This study evaluated the subchronic toxicity of selected halomethanes which are drinking water contaminants. The compounds studied were trichloromethane, bromodichloromethane, dibromochloromethane and tribromomethane. Subchronic 14-day gavage studies were performed with the use of doses encompassing one-tenth the LD50 for the compounds. A 90-day gavage study of one of the compounds, trichloromethane, was also done. Parameters observed included body and organ weights, histopathology, hematology, clinical chemistries, and hepatic microsomal enzyme activities. Toxicity to the humoral immune system was assessed by measuring the number of splenic IgM antibody-forming cells and the serum antibody level to sheep erythrocytes. Cell-mediated immunity was evaluated by measuring the delayed type hypersensitivity response and popliteal lymph node proliferation response to sheep red blood cells. The functional activity of the reticuloendothelial system, as measured by the vascular clearance rate and tissue uptake of 51Cr sheep red blood cells was also determined. The major effects of the halomethanes were increased liver weights, elevations of SGPT and SGOT, decreased spleen weights and a decrease in the number of splenic IgM antibody-forming cells. The humoral immune system appeared to be an indicator of halomethane toxicity. There is evidence that subchronic 14-day exposure may be of greater value than long-term studies in determining the toxicity of these compounds. water was the original source and in which disinfection
The organs, tissues, and cells of the lymphoreticular system have received considerable attention as targets for chemicals causing adverse effects. A basic toxicological approach is described for assessing the risk of a chemical perturbing the immune system. CD-1 mice were exposed for 14 or 90 days to one of several chlorinated hydrocarbons: 1,2-dichloroethane, 1,2-dichloroethylene or 1,1,2-trichloroethylene. Other mice were exposed to dexamethasone, a known immunosuppressive agent. The immune system is evaluated against a background of the more standard toxicological parameters such as fluid consumption, body and organ weights, hematology, clinical chemistries, and blood coagulation. Reported here are the results for the male mice after 14-day exposure to three chlorinated hydrocarbons and after 90-day exposure to 1,2-dichloroethane and dexamethasone. Acute toxicity studies were performed to provide a basis for doses used in the subchronic studies. The LD50 values are reported. The status of the humoral immune system was determined by measuring the number of IgM spleen antibody-forming cells to sRBC, the serum antibody level to sRBC, and the lymphocyte response to the B-cell mitogen, LPS. Of the three chlorinated hydrocarbons, only dichloroethane produced a significant (p < 0.05) reduction in antibody-forming cells. The other two chemicals produced trends towards suppression. Mice exposed to dichloroethane in the drinking water for 90 days showed no alteration in AFC, serum antibody titers or response to the B-lymphocyte mitogen, LPS. Subchronic 90-day exposure to dexamethasone produced a dose-dependent inhibition of AFC/spleen but not AFC/106 spleen cells when measured on the peak day of response. Response to LPS was not altered, and spleen weight and spleen cell number were reduced as much as 42%. These data suggest that dexamethasone administered in the drinking water is nonspecifically cytotoxic to the spleen cells. Cell-mediated immunity was assessed by measuring the DTH response to sRBC and the response to the T-lymphocyte mitogen, concanavalin A. After 14 days of exposure, trichloroethylene produced a 15 and 60% suppression at 24 and 240 mg/kg, respectively. Dichloroethylene produced a non-dose-dependent inhibition at 4.9 and 49 mg/kg, which was slight, but significant (p < 0.05). Subchronic 90-day exposure to dichloroethane did not alter the DTH response or spleen lymphocyte response to concanavalin A. In contrast, dexamethasone produced a dose-dependent inhibition of the DTH response and a hyperresponsiveness to concanavalin A. Dichloroethane did not alter the functional activity of the reticuloendothelial system, as measured by the vascular clearance rate and tissue uptake of 51Cr sRBC. In the case of dexamethasone exposure, only the spleen and thymus showed decreased uptake of 51Cr sRBC, which was directly related to decrease in size. The approaches and results from these types of studies provide a basis for judging a chemical's potential risk to the immune system.
Chloral hydrate has been found in our drinking water supplies at levels up to 5 ,ug/l. The purpose of this study was to evalute the acute and subchronic toxicology of chloral hydrate in the random-bred CD-1 mouse, to provide data for risk assessment. The acute oral LD50 of this compound was 1442 and 1265 mg/kg in male and female mice, respectively. Acute toxicity appeared to be related to depression of the central nervous system. Fourteen-day exposure by gavage in male mice at doses 1/10 and 1/100 the LD50 caused an increase in liver weight and a decrease in spleen weight at the highest dose level. Based on the data derived from 14 days of exposure, a 90-day study was performed. The compound was delivered via the drinking water; levels of the compound delivered per day were equivalent to those dosed in the 14-day study. The target organ in both sexes appeared to be the liver, with the males most affected. Male mice demonstrated a dose-related hepatomegaly accompanied by significant changes in serum chemistries and hepatic microsomal parameters. The females did not demonstrate the hepatomegaly observed in males, but did show alterations in hepatic microsomal parameters. No other significant toxicological changes were observed in either sex following 90 days of exposure.
This study evaluated the subchronic toxicity of selected halomethanes which are drinking water contaminants. The compounds studied were trichloromethane, bromodichloromethane, dibromochloromethane and tribromomethane. Subchronic 14-day gavage studies were performed with the use of doses encompassing one-tenth the LD50 for the compounds. A 90-day gavage study of one of the compounds, trichloromethane, was also done. Parameters observed included body and organ weights, histopathology, hematology, clinical chemistries, and hepatic microsomal enzyme activities. Toxicity to the humoral immune system was assessed by measuring the number of splenic IgM antibody-forming cells and the serum antibody level to sheep erythrocytes. Cell-mediated immunity was evaluated by measuring the delayed type hypersensitivity response and popliteal lymph node proliferation response to sheep red blood cells. The functional activity of the reticuloendothelial system, as measured by the vascular clearance rate and tissue uptake of 51Cr sheep red blood cells was also determined.The major effects of the halomethanes were increased liver weights, elevations of SGPT and SGOT, decreased spleen weights and a decrease in the number of splenic IgM antibody-forming cells. The humoral immune system appeared to be an indicator of halomethane toxicity. There is evidence that subchronic 14-day exposure may be of greater value than long-term studies in determining the toxicity of these compounds.
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