Tri-isobutylphosphate: a prenatal toxicity study in rats.
To assess the prenatal toxicity to rats of the anti-foaming agent, tri-isobutylphosphate (CAS 126-71-6), a study was conducted in which daily dosages of 0, 100, 300 and 1000 mg/kg were administered to different treatment groups by gavage from day 6 to 15 of pregnancy. Dams were killed and foetuses examined on day 20 of pregnancy. Maternal effects during the dosing period included a dosage-related increase in the frequency, persistence and severity of post dosing salivation in all test groups and significantly increased water consumption at 1000 mg/kg. Bodyweight gain at 1000 and 300 mg/kg was lower than that of controls but the differences were not statistically significant. The lowest dosage of 100 mg/kg could be considered as the maternal 'lowest observed adverse effect level' (LOAEL) or 'no observed adverse effect level' (NOAEL) according to whether increased salivation is perceived to be a true toxic effect or simply a reaction to the taste of the test material. Neither litter values nor the prevalence of foetuses with abnormalities indicated any embryotoxic effects (including teratogenicity) at any dosage. The most notable feature of the results was the occurrence of a cluster of foetuses with the congenital abnormality referred to as 'hunched posture syndrome' or 'squat foetus syndrome'. However, the incidence of this finding was similar to that noted among background data for the same strain and, in the absence of any other embryotoxic findings, was considered likely to have arisen coincidentally.
Ruckman
S A
SA
Huntingdon Life Sciences Limited, Cambridgeshire, UK. ruckmans@ukorg.huntingdon.com
Green
O P
OP
Palmer
A K
AK
Klimisch
H J
HJ
D000818:Animals; D000831:Animals, Newborn; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian / Q000002:abnormalities / Q000187:drug effects; D005314:Embryonic and Fetal Development / Q000187:drug effects; D005260:Female; D005313:Fetal Death / Q000139:chemically induced; D008098:Litter Size / Q000187:drug effects; D008297:Male; D009943:Organophosphorus Compounds / Q000008:administration & dosage / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012472:Salivation / Q000187:drug effects
D009943:Organophosphorus Compounds; C119434:tri-isobutylphosphate