ACUTE ACRYLONITRILE INTOXICATION--ANTIDOTAL ASSESSMENT

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Acrylonitrile is a chemical widely used in the production of synthetic fibers, plastics and rubber. Acrylonitrile is a reactive chemical with an acute lethal action in experimental animals. Deaths in humans accidentally exposed to acrylonitrile have been reported. Current industrial hygiene practices can limit the exposure of workers to acrylonitrile during normal occupational procedures. However, accidental exposures to high levels can acutely affect the health of individuals involved in the production, transportation, and end use of acrylonitrile. In the event of a large accidental release of acrylonitrile, even the health of the general populace could be affected. Acrylonitrile can be oxidatively metabolized to cyanide which is some ten times more toxic than the parent molecule on a molar basis. However, because of its high chemical reactivity with thiol groups in the body, the parent acrylonitrile molecule is also thought to be toxic. Thus acrylonitrile is a double edged sword and antidotal measures must take into account both the cyanide component and the 'other' component(s) of its toxic action. Unfortunately, the currently recommended antidotal therapy for acrylonitrile poisoning focuses solely on the management of cyanide intoxication. Our objective is to mimic an acute dermal acrylonitrile exposure and simultaneously measure three important biochemical markers associated with acrylonitrile toxicity. These markers include tissue cyanide levels, irreversible acrylonitrile binding to tissue macromolecules and tissue glutathione levels. Antidotes selected for their ability to ameliorate each of these markers of acrylonitrile toxicity will be evaluated. The significance of this work is that we hope to be able to correlate the favorable effects of the antidotes on the biochemical markers with efficacy as antidotes for acute acrylonitrile intoxication. In this way some insight into the relative importance of the various effects of acrylonitrile in the body on toxicity will be realized. In addition, we anticipate that more effective antidotes or combinations of antidotes for acute acrylonitrile intoxication will emerge from these studies.