Use of computational toxicology (CompTox) tools to predict in vivo toxicity for risk assessment.

Use of computational toxicology (CompTox) tools to predict in vivo toxicity for risk assessment. Regul Toxicol Pharmacol. 2020 Jul 05;:104724 Authors: Silva MH Abstract Computational Toxicology tools were used to predict toxicity for three pesticides: propyzamide (PZ), carbaryl (CB) and chlorpyrifos (CPF). The tools used included: a) ToxCast/Tox21 assays (AC50 s μM: concentration 50% maximum activity); b) in vitro-to-in vivo extrapolation (IVIVE) using ToxCast/Tox21 AC50s to predict administered equivalent doses (AED: mg/kg/d) to compare to known in vivo Lowest-Observed-Effect-Level (LOEL)/Benchmark Dose (BMD); c) high throughput toxicokinetics population based (HTTK-Pop) using AC50s for endpoints associated with the mode of action (MOA) to predict age-adjusted AED for comparison with in vivo LOEL/BMDs. ToxCast/Tox21 active-hit-calls for each chemical were predictive of targets associated with each MOA, however, assays directly relevant to the MOAs for each chemical were limited. IVIVE AEDs were predictive of in vivo LOEL/BMD10s for all three pesticides. HTTK-Pop was predictive of in vivo LOEL/BMD10s for PZ and CPF but not for CB after human age adjustments 11-15 (PZ) and 6-10 (CB) or 6-10 and 11-20 (CPF) corresponding to treated rat ages (in vivo endpoints). The predictions of computational tools are useful for risk assessment to identify targets in chemical MOAs and to support in vivo endpoints. Data can also aid is decisions ...
Source: Regulatory Toxicology and Pharmacology : RTP - Category: Toxicology Authors: Tags: Regul Toxicol Pharmacol Source Type: research