Establishment of the cumulative margin of exposure for a group of polychlorinated biphenyl (PCB) congeners using an improved approach that accounts for both variability and uncertainty

Fereshteh Kalantari, Charlotte Bergkvist, Marika Berglund, Elena Fattore, Anders Glynn, Helen Håkansson, Salomon Sand

Research output: Contribution to journalArticle

Abstract

In this study, the cumulative margin of exposure (MOE) was estimated for a group of polychlorinated biphenyls (PCBs) based on reduction of hepatic retinoids as a mode-of-action relevant toxicological endpoint. The MOE was defined as the ratio between a reference dose, derived using the benchmark dose (BMD) approach, and the estimated human dietary PCB exposure. A distribution for the cumulative MOE was established, taking into account inter- and intra-individual variability as well as uncertainty in data measurements. The cumulative MOE reflected mainly the MOE for PCB 126; other PCB congeners had little contribution to the cumulative exposure and MOE. The median of the 0.1st percentile for the cumulative MOE was about 20 for women; depending on the percentile, cumulative MOE was 2-4. times higher for men compared to women. Furthermore, a relative potency factor (RPF) based approach was compared to an RPF-free approach for estimating the cumulative MOE. The RPF-free approach more completely accounts for variability and uncertainty but is more data intensive than the RPF-based approach, which can be more easily implemented in practice and allows for a use of historical data on RPFs. Consideration of the discussed approaches may contribute to improving cumulative health risk assessments.

Original languageEnglish
Pages (from-to)325-333
Number of pages9
JournalRegulatory Toxicology and Pharmacology
Volume65
Issue number3
DOIs
Publication statusPublished - Apr 2013

Keywords

  • Benchmark dose
  • Cumulative risk assessment
  • Dietary exposure
  • Health-based guidance value
  • Hepatic vitamin A
  • Margin of exposure
  • Polychlorinated biphenyls
  • Retinoid system

ASJC Scopus subject areas

  • Toxicology

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