Incorporation of Pharmacokinetics in Noncancer Risk Assessment: Example with Chloropentafluorobenzene

Harvey J. Clewell and Bruce M. Jarnot

Risk Analysis, 1994, vol. 14, issue 3, 265-276

Abstract: Noncancer risk assessment traditionally relies on applied dose measures, such as concentration in inhaled air or in drinking water, to characterize no‐effect levels or low‐effect levels in animal experiments. Safety factors are then incorporated to address the uncertainties associated with extrapolating across species, dose levels, and routes of exposure, as well as to account for the potential impact of variability of human response. A risk assessment for chloropentafluorobenzene (CPFB) was performed in which a physiologically based pharmacokinetic model was employed to calculate an internal measure of effective tissue dose appropriate to each toxic endpoint. The model accurately describes the kinetics of CPFB in both rodents and primates. The model calculations of internal dose at the no‐effect and low‐effect levels in animals were compared with those calculated for potential human exposure scenarios. These calculations were then used in place of default interspecies and route‐to‐route safety factors to determine safe human exposure conditions. Estimates of the impact of model parameter uncertainty, as estimated by a Monte Carlo technique, also were incorporated into the assessment. The approach used for CPFB is recommended as a general methodology for noncancer risk assessment whenever the necessary pharmacokinetic data can be obtained.

Date: 1994
References: View complete reference list from CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://doi.org/10.1111/j.1539-6924.1994.tb00241.x

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:wly:riskan:v:14:y:1994:i:3:p:265-276

Access Statistics for this article

More articles in Risk Analysis from John Wiley & Sons
Bibliographic data for series maintained by Wiley Content Delivery ().