Long-term toxicity study of Ponceau 4R in rats using animals exposed in utero.

Groups of 66 (treated) or 114 (control) rats of each sex were fed diets providing 0 (control), 50, 500 or 1250 mg Ponceau 4R/kg body weight/day for 60 days. The animals were then mated and allowed to rear their litters. At weaning, pups were selected for the long-term study to give treated groups of 54 (of each sex) and a control group of 96 (of each sex), with offspring always receiving the same treatment as their parents. Treatment continued until approximately 20% of animals survived, resulting in a duration of 114 wk for males and 118 wk for females. Body weight, food and water intake and clinical conditions were monitored regularly throughout the study. Blood and urine from 20 rats/sex/group from the high-dose and control groups were examined at months 3, 6, 12, 18 and 24. At the end of the study each animal was autopsied, selected organs were weighed, and a full range of tissues was preserved. High-dose animals showed a lower body-weight gain without any reduction in food intake. Water intake was higher than that of the controls in the medium- and high-dose groups and this was related to caecal enlargement and softening of faeces. No adverse changes were seen in the investigations of blood or urine apart from a higher incidence of females with higher levels of protein in urine at the 1250 mg/kg/day dose. No other findings of significance were seen and survival and tumour incidence were similar in all groups. A no-untoward-effect level was established at 500 mg Ponceau 4R/kg/day.