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

CanTox, Inc, Mississauga, Ontario, Canada

Douglas W. Bryant

CanTox, Inc, Mississauga, Ontario, Canada

Graham J. Hook

CanTox, Inc, Mississauga, Ontario, Canada

Earle R. Nestmann

CanTox, Inc, Mississauga, Ontario, Canada

Ian C. Munro

CanTox, Inc, Mississauga, Ontario, Canada

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.

Key Words: carcinogenicity • chlorohydrin • 3-chloro-1,2-propanediol • genotoxicity • hormonal induction • Leydig cell

International Journal of Toxicology, Vol. 17, No. 1, 47-76 (1998)
DOI: 10.1080/109158198226756


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