US EPA

2772763 

Journal Article 

[Reproductive and developmental toxicity study of tocoretinate (IV) -- administration to female rats during the perinatal and postnatal periods] 

Murakami, Y; Ogasawara, H; Sakauchi, N; Narita, H; Hamada, S; Ohashi, M; Noguchi, O; Tanaka, N; Misawa, N; Inomata, N 

1992 

1 

Oyo Yakuri
ISSN: 0300-8533 

DART/TER/93000442 

43 

4 

Japanese 

Tocoretinate, a newly synthesized ester compound of retinoic acid with dl-alpha-tocopherol, is expected to be clinically useful in treating skin ulcer and keratosis. A perinatal and postnatal toxicity study was carried out to evaluate the effect of tocoretinate on the parturition and nursing behavior of female rats and on the growth and development of the first (F1) generation offspring. Tocoretinate was administered orally to female rats at a dose of 100, 300 or 1,000 mg/kg/day from day 17 of pregnancy to day 21 after delivery. Vehicle-treated female rats were used as controls. Results showed: Food consumption was reduced in the tocoretinate-treated dams although their body weight, delivery or nursing were not affected. The drug given to mothers had no effects on the growth, physical differentiation, learning behavior, emotionality, sexual maturation or reproductive performance of the F1 offspring. External, skeletal and visceral examinations showed no significant increase in the incidence of malformations of the second (F2) generation fetuses due to tocoretinate given to grandmothers. No changes attributable to tocoretinate occurred in the viability or growth of the F2 pups. The results indicate that the maximum safety dose of tocoretinate is above 1,000 mg/kg/day in terms of general toxicity to dams, reproductive toxicity to dams and the toxicity in growth and development of the next generation offspring.