Relative toxicological ranking of eight polybrominated diphenyl ether congeners using cytotoxicity, chemical properties and exposure data

Abstract

Polybrominated diphenyl ethers are widely used flame retardants which persist and diffuse in the environment thus entering the food chain. Eight congeners, most relevant for human exposure (BDE-28, 47, 99, 100, 153, 154, 183 and 209), were analyzed in vitro and in silico to derive a relative toxicological ranking. Cytotoxicity was assessed on human liver (HepG2) and colon (DLD-1) cell lines, by three assays (MTS, ATP and DNA content) in a range of realistic concentration (1pM - 10 nM). Jejunum and Caco-2 passive absorptions were calculated in silico. Exposure estimates were calculated using EFSA database. By ToxPi we integrated the overall data. No reduction of DNA content was observed, supporting absence of cytotoxicity. Otherwise, hormetic effects were exerted by all the congeners, except BDE-183. BDE-28, 47, 99, 100 differently affected the ATP content inducing a dose-related increase in HepG2 and depletion in DLD-1. Jejunum coefficients did not differ among congeners, whereas a higher Caco-2 coefficient indicates rapid absorption of BDE-28. ToxPi relative rankings support the toxicological relevance of BDE-153 and 28 congeners for their potential hazard; the inclusion of exposure data in young and adult populations shifted BDE-209 and BDE-47 as top ranked due to their widespread occurrence in the diet.

Keywords: Cytotoxicity; Gastrointestinal absorption; Human exposure; Polybrominated diphenyl ethers; ToxPi; Toxicological ranking.