Effects of polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) on thyroid hormone and vitamin A levels in rats and mice

Abstract

The ability of the commercial polybrominated diphenyl ether (PBDE) preparation Bromkal 70-5 DE to alter thyroid hormone and vitamin A levels as well as microsomal enzyme activities was compared with that of the commercial polychlorinated biphenyl (PCB) preparation Aroclor 1254 in orally exposed female rats (Sprague-Dawley) and mice (C57BL/6 N). Additional mice were exposed to the PBDE congener 2,2',4,4'-tetrabromodiphenyl ether (DE-47), or to the PCB congener 2,3,3',4,4'-pentachlorobiphenyl (CB-105). For 14 days the animals were given approximately isomolar daily oral doses of Aroclor 1254, CB-105 (both 10 mg/kg body weight), Bromkal 70-5 DE or DE-47 (both at 18 mg/kg body weight). In addition, further groups of rats and mice received a higher dose of Bromkal 70-5 DE, 36 mg/kg body weight. Bromkal 70-5 DE and DE-47 decreased plasma free and total thyroxine (T4) levels in both rats and mice, although with lower potency than that of Aroclor 1254 and CB-105. By contrast, thyroid-stimulating hormone (TSH) levels were not significantly changed in any of the groups. Reduction of hepatic vitamin A levels was seen in rats after Aroclor 1254 and Bromkal 70-5 DE exposure. A similar tendency was seen also in mice, but the effects were significant only for concentration data and not the total amount. Induction ofmicrosomal phase I enzymes, measured as ethoxy, methoxy and pentoxy resorufin O-dealkylase (EROD, MROD, PROD) activities, was greatest after exposure to Aroclor 1254/CB-105 but were also significant in the Bromkal 70-5 DE/DE-47-treated groups. However, induction of uridine diphosphoglucuronosyl transferase (UDPGT) was small and for most groups insignificant. In conclusion, the PBDE compounds studied, although having a lower potency than the PCB compounds, decreased thyroxine and vitamin A levels and induced microsomal enzyme activities. Rats were more sensitive to the observed effects than mice. Microsomal phase I activity might be related, directly or indirectly, to the T4 and vitamin A effects, whereas several factors (such as weak enzyme induction and lack of correlation with altered T4 and vitamin A levels) argue against any UDPGT-related effects.

Developmental neurotoxicity of polybrominated diphenyl ether (PBDE) flame retardants

“…Indeed, in the Zhou et al (2002) study, a decrease in T 4 levels was seen at a lower dose level (10 mg/kg/day) than that necessary to cause UDPGT induction (30 mg/kg/day). Hallgren et al (2001) reported a similar finding in adult rats; additionally, in the same study, T 4 levels were also decreased in mice, where no induction of UDPGT was present. Similarly, in adult mice, the decrease in serum T 4 caused by was not paralled by an increase of hepatic UDPGT activity, though its hepatic mRNA levels were increased (Richardson et al 2006).…”

“…Hydroxylated BDEs are structurally very similar to thyroid hormones, and have been shown to displace thyroid hormones from the thyroxin plasma transporter transthyretin (TTR) (Meerts et al 2000). PBDEs have also been reported to decrease levels of total and free T 4 in adult animals (Fowles et al 1994;Hallgren et al 2001), and following developmental exposure (discussed below). Various PBDEs have been reported to induce mixed-type monoxygenase in vivo.…”

“…Fowles et al (1994) first reported that adult mice exposed for two weeks to DE-71 had decreased levels of circulating T 4 . Exposure of adult mice and rats to BDE-47 or to the pentaBDE mixture Bromkal 70-5DE, decreased serum total and free T 4 levels, without altering thyrotropin (TSH) levels (Hallgren et al 2001;Hallgren and Darnerud, 2002). Exposure of two month-old C57BL/6 mice to BDE-47 for 4 days was found to cause a significant decrease of total T 4 levels (Richardson et al 2006).…”

Effects of acute exposure to polybrominated diphenyl ethers on retinoid signaling in zebrafish larvae

“…No change in plasma retinol levels was observed in laboratory rats following exposure to DE-71 under sufficient vitamin A status (Ellis-Hutchings et al, 2006). Nonetheless, exposure to PBDEs has been shown to decrease the retinol concentrations in several organisms (EllisHutchings et al, 2006;Fernie et al, 2005;Hallgren et al, 2001). Decreased concentrations of retinol have also been observed in wildlife exposed to polychlorinated biphenyls (PCBs) (Boily et al, 2003;Braathen et al, 2004;Mos et al, 2007); however, there was no change in plasma retinol levels in Arctic grayling exposed to PCBs (Palace et al, 2001).…”

“…However, increasing evidence shows that vitamin A (retinoid) homeostasis is affected in rats, mice and American kestrels after exposure to PBDEs (Ellis-Hutchings et al, 2006;Fernie et al, 2005;Hallgren et al, 2001;van der Ven et al, 2008). Exposure to PBDEs could decrease hepatic retinoid storage and interfere with retinoid dynamics.…”