venalot and Abnormalities--Drug-Induced

The influence of the benzopyrone preparation Venalot (active substances: coumarin and troxerutin; in the following briefly called CT) on the fertility and teratogenicity as well as on the perinatal and postnatal development of a total of 3 generations was evaluated in a combined study. The 1-, 8-, 64-, and 128fold of the daily therapeutical doses for humans was suspended in tap water and administered orally by gavage to 95 male and 190 female SPF rats (Wistar) (test groups 2 to 5). 23 male and 46 female rats (test group 1) served as controls and were given tap water alone. The male animals were subjected to a pretreatment of 10, the female animals to one of 3 weeks. The treatment was continued during the phase of mating. The animals scheduled for cesarian section received the test substance until the day of the laparatomy (gestation day 20), those selected for littering throughout lactation (day 24 post partum). With the aid of a stepwise histological technique, the teratological examination could also disclose non lethal malformations of the organs. The treatment resulted in a decreased food consumption in the animals of group 5 and in a reduced gain of body weight as well as pathologic-anatomically and histologically demonstrable, definitely dose related hepatic lesions. The test substance had no effect on either the treated P generation nor the untreated F1 generation. As teratogenic effects could also not be demonstrated and the peri- and postnatal development of the filial generations 1 and 2 was undisturbed, the present study does not indicate a reproduction toxicological risk.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Abnormalities, Drug-Induced; Animals; Behavior, Animal; Coumarins; Drug Combinations; Eating; Female; Fertility; Hydroxyethylrutoside; Male; Pregnancy; Rats; Rats, Inbred Strains; Rutin