Concentration-Time Relationships for Short-Term Inhalation Exposures to Hazardous Substances Open Access

Manimaran, Rajkumar (2013)

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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 They are derived from various published and unpublished experimental studies described in the Technical Support Documents prepared by the committee.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


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


VI. REFERENCES------------------------------------------24

VII. TABLES / FIGURES-----------------------------------26

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