Document 4J1m1aDEGvL7joj6OL6kZ1MoG

The shift to toxicology tests in vitro URL 05070 Early this month, a House Science and Technology subcommittee heard testi mony on a new bill (H R. 6245) that would encourage a switch in all federal ly funded research from tests in vivo-- those making use of live animals--to in vitro techniques using laboratory appa ratus. The bill joins other similar pieces of legislation introduced last year and is a strong indication that the long-stand ing and often bitter controversy over the use of living animals in toxicological testing of drugs, cosmetics and chemi cals remains as vigorous as ever. But even as this new bill is debated in Congress, in vitro procedures are edg ing out animal tests in many toxicology laboratories. While humanitarian consid erations have certainly contributed to this trend, another important factor is at work: In many applications, in vitro techniques are actually more cost-effec tive than tests using animals. `It is eas ier and faster, all things being equal, to carry out testing on organisms in a lab oratory dish than to maintain and work with an aniini colony," William F. Raub, asso ciate director for extra mural research training at the National Insti tutes of Health, told the House Subcommit tee on Science, Re search and Technology in the H.R. 6245 hear ings. Almost all toxicol ogy professionals ac knowledge that Miima.1 testing is a vital screen ing component fee new chemicals or drugs, but the sheer volume of tests required under such laws as the Toadc Substances Control Act is a shift to in vitro techniques, particularly in preliminary screening. Latest aftamattvaa. Evidence of this was abundant at last month's sympo sium on animals in biotnedkal research, held at the New York Academy of Sci ences. Researchers described some of the latest alternatives to animal test ing--in particular, the checking of new or existing chemicals for carcinogenicity and mutagenicity factors. Hie reason for toe growing popularity of toe in vitro procedures, says Dennis M. Stark of Rockefeller University (New York), is that, quite apart from being more humane, they are more sensitive, faster, i easier to quantify, and easier to repro duce accurately than in vivo tests, to Refinements are even being added to the Ames test, the oldest and roost use ful of toe mutagenicity procedures. De veloped in the early 1970s by biochemist Bruce Ames of the University of Cali fornia (Berkeley), this test examines the effect of a chemical on bacterial chro mosomes. Some of the latest tech niques, says Byron E. Butterworth, head of the Chemical Industry Institute of Toxicology's department of genetic toxicology, apply a chemical to cultured rat liver cells before it is subjected to Lab-dteh teats are often more sensitive, sealer end fester than those with Ive animals an Ames-type test These cells often convert the chemical to a metabolic product similar to that likely to be pro duced in a live anima.1 or human. Since it is frequently a metabo lite that is the bad actor in mutagenicity or carci nogenicity, the added screening step, says Butterworth, gives a more reliable picture of a chemical's behavior in living systems. Prescreening of anti cancer agents also is moving rapidly away from animal tests. At the Bristol-Myers research laborato ry in Syracuse, N.Y., for instance, sin gle cells from a human tumor sample are grown on dozens of test culture plates. Potential anticancer compounds are applied to the dividing cells and the results are compared with nontreated control plates. Bristol-Myers says the predictability of anticancer activity us ing this method should be much better than with animal studies." Rabbits, horaaahoa crab*. Along with these carcinogenicity and mutagenicity procedures are several other areas where in vitro techniques are challeng ing traditional in vivo testing. One is the determination of toe pyrogenic, or fever-inducing, properties of experimen tal drugs or chemicals. The traditional test involves intravenous injection of the agent into rabbits. However, Rocke feller University's Stark points out that, since 1977, tests for pyrogenic activity have also been carried out by observing the effect of a chemical on a serum from the blood of the horseshoe crab; coagulation of the blood serum is read as a sign of pyrogenic activity. Hie pyrogen test using rabbits has been easy to replace with an in vitro counterpart because it measures only one property. And while scientists are confident that in vitro alternatives will be found in many cases, they point out that the controversial Draize eye-irrita tion that will be a lot harder to eliminate UweiMna > is but Utton BtonsScs' Brusick sty* ft won't dtappMr as ChwMoa wEAE??5r Gt@fnts(h) because it measures a multitude of example, John McCormack of Johnson properties. Stark says that because of & Johnson's Baby Products Laborato this the new procedures will probably ries in Skillman, NJ., is using the sero comprise a whole battery of tesla. tonin release test to check the degree to Among the in vitro techniques that which shampoo ingredients may hurt Stark foresees as competing with the the eyes. While a Johnson & Johnson Draize test--all of them depending on spokesman admits that "the method the response of cell cultures to the chemical under test--are: The release of serotonin by cells de rived from the peritoneum--the mem Some experts ttffl believe that tests using animals show brane that lines the abdominal cavity-- higher standards of accuracy of a rat: The chemical's potential for causing irritation can be inferred from the amount of serotonin released by the can't be used on complex formulations," cells. McCormack says the test has a high The release of albumin from cultured correlation with animal tests. hepatoma (liver cancer) cells: The more Questioned accuracy. Although these albumin released, the more irritating procedures, like many others under the added chemical. study, show great promise as alterna r The local accumulation of macro phages (a kind of cell) in the blood of mice: The greater the accumulation of these cells where a chemical is added to a culture dish, the more irritating the chemical. Industrial researchers are already tives to animal tests, Rockefeller Uni versity's Stark gives one important warning: While needless animal Buffer ing should be avoided, any alternatives to tests in vivo "must produce equiva lent or better results." And the Nation al Institutes of Health's Raub told the starting to use some of these tests. For House subcommittee hearings early this month that the results of in vitro meth ods are only 60-80% as accurate as of established animal tests. --- There are many animal-based chemi- cal safety tests "not amenable to re placement at the present time," toxicol ogist David J. Brusick of Litton Bionetics (Kensington, Md.) told the re cent New York Academy of Sciences symposium. And Lance L. Simpson of Columbia University's Dept of Pharma cology warned: "The use of ftnimala is critically important to our ability to de velop new drugs" against cancer and heart disease. At the same time, as the Chemical Industry Institute of Toxicology's But- terworth points out animal tests are be coming more sophisticated. "Now we can use just a handful of animals," he says, "typically less than 10, and get the same information that formerly re quired several hundred animals." The move aw&y from tests in vivo is accelerating, however, regardless of the latest procedures' sophistication; and if Congress passes the legislation now be fore it, that will add an extra push. EmerzoneTMgenerators from Emery produce safe, economical, dependable ozone for water and air pollution treatment--and for chemical processing. 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