Is the mechanisms of fipronil-induced thyroid disruption specific of the rat: Re-evaluation of fipronil thyroid toxicity in sheep?
In rat, fipronil treatment increases the elimination of thyroid hormones (TH). Relevance of this mechanism for the risk of fipronil for human health is subject to controversy because of the specificities of adult rat for TH plasma binding properties which often lead to the assumption that rats are more sensitive than human to thyroid disruption. This study aimed at determining if the mechanism of fipronil-induced thyroid disruption is altered in sheep a species more relevant to human from the standpoint of TH plasma binding. TSH, total triiodothyronine and free and total tetra-iodothyronine 24 h secretory profiles were not modified by fipronil treatment (5 mg/kg every 4 days per os) in rams. In euthyroid-like thyroidectomised ewes, the effect of this treatment was limited to a moderate increase in free T4 clearance. In contrast with the rat, fipronil treatment (0.5 mg/kg/day, IV for 14 days) had no effect on antipyrine clearance, a marker for hepatic cytochrome activity, in ewes. The differences between rat and sheep for the potential of fipronil as a thyroid disruptor might be related to the difference in the exposure to the toxicant, the actual exposure to the sulfone metabolite of fipronil being lower in sheep than in rat.
Leghait
Julien
J
UMR181 Physiopathologie et Toxicologie Expérimentales INRA, ENVT, 31076 Toulouse cedex 3, France.
Gayrard
Véronique
V
Toutain
Pierre-Louis
PL
Picard-Hagen
Nicole
N
Viguié
Catherine
C
D000818:Animals; D019540:Area Under Curve; D004195:Disease Models, Animal; D005260:Female; D007306:Insecticides / Q000493:pharmacokinetics / Q000633:toxicity*; D008297:Male; D011720:Pyrazoles / Q000378:metabolism / Q000493:pharmacokinetics / Q000633:toxicity*; D011897:Random Allocation; D051381:Rats; D012756:Sheep; D013959:Thyroid Diseases / Q000139:chemically induced*; D013961:Thyroid Gland / Q000187:drug effects* / Q000378:metabolism; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
D007306:Insecticides; D011720:Pyrazoles; D014284:Triiodothyronine; D013972:Thyrotropin; C534368:fipronil sulfone; D013974:Thyroxine; C082360:fipronil