The subchronic toxicity of 0.2-200 ppm dichloramine and 0.2-90 ppm trichlor
amine in the drinking water of rats was investigated using biochemical, hem
atological, and histopathological parameters. Animals in the highest dose g
roups consumed 5-15% less fluid than controls with no significant decrease
in body weight gain. No clinical signs of toxicity were observed in either
case. Both males and females dosed with 90 ppm trichloramine had significan
tly increased relative kidney/body weights and the females had increased he
patic glutathione S-transferase and UPD-glucuronosyltransferase activities.
No significant changes were detected in other xenobiotic metabolizing enzy
mes or in serum biochemistry, urine biochemistry, or hematology. Both dichl
oramine and trichloramine induced minimal to mild adaptive histopathologica
l changes in thyroids and kidneys of animals of both sexes. Dichloramine, b
ut not trichloramine, was associated with histological changes in the gastr
ic cardia characterized by epithelial hyperplasia at concentrations of 2 pa
m and above in the males and 200 ppm in the females. This study indicates t
hat dichloramine produced mild histological effects at drinking water conce
ntrations of >0.2 ppm in males (0.019 mg/kg/day) and >2 ppm in females (0.2
6 mg/kg/day) while trichloramine produced biochemical and mild histological
effects at levels of >2 ppm both in males (0.23 mg/kg/day) and in females
(0.29 mg/kg/day). (C) 2000 Academic Press.