Comparative teratogenicity of three retinoids: the arotinoids Ro 13-7410, Ro 13-6298 and Ro 15-1570.
Three retinoids of the arotinoid series, namely the free carboxylic acid Ro 13-7410, its ethyl ester Ro 13-6298, and the new arotinoid ethyl sulfone Ro 15-1570, were tested for their embryotoxic and teratogenic activity in rats. The retinoids were administered orally on either day 9 or 13 of gestation. Treatment on day 9 of gestation resulted mainly in malformations of the head and the trunk; whereas, on day 13 limb malformations were prominent. Ro 13-7410 and Ro 13-6298 were about 1000 times more embryotoxic and teratogenic than retinoic acid but induced a similar malformation pattern to retinoic acid. In contrast, the sulfur-containing arotinoid Ro 15-1570 was active at similar dose levels to retinoic acid but caused a peculiar malformation pattern on day 13 of gestation. This finding supports the hypothesis that the arotinoid ethyl sulfone Ro 15-1570 has unique biological properties, inducing no bone toxicity in adult rats and distinctly affecting limb development.
Kistler
A
A
Pharmaceutical Research, F. Hoffmann-La Roche & Co., Ltd, Basle, Switzerland.
Galli
B
B
Howard
W B
WB
D000014:Abnormalities, Drug-Induced; D000818:Animals; D001565:Benzoates / Q000633:toxicity*; D004622:Embryo, Mammalian / Q000187:drug effects; D005260:Female; D005865:Gestational Age; D011247:Pregnancy; D051381:Rats; D012176:Retinoids / Q000633:toxicity*; D013997:Time Factors
D001565:Benzoates; D012176:Retinoids; C034814:ethyl-p-((E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-1-propenyl)benzoic acid; C038864:4-(2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic acid; C045042:Ro 15-1570