Technical Analysis of New Methods and Data Regarding Dichloromethane Hazard Assessments. External Review Draft

摘要

New information on cytotoxicity, genotoxicity, and epidemiology has raised some questions about the federal regulatory agencies' cancer risk assessments for dichloromethane (DCM, methylene chloride). In addition, physiologically based pharmacokinetic models have been developed, showing that tissue-level delivery of metabolically activated DCM may be disproportionately reduced at low exposure levels. These studies suggest to some that the clear carcinogenic response seen in mice under chronic high exposures does not imply substantive human risk at low doses. The Health/Risk Assessment Committee (HRAC), comprising representatives of four federal regulatory agencies, was convened to conduct joint analyses of these new data. The document reports on the HRAC's consideration of the data and the questions they raise about human cancer risk from DCM. It serves as a source of up-to-date analyses that may be drawn upon by each agency as it considers modifying its cancer risk assessment. The HRAC finds that, despite new data, the mechanism of carcinogenic action of DCM remains problematical; there is no basis at present to conclude that carcinogenic response is unique to mice or confined to high exposure levels.