Estimating Human Equivalent No Observed Adverse Effect Levels for VOCs (Volatile Organic Compounds) Based on Minimal Knowledge of Physiological Parameters

摘要

The U.S. EPA advocates the assessment of health effects data and calculation of 'inhaled reference doses' as benchmark values for gauging systemic toxicity to inhaled gases. The assessment often requires an inter- or intra-species dose extrapolation from 'no observed adverse effect level' (NOAEL) exposure concentrations in animals to human equivalent NOAEL exposure concentrations. To achieve this, a dosimetric extrapolation procedure has been developed based on the form or type of equations that describe the uptake and disposition of inhaled volatile organic compounds (VOCs) in physiologically-based pharmacokinetic (PB-PK) models. The procedure assumes allometric scaling of most physiological parameters and that the value of the time integrated human arterial blood concentration must be limited to no more than to that of experimental animals. The scaling assumption replaces the need for most parameter values and allows the derivation of a simple formula for dose extrapolation of VOCs that gives equivalent or more conservative exposure concentrations values than those that would be obtained using a PB-PK model in which scaling was assumed.