Prechronic Test Phase Review

摘要

Subchronic inhalation toxicity was evaluated in a range finding study using 1,2 epoxybutane (purity not reported) to determine the exposure concentrations for a chronic study. Groups of 20 Fischer-344 rats (10 male, 10 female) and 20 B6C3F1 mice (10 male, 10 female) were exposed to 0,50,100,200,400 or 800 ppm 1,2 epoxybutane for 13 weeks. The number of hours/day and days/week of exposure were not reported. The investigators observed severe inflammation of the nasal cavity, hemorrhage of the tracheobronchial lymph nodes, and statistically significantly decreased body weight gain in rats exposed at 800 ppm; the incidence and severity of lesions in rats exposed at other levels were not considered to be different from controls. Observations in mice exposed to 800 ppm included inflammation of the nasal cavity, red discoloration of the lungs, paleness of the spleen, distension of the G.I. tract, thymic necrosis, thymic atrophy, splenic atrophy, splenic necrosis, along with renal tubular necrosis and inflammation. At 200 and 400 ppm mice exhibited a reduction in the number of cell layers in the olfactory epithelium and an increase in amount of serous fluid, especially in the recesses of the turbinate area; but no effects on the thymus, spleen or kidneys.