The chronic oral toxicity of paracetamol at the range of the LD50 (100 days) in albino rats

Abstract

The LD50 (100 days) ± S.E. (oral dose of paracetamol which killed 50% of young male albino rats when given daily for 100 days) was found to be 0.77 ± 0.02 g/kg per day. The maximal LD0 (100 days) was estimated to be 0.4 g/kg per day, and the minimal LD100 (100 days) 1.1 g/kg per day. Signs of toxicity at the LD0 (100 days) were hyperreflexia, aciduria, hypertrophy of the cardiac stomach, atrophy of the testes, minor degrees of hepatic necrosis and nephritis, and augmented susceptibility to infection. Signs at the LD50 (100 days) were listlessness, pallor, inhibition of growth, diuresis, aciduria, a stress reaction, testicular atrophy, hepatic necrosis, tubular and calyxial nephritis, augmented susceptibility to infection, dehydration, and capillary–venous congestion of many body organs. Doses at and above the minimal LD100 (100 days) produced a toxicity syndrome which included in addition anorexia, hypothermia, hyporeflexia, prostration, and degenerative changes in several body organs. The abrupt withdrawal of paracetamol in survivors at 100 days was followed by a minor abstinence syndrome, with recovery within 2 weeks apart from residual testicular atrophy.