[Twenty-eight-day repeated dose toxicity test of p-phenetidine in F344 rats]

A twenty-eight-day repeated dose toxicity test of p-phenetidine was carried out in male and female F344 rats at dose levels of 160, 40, 10 or 0 mg/kg/day. Thirty animals of both sexes were divided into 6 groups of equal number. All groups were treated daily by i.g. administration for 28 days, two extra groups of animals at dose levels of 160 and 0 mg/kg being used for investigation of recovery over 14 days. Hematological and urinary examinations revealed decrease in erythrocytes and increased serum reticulocytes and urinary urobilinogen in the 160 and 40 mg/kg groups of both sexes, and methemoglobinemia occurred in the 160 mg/kg group. Increase in spleen weight was noted in the 160 and 40 mg/kg groups. On histopathological examination, hemosiderosis, increased extramedullary hemopoiesis, congestion of the spleen and myeloid hyperplasia of the bone marrow were observed in the 160 and 40 mg/kg groups of both sexes. Repair of these lesions occurred within 14 days after the cessation of administration. Based on these findings, a no-observed-effect level for p-phenetidine would be concluded 10 mg/kg/day.