Toxicologic and immunologic effects of perinatal exposure to the brominated diphenyl ether (BDE) mixture DE‐71 in the Sprague‐Dawley rat

Abstract

Brominated diphenyl ethers (BDEs) are persistent environmental contaminants found in human blood, tissues, and milk. To assess the impact of the commercial BDE mixture DE-71 on the developing immune system in relation to hepatic and thyroid changes, adult (F0) rats were exposed to DE-71 by gavage at doses of 0, 0.5, 5, or 25 mg/kg body weight (bw)/d for 21 weeks. F0 rats were bred and exposure continued through gestation, lactation and postweaning. F1 pups were weaned and exposed to DE-71 by gavage from postnatal day (PND) 22 to 42. On PND 42, half of the F1 rats were assessed for toxicologic changes. The remaining F1 rats were challenged with the T-dependent antigen keyhole limpet hemocyanin (KLH) and immune function was assessed on PND 56. Dose-dependent increases in total BDE concentrations were detected in the liver and adipose of all F0 and F1 rats. In F0 rats, increased liver weight, hepatocellular hypertrophy, and decreased serum thyroxine (T4) were characteristic of DE-71 exposure. In F1 rats perinatal DE-71 exposure caused a nondose-dependent increase in body weight and dose-dependent increases in liver weight and hepatocellular hypertrophy. Serum T3 and T4 levels were decreased. In spleen from DE-71 exposed rats the area occupied by B cells declined while the area occupied by T cells increased; however, cellular and humoral immune responses to KLH challenge were not altered. Thus hepatic and thyroid changes in rats exposed perinatally to DE-71 were associated with altered splenic lymphocyte populations, an effect which has been linked to hypothyroidism.

The flame retardant DE-71 (a mixture of polybrominated diphenyl ethers) inhibits human differentiated thyroid cell function in vitro

“…Several in vivo rodent studies have pointed towards a thyroid hormone disturbance after PBDE-exposure, where lowered concentrations of T4 were the most frequent and significant finding [28;29;52–55]. Three of six studies found no changes in T3 levels in mice and rats [28;29;54], three studies measured TSH [28;54;55] where only one found an effect, and only in male rats [55].…”

In vitro immune toxicity of polybrominated diphenyl ethers on murine peritoneal macrophages: Apoptosis and immune cell dysfunction

“…Recently, experimental data using animal models strongly suggested the occurrence of PBDE immunotoxicity, manifested as altered splenic lymphocyte populations, increased susceptibility to infections, and the release of pro-inflammatory cytokines (Zhong et al, 2011;Pellacani et al, 2012;Bondy et al, 2013). However, the data on PBDE immunotoxicity are still limited, and the mechanism(s) remains largely unclear.…”

Prenatal Polybrominated Diphenyl Ether Exposure and Body Mass Index in Children Up To 8 Years of Age

“…Although some animal models have reported weight gain with PBDE exposure (Bondy et al 2013; Dufault et al 2005; Fernie et al 2006; Gee and Moser 2008; Suvorov et al 2009), others have indicated null or inverse associations (Daubié et al 2011; Ta et al 2011; Talsness et al 2008). One possibility is that the direction of the association between PBDEs and growth measures differs between species.…”

“…Their ability to persist, bioaccumulate, and biomagnify has resulted in chronic and prolonged exposure despite the voluntary cessation of penta- and octaBDE manufacturing in the United States in 2004. PBDEs have been associated with weight gain in animal studies (Bondy et al 2013; Dufault et al 2005; Fernie et al 2006; Gee and Moser 2008; Suvorov et al 2009). PBDEs have been reported to increase adipocyte differentiation, decrease glucose oxidation, disturb glucose homeostasis, and alter gene expression in the metabolic pathways by directly interacting with retinoic X receptor (RXR), a key regulatory transcription factor in the adipogenic pathway in vertebrates (Bastos Sales et al 2013; Hoppe and Carey 2007; Kamstra et al 2014; Suvorov and Takser 2010; Tung et al 2014).…”