RESUMEN

Hearing loss (HL) is associated with poorer language development and school performance. Ototoxic substances such as metals and solvents, including benzene, are a risk factor associated with HL. This study examines potential associations between the benzene metabolite trans,trans-muconic acid (t,t-MA) and HL in youth of the National Health and Nutrition Examination Survey (NHANES). Logistic regression calculated adjusted odds ratio (aOR) associations between HL and urinary t,t-MA quartiles, natural-log transformed, and doubled urinary t,t-MA. Hearing threshold pure-tone average (PTA) at speech frequencies (SF) 0.5, 1, 2, and 4 kHz and high frequencies (HF) 3, 4, and 6 kHz were analyzed for slight HL (PTA > 15 dB) and mild HL (PTA > 20 dB). Urinary t,t-MA was statistically significantly associated with both slight SF and HF HL. For each doubling of t,t-MA there were increased odds of having slight SFHL (aOR = 1.42; 95% CI: 1.05, 1.92), slight HFHL (aOR = 1.31; 95% CI: 1.03, 1.66), mild SFHL (aOR = 1.60; 95% CI: 1.10, 2.32), and mild HFHL (aOR = 1.45; 95% CI: 1.03, 2.04). To our knowledge, this is the first population-based report of an association between SFHL, HFHL, and the benzene metabolite t,t-MA in youth 6 to 19 years old.

RESUMEN

Based on previous findings in dietary studies with carp (Cyprinus carpio), we investigated the mechanism of 2,2',4,4',5-pentabromodiphenyl ether (BDE-99) debromination to 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) using liver and intestinal components. In vitro aerobic and anaerobic experiments tested the ability of carp intestinal microflora to debrominate BDE-99. No debromination of BDE-99 to BDE-47 was observed in microfloral samples; therefore, carp enzymatic pathways were assessed for debromination ability. After sixty-min incubation, intestine and liver microsomes exhibited 83+/-34% and 106+/-18% conversions, respectively, of BDE-99 to BDE-47; with no significant (p>0.05) difference between organ debromination capabilities. Microsomal incubations with BDE-99, enzyme cofactors and competing substrates assessed the potential mechanisms of debromination. The presence of NADPH in the microsomal assay did not significantly (p>0.05) affect BDE-99 debromination, which suggest that cytochrome P450 enzymes are not the main debrominating pathway for BDE-99. Co-incubation of BDE-99 spiked microsomes with reverse thyronine (rT3) significantly (p<0.05) decreased the debromination capacity of intestinal microsomes indicating the potential of catalytic mediation via thyroid hormone deiodinases. The significant findings of this study are that intestinal microflora are not responsible for BDE-99 debromination, however, it is an endogenous process which occurs with approximately equal activity in intestine and liver microsomes and it can be inhibited by rT3.

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RESUMEN

Decabromodiphenyl ether (BDE 209), the major congener in the high volume industrial flame retardant mixture "DecaBDE", has recently been shown to be metabolized by carp. To further explore this phenomenon, juvenile rainbow trout were exposed to BDE 209 via the diet for a five month period. Analysis of the whole body homogenate, liver, serum, and intestinal tissues revealed that BDE 209 accumulated in rainbow trout tissues and was most concentrated in the liver. In addition to BDE 209, several hepta-, octa-, and nonaBDE congeners also accumulated in rainbow trout tissues over the same period as a result of BDE 209 debromination. Based on the total body burden of the hepta- through decaBDE congeners, uptake of BDE 209 was estimated at 3.2%. Congener profiles were different among whole body homogenate, liver, and serum, with the whole body homogenates having a greater contribution of the debrominated biotransformation products. Extracts of the rainbow trout whole body homogenates were compared with extracts from a previous experiment with common carp. This comparison revealed that BDE 202 (2,2',3,3',5,5',6,6'-octabromodiphenyl ether) was a dominant debromination product in both studies. To determine whether the observed debromination was metabolically driven, liver microsomal fractions were prepared from both common carp and rainbow trout. Analysis of the microsomal fractions following incubation with BDE 209 revealed that rainbow trout biotransformed as much as 22% of the BDE 209 mass, primarily to octa- and nonaBDE congeners. In contrast, carp liver microsomes biotransformed up to 65% of the BDE 209 mass, primarily down to hexaBDE congeners. These microsomal incubations confirm a metabolic pathway for BDE 209 debromination.

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