chocolate-brown-ht and Abnormalities--Drug-Induced

Brown HT was fed to rats of both sexes over three generations at dietary concentrations designed to provide daily intakes of 0, 50, 250 and 500 mg Brown HT/kg body weight/day. During the study a number of females died or failed to nurse their litters. This was so severe following the first mating of F1 adults that the animals were remated to provide the next generation. None of these effects were related to treatment. Body weight and food and water intakes were not adversely affected by treatment. No effects of treatment were seen on reproductive performance or foetal and pup development, apart from slight evidence of a treatment-related retarded ossification of the third sternebrae. Organ weights at autopsy showed two changes, one of which was increased kidney weights which, although not present in every generation, seemed to be related to treatment. The other, increased caecum weights, occurred in adult high-dose females of early generations, but not in males or later generations of the study. Apart from brown coloration of tissues, macroscopic and microscopic examination revealed no treatment-related changes. It was concluded that the no-untoward-effect level in the present study was 250 mg Brown HT/kg/day.

Topics: Abnormalities, Drug-Induced; Animals; Azo Compounds; Cecum; Fetus; Food Coloring Agents; Kidney; Male; Organ Size; Rats; Reproduction

In a preliminary study, groups of ten female rats received daily doses of either water or solutions of Brown HT providing 250, 500 or 1000 mg Brown HT/kg body weight for 19 consecutive days. While there was no indication of overt toxicity, treated animals at all doses had brown discoloration of lymph nodes, caecum and colon. In the subsequent main study, groups of 30 female rats were given daily oral doses of 0 (water vehicle), 250, 500 or 1000 mg Brown HT/kg from day 0 to day 19 of pregnancy. There were no adverse effects on the numbers of implantations, pre- and post-implantation losses, litter weights, foetal numbers, foetal weights or sex ratio. No abnormalities related to treatment were found in either the skeleton or soft parts of the offspring. It is concluded that doses of up to 1000 mg Brown HT/kg/day given throughout pregnancy failed to exert detectable embryotoxicity or teratogenicity in rats.

Topics: Abnormalities, Drug-Induced; Animals; Azo Compounds; Bone and Bones; Dose-Response Relationship, Drug; Embryo, Mammalian; Female; Food Coloring Agents; Male; Pregnancy; Rats; Rats, Inbred Strains