Predicting Prenatal Developmental Toxicity Based On the Combination of Chemical Structures and Biological Data

Heather L. Ciallella, Daniel P. Russo, Swati Sharma, Yafan Li, Eddie Sloter, Len Sweet, Heng Huang, Hao Zhu

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


For hazard identification, classification, and labeling purposes, animal testing guidelines are required by law to evaluate the developmental toxicity potential of new and existing chemical products. However, guideline developmental toxicity studies are costly, time-consuming, and require many laboratory animals. Computational modeling has emerged as a promising, animal-sparing, and cost-effective method for evaluating the developmental toxicity potential of chemicals, such as endocrine disruptors, without the use of animals. We aimed to develop a predictive and explainable computational model for developmental toxicants. To this end, a comprehensive dataset of 1244 chemicals with developmental toxicity classifications was curated from public repositories and literature sources. Data from 2140 toxicological high-throughput screening assays were extracted from PubChem and the ToxCast program for this dataset and combined with information about 834 chemical fragments to group assays based on their chemical-mechanistic relationships. This effort revealed two assay clusters containing 83 and 76 assays, respectively, with high positive predictive rates for developmental toxicants identified with animal testing guidelines (PPV = 72.4 and 77.3% during cross-validation). These two assay clusters can be used as developmental toxicity models and were applied to predict new chemicals for external validation. This study provides a new strategy for constructing alternative chemical developmental toxicity evaluations that can be replicated for other toxicity modeling studies.

Original languageEnglish (US)
Pages (from-to)5984-5998
Number of pages15
JournalEnvironmental Science and Technology
Issue number9
StatePublished - May 3 2022
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Environmental Chemistry


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