Combined repeated-dose and reproductive/developmental oral toxicity of 3-methylpentane, isooctane, and isononane in rats

A. Kawashima, Kaoru Inoue, Y. Yoshizaki, K. Ushida, K. Kai, Hiroshi Suzuki, M. Takano, S. Fujii, Kaoru Yabe, M. Matsumoto, Takashi Yamada, A. Hirose
{"title":"Combined repeated-dose and reproductive/developmental oral toxicity of 3-methylpentane, isooctane, and isononane in rats","authors":"A. Kawashima, Kaoru Inoue, Y. Yoshizaki, K. Ushida, K. Kai, Hiroshi Suzuki, M. Takano, S. Fujii, Kaoru Yabe, M. Matsumoto, Takashi Yamada, A. Hirose","doi":"10.2131/fts.7.259","DOIUrl":null,"url":null,"abstract":"ABSTRACT — 3-Methylpentane, isooctane, and isononane are acyclic branched saturated hydrocarbons with carbon numbers C6, C8, and C9, respectively. To assess human risk, we conducted a combined repeated-dose and reproductive/developmental oral toxicity studies in rats. [Organization for Economic Co-operation and Development (OECD) Test Guideline 422]. Each hydrocarbon was administered by gavage to rats at three doses (plus a control group). All three chemicals targeted the liver and kidney. An increase in liver weight without hepatic injury was observed as the adaptive response to the chemical treatments. Males treated by each chemical showed α2u-globulin nephropathy, which is a rat-specific finding that bears no human relevance. Reproduction/developmental toxicity parameters showed no treatment-related effects in parents or offspring at any dose for the three chemicals, except for the retardation of offspring bodyweight development which may be a secondary effect of a maternal systemic condition or direct effect on offspring in isononane. No observed adverse effect levels (NOAELs) of repeated toxicity in either sex were determined to be 300 mg/kg/day for 3-methylpentane, 100 mg/kg/day for isooctane, and 250 mg/kg/day for isononane. NOAELs of reproductive/developmental toxicity in parents and offspring were determined to be 1000 mg/kg/day for 3-methylpentane, and 300 mg/kg/day for isooctane. For isononane, NOAELs were determined to be 1000 mg/kg/day for reproduction, and 250 mg/kg/day for offspring development. These results provide new toxicological information and support the category assessment of published reports that evaluate the acyclic branched saturated hydrocarbons as low-toxicity substances.","PeriodicalId":12489,"journal":{"name":"Fundamental Toxicological Sciences","volume":"13 1","pages":"259-279"},"PeriodicalIF":0.0000,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"1","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Fundamental Toxicological Sciences","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2131/fts.7.259","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 1

Abstract

ABSTRACT — 3-Methylpentane, isooctane, and isononane are acyclic branched saturated hydrocarbons with carbon numbers C6, C8, and C9, respectively. To assess human risk, we conducted a combined repeated-dose and reproductive/developmental oral toxicity studies in rats. [Organization for Economic Co-operation and Development (OECD) Test Guideline 422]. Each hydrocarbon was administered by gavage to rats at three doses (plus a control group). All three chemicals targeted the liver and kidney. An increase in liver weight without hepatic injury was observed as the adaptive response to the chemical treatments. Males treated by each chemical showed α2u-globulin nephropathy, which is a rat-specific finding that bears no human relevance. Reproduction/developmental toxicity parameters showed no treatment-related effects in parents or offspring at any dose for the three chemicals, except for the retardation of offspring bodyweight development which may be a secondary effect of a maternal systemic condition or direct effect on offspring in isononane. No observed adverse effect levels (NOAELs) of repeated toxicity in either sex were determined to be 300 mg/kg/day for 3-methylpentane, 100 mg/kg/day for isooctane, and 250 mg/kg/day for isononane. NOAELs of reproductive/developmental toxicity in parents and offspring were determined to be 1000 mg/kg/day for 3-methylpentane, and 300 mg/kg/day for isooctane. For isononane, NOAELs were determined to be 1000 mg/kg/day for reproduction, and 250 mg/kg/day for offspring development. These results provide new toxicological information and support the category assessment of published reports that evaluate the acyclic branched saturated hydrocarbons as low-toxicity substances.
3-甲基戊烷、异辛烷和异壬烷对大鼠的复合重复剂量和生殖/发育口服毒性
摘要- 3-甲基戊烷、异辛烷和异壬烷是碳数分别为C6、C8和C9的无环支链饱和烃。为了评估人类风险,我们在大鼠中进行了重复给药和生殖/发育口服毒性联合研究。[经济合作与发展组织(OECD)测试指南422]。每种碳氢化合物以三种剂量灌胃给鼠(外加一个对照组)。这三种化学物质的目标都是肝脏和肾脏。肝脏重量增加,但没有肝损伤,这是对化学处理的适应性反应。每一种化学药物治疗的雄性都表现出α - 2u-球蛋白肾病,这是大鼠特有的发现,与人类无关。生殖/发育毒性参数显示,在任何剂量下,这三种化学物质对父母或后代都没有治疗相关的影响,除了后代体重发育迟缓,这可能是母亲全身状况的继发性影响或异壬烷对后代的直接影响。未观察到男女重复毒性的不良反应水平(NOAELs)确定为3-甲基戊烷300 mg/kg/天,异辛烷100 mg/kg/天,异壬烷250 mg/kg/天。测定3-甲基戊烷对父母和后代生殖/发育毒性的NOAELs为1000 mg/kg/d,异辛烷为300 mg/kg/d。异烟醚的NOAELs测定值为繁殖用1000mg /kg/d,子代发育用250mg /kg/d。这些结果提供了新的毒理学信息,并支持已发表的评价无环支链饱和烃为低毒性物质的分类评估。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
自引率
0.00%
发文量
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信