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Toxicity In acute toxicity tests in rats, the LD50 was shown to be 226 - 240 mg/kg while chronic toxicity studies demonstrated a dose-dependent gastrointestinal haemorrhage, ulceration and, sometimes, perforation. No toxic changes other than these gastrointestinal lesions were observed. The LD50 values for dogs was about 500 mg/kg and for monkeys about 3200 mg/kg. Carcinogenic Effects Long term carcinogenicity studies in rats given upto 2 mg/kg/day (approximately the human dose) have revealed no significant increase in tumour incidence. Mutagenic Effects Diclofenac did not show mutagenic potential in various mutagenicity studies including Ames test. Diclofenac administered to male and female rats at 4 mg/kg/day did not affect fertility. Teratogenicity Diclofenac sodium exhibited no teratogenic effects in the mouse at doses up to 20 mg/kg orally throughout the entire gestational period. In rats, the fertility of both males and females was unaffected although some embryotoxicity was noted in dams on 2 - 4 mg/kg daily. This manifested itself in increased intrauterine reabsorption and/or decreased number of offsprings in a full term litter together with a decreased average neonate weight. Subsequent growth and survival was, however, comparable with controls. In rats given doses of diclofenac sodium up to 10 mg/kg throughout gestation, no teratogenic effects were observed. In rabbit studies no teratogenic effects were observed and foetal development was satisfactory in animals given 10 mg daily on days 7 - 16 post-coitus.
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