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高碳烯烃对汉 Wistar 大鼠的亚慢性毒性。

The subchronic toxicity of higher olefins in Han Wistar rats.

机构信息

Shell Product Stewardship, Shell Global Solutions International B.V., Carel van Bylandtlaan 16, The Hague, 2596 HR, The Netherlands.

Higher Olefins and Polyalpha Olefins vzw c/o Penman Consulting BV., Avenue des Arts 10, Brussels, 1210, Belgium.

出版信息

BMC Pharmacol Toxicol. 2024 Sep 6;25(1):62. doi: 10.1186/s40360-024-00786-y.

DOI:10.1186/s40360-024-00786-y
PMID:39243062
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11380337/
Abstract

Higher olefins (HO) are a category of unsaturated hydrocarbons widely used in industry applications to make products essential for daily human life. Establishing safe exposure limits requires a solid data matrix that facilitates understanding of their toxicological profile. This in turn allows for data to be read across to other members of the category, which are structurally similar and have predictable physico-chemical properties. Five independent subchronic oral toxicity studies were conducted in Wistar rats with Oct-1-ene, Nonene, branched, Octadec-1-ene, Octadecene and hydrocarbon C12-30, olefin-rich, ethylene polymn. by product, at doses ranging from 20 to 1000 mg/kg bw. These HO were selected considering gut absorption, carbon chain length, double-bond position and carbon backbone structural variations. Generally, limited and non-adverse toxicity effects were observed at the end of the treatment for short carbon chain HO. For instance, alpha 2u-globulin nephropathy in the male rats and liver hypertrophy. No clear trend in systemic toxicity was linked to the double-bond position. Key factors for hazard assessment include absorption, carbon chain length, and branching, with Nonene, branched, identified as the worst-case substance. Taken together, the no observed adverse effect level (NOAEL) of each HO in these subchronic studies was set at the highest dose tested.

摘要

高烯烃(HO)是一类广泛应用于工业领域的不饱和烃,用于制造对人类日常生活至关重要的产品。制定安全暴露限值需要一个坚实的数据矩阵,以帮助了解其毒理学特征。这反过来又允许将数据跨类别读取到其他结构相似且具有可预测物理化学性质的成员。在 Wistar 大鼠中进行了五项独立的亚慢性口服毒性研究,涉及 1-辛烯、壬烯、支链十八碳-1-烯、十八碳烯和烃 C12-30、富含烯烃、乙烯聚合的副产物,剂量范围为 20 至 1000mg/kg bw。选择这些 HO 时考虑了肠道吸收、碳链长度、双键位置和碳骨架结构变化。通常,短碳链 HO 在治疗结束时观察到有限的和非毒性的毒性作用。例如,雄性大鼠的α2u-球蛋白肾病和肝脏肥大。双键位置与系统毒性之间没有明显的趋势。危害评估的关键因素包括吸收、碳链长度和支化,其中壬烯和支链被确定为最坏情况物质。总的来说,这些亚慢性研究中每种 HO 的未观察到不良效应水平(NOAEL)设定在最高测试剂量。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f53/11380337/cb0e6861357a/40360_2024_786_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f53/11380337/4081146cef5a/40360_2024_786_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f53/11380337/cb0e6861357a/40360_2024_786_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f53/11380337/4081146cef5a/40360_2024_786_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f53/11380337/cb0e6861357a/40360_2024_786_Fig2_HTML.jpg

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