Document epgk0RJOnKw2jLayndLMnmjM

A Division ot The Society of The Plastics Industry, Inc. Roy T. Gottesman EmcutivDitvcr ,April 16 1990 To: VI Health Safety & Environment Comm. VI Medical subcommitee FOR YOUR INFORMATION l I j i Wayne interchange Piaza // 755 Route 46 West * Wayne, New Jersey 07470 (201) 890-9299 ID P V) <n o CD rfoc* TOXICOLOGY -- * Measuring Chemicals' Dangers: Tbo Much Guesswork? fly Malcolm Oladwsli W**hr*m IVw UUf W|,,, hen sciential] calculate whether Wpesticide residues hill little children or automobile exhaust causes can* 'Ci. tliere comes a point when they put aside their hard data anil their complex the orems and make a guess. They know the elfccl of massive doses of each chemical on cats and mice. But public I'oliry is aboul humans, nol animals, and it must apply to chemicals often found in very onatl amounts. To draw any conclusions about the real world from what they have seen in the laboratory, scientists have had to speculate. For 20 years, toxicologists have lived With this uneertaioty in trying to measure the dangers posed by the chemicals we eat, drink and breathe. Rut when rising public concern aboul potentially dangerous chem icals is m conflict with rising costs of elim inating risk, society is faced with increas ingly difficult chokes. Many scientists are I'cginnmg to argue that the guesses made in the name of risk assessment are no longer good enough. `Many of the leading people in the field are getting very suspicious about animal testa and wluit they mean,* aaid Bruce Ames, director of the environmental health center at the University of California at Berkeley. *1 think we may be being led down the wrong path.* A Linear Assumption The problem arises from the (act that the risks of developing cancer from typical expo sure to many toxic chemlcala may be in the range of one In a million or even leu. That meana that (or a laboratory animal experi ment to have a chance of detecting a chem ical's carcinogenicity at realistic doses, it would have to use millions of animals. Because that la hardly practical, scien tists do the next best thing. They feed a far smaller group of rats or mice a much higher than normal amount of the chemical. It Is understood that this creates an unrealistic ally high incidence of cancer. Then the re searchers extrapolate backward to estimate how many cancers would have been caused at a more realistic dose. In extrapolating, both the Environmental Protection Agency and the Pood and Drug Administration make what is called a linear assumption. For example, if 50 out of 100 rats got cancer from eating a bowl of a par ticularly nasty chemical every day, then fed- eial health oifidals assume that at half a bowl a day, half as many would get cancer, and at quarter bowl, a quarter would get lick and so on down to the point where if the rata were nibbling on the chemical only once a month, Juat one or two would develop tumors. This is caBed a linear assumption because a graph of it, called a dose-response curve, ' would be as straight as i yardstick (see dia gram). Here is where the controversy begins. Although It seems logical that the risk l cancer should change ht proportion to the chemical dose, that h only a guess--a guess that is now being called into question. "When ll comes right down to It, why should we expect nature to give us dose-re sponse curves thst follow any predictable mathematical formulae said John Ballar, a toxicologist at Montreal's McGill Univer sity. *Why should they follow straight line or some regular curve) (don't think you an make an Iron law about these things.* What if, for example, a chemical is so po tent that it poses a pave risk ht even the smallest amounts) If tow doses do about as much damage as it possible, then large doses could not make modi difference. The dose-response curve ht this case would be shaped like a kind of street tsmp, rising very shsrpty In Ike beginning and leveling off it M*i*r doses (Sea dhtgrsm, baaed on findings (or vinyl chloride, a potent carcin ogen). If policy decisions an made on the assumption of a straight-Hno retstkonaMp, the risk of intermediate dotes would be un derestimated. It m*y be that a bowlful of thia chemical every day, like the hypothetical nasty chem ical, stilt kills 50 out of 100 rats. But a nibble every month, which the linear assumption guessed was killing put one or two, might actually cause cancer m 15 or 20 rata. Or consider the opposite. What if high doses of a chemical ate needed to trigger the complex chain of eventa that cause can cer) This b a well-known phenomenon among some carcinogens. Formaldehyde b an example (See diagram). In such cases the risk of cancer would took like a hockey stick, increasing only slightly until the crit ical man of the chemical b reached and then rising sharply. Here as well the typical extrapolations bout the dangers of low doses might be wrong. A bowl of this chemicsl. like the hy pothetical nasty chemical, might still kill 50 out of 100 rats. But a quarter dose might not even come close to killing a quarter of the rats.!(that quantity fell below the can cer threshold, it wouldn't be any more dan gerous than a monlhly nibble. The differences among various dnse-re* spouse curves have implications for (-licvmaking. A chemical the governin' nr flunks is Safe fur hum.iu i oov.riM|i! II n ............... . Isafe at all tf its curve rcvuihies flu- sireel tamp. Hockey sinlr chemicals, on lie- other hand, ciiuhl fv ptonmvmt'il n:>.v. ,f|iaV' risks when tn lac! at realistic doses 111*-v VIvirtually harmless. Large sums spent tn reduce rxposurrs to a hockey-stick chemical to extreme lows might buy very litlie a third safely. Thr morinv might be better spent rntnuhlmg efforts to [rO't society against si reel-lamp chenue.iK A `Default Position' _ llow might chemicals deviate (roil) lie yardstick model? Vinyl chloride, a street lamp chemical, is dangerous because the body processes it into another substance that causes potentially cancerous mulllions. Bill (hr hotly can only mrtaholire a limited amount id vinyl chloride at one time While cancer usks from thr rhenurat rise steeply at lower doses, they level nil as the body can no longer process any more of it. At the same time, recent research into how cancer begins lends some credence to the idea that some chemicals may have a hockey tick shaped-curve. For example, the greatest risk of cancer from chemical toxins appears to be when cells are dividing rapidly, replacing celts killed by ihe toxin. But low levels of a chemical might not cause enough cell damage to kill cells and cause rapid cell proliferation, in many cases, wholesale ceH killing--with its ac companying increased risks of cancer--oe curs only when a toxin reaches a critical level hi the body. The problem, however, is that scientists understand very few chemicals well enough to know which model they fit, if any. "Our position is that linear dose extrapoblions ire Ihe only Ones are can justify as a general principle,' said David Gaylor, director of the biometry staff of the National Toxicol ogy Program. 'It's a default position unless there is convincing evidence to the contrary, which there rarely is. It would be very risky to assume hockey sticks is a rule* *In most cases the (government's! pro cedure probably overestimates cancer risks,* said John Graham, a professor at Harvard University's School of Public Health. *ln some cases they are prohab^ underestimating it, and sometime* they1 might be right on the mark. But what we have to keep in mind is that no one realty knows the right answtr.* et?909lS'8H