes of exposure, however, no such estimate has been established by a regulatory agency for dermal exposure. The main objectives of the current investigation were to: evaluate approaches used to examine the relative carcinogenicity of PAHs; to conduct a review of mammalian dermal carcinogenicity studies for B[a]P; and derive a cancer slope factor for dermal exposure to PAHs using B[a]P as a surrogate for other PAHs. The toxicological database of dermal B[a]P studies was examined for relevant animal bioassays. Seven relevant studies were identified. A cancer slope factor for B[a]P was developed using the benchmark dose approach and the linearized multistage model. The upper 95th CI at the 5% effect level above background incidence was used as the point of departure for low-dose linear extrapolation. An average slope factor of 0.55 (microg/animal day)(-1) was calculated for mice, which was converted to a dose-equivalent slope factor of 25 (mg/kg day)(-1). This latter slope factor is proposed for application to human health risk assessment with no scaling adjustment. Dermal potency equivalency factor values were identified which may be used with other carcinogenic PAH in the calculation of total B[a]P equivalent dermal cancer risk estimates. An identified area for further investigation is the consideration of scaling in extrapolating the calculated dermal cancer slope factor from mice to humans.

Risk assessment.

Risk assessment, when applied to living systems, is the process of determining the types and likelihoods of adverse effects that may result from exposure to chemical, biological, or physical hazards. Risk assessment is used as a tool to help set regulations and guidelines to prevent or minimize adverse health effects of long-term exposures to low levels of toxicants. It is also applied to evaluating the safety of pharmaceuticals, to protecting workers exposed intermittently to hazardous materials in the workplace, and to evaluating the potential future consequences of past or current exposures. Most toxicological information used in human health risk assessment comes from in vivo experiments in animals and focuses on the pathological response occurring as a result of exposure to the toxicant. Dose and response data must then be extrapolated between individuals and species and from high to low doses, all of which increase the degree of uncertainty in risk estimates. This presentation provides a general overview of risk assessment, exploring its strengths, weaknesses, and ongoing evolution. The distinction between real and perceived risks is also discussed and is shown to be driven by the extent to which mechanistic information is available and how it is integrated into the risk assessment process. Finally, the presentation explores ways in which pathologists and risk assessors can work more closely to enhance risk assessment's ability to be a defensible tool for evaluating health concerns associated with chronic low-level exposures to toxicants in our environment.