Calabrese Edward J, Baldwin Linda A
Environmental Health Sciences, University of Massachusetts, Amherst, MA.
Nonlinearity Biol Toxicol Med. 2003 Oct;1(4):455-67. doi: 10.1080/15401420390271056.
The National Toxicology Program (NTP) dose-ranging studies typically employ five dosages and a concurrent control and are conducted for 2- and 13-week exposure periods. Because five doses are employed it suggested the possibilities of the occurrence of sub-NOAEL doses in many of these bioassays and of evaluating the occurrence of hormesis within the NTP bioassay. As a result, 59 environmentally relevant agents in the NTP toxicity database were assessed for their capacity to affect hormetic dose responses for growth as measured by change in weight gain. Hormetic effects were observed with 51 (88%) of the 58 agents evaluated. When considered by species, hormetic effects were observed in 48% (98/205) of bioassays involving mice and 14% (29/204) of bioassays involving rats. Hormetic effects were seen in a comparable fashion between males and females of both mice (i.e., 47 male and 51 female) and rats (13 male and 16 female rats). These observations represent a new finding within the NTP bioassay database that have potential implications for issues relating to study design and endpoint measured, as well as underlying biological mechanisms that affect efficiency of nutrient utilization under conditions of low-level toxicant exposure.
美国国家毒理学计划（NTP）的剂量范围研究通常采用五种剂量，并设一个同期对照，进行为期2周和13周的暴露期研究。由于采用了五种剂量，这表明在许多此类生物测定中可能出现低于未观察到有害作用水平（NOAEL）的剂量，并有可能在美国国家毒理学计划生物测定中评估兴奋效应的发生情况。因此，对NTP毒性数据库中的59种环境相关物质影响生长的兴奋剂量反应能力进行了评估，生长通过体重增加变化来衡量。在所评估的58种物质中，有51种（88%）观察到了兴奋效应。按物种考虑，在涉及小鼠的生物测定中有48%（98/205）观察到兴奋效应，在涉及大鼠的生物测定中有14%（29/204）观察到兴奋效应。在小鼠（即47只雄性和51只雌性）和大鼠（13只雄性和16只雌性大鼠）的雄性和雌性中，以类似方式观察到了兴奋效应。这些观察结果代表了NTP生物测定数据库中的一项新发现，对与研究设计和测量终点相关的问题以及影响低水平毒物暴露条件下营养物质利用效率的潜在生物学机制具有潜在意义。
