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基于巴豆醛相对于丙烯醛的相对效力,利用体内和体外数据推导巴豆醛的慢性参考值。

Use of In Vivo and In Vitro Data to Derive a Chronic Reference Value for Crotonaldehyde Based on Relative Potency to Acrolein.

作者信息

Grant Roberta L, Jenkins Allison F

机构信息

a Toxicology Division , Texas Commission on Environmental Quality , Austin , Texas , USA.

出版信息

J Toxicol Environ Health B Crit Rev. 2015;18(7-8):327-43. doi: 10.1080/10937404.2015.1081574. Epub 2015 Nov 18.

DOI:10.1080/10937404.2015.1081574
PMID:26580244
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4706029/
Abstract

The Texas Commission on Environmental Quality (TCEQ) conducted a chronic inhalation noncancer toxicity assessment for crotonaldehyde (CRO). Since there were limited toxicity data for CRO, a reference value (ReV) was derived using a relative potency factor (RPF) approach with acrolein as the index chemical. Both CRO and acrolein are α,β-unsaturated carbonyls and share common steps in their mode of action (MOA). Only studies that investigated the effects of CRO and acrolein in the same study were used to calculate a CRO:acrolein RPF. In vivo findings measuring both 50% respiratory depression in rats and two species of mice and subcutaneous 50% lethality in rats and mice were used to calculate an RPF of 3 (rounded to one significant figure). In vitro data were useful to compare the MOA of CRO and acrolein and to support the RPF determined using in vivo data. In vitro cell culture studies investigating cytotoxicity in normal human lung fibroblast cultures using the propidium iodide cytotoxicity assay and in mouse lymphocyte cultures using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity assay were used to calculate an in vitro RPF of 3, which supports the in vivo RPF. The chronic ReV for acrolein of 1.2 ppb derived by TCEQ was multiplied by the RPF of 3 to calculate the ReV for CRO of 3.6 ppb (10 μg/m(3)). The ReV for CRO was developed to protect the general public from adverse health effects from chronic exposure to CRO in ambient air.

摘要

得克萨斯州环境质量委员会(TCEQ)对巴豆醛(CRO)进行了慢性吸入非致癌毒性评估。由于CRO的毒性数据有限,采用以丙烯醛为指标化学物质的相对效能因子(RPF)方法得出了参考值(ReV)。CRO和丙烯醛均为α,β-不饱和羰基化合物,且在其作用模式(MOA)上有共同步骤。仅使用在同一研究中调查CRO和丙烯醛影响的研究来计算CRO:丙烯醛RPF。用于计算RPF为3(四舍五入至一位有效数字)的体内研究结果包括测量大鼠和两种小鼠的50%呼吸抑制以及大鼠和小鼠的皮下50%致死率。体外数据有助于比较CRO和丙烯醛的MOA,并支持使用体内数据确定的RPF。使用碘化丙啶细胞毒性测定法研究正常人肺成纤维细胞培养物中的细胞毒性以及使用3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐(MTT)细胞毒性测定法研究小鼠淋巴细胞培养物中的细胞毒性的体外细胞培养研究用于计算体外RPF为3这一结果,该结果支持体内RPF。TCEQ得出的丙烯醛慢性ReV为1.2 ppb,乘以RPF 3以计算CRO的ReV为3.6 ppb(10 μg/m³)。制定CRO的ReV是为了保护公众免受环境空气中慢性接触CRO所产生的不良健康影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e5c/4706029/a769df8895fa/uteb_a_1081574_f0001_b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e5c/4706029/a769df8895fa/uteb_a_1081574_f0001_b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e5c/4706029/a769df8895fa/uteb_a_1081574_f0001_b.jpg

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