OECD TG 422重复给药和汉族Wistar大鼠生殖/发育毒性筛选试验中高级烯烃的毒理学评估。

IF 1.2 4区 医学 Q4 PHARMACOLOGY & PHARMACY International Journal of Toxicology Pub Date : 2024-05-01 Epub Date: 2023-11-07 DOI:10.1177/10915818231210856
Quan Shi, Juan-Carlos Carrillo, Michael G Penman, Hua Shen, Colin M North, Sophie Jia, Tilly Borsboom-Patel, Yuan Tian, Fabienne Hubert, Jason C Manton, Peter J Boogaard
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引用次数: 0

摘要

高级烯烃(HO)主要用作生产其他化学品的中间体,如聚合物、脂肪酸、增塑剂醇、表面活性剂、润滑剂、胺氧化物和洗涤剂醇。在重复剂量和生殖/发育毒性联合筛选研究中,检测了五种HO(即1-辛烯、壬烯、癸烯、十六烯和1-十八烯)对C8至C18碳的潜在毒性(OECD TG 422)。这五种HO分别以0(对照)、100、300和1000 mg/kg bw/天灌胃给药于汉族Wistar大鼠。作为一组物质,在HO中观察到肝脏的适应性变化(在没有病理学证据的情况下肝脏重量增加),以及雄性大鼠肾脏重量增加,碳数从C8到C10。所有HO的全身无不良反应水平(NOAEL)测定为1000 mg/kg体重/天。在生殖/发育毒性评估中,用1000毫克/公斤体重/天的壬烯处理的雌性窝仔的后代生存能力、大小和重量都有所降低。生殖毒性的总体无观测效应水平(NOEL)被认为对壬烯分别为300毫克/公斤体重/天,对其他四种HO分别为1000毫克/公斤重量/天。这些数据显著丰富了关于线性和支链HO毒性的数据库,允许与一系列线性和支链HO的类似数据进行比较。结构类别和研究结果之间的比较提供了进一步的支持性数据,以验证作为整体测试策略一部分的跨读假设。
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Toxicological Assessment of Higher Olefins in OECD TG 422 Repeated Dose and Reproductive /Developmental Toxicity Screening Tests in Han Wistar Rats.

Higher olefins (HO) are used primarily as intermediates in the production of other chemicals, such as polymers, fatty acids, plasticizer alcohols, surfactants, lubricants, amine oxides, and detergent alcohols. The potential toxicity of five HO (i.e., 1-Octene, Nonene, Decene, Hexadecene, and 1-Octadecene) with carbon ranging from C8 to C18 was examined in a combined repeated dose and reproduction/developmental toxicity screening study (OECD TG 422). These five HO were administered to Han Wistar rats by gavage at 0 (controls), 100, 300, and 1000 mg/kg bw/day. As a group of substances, adaptive changes in the liver (liver weight increase without pathological evidence), as well as increased kidney weight in male rats, were observed in HO with carbon numbers from C8 to C10. The overall systemic no observed adverse effect level (NOAEL) for all HO was determined at 1000 mg/kg bw/day. In the reproductive/developmental toxicity assessment, offspring viability, size, and weights were reduced in litters from females treated with Nonene at 1000 mg/kg bw/day. The overall no observed effects level (NOEL) for reproductive toxicity was considered to be 300 mg/kg bw/day for Nonene and 1000 mg/kg bw/day for the other four HO, respectively. These data significantly enrich the database on the toxicity of linear and branched HO, allowing comparison with similar data published on a range of linear and branched HO. Comparisons between structural class and study outcome provide further supportive data in order to validate the read-across hypothesis as part of an overall holistic testing strategy.

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来源期刊
CiteScore
3.40
自引率
4.50%
发文量
53
审稿时长
4.5 months
期刊介绍: The International Journal of Toxicology publishes timely, peer-reviewed papers on current topics important to toxicologists. Six bi-monthly issues cover a wide range of topics, including contemporary issues in toxicology, safety assessments, novel approaches to toxicological testing, mechanisms of toxicity, biomarkers, and risk assessment. The Journal also publishes invited reviews on contemporary topics, and features articles based on symposia. In addition, supplemental issues are routinely published on various special topics, including three supplements devoted to contributions from the Cosmetic Review Expert Panel.
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