Abstract
Adult male Wistar rats administered i.p. with 2-chlorobenzylidene malononitrile (CS) excreted one mercapturic acid in urine. The amount of mercapturic acid determined gaschromatographically was about 4% of the dose (0.07 mmol/kg,n = 12). The structure of the mercapturic acid methylester was identified by t.l.c. and confirmed by synthesis and mass-spectrography. The acid appeared to be 2-chlorobenzylmercapturic acid [N-acetyl-S-(2-chlorobenzyl)-l-cysteine].
CS and some of its metabolites were also tested in the Ames Salmonella/ microsome assay. Both mutagenic and toxic effects were measured with strain TA 100 as the indicator organism. No mutagenic effects were found with any of the tested substances. At dosages of CS, higher than 1,000 μg/ plate a bacteriotoxicity was revealed.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Ames BN, McCann J, Yamasaki E (1975) Methods for detecting carcinogens and mutagens with the Salmonella/mamalianmicrosome mutagenicity test. Mutat Res 31:347–364
Beswick FW, Holland P, Kemp KH (1972) Acute effects of exposure to ortho-chlorobenzylidene malononitrile (CS) and the development of tolerance. Br J Ind Med 29:298–306
Boyland E, Chasseaud LF (1967) Enzyme catalysed conjugation of glutathione with unsaturated compounds. Biochem J 104:95–102
Clapp JJ, Young L (1970) Formation of mercapturic acids in rats after administration of aralkyl esters. Biochem J 118:765–771
Corson BB, Stoughton RW (1928) Reactions of alpha, beta-unsaturated dinitriles. JACS 50:2825–2837
Cucinell SA, Swentzel KC, Biskup R, Snodgrass H, Lovre S, Stark W, Feinsilver L, Vocci F (1971) Biochemical interactions and metabolic fate of riot control agents. Fed Proc 30:86–91
Holland P, White RG (1972) The cutaneous reactions produced by o-chlorobenzylidene malononitrile and w-chloroacetophenone when applied directly to the skin of human subjects. Br J Dermatol 86:150–154
Jones GRN (1972) CS and its chemical relatives. Nature 235:257–261
Knight RH, Young L (1958) Biomedical studies of toxic agents II. The occurence of premercapturic acids. Biochemic J 70:111–119
Leadbeater L (1973) The absorption of ortho-chlorobenzylidene malononitrile (CS) by the respiratory tract. Toxicol Appl Pharmacol 25:101–110
Marrs TC, Colgrave HF, Cross NL, Gazzard MF, Brown RFR (1983) A repeated dose study of the toxicity of inhaled 2-chlorobenzylidene malononitrile (CS) aerosol in three species of laboratory animal. Arch Toxicol 52:183–198
Patai S, Rappoport Z (1962) Nucleophilic attacks on carbon-carbon double bonds. Part II. Cleavage of arylmethylenemalononitriles by water in 95% ethanol. J Chem Soc 383–392
Rietveld EC, Plate R, Seutter-Berlage F (1983) Mechanism of formation of mercapturic acids from aromatic aldehydes in vivo. Arch Toxicol 52:199–207
Seutter-Berlage F, Rietveld EC, Plate R, Klippert PJM (1982) Mercapturic acids as metabolites of aromatic aldehydes and alcohols. In: Snyder R, Parke DV, Kocsis J, Jollow DJ, Gibson GG (eds) Biological reactive intermediates IIA: Chemical mechanisms and biological effects. Plenum Publ. Corp., New York, pp 359–368
Shmunes E, Taylor JS (1973) Industrial contact dermatitis. Effect of the riot control agent ortho-chlorobenzylidene malononitrile. Arch Dermatol 107:212–216
Von Däniken A, Friederich U, Lutz WK, Schlatter C (1981) Tests for mutagenicity in salmonella and covalent binding to DNA and proteine in the rat of the riot control agent o-chlorobenzylidene malononitrile (CS). Arch Toxicol 49:15–27
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Rietveld, E.C., Delbressine, L.P.C., Waegemaekers, T.H.J.M. et al. 2-Chlorobenzylmercapturic acid, a metabolite of the riot control agent 2-chlorobenzylidene malononitrile (CS) in the rat. Arch Toxicol 54, 139–144 (1983). https://doi.org/10.1007/BF01261382
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF01261382