13-week drinking water toxicity study of hydrogen peroxide with 6-week recovery period in catalase-deficient mice

A GLP OECD guideline study was conducted to evaluate the subchronic toxicit y of hydrogen peroxide (HP) when administered continuously in the drinking water of catalase-deficient (C57BL/6N) mice and reversibility of toxic effe cts. Groups of mice (15/sex/group) received solutions of 0, 100, 300, 1000 or 3000 ppm HP in distilled water for 13 weeks; five/sex/group continued on untreated distilled water for an additional 6 weeks. Animals drinking 3000 ppm HP exhibited depressed water and food consumption and body weight. Fem ales drinking 1000 ppm HP had reduced water consumption with intermittent e ffects on food consumption, but no body weight effects. HP administration d id not produce any mortality, clinical signs, hematological effects or orga n weight effects on brain, liver, kidneys, adrenals, testes, heart or splee n. Total protein and globulin were depressed among high dose males. Mild to minimal duodenal mucosal hyperplasia was noted in animals receiving 1000 a nd 3000 ppm HP and one male receiving 300 ppm for 13 weeks. There were no o ther histopathological findings. All effects noted during the treatment per iod, including the duodenal hyperplasia, were reversible during the 6-week recovery period. Females dosed with 300-3000 ppm HP during the treatment pe riod showed increased water consumption during the recovery period. The no- observed-effect level (NOEL), based on duodenal mucosal hyperplasia, is 100 ppm in drinking water or 26 and 37 mg/kg/day HP, respectively, for males a nd females. (C) 2000 Published by Elsevier Science Ltd. All rights reserved .