On 24 November 2004 EPA changed the
cancer classification of
captan from a 'probable human
carcinogen' (Category B2) to 'not likely' when used according to label directions. The new
cancer classification considers
captan to be a potential
carcinogen at prolonged high doses that cause cytotoxicity and regenerative cell
hyperplasia. These high doses of
captan are many orders of magnitude above those likely to be consumed in the diet, or encountered by individuals in occupational or residential settings. This revised
cancer classification reflects EPA's implementation of their new
cancer guidelines. The procedures involved in the reclassification effort were agreed upon with EPA and involved an Independent Transparent Review as it related to four components that formed the basis of the original 1986 B2 classification: mouse
tumors; rat
tumors; mutagenicity; and structural similarity to other
carcinogens. A Peer Review Panel organized and administered by Toxicology Excellence for Risk Assessment (TERA) met on 2-3 September 2003. The Panel concluded that
captan acted through a non-mutagenic threshold mode of action that required prolonged irritation of the duodenal villi as the initial key event. EPA's
Cancer Assessment Review Committee (CARC) met on 9 June 2004 and endorsed the Peer Review findings. EPA intended to have the FIFRA Scientific Advisory Panel (SAP) consider the basis for this reclassification but found the science was robust and judged that a SAP review was not warranted. Using the revised classification, the margin of exposure is approximately 1,200,000, supporting the 'not likely' characterization.