National Clothesline

A scientific review panel has agreed with the Environmental Protection Agency that perchloroethylene should be classified as a “likely human carcinogen,” thus setting the stage for tougher regulations of the drycleaning solvent.

EPA had proposed the new classification in 2008 as part of its draft toxicological review of the chemical. The draft review was part of EPA’s process of updating information on perc for its Integrated Risk Information System (IRIS), a database of human health effects resulting from exposure to various substances. The information is used in risk assessments, decision-making and regulatory activities to establish air and water quality standards and to set clean-up standards for hazardous waste sites.

The review of EPA’s draft by an independent group of scientists was another step in the process. The National Research Council, which spent more than 15 months reviewing EPA’s draft, agreed in general with EPA’s conclusions while taking issue with the agency concerning how those conclusions were reached, particularly in regards to assessing safe levels of exposure.

Tagging perc as a likely human carcinogen would place it in the second highest of five categories under EPA’s cancer assessment guidelines. The highest risk category is “carcinogenic to humans.” That represents an elevation of EPA’s official evaluation of perc’s cancer risk. Under previous guidelines, perc was considered in between a “possible” and “probable” cancer risk.

The review panel noted that EPA faced a “formidable challenge” in characterizing the carcinogenic properties of perc.

“There appears to be general agreement in the scientific community that tetrachloroethylene (perc) is carcinogenic in laboratory animals, but there is a long-standing debate about how to interpret and use the laboratory findings to predict human cancer risks,” the panel said.

“EPA’s decision to characterize tetrachloroethylene as likely to be a human carcinogen as opposed to ‘carcinogenic to humans’ appropriately reflects the possibility that there are deficiencies or potential inaccuracies in interpretation of the data.”

The scientific debate is reflected in the committee's examination of which possible perc-related cancers — leukemia, liver tumors, or kidney cancer — provides the strongest data for EPA to estimate its cancer potential.

The report summarized the three types of cancer as follows:

Leukemia. Two studies show an increased incidence of mononuclear cell leukemia in rats, but that was observed in a type of rat known to have a high background incidence of the disease. Also, there are differences of opinion on the relevance of rodent leukemia for predicting human cancer.

Liver cancer. While significant increases in liver tumors were observed in male and female mice after exposure to perc, that significance is debated because the strain of mouse used in the studies has a high background incidence of liver cancer. However, those findings have been reproduced by several laboratories and show a dose-dependent relationship, i.e., the tumors increased with dose.

Kidney cancer. While the increase in tumors was not statistically significant, the background incidence of kidney cancer in rats is low, making it unlikely that the increase was due to chance. Also, the tumors in exposed rates were malignant while those in the control group were not.

The review committee said that the leukemia data used by EPA to calculate risks contained uncertainties that were too great to use. Instead, committee members said EPA should use the data with the least uncertainty rather than the greatest cancer risk. That would mean using the liver cancer data first, followed by kidney cancer data, then leukemia.

Overall, the committee said it was concerned about approaches EPA used to evaluate the data on perc, and that inadequate information or rationales were used to support parts of its assessment.

It recommended that EPA use better designed studies to calculate the quantitative risks and suggested improvements for characterizing and analyzing the evidence to strengthen the scientific basis for estimating safe exposures to perc and cancer risks.

The committee also recommended that EPA give consideration to the modes of action for cancer to support its conclusions.

The committee also addressed EPA’s review of non-cancer health effects of perc exposure. These include damage to the nervous and reproductive systems, kidney and liver.

For these health effects, EPA estimated the inhalation and oral exposures allowed per day that will likely not cause harm.

For its inhalation “reference concentration” calculation, EPA selected one study that observed adverse neurotoxic effects in people who lived near drycleaning facilities. Based on this study, EPA derived a value of 2 parts per billion (ppb) per day.

The committee recommended instead that EPA use four other human studies and one animal study that it said applied stronger methods and provided more reliable findings. When these five were applied using EPA’s same estimation methods, it produced a range of daily allowable inhalation of 6 to 50 ppb.

The committee also criticized EPA for selecting studies and conclusions that appeared to be based heavily on results that showed positive associations while other data and the strength and weaknesses of the selected studies were not adequately considered.

When EPA released its draft in 2008 it was criticized by the industry for not seriously considering an epidemiology study of drycleaning workers in Nordic countries that found no evidence of an increased cancer risk related to perc exposure.

The review committee voiced similar concerns for EPA’s evaluation of the genotoxicity evidence, in which it said preference appeared to be given to studies that reported positive results. EPA did not analyze studies critically with respect to their methodological strengths and weaknesses, the committee said, nor did it organize its discussion clearly to provide an integrated consideration of the weight of evidence on the genotoxicity of perc.

With the review panel’s report in hand, EPA will complete its perc assessment for the IRIS database. That information will then inform future regulations concerning air and water quality and hazardous waste clean-ups.

The review panel, appointed by the National Academies, consisted of 20 members, primarily from universities. Copies of the review are available on the National Academies web site www.nap.edu. Search with the keyword tetrachloroethylene.



								National Clothesline




						Science panel concurs with EPA that perc is a likely human carcinogen



						A scientific review panel has agreed with the Environmental Protection Agency that perchloroethylene should be classified as a “likely human carcinogen,” thus setting the stage for tougher regulations of the drycleaning solvent. EPA had proposed the new classification in 2008 as part of its draft toxicological review of the chemical. The draft review was part of EPA’s process of updating information on perc for its Integrated Risk Information System (IRIS), a database of human health effects resulting from exposure to various substances. The information is used in risk assessments, decision-making and regulatory activities to establish air and water quality standards and to set clean-up standards for hazardous waste sites. The review of EPA’s draft by an independent group of scientists was another step in the process. The National Research Council, which spent more than 15 months reviewing EPA’s draft, agreed in general with EPA’s conclusions while taking issue with the agency concerning how those conclusions were reached, particularly in regards to assessing safe levels of exposure. Tagging perc as a likely human carcinogen would place it in the second highest of five categories under EPA’s cancer assessment guidelines. The highest risk category is “carcinogenic to humans.” That represents an elevation of EPA’s official evaluation of perc’s cancer risk. Under previous guidelines, perc was considered in between a “possible” and “probable” cancer risk. The review panel noted that EPA faced a “formidable challenge” in characterizing the carcinogenic properties of perc. “There appears to be general agreement in the scientific community that tetrachloroethylene (perc) is carcinogenic in laboratory animals, but there is a long-standing debate about how to interpret and use the laboratory findings to predict human cancer risks,” the panel said. “EPA’s decision to characterize tetrachloroethylene as likely to be a human carcinogen as opposed to ‘carcinogenic to humans’ appropriately reflects the possibility that there are deficiencies or potential inaccuracies in interpretation of the data.” The scientific debate is reflected in the committee's examination of which possible perc-related cancers — leukemia, liver tumors, or kidney cancer — provides the strongest data for EPA to estimate its cancer potential. The report summarized the three types of cancer as follows: Leukemia. Two studies show an increased incidence of mononuclear cell leukemia in rats, but that was observed in a type of rat known to have a high background incidence of the disease. Also, there are differences of opinion on the relevance of rodent leukemia for predicting human cancer. Liver cancer. While significant increases in liver tumors were observed in male and female mice after exposure to perc, that significance is debated because the strain of mouse used in the studies has a high background incidence of liver cancer. However, those findings have been reproduced by several laboratories and show a dose-dependent relationship, i.e., the tumors increased with dose. Kidney cancer. While the increase in tumors was not statistically significant, the background incidence of kidney cancer in rats is low, making it unlikely that the increase was due to chance. Also, the tumors in exposed rates were malignant while those in the control group were not. The review committee said that the leukemia data used by EPA to calculate risks contained uncertainties that were too great to use. Instead, committee members said EPA should use the data with the least uncertainty rather than the greatest cancer risk. That would mean using the liver cancer data first, followed by kidney cancer data, then leukemia. Overall, the committee said it was concerned about approaches EPA used to evaluate the data on perc, and that inadequate information or rationales were used to support parts of its assessment. It recommended that EPA use better designed studies to calculate the quantitative risks and suggested improvements for characterizing and analyzing the evidence to strengthen the scientific basis for estimating safe exposures to perc and cancer risks. The committee also recommended that EPA give consideration to the modes of action for cancer to support its conclusions. The committee also addressed EPA’s review of non-cancer health effects of perc exposure. These include damage to the nervous and reproductive systems, kidney and liver. For these health effects, EPA estimated the inhalation and oral exposures allowed per day that will likely not cause harm. For its inhalation “reference concentration” calculation, EPA selected one study that observed adverse neurotoxic effects in people who lived near drycleaning facilities. Based on this study, EPA derived a value of 2 parts per billion (ppb) per day. The committee recommended instead that EPA use four other human studies and one animal study that it said applied stronger methods and provided more reliable findings. When these five were applied using EPA’s same estimation methods, it produced a range of daily allowable inhalation of 6 to 50 ppb. The committee also criticized EPA for selecting studies and conclusions that appeared to be based heavily on results that showed positive associations while other data and the strength and weaknesses of the selected studies were not adequately considered. When EPA released its draft in 2008 it was criticized by the industry for not seriously considering an epidemiology study of drycleaning workers in Nordic countries that found no evidence of an increased cancer risk related to perc exposure. The review committee voiced similar concerns for EPA’s evaluation of the genotoxicity evidence, in which it said preference appeared to be given to studies that reported positive results. EPA did not analyze studies critically with respect to their methodological strengths and weaknesses, the committee said, nor did it organize its discussion clearly to provide an integrated consideration of the weight of evidence on the genotoxicity of perc. With the review panel’s report in hand, EPA will complete its perc assessment for the IRIS database. That information will then inform future regulations concerning air and water quality and hazardous waste clean-ups. The review panel, appointed by the National Academies, consisted of 20 members, primarily from universities. Copies of the review are available on the National Academies web site www.nap.edu. Search with the keyword tetrachloroethylene.