Toxicity testing, normal variations

Similar to 5-FU, there is a polymorphism associated with irinotecan toxicity. UDP-glucuronosyltransferase (UGT1A1) is an enzyme responsible for the glucuronidation of SN-38 to inactive metabolites, and reduced or deficient levels of this enzyme correlate with irinotecan-induced diarrhea and neutropenia.39 Recently the FDA approved a blood test that detects variations in this gene. This test will assist health care providers in predicting which patients may develop severe toxicities from normal doses of irinotecan and can be ordered prior to patients receiving irinotecan. binotecan is administered as an IV bolus over 60 to 90 minutes in a variety dosing schedules. 

Life history models may be useful for considering age- or stage-specific variability in sensitivity in the extrapolation of response however, it should not be assumed that smaller or younger stages are always the most sensitive. The few studies that have addressed the impact of time of year on responses of aquatic communities to a stressor indicate that, in freshwater communities, threshold concentrations for direct toxic effects vary within a factor of 2 among seasons — well within the normal range of variation observed in laboratory toxicity tests. However, at greater exposures, the intensity and duration of direct and indirect responses may vary considerably between different periods of the year because of the influence of climatic and seasonal factors on recovery. 

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