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

• Published in: Regulatory toxicology and pharmacology Vol. 65; no. 3; pp. 325 - 333
• Main Authors: Kalantari, Fereshteh, Bergkvist, Charlotte, Berglund, Marika, Fattore, Elena, Glynn, Anders, Håkansson, Helen, Sand, Salomon
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.04.2013
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Animals; Benchmark dose; Benchmarking; Cumulative risk assessment; Dietary exposure; Dose-Response Relationship, Drug; Environmental Exposure - analysis; Environmental Pollutants - toxicity; Female; Food Contamination - analysis; Food Contamination - prevention & control; Health-based guidance value; Hepatic vitamin A; Humans; Male; Margin of exposure; Medicin och hälsovetenskap; Middle Aged; Polychlorinated biphenyls; Polychlorinated Biphenyls - toxicity; Rats; Rats, Sprague-Dawley; Reproducibility of Results; Retinoid system; Risk Assessment; Sex Factors; Uncertainty; Young Adult; Health-based guidance value; Hepatic vitamin A; Cumulative risk assessment; Retinoid system; Polychlorinated biphenyls; Margin of exposure; Benchmark dose; Dietary exposure
• ISSN: 0273-2300; 1096-0295; 1096-0295
• DOI: 10.1016/j.yrtph.2013.01.005

► 1 out of 1000 individuals may have a cumulative MOE less than 20. ► The cumulative MOE mainly reflected the MOE for PCB 126. ► The MOE approaches discussed account for both variability and uncertainty. ► The RPF-based MOE approach is easier to implemented than the RPF-free approach. 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 2–4times 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.