Paracetamol is a well-known analgesic and anti-pyretic drug. Its hepatotoxicity is still a big challenge for scientific and clinical community. There is rich data available regarding its benefits and hazards. However very rear data is available to their positional isomers i.e., metacetamol and orthocetamol. Metacetamol is previously reported as non-hepatotoxic isomer with analgesic and antipyretic potential. The preclinical acute toxicological activities of Paracetamol (4-acetamidophenol) positional isomers; 2-acetamidophenol and 3-acetamidophenol was aimed in this research work. In acute toxicological studies, paracetamol isomers were analyzed for lethal dose toxicity in 50% rats population. LD₅₀ of 2-acetamidophenol, 3-acetamidophenol and 4-acetamidophenol (Paracetamol) were found 1.30g/kg,1.15g/kg and1.25g/kg, respectively. The results showed that all the isomers were safer and having wide therapeutic window. 2-acetamidophenol was found to be non-hepatotoxic, non-nephrotoxic and non- hemotoxic when 100mg/kg dose (i.p) administered to female Sprague dawley rats. At 500 and 1000mg/kg doses of 2-acetamidophenol, it was found to be hepatotoxic and mild nephrotoxic. 3-acetamidophenol showed mild hepatotoxicity but severe nephrotoxicity when 1000mg/kg (i.p) dose administered to female Sprague dawley rats. No haematotoxicity was observed in 3-acetamidophenol at toxic dose range.

Keywords: Paracetamol, Metacetamol, Orthocetamol, Toxicity studies, Hepatotoxicity, Haematology, Nephrotoxicity