Advisory on EPA’s assessments of carcinogenic effects of organic and inorganic arsenic: A report of the US EPA Science Advisory Board
HERO ID
736138
Reference Type
Technical Report
Year
2007
Language
English
| HERO ID | 736138 |
|---|---|
| Year | 2007 |
| Title | Advisory on EPA’s assessments of carcinogenic effects of organic and inorganic arsenic: A report of the US EPA Science Advisory Board |
| Authoring Organization | Science Advisory Board |
| Publisher Text | U.S. Environmental Protection Agency |
| City | Washington, D.C. |
| Abstract | The U. S. Environmental Protection Agency’s (EPA) Office of Pesticide Programs (OPP), Office of Water (OW), and Office of Research and Development (ORD) coordinated the development of two scientific documents that address the carcinogenicity of Dimethylarsinic Acid (DMAV) and inorganic arsenic (iAs). In response to an Agency request, the Science Advisory Board (SAB) convened an expert panel to review and comment on key scientific issues presented in these two documents, including: (a) the metabolism and toxic responses of arsenic species; (b) mode(s) of carcinogenic action; (c) data selection for dose-response assessment; and (d) approaches and methods for low-dose extrapolation for DMAV and iAs. The SAB Panel supported the Agency’s conclusion that on the basis of available data, human exposure to DMAV appears to result in a narrower spectrum of active metabolites than those expected in the metabolic profile associated with exposure to iAs. Therefore, the Panel agreed with EPA that, in the absence of human data on DMAV, the bladder tumor data from DMAV rat bioassays is better suited for DMAV cancer risk assessment than is epidemiology data from iAs exposure. The Panel, however, noted that there remain significant uncertainties associated with the use of animal data for DMAV cancer risk assessment due to the observed metabolic differences between rats and humans. The Panel agreed with the Agency’s conclusion that DMAV-induced bladder cancer in rats, at high dose, is mediated by a cytotoxic mode of action, and that this MOA should be considered relevant to humans. However, the Panel concluded there are not sufficient data to support a reactive oxygenated species-mediated mode of direct genetic action for DMAV. The Panel supported the nonlinear approach for low dose extrapolation of DMAV and the use of uncertainty factors to account for interspecies differences and human variability for sensitive human populations, and concluded that presently there is no arsenic-specific information that can inform the choice of specific values. This means that, at least for now, such choices must be based on more general considerations, including EPA’s science policy judgment of the degree of precaution that it deems appropriate. EPA concluded that the mechanisms by which inorganic arsenic induces bladder cancer in humans are not yet known, but they are likely to be mediated by multiple modes of action. The Agency used a linear default approach for low dose extrapolation because it lacked a full understanding of the iAs modes of carcinogenic action. The Panel agreed that available human and animal data do not fully describe the shape of the iAs carcinogenic dose-response curve at low doses. Given the considerable uncertainties regarding low dose extrapolation, the Panel supported the use of a linear cancer risk model for iAs as recommended by the National Research Council in its 2001 report. The Panel also supported the use of the epidemiologic data on the Taiwanese population for estimating human cancer risk for iAs especially to identify the potential range of responses of human populations. However, the Panel recognized limitations to these data, and that there is some evidence on iAs from animal toxicology, pharmacokinetics, and pharmacodynamics research, that suggests other than a linear bladder cancer dose-response. The Panel urged the Agency to consider other epidemiologic studies from the U.S. and other countries, utilizing a uniformset of evaluative criteria. The Panel also recommended sensitivity analyses be conducted to account for human variability in drinking water consumption rates, dietary intake of iAs from food, and certain other assumptions currently used in EPA’s assessment. The Panel made several suggestions for improvements in the currently applied risk model’s programming and documentation conventions. Finally, the Panel believes there is a critical need for a continued research effort to strengthen EPA’s cancer risk assessment for DMAV and iAs. The scientific bases for the Panel’s conclusions and research recommendations are detailed throughout this report. |
| Report Number | EPA-SAB-07-008 |
| Url | http://cfpub.epa.gov/ncea/iris_drafts/recordisplay.cfm?deid=219111 |
| Is Certified Translation | No |
| Dupe Override | No |
| Number Of Pages | 88 |
| Is Public | Yes |
| Language Text | English |
| Is Qa | No |
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