Concentration-Time Relationships for Short-Term Inhalation Exposures to Hazardous Substances Open Access
Manimaran, Rajkumar (2013)
Abstract
Acute Exposure Guideline Levels (AEGLs) are developed by the
USEPA AEGL committee to reduce the risk of acute exposures to
airborne hazards. AEGLs are the threshold limits for
once-in-a-lifetime or rare chemical exposures at five exposure
durations (1/6, 1/2, 1, 4, 8h), across the three-health effect
severity tiers (AEGL-1: mild, AEGL-2: disabling, and AEGL-3:
life-threatening). They are derived from various published and
unpublished experimental studies described in the Technical Support
Documents prepared by the committee. An AEGL concentration
(C) for duration (t) is extrapolated from available
experimental data. The extrapolation is carried out using the
Haber-ten Berge exponential function, Cn *
t = k, where n, the temporal scaling factor
(TSF), is chemical-specific. Preferably, TSF is derived
experimentally, but so far only for a small number of chemicals the
experimental TSFs have been derived. For most of 272 chemicals on
the AEGL list, TSFs are unknown. For them, the AEGL committee
carried out temporal extrapolation using expert-panel judgment.
Thus, the AEGL database contains rich expert-validated
chemical-specific information about temporal extrapolation.
The objective of the present study was to extract this
information by four different approaches, analyze it, and derive
statistically-justified guidelines for TSFs for chemicals without
experimentally-derived TSFs. The AEGL values (concentrations) were
log-transformed and regressed against the logarithm of time using
SAS. TSFs were derived from regression slopes. For each chemical in
the database, up to three TSFs were derived across the three AEGL
health effect severity tiers.
TSFs derived using Approach 4 for chemicals, whose all AEGL
values within a tier are different, were in agreement with AEGL
Committee's empirically derived n-values and also with most
of empirically derived n-values known from the literature.
The range and mean of n-values derived in Approach 4 were in
agreement with the range and mean of n-values published in
the literature. Because the 95th percentile on
n-values could not be reliably estimated from small datasets
available in the past, the 90th percentile has been
introduced in public health practice.
A dataset analyzed in the present study is sufficiently large
for reliable estimation of 95th and even 99th
percentiles. Applying Approach 4 to these data, the 95th
percentile for n-values was derived, which was estimated as
n = 3.5 (95% CI: 2.8-4.4). Based on AEGL Committee practice
of using uniform threshold concentrations across all durations in
the AEGL-1 tier (i.e. using Approach 1), an n-value that
maybe appropriate for this tier was estimated as 6.87 (95% CI:
6.45-7.35).
Thus, using an n-value of 3.5, a more health-protective
scientifically-justified health guidance for acute severe airborne
hazards can be implemented and for less-severe AEGL-1 hazards,
however, even a higher TSF may be appropriate.
Table of Contents
TABLE OF CONTENTS
I.
INTRODUCTION------------------------------------------1
i. Temporal Scaling Factor
(TSF)--------------------------4
ii. Temporal extrapolation by AEGL
committee-----------8
II. MATERIALS AND
METHODS---------------------------13
i. Database
development---------------------------------13
ii. Methods of
analysis------------------------------------13
III.
RESULTS----------------------------------------------16
i. Approach
1----------------------------------------------16
ii. Approach
2---------------------------------------------17
iii. Approach
3---------------------------------------------18
iv. Approach
4---------------------------------------------19
IV.
DISCUSSION------------------------------------------20
V. CONCLUSIONS/
RECOMMENDATIONS----------------22
VI.
REFERENCES------------------------------------------24
VII. TABLES /
FIGURES-----------------------------------26
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