Carcinogenicity of Monochloro-1,2-Propanediol (α-Chlorohydrin, 3-MCPD)

3-Monochloro-1,2-propanediol (3-MCPD) is a by-product found in trace amounts, generally less than 1 mg/kg (<1 ppm), in hydrolyzed vegetable protein produced through acid hydrolysis. In a chronic study with F344 rats, high doses of 3-MCPD produced benign renal tumors in both sexes and Leydig-cell and mammary tumors in males. 3-MCPD is genotoxic in vitro, but there is no evidence of genotoxicity in vivo. There is some question about the mechanism responsible for the carcinogenicity of 3-MCPD in certain species. Here we present a critical review of the toxicological, metabolic, and mechanistic data on 3-MCPD. On the basis of this review, the tumors reported in F344 rats are concluded to have developed as a result of nongenotoxic mechanisms and are considered not to be relevant to humans exposed to trace amounts of 3-MCPD. This conclusion was based on the lack of carcinogenicity of 3-MCPD in mice or Sprague-Dawley rats; the benign nature of the tumors involved; the dependence of the Leydig-cell and mammary tumors on species-and strain-dependent mechanisms involving chronic changes in hormone balance; the association of the renal tumors with chronic nephropathy and nephrotoxicity; and differences between bacterial and mammalian systems in the metabolism of 3-MCPD that likely account for its genotoxic activity in certain in vitro test systems. At trace levels in foods, 3 MCPD is considered not to pose a carcinogenic risk to humans.