The subchronic toxicity of higher olefins in Han Wistar rats

被引:1
|
作者
Shi, Quan [1 ]
Penman, Michael G. [2 ]
Carrillo, Juan-Carlos [1 ]
Van Rompay, An R. [2 ]
Kamelia, Lenny [1 ]
Rooseboom, Martijn [1 ]
Shen, Hua [3 ]
Jia, Sophie [4 ]
Tian, Yuan [5 ]
Dunn, Jamie [2 ]
Hubert, Fabienne [6 ]
Boogaard, Peter J. [7 ]
机构
[1] Shell Global Solut Int BV, Carel Bylandtlaan 16, NL-2596 HR The Hague, Netherlands
[2] Penman Consulting BV, Higher Olefins & Polyalpha Olefins vzw, Ave Arts 10, B-1210 Brussels, Belgium
[3] Shell Oil Co, 150 N Dairy Ashford Rd, Houston, TX 77079 USA
[4] Chevron Phillips Chem Co, 10001 Six Pines Dr, The Woodlands, TX 77380 USA
[5] UCL, Inst Ophthalmol, 11-43 Bath St, London EC1V 9EL, England
[6] INEOS Oligomers, Hawkslease, Chapel Lane, Lyndhurst SO43 7FG, England
[7] Wageningen Univ & Res, Div Toxicol, Stippeneng 4, NL-6708 WE Wageningen, Netherlands
来源
BMC PHARMACOLOGY & TOXICOLOGY | 2024年 / 25卷 / 01期
关键词
Subchronic toxicity; OECD; 408; No observed adverse effect level (NOAEL); Higher olefins; Unknown or variable composition; Complex reaction products and biological materials (UVCBs); NEPHROPATHY; OXIDATION;
D O I
10.1186/s40360-024-00786-y
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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.
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页数:14
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