Compendium of Information on the Use of Guideline-Based Developmental Neurotoxicity Studies*

Recent regulatory use of in vitro assays for developmental neurotoxicity have promulgated the development of initial OECD guidance for use of data from the developmental neurotoxicity in vitro battery (DNT IVB). One limitation in use of data from NAMs like the DNT IVB are the uncertainties of in vitro to predict in vivo effects. The lack of any curated database of in vivo DNT studies hampers such a comparison. The goal of the current effort was construction of a repository of all DNT studies defined as publicly available studies that followed DNT and/or reproductive guidelines containing a DNT cohort. The first specific aim was construction of a dataset that identified published studies and regulatory documents that mention completed, underway or planned DNT studies. This included documents which use read across as well agency waivers for DNT studies. The second aim identified those documents from Aim 1 that report the results of completed DNT studies. The third aim identified DNT studies that provide regulatory reviews with summary data. A total of 1648 documents were found from the overall search that had evidence of, 1) a completed, ongoing, or planned DNT study; 2) a read-across or planned read-across; or 3) a waiver. The 1648 documents included 324 DNT study citations. Final filtering of these data yielded a list of 153 DNT studies conducted on 144 chemicals and one stressor (diet restriction) for which there were both extensive data summaries and regulatory reviews. These results likely undercount the number of conducted studies due to the limited release of information from many regulatory agencies. In addition, the amount of information provided publicly available reviews ranges widely, from a one sentence summary to an extensive review with summaries of the methods, results and data interpretations. It is hoped that this paper will persuade regulatory agencies to release more DNT studies that provide comprehensive information. This will foster transparency and ensure public confidence in regulatory decisions. In addition, these results should provide data that promotes comparisons between in vitro and in vivo DNT methods.