Interaction study with rats given two flame retardants: polybrominated diphenyl ethers (Bromkal 70-5 DE) and chlorinated paraffins (Cereclor 70L)
This study explored possible interaction effects on animal liver microsomal enzymes and thyroid hormones of two flame retardants: Bromkal 70-5 DE, a mixture of polybrominated diphenyl ethers (hereafter called PBDE); and Cereclor 701, a mixture of chlorinated paraffins (hereafter called CP). Female Sprague-Dawley rats were exposed to these compounds in dose ranges of 1.3-18.7 mg/kg bw/day (PBDE) and 1-55 mg/kg bw/day (CP), by gavage for 14 days. Biological responses were measured on liver somatic index (151) and hepatic enzyme activity of (a) ethoxyresorufin-O-deethylase (EROD) (indicating CYP1A1 activity), (b) pentoxyresorufin-O-depentylase (PROD) (indicating CYP2B activity) and (c) the phase II conjugation enzyme uridine diphosphoglucuronosyl transferase (UDP-GT). The levels of total and free thyroxine hormone in rat plasma (TT(4) and FT(4), respectively) were also measured. In the experimental work, a Doehlert uniform shell design was used in order to select the combination of concentrations of PBDE and CP administered to the rats. Eight different combinations were used, including a control. The measured responses were modelled with multiple linear regression (MLR), giving response surface plots. The results showed strong synergism between the two flame retardants at one particular exposure combination, resulting in increased hepatic microsomal enzyme responses and decreased serum T(4) concentrations. Notably, the exposure combination causing the most marked effects represented intermediate doses of both substances. The mechanisms behind the observed effects are unknown, but may involve induction or inhibition of enzyme systems. Copyright (C) 2010 John Wiley & Sons, Ltd.
thyroxine synergism combination toxicity