Thyroid axis disruption in juvenile brown trout (Salmo trutta) exposed to the flame retardant ß-tetrabromoethylcyclohexane (ß-TBECH) via the diet.

Tetrabromoethylcyclohexane (TBECH) is an additive brominated flame retardant used in domestic and industrial applications. It has been detected in wildlife, and there is early evidence that it is an endocrine disruptor. Whereas other brominated flame retardants with similar physicochemical properties have been shown to disrupt the thyroid axis, no such evaluation has been conducted for TBECH. To elucidate this, juvenile brown trout (Salmo trutta) were fed either a control diet or diets containing low, medium, or high doses of ß-TBECH, the isomer most frequently detected in wildlife, for 56 days (uptake phase) followed by a control diet for an additional 77 days (depuration phase). Eight fish per treatment were lethally sampled on uptake days 7, 14, 21, 35, 49, and 56 and on depuration days 7, 21, 35, 49, and 77 to assess fish condition, circulating free and total triiodothyronine and thyroxine, and thyroid epithelial cell height. Although there was no effect on condition factor, there was a significant reduction in total plasma thyroxine in the high dose group and a significant increase in mean thyroid epithelial cell height in the low, medium, and high dose groups during the uptake phase, whereas there were no differences in the depuration phase. These results indicate that ß-TBECH may modulate the thyroid axis in fish at environmentally relevant concentrations.

Toxicokinetics of tetrabromoethylcyclohexane (TBECH) in juvenile brown trout (Salmo trutta) and effects on plasma sex hormones.

Technical 1,2-dibromo-4-(1,2 dibromoethyl)cyclohexane or tetrabromoethylcyclohexane (TBECH) used primarily as an additive flame retardant in polystyrene foams, contains two diastereoisomers, α- and ß- present in equimolar amounts. At temperatures in excess of 125°C, isomerization to two other isoforms, δ- and γ- is possible. The recent detection of TBECH in the environment and studies suggesting that isomers are androgenic prompted us to examine the toxicokinetics and biochemical effects of one of the isomers, ß-, in a controlled laboratory environment. Juvenile brown trout (Salmo trutta) were exposed to three different amounts of the ß-isomer (low, medium and high) via the food followed by a period in which they were exposed to unfortified food. A fourth group of fish was exposed to unfortified food for the duration of the experiment. On days 0, 7, 14, 21, 35, 49, 56, 63, 77, 91, 105, and 133, eight fish from each treatment group were euthanized and liver, plasma, lower jaw (i.e., thyroid tissue) and gonad were collected and the remaining tissue ('whole-fish') was retained. ß-Isomer content was measured in whole-fish and in liver while estradiol (E2), 11-ketotestosterone (11-KT) and testosterone (T) were measured in plasma. Based on liver and gonad somatic indices, no apparent effects on liver or gonad development in fish from any of the treatment groups were observed. The bioaccumulation of ß-isomer was similar in fish from all treatment groups with steady-state occurring before the end of the uptake phase. Depuration of the ß-isomer from fish obeyed first order kinetics and there were no statistically significant differences in the depuration half life (t(1/2)) among the treatment groups: 22.5 ± 10.4 (low), 13.5 ± 5.9 (med) and 13.8 ± 2.2 (high) days. Steady-state biomagnification factors were much smaller than 1 for fish in all treatment groups. Debrominated metabolites were not detected in composite liver or whole-fish extracts and there was no evidence of isomerization of the ß-isomer to other isoforms in vivo. While there were occasional differences among treatment groups in circulating plasma E2, T and 11-KT levels there was no clear, temporal trend or dose-response.

Altered thyroxine metabolism in rainbow trout (Oncorhynchus mykiss) exposed to hexabromocyclododecane (HBCD).

Hexabromocyclododecane (HBCD) is an additive flame retardant used in consumer and industrial applications. Our earlier work suggested that fish exposed to HBCD exhibited an increase in the rate of turnover of thyroxine (T4), the precursor molecule to the active thyroid hormone triiodothyronine (T3). To examine this further, juvenile rainbow trout were held in the laboratory and fed diets containing environmentally relevant concentrations of the individual alpha, beta or gamma isomers. Thirty-two days after feeding began, 20 fish from each group were gavaged with gelatin containing 1microCi [(125)I]-T4. Uptake of [(125)I]-T4 from the gut was low and recoveries of the initial [(125)I]-T4 were <10% after 2d and <3% and <2% after 6 and 14d respectively, with no differences among groups. However, measurements of the labeled T4 in tissues 2, 4, 6 and 14d after gavage showed that tissue disposition and elimination rates of the hormone were altered by HBCD. In particular, on day 14 after gavage feeding, there was significantly lower radioactivity in the thyroid of fish exposed to the HBCD isomers relative to the reference group. This implies that either there was lower iodide uptake by the gland in fish exposed to HBCD or that the rate of thyroid hormone turnover in HBCD treated fish was elevated. There was also a significantly higher type II outer ring deiodinase enzyme activity in livers of fish exposed to the beta and gamma isomers. Taken together, these results indicate that HBCD can potentially impact the thyroid system of fish.