Acrylamide is an industrial chemical used mainly in the production of polyacrylamides. Acrylamide and polyacrylamides have many uses, including uses as flocculants and flow control agent for enhancing oil production from wells, in the production of dyes, organic chemicals, contact lenses, cosmetics and toiletries, in sugar refining, and as a chemical grouting agent and soil stabilizer. Acrylamide is also commonly present in fried foods and the primary route of human exposure in the general population is diet. In their most recent risk assessment for acrylamide, USEPA developed an oral cancer slope factor (OSF) of 0.5 (mg/kg-day)-1 based on a 2-year drinking water study that reported increased incidences of thyroid tumors and tunica vaginalis mesotheliomas (TVMs) in male F344 rats. However, there is considerable evidence that F344 rats are particularly susceptible to TVMs, and therefore TVMs may not be relevant to humans. As such, our objective was to evaluate the overall weight of the evidence regarding each tumor type and to derive an OSF for acrylamide based on those tumors relevant to humans. Among the tumors induced by acrylamide (thyroid tumors, TVMs, mammary gland tumors, CNS tumors), thyroid and mammary gland tumors were considered most relevant to humans. Using the rat OSF for the combined increased incidences of thyroid and mammary gland tumors observed in female F344 rats, we derived a human OSF using a rat-to-human dose metric conversion factor based on serum levels of the primary acrylamide metabolite, glycidamide (widely considered to be the putative proximal carcinogen). The final human OSF for combined thyroid and mammary gland tumors was determined to be 0.09 (mg/kg-day)-1. This OSF suggests a lower cancer potency for acrylamide based on target tissues more relevant to humans. It should be noted however, the FDA and NTP just completed a 2-year, multi-species drinking bioassay and the results of this study may impact future OSF estimates for acrylamide.