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荷兰带兔:发育毒性试验的替代品种。

The Dutch-Belted rabbit: an alternative breed for developmental toxicity testing.

作者信息

Spence Stan

机构信息

Developmental and Reproductive Toxicology, Safety Assessment Operations, Merck Research Laboratories (WP45-118), West Point, PA 19486, USA.

出版信息

Birth Defects Res B Dev Reprod Toxicol. 2003 Oct;68(5):439-48. doi: 10.1002/bdrb.10040.

Abstract

BACKGROUND

Historical control data play a crucial role in the interpretation of observations made from developmental and reproductive toxicity studies.

METHODS

In our effort to develop the Dutch-Belted rabbit as an alternative breed of rabbit for testing of small molecule pharmaceuticals, data collected from 236 untreated pregnant Dutch Belted rabbits are summarized and compared to data collected from 350 untreated pregnant New Zealand White Rabbits.

RESULTS

The data presented include mean maternal body weight and food consumption values, mean maternal hematological and serum biochemical values collected during gestation, maternal reproductive (laparotomy) parameters collected at cesarean section, and incidences of spontaneous fetal morphological alterations collected during 1999-2002. Due to their smaller size the use of this breed of rabbit would require approximately 40% less drug than studies conducted with New Zealand White rabbits. Because the Dutch-Belted rabbit is pigmented this breed also offers the ability to test the potential effects of various xenobiotics on melanocyte development and to evaluate the potential sequela of drugs that have a propensity to bind melanin in the skin and pigmented retinal epithelium.

CONCLUSIONS

Based on these data, the Dutch-Belted rabbit is considered to be a practical alternative to use of the New Zealand White rabbit for these types of studies.

摘要

背景

历史对照数据在发育和生殖毒性研究的观察结果解释中起着关键作用。

方法

为了将荷兰带兔培育成用于小分子药物测试的替代兔种,我们总结了从236只未经处理的怀孕荷兰带兔收集的数据,并与从350只未经处理的怀孕新西兰白兔收集的数据进行了比较。

结果

所呈现的数据包括平均母体体重和食物消耗量值、妊娠期间收集的平均母体血液学和血清生化值、剖宫产时收集的母体生殖(剖腹术)参数,以及1999年至2002年期间收集的自发胎儿形态改变发生率。由于其体型较小,使用这种兔种进行研究所需的药物比用新西兰白兔进行的研究大约少40%。因为荷兰带兔有色素沉着,这种兔种还能够测试各种外源性物质对黑素细胞发育的潜在影响,并评估有倾向于结合皮肤和色素沉着视网膜上皮中黑色素的药物的潜在后遗症。

结论

基于这些数据,荷兰带兔被认为是在这些类型的研究中使用新西兰白兔的一种切实可行的替代选择。

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