Mutagenicity of N-acetyl and N,N′-diacetyl derivatives of 3 aromatic amines used as epoxy-resin hardeners

Toray Research Center Inc., 3-2-1 Sonoyama, Otsu 520, Japan
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis (Impact Factor: 3.68). 05/1985; 143(1-2):11-5. DOI: 10.1016/0165-7992(85)90097-1
Source: PubMed


3 epoxy-resin hardeners, 4,4'-diaminodiphenyl ether (DDE), 4,4'-diaminodiphenylmethane (DDM), and 4,4'-diaminodiphenylsulfone (DDS), and their N-acetyl and N,N'-diacetyl derivatives were examined for their mutagenicity using Salmonella typhimurium TA98 and TA100 as the tester stains and an S9 mix containing a rat-liver 9000 X g supernatant fraction as the metabolic activation system. DDE and DDM were mutagenic towards TA98 and TA100 in the presence of S9 mix while DDS exhibited no significant mutagenic activity towards these tester strains. These epoxy-resin hardeners were metabolized in vivo and their N-acetyl and N,N'-diacetyl metabolites were found in the urine. Among these acetyl metabolites, only N-acetyl-DDE was found to be mutagenic towards TA98 and TA100 in the presence of S9 mix. None of these acetyl metabolites exhibited significant mutagenic activity towards these tester strains in the absence of S9 mix.

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    • "Although a primary investigation on in-vivo mutagenicity of 4,4 0 -diaminodiphenyl ether and its N-acetyl derivative towards Salmonella typhimurium TA98 and TA100 was reported in 1985 by Tanaka et al. [12], there is no reports on further investigations of biological properties of 4,4 0 -diaminodiphenyl ether and its derivatives . Moreover, no data are available to assess the mutagenicity or teratogenicity of any derivative of 4,4 0 -diaminodiphenyl ether to human. "
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    European Journal of Medicinal Chemistry 01/2014; 74C:552-561. DOI:10.1016/j.ejmech.2013.12.035 · 3.45 Impact Factor
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    • "N-acetyl-MDA is a major metabolite in urine samples of workers exposed to MDA (Robert et al., 1995; Schutze et al., 1995) or to MDI (Sepai et al., 1995; Dalene et al., 1996). Both the N-acetyl and the N,N'diacetyl-MDA metabolites have been identified in urine following administration of MDA (Tanaka et al., 1985) or MDI (Gledhill et al., 2005) to rats. Whereas N-acetyl-MDA represents more than half of all MDA metabolites in human urine in MDA-exposed workers, the N,N'diacetyl-MDA metabolite represents less than 3%. "
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