PubMed Health⌕ Search

Biomedical subjects

R W Brecher

Publications and source records attributed to R W Brecher.

3 recordsLinked to original sources

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.

Administration, Cutaneous↗

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.

Humans↗