Gestational and Early Postnatal Exposure to an Environmentally Relevant Mixture of Brominated Flame Retardants: General Toxicity and Skeletal Variations

Birth Defects Res B Dev Reprod Toxicol. 2016 Jun;107(3):157-68. doi: 10.1002/bdrb.21180. Epub 2016 Jun 10.

Abstract

Brominated flame retardants (BFRs) are stable environmental contaminants known to exert endocrine-disrupting effects. Developmental exposure to polybrominated diphenyl ethers (PBDEs) is correlated with impaired thyroid hormone signaling, as well as estrogenic and anti-androgenic effects. As previous studies have focused on a single congener or technical mixture, the purpose of the current study was to examine the effects of gestational and early postnatal exposure to an environmentally relevant mixture of BFRs designed to reflect house dust levels of PBDEs and hexabromocyclododecane on postnatal developmental outcomes. Pregnant Sprague-Dawley rats were exposed to the PBDE mixture from preconception to weaning (PND 21) through the diet containing 0, 0.75, 250, and 750 mg mixture/kg diet. BFR exposure induced transient reductions in body weight at PND 35 in male and from PND 30-45 in female offspring (250 and 750 mg/kg). Liver weights (PND 21) and xenobiotic metabolizing enzyme activities (PND 21 and 46) were increased in both male and female offspring exposed to 250 and 750 mg/kg diets. Furthermore, serum T4 levels were reduced at PND 21 in both,male and female offspring (250 and 750 mg/kg). At PND 21, Serum alkaline phosphatase (ALP) was decreased in males exposed to 750 mg/kg dietat, and females exposed to 250 and 750 mg/kg diets. At PND 46 ALP was significantly elevated in males (250 and 750 mg/kg). Variations in the cervical vertebrae and phalanges were observed in pups at PND 4 (250 and 750 mg/kg). Therefore, BFR exposure during gestation through to weaning alters developmental programming in the offspring. The persistence of BFRs in the environment remains a cause for concern with regards to developmental toxicity.

Keywords: brominated flame retardants; hexabromocyclododecane; polybrominated diphenyl ethers.

MeSH terms

  • Alanine Transaminase / blood
  • Alkaline Phosphatase / blood
  • Animals
  • Aspartate Aminotransferases / blood
  • Biomarkers / blood
  • Body Weight
  • Bone Development / drug effects*
  • Bone and Bones / drug effects*
  • Bone and Bones / pathology
  • Creatine Kinase / blood
  • Creatinine / blood
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Female
  • Flame Retardants / toxicity*
  • Halogenated Diphenyl Ethers / toxicity*
  • Hydrocarbons, Brominated / toxicity
  • Liver / drug effects
  • Liver / metabolism
  • Maternal Exposure / adverse effects*
  • Organ Size / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Reproduction / drug effects
  • Serum Albumin / metabolism

Substances

  • Biomarkers
  • Flame Retardants
  • Halogenated Diphenyl Ethers
  • Hydrocarbons, Brominated
  • Serum Albumin
  • hexabromocyclododecane
  • Creatinine
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Creatine Kinase
  • Alkaline Phosphatase