Quantitative property–property relationships for computing Occupational Exposure Limits and Vapour Hazard Ratios of organic solvents

Abstract

Vapour Hazard Ratio (VHR) is used in solvent substitution to select the best replacement option regarding overexposure potential of solvents. However, VHR calculations are limited by the availability of Occupational Exposure Limits (OELs). The overall objective of this study was to develop quantitative property–property relationship (QPPR) approaches for computing OELs, in view of supporting the derivation of VHRs for solvents without OELs. QPPRs were developed for estimating OELs using a database of 88 solvents which have health-based Time-Weighted Average (TWA) OELs published by the American Conference of Governmental Industrial Hygienists (ACGIH). Three surrogates of biotic lipid : air partition coefficients [n-octanol : air (K_oa ), olive oil : air (K_oila ) and fat : air (K_fa )] were selected for evaluating the descriptive/predictive relationship with OELs for solvents with local modes of action. For solvents with systemic modes of action, the prediction of OEL needs to consider quantitative differences in toxicokinetics (i.e. kinetic variability factor, KVF) and toxicological potency (i.e. effective internal concentration, EIC). The n-octanol : water (K_ow ), the oil : water (K_oilw ) and the fat : water (K_fw ) partition coefficients were selected for evaluating the relationship with EICs. For local modes of action, K_oa is the most accurate predictor of OELs [OEL (ppm) = ; n = 21, r ²= 0.71, PRESS/SSY = 0.36, F = 45.5 with p < 0.001] and the mean (±SD) (range) of the recommended to predicted OELs was 1.04 ± 0.61 (0.2–2.5). For systemic modes of action, KVFs and EICs vary in a range from 0.73 to 41.4 µmol L⁻¹ and 1.20–848 µmol L⁻¹, respectively. K_ow is an accurate predictor of calculated EICs [EIC (µmol L⁻¹) = ; n = 27, r ²= 0.88, PRESS/SSY = 0.12, F = 181 with p < 0.001] and 50% of the predicted OEL values were within a factor of two of the recommended TWA OELs. Overall, 61% and 87% of the predicted VHRs were within a factor of two and five, respectively, of the calculated VHRs. The QPPR models developed in this study represent potentially useful tools for estimating provisional OELs for solvents lacking such guideline values. These provisional OELs are developed only to support initial estimations of VHR for dealing with the challenge of solvent substitution where relative values rather than absolute values of OEL and vapour pressure guide the hygienist in making pragmatic decisions for managing occupational health hazards.

Keywords:

• QPPR
• partition coefficients
• OEL
• VHR
• solvents
• substitution

Acknowledgements

This work was supported by grants from AFSSET and NSERC (operating).