October 2001 News

Federal Reports Recommend In Vitro Screens to Cut Lab Animal Use

October 10, 2001

Two federal reports issued this month suggest that wider use of cell lines to screen chemicals for toxicity could eliminate the need for nearly a third of current animal tests.

The documents, "Report of the International Workshop on In Vitro Methods for Assessing Acute Systemic Toxicity" (NIH Publication 01-4499) and an accompanying "Guidance Document on Using In Vitro Data to Estimate In Vivo Starting Doses for Acute Toxicity" (NIH Publication 01-4500), resulted from a workshop earlier this year sponsored by multiple federal agencies interested in assessing acute toxicity. The National Institute for Environmental Health Sciences, the National Toxicology Program (NTP), and the U.S. Environmental Protection Agency co-sponsored the workshop, which was attended by more than 100 scientists from eight countries.

Although the reports focused on the future potential of in vitro tests to eliminate much animal use, both documents suggested that industry could use cell lines far more widely today to screen for relative toxicity.

The traditional approach for determining acute toxicity -- how deadly a chemical is -- has been the LD50 test. The original LD50 test (which stands for lethal dose 50 percent)rated the toxicity of chemicals by finding the dose that killed half the test animals. In addition to using death as an endpoint, the tests required large numbers of animals -- 50 to 100 per test. For obvious reasons, animal welfare organizations have long raised strenuous objections to the use of this method, and organizations dedicated to the 3Rs have made finding alternatives to the LD50 a high priority.

Progress has been slow, but it has happened. More humane approaches to the LD50 have gradually reduced the number of animals required (8 to 12 today). And other recent developments make it clear that the LD50's days are numbered:

On Aug. 21, in a meeting organized by the NTP, U.S. scientists agreed on final adjustments to a test called the Up-and-Down Procedure that will make it possible for the method to replace the LD50 test. Although this method takes longer, the Up-and-Down test gives good results with as few as six to nine rats.
Two other alternative tests, each using only eight to 14 rodents, have been developed in Europe. The Fixed Dose Procedure, first suggested by the British Toxicological Society in 1984, is based on dosing at a series of fixed dose levels, with 5 animals dosed at each level. The approach avoids the use of death as an endpoint, instead relying on the observation of clear signs of toxicity. The Acute Toxic Class Method, developed in Germany, is a stepwise procedure with the use of 3 animals per step. It is based on biometric evaluations of the results of fixed doses (the same series of dose levels in the FDP), which are adequately separated to enable a substance to be ranked for hazard classification purposes.
Most promising, the Organization for Economic Cooperation and Development (OECD), an international trade group that includes several European countries, Japan and the United States, is removing the old LD50 test from its guidelines. Within a year of final OECD approval, the older animal-intensive LD50 method can be replaced by the regulatory agencies of the member governments with less animal-intensive tests such as the three described above. The OECD expects the switch to occur by the end of 2002.

For additional information see this page. For full text of both the report and the guidance document, go to this page.