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.
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.
Institute of Environmental Medicine, Karolinska Institutet, P.O. Box 210, 17177 Stockholm, Sweden. Fereshteh.Kalantari@ki.se
Fereshteh
F
Kalantari
Charlotte
C
Bergkvist
Marika
M
Berglund
Elena
E
Fattore
Anders
A
Glynn
Helen
H
Håkansson
Salomon
S
Sand
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D019985:Benchmarking; D004305:Dose-Response Relationship, Drug; D004781:Environmental Exposure / Q000032:analysis*; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D005506:Food Contamination / Q000032:analysis / Q000517:prevention & control; D006801:Humans; D008297:Male; D008875:Middle Aged; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D018570:Risk Assessment; D012737:Sex Factors; D035501:Uncertainty; D055815:Young Adult
D004785:Environmental Pollutants; D011078:Polychlorinated Biphenyls