The second in a series re-evaluating hazards identified in the 1950s and 60s

Jacobson, Kevin

Mazur, Allan

English

UNH Scholars' Repository

RISK: Health, Safety & Environment (1990-2002)Volume 10 | Number 2 Article 3March 1999Looking Back: CyclamateAllan MazurKevin JacobsonFollow this and additional works at: https://scholars.unh.edu/riskPart of the Chemical Engineering Commons, Food and Drug Law Commons, Food ChemistryCommons, and the Health Policy CommonsThis Comment is brought to you for free and open access by the University of New Hampshire – School of Law at University of New HampshireScholars' Repository. It has been accepted for inclusion in RISK: Health, Safety & Environment (1990-2002) by an authorized editor of University ofNew Hampshire Scholars' Repository. For more information, please contact ellen.phillips@law.unh.edu.Repository CitationAllan Mazur & Kevin Jacobson, Looking Back: Cyclamate, 10 RISK 95 (1999).Looking Back: CyclamateCover Page FootnoteBased on work under National Science Foundation Grant SBR-9808684 to Allan Mazur for the re-evaluationof public warnings raised during the 1950s and 60s about ostensible hazards to health or the environment.Nothing expressed here necessarily reflects the views of the NSFThis comment is available in RISK: Health, Safety & Environment (1990-2002): https://scholars.unh.edu/risk/vol10/iss2/3Looking Back: Cyclamate*Allan Mazur & Kevin Jacobson**IntroductionCyclamates are a class of synthetic, non-caloric sugar substitutes,not as sweet as, but without the unpleasant aftertaste of, saccharin. Firstapproved in 1950 for use by diabetics and severely obese people, theFood and Drug Administration (FDA) in 1958 reclassified them asacceptable food additives, based on a rather short history of apparentlysafe use. Then the American image of feminine beauty was busty andhippy, but, during the 1960s, as slender figures became the ideal, themarket increased for diet foods, especially sodas; use grew rapidly untilcyclamate was consumed by three-quarters of Americans. 1The 1960s were also a time of increasing public concern aboutchemical adulteration of food and water. The battle against microbeadulteration had largely been won in the early decades of the century,and scarcity was the major food concern during the Depression andWorld War II. In the bountiful 1950s we were warned to vary our dietso that we would get all necessary nutrients, as when television's popularscience teacher, "Mr. Wizard," advised us incessantly to start each daywith a "better breakfast" of fruitcerealmilkbreadandbutterwitheggs-orbreakfastmeatforvariety. No concern here with fat or cholesterol,much less chemical additives or pollutants. We bought DDT"bugbombs" to destroy insects in homes and gardens, while trucks andairplanes sprayed clouds of that inexpensive insecticide over fields andneighborhoods, often far more than recommended, carelessly engulfinganimals and people. Most people didn't care then.* Based on work under National Science Foundation Grant SBR-9808684 to AllanMazur for the re-evaluation of public warnings raised during the 1950s and 60s aboutostensible hazards to health or the environment. Nothing expressed here necessarilyreflects the views of the NSF.** Dr. Mazur is Professor of Public Affairs, Maxwell School, Syracuse University.Mr. Jacobson is a doctoral student in the Maxwell School.1 Edward Lawless, Technology and Social Shock (1977); Allan Mazur, U.S.Trends in Feminine Beauty and Overadaptation, 22 J. Sex Res. 281 (1986).10 Risk. Health, Safety & Environment 95 [Spring 1999]By the late 1950s, Americans on the political left were complainingof the hazard of trace doses of radioactivity from the atmospherictesting of atomic bombs. At nearly the same time, but on the politicalright, was a mass protest against adding fluoride - toxic in high doses- to public water supplies at one part per million to prevent dentalcavities. Despite little overlap in memberships of these movements, thearguments were basically the same. In 1958 a clause introduced byantifluoridationist U.S. Representative James Delaney forbade the FDAfrom approving as, e.g, a food additive, any chemical that causes cancerin man or animal. 2 These political movements paved the way forRachel Carson's best-seller, Silent Spring, warning of trace pesticides.It appeared in 1962, just as the tranquilizer thalidomide was announcedto cause birth defects when taken by pregnant women. Approved foruse in Europe but not here, thalidomide had caused babies to be bornwith flipper-like stumps instead of arms and legs. Dr. Frances Kelsey ofthe FDA had single-handedly stood firm against great pressure andabuse in denying its approval, thus saving America from tragedy. Sheprovided the best press the FDA ever had.3Cyclamate was among several food additives and drugs thatbecame suspect during the 1960s. 4 The National Academy ofSciences, in periodic reviews for the FDA of cyclamate toxicity, foundthe sweetener generally safe but warned against uncontrolled publicdistribution because of physiological effects including diarrhea, and theunknown consequences of prolonged exposure. Also, doubts were raisedthat people using cyclamates actually lose weight. In 1968 FDAscientists led by Dr. Marvin Legator showed that cyclohexylamine, ametabolite of cyclamate that forms in the digestive tract, causeschromosome breakage in rats, suggesting the possibility of genedamage. Responding to these concerns in December 1968, the FDAreduced its recommended daily upper limit for cyclamate to 50milligrams per kilogram of body weight, which meant that two cans ofdiet soda might exceed the limit for a 60-pound child.In the meantime, another FDA scientist, Dr. Jacqueline Verrett,had been injecting cyclamate into chicken eggs, producing embryo2 See Public Citizen v. Young, 831 F.2d 1108, n.1 (D.C. Cir. 1987).3 Allan Mazur, Why Do We Worry About Trace Poisons? 7 Risk 35 (1996).4 James Turner, The Chemical Feast (1970).Mazur & Jacobson: Cyclamate 97deformities. These results were forcefully brought to the attention ofFDA Commissioner Herbert Ley in April 1969 when one of Verrett'ssuperiors carried deformed chicken embryos into Ley's office, but theCommissioner took no action. On October 1, 1969, Dr. Verrett wasinterviewed on NBC television news, apparently with the consent of anFDA deputy commissioner. Setting off a wave of concern, shedescribed her finding that cyclamate deforms chicken embryos, itsthalidomide-like inference to human embryos fairly obvious. Verrett'sappearance drew an immediate rebuttal from Commissioner Ley,saying "Cyclamates are safe within the present state of knowledge andscientific opinion available to me." Spokesmen for Abbott Laboratories,one of the largest cyclamate producers, also declared the sweetener safeand attributed the alarm to the sugar industry.5 Commissioner Ley'sboss, Secretary of Health, Education and Welfare, Robert Finch, wasdrawn into the controversy, criticizing in the press FDA's handling ofsafety questions about cyclamate and indicating that reorganization ofthe agency's procedures and personnel was inevitable.Two weeks later, Abbott Laboratories released a study it hadcommissioned showing that 8 out of 80 rats fed large amounts of amixture of ten parts cyclamate to one part saccharin (proportions mostoften used in diet sodas) developed bladder tumors, some cancerous.This was the basis for Secretary Finch's announcement, at an October18 press conference, that indications of cancer clearly placed cyclamatein violation of the Delaney Clause. Therefore the FDA could no longerallow it to be used in nonprescription drinks and foods, and productswith cyclamate must be recalled from stores. The following year, 1970,the FDA banned cyclamate from prescription products too.Risk AssessmentIt had not been cancer but the thalidomide-like birth defects intelevised chick embryos that had spurred public concern over cyclamatein 1969. Today this is not an issue of scientific concern. Injection of achemical into a chicken egg is devalued by authorities as a test forhuman birth defects because there is no parallel between the chickenembryo and a mammal's placenta. In any case, new feeding tests5 Id.; Morton Mintz, Rise and Fall of Cyclamates, Washington Post, Oct. 26,1969, at Al.10 Risk. Health, Safety & Environment 95 [Spring 1999]showed that cyclamate does not produce birth defects in mammals.6The FDA's judgement that cyclamate may cause bladder cancerwas based on one study of rats fed a combination of cyclamate andsaccharin. (Tests where cyclamate materials were implanted into rodentbladders were generally discounted because implantation does notcorrespond with feeding as a route of administration.) By 1982, whenAbbott Labs and a trade organization, the Calorie Control Council,petitioned anew for approval of the sweetener, some twenty new cancerbioassays had been conducted in which cyclamate was fed to a varietyof animals species without showing any cancer-causing effect, even athigh doses. Two attempts to replicate the original study linkingcyclamate to bladder cancer failed to produce cancer in rats. The causeof the tumors in the original rats was never established, but conjecturedcauses include parasites or stones in the rats' bladders, or environmentalcontamination of some of their cages. 7In 1984 the FDA's own Cancer Assessment Committee concludedthat cyclamate is not carcinogenic. The Agency, under embarrassingpressure to reverse its ban, asked the prestigious National Academy ofSciences to evaluate the cancer causing potential of the sweetener. TheAcademy concluded the next year, on the basis of epidemiological andanimal studies, that neither cyclamate nor its metabolitecyclohexylamaine are carcinogenic. However the Academy did notfully exonerate cyclamate, instead suggesting more investigation ofhints that it could be a co-carcinogen, promoting the action of othercancer-causing substances that might be in the body.8While the cancer issue was moving toward resolution, the prospectof genetic damage remained ambiguous. Legator's 1968 finding, thatthe metabolite cyclohexylamine causes chromosome breakage in rats,6 M. Jacqueline Verrett, et al., Toxicity and Teratogenicity of Food AdditiveChemicals in the Developing Chicken Embryo, 56 Toxicol. & Appl. Pharm. 273(1980); Barbara Bopp, Robert Sonders & James Kesterson, Toxicological Aspects ofCyclamate and Cyclohexylamine, 16 CRC Critical Reviews of Toxicology 213(1986); Sweeteners: Health Effects (Gary Williams, Ed. 1988).7 Calorie Control Council and Abbott Laboratories, Food Additive Petition forCyclamate, 2A3672 (1982); Kathleen Meister, Low-Calorie Sweeteners (Amer.Council on Science and Health 1993).8 National Academy of Sciences, Evaluation of Cyclamate for Carcinogenicity(1985). The same conclusion had been reached by the FDA's Cancer AssessmentCommittee a year earlier.Mazur &Jacobson: Cyclamate 99could not be confirmed by other investigators. Many other tests wererun using diverse methods; some supported the possibility of genedamage, some did not. This matter was complicated by greatuncertainty, still not fully resolved, about how to test for mutageniceffects. Scientists associated with Abbott or sponsored by the CalorieControl Council, evaluating the entire battery of tests, concluded thatneither cyclamate nor its metabolite represent a significant mutagenichazard. 9 We are not aware of a serious challenge to their conclusion,but the issue may never be fully resolved.Nothing can be proven 100% safe. By 1989, cyclamate seemed tohave sufficiently passed muster. The front page of the Washington Postclaimed the FDA waswidely expected to reapprove it, possibly this year. Onceaccused of causing everything from bladder cancer to birthdefects, cyclamate is now widely thought to be harmless.The acting director for the FDA's Center for Food Safety and AppliedNutrition was quoted "saying that with cyclamate we made a mistake."Referring to a 1980 FDA refusal to lift the ban, back in 1980, he said,"The matter was taken out of the hands of the scientists here andhandled by attorneys." 10Whether because of its attorneys or scientists, the FDA did notreapprove cyclamate in 1989 nor has it acted on the petition as of thiswriting, ten years later. New suspicions had arisen about cyclamate'smetabolite. Male animals show testicular atrophy when fedcyclohexylamine at high doses. The petitioners responded that therewould be no diminution of testicles if the acceptable daily dose ofcyclamate were suitably low. Also, the FDA was concerned that themetabolite elevated blood pressure in test animals and humans, leadingto a new round of research.ConclusionThe diet soda industry, representing about 60% of cyclamate use,quickly responded by substituting a saccharin-sugar mixture, and9 Bopp, et al., supra note 5, at 276; see also Brusick et al., Assessment of theGenotoxicity of Calcium Cyclamate and Cyclohexylamine, 14 Envt'l & MolecularMutagenesis 188 (1989).10 Malcolm Gladwell, U.S. Expected to Lift Ban on Cyclamate, Washington Post,May 16 1989 (quoting Robert Scheuplein).10 Risk- Health, Safety & Environment 95 [Spring 1999]consumption of diet products continued upward. Industry criticizedthe Delaney Clause as too restrictive, preventing any balancing ofbenefits and risks of additives, but it remains in effect. Then, the FDAin 1977 proposed to ban saccharin too when animal research suggestedthat it caused bladder cancer. However, Congress quickly set the banaside. Today saccharin remains in use, along with the newer aspartameand the newest non-caloric sweetener, acesulfame potassium.Cyclamate does not cause cancer or birth defects as once feared.Yet, as each suspected harm was ruled out, others surfaced, e.g., co-carcinogenicity, testicular atrophy and high blood pressure. Fordefenders, this resembles the carnival game, Whack-A-Mole; as molesare beaten back into their holes, others emerge. For critics, it resemblesa pearl-rich bed of oysters; if enough are opened, a pearl may appear:There will always be more to open until assessors lose interest, as maybe happening.More than 50 nations, including most of Europe, approvecyclamate. The World Health Organization's Joint Expert Committeeon Food Additives has consistently found cyclamate safe. Canada, in atwist from the U.S. position, has more stringent restrictions onsaccharin than on cyclamate, allowing both as table-top sweeteners butonly cyclamate to sweeten drugs. Sweden, another nation with acyclamate ban, was told by the European Commission in 1999 thatEuropean Union law forbids that because cyclamate is not harmful.11The petition for approval of cyclamate that Abbott Labs and theCalorie Control Council submitted to the FDA in 1982 is still pending.The FDA will not comment on pending petitions, so we do not know ifit is under active consideration. Abbott says it is no longer interested,but a spokesperson for the Calorie Control Council tells us that somecompanies still want to use it. Given considerable public suspicion aboutchemical sweeteners, probably including several now awaiting approval,the industry would no doubt enjoy seeing cyclamate's reputationrestored, even if it never appears in U.S. markets.11 Reuters, EU Rejects Swedish Restrictions on Food Additives, Jan. 8, 1999.

Looking Back: Cyclamate

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Looking Back: Cyclamate

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