Biomedicine Source: Science News, Vol. 142, No. 3 (Jul. 18, 1992), p. 46 Published by: Society for Science & the Public Stable URL: http://www.jstor.org/stable/3976871 Accessed: 06/10/2008 13:49

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http://www.jstor.org Biomedicine Environment

Heartarrhythmias from drug Modeling a shower'stoxic threat The Food and Drug Administration(FDA) last week asked Studies have documentedthe presence in drinkingwater of the manufacturerof the popular prescription allergy drug many potentially toxic volatile organic chemicals (VOCs)- terfenadine - sold under the trade name Seldane - to warn fromchloroform and pesticides to carbon tetrachloride.Such physiciansthat the drug can cause potentially fatalabnormal findings have spurred investigationsinto the inhalation haz- heart rhythms in some patients. ards these compounds may pose when released into the air Terfenadine'smanufacturer, Marion Merrell Dow, Inc., of during baths and showers. However,because shower and tub KansasCity, Mo., responded by sending 600,000mailgrams to equipment,as well as other design features,differed widely in care professionals, informingthem of "rare cases of these experiments,air releases for a single VOCcould vary up serious cardiovascularadverse events" following use of the to 10-foldfrom one studied system to another,observes JohnC. drug, especially in patients also taking the antifungaldrug Littleof LawrenceBerkeley (Calif.) Laboratory ketoconazoleor the antibiotic erythromycin. A general model incorporating known factors such as a Since terfenadinewas approvedin the UnitedStates in 1985, chemical'svolatility, water temperature,and the flow rates of the FDAhas recorded 64 serious cardiac events - including water and air would help gauge the relative impacts of other cardiac arrest and various types of life-threatening ar- showervariables. Little developed such a model, described in rhythmias-among the 200 millionpatients who havetaken the the July ENVIRONMENTALSCIENCE AND TECHNOLOGY, by applying a drug. Fourpatients who experienced the adverse events died. classic engineeringtheory to datafrom five showerstudies that A Marion Merrell Dow spokesman said that most of the others conducted.The trick to modelinga shower'sturbulent events are attributableeither to drug interactionswith keto- air-waterinterface, he explains,is to treatthe materialon either conazole or erythromycin,or to preexistingliver damage that side of that interfaceas a stagnantthin film. allowed terfenadine to build up to toxic levels in patients' The most volatilechemical studied in the experimentswas a bloodstreams.He said the companyhas changedterfenadine's Freon known as CFC-11.Little's worst-case analyses indicate label to advise against its use by such patients. He added that that people showeringfor 10minutes in water containingthis Marion Merrell Dow has deferred a decision on whether to VOCwould inhale 50 percent more of the potential toxicant apply for approvalto sell an over-the-counterpreparation of than they would ingest by drinking two liters of that water. terfenadine,pending furthertests of the drug'ssafety Indeed, his analyses indicate, under the same shower condi- tions, exposures to CFC-11would be three times higher than Renewedflap over AIDS test patent those to the lowest-volatilityVOCs studied - the pesticide 1,2- The of Paris has requested millions of dibromo-3-chloropropane,a suspected carcinogen. dollarsin past and futureroyalties from the U.S.government on The more volatile chemicals also take longer to saturate sales of the patented AIDSblood test developed by U.S.and indoorair. "I don't want to sound alarmist,"Little says, "butthis Frenchscientists, according to an American attorney repre- could have serious implicationsfor institutionalshower facili- senting the Frenchresearch center. ties, likehealth clubs," that are in use all dayand don'tprovide a The request was made on the grounds that U.S.negotiators lot of ventilation.While air concentrationsof the low-volatility misled the French over the timing and sequence of the compounds peak in enclosed spaces in about three hours, scientific discoveries that led up to the test's roughly simul- Little's model indicates that concentrations of very volatile taneous development by U.S. National Institutes of Health compoundscan keep growingfor up to 16hours. researcherRobert C. Galloand PasteurInstitute scientist Luc By confirmingthat water turbulence represents one of the Montagnier.Those negotiations ended with a 1987agreement biggest factorsaffecting a VOC'srelease, Littlesays, the model to share the royaltieson the AIDStest patent,which have so far suggests that ways to minimize a shower head's creation of totaled roughly$50 million. turbulentmists may offer a fertile field for study. The PasteurInstitute's U.S. attorney, Michael Epstein of the The new model makes possible "muchbetter predictionsof New YorkCity law firmWeil, Gotshal & Manges,says his client VOC-inhalationexposures from showers"for chemicals and has not receiveda response fromthe U.S.Department of Health conditions not yet studied, Little says. At a minimum, that and HumanServices (HHS)regarding a Januaryrequest for all should help drinking-waterregulators, he adds, since it makes of the royalties from sales of the test. He says the Pasteur no sense to regulatecontaminants solely on ingestion risks if Institute is "actively considering"filing suit against HHS to daily showers can present comparableor greaterdangers. resolve the issue. The Frenchare demandingall of the royaltiesfrom the test on Insectsmine lake contaminants the basis of a public admission by Gallo that his laboratory Manywinged insects spend their early life at the bottomof a isolated the upon which the test is based from samples lake,feeding in or nearsediment. As they matureand away- that had been inadvertently contaminated by a virus in a often to become dinner for birds, amphibians,or bats - they separatesample sent to him by Montagnier.Gallo admitted the can transport back into the food chain pollutants formerly mix-up last summer in a letter published in NATURE.Montag- locked away in sediment, a new study shows. nier has subsequentlyconceded that he and his colleagues did Canadian researchers deposited tetrachlorodibenzofuran not knowof the existence of thatvirus and thatthey based their (TCDF)- a dioxin-likechemical - into 5-meter-diametertubes blood test on another,slightly differentvirus. anchored in shallow lake water.TCDF levels in mature bugs Gallo'sattorney, Joseph Onek of the Washington,D.C., law leaving the tubes over succeeding weeks were compared to firm Crowell& Moring,contends that the source of the virus those of insects from tubes with no added TCDEThe data used in either the U.S.or the Frenchblood test is irrelevantto indicate that insects from even a relatively unproductive the issue of the AIDStest patent.What's important, he says, is northern lake can remove "a small [about 1 percent] but who first performedthe tricky feat of using from an biologically significant portion" from sediments each year, AIDSvirus to detect AIDSantibodies in the blood of infected reportWayne L. Fairchildand his co-workersat the Freshwater individuals. Institute in Winnipeg,Manitoba. Moreover, they write in the "Nothing has been learned that gives [the French] any June ENVIRONMENTALTOXICOLOGY AND CHEMISTRY,these totals justificationfor changing the settlement,"says Onek. "Ifthey don't count the contribution of insects too big for effective want to go to court, let them ..,. they don'thave a case." trapping,such as mayflies and dragonflies.

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