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Endocrine effects of tetrabromobisphenol-A (TBBPA) in Wistar rats as tested in a one-generation reproduction study and a subacute toxicity study.
- Source :
-
Toxicology [Toxicology] 2008 Mar 12; Vol. 245 (1-2), pp. 76-89. Date of Electronic Publication: 2007 Dec 23. - Publication Year :
- 2008
-
Abstract
- Endocrine effects of the brominated flame retardant tetrabromobisphenol-A (TBBPA) were studied in a one-generation reproduction assay in Wistar rats via repeated dietary exposure, applying eight dose groups at 0-3-10-30-100-300-1,000-3,000 mg/kg body weight/day (mkd). This design enables dose-response analysis and calculation of benchmark doses (BMDL). This reproduction study was preceded by a 28-day repeat dose subacute toxicity study, at 0-30-100-300 mkd. Major effects in the reproduction study included decreased circulating thyroxine (T4) with BMDLs of 31 (m) and 16 (f) mkd, and increased weight of testis and male pituitary (BMDLs of 0.5 and 0.6 mkd). The hypothyroxinemia correlated to a cluster of developmental parameters including delayed sexual development in females, decreased pup mortality, and effects on brainstem auditory evoked potentials [Lilienthal, H., Verwer, C.M., Van der Ven, L.T.M., Piersma, A.H., Vos, J.G., 2008. Neurobehavioral effects of tetrabromobisphenol A (TBBPA) in rats after pre- and postnatal exposure. Toxicology]. A second cluster of parameters in F1 animals was correlated to increased testis weight, and included female gonad weight, endometrium height, CYP19/aromatase activity in the ovary, and plasma testosterone levels in males. These two correlation clusters suggest a dual action of TBBPA. The only effects in the subacute study were decreased circulating T4 and increased T3 levels in males (BMDLs 48 and 124mkd), and non-significant trends for these parameters in females, suggesting that the other effects in the reproduction study were induced during development. Combined with data of human exposure to environmental TBBPA, the margin of exposure for highly exposed populations can be calculated at 2.6, and current use of TBBPA may therefore be a matter of concern for human health.
- Subjects :
- Administration, Oral
Animals
Body Weight drug effects
Bone Development drug effects
Bone and Bones drug effects
Dose-Response Relationship, Drug
Endocrine Disruptors pharmacokinetics
Female
Male
Organ Size drug effects
Polybrominated Biphenyls pharmacokinetics
Rats
Rats, Wistar
Thyroid Hormones blood
Tissue Distribution
Toxicity Tests methods
Endocrine Disruptors toxicity
Polybrominated Biphenyls toxicity
Reproduction drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 0300-483X
- Volume :
- 245
- Issue :
- 1-2
- Database :
- MEDLINE
- Journal :
- Toxicology
- Publication Type :
- Academic Journal
- Accession number :
- 18255212
- Full Text :
- https://doi.org/10.1016/j.tox.2007.12.009