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Abstract for IMM20201

Range-Finding Report on the Immunotoxicity of 1,3-Dichloropropene (Telone II) in Female B6C3F1 Mice

CASRN: 542-75-6
Chemical Formula: C3H4Cl2
Molecular Weight: 110.971
Report Date: August 2012

Abstract

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 The findings have not been peer reviewed and were not evaluated in accordance with the levels of evidence criteria established by NTP in March 2009.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.

Dichloropropenes are synthetic chemicals with a double bond connecting two of the three carbons present in the molecule. Two chlorines are attached at various positions, giving rise to five isomers. The 1,3-dichloropropene isomer, also known as Telone II, exists as a mixture of the geometric isomers cis-1,3-dichloropropene and trans-1,3-dichloropropene, and these two isomers have very similar properties (EPA, 2008). DCP is produced and used in much higher amounts (20-25 million pounds annually) than the other dichloropropene isomers (Costa, 2007; NTP Substance Profile, 2010). DCP is used as a pre-plant soil fumigant to control nematodes and other pests in soils to be planted with all types of food and feed crops, including vegetables, fruit and nut crops, forage crops (grasses, legumes, and other non-grass forage crops), tobacco, fiber crops, and nursery crops (ornamental, non-bearing fruit/nut trees and forestry crops).

DCP is released into the environment, including into the drinking water, primarily as a result of its use on farms, fine turf, golf courses, sports fields, greenhouses, and lawns, etc. (Trenholm et al., 2005). The primary routes of potential human exposure to DCP are inhalation of vapors and dermal contact during the formulation and application of DCP. Additional routes of exposure include ingestion of contaminated foods (e.g. pineapples fumigated with DCP) and drinking water (NTP, 1985; Albrecht 1987; ATSDR 1992; HSDB 2000). DCP has not been detected in foods grown in fields treated with the chemical, and it has also been reported that DCP and its metabolites are not likely to accumulate in animal tissues, eggs, nor be secreted in milk to a significant extent following oral ingestion of crops grown on soil fumigated with DCP (Dow AgroSciences, 1996). Although DCP can leach into the ground water with normal agricultural use, the presence of DCP in various water samples suggests that it may be formed during chlorination (Rogers et al., 1987; ATSDR 1992). Low levels of DCP have been measured in water samples; the range of quantifiable concentrations in water are reported to be 0.001–5 ppb with a mean of 0.4 ppb (ATSDR, 2008). The United States Environmental Protection Agency has determined that exposure to DCP in the drinking water at concentrations of 0.03 parts per million for up to 10 days is not expected to cause any noncancerous adverse effects in children (ATSDR, 2008).

The potential for DCP to cause skin sensitization following repeated or prolonged exposure has been demonstrated in case reports and animal studies (van Joost and de Jong 1988; Bousema et al. 1991; Vozza et al. 1996; Corazza et al. 2003; Department of Health and Human Services, 2010). Although no lesions were identified following gross and histological examinations of the thymus and lymph nodes of rats and mice exposed to 150 ppm or less of DCP for 13 weeks (Stott et al., 1988), to 60 ppm DCP for 6-24 months (Lomax et al., 1989), or to 50 ppm of DCP for 6-12 weeks (Parker et al., 1982), more extensive testing of effects on immune system functions were not conducted in those studies.

The EPA requires that it be notified of spills of 100 pounds of DCP (or more) into the environment. In addition, the EPA has established a health advisory maximum level of 0.03 mg DCP per liter of drinking water in order to protect the health of children (ATSDR, 2008).

The purpose of these studies was to determine the potential effects of DCP on the immune system when administered in drinking water. These studies were conducted in female B6C3F1 mice. The animals were exposed to DCP based on the concentration of the test substance in the drinking water. DCP solutions were freshly prepared every two weeks in tap water and stored refrigerated.

Administration of DCP produced a significant dose-related decrease in terminal body weight and body weight gain; however, a majority of the toxicological and immunological parameters evaluated were unaffected. A dramatic decrease in body weight gain was observed, with all animals losing weight during the first week of study. At the highest DCP concentration (1000 μg/ml), the body weight never returned to the starting weight, and weight loss was accompanied by a dose-dependent decrease in water consumption throughout the exposure period. In contrast, no effect was observed on either relative spleen or relative thymus weight at any of the dose levels evaluated and, overall, hematological parameters were unaffected. Effects observed on the phenotypic analysis of spleen cell populations appeared to be due to the changes observed in spleen cell numbers. Immunological parameters that were not affected by DCP exposure included cell-mediated immune parameters (the mixed leukocyte response, and anti-CD3-mediated spleen cell proliferation) and innate immune parameters (natural killer cell activity). Humoral immunity, as measured by the spleen Immunoglobulin M antibody-forming cell response to the T cell dependent antigen sheep erythrocytes, was dose dependently decreased, reaching the level of statistical significance at dose levels > 250 μg/ml. Serum anti-sRBC IgM antibody levels were decreased in a dose-dependent manner, but the decreases at the individual doses did not reach the level of statistical significance.

In conclusion, humoral immune parameters were adversely affected to a greater extent than those of the innate immune response or cell-mediated immunity following exposure to DCP.