Effects of subchronic exposure of monochloramine in drinking water on male rats.

A subchronic rat study with paired-water control was conducted to resolve the question of whether monochloramine at 200 ppm in drinking water can cause reduced body weight gain and other changes observed in earlier investigations. Male Sprague-Dawley rats (93 +/- 5 g) were divided into three groups of 10 rats each: the treatment group was fed drinking water containing 200 ppm monochloramine, the control group was fed bicarbonate-buffered water ad libitum, and the paired-water control rats were given a daily volume of bicarbonate-buffered water equal to that consumed by the monochloramine treatment group. Compared to the control group, rats in the treatment group consumed an average of 42% less fluid and 16% less food over the 13-week treatment period and had 15-20% lower final body weight gain. Similar degrees of reduction in food consumption and body weight gain were observed in the paired-water rats. A decreased liver to body weight ratio occurred in the treatment and paired-water groups. Increased inorganic phosphate, albumin, total protein, and urea nitrogen were detected in sera from both the treatment group and the paired-water groups. The paired-water animals had lower levels of white blood cells and lymphocytes, while the paired-water and monochloramine-treated groups had reduced monocyte counts. Except for a slightly increased response to Con A observed in splenic lymphocytes of the monochloramine-treated rats (versus the paired-water), no significant changes were found in mitogen responsiveness to T cell, B cell, and B plus T cell mitogens or in splenic natural killer (NK) cell activities. There were no significant changes in serum levels of IgG, IgA, and IgM. The following biochemical parameters showed no significant variations among the three groups: serum thyroxin, liver phase I (PROD, EROD, and MROD) and phase II (UDPGT and GST) drug-metabolizing enzyme activities; serum and liver thiobarbituric acid-reactive substances (TBARS); bronchoalveolar lavage fluid protein and N-acetylgluosaminidase (NAGA) activity; and urinary ascorbic acid, protein, and NAGA activity. Histopathological examination revealed minimal to mild adaptive changes in the liver of the paired-water and monochloramine-treated rats and in the thyroid of the monochloramine-treated animals. No treatment-related cytological changes were found in red cells and bone marrow. The results indicate that the reduced body weight gain and the minor biochemical, hematological, immunological, and histopathological changes associated with subchronic exposure to 200 ppm monochloramine in drinking water (equivalent to an intake of 21.6 mg/kg/day) were largely related to the reduced water intake and food consumption and not caused by monochloramine. (C) 1997 Academic Press.