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).
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).
As long as 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.
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 autoimmune diabetes. Ravel et al. (2004) 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. These conflicting results are similar to findings in studies comparing the effects of mercury exposure in NOD mice vs. other strains of mice (see the heavy metals page). 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. In addition, the usefulness of NOD mice for measuring a substance's ability to affect type 1 diabetes in humans is in question, since many substances are protective against diabetes in these mice, but have not had the same effect in humans (Roep and Atkinson 2004) (see the of mice and men page for more on NOD mice).
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.
Evidence is growing that exposure to pollution during critical developmental periods, such as in utero or during childhood, may have effects later in life.
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). But do these developmental exposures promote autoimmunity? This question has not yet been answered. Developmental exposure to TCE has not been found to increase autoantibody levels in mice (Peden-Adams et al. 2008), but on the other hand, at higher levels of exposure, TCE does affect cells in the thymus, which may have implications for the development of autoimmunity (Blossom and Doss 2007) (see the autoimmunity page for more on the thymus and how substances can be toxic to the developing immune system).
Type 1 diabetes cluster?
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 studies on TCE and diabetes have been done (Davis et al. 2005).
In his book Diabetes Rising (2010), science writer Dan Hurley describes a cluster of type 1 diabetes cases in an area of Massachusetts (of A Civil Action fame) where the children's parents may have been exposed to TCE in their drinking water. Hurley writes, "Whether parents' exposure to trichloroethylene would increase their children's risk of developing type 1 diabetes later in life is entirely unknown; no study on the question has ever been published" (p. 133). The Massachusetts Department of Public Health has conducted a cluster investigation on type 1 diabetes in families living in Newton, Wellesley, and Weston MA. The results were released in Feb. 2012, and are available at this MDPH webpage. A cluster was found, but only in certain portions of Wellesley and Weston. Note that this is not the same area of Massachusetts that was affected by TCE contamination, but nearby. MDPH will now be analyzing various environmental factors that could have contributed to this cluster.
Studies from Woburn have found that children exposed to TCE in utero had a higher incidence of leukemia and recurrent infections. An old study of family members of these children did find damage to their immune systems, including increased incidence of autoantibodies (Byers et al. 1988). There is also animal evidence that exposure to some contaminants can have effects on the immune systems of subsequent generations: changes induced by embryonic exposure to a pesticide, including immune system abnormalities, were transmitted across four generations in rats (Anway et al. 2006). And, type 1 diabetes has been occasionally found to occur in clusters (see the type 1 diabetes incidence page). Taken together, these findings imply that it is conceivable that parental exposure to TCE could increase their children's risk of developing type 1 diabetes.
Evidence suggests that it is possible that TCE could influence the progression of type 1 diabetes, and this possibility should be investigated. I do not know of any studies on TCE and type 2 diabetes.