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首页> 外文期刊>Risk analysis >Duration Adjustment of Acute Exposure Guideline Level Values for Trichloroethylene Using a Physiologically-Based Pharmacokinetic Model
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Duration Adjustment of Acute Exposure Guideline Level Values for Trichloroethylene Using a Physiologically-Based Pharmacokinetic Model

机译：使用基于生理学的药代动力学模型调整三氯乙烯急性暴露指导水平值的持续时间

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Acute Exposure Guideline Level (AEGL) recommendations are developed for 10-minute, 30-minute, 1-hour, 4-hours, and 8-hours exposure durations and are designated for three levels of severity: AEGL-1 represents concentrations above which acute exposures may cause noticeable discomfort including irritation; AEGL-2 represents concentrations above which acute exposure may cause irreversible health effects or impaired ability to escape; and AEGL-3 represents concentrations above which exposure may cause life-threatening health effects or death. The default procedure for setting AEGL values across durations when applicable data are unavailable involves estimation based on Haber's rule, which has an underlying assumption that cumulative exposure is the determinant of toxicity. For acute exposure to trichloroethy-lene (TCE), however, experimental data indicate that momentary tissue concentration, and not the cumulative amount of exposure, is important. We employed an alternative approach to duration adjustments in which a physiologically-based pharmacokinetic (PBPK) model was used to predict the arterial blood concentrations [TCE_a] associated with adverse outcomes appropriate for AEGL-1, -2, or -3-level effects. The PBPK model was then used to estimate the atmospheric concentration that produces equivalent [TCE_a] at each of the AEGL-specific exposure durations. This approach yielded [TCE_a] values of 4.89 mg/l for AEGL-1, 18.7 mg/l for AEGL-2, and 310 mg/l for AEGL-3. Duration adjustments based on equivalent target tissue doses should provide similar degrees of toxicity protection at different exposure durations.
机译：急性暴露指导水平（AEGL）建议针对10分钟，30分钟，1小时，4小时和8小时的暴露持续时间制定，并指定了三种严重程度：AEGL-1代表高于此浓度的急性浓度暴露可能引起明显的不适，包括刺激； AEGL-2表示高于该浓度的急性暴露可能会导致不可逆的健康影响或逃逸能力受损； AEGL-3表示高于该浓度可能会危及生命的健康影响或死亡。在没有可用数据时，跨持续时间设置AEGL值的默认过程包括基于Haber规则的估算，该规则有一个基本假设，即累积暴露量是毒性的决定因素。然而，对于急性暴露于三氯乙烯-lene（TCE），实验数据表明瞬时组织浓度而不是累积暴露量很重要。我们采用了一种持续时间调整的替代方法，其中使用基于生理的药代动力学（PBPK）模型来预测与适合AEGL-1，-2或-3-级影响的不良预后相关的动脉血浓度[TCE_a]。然后，使用PBPK模型估算在每个AEGL特定暴露持续时间下产生等效[TCE_a]的大气浓度。该方法的[TCE_a]值对于AEGL-1为4.89 mg / l，对于AEGL-2为18.7 mg / l，对于AEGL-3为310 mg / l。基于等效目标组织剂量的持续时间调整应在不同的暴露持续时间提供相似程度的毒性保护。

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