Development and application of a skin cancer slope factor for exposures to benzo[a]pyrene in soil

Regul Toxicol Pharmacol. 2011 Feb;59(1):101-10. doi: 10.1016/j.yrtph.2010.09.011. Epub 2010 Oct 1.

Abstract

Humans may be dermally exposed to the carcinogenic substance benzo[a]pyrene (B[a]P) via contact with soil at contaminated sites. The potential for risk is typically assessed using the proportion of dose estimated to penetrate through exposed skin for comparison with an oral route slope factor. An alternate dermal slope factor of 25 (mg/kg day)(-1) was previously developed (Knafla et al., 2006) based on skin carcinogenicity, since skin painting studies with mice suggest the formation of epidermal tumors may be a more sensitive endpoint than systemic tumors following dermal exposure. An extension of this work resulted in a skin cancer slope factor derived on a per unit skin surface area basis of 3.5 (μg/cm(2)day)(-1) that can be used to estimate risk as a function of exposed surface area. Various factors were examined for interspecies extrapolation of risks from mice to humans and for estimating skin exposures to B[a]P in soil. Using a nominal soil concentration of 1.0mg/kg, a range of cancer risk values of 29-220 in 100,000 was calculated. Soil concentrations associated with a one in 100,000 risk ranged from 0.0046 to 0.035 μg/g, which are lower than those derived using an oral slope factor. These results suggest that B[a]P-related skin cancer (point of contact) risks should be considered at contaminated sites.

MeSH terms

  • Administration, Cutaneous
  • Administration, Oral
  • Animals
  • Benzo(a)pyrene / administration & dosage
  • Benzo(a)pyrene / metabolism
  • Benzo(a)pyrene / toxicity*
  • Body Surface Area
  • Carcinogenicity Tests*
  • Carcinogens, Environmental / administration & dosage
  • Carcinogens, Environmental / metabolism
  • Carcinogens, Environmental / toxicity*
  • Dose-Response Relationship, Drug
  • Environmental Exposure
  • Humans
  • Mice
  • Reproducibility of Results
  • Risk Assessment
  • Skin Absorption
  • Skin Neoplasms / chemically induced*
  • Soil Pollutants / administration & dosage
  • Soil Pollutants / metabolism
  • Soil Pollutants / toxicity*
  • Species Specificity

Substances

  • Carcinogens, Environmental
  • Soil Pollutants
  • Benzo(a)pyrene