Results of teratogenicity testing of m-aminophenol in Sprague-Dawley rats

Abstract

meta-Aminophenol ( m-AP) was administered in the diet to female Sprague-Dawley rats for a period of at least 90 days at levels of 0.1, 0.25, and 1.0%. In the 0.25% group a significant reduction in body weight was noted, in comparison with control values, and in the 1.0% group a significant reduction in both body weight and food consumption was noted. Ten of the rats in each group were necropsied. Deposition of iron positive pigment in the spleen, liver, and kidney combined with decreased red blood cell count and hemoglobin and increased mean corpuscular volume indicated a hemolytic effect. There were also morphologic changes in the thyroid which were consistent with hyperactivity. The remaining 25 rats in each group were removed from m-AP treatment and immediately mated to untreated males of the same strain. After the mating period the dams again were given m-AP for the duration of gestation. All dams were killed on Day 20 of gestation; one-third of the fetuses were examined for visceral malformations and two-thirds for skeletal malformations and variations. An additional significant reduction in body weight gain was noted during gestation in the 1.0% group as compared to the control group. There were no other adverse dose-related findings demonstrated in the reproduction performance of the dams or in the survival or development of their offspring. Therefore, although maternal toxicity was demonstrated at the highest dose level, there was no evidence of teratogenic or embryofetal toxicity at any dose level tested.