Département de santé environnementale et santé au travail, Faculté de médecine, Université de Montréal, Montréal, Québec, Canada.
SAR QSAR Environ Res. 2010 Oct;21(7-8):583-601. doi: 10.1080/1062936X.2010.528241.
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) = 10(((-0.45 x log K(oa)) + 3.65)); n = 21, r²= 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) = 10 (((-1.16 x log K(ow)) + 3.65)); n = 27, r²= 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.
蒸气危害比（VHR）用于溶剂替代，以选择有关溶剂过度暴露潜力的最佳替代选项。然而，VHR 计算受到职业暴露限值（OEL）的可用性限制。本研究的总体目标是开发定量性质-性质关系（QPPR）方法来计算 OEL，以支持为没有 OEL 的溶剂推导 VHR。使用美国政府工业卫生学家会议（ACGIH）公布的具有基于健康的时间加权平均值（TWA）OEL 的 88 种溶剂的数据库，开发了用于估算 OEL 的 QPPR。选择了三种生物脂质的替代物：正辛醇与空气的分配系数 [n-辛醇：空气（K（oa））、橄榄油与空气的分配系数（K（oila））和脂肪与空气的分配系数（K（fa））]，用于评估具有局部作用方式的溶剂的 OEL 的描述性/预测性关系。对于具有全身作用方式的溶剂，需要考虑毒代动力学（即动力学变异性因子，KVF）和毒理学效力（即有效内部浓度，EIC）的定量差异来预测 OEL。正辛醇与水的分配系数（K（ow））、油与水的分配系数（K（oilw））和脂肪与水的分配系数（K（fw））被选择来评估与 EIC 的关系。对于局部作用方式，K（oa）是 OEL 的最准确预测因子[OEL（ppm）=10^（（（-0.45 x log K（oa））+3.65））；n=21，r²=0.71，PRESS/SSY=0.36，F=45.5，p<0.001]，推荐值与预测值的 OEL 平均值（±SD）（范围）为 1.04±0.61（0.2-2.5）。对于全身作用方式，KVF 和 EIC 的范围分别为 0.73-41.4 µmol L⁻¹和 1.20-848 µmol L⁻¹。K（ow）是计算 EIC 的准确预测因子[EIC（µmol L⁻¹）=10^（（（-1.16 x log K（ow））+3.65））；n=27，r²=0.88，PRESS/SSY=0.12，F=181，p<0.001]，并且预测的 OEL 值中有 50%在推荐的 TWA OEL 的两倍以内。总体而言，预测的 VHR 有 61%和 87%分别在计算的 VHR 的两倍和五倍以内。本研究开发的 QPPR 模型代表了用于估算缺乏此类指导值的溶剂的临时 OEL 的潜在有用工具。这些临时 OEL 仅用于支持 VHR 的初步估算，以应对溶剂替代的挑战，其中相对值而不是 OEL 和蒸气压的绝对值指导卫生保健人员在管理职业健康危害方面做出务实的决策。
