Due to concerns about its toxicity, the use of trichloroethylene in the food and pharmaceutical industries has been banned in much of the world since the 1970. In Europe, legislation has forced the substitution of trichloroethylene in many processes due to the fact it has been classified as a carcinogen carrying an R45 risk phase, May cause cancer. The manufacture of trichloroethylene largely ceased after it was banned
by the Montreal Protocol in 1996. Environmental Health: A Global Access Science Source, published an article in October of 2006 entitled, “Mortality among US employees of a large computer manufacturing company: 1969-2201,” by Richard W. Clapp, the following statement is
made, “In comparison to the PMRs (Proportional Mortality Ratios), only the PCMRs for pancreatic cancer (PCMR = 126; 95%CI = 101, 157), kidney cancer (PCMR = 162; 95%CI = 124, 212), malignant melanoma of the skin (PCMR = 179; 95%CI = 131, 244), and brain and central nervous system cancer (PCMR = 166; 95%CI =129, 213) remained statistically significant.”
The Environmental Protection Agency released a final human health assessment for trichloroethylene Sept. 28, 2011, that for the first time classifies the widely used solvent as “carcinogenic to humans” by all routes of exposure; EPAʼs final assessment concluded that TCE is a mutagenic carcinogen. That means risk assessors will have to take into account that early life exposures to the solvent could increase the risk of
eventual cancer; EPAʼs classification of TCE is consistent with the World Health Organizationʼs classification of TCE as a probable human carcinogen and the U.S. National Toxicology Programʼs listing of it as “reasonable anticipated” to cause human cancer. The EPA reaffirmed their position on June 10, 2016, when they again stated, “TCE is carcinogenic to humans by all routes of exposure.”
The IARC Working Group on the Evaluation of Carcinogenic Risk to Humans. Trichloroethylene, Tetrachloroethylene, and Some Other Chlorinated Agents, Lyon (FR): International Agency for Research on Cancer; 2014 made the following statements: Trichloroethylene was considered by previous IARC Working Groups in 1979, 1987, and New data have since become available, and these have been taken into
consideration in the present evaluation. Under Other Sites it states: “A significantly increased risk of death from cancer of the pancreas was found in black females with a low or medium level of exposure to trichloroethylene, and in white females with a low or high level of exposure, and in white males with a medium level of exposure.”
The molecular alterations in pancreatic carcinogenesis can occur either spontaneously or as the result of a mutagenic carcinogen. TCE has been classified by the EPA as a mutagenic carcinogen. As discussed above in an article entitled “Risk of Pancreatic Cancer in Workers Exposed to Chlorinated Hydrocarbon Solvents and Related
Compounds: A Metal Analysis,” Journal of Epidemiology, vol 153, issue 9 2001:841-850 it was stated, “One case-control study found an association between organochlorine levels and K-ras mutations in pancreatic cancer.”
The International Agency for Research on Cancer, 1995, stated the following: trichloroethylene is a probable carcinogen to humans based on limited human evidence and sufficient animal evidence.” In this monograph, under mutations in protooncogenes in tumors from trichloroethylene-treated animals it was stated, “H-ras
and K-ras mutations each contributed to 4% to the total in treated mice.
The molecular alterations induced by mutagenic carcinogens like TCE regarding the genesis of pancreatic carcinoma are as follows: Kras, Kras (chromosome 12p) is the most frequently altered oncogene in pancreatic cancer, with activating point mutations being present in 90%-95% of cases. CDKN2A. The CDKN2A gene (chromosome 9p) is
inactivated in 95% of pancreatic cancers, making it the most frequently inactivated tumor suppressor gene in these tumors. SMAD4. The SMAD4 tumor suppressor gene (chromosome 18q) is inactivated in 55% of pancreatic cancers. TP53. Inactivation of the TP53 tumor suppressor gene (chromosome 17p) occurs in 70%-75% of pancreatic
cancers. DNA Methylation Abnormalities. Several DNA methylation abnormalities also occur in pancreatic cancer.