This proposal aims to introduce a new imaging approach for fast toxicological screening and toxicity evaluation. Toxicity testing with animals has limitations with regards to cost, time, reliability, and animal welfare. However, the most challenging situation is that thousands of chemicals cant be tested for safety assessment using existing testing methods. Of the USEPA list of 85,000 chemicals, only 2% of them have detailed safety data. Together with another approximately 700 new chemicals being introduced each year, the tremendous number of chemicals with unknown safety information pose a potentially serious threat to public health. In traditional animal testing, adverse effects of chemicals can typically only be detected after the onset of adverse health effects, disease or death in animals exposed to relatively high doses of the substance. Our new imaging approach detects real time damage at the cellular level in the animals exposed to test substances. Thus, the adverse effects can be monitored at any time as long as cellular damage occurs. It provides a rapid method for toxicological screening, and it becomes possible to test substances at environmentally- or biologically-relevant concentrations. Based on this imaging approach, we can develop new methods for large scale chemical testing. In this proposal, we will first demonstrate the ability of the imaging system to detect and identify sites of toxicity produced by well establish toxic chemicals. We will then explore the application of the imaging approach for acute toxicity testing.
Public Health Relevance Statement: Public Health Relevance The success of this proposal will demonstrate the utility of a new imaging method for rapidly detecting adverse effects that can be applied to toxicity testing strategies. The new imaging based toxicity testing will allow continuous monitoring of real time damage with high sensitivity allowing testing of chemicals at concentrations close to the environmentally-relevant exposure levels, thus providing a more accurate prediction of human response. It will also help to alleviate animal suffering during the tests by looking for effects soon after chemical exposure. Most importantly, this imaging approach would make it possible to develop methods to address the critical need for methods to test large numbers of chemicals.
Project Terms: Acute Toxicity Tests; Address; Adverse effects; Alpha Cell; Animal Testing; Animal Welfare; Animals; base; Biochemical; Biological; Biological Markers; Carbon Tetrachloride; Cessation of life; Chemical Exposure; Chemicals; cost; Data; Detection; Disease; Dose; Environment; Enzymes; Ethics; Evaluation; Excision; extracellular; Extracellular Matrix; Extracellular Space; Firefly Luciferases; Health; Housekeeping; Human; Image; imaging approach; imaging modality; imaging system; in vivo; Measurable; Measurement; Methods; Monitor; Morphology; Mouse Strains; Mus; novel; novel strategies; Organ; Paraquat; Poisons; Proteins; Protocols documentation; Public Health; public health relevance; rapid detection; rapid technique; Reporter; response; Safety; safety testing; screening; sensor; Site; success; Testing; Time; Tissues; Toxic effect; toxicant; Toxicity Tests; Toxicology
