National Toxicology Program

National Toxicology Program
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Abstract from Report IMM96007 on Trichloroethylene

Time Course Autoimmunity Study of Trichloroethylene in Female Brown Norway Rats (CAS No. 79-01-6)

Report Date: January 1997

The following abstract presents results of a study conducted by a contract laboratory for the National Toxicology Program. The findings have not been peer reviewed and were not evaluated in accordance with the levels of evidence criteria established by NTP in March 2009. The findings and conclusions for this study should not be construed to represent the views of the NTP or the U.S. Government.


Abstract

Trichloroethylene is an environmental contaminant found in both municipal drinking water and in well water. In areas which have high concentrations in the drinking water, TCE has been associated with changes in the immunological system and elevated rates of childhood leukemia. Exposure to TCE has also been associated with the development of autoimmune disease.

The purpose of this time course study was to determine the potential effects of TCE to induce autoimmunity in the Brown Norway Rat model and to determine the time of maximum effect.

The studies were conducted in female Brown Norway Rat. The animals were administered TCE (500 mg/kg) five days a week for an 8-week period by oral gavage. Trichloroethylene was prepared weekly in a 10% Alkamus-deionized water solution. Additional groups of vehicle- and TCE-exposed animals also received mercuric chloride (1 mg/kg) three times per week by subcutaneous injection for 2 additional weeks. Various parameters of autoimmunity were evaluated weekly, at the time of sacrifice following TCE treatment, and at time of sacrifice following challenge with mercuric chloride. The in-life phase began 8, April 1996 and was completed on 17, June 1996.

The results of the time course study demonstrate that female Brown Norway rats have a strong aversion to being exposed to TCE by oral gavage. Furthermore, during the study 3 deaths directly related to chemical exposure were observed in the TCE exposure group which consisted of 15 animals. Animals exposed to TCE had decreased body weights compared to the vehicle control animals during the first two weeks of the study and a decrease in body weight gain over the course of the study period. While no effect was observed on spleen, lungs, thymus or adrenal weights, increases were observed in relative kidney (8%) and liver (14%) weights compared to the vehicle controls.

When parameters indicative of autoimmune responses were evaluated, no effect was observed on serum immunoglobulin E levels evaluated weekly, at the time of sacrifice or following challenge with mercuric chloride. No effect was observed on total serum IgG levels at the time of sacrifice; however, a decreased total IgG response was observed in the TCE-exposed animals following challenge with mercuric chloride. No effect was observed on serum IgG antibody titers to dinitrophenol-human serum albumin evaluated weekly or at the time of sacrifice. Decreased serum IgG antibody titers to DNP-HSA response were observed in the TCE-exposed animals following challenge with mercuric chloride. While no effect was observed on serum IgG antibody titers to sheep erythrocytes at the time of sacrifice, a decrease in serum IgG antibody titers to sheep erythrocytes was observed in the TCE-exposed animals following challenge with mercuric chloride.

When parameters related to autoimmune disease were evaluated, no effects were observed in blood urea nitrogen levels at the time of sacrifice or following challenge with mercuric chloride. No effect was observed on urinalysis parameters which included glucose, protein, pH, and blood in the urine as measured using Hema-Combistix. No effect was observed on serum IgG antibody titers to laminin evaluated weekly or at the time of sacrifice. A decrease in serum IgG antibody titers to laminin was observed in the TCE-exposed animals following challenge with mercuric chloride; however, the decrease did not reach the level of statistical significance. No effects were observed in serum IgG antibody titers to double stranded DNA at the time of sacrifice or following challenge with mercuric chloride.

In conclusion, this time course study demonstrates that exposure to TCE at a dose level of 500 mg/kg for eight weeks results in significant changes in parameters of autoimmunity and that the time of maximum effect on IgG responses occurred 6 weeks after initiation of TCE exposure. Although no effects were observed on IgE responses, significant changes were observed in IgG antibody-mediated parameters following mercuric chloride challenge. TCE, at a dose level of 500 mg/kg, produced no significant effect on any of the indicators of autoimmune disease. Due to the exposure-related loss of animals at the 500 mg/kg dose level, future studies using the Brown Norway rat should be conducted at lower doses.


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