Abstract

Polybrominated diphenyl ethers (PBDEs) are legacy compounds with continued widespread human exposure. Despite this, developmental toxicity studies of DE-71, a mixture of PBDEs, are scarce and its potential for endocrine disrupting effects in vivo is not well covered. To address this knowledge gap, we carried out a developmental exposure study with DE-71. Pregnant Wistar rat dams were exposed to 0, 40 or 60 mg/kg bodyweight/day from gestation day 7 to postnatal day 16, and both sexes were examined. Developmental exposure affected a range of reproductive toxicity endpoints. Effects were seen for both male and female anogenital distances (AGD), with exposed offspring of either sex displaying around 10% shorter AGD compared to controls. Both absolute and relative prostate weights were markedly reduced in exposed male offspring, with about 40% relative to controls. DE-71 reduced mammary gland outgrowth, especially in male offspring. These developmental in vivo effects suggest a complex effect pattern involving anti-androgenic, anti-estrogenic and maybe estrogenic mechanisms depending on tissues and developmental stages. Irrespective of the specific underlying mechanisms, these in vivo results corroborate that DE-71 causes endocrine disrupting effects and raises concern for the effects of PBDE-exposure on human reproductive health, including any potential long-term consequences of disrupted mammary gland development.

Highlights

  • Normal development through gestation and early postnatal life is essential for lifelong health and disruption to developmental processes can result in adverse effects and increased susceptibility to disease

  • Developmental exposure to the DE-71 mixture of polybrominated diphenyl ether (PBDE) flame retardants induce a complex pattern of endocrine disrupting effects in rats

  • While production and use of DE-71 is no longer permitted, the constituents of the DE-71 mixture still account for a significant proportion of the brominated flame retardants found

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Summary

INTRODUCTION

Normal development through gestation and early postnatal life is essential for lifelong health and disruption to developmental processes can result in adverse effects and increased susceptibility to disease. Contribute new knowledge to the in vivo endocrine modes of action of PBDEs, we conducted a developmental rat toxicity study to determine the effects of early life exposure to DE-71 on endocrine-sensitive endpoints that have not previously been investigated or only investigated at lower doses with smaller statistical power. These endpoints were anogenital distance (AGD) (Schwartz et al, 2019), nipple retention (NR) (Schwartz et al, 2021), and a few selected reproductive postnatal and adult organ weights. Our study corroborates the endocrine activity of DE-71 in vivo and shows how multiple active endocrine mechanisms can result in a complex in vivo effect pattern

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