Cory-Slechta D A, Weiss B, Cox C
Toxicol Appl Pharmacol. 1985 Apr;78(2):291-9. doi: 10.1016/0041-008x(85)90292-3.
To further characterize the lower end of the function relating lead exposure and biological exposure indices to behavior, male weanling rats were exposed chronically to drinking solutions containing 25 ppm sodium acetate (controls) or 25 ppm lead acetate. Behavioral training began when the animals reached 50 days of age, and performance on a fixed-interval 1-min schedule of food reinforcement was then assessed over 90 experimental sessions (136 days). This exposure produced overall response rate increases over the first 40 sessions that were similar to those observed previously with higher concentrations of lead. Response rates of the two groups tended to merge subsequently. The increased overall response rates in the treated group derived primarily from an increased frequency of shorter interresponse times (IRTs) and increased running rates (calculated without the postreinforcement interval). Blood lead (PbB) and zinc protoporphyrin (ZPP) values were determined following sessions 30, 60, and 90. PbB values of the lead-exposed group averaged 15 to 20 micrograms/dl throughout the study; ZPP did not differ. The mean brain lead value of the treated group was 0.07 micrograms Pb/g. Blood-brain ratios (1.38 to 4.06) were substantially greater than those previously observed at higher exposures. These data extend to even lower exposures, and lower blood lead concentrations, the effective concentration for behavioral effects, and further emphasize the importance of the sensitivity of the endpoint in assessing behavioral toxicity.
为了进一步描述铅暴露和生物暴露指数与行为之间函数关系的下限,将雄性断乳大鼠长期暴露于含有25 ppm醋酸钠(对照组)或25 ppm醋酸铅的饮用溶液中。当动物达到50日龄时开始行为训练,然后在90次实验(136天)中评估其在固定间隔1分钟食物强化时间表上的表现。这种暴露在最初40次实验中使总体反应率增加,与之前在较高铅浓度下观察到的情况相似。两组的反应率随后趋于合并。处理组总体反应率的增加主要源于较短反应间隔时间(IRT)频率的增加和奔跑速度的增加(不包括强化后间隔计算)。在第30、60和90次实验后测定血铅(PbB)和锌原卟啉(ZPP)值。在整个研究过程中,铅暴露组的PbB值平均为15至20微克/分升;ZPP没有差异。处理组的平均脑铅值为0.07微克铅/克。血脑比(1.38至4.06)显著高于之前在较高暴露水平下观察到的数值。这些数据将行为效应的有效浓度扩展到甚至更低的暴露水平和更低的血铅浓度,并进一步强调了该终点敏感性在评估行为毒性中的重要性。