RESUMO
A GLP OECD guideline study was conducted to evaluate the subchronic toxicity of hydrogen peroxide (HP) when administered continuously in the drinking water of catalase-deficient (C57BL/6N) mice and reversibility of toxic effects. 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. Females drinking 1000 ppm HP had reduced water consumption with intermittent effects on food consumption, but no body weight effects. HP administration did not produce any mortality, clinical signs, hematological effects or organ weight effects on brain, liver, kidneys, adrenals, testes, heart or spleen. Total protein and globulin were depressed among high dose males. Mild to minimal duodenal mucosal hyperplasia was noted in animals receiving 1000 and 3000 ppm HP and one male receiving 300 ppm for 13 weeks. There were no other histopathological findings. All effects noted during the treatment period, including the duodenal hyperplasia, were reversible during the 6-week recovery period. Females dosed with 300-3000 ppm HP during the treatment period 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 and females.
Assuntos
Acatalasia , Peróxido de Hidrogênio/toxicidade , Animais , Peso Corporal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ingestão de Líquidos/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Feminino , Peróxido de Hidrogênio/análise , Hiperplasia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Masculino , Camundongos , Nível de Efeito Adverso não Observado , Fatores Sexuais , Água/análiseRESUMO
Animal studies were carried out using an oral solution of a low osmolality non ionic contrast medium iopamidol, developed for gastrointestinal examinations. The new formulation was evaluated for image quality in studies of the upper and lower gastrointestinal tract. Margins of safety were defined by subjecting the compound to a number of toxicological and pharmacological experiments. The experiments were designed to reveal qualitative and quantitative differences between the formulation of iopamidol and Gastrografin, a conventional ionic contrast medium. The results indicate that the formulation of iopamidol is safer than a conventional hypertonic water soluble contrast medium and diagnostically superior in the gastrointestinal tract examinations.