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CONCENTRATION - DURATION RELATIONSHIPS FOR NON-CANCER HEALTH EFFECTS OF EXPOSURE TO HAZARDOUS AIR POLLUTANTS.
Citation:
Boyes, W K. CONCENTRATION - DURATION RELATIONSHIPS FOR NON-CANCER HEALTH EFFECTS OF EXPOSURE TO HAZARDOUS AIR POLLUTANTS. Presented at Society of Toxicology, Nashville, TN, March 17-21, 2002.
Description:
EPA is charged with assessing the risks of both acute and chronic exposures to hazardous air pollutants
(HAPs). The emissions from sources of HAPs are often characterized as temporally-averaged values,
however, patterns of exposure not captured in such measures may influence non-cancer toxicity. This
research program examined non-cancer health effects as a function of temporal exposure patterns, with
the goal of improving models to predict toxicity across exposure scenarios. Currently, temporal
adjustments in risk assessment typically are based on Haber's rule (C x t = K) or (Cn x t =K), where C
represent concentration, t time (duration) of exposure, K a constant toxic effect and n, when used, is
empirically derived. Several general conclusions were derived from this work. Concentration is more
important than time: where C and t were manipulated the influence of concentration predominated over
time in contrast to the equal influence of C and t in the linear form of Haber's rule. Target tissue dose.
Understanding the relationship between exposure and target tissue dose was better at predicting toxicity
than was Haber's rule. Target tissue sensitivity changes over time: variations in target tissue sensitivity
are not accounted for in standard C x t calculations. Interpretation of standard toxicity assays: standard
toxicity assays do not address acute exposures during critical windows of sensitivity. Quantitative
models: models with parameters reflecting physiological entities improved extrapolation across species
and age as well as exposure concentration and duration. Understanding Mechanisms: having mechanistic
information improved predictions across exposure conditions. These results demonstrate the importance
of considering temporal exposure variations when predicting the risks of adverse non-cancer health
outcomes. This abstract does not reflect EPA policy.