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Chemical Reaction: The New Toxicology

By: Steve Herman
Posted: September 5, 2008, from the August 2006 issue of GCI Magazine.

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The New Toxicology can be viewed through the alternatives categorized in 1959 as the three Rs: reduction, refinement and replacement. While reality is a little more complicated than the three Rs, they remain a handy guide to the field.

Reduction aims to design experiments using the least number of animals. The standard acute toxicity test is the LD50, the amount of material needed to kill half the test animals.3 Older methods used up to 140 animals, which dropped to 45 by statistical methods used since 1989. The OECD now accepts a method using 16 animals, and a new study opens the possibility of reducing the number to six.

While traditional methods involved killing an animal at each stage of the test, refinement includes noninvasive imaging techniques such as x-rays, PET scans and MRI, which allows the course of an experiment to be followed in a single animal.

Another refinement is to substitute species lower on the evolutionary scale, such as zebra fish. A chip can be made of the 9,000 genes of the zebra fish and washed with test chemicals, showing which genes the chemical activates.

Replacement requires completely eliminating animals from the testing protocol. The Draize test is a prime target for this advance. First, rabbit eyes were replaced by eyeballs from slaughterhouses. Then a membrane from a hen’s egg was used. Now tissue cultures have been created. Of course, the alternatives must yield results comparable to the standard tests. This proved difficult with the Draize test, not because the alternatives were bad, but because the Draize test itself yields many false positives.