Use of toxicant sensitivity distributions (TSD) for development of exposure guidelines for risk to human health from benzene

Abstract

This technique for setting guideline values differs from that currently used by regulatory agencies throughout the world. Data for benzene were evaluated from epidemiological studies on human populations (29 studies). Exposure durations were evaluated in terms of Long Term Exposure (LTE) and Lifetime Exposure. All data was reported as Lowest Observed Adverse Effect Levels (LOAEL) and converted into exposure doses using Average Daily Dose (ADD) and Lifetime Average Daily Dose (LADD). These values were plotted as a Toxicant Sensitivity Distribution (TSD) which was the cumulative probability of LOAEL-ADD and LOAEL-LADD. From the TSD plots, linear regression equations gave correlation coefficients (R²) ranging from 0.69 to 0.97 indicating normal distributions. Guideline Values (GVs) for LTE (8hr/day) and Lifetime (24hr/70yrs) exposure to benzene were calculated using data from human epidemiological studies as 5% level of cumulative probability (CP) of LOAEL-ADD and LOAEL-LADD from the cumulative probability distributions (CPD). The derived guideline values from the human epidemiological studies were 92 μg/kg/day for LTE and 3.4 μg/kg/day for lifetime exposure. GV for LTE is appropriate for occupational exposure and GV derived for lifetime exposure appropriate for the general population. The guideline value for occupational exposure limit was below all the guideline values developed by regulatory agencies. But the general population guideline is within the range of values formulated by European Union, ATSDR, EPAQS, USEPA and OEHHA for air quality for the general population. This is an alternative method which eliminates the application of safety factors and other sources of errors in deriving guideline values for benzene.

Keywords: Benzene; Guideline values; Human epidemiological studies; Lifetime exposure; Long term exposure; Lowest observed adverse effects level.