Exposure limits for unconventional shifts: toxicokinetic and toxicodynamic considerations

Adjustment factors (AF) for inhalation exposure to chemical agents during unconventional work schedules were derived on toxicokinetic bases. AFs depend on the half-life of the agent and on the work schedule. Because they are grossly affected by cumulation, AFs were calculated for steady-state conditions. They were based on the following measures of chemical body burden: (1) end-of-shift biological level as used previously by other investigators; and (2) areas under the curves, AUCexp, AUCday, and AUCweek, which correlate with average biological levels during the shift, work day, and work week, respectively. The dependence of AFs on the half-life was studied on 50 possible work schedules using agents with a half-life of 1 hr to 2 years. Based on the data, simple equations suitable for field conditions were derived for determination of AFs. Since AFs based on individual measures of body burden are not the same, the pharmacodynamics of the toxic endpoint should be considered when selecting the measure of body burden and the half-life for AF determination.