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Solvents and TCE

Trichloroethylene (TCE) is an industrial solvent and environmental contaminant, commonly found in hazardous waste sites. Exposure can occur via drinking water, food, or air, or in occupational settings (Blossom et al. 2007). The U.S. government estimates that 9-34% of drinking water in this country contains TCE, and in some communities, TCE contamination in drinking water is quite high. TCE can enter the body by ingesting contaminated water, and from showering in it, both by absorption through the skin or via inhalation (Keil et al. 2009).

Type 1 diabetes and autoimmunity

Human studies

TCE has long been suspected of contributing to the development of autoimmune disease because of studies that have shown associations between TCE exposure (through drinking water or occupationally) and various autoimmune diseases, including systemic lupus erythematous (SLE) and scleroderma. People living in areas with TCE-contaminated drinking water have been found to have signs of autoimmunity or autoimmune disease (Keil et al. 2009).

A U.S. EPA risk assessment review of TCE concluded that, "Recent evidence from studies in both humans and experimental animals point to the involvement of TCE exposure in autoimmune disease," among other health effects (Chiu et al. 2013).

A meta-analysis of 33 human studies found that there was an association between exposure to solvents (including TCE and others) and autoimmune diseases (Barragán-Martínez et al. 2012). Unfortunately, the authors did not include type 1 diabetes as part of this study (perhaps because they were under the mistaken impression that type 1 usually occurs in children, not adults, or perhaps because there were no studies on solvents and diabetes, I don't know why not).

Exposure during development

Evidence is growing that exposure to pollution during critical developmental periods, such as in utero or during childhood, may have effects later in life.

Studies from Woburn, Massachusetts (of A Civil Action fame), have found that children exposed to TCE in utero had a higher incidence of leukemia and recurrent infections than those unexposed. An old study of family members of these children found damage to their immune systems, including increased incidence of autoantibodies Byers et al. 1988).

Laboratory studies

Over 15 years ago, TCE was found to induce autoimmunity in animals (Khan et al. 1995). Subsequent studies have confirmed that TCE can promote autoimmunity in genetically susceptible mice, using different doses and routes of exposure (e.g., Gilbert et al. 2006; Wang et al. 2007, Blossom et al. 2004). The effects of TCE exposure can also depend on the strain of mouse. Interestingly, Keil et al. (2009) found that at low doses, TCE did not contribute to the progression of autoimmune disease in genetically susceptible mice, but did lead to increased markers of autoimmunity in mice that were not genetically prone to autoimmune disease. In addition, mice exposed to both TCE and mercury developed signs of autoimmune disease before mice exposed to either chemical alone (Gilbert et al. 2011).

Researchers are working to identify the mechanisms by which TCE may contribute to autoimmunity. TCE can induce oxidative stress in conjunction with the induction and exacerbation of autoimmunity in animals (Wang et al. 2007). TCE exposure may also involve inflammation (Gilbert et al. 2006; Blossom et al. 2007). Cooper et al. (2009) summarizes some possible mechanisms through which TCE could affect autoimmunity, including via inflammation and oxidative stress. Also, animals exposed to TCE have been found to have changes in gene expression (Baccarelli and Bollati 2009).

One study has examined the effects of TCE on NOD (non-obese diabetic) mice, an animal model of type 1 diabetes. Ravel et al. (2005) found that TCE did not accelerate diabetes in NOD mice. To the contrary, TCE showed almost opposite effects than have been found in other strains of mice. The authors conclude that the mechanisms involved in autoimmune disease development are more complex than previously thought, and that people with differing levels of susceptibility may have differing levels of risk to environmental contaminant exposures (see the Of mice, dogs, and men page for more discussion).

A review examined experimental and human studies of the immune-related, especially autoimmune-related, effects of TCE. It found that the consistent findings of the studies and the similarities between studies in mice and humans support the idea that TCE may cause autoimmune disease (Cooper et al. 2009). The health effects of TCE exposure during development (e.g., in utero were not included in this review.

Exposure during development

Developmental exposures to TCE show that TCE affects the development of the immune system. These immune system effects occurred at lower doses than those producing effects in adult animals (Peden-Adams et al. 2006).

Gestational exposure to TCE may induce immune system changes that could contribute to autoimmune disease later in life. A study compared exposure during gestation, and exposure during early life (in mice), to see which had the most profound effects. Certain immune system effects were found in both sets of mice. Some additional changes were found in the mice exposed during gestation, while other changes were found in those exposed early in life. These changes may affect the likelihood of autoimmune disease later in life, but that remains to be determined (Gilbert et al. 2014).

Type 2 Diabetes


The U.S. Agency of Toxic Substances and Disease Registry (ATSDR) monitors groups of people exposed to TCE in drinking water in Michigan, Indiana, Illinois, Pennsylvania, and Arizona. They document some of the health effects found in people exposed to TCE, as compared to others in the general U.S. population. They have found higher levels of diabetes in people exposed to TCE, but did not distinguish between type 1 and type 2; unfortunately no other studies on TCE and diabetes have been done (Davis et al. 2005).

The bottom line

It is possible that TCE could influence the progression of autoimmune diseases such as type 1 diabetes.

References

To download or see a list of all the references cited on this page, see the collection Solvents and TCE and diabetes/obesity in PubMed.