Dataset contains summary data (mean, standard error, sample size (n)) for all measured endpoints reported and depicted in the corresponding manuscript. This dataset is associated with the following publication: Conley, J., C. Lambright, N. Evans, M. Strynar, J. McCord, B. McIntyre, G. Travlos, M. Cardon, E. MedlockKakaley, P. Hartig, V. Wilson, and E. Gray. Adverse maternal, fetal, and postnatal effects of Hexafluoropropylene oxide dimer acid (GenX) from oral gestational exposure in Sprague Dawley rats. ENVIRONMENTAL HEALTH PERSPECTIVES. National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, NC, USA, 1-13, (2019).

In an effort to address a major challenge in chemical safety assessment, alternative approaches for characterizing systemic effect levels, a predictive model was developed. Systemic effect levels were curated from ToxRefDB, HESS-DB and COSMOS-DB from numerous study types totaling 4382 in vivo studies for 1201 chemicals. Observed systemic effects in mammalian models are a complex function of chemical dynamics, kinetics, and inter- and intra-individual variability. In order to address the complexity problem, systemic effect levels were modeled at the study-level by leveraging study covariates (e.g., study type, strain, administration route) in addition to multiple descriptor sets, including chemical (ToxPrint, PaDEL, and Physchem), biological (ToxCast), and kinetic descriptors. Using Random Forest modeling with cross-validation and external validation procedures, study-level covariates alone accounted for approximately 20% of the variance reducing the root mean squared error (RMSE) from 0.96 log10 mg/kg/day to 0.85 log10 mg/kg/day, providing a baseline performance metric (lower expectation of model performance). A consensus model developed using a combination of study-level covariates, chemical, biological, and kinetic descriptors explained a total of 38% of the variance with an RMSE of 0.76 log10 mg/kg/day. A benchmark model (upper expectation of model performance) was also developed with an RMSE of 0.5 log10 mg/kg/day by incorporating study-level covariates and the mean effect level per chemical. To achieve a representative chemical-level prediction, the minimum study-level predicted and observed effect level per chemical were compared reducing the RMSE from 1.1 to 0.8 log10 mg/kg/day. Although biological descriptors did not improve model performance, the final model was enriched for biological descriptors that indicated xenobiotic metabolism gene expression, oxidative stress, and cytotoxicity, demonstrating the importance of accounting for kinetics and non-specific bioactivity in predicting systemic effect levels. Herein, we have generated an externally predictive model of systemic effect levels for use as a safety assessment tool and have generated forward predictions for thousands of chemicals. This dataset is associated with the following publication: Truong, L., G. Ouedraogo, L. Pham, J. Clouzeau, S. Loisel-Joubert, D. Blanchet, H. Noçairi, W. Setzer, R. Judson, C. Grulke, K. Mansouri, and M. Martin. (Archives of Toxicology) Predicting In Vivo Effect Levels for Repeat Dose Systemic Toxicity using Chemical, Biological, Kinetic and Study Covariates. Archives of Toxicology. Springer, New York, NY, USA, 92(2): 587-600, (2018).

Supplemental data for "Schaupp CM, Maloney EM, Mattingly K, Olker JH, Villeneuve DL. Comparison of in silico, in vitro, and in vivo toxicity benchmarks suggests a role for ToxCast data in ecological hazard assessment. Toxicol Sci. 2023 Jul 25:kfad072. doi: 10.1093/toxsci/kfad072. Epub ahead of print. PMID: 37490521.". This dataset is associated with the following publication: Schaupp, C., E. Maloney, K. Mattingly, J. Olker, and D. Villeneuve. Comparison of in silico, in vitro, and in vivo toxicity benchmarks suggests a role for ToxCast data in ecological hazard assessment.. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 195(2): 145-154, (2023).

Data for the exposure-response arrays comparing effect levels for non-cancer and cancer endpoints for p,p'-DDD and analogues were sourced from the links provided. This dataset is associated with the following publication: Lizarraga, L., J. Dean, J. Kaiser, S. Wesselkamper, J. Lambert, and J. Zhao. A Case Study on the Application of An Expert-driven Read-Across Approach in Support of Quantitative Risk Assessment of p,p’-Dichlorodiphenyldichloroethane. REGULATORY TOXICOLOGY AND PHARMACOLOGY. Elsevier Science Ltd, New York, NY, USA, 103: 301-313, (2019).

ToxCast bioactivity data and model predictions for the estrogen receptor (ER) and androgen receptor (AR) pathways were obtained from the inks provided. This dataset is associated with the following publication: Lizarraga, L., J. Dean, J. Kaiser, S. Wesselkamper, J. Lambert, and J. Zhao. A Case Study on the Application of An Expert-driven Read-Across Approach in Support of Quantitative Risk Assessment of p,p’-Dichlorodiphenyldichloroethane. REGULATORY TOXICOLOGY AND PHARMACOLOGY. Elsevier Science Ltd, New York, NY, USA, 103: 301-313, (2019).

The US Environmental Protection Agency conducts ecological risk assessments with a battery of fish toxicity tests that include acute, early life stage, and reproduction tests. While endpoints in these tests (survival, growth and reproduction) are conceptually related, because they are measured in separate exposures, the quantitative relationships between them are difficult to determine and largely ignored. In the current test, fathead minnows (FHM) were exposed for 28 days to 1 mg/L or 2 mg/L carbaryl, a well-studied carbamate insecticide, in early life stages and then reared in clean water until adulthood, when reproduction was assessed. Also. weekly growth measurements were taken throughout the test to determine growth rates during and after exposure. Growth curves derived from these measurements were then compared to the reproductive output. The data indicate that carbaryl reduced growth rate only for a brief time early in the exposure. However, this brief effect impacted overall growth into adulthood and lowered the reproductive output of exposed FHM. The effect of a transient exposure early in life to carbaryl could have later population-level impacts by causing mortality, lowering growth rates, and reducing reproductive output. This dataset is associated with the following publication: Flynn, K., S. Kadlec, V. Kurker, and M. Etterson. Effects of a 28-day early life stage exposure to carbaryl on fathead minnow long-term growth and reproduction. AQUATIC TOXICOLOGY. Elsevier Science Ltd, New York, NY, USA, 242: 106018, (2022).

individual values for liver detoxification for each human sample and for each chemical. This dataset is associated with the following publication: Moser, G., and S. Padilla. Esterase detoxification of acetylcholinesterase inhibitors using human liver samples in vitro. TOXICOLOGY. Elsevier Science Ltd, New York, NY, USA, 11-20, (2016).

Publicly available dataset containing chemical exposure data. This dataset is associated with the following publication: Lin, Y., V. Morozov, A. Kadry, J. Caffrey , and W. Chou. Reconstructing population exposures to acrylamide from human monitoring data using a pharmacokinetic framework. CHEMOSPHERE. Elsevier Science Ltd, New York, NY, USA, 331: 138798, (2023).

Dataset includes summary statistics (mean, standard error, sample size) for all endpoints measured and reported from the the experiments described in the published manuscript. This dataset is associated with the following publication: Conley, J., C. Lambright, N. Evans, J. Bangma, J. Ford, D. Jenkins-Hill, E. Medlock Kakaley, and L. Gray. Maternal and neonatal effects of maternal oral exposure to perfluoro-2-methoxyacetic acid (PFMOAA) during pregnancy and early lactation in the Sprague-Dawley rat. ENVIRONMENTAL SCIENCE & TECHNOLOGY. American Chemical Society, Washington, DC, USA, 58(2): 1064-1075, (2024).