Developmental neurotoxicity (DNT) studies could benefit from revisions to study design, data analysis, and some behavioral test methods to enhance reproducibility. The Environmental Protection Agency (EPA) reviewed 69 studies submitted to the Office of Pesticide Programs. Two of the behavioral tests identified the lowest observable adverse effect level (LOAEL) 20 and 13 times, respectively, while the other two tests identified the LOAEL only 3 and 4 times, respectively. The EPA review showed that the functional observational battery (FOB) was least effective at detecting the LOAEL, whereas tests of learning and memory (L&M) had methodological shortcomings. Human neurodevelopmental toxicity studies over the past 30 years show that most of the adverse effects are on higher cognitive functions such as L&M. The results of human studies together with structure-function relationships from neuroscience, suggest that tests of working memory, spatial navigation/memory, and egocentric navigation/memory should be added to guideline studies. Collectively, the above suggest that EPA and EU DNT studies would better reflect human findings and be more relevant to children by aligning L&M tests to the same domains that are affected in children, removing less useful methods (FOB), and using newer statistical models to better account for random factors of litter and litter × sex. Common issues in study design and data analyses are discussed: sample size, random group assignment, blinding, elimination of subjective rating methods, avoiding confirmation bias, more complete reporting of species, housing, test protocols, age, test order, and litter effects. Litter in DNT studies should at least be included as a random factor in ANOVA models and may benefit from inclusion of litter × sex as random factors.

发育神经毒性（DNT）研究可以受益于研究设计、数据分析和一些行为测试方法的修订，以提高可重复性。美国环境保护署 (EPA) 审查了提交给农药项目办公室的 69 项研究。其中两项行为测试分别确定了 20 次和 13 次最低可观察不良反应水平 (LOAEL)，而另外两项测试分别仅确定了 3 次和 4 次 LOAEL。 EPA 审查表明，功能观察组 (FOB) 在检测 LOAEL 方面效率最低，而学习和记忆测试 (L&M) 则存在方法上的缺陷。过去 30 年的人类神经发育毒性研究表明，大多数不良影响是对 L&M 等高级认知功能的影响。人类研究的结果以及神经科学的结构-功能关系表明，工作记忆、空间导航/记忆和自我中心导航/记忆的测试应该添加到指导研究中。总的来说，上述内容表明，EPA 和 EU DNT 研究将通过将 L&M 测试与儿童受影响的相同领域对齐、删除不太有用的方法 (FOB) 以及使用更新的统计模型来更好地反映人类发现并与儿童更相关。更好地考虑同窝随机因素和同窝×性别。讨论了研究设计和数据分析中的常见问题：样本量、随机分组、盲法、消除主观评级方法、避免确认偏差、更完整地报告物种、住房、测试方案、年龄、测试顺序和窝效应。 DNT 研究中的窝至少应作为 ANOVA 模型中的随机因素包括在内，并且可能受益于将窝×性别作为随机因素。