01926nas a2200325   4500000000100000000000100001008004100002260001500043100001800058700002200076700001600098700001600114700002600130700001500156700001800171700001900189700001600208700001700224700002400241700002400265700002200289700001900311700001700330245011300347856009000460300001200550490000700562520100600569022002501575       2024                            d  c2024/01/231 aCaitlin Lynch1 aSrilatha Sakamuru1 aMasato Ooka1 aRuili Huang1 aCarleen Klumpp-Thomas1 aPaul Shinn1 aDavid Gerhold1 aAnna Rossoshek1 aSam Michael1 aWarren Casey1 aMichael F. Santillo1 aSuzanne Fitzpatrick1 aRussell S. Thomas1 aAnton Simeonov1 aMenghang Xia00aHigh-Throughput Screening to Advance In Vitro Toxicology: Accomplishments, Challenges, and Future Directions  uhttps://www.annualreviews.org/content/journals/10.1146/annurev-pharmtox-112122-104310  a191-2090 v643 aTraditionally, chemical toxicity is determined by in vivo animal studies, which are low throughput, expensive, and sometimes fail to predict compound toxicity in humans. Due to the increasing number of chemicals in use and the high rate of drug candidate failure due to toxicity, it is imperative to develop in vitro, high-throughput screening methods to determine toxicity. The Tox21 program, a unique research consortium of federal public health agencies, was established to address and identify toxicity concerns in a high-throughput, concentration-responsive manner using a battery of in vitro assays. In this article, we review the advancements in high-throughput robotic screening methodology and informatics processes to enable the generation of toxicological data, and their impact on the field; further, we discuss the future of assessing environmental toxicity utilizing efficient and scalable methods that better represent the corresponding biological and toxicodynamic processes in humans.  a0362-1642, 1545-4304