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High-Throughput Screening to Advance In Vitro Toxicology: Accomplishments, Challenges, and Future Directions
Caitlin Lynch1, Srilatha Sakamuru1, Masato Ooka1
1National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, Maryland, USA; email: Caitlin.Lynch@nih.gov, mxia@mail.nih.gov.
Abstract:
Traditionally, 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.
Insights
High-throughput in vitro screening methods are crucial for assessing chemical toxicity, overcoming limitations of traditional animal studies. These advanced methods improve efficiency and human relevance in toxicology.
Area of Science:
- Toxicology and Environmental Health
- Biotechnology and Cheminformatics
Background:
- Traditional in vivo animal studies for chemical toxicity are slow, costly, and often inaccurate for human outcomes.
- The growing number of chemicals and high drug failure rates necessitate faster, more reliable toxicity assessment methods.
- The Tox21 program was established to address these challenges through a collaborative, high-throughput in vitro approach.
Purpose of the Study:
- To review advancements in high-throughput screening (HTS) methodologies for generating toxicological data.
- To discuss the impact of HTS and informatics on the field of toxicology.
- To explore future directions for environmental toxicity assessment using scalable, human-relevant methods.
Main Methods:
- Utilizing a battery of in vitro assays for high-throughput, concentration-responsive toxicity screening.
- Implementing advanced robotic screening methodologies for increased efficiency and throughput.
- Leveraging informatics processes for the generation and analysis of toxicological data.
Main Results:
- Significant progress has been made in developing and applying HTS methodologies in toxicology.
- Informatics plays a key role in enabling the generation and interpretation of large-scale toxicological datasets.
- These advancements facilitate a more efficient and comprehensive understanding of chemical toxicity.
Conclusions:
- High-throughput in vitro assays offer a powerful alternative to traditional animal testing for toxicity assessment.
- Continued innovation in screening technology and informatics is essential for advancing toxicological science.
- Future efforts should focus on developing scalable methods that accurately reflect human biological and toxicodynamic processes.
