Statistical analysis of concentration-time extrapolation factors for acute inhalation exposures to hazardous substances Open Access

Snyder, Jedidiah Samuel (2015)

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Background: Acute Exposure Guideline Levels (AEGLs) are exposure limits for the general public that are designed for assessing the risk of rare exposures to hazardous airborne substances. For each chemical substance, AEGLs may be developed for up to five exposure durations (10 min, 30 min, 1 hr, 4 hr, and 8 hr). It is rare to find supporting data that describe concentration thresholds for all five AEGL-specific exposure periods, and concentration-exposure duration extrapolation is often applied, by which Cn x t = k, where C is exposure concentration, n is an empirical chemical-specific "toxic load exponent," t is exposure duration, and k is toxic load.

Rational: In absence of empirical data, the AEGL Committee selects a default toxic load exponent (TLE) of 1 for short-to-long term extrapolation and 3 for long-to-short extrapolation. These upper and lower boundaries for default TLEs are associated with the work of ten Berge et al. 1986, as approximately 90% of the values of n for chemicals (N = 20) analyzed in their study ranged from 1 to 3. Because of the small sample size these defaults have poor statistical power.

Methods: In the present work, we reevaluate the numbers using more representative statistics. A thorough review of data from ten Berge et al. 1986, AEGL technical support documents and literature identified 127 unique chemical substances with empirically supported TLEs.

Results: Non-parametric estimates revealed that 90% of the chemical substances (N = 127) had designated values of n that were confined between 0.77 (95%CI: 0.66 - 0.88) and 3.62 (95%CI: 3.03 - 4.32). Notably, our interval estimation failed to include the AEGL Committee's default n value of 1 for short-to-long term extrapolation and 3 for long-to-short term extrapolation at the 95% confidence level.

Conclusion: Thus, our estimation suggests 0.75 and 3.5 as appropriate defaults for concentration-exposure duration extrapolation. Therefore, AEGLs and other inhalation health guidance values that have been derived using defaults of 1 and 3 for concentration-exposure duration extrapolation may be insufficiently protective and may need reexamination.

Table of Contents

Thesis Chapters

Chapter 1: Background and Literature Review

  • Background
  • Acute Exposure Guideline Levels
  • Development of Acute Exposure Guideline Levels
  • Concentration-Exposure Duration Relationships
  • Derivation of Toxic Load Exponents
  • Extrapolation Without Empirical Data
  • AEGL Program's Future
  • Moving Forward
  • References

Chapter 2: Manuscript (Peer Reviewed Style)

  • Title and Authors
  • Abstract
  • Introduction
  • Methods
  • Results
  • Discussion
  • Conclustion
  • References
  • Tables
  • Figures/Figure Legends

Chapter 3: Public Health Implications


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