Toxicity study of a rubber antioxidant, mixture of 2-mercaptomethylbenzimidazoles, by repeated oral administration to rats

2-Mercaptobenzimidazole (2-MBI), a rubber antioxidant, is known to exhibit potent antithyroid toxicity in rats and is a candidate as an environmental endocrine disrupter. 2-Mercaptomethylbenzimidazoles (a I:1 mixture of 4-met hyl and 5-methyl isomers, MMBIs), are also employed industrially as rubber antioxidants and are suspected to exert antithyroid toxicity such as 2-MBI. In this investigation, acute and subacute oral toxicity studies of MMBIs i n Wistar rats were conducted. The clinical signs of acute oral toxicity wer e observed including decreased spontaneous movement, a paralytic gait, sali vation and lacrimation, and adoption of prone and lateral positions. The LD 50 was estimated to be 330 mg/kg. In the subacute oral toxicity study, male and female rats were treated with MMBIs by gavage at doses of 0 (corn oil) , 4, 20 and 100 mg/kg for 28 consecutive days followed by a 2-week recovery period for the control and highest dose gn,ups. Body weight and food consu mption, clinical signs, organ weights, clinical biochemistry and haematolog ical parameters including clotting times and micronuclei induction in bone marrow erythropoeitic cells, and histopathology were examined. Relative org an weights of lung, liver and kidney, and serum cholesterol and phospholipi d significantly increased in male rats treated with MMBIs at doses of 20 an d 100 mg/kg. Male rats administered 100 mg/kg MMBIs exhibited a 1.8-fold in crease in thyroid weight associated with histopathological changes but not altered serum thyroid hormone levels. Female rats administered 100 mg MMBIs /kg exhibited significant increases of liver and kidney but not thyroid wei ghts, and serum cholesterol level. The antithyroid toxicity of MMBIs in rat s was estimated to be one-tenth that of 2-MBI. No-observed-effect levels fo r male and female rats were found to be 4 and 20 mg/kg, respectively, in th is subacute oral toxicity study. (C) 1999 Elsevier Science Ltd. All rights reserved.