Previous studies demonstrated that
tris(1,3-dichloro-2-propyl)phosphate (
TDCIPP) caused adverse effects on
thyroid hormone (TH) imbalance in aquatic and avian organisms. This study focused on the effects of
TDCIPP on thyroid function and
hormone homeostasis in mammals. Pubertal female Sprague-Dawley rats were orally administered 50, 100, or 250 mg per kg per d of
TDCIPP from postnatal day (PND) 22 to PND42 for 21 days. The serum
triiodothyronine (T3) levels increased significantly at 250 mg per kg per d of
TDCIPP. There were no significant differences in the
body weight, serum
thyroxine (T4) and free
thyroxine (FT4) levels between the control and
TDCIPP treated groups. There were significant dose-dependent increases in the
mRNA and
protein expression levels of genes related to drug metabolism (cytochrome-p450-3A1, CYP3A1) and TH clearance (udp-glucuronosyltransferase-1A6, UGT1A6) in the liver. Treatment with
TDCIPP increased hepatic
type 1 deiodinase (DIO1)
mRNA at 250 mg per kg per d but down-regulated hepatic TH receptor beta (TRβ)
mRNA expression. In addition,
TDCIPP exposure induced slight thyroid follicular
hyperplasia, and several genes involved in TH biosynthesis (NIS, TPO, Tg) were altered at 100 and 250 mg per kg per d of
TDCIPP. Nevertheless, serum
thyroid stimulating hormone (TSH) levels and the receptor (TSHr)
mRNA significantly decreased at only the low dose group. Based on these results, we certified that
TDCIPP disturbs the normal bioprocess on TH synthesis, biotransformation or clearance, and hepatic detoxification of pubertal female SD rats, causing thyroid function disorder.