Methylenedioxyphenyl insecticide synergists as potential human health hazards

Abstract

The effects of methylenedioxyphenyl insecticide synergists on human health arise, not from their intrinsic toxicity which is relatively low, but from their dual effect on the oxidative detoxication or intoxication processes of the body. They are able to inhibit these reactions by two mechanisms. They are substrates for mixed function oxidation and, thus, compete with other xenobiotics for available enzyme, and an intermediate in their metabolism is able to bind with cytochrome P 450 to form an inactive complex which absorbs maximally at 455 nm. In addition, they are able to activate xenobiotic metabolism by induction (the increased synthesis and retention) of microsomal oxidative enzymes. Evidence for these effects is presented, including spectroscopic and enzyme kinetic data. Correlations with existing in vivo observations are outlined. The inhibition and induction of cytochrome P 450, the central enzyme in the metabolism of xenobiotics, thus provides the focus for consideration of methylenedioxyphenyl synergists as potential hazards.