Chronic Toxicity Test of o-Phenylphenol and Thiabendazole by Simultaneous Administration to Mice

Abstract

o-Phenylphenol (OPP) and thiabendazole (TBZ), which are fungicides, have been approved as food additives in Japan. OPP induces urinary bladder tumor and renal lesions in rats but not in mice. TBZ has an enhancing effect on urinary bladder carcinogenesis induced by OPP in rats. The present study was performed to examine the combined effects of OPP and TBZ on mice. Groups of 20 male Crj: B6C3F1, mice were fed the basal diet (control, group C), diet containing 0.2% TBZ (group T), 0.65% OPP (group O-1), 1.3% OPP (group O-2), 2.6% OPP (group O-3), 0.65% OPP plus 0.2% TBZ (group OT-1), 1.3% OPP plus 0.2% TBZ (group OT-2) or 2.6% OPP plus 0.2% TBZ (group OT-3) for 52 weeks. The survival rates were 100% (20/20), 90% (18/20), 100% (20/20), 95% (19/20), 100% (20/20), 90% (18/20), 75% (15/20) and 70% (14/20) in group C, T, O-1, O-2, O-3, OT-1, OT-2 and OT-3, respectively. The treated groups suffered growth retardation throughout the study. The kidney weights showed a dose-related decrease in the O and OT groups. No treatment-related increase in tumor formation of any organ or tissue was observed. Dose-related increases were observed in the incidences of degenerative and necrotic changes in tubular epithelium and transitional cells of the kidney, and of anisonucleosis and pigmentation in liver cells in the O and OT groups. Under the experimental conditions employed, OPP plus TBZ induced no urinary bladder tumor in mice.