Setting Bench Mark Dose Limits for Perfluorinated Substances with Epidemiological Data

摘要

Background/Aim: Limits set for exposure to PFOA (perfluoro-octanoic acid) and other perfluorinated alkyl substances (PFAS), whether as daily intake, water concentrations or serum concentrations, have mostly relied on extrapolation from animal experimental data, with attendant uncertainties. Using the largest available database with a wide range of serum PFOA concentrations, Bench Mark Doses (BMD) as a basis for limits are proposed using the epidemiological data directly. The European Food Standards Authority is also proposing BMDs for these chemicals drawing on epidemiological data. Methods: Using the most replicated health effect associated with serum PFOA -increased lipids, BMD methods have been applied to the largest suitable dataset, the C8 study. With no strong evidence of a threshold, at the lower end of the range (1 to 30 ng/ml) the relation between lipids and serum PFOA is close to linear, so a benchmark limit for hypocholesteremia (total cholesterol>240 mg/dl) can be established for a given additional risk of this condition. A benchmark response rate (BMR) of a 1% change in response has been used for some epidemiological data and is used here. Results: Serum PFOA in 54,000 adults was median 28 ng/ml (1-99 pctile range 3 to 889). The BMD for PFOA at a 1% BMR, from models not including other PFAS, in terms of serum concentration of PFOA was 4.1 ng/ml, with corresponding BMDL at the lower confidence level of 2.8 ng/ml. PFOA and other PFAS are correlated and models with both exposures yielded shallower slopes and higher BMD values. Conclusions: A BMDL for PFOA of 2.8 ng/ml is close to population background average serum levels, although the BMDL is sensitive to several factors: selecting either change in average cholesterol or risk of high cholesterol, the arbitrary choice of BMR which should reflect the severity of the outcome (other have chosen 5%), and whether other PFAS are included. The inclusion of other PFAS leads to substantially higher BMDL values.