Toxicology and Applied Pharmacology 1987-10-01

Chemical reactivity, cytotoxicity, and mutagenicity of chloropropanones.

B A Merrick, C L Smallwood, J R Meier, D L McKean, W H Kaylor, L W Condie, B.Alex Merrick, Carolyn L. Smallwood, John R. Meier, Deborah L. McKean, William H. Kaylor, Lyman W. Condie

Index: Toxicol. Appl. Pharmacol. 91(1) , 46-54, (1987)

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Abstract

Studies were conducted to assess the in vitro toxicity of three chloropropanones: monochloropropanone (MCP), 1,1-dichloropropanone (1,1-DCP), and 1,3-dichloropropanone (1,3-DCP). Chloropropanones reacted directly with reduced glutathione (GSH) in sodium phosphate buffer at pH 7.4. All chloropropanones were cytotoxic to suspensions of male rat hepatocytes in a concentration range of 0.5-10 mM. Cytotoxicity was preceded by rapid decline in cellular GSH levels. Mutagenic potencies among the chloropropanones in Salmonella typhimurium bacteria differed greatly. 1,3-DCP was mutagenic in the nanomole range, 1,1-DCP was weakly mutagenic in the micromole range, and MCP was not mutagenic. Mutagenicity of the dichloropropanones was evident without metabolic activation. These results suggest that the three chloropropanones may, in part, be directly cytotoxic but only 1,3-DCP and 1,1-DCP are directly mutagenic.