Subject: Assessing the Potential Risk of Human Exposure to Tetrachloroethylene (Perchloroethylene) and Formaldehyde

Transcription

1 Memo Date: June 20, 2006 To: From: Shelly Burman, Minnesota Pollution Control Agency Hillary Carpenter, Health Risk Assessment Unit Subject: Assessing the Potential Risk of Human Exposure to Tetrachloroethylene (Perchloroethylene) and Formaldehyde This memo is a follow-up to our conversation in 2005 concerning your request for assistance in assessing the potential risk of human exposure to tetrachloroethylene (CASRN , perchloroethylene or PERC) and formaldehyde (CASRN ) in ambient air. Regrettably, following a thorough literature review of both chemicals MDH has decided that it is unable to provide the MPCA with an HBV for PERC or an updated health-based value for formaldehyde at this time. The information on which these decisions are based is summarized below. Also included in these discussions is information that may be of assistance in site-specific risk management decisions. As you are no doubt aware, there is a great deal of controversy surrounding both of these chemicals and whether or not they present risks to humans at low level exposures. MDH will continue to monitor new information as it becomes available and, when information sufficient to rectify the current controversies becomes available, an HBV for each will be developed. If you have any questions please call me at (651) Background Information Tetrachloroethylene. The decision not to develop a HBV for PERC was based in part on the following information. The carcinogenicity of PERC in humans is controversial. Despite the fact that IARC lists PERC as a 2A carcinogen (likely) and the National Toxicology Program (NTP) has listed PERC as reasonably anticipated to be carcinogenic in humans, an U.S. EPA Scientific Advisory Board (U.S. EPA, 1991) charged with examining the carcinogenicity of PERC found that the evidence for carcinogenicity was insufficient to classify PERC as a B2 carcinogen. This group suggested that the proper cancer classification actually fell somewhere in between the B2 and C categories. In fact, serious questions regarding the carcinogenicity of PERC in humans have been raised. The epidemiological information for the carcinogenicity of PERC is not strong. Studies that indicate a relationship between exposure to PERC and cancer in various sites are confounded by not accounting for smoking, alcohol consumption and socioeconomic status. Frequently Environmental Health Division; 625 N Robert St; St. Paul, MN 55155;(651)

2 in these studies exposures are not to PERC alone but to multiple halogenated solvents. A recent review of 44 published epidemiological studies that provided reasonable data on up to 17 cancer sites reached the conclusion that the current evidence does not support the conclusion that occupational exposure to PERC is a risk factor for cancer at any specific site (Mundt et. al., 2003). Health Canada (CEPA 1993) has classified PERC as unlikely to be carcinogenic to humans, and developed a Tolerable Concentration (TC) of 360 μg/m 3. The justification used for this approach was the available evidence indicates that PERC s carcinogenicity is both species and gender specific and is likely to be induced by mechanisms that are not relevant to humans, or a least for which humans are much less sensitive. The World Health Organization (WHO 2000) stated in a report released in 2000 given the limitations of the epidemiological evidence and uncertainty of the relevance to humans of the induction of the tumors in animals exposed to tetrachloroethylene, the derivation of the guideline values is at present based on non-neoplastic effects rather than on carcinogenicity as the critical endpoint. The WHO has adopted a guideline of 250 μg/m 3 (annual averaging time) based on PERC s effects on the kidney. The U.S. EPA s IRIS database has removed both the cancer and non-cancer inhalation values for PERC from its database, and the agency has rather than attempting to develop inhalation health-based values elected to develop NESHAP MACT guidance for the dry cleaning industry. An IRIS review of PERC was begun in 1998 and is scheduled for completion in June of Despite the decision that MDH would not develop an HBV for PERC, MDH is able to provide information that may be of use when reaching risk management decisions regarding exposures to PERC. The California EPA s Office of Environmental Health Hazards Assessment developed a unit risk that predicts that an ambient concentration of PERC of 1.7 μg/m 3 would result in an increased cancer risk of 1 in 100,000. Using a slope value derived by the U.S. EPA s National Center for Environmental Assessment would indicate that chronic exposure to a level of up to 20 μg/m 3 would result in an increased cancer risk of no more than one in one hundred thousand. There is not an agency consensus as to the accuracy of the risk estimate and the IRIS database no longer contains a unit risk for PERC. Given the controversy regarding the carcinogenicity of PERC the NCEA cancer number would likely provide a conservative screening value for PERC. The New York State Department of Health has established an ambient air guideline of 100 μg/m 3 that is intended to protect against mild neurological effects that can occur with chronic exposures to PERC. ATSDR s non-cancer MRLs for PERC are 270 μg/m 3 for chronic exposures and 1350 μg/m 3 for acute exposures (ATSDR, 1997) and both are based on neurological responses. Environmental Health Division; 625 N Robert St; St. Paul, MN 55155;(651)

3 A fact sheet developed for PERC by MDH s Site Assessment and Consultation Unit in consultation with staff from Health Risk Assessment advises that 20 μg/m 3 would provide a reasonably conservative screening value for carcinogenicity and that 100 μg/m 3 would be an appropriate value for screening for non-cancer effects. MDH realizes the importance of developing health-based values for common contaminants such as PERC and will continue monitoring new information as it becomes available. For instance, the Department is in the process of obtaining and evaluating information from New York State regarding PERC s neurotoxic effects. This will no doubt prove useful when attempting to develop a non-cancer HBV for PERC. Formaldehyde. The decision not to develop a HBV for formaldehyde was based in part on the following information. In the case of formaldehyde there is no doubt as to this chemical s carcinogenicity. It has been classified as reasonably anticipated to be carcinogenic by the NTP (a nomination to reclassify formaldehyde as a known human carcinogen is currently under consideration), a probable carcinogenic by the U.S. EPA, and was recently reclassified as a known human carcinogen by IARC. The controversy surrounding the risk of exposure to formaldehyde is a question of the level of exposure necessary to present a risk to exposed populations. The chronic HRV of 0.8 μg/m 3 developed by MDH was based on the IRIS database. The U.S. EPA in their 1987 analysis used default assumptions and modeled the dose response data for formaldehyde as if there was no threshold for carcinogenicity and made no kinetic adjustments. EPA staff began a reassessment of the unit risk for formaldehyde in January of 1998 but the analysis is not scheduled to be finalized until June of Questions regarding the appropriateness of an assumption of low dose linearity for formaldehyde have been raised by a 1999 CIIT Centers for Health Research (CIIT) analysis of the very large database that has been generated for formaldehyde (CIIT 1999, Conolly et. al. 2004). CIIT scientists have suggested that there is no risk of carcinogenicity until concentrations of formaldehyde are sufficient to elicit cellular damage (around 600 μg/m 3 ). There has been a good deal of discussion regarding the merits of the CIIT model, but it has been used to develop a Tolerable Concentration (TC) of 120 μg/m 3 formaldehyde for ambient air in Canada (CEPA. 1999) and by the U.S. EPA s Office of Air and Radiation (OAR) in development of a proposed NESHAP for plywood and composite wood products (Federal Register, 2003). In a second situation the OAR, when developing a proposed NESHAP for stationary combustion turbines, elected not to use the IRIS value (Federal Register, 2004). The office instead chose to use a value developed by the U.S. EPA s Office of Air Quality Planning and Standards (OAQPS) using the CIIT model and risk assessment. The unit risk developed by the OAQPS is 5.5 x 10-9 (μg/m 3 ) -1 which, at an additional lifetime risk of 1 in 100,000, results in an air concentration of 1,830 μg/m 3. The OAR offered the following explanation for this decision. For formaldehyde we do not use the dose-response value reported in IRIS. The dose response value in IRIS is based on a 1987 study, and no longer represents the best available science in the peer-reviewed literature. Since that time, significant new data and analysis have become available. We based the dose-response value we used for formaldehyde on work conducted by the CIIT Centers for Health Research (CIIT). In 1999, the CIIT published a risk assessment which incorporated mechanistic and dosimetric information on Environmental Health Division; 625 N Robert St; St. Paul, MN 55155;(651)

4 formaldehyde that had been accumulated over the past decade. The risk assessment analyzed carcinogenic risk from inhaled formaldehyde using approaches that are consistent with EPA s draft guidelines for carcinogenic risk assessment. CIIT and the Formaldehyde Council recently petitioned the California EPA s Office of Environmental Health Hazard Assessment (OEHHA) to reassess the unit risk they developed in 1991 for formaldehyde using the CIIT model. The OEHHA s Scientific Review Panel reviewed the petition in the spring of 2004 and advised the OEHHA group to postpone a reanalysis until CIIT s model has undergone additional refinement and validation. Additional concerns were raised regarding several recently published studies that support the possibility that there is an increased risk of certain types of leukemia associated with occupational exposure to formaldehyde. Until these issues are clarified there will continue to be reluctance on the part of the public health community to change potency estimates for formaldehyde to the degree suggested by the CIIT model. OEHHA has retained their original unit risk of 6 x 10-6 (μg/m 3 ) -1. Using this value would give a value of 2μg/m 3 at an additional lifetime risk of Despite the decision that MDH would not develop an HBV that would superseded the current HRV for formaldehyde, MDH is able to provide information that may be of use when reaching risk management decisions regarding exposures to formaldehyde. Because the Cal OEHHA unit risk of 6 x 10-6 (μg/m 3 ) (2μg/m 3 at 10-5 risk) was derived using a more refined approach than the default approach used by the U.S. EPA it is a more scientifically defensible number than the IRIS unit risk. MDH recommends that risk managers consider this information when issues concerning formaldehyde arise. Cal OEHHA has also developed a chronic REL for formaldehyde of 3 μg/m 3 with airway irritation as the critical effect ATSDR s non-cancer MRL for formaldehyde is 10 μg/m 3 for chronic exposures (airway irritation) (ATSDR, 1999). The Federal Institute for Risk Assessment (BfR 2006) in Germany in a recent toxicological assessment of formaldehyde concluded that limiting air concentration of formaldehyde to less than 125 μg/m 3 would protect against carcinogenic effects in the population. Given the new information that has become available since the development of the IRIS unit risk and subsequent promulgation of MDH s HRV of 0.8 μg/m 3 for formaldehyde, it is apparent that that these numbers are overprotective. The range of values developed by other governmental agencies is an indication of the uncertainty inherent in the available data, but when these data are considered in total it is apparent that exposures to formaldehyde in the range of 2-10 μg/m 3 are not likely to result in impacts on public health. References Cited ATSDR (1997). Toxicological Profile for Tetrachloroethylene, U.S. Department of Health and Human Services. Environmental Health Division; 625 N Robert St; St. Paul, MN 55155;(651)

5 ATSDR (1999). Toxicological Profile for Formaldehyde, U.S. Department of Health and Human services. BfR (2006). Toxicological Assessment of Formaldehyde: opinion of BfR No. 023/2006. ( CEPA (1993). Priority Substances List Assessment Report for tetrachloroethylene ( index_e.html) CEPA (1999). Priority Substances List Assessment Report for Formaldehyde ( CIIT (1999). Formaldehyde: hazard characterization and dose-response assessment for carcinogenicity by the route of inhalation. Conolly, R.B., Kimbrell, J.S., Janszen, D., Schlosser, P.M., Kalisak, D., Preston, J. and Miller, F.J. Human respiratory tract cancer risks of inhaled formaldehyde: dose-response predictions derived from biologically-motivated computational modeling of a combined rodent and human dataset. Tox. Sci. 82: Federal Register (2003) 68(6): , NESHAP for Plywood and Composite Wood Priducts. Federal Register (2004) 69(7): , NESHAP for Stationary Combustion Turbines. Mundt, K.A., Birk, T. and Burch, M.T. (2003). Critical review of the epidemiological literature on occupational exposure to perchloroethylene and cancer, Int. Arch. Occup. Environ. Health, 76: U.S. EPA (1991). Science advisory board s review of the Office of Research and Development draft document: response to issues and data submissions on the carcinogenicity of tetrachloroethylene (perchloroethylene) (February 1991). EPA-SAB-EHC WHO (2000). Air Quality Guidelines, Chapter 5.13 Tetrachloroethylene. Environmental Health Division; 625 N Robert St; St. Paul, MN 55155;(651)