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二醇和二醇醚的发育毒性及结构/活性关系

Developmental toxicity and structure/activity correlates of glycols and glycol ethers.

作者信息

Johnson E M, Gabel B E, Larson J

出版信息

Environ Health Perspect. 1984 Aug;57:135-9. doi: 10.1289/ehp.8457135.

DOI:10.1289/ehp.8457135
PMID:6499797
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1568310/
Abstract

In recent years, the National Toxicology Program (NTP) has selected numerous glycol ethers for testing in routine laboratory mammals to ascertain the magnitude of their ability to injure the conceptus. From the lists available of ongoing and projected NTP test chemicals, a series of glycol ethers was selected for examination in vitro in the hydra assay. Also tested were additional chemicals of similar molecular configuration and/or composition. This short-term screening test placed the 14 glycols and glycol ethers tested into a rank order sequence according to their degree of hazard potential to developmental biology, i.e., their ability to interfere with the developmental events characteristic of all ontogenic systems. They were ranked according to the difference between the lowest dose or concentration overtly toxic to adults (A) and the lowest concentration interfering with development (D) of the artificial embryo of reaggregated adult hydra cells and the A/D ratio. Published data from mammalian studies were available for a few of the test chemicals, and in each instance the hydra assay was in direct agreement with the outcomes reported of the more elaborate and standard animal tests. Ethylene glycol and ethylene glycol monomethyl ether were shown by both standard evaluations in mammals, and by the hydra assay, to disrupt embryos only at or very near to their respective adult toxic doses, whereas the mono-ethyl ether perturbed development at approximately one-fifth of the lowest dose overtly toxic to adults.(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

近年来,国家毒理学计划(NTP)挑选了多种乙二醇醚,在常规实验哺乳动物中进行测试,以确定它们损害胚胎的能力大小。从NTP正在进行和计划进行测试的化学品清单中,挑选了一系列乙二醇醚,在水螅试验中进行体外检测。还对分子结构和/或组成相似的其他化学品进行了测试。这项短期筛选试验根据14种测试的二醇和乙二醇醚对发育生物学的潜在危害程度,即它们干扰所有个体发育系统特征性发育事件的能力,将它们排成一个等级顺序。它们是根据对成年动物明显有毒的最低剂量或浓度(A)与干扰成年水螅细胞重聚集人工胚胎发育的最低浓度(D)之间的差异以及A/D比值来排序的。部分测试化学品有来自哺乳动物研究的已发表数据,在每种情况下,水螅试验的结果都与更精细的标准动物试验报告的结果直接一致。乙二醇和乙二醇单甲醚在哺乳动物的标准评估以及水螅试验中均显示,仅在其各自的成年动物毒性剂量或非常接近该剂量时才会破坏胚胎,而乙二醇单乙醚在对成年动物明显有毒的最低剂量的约五分之一时就会干扰发育。(摘要截选至250字)

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/634f/1568310/574ceb540302/envhper00451-0138-c.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/634f/1568310/bf8d4d21f58a/envhper00451-0138-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/634f/1568310/8aef6aa420bc/envhper00451-0138-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/634f/1568310/574ceb540302/envhper00451-0138-c.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/634f/1568310/bf8d4d21f58a/envhper00451-0138-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/634f/1568310/8aef6aa420bc/envhper00451-0138-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/634f/1568310/574ceb540302/envhper00451-0138-c.jpg

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RSC Adv. 2014;4(22):11251-11287. doi: 10.1039/C3RA47191H.
2
Teratological research using in vitro systems. V. Nonmammalian model systems.使用体外系统的致畸学研究。V. 非哺乳动物模型系统。
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本文引用的文献

1
Screening for teratogenic potential: are we asking the proper question?筛查致畸潜力:我们问对问题了吗?
Teratology. 1980 Apr;21(2):259. doi: 10.1002/tera.1420210220.
2
Screening for teratogenic hazards: nature of the problems.致畸危害筛查:问题的本质
Annu Rev Pharmacol Toxicol. 1981;21:417-29. doi: 10.1146/annurev.pa.21.040181.002221.
3
Regeneration by dissociated adult Hydra cells: a histologic study.成年水螅解离细胞的再生:一项组织学研究。
Teratology. 1983 Feb;27(1):81-7. doi: 10.1002/tera.1420270112.
4
The Hydra attenuata system for detection of teratogenic hazards.用于检测致畸危害的水螅系统。
Teratog Carcinog Mutagen. 1982;2(3-4):263-76. doi: 10.1002/1520-6866(1990)2:3/4<263::aid-tcm1770020308>3.0.co;2-i.