Summary of Observations Bearing on Exposures to Diazinon/Diazoxon (DZS/DZO) and Chlorpyrifos/ Chlorpyrifos Oxon (CPS/CPO).
There are significant genetic and developmental differences in individual sensitivities to OP exposure. Newborns have low PON1 levels which contribute to their increased sensitivity to exposure.
Within populations of adults, there is significant variability in PON1 levels (~15 fold) which based on animal model studies, indicate a significant variability in sensitivity to OP exposure.
The genetic and developmental variability of PON1 are primarily reflected in sensitivity to the oxon contents of the exposure that have not been considered in product safety studies.
Sensitivity to CPS/CPO exposures is governed not only by variability in PON1 levels but also by the PON1-192 Q/R polymorphism with the PON1-R192 alloform protecting better than the PON1-Q192 alloform against exposure.
Catalytic efficiency of hydrolysis (oxon inactivation) is the key for determining whether PON1 can protect against a given OP compound.
Exposure to the parent compounds can inhibit cytochrome P450 3A4, an enzyme that is very important in hormone metabolism.