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使用 [C]-莠去津通过大鼠、野鸭和北美野鹌鹑全层皮肤的体外经皮吸收,推导禽类皮肤 LD50 值用于皮肤暴露模型。

Derivation of avian dermal LD50 values for dermal exposure models using in vitro percutaneous absorption of [C]-atrazine through rat, mallard, and northern bobwhite full thickness skin.

机构信息

Syngenta Crop Protection, Greensboro, NC, USA.

Charles River Laboratories Edinburgh Ltd, Elphinstone Research Centre, Tranent, East Lothian, UK.

出版信息

Sci Total Environ. 2018 Jul 15;630:517-525. doi: 10.1016/j.scitotenv.2018.02.206. Epub 2018 Feb 24.

DOI:10.1016/j.scitotenv.2018.02.206
PMID:29486444
Abstract

Understanding dermal exposure is important for higher-tier avian ecological risk assessments. However, dermal exposure and toxicity are often unknown for avifauna. The US EPA's Terrestrial Investigation Model (TIM) uses a method to estimate avian dermal LD50 values (and ultimately dermal exposure) that frequently results in unusually high dermal exposure and low dermal LD50 estimates. This is primarily a result of using organophosphate and carbamate toxicity data to develop the oral-dermal relationship. An estimated dermal LD50 is necessary to generate a dermal route equivalency factor that normalizes potency relative to oral toxicity within the dermal pathway dose equation. In this study, atrazine dermal absorption experiments were conducted with mallard, northern bobwhite, and rat skin. These data were used to derive an avian-mammal dermal route equivalency factor for atrazine and introduce a new approach for estimating dermal LD50 values and ultimately predicting exposure via the TIM dermal pathway. Compared to the default TIM method, this new approach yielded TIM output with lower mean total dose, lower dermal fraction of total dose, greater oral fraction of total dose, and reduced model predicted mortality for atrazine. In addition, the new approach was compared with other methods for estimating avian dermal LD50 values such as those proposed for use with mammalian data and physico-chemical properties and a triazine-specific oral-dermal equation using mammalian LD50 data. The three alternative approaches resulted in output similar to one another and different from the default TIM methods. These results indicate that a dermal route equivalency factor derived from empirical data provides a higher avian dermal LD50 estimate that is consistent with other methods. In addition, the use of this dermal route equivalency factor results in greatly reduced modeled atrazine risk to birds than previously reported in US EPA risk assessments using TIM.

摘要

了解皮肤接触暴露对高等级鸟类生态风险评估很重要。然而,鸟类的皮肤接触暴露和毒性往往未知。美国环保署的陆地调查模型(TIM)使用一种方法来估计鸟类皮肤 LD50 值(最终是皮肤接触暴露量),这种方法经常导致异常高的皮肤接触暴露和低皮肤 LD50 估计值。这主要是由于使用有机磷和氨基甲酸酯毒性数据来开发口服-皮肤关系。估计皮肤 LD50 是生成皮肤途径等效因子的必要条件,该因子可使皮肤途径剂量方程中的毒性相对于口服毒性归一化。在这项研究中,用野鸭、北部鹌鹑和大鼠皮肤进行了阿特拉津皮肤吸收实验。这些数据用于推导阿特拉津的鸟类-哺乳动物皮肤途径等效因子,并引入了一种新的方法来估计皮肤 LD50 值,最终通过 TIM 皮肤途径进行预测。与默认的 TIM 方法相比,这种新方法产生的 TIM 输出具有更低的总剂量平均值、更低的皮肤剂量分数、更高的口服剂量分数和更低的模型预测死亡率。此外,还将新方法与其他估计鸟类皮肤 LD50 值的方法进行了比较,例如那些用于哺乳动物数据和物理化学性质的方法,以及使用哺乳动物 LD50 数据的三嗪特异性口服-皮肤方程。这三种替代方法的输出结果彼此相似,与默认的 TIM 方法不同。这些结果表明,从经验数据推导出来的皮肤途径等效因子提供了更高的鸟类皮肤 LD50 估计值,与其他方法一致。此外,与以前使用 TIM 进行的美国环保署风险评估相比,使用该皮肤途径等效因子大大降低了模型化的阿特拉津对鸟类的风险。

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