From Classical Toxicology to Tox21: Some Critical Conceptual and Technological Advances in the Molecular Understanding of the Toxic Response Beginning From the Last Quarter of the 20th Century.

Toxicology has made steady advances over the last 60+ years in understanding the mechanisms of toxicity at an increasingly finer level of cellular organization. Traditionally, toxicological studies have used animal models. However, the general adoption of the principles of 3R (Replace, Reduce, Refine) provided the impetus for the development of in vitro models in toxicity testing.

In silico toxicological screening of natural products.

ABSTRACT This study closely examines six well-known naturally occurring dietary chemicals (estragole, pulegone, aristolochic acid I, lipoic acid, 1-octacosanol, and epicatechin) with known human exposure, chemical metabolism, and mechanism of action (MOA) using in silico screening methods. The goal of this study was to take into consideration the available information on these chemicals in terms of MOA and experimentally determined toxicological data, and compare them to the in silico predictive modeling results produced from a series of computational toxicology software. After these analyses, a consensus modeling prediction was formulated in light of the weight of evidence for each natural product.

Prediction of rodent carcinogenic potential of naturally occurring chemicals in the human diet using high-throughput QSAR predictive modeling.

Consistent with the U.S. Food and Drug Administration (FDA) Critical Path Initiative, predictive toxicology software programs employing quantitative structure-activity relationship (QSAR) models are currently under evaluation for regulatory risk assessment and scientific decision support for highly sensitive endpoints such as carcinogenicity, mutagenicity and reproductive toxicity.