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About the Authors:
Reuben Thomas
Affiliation: Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, California, United States of America
Russell S. Thomas
Affiliation: The Hamner Institutes for Health Sciences, Research Triangle Park, North Carolina, United States of America
Scott S. Auerbach
Affiliation: Biomolecular Screening Branch, National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, United States of America
Christopher J. Portier
* E-mail: [email protected]
Affiliation: National Center for Environmental Health and Agency for Toxic Substances and Disease Registry, United States Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America
Introduction
There is push to use a broad array of biological data in toxicity testing to improve reliability and provide reasonably quick indications of animal and human toxicity of chemical compounds. The National Toxicology Program (NTP) 's High Throughput Screening (HTS) [1] and the Environmental Protection Agency's ToxCast programs [2] are efforts in this direction. These efforts have been initiated in light of the fact that for a lot of the 100,000 chemicals in commerce in the U.S. and Europe, information on toxicity is extremely limited [3]. Data provided from the long term chronic testing of chemicals on animals, like those from NTP's two-year cancer bioassay though invaluable in providing carcinogenicity information in vivo over a wide range of animal tissues and across multiple doses, is not suitable when one needs to rapidly identify potential harm from chemical exposure. Over the past approximately 40 years, only around 600 chemicals have been tested by the NTPs in their two-year cancer bioassay and only about 5–6 times this number have been tested worldwide.
The goal of toxicity testing is ultimately to protect human health. Even though the two-year cancer bioassay is performed on rats and mice, there is considerable data supporting its use to screen for carcinogens in humans [4]. The HTS and ToxCast programs are performed on cell lines; these can be both human and animal and thus provide a logical path for extrapolation between species. However, cell lines are distantly removed from a functional whole organism so it becomes necessary to extrapolate the in vitro results from the various cell lines to the human in vivo context.
An alternative to the cell-based assays...