Developmental toxicity of brominated flame retardants, tetrabromobisphenol A and 1,2,5,6,9,10-hexabromocyclododecane, in rat offspring after maternal exposure from mid-gestation through lactation.
To evaluate developmental exposure effects of two brominated flame retardants, tetrabromobisphenol A (TBBPA) and 1,2,5,6,9,10-hexabromocyclododecane (HBCD), pregnant Sprague-Dawley rats were administered either chemical at doses of 100, 1000 or 10,000 ppm in a soy-free diet from gestation day 10 until the day 20 after delivery. Offspring exposed to TBBPA showed dose-unrelated slight decreases of serum triiodothyronine (T(3)) concentration at postnatal day 20, and there was no evidence of hypothyroidism-related neuronal mismigration and impaired oligodendroglial development as judged by morphometric analyses of NeuN-immunoreactive neuronal distribution in the hippocampal CA1, and area of corpus callosum as well as density of 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase)-immunoreactive oligodendrocytes in the cingulate deep cortex at the adult stage. On the other hand, HBCD exerted a weak hypothyroidism evident with increases in thyroid weight, thyroid follicular cell hypertrophy and serum concentrations of thyroid-stimulating hormone as well as decreases of serum T(3) concentrations in offspring at 10,000 ppm at weaning. Increased thyroid weights and decreased serum T(3) concentrations were also observed in the adult stage from 1000 ppm. With regard to the effect on brain development, HBCD reduced density of CNPase-positive oligodendrocytes at 10,000 ppm, suggesting an impaired oligodendroglial development. Results thus suggest that TBBPA did not exert developmental brain effects, while HBCD did, and 100 ppm was determined to be the no-observed-adverse-effect level of HBCD from changes in thyroid parameters at the adult stage by maternal exposure, translating into 8.1-21.3mg/kg-d.
Saegusa
Yukie
Y
Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509, Japan.
Fujimoto
Hitoshi
H
Woo
Gye-Hyeong
GH
Inoue
Kaoru
K
Takahashi
Miwa
M
Mitsumori
Kunitoshi
K
Hirose
Masao
M
Nishikawa
Akiyoshi
A
Shibutani
Makoto
M
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D005333:Fetus / Q000187:drug effects*; D005411:Flame Retardants / Q000633:toxicity*; D006842:Hydrocarbons, Brominated / Q000633:toxicity*; D018811:Maternal Exposure; D019055:No-Observed-Adverse-Effect Level; D009929:Organ Size / Q000187:drug effects; D011075:Polybrominated Biphenyls / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013961:Thyroid Gland / Q000187:drug effects / Q000473:pathology; D013972:Thyrotropin / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
D005411:Flame Retardants; D006842:Hydrocarbons, Brominated; D011075:Polybrominated Biphenyls; D014284:Triiodothyronine; C089796:hexabromocyclododecane; D013972:Thyrotropin; C020806:tetrabromobisphenol A