Effect of low dose mono-ortho 2,3',4,4',5 pentachlorobiphenyl on thyroid hormone status and EROD activity in rat offspring: consequences for risk assessment.
Toxic equivalency factor (TEF) has been proposed to estimate the risk of polychlorinated biphenyl (PCB) congeners. However, ortho chlorine substitution in the two phenyl rings gives each PCB its own pattern of toxicity which is different from the mechanism of action of 2,3,7,8-tetrachlorodibenzo-p-dioxin. The present study evaluated the effect of prenatal and postnatal exposure to a low dose of the mono-ortho pentachlorobiphenyl PCB 118 on thyroid hormone concentrations and EROD activity in rats. Moreover, the tissue distribution of PCB 118 following one oral dose was evaluated. Sprague-Dawley rats were treated by gavage on GD 6 with 375 microg of PCB 118/kg b.w. Decreases in thyroxine and TSH levels were observed in dams at the end of lactation. Perinatal exposure to a low dose of PCB 118 permanently disrupted the hypothalamo-pituitary-thyroid (HPT) axis leading to a significant increase in thyroxine levels in offspring, as a 'thyroid resistance syndrome'. It is noteworthy that no changes in hepatic EROD activity were detected in dams at the end of lactation, even in the presence of high amounts of PCB in liver. Based on hepatic EROD activity (as a biomarker for aryl hydrocarbon receptor (AhR) induction), the mechanism of thyroid homeostasis disruption seems to be AhR-independent. Additionally, the 'thyroid resistance syndrome' observed in our study indicates the need for further detailed investigations on the HPT axis. We conclude that not only TEF, but also AhR-independent responses should be taken into account for risk assessment of mono-ortho PCB congeners.
Kuriyama
Sergio
S
Institute of Clinical Pharmacology and Toxicology, Benjamin Franklin Medical Center, Freie Universität Berlin, 14195 Berlin, Germany.
Fidalgo-Neto
Antonio
A
Mathar
Wolfgang
W
Palavinskas
Richard
R
Friedrich
Karen
K
Chahoud
Ibrahim
I
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism*; D005260:Female; D008099:Liver / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D018570:Risk Assessment / Q000379:methods; D013961:Thyroid Gland / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D013963:Thyroid Hormones / Q000097:blood*; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
D013963:Thyroid Hormones; D014284:Triiodothyronine; C070055:2,3',4,4',5-pentachlorobiphenyl; D013972:Thyrotropin; D011078:Polychlorinated Biphenyls; D019363:Cytochrome P-450 CYP1A1; D013974:Thyroxine