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  • Title: Muscle necrosis by N-methylated p-phenylenediamines in rats: structure-activity relationships and correlation with free-radical production in vitro.
    Author: Munday R, Manns E, Fowke EA, Hoggard GK.
    Journal: Toxicology; 1989 Aug; 57(3):303-14. PubMed ID: 2756530.
    Abstract:
    Certain derivatives of p-phenylenediamine have been shown to cause necrosis of cardiac and skeletal muscle in rats; in vitro, such compounds are known to autoxidize to the corresponding radical cations, with concomitant formation of oxygen free-radicals. In the present study, the autoxidation rates of p-phenylenediamine and its N-methyl, dimethyl, trimethyl and tetramethyl derivatives have been determined and compared with the severity of the muscle necrosis induced by each of these compounds in rats. A close correlation was observed between autoxidation rate in vitro and toxicity in vivo, suggesting that free-radical species may be involved in the initiation of the muscle damage caused by these substances.
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