Trichloroethylene cancer risk

BogenKT, Gold LS. Trichloroethylene cancer risk Simplified calculation of PBPK-based MCLs for cytotoxic end points. Regul Toxicol Pharmacol 1997 25 26-42. 

Several retrospective cohort studies of workers exposed to unquantified levels of trichloroethylene have been conducted. All of these studies have limitations that restrict their usefulness for evaluating the carcinogenicity of trichloroethylene. None has shown clear, unequivocal, evidence that trichloroethylene exposure is linked to increased cancer risk. 

Monte Carlo simulation, an iterative technique which derives a range of risk estimates, was incorporated into a trichloroethylene risk assessment using the PBPK model developed by Fisher and Allen (1993). The results of this study (Cronin et al. 1995), which used the kinetics of TCA production and trichloroethylene elimination as the dose metrics relevant to carcinogenic risk, indicated that concentrations of 0.09-1.0 pg/L (men) and 0.29-5.3 pg/L (women) in drinking water correspond to a cancer risk in humans of 1 in 1 million. For inhalation exposure, a similar risk was obtained from intermittent exposure to 0.07-13.3 ppb (men) and 0.16-6.3 ppb (women), or continuous exposure to 0.01-2.6 ppb (men) and 0.03-6.3 ppb (women) (Cronin et al. 1995). 

This study, like that of Fisher and Allen (1993), incorporated a linear multistage model. However, the mechanism of trichloroethylene carcinogenicity appears to be non-genotoxic, and a non-linear model (as opposed to the linearized multistage model) has been proposed for use along with PBPK modeling for cancer risk assessment. The use of this non-linear model has resulted in a 100-fold increase in the virtually safe lifetime exposure estimates (Clewell et al. 1995). 

Because of its carcinogenic potential, the EPA-recommended concentration for trichloroethylene in ambient water is zero. However, because attainment of this level may not be possible, levels that correspond to upper-bound incremental lifetime cancer risks of 10, lO , and 10 are estimated. 

Axelson O, Selden A, Andersson K, et al. 1994. Updated and expanded Swedish cohort study on trichloroethylene and cancer risk. J Occup Med 36 556-562. 

Clewell HJ, Gentry PR, Gearhart JM, et al. 1995. Considering pharmacokinetic and mechanistic information in cancer risk assessments for environmental contaminants Examples with vinyl chloride and trichloroethylene. Chemosphere 31 2561-2578. 

The assessment of liver cancer risks associated with human exposure to trichloroethylene (TCE) was initially conducted by Fisher and Allen (1993) using a PBPK-modeling approach. The use of the amount of TCE metabolized per day as dose metric used in the linearized multistage model led to lOppb in air and 7 ag/L in water as acceptable concentrations—that is, environmental levels corresponding to a population cancer risk of 1 in 10 (Fisher and Allen 1993). Corresponding values based on circulating levels of the metabolite, trichloroacetic acid, were 10 times and twice lower than those based on the amount of TCE metabolized per unit time, whereas the acceptable TCE concentration in air as defined by the EPA at the time was 90 times lower. A number of authors subsequently investigated the dose metrics and cancer risks associated with TCE [e.g., Bois (2000), CleweU and Andersen... 

Clewell, H. J., and Andersen, M. E. (2(X)4). Applying mode-of-action and pharmacokinetic considerations in contemporary cancer risk assessments An example with trichloroethylene. Crit Rev Toxicol 34, 385-445. 

Trichloroethylene (TCE) Possible cancer risk 0.005-0 Waste from disposal of dry cleaning material and manufacture of pesticides, paints, waxes metal degreaser... 

Trichloroethylene zero 0.005 Liver problems increased risk of cancer Discharge from petroleum refineries... 

Fisher JW. 1993. Estimating the risks of liver and lung cancer in humans exposed to trichloroethylene using a physiological model. Toxicol Lett 68 127-129. 

Fisher JW, Allen BC. 1993. Evaluating the risk of liver cancer in humans exposed to trichloroethylene using physiological models. Risk Anal 13 87-95. 

Blair et al. (1998) performed a retrospective cohort mortality study of 14 457 workers employed for at least one year between 1952 and 1956 at an aircraft maintenance facility in the United States. Among this cohort were 6737 workers who had been exposed to carbon tetrachloride (Stewart et al., 1991). The methods used for this study are described in greater detail in the monograph on dichloromethane. An extensive exposure assessment was performed to classify exposure to trichloroethylene quantitatively and to classify exposure (ever/never) to other chemicals qualitatively (Stewart et al., 1991). Risks from chemicals other than trichloroethylene w ere examined in a Poisson regression analysis of cancer incidence data. Among women, exposure to carbon tetrachloride was associated with an increased risk of non-Hodgkin lymphoma (relative risk (RR), 3.3 95% CI,... 

Green, T., Trichloroethylene and human cancer, Hum. Ecol. Risk Assess., 1, 677-685, 2001. 

Some VOCs are known human carcinogens (e.g., benzene, vinyl chloride). Others are animal carcinogens and may be human carcinogens (methylene chloride, trichloroethylene, tetrachloroethylene, chloroform, and p-dichlorobenzene). The unit risks for these compounds are shown in the table below (Unit risks reflect the probability of attracting cancer in a hypothetical population during lifetime exposure to lpgm of VOCs.)... 

Lock EA, Reed CJ. Trichloroethylene Mechanisms or renal toxicity and renal cancer and relevance to risk assessment. Toxicol Set 2006 91 (2) 313—31. 

Moore LE, Boffetta P, Karami S, Brennan P, Stewart PS, Hung R, Zaridze D, Matveev V, Janout V, Kollarova H, Bencko V, Navratilova M, Szeszenia-Dabrowska N, Mates D, Gromiec J, Holcatova I, Merino M, Chanock S, Chow WH, Rothman N. Occupational trichloroethylene exposure and renal carcinoma risk evidence of genetic susceptibility by reductive metabolism gene variants. Cancer Res 2010 70 6527-36. 

The risk is of cancer Methylene chloride (MC), trichloroethylene (TCE), and perchloroethylene (PCE, or "perc"), which produce acute and/or chronic, non-cancerous health effects at sufficient concentrations, have also been classified as probable or possible human carcinogens by either the EPA or other governmental or international agencies (Ref. 3, Table 20 1)... 

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