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

Environ Toxicol. 2013 Apr;28(4):215-28. doi: 10.1002/tox.20713. Epub 2011 May 4.

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.

MeSH terms

  • Adult
  • Animals
  • Body Weight / drug effects
  • Environmental Pollutants / analysis
  • Environmental Pollutants / immunology
  • Environmental Pollutants / toxicity*
  • Female
  • Halogenated Diphenyl Ethers / analysis
  • Halogenated Diphenyl Ethers / immunology
  • Halogenated Diphenyl Ethers / toxicity*
  • Humans
  • Immune System / drug effects*
  • Immune System / embryology
  • Immune System / growth & development
  • Lactation
  • Liver / drug effects
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Maternal Exposure / adverse effects
  • Milk / chemistry
  • Organ Size / drug effects
  • Paternal Exposure / adverse effects
  • Pregnancy
  • Prenatal Exposure Delayed Effects*
  • Rats
  • Rats, Sprague-Dawley
  • Reproduction / drug effects
  • Spleen / drug effects
  • Spleen / pathology
  • Thyroid Hormones / blood
  • Time Factors
  • Tissue Distribution
  • Weaning

Substances

  • Environmental Pollutants
  • Halogenated Diphenyl Ethers
  • Thyroid Hormones
  • pentabromodiphenyl ether