Chemical Toxicity Testing Going Digital
EPA is using computer models to predict the human health and environmental hazards of new chemicals and advance the design and use of green chemistry.
With thousands of new chemicals introduced into the market each year, EPA needs a better way to predict which ones are most likely to pose the greatest threats to human and environmental health. Now there is T.E.S.T (or the Toxicity Estimation Software Tool), a computer program developed by EPA that enables scientists to conduct analyses to estimate toxicity from a chemical’s molecular structure—the atoms from which it is built and the particular way they are linked together.
It can take months or even years to measure toxicity in the laboratory using test animals, but “it can take only seconds on the computer,” says EPA scientist Dr. Douglas Young. “Animal testing is very expensive,” he adds, but T.E.S.T. “utilizes data that are already out there.” Dr. Young and colleagues Drs. Paul Harten, Raghuraman Venkatapathy, and Todd Martin developed the T.E.S.T. software program. Both are part of an EPA research team working to advance green chemistry and engineering methods to advance sustainable technologies.
T.E.S.T. gleans mutagenicity and developmental toxicity data from thousands of in vivo exposure tests conducted under strictly controlled laboratory conditions. The scientists used such existing toxicity data to develop models that the program then uses to predict quantitative toxicity values, such as the concentration of a certain chemical (in mg/L) it would take to result in a 50% mortality rate for a commonly used study animal (such as fathead minnows) in a given amount of time.
The program’s results have been impressive. “We’ve tested it against a number of different software tools and approaches [including commercial software], and our tool always seems to come out either on top or as good as anything else,” says Young. T.E.S.T. is free and has been downloaded from EPA’s website more than 4,000 times.
With more than 80,000 chemicals in commerce and thousands more being added into commercial applications each year, the utility of T.E.S.T. is becoming increasingly apparent.
Users range from chemical and pharmaceutical companies to academic researchers and environmental health specialists. They can input the structure of a chemical to be tested into a computer by drawing it using a built-in structure drawing tool, importing it from standard chemical structure file formats, or selecting it from the program’s structure database. The databases in T.E.S.T. relate molecular descriptors or characteristics to the result of a given toxicity test. Each type of test contains its own library of comparison chemicals that vary in size and composition.
The European community has embraced using similar programs like T.E.S.T. to reduce the need for animal testing. The goals of the Registration Evaluation Authorization and Restriction of Chemical Substances (REACH) legislation, which was enacted by the European Union and went into effect in 2007, are to manage chemical risks and develop more chemical safety information, but the burdens of increased animal testing associated with more testing were at first thought to be enormous. New types of toxicity tests and database programs are the main approaches Europeans are taking to answer this challenge.
T.E.S.T. is a key part of the toolkit that EPA has developed in support of its mission to advance technologies to reduce environmental risks to human health and ecosystems. For example, T.E.S.T. can supply missing toxicity estimates needed for “green process” design, a new approach to designing industrial processes to reduce the environmental impacts of the waste that is generated while at the same time minimizing manufacturing costs. EPA also has developed a green process design software program called the Waste Reduction Algorithm (WAR), which can be downloaded at its Clean Processes website.
Today, scientists in the fields of genomics and bioinformatics are measuring the effects of chemicals directly on genes and proteins. T.E.S.T. was designed so that these and other types of new information about chemicals can be added easily to the program as the science evolves. EPA is using T.E.S.T. as part of its strategy to continue advancing sustainable toxicity testing into the 21st century and beyond.