Ashby John
Syngenta Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire, UK.
Nonlinearity Biol Toxicol Med. 2003 Oct;1(4):439-53. doi: 10.1080/15401420390271038.
Our attempts to confirm reports of low-dose/hormetic effects in rodent endocrine toxicity studies are reviewed. It is concluded that our present failure to confirm any such effects is due, in large part, to a general lack of understanding of confounding influences and the failure of most investigators to confirm their findings before publication. The major potential confounding factor is suggested to be variability of the parameters under study within control groups, a factor that assumes increased importance when attempting to demonstrate weak low-dose effects. This is illustrated by our studies with bisphenol A in the mouse uterotrophic assay and of finasteride in the Hershberger antiandrogenicity assay. In both of these cases our ability to demonstrate a low-dose effect is dependent on whether concurrent or recent control values are used.
我们回顾了在啮齿动物内分泌毒性研究中证实低剂量/兴奋效应报告的尝试。得出的结论是，我们目前未能证实任何此类效应，在很大程度上是由于普遍缺乏对混杂影响的理解，以及大多数研究人员在发表前未能证实其研究结果。主要的潜在混杂因素被认为是对照组中所研究参数的变异性，在试图证明微弱的低剂量效应时，这个因素的重要性会增加。这在我们用双酚A进行的小鼠子宫增重试验以及用非那雄胺进行的赫什伯格抗雄激素活性试验中得到了说明。在这两种情况下，我们证明低剂量效应的能力取决于使用的是同期还是近期的对照值。
