...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Environmental research >Dose-response relationships of rat fetal skeleton variations: Relevance for risk assessment
【24h】

Dose-response relationships of rat fetal skeleton variations: Relevance for risk assessment

机译：大鼠胎儿骨骼变异的剂量反应关系：风险评估的相关性

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

In developmental toxicity studies, skeleton abnormalities found in fetuses at term are classified as variations or malformations. The relevance of skeleton variations for human risk assessment, however, is a controversial issue. This paper is a contribution to the discussion on the interpretation of fetal skeleton variations in the context of risk assessment. Dose-response relationships of skeleton variations and malformations induced by three antineoplastic drugs (FUDR: 5-fluoro-2'-deoxyuridine, HU: hydroxyurea and 6-MPr: 6-mercaptopurine-riboside) were evaluated. FUDR (0, 3,14, 25, 35,45, 55 and 65 mg/kg body wt sc) and HU (0, 250, 300, 350, 400, 450, 500 and 550 mg/kg body wt ip) were administered to rats on gestation day 11 (GD 11) while 6-MPr (0, 3, 7,10 and 14 mg/kg body wt sc) was given on GD 11, or on GD 12. Caesarean sections were performed on GD 21 and all fetuses were cleared and stained with alizarin red S for skeleton examination. Drugs given on GD 11 increased the incidence of thoracic and lumbar vertebra (dumbbell-shaped and bipartite ossification center (o.c.) and sternum (misaligned sternebrae) variations in a dose-dependent manner. Occurrence of zygomatic bone fused with maxilla (a variation in our rats) was also increased by HU and 6-MPr (GD 11) but it was not altered by FUDR. Spontaneous occurrence of wavy ribs was reduced by all treatments. Malformations such as cleft palate, tympanic bone absent and tibia absent were also increased in a dose-dependent manner by the three compounds. No observed effect levels (NOEL) for variations, irrespective of the compound administered, were generally lower than NOELs for malformations. In the discussion, we supported the view that any dose-related increase in the incidence of variations should be taken into account for determination of NOELs in routine studies. Increased occurrences of skeleton variations in term fetuses are also to be considered in risk assessment, unless experimental evidence exists that a particular change has no detrimental effect on the animal survival or health after birth or that it does not occur in humans.
机译：在发育毒性研究中，足月胎儿中发现的骨骼异常被分类为变异或畸形。然而，骨骼变异与人类风险评估的相关性是一个有争议的问题。本文有助于在风险评估的背景下解释胎儿骨骼变异。评估了三种抗肿瘤药（FUDR：5-氟-2'-脱氧尿苷，HU：羟基脲和6-MPr：6-巯基嘌呤-核糖核苷）诱导的骨骼变异和畸形的剂量反应关系。 FUDR（0、3、14、25、35、45、55和65 mg / kg体重皮下）和HU（0、250、300、350、400、450、500和550 mg / kg体重皮下）在妊娠第11天（GD 11）给予大鼠，而在GD 11或GD 12上给予6-MPr（0、3、7,10和14 mg / kg体重sc），剖宫产在GD 21上进行清除所有胎儿并用茜素红S染色以进行骨骼检查。 GD 11上的药物以剂量依赖性方式增加了胸椎和腰椎（哑铃形和两部分骨化中心（oc）和胸骨（错位的胸骨））的发生率。.骨合并上颌骨的发生（我们的变异HU和6-MPr（GD 11）也会增加大鼠，但FUDR并没有改变它；所有治疗均减少了波浪状肋骨的自发发生；同时，in裂，鼓室骨缺失和胫骨缺失等畸形也增加了。这三种化合物的剂量依赖性方式。对于变异，观察到的效应水平（NOEL）均不低于畸形的NOEL（在讨论中），在讨论中，我们支持以下观点：剂量随剂量的增加而增加在常规研究中确定NOEL时应考虑变异发生率，在风险评估中也应考虑足月胎儿骨骼变异发生率的增加，除非有实验证据表明特定变化对出生后的动物存活或健康没有有害影响，或者在人类中不会发生。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号