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在一项初步发育毒性试验中对60种化学物质进行评估。

Evaluation of 60 chemicals in a preliminary developmental toxicity test.

作者信息

Hardin B D, Schuler R L, Burg J R, Booth G M, Hazelden K P, MacKenzie K M, Piccirillo V J, Smith K N

出版信息

Teratog Carcinog Mutagen. 1987;7(1):29-48. doi: 10.1002/tcm.1770070106.

Abstract

The number of chemicals in commerce which have not been evaluated for potential developmental toxicity is large. Because of the time and expense required by conventional developmental toxicity tests, an abbreviated assay is needed that will preliminarily evaluate otherwise untested chemicals to help prioritize them for conventional testing. A proposed short-term in vivo assay has been used in a series of studies in which a total of 60 chemicals were tested. Some were independently tested two or four times each. In this preliminary test, pregnant mice were dosed during mid-pregnancy and were then allowed to deliver litters. Litter size, birth weight, and neonatal growth and survival to postnatal day 3 were recorded as indices of potential developmental toxicity. Results in this assay and conventional mouse teratology tests were generally concordant. Conventional data were available for 14 chemicals (ten teratogens, one fetotoxin, three nonteratogens), of which 11 (nine teratogens, one fetotoxin, one nonteratogen) produced evidence of developmental toxicity. This included conventional data for three chemicals (ethylene glycol, diethylene glycol dimethyl ether, and triethylene glycol dimethyl ether) that were untested before the present study. As high priority candidates for conventional testing on the basis of results here, all were subsequently studied in a standard teratology assay and were confirmed to be teratogenic in mice. Additionally, one of them (ethylene glycol) plus a fourth high priority candidate for conventional study (diethylene glycol monomethyl ether) were subsequently tested in rats and were found to be teratogenic in that species.

摘要

尚未对潜在发育毒性进行评估的商用化学品数量众多。由于传统发育毒性试验需要耗费时间和费用,因此需要一种简化的试验方法,以便对未经测试的化学品进行初步评估,从而帮助确定其进行传统测试的优先级。一种提议的短期体内试验已用于一系列研究中,共测试了60种化学品。其中一些化学品分别独立进行了两次或四次测试。在这项初步试验中,在妊娠中期给怀孕小鼠给药,然后让其产仔。记录产仔数、出生体重以及出生后第3天的新生儿生长和存活情况,作为潜在发育毒性的指标。该试验结果与传统小鼠致畸试验结果总体一致。有14种化学品(10种致畸剂、1种胎儿毒素、3种非致畸剂)有传统数据,其中11种(9种致畸剂、1种胎儿毒素、1种非致畸剂)产生了发育毒性证据。这包括本研究之前未测试的三种化学品(乙二醇、二乙二醇二甲醚和三乙二醇二甲醚)的传统数据。根据此处的结果,作为传统测试的高优先级候选物,随后对所有这些化学品进行了标准致畸试验研究,并证实它们在小鼠中具有致畸性。此外,其中一种化学品(乙二醇)加上传统研究的第四个高优先级候选物(二乙二醇单甲醚)随后在大鼠中进行了测试,发现它们在该物种中具有致畸性。

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