PHYSIOLOGICAL DAMPING OF EXPOSURE VARIABILITY DURING BRIEF PERIODS

Abstract

This paper offers a theoretical framework for considering transient exposures to chemicals which are not acutely toxic. Using a first-order autoregressive model to describe short-term exposures over time in conjunction with linear toxicokinetic models of chemical disposition, distributions of body burdens are compared with those of exposure. The physiological damping of exposure variability is quantitated in terms of a transmission factor defined as the ratio of the coefficients of variation of burden and exposure, respectively, as first suggested by ROACH [ Am. ind. Hyg. Ass. J.27 , 1–12 (1966)]. Theoretical transmission factors are derived for situations representing an inhaled chemical and/or its toxic metabolite. Empirical transmission factors, based upon numerical analyses with log-normally-distributed series, are found to agree well with theoretical values. Transmission of exposure variability to the body is diminished as the biological half-times of elimination and metabolism increase and is enhanced as the autocorrelation of the series of inhaled air concentrations increases. The dependence of damping upon biological elimination provides a basis for considering short-term exposure limits. Since the theoretical model relates autocorrelation to the air-exchange rate in the breathing zone, the results also raise intriguing questions concerning the selection of appropriate intervention strategies.