120 



ic^uay, MAKLH 23, 199] 



Many Say Lab-Animal Tests 

 Fail to Measure Human Risk 



ce spend 



B, JOEL HRINKLEY 



GAITHERSBUKC. Md . Mai 

 Dozens of caged rats an 

 ihor days here m a labor nioi y chewing 

 on Purina rodent chow laced with as 

 much boric acid as ihey can tolerate 

 without risk of death from poisonmj; 



These rodenis and moie than 1,000 

 others are being used to study seven 

 common environmental and household 

 chemicals to see if any cause reproduc- 

 tive problems The rats and mice are 

 allowed to breed at will Then scientists 

 here at ROW Sciences, a icsearch 

 laboratory that works under Federal 

 contract, examine several generations 

 of offspring for abnormalities or de- 

 fects 



This project is just one of roughly 65 

 rodent studies under way at I 5 labora- 

 tories across the country at an average 

 cost of about S2 million each For much 

 of the last two decades, these studies 

 have been the Government's most im- 

 portant diagnostic tool for identifying 

 environmental problems that are 

 health haiards and setting priorities 

 for Federal regulation. 



Billions Down the Drain? 



But now the animal-studies program j 

 is being hobbled by doubts about its I 

 worth. So much evidence has accumu ! 

 lated that chemicals frequently have 

 wholly different effects in animals and 

 humans that officials throughout Gov- 

 ernment and industry often do not act 

 on the studies' findings 



And with that growing skepticism, 

 the rationale behind a large portion of 

 the nation's environmental regulation 

 is thrown into question 



As a result, even Dr. Kenneih Olden, 

 director of the National Institute of 

 Environmental Health Sciences, the 

 branch of the National institutes of 

 Health that directs the animal studies. 

 asks whether the nation is wasting 

 billions of dollars regulating sub- 

 stances that might pose little risk. 



The findings from about 450 animal | 

 studies over the last several decades, 



Dr Olden said, have led Federal and state 

 governments to write thousands of regula- 

 tions forcing government and industry to 

 :; id lens of billions of dollars a year regu- 



... ^ the use and disposal of several do2en 

 chemicals, or finding alternatives for chemi- 

 cals Ihat have been restricted or banned 



For instance, it was data from rodent 

 studies that \e* the Government to ban or 



the us*: ni two kinds of artif 

 iers. cycla males and saccharin 

 the pesticide DDT and the nidus 



In Di Oldens view, Thai's an awful lot ol 

 money to be spending to be regulating sub- 

 stances we might not have to be regulating ai 

 all if we had more information " 



Afiei spending many billions of dollars to 

 clean up dioxin, the Government is midway 



[ bee a 



,Uld!. 



of people exposed to dioxin — once consid- 

 ered one of the most poisonous substances in 

 the world — show it is not nearly as hai mful 

 as originally believed 



Similarly. John A Moore, a formei assist- 

 ant administrator for the Environmental 

 Protection Agency who now heads the pri- 

 vate Institute lor Evaluating Health Ri.ks, 

 noted that DDT was banned because it was 

 believed to be a carcinogen 



But new data show that it poses "a rela- 

 tively modest cancer risk.'" Dr. Moore said, 

 though DDT docs present other environmen- 

 tal hazards And as for some of the other 

 chemicals that have caused cancer in. ro- 

 dents. Dr. Richard A. Gnesemer, deputy 

 director of Dr Olden s institute, offered some 

 additional revisionist ideas 



"Saccharin doesn't have much risk," he 

 said, "and I don't think cyclamaies have any 

 risk at all " 



Scott Green understands the weaknesses 

 of his research He is R.O W.'s laboratory 

 manager, and he did note that the reproduc- 

 tive studies "are already finding some ef- 

 fects " Some rats and mice are producing 

 fewer litters that are smaller than average 

 'But is that relevant to what's happening out 

 there in the environment?" he asked "I can't 

 tell you." 



Origins 



Rodents Are Used 

 In War on Cancer 



The Government first began experiment- 

 ing with rodent studies in the early 1960's. 

 and the program grew exponentially after 

 the Nixon Administration announced the 

 Government's "war on cancer" in 1971. Even 

 with some known weaknesses, scientists en- 

 thusiastically embraced the animal studies 

 as clear indicators of cancer risks. 



Though there was no legal requirement to 

 act on the studies' results, a welter of laws 

 did lequire Government agencies to protect 

 the public from foods, drugs, household prod- 

 ucts, industrial chemicals and other sub- 

 stances that caused cancer. So Government 

 officials responsible for protecting the public 

 health accepted the data as justification for 

 many new regulations in the 19?0's 



1980s, new data f.om ihe 

 helped fuel anoihci wave of 

 nmcntalism — the push to 

 am compounds believed to be 

 present in an. water or the 



Wi 



lew piece of environmental leg- 

 I'.lation — the Super fund law, i cvisions to the 

 Safe Dunking Water Act and others — Con- 

 gress required the EPA. and other agencies 

 iu set safe exposure limits for hundreds of 

 specific pesticides, industrial chemicals and 

 other substances Those new limits were 

 derived from rodcni-study data, thousands 

 of new regulations were written as a result 



Ily the mid-1980s, however, new research 

 findings began to cast new doubts on the 

 validity of the animal research Government 

 was no longer so quick to accept the results 

 automatically in every case But by then, 

 dozens of substances had been ruled safe or 

 dangerous based on the animal studies alone 



By the lime Dr. Olden took over as director 

 ol the Health Sciences Institute in 1991, the 

 animal studies were increasingly being 

 called into question Almost immediately, he 

 empaneled a group of the nation's leading 

 experts io study his agency's toxicology- 

 research program to help him decide wheth- 

 er to look for a new approach. 



Last summer, the group's report said 

 many of the assumptions driving the rat and 

 mouse research "do not appear to be valid " 

 The experts particularly questioned the prac- 

 tice of feeding rodenis the "maximum toler- 

 ated dose" of the chemical being tested, the 

 M.T.D.. as It Is called 



Finding the Poison Level 



With thai technique, used in almost every 

 animal study, scientists feed a lest group of ' 

 mice largeij and larger quantities of a sub- ' 

 stance until, they find the level that actually 

 poisons the animals. Then during the actual ' 

 lest, ihey feed new animals what they have j 

 determined is the maximum dose the animal 

 can tolerate without death from poisoning. . 



The reasoning is that high doses will more 

 reliably produce lumors or other effects in 

 statistically 'significant numbers. Scientists 

 might have to use thousands of animals to get ' 

 a meaningful result at doses close to normal ' 

 human exposure — 85,000 mice for the sac- 1 

 charin study., Dr Gnesemer said. 



So using the high-dose reactions, scientists ' 

 devised scales helping them to speculate on j 

 how people might react at lower levels. But 

 Dr Olden's review committee said it did not 

 believe that this reasoning was valid- The 

 review committee wrote, "Approximately i 

 two-thirds of the carcinogens would not be 

 positive, i.e., not considered as carcinogens, if 

 [he M.T.D. was not used." 



In other words, two-thirds of the sub- I 

 stances that proved to be cancerous in the I 

 animal tests would present no cancer danger l 

 to humans at normal doses 



Dr Gnesemer and others disagreed with i 

 that particular finding. They said that proba- 

 bly only one-third, not two-thirds, of ihe 

 chemicals shown lo be carcinogens in ani- ' 

 mals would likely be benign at lower levels. j 

 Still, Dr. Criescmer acknowledged, a possi- 

 ble error rale of even 33 percent is worn- j 

 some 



