Political Toxicology and Its Impact
"The whole aim of practical politics is to keep the populace alarmed by menacing it with an endless series of hobgoblins, all of them imaginary." H. L. Mencken
Ever since James J. Delaney and the eighty-fifth Congress foisted the Delaney Clause on the world in the form of a legislative mandate included in the first piece of food additive legislation,[1] a variety of well-meaning, but sometimes suspiciously motivated scientists have been fingering a variety of chemicals to indict as human hazards[2]. True, indeed, that the modern crop of chemicals had some predecessors such as the elixir of sulfanilamide that caused 100 deaths as a result of drug contamination in the thirties,[3] but it at least seemed in the pre-1958 era to require actual proof of harm to bring about public reaction and federal legislation. Now the legislators are leaping to introduce bills that purport to ban useful materials because someone, somewhere, has reported controversial results on the basis of esoteric or unconventional studies to try to show that specific chemicals are reproductive or developmental toxicants, and may be potential carcinogens. The horse they most often ride is a pseudo-scientific concept deftly labeled "The Precautionary Principle"[4].*
As a prelude to the 1958 Food Additives Amendment, substances such as diethylstilbestrol (DES), proven to cause cancer to the daughters of pregnant women given the drug to help ease them through pregnancy; beta-naphthyl amine used to manufacture azo dyes but shown to cause cancer in the workplace; and a myriad of metals such as cobalt and nickel were shown to cause cancer when fed to animals. These substances were not used, per se, as food additives but were put forth as examples of the type of chemical to be feared if deliberately added to foods. As a result of the substantial testimony presented on these situations during the House of Representatives hearings that led to the Food Additives Amendments,[5] and despite vigorous industry efforts to have all additives subject only to the requirement that they are proven safe under their intended conditions of use, at the last minute the Congress did include a Delaney Clause in the Food Additive Amendments of 1958. This clause, incorporated in Section 409 (c)(3) of the Federal Food, Drug and Cosmetic Act of 1938, as amended, provides that "no additive shall be deemed to be safe if it is found to induce cancer when ingested by man or animal." Here then was a clause that effectively ordered the Food and Drug Administration (FDA) to forego issuing a food additive regulation for any chemical proven by any sort of feeding test to cause cancer, whereas other additives could be deemed safe so long as adverse effects did not occur when they were tested in a manner generally simulating their intended conditions of use. This was a completely disqualifying proviso opening the door for all sorts of testing that might show a substance caused cancer at some level of exposure, greatly exaggerating, or in some other way, perverting the intended conditions of use.
Early on, after 1958, most observers felt that the Delaney Clause would not be implemented in such a way as to cause much discomfort since the FDA topside had not proposed the clause and was believed to be opposed to its inclusion. This view was probably a correct one as FDA did find ways to distinguish a number of types of cases. For example, it ruled that Delaney would not be applied to bar an additive that contained a carcinogenic component if it were shown that the food additive as a whole, including the component, was not a carcinogen, and the carcinogenic component did not present a significant risk[6]. In some other cases, it deemed Delaney inapplicable if evidence of cancer-causing was so remote that it could be held irrelevant to any real-life dietary situation[7].
Nonetheless, in 1969, Abbot Laboratories, the main supplier presented data to FDA showing that a then very popular sweetener, cyclamates, could cause cancer in animals if ingested in huge amounts (the equivalent of 350 cans of diet soda per day). The Agency reacted by ruling on October 18, 1969, that Delaney applied so that cyclamates could not continue to be marketed on the basis of long-time safe use as a sweetener and, that, therefore they had to be taken off the market.[8] The producers and commercial users of cyclamates protested vigorously and spent a great deal of time and money attempting to convince FDA that this ruling was inappropriate[9]. This effort has been unavailing to this time even though cyclamates have been found safe and permitted for use in most other countries, including Canada.
At the time the cyclamates ban left only saccharin on the market as a non-sugar sweetener available for use by diabetics and dieters. In 1977, the marketplace and many consumers were hit again with data tending to show that gross exposure of animals to saccharin (the equivalent of 800 cans of soda a day) could also lead to stomach cancer. FDA was faced with banning the only remaining non-sugar sweetener on the market and was ruefully considering doing so[10]. This led Congress to hold hearings on the situation, and, in due course, it passed the Saccharin Study and Labeling Act of 1977, derogating from Delaney and permitting saccharin compounds to remain on the market[11]. Much time passed, and other sweeteners such as aspartame, acesulfame-K, and sucralose came along to meet the needs of diabetics and dieters so some began to ask if it was not time to reconsider saccharine and perhaps ban compounds using it. This has not been done and seems unlikely, at least, unless some new outcry comes along.
Other substances began to receive industry and consumer group attention as the years went by and the environmental movement spawned many new advocates, some dedicated and well-meaning, some merely opportunistic. In the fifties, the plastics industry began to study phthalates generally used to modify polyvinyl chloride and for many other product modification purposes. The early studies showed some effects on test animals but the effects noted were peroxisome proliferation in the liver of the test animals, an effect irrelevant to humans since such proliferations do not occur in the human liver except perhaps at unrealistically high exposure levels[12]. As a result, industry, and FDA were not unduly alarmed by the test results and, in fact, in 1982, the National Toxicology Program released a study and report indicating it did not believe there was data to indicate that most of the phthalates used in toys, medical devices, or for packaging presented any cancer hazard for humans[13].
More recently, however, the Consumer Product Safety Commission (CPSC) found it might have a way to increase Congressional support for its activities by focusing on phthalates and child safety issues[14]. CPSC started questioning toy manufacturers and the plastics industry over the use of phthalates in toys and devices such as pacifiers. In the opinion of most in industry, this was an act or series of acts grounded only in political motivation because there were no scientific studies to indicate that any safety hazard exists or existed[15]. The CPSC movement was heavily supported by such organizations as Greenpeace, Healthy Child for Healthy World, and Health Care Without Harm, among others[16]. The issue of what to do about phthalates is currently on the legislative agenda in Congress and in many state legislatures[17]. Strangely enough, it has even transcended the child safety area and has resulted in some proposals to ban the use of phthalates generally, FDA clearance of the same as indirect food additives notwithstanding[18]. While there is some worldwide attention being devoted to the evaluation of phthalates as hazardous to children, nowhere else is there talk of broad bans on what is a very useful and widely used family of adjuvants.
Other emanations of health risks from chemicals were also occurring during these times. Thus, in the early seventies, FDA was presented with data and ultimately a petition to clear acrylonitrile/styrene (called Cycle-Safe) polymers for use as beverage containers. It is well known that acrylonitrile as a monomer is toxic,[19] the petitioner, Monsanto Company, had gone through many stages of development and finally came up with an acrylonitrile/styrene polymer that could be demonstrated to be so stable when molded into bottles that one could not detect any being extracted in tests with dry, aqueous and oily solutions sensitive to 50 parts per billion. Later tests were made sensitive to 10 parts per billion, and still, there was no migration from the Monsanto test bottles. At first, the company took a self-determined position that it did not have a food additive issue because there was no migration of any substance from the bottles, i.e., that there was no reasonable expectation of migration and, hence, no food additive problem under the provisos of the Food Additive Amendments of 1958. Indeed, on June 5, 1972, after the data indicating no migration was presented to FDA at its request, the Agency issued a letter confirming the acceptable status of the bottles[20]. Construction of plants to make the bottles for Coca-Cola commenced.
Soon after this, however, partly because of data submitted by DuPont, the Commissioner determined that, because of putative migration, acrylonitrile copolymer was a "food additive" within the meaning of the statute. The Agency, therefore, published a regulation prescribing the conditions under which the chemical could be used safely in beverage containers. Acceptable migration of the monomer was set at 300 parts per billion.
Two years later, FDA noted test results adverse to acrylonitrile on the basis of animal studies so the Agency announced that the migration limit would be lowered to 50 ppb and all approval for beverage containers would be withdrawn. This regulation was held to be invalid by the Court of Appeals, and the Court told FDA it could not do this without a hearing. It ordered FDA to stay the administrative action on March 18, 1977[21] and ordered that the required hearing be completed within 60 days. Subsequently, on a joint motion of the parties, the time limitation was extended by 120 days.
A hearing then ensued with FDA's Administrative Law Judge Daniel Davidson issuing a decision in 1977 upholding the ban on beverage bottles[22]. This Initial Decision resulted in a Final Order prohibiting the manufacture of beverage containers made from acrylonitrile polymers irrespective of residual monomer or migration levels[23]. The issue in the case that was deemed determinative was the question of whether or not there was a migration of anything to food that would bring the acrylonitrile/styrene bottle under the Food Additives Amendment of 1958. The Hearing Examiner and the Commissioner sided with the Agency's attorneys and held that since the bottle would be in contact with food, there had to be migration sufficient to bring into play the Food Additives Amendment because the Second Law of Thermodynamics decrees that substances in contact will result in the diffusion of some molecules from one to the other.
The Agency decision was appealed to the United States Court of Appeals for the District of Columbia Circuit[24]. Extensive briefs were filed by all parties, and lengthy oral arguments took place on March 15, 1979. On November 6, 1979, Judge Harold Leventhal, writing for a unanimous panel ruled that FDA's reliance on the Second Law of Thermodynamics was ill-founded and that it could only sustain its view if it could show that there was significant and substantial evidence of migration in the test data. Said the Leventhal opinion:
Congress did not intend that the component requirement of "food additive" would be satisfied by...a mere finding of any contact with food...For the component element of the definition to be satisfied, Congress must have intended the Commissioner to determine, with a fair degree of confidence that a substance migrates to food in more than insignificant amounts[25].
Since FDA could not make such a determination, in due course, a Food Additive Regulation was issued in 1984 for acrylonitrile/styrene copolymers for use in making beverage bottles[26]. Here was yet another case where protestations from consumerist groups like the Natural Resources Defense Council, Inc. led to exhaustive government action that finally resulted in a reaffirmation of the safety of the package attacked; more significantly, however, all of the due processes here led the market for the container to go elsewhere so that by the time FDA finally issued its regulation, the safety issue was moot.
Unfortunately, the phenomenon of raising questions about materials, no matter how spurious, often, if not always, leads to the abandonment of a material by the food processor, and sometimes his retailer customers make this decision with little or no scientific basis so that there occurs a departure from the use of the substance for reasons having no relationship to the science. Even more interesting, it can lead to the use of substitutes that are less safe or less desirable, but about which there is not yet data to indicate any problem.
A very current debacle points up the problem here. Beginning in 1997 Frederick vom Saal, a biology professor at the University of Missouri, announced to the world that he had conducted studies that showed that Bisphenol A (BPA), a very valuable monomer used in making polycarbonate containers, can enamels, compact discs, dental fillings, and in other cases where a very stable polymer or modified coating composition is required, could result in some form of reproductive toxicity to animals when administered at extremely low doses[27]. Amounts like 0.05 trillionths of a gram were held by vom Saal to affect prostate glands in fetuses and to have a likely long-term impact on human development[28]. He noted that the effects he observed occurred only at low-dose exposures and did not occur with higher dosages. These reports aroused considerable reaction from the toxicological community since, inter alia, if vom Saal's work could be validated, a very fundamental toxicological proposition, Paracelsus's theorem that "the dose makes the poison," might be negated. Indeed, in another vein, even today, vom Saal continues to label BPA as a carcinogen in the public media despite the fact that almost all expert panels have rejected this conclusion.
Various government and industry scientists have attempted to reproduce the studies vom Saal conducted and relied upon to derive his theory that there are low-dose effects with irreproducible dose-response effects but have been unable to confirm his results. Indeed, since his revelations were made, there have been a number of studies including especially a very comprehensive set conducted by the scientists at the National Toxicology Program, and very recently reported with the conclusion that there is, by and large, no safety hazard presented[29].
Reviews of the now massive amounts of data on BPA have been conducted by the relevant officials at the United States Food and Drug Administration, the European Food Safety Authority (EFSA) of the European Union, and Health Canada[30]. In every case the conclusions reached were to the effect that there is no safety problem presented by the current uses of BPA. At the same time, however, passing mention has been made of the possibility of neural and behavioral effects on fetuses, all without citation of any hard data to support this conjecture.
Demands have been made by some authorities, and especially some of the self-proclaimed consumerists,[31] that legislation should impose restrictions on the use of polycarbonate baby bottles and any children's toys made from the polymer on the basis of the so-called "precautionary principle." This "principle" espouses the view, characterized here as an especially dangerous bit of political toxicology, that action should be taken by governments and others whenever a threat of possible danger is at hand, with or without any supporting data. In a sense, at least, the "precautionary principle" can be viewed as a revival of Ludditeism with a bit of linguistic subtlety.
Nonetheless, on the strength of the outcries from consumer groups based on the vom Saal work, and the precautionary principle champions, legislators in California, a few other states, and in Congress have introduced measures[32] expressly aimed at banning the use of polycarbonates and other BPA containing products[33]. Most of this legislation targets use in baby bottles, toys, and other children's products but there are some that propose outright bans on all products containing BPA[34].
The fact that there is now a plethora of legislation pending that purports to protect the public from phthalates, and BPA is the penultimate manifestation of the mischief of political toxicology. The ultimate manifestation is the simple fact that a number of major retailers and manufacturers of end products are now putting a ban into effect in their stores and factories. This is undoubtedly the most desirable end from the viewpoint of the pseudo-scientists and activists (in this author's view, the neo-Luddites) who embrace the precautionary principle. What is happening will probably be a featured story in the next version of "Alice in Wonderland," whenever it is written.
[1] 21 U.S.C. § 409(c)(3)(A) (2008).
[2] Lest there be any misunderstanding, this is not a critique of toxicology or its legitimate practitioners. The quarrel is with those who misuse or mischaracterize the toxicological data and pervert it to indict materials for reasons that have nothing to do with valid toxicological principles.
[3] See Carol Ballentine, Taste of Raspberries, Taste of Death, The 1937 Elixir Sulfanilamide Incident, FDA CONSUMER MAGAZINE, June 1981.
[4] See John D. Graham, The Perils of the Precautionary Principle: Lessons from the American and European Experience, Jan. 15, 2004, http://www.heritage.org/Research/Regulation/hl818.cfm.
[5] Food Additives: Hearing before the Subcomm. of the H. Comm. on Interstate and Foreign Commerce, 85th Cong. 26 (1958).
[6] See Scott v. Food and Drug Administration, 728 F.2d 322 (6[th] Cir. 1984).
[7] See Chris Lecos, Cancer, the Law, and Methylene Chloride, FDA CONSUMER MAGAZINE, March 1986. http://findarticles.com/p/articles/mi_m1370/is_v20/ai_4153691/print?tag=artBody;coll.
[8] See Malcolm Gladwell, U.S. Expected to Lift Ban On Cyclamate, Sweetener Harmless, Most Experts Say, WASHINGTON POST, May 16, 1989, at A1:6.; See also, FDA's Cyclamate Update, May 16, 1989.
[9] 39 Fed. Reg. 4935 (Feb. 8, 1974); 41 Fed. Reg. 43754-43755 (Oct. 4, 1976); 47 Fed. Reg. 51227-51228 (Nov. 12, 1982).
[10] John Henkel, Sugar Substitutes: Americans Opt for Sweetness and Lite, FDA CONSUMER MAGAZINE, Nov.-Dec. 1999, available at http://permanent.access.gpo.gov/lps1609/www.fda.gov/fdac/features/1999/699_sugar.html; See also, Moratorium on Saccharin Ban Extended, Sept. 1, 1987.
[11] 42 Fed. Reg. 62160 (Dec. 9, 1977). This Act instructed FDA not to ban saccharin for two years pending a further study of its effects. The Act was subsequently extended so that saccharin remains on the market to this time.
[12] See R.L. Melnick, Is peroxisome proliferation an obligatory precursor step in the carcinogenicity of di(2-Ethylhexyl) phthalate (DEHP)?, 109 ENVIRONMENTAL HEALTH PERSPECTIVES, 437-42 (2001).
[13] See National Toxicology Program, National Institutes of Health, Carcinogenesis bioassay of di(2-Ethylhexyl) phthalate (CAS no. 117-81-7) in F344 rats and B6C3F1 mice (March 1982), available at http://ntp-server.niehs.nih.gov/ntp/htdocs/LT_rpts/tr217.pdf. Some phthalates, specifically dibutyl phthalate, are developmental toxicants in test animals. Most of the other phthalates, such as DINP, have exhibited an absence of toxicological effects.
[14] See Press Release, Consumers Press Congress to Pass Strong Product Safety Bill: Safety of toys and child care products stressed, May 16, 2008, http://www.consumeraffairs.com/news04/2008/05/cpsc_congress.html.
[15] See Press Release, ACC Believes Amendment to Consumer Products Safety Commission Reform Act Will Not Produce Benefits Envisioned by Authors, May 5, 2008, http://www.americanchemistry.com/s_acc/sec_news_article.asp?SID=1&DID=7090&CID=206&VID=142&RTID=0&CIDQS=&Taxonomy=False&specialSearch=False.
[16] See, e.g., Press Release, Last Push for Phthalate-Free Toys: Take Action Now!, July 14, 2008, http://healthychild.org/blog/comments/last_push_for_phthalate_free_toys_take_action_now (Healthy Child Healthy World urges the public to persuade Congress to approve the Consumer Product Safety Commission Reform Act); Press Release, Vinyl Products Expose Children to Toxic Additives: Consumer Product Safety Commission Should Recall Vinyl Plastic Products, June 15, 2001, http://www.greenpeace.org/usa/press-center/releases2/vinyl-products-expose-children# (Greenpeace calls for the phase-out of PVC in consumer products); Health Care Without Harm, Phthalates/DEHP, http://www.noharm.org/us/pvcDehp/phthalatesDehp (HCWH encourages health care providers and manufacturers to identify products that contain DEHP).
[17] See Op-Ed by Representative Joe Barton of Texas, "Don't Ban Good Products Based on Bad Science," Dallas News, July 25, 2008; http://www.dallasnews.com/sharedcontent/dws/dn/opinion/viewpoints/stories/DN-barton_25edi.ART.State.Edition1.4d4f022.html
[18] See States to Ban Products with Phthalates, DSN RETAILING TODAY, June 27, 2005.
[19] See ToxFAQs[TM]for Acrylonitrile, July 1999, http://www.atsdr.cdc.gov/tfacts125.html.
[20] Communication from Richard J. Ronk, Acting Director of FDA's Center for Food Safety and Nutrition to Jerome H. Heckman, Counsel for Monsanto, June 5, 1972 (on file with author).
[21] 42 Fed. Reg. 13,546 (Mar. 11, 1977).
[22] Acrylonitrile Copolymers Used to Fabricate Beverage Containers, Initial Decision 35 (August 4, 1977)
[23] 21 C.F.R. § 177.1040 (1978) was promulgated and was the Regulation under which Monsanto manufactured its containers.
[24] Monsanto v. Kennedy, 613 F.2d 947, 955 (D.C. Cir. 1979).
[25] Id. at 955.
[26] See 47 Fed. Reg. 11,841 (Mar. 19, 1982) and 49 Fed. Reg. 36,643 (Sept. 19, 1984).
[27] F.S. vom Saal et al., Prostate enlargement in mice due to fetal exposure to low doses of estradiol or diethylstilbestrol and opposite effects at high doses. 94 Proceedings of the National Academy of Sciences of the United States of America 2056 (1997).
[28] Id. at 2061 ("The possibility now must be considered that permanent enlargement of the prostate, as well as the permanent alteration in the functioning of other estrogen-responsive organs in animals and humans, could occur due to exposure during fetal life to low doses of estrogenic chemicals present in drugs (birth control pills) or to environmentally relevant concentrations of estrogenic chemicals present in food, water, and air (from pesticides, components of plastics, detergents, hand creams, and other products).")
[29] R. W. Tyl et al., Three-Generation Reproductive Toxicity Study of Dietary Bisphenol A in CD Sprague-Dawley Rats, 68 Toxicological Sciences 121 (2002). R. W. Tyl et al., Two-Generation Reproductive Toxicity Study of Dietary Bisphenol A (BPA) in CD-1 (Swiss) Mice, 104 Toxicological Sciences 362 (2008). More specifically, National Toxicology Program reviews indicate that there is a negligible concern for adult exposures, including pregnant women, but that there is some concern for fetuses, infants, and children. The concern is based on reproducible developmental effects in mice and rats.
A later report from Leranth, C. et al. (2008) entitled "Bisphenol A prevents the synaptogenic response to estradiol in hippocampus and prefrontal cortex of ovariectomized nonhuman primates," published by the National Academy of Sciences at Proc. Natl. Acad. Sci., vol 105(37), pages 14187-14191, received a great deal of publicity including a long article in the Washington Post on September 4, 2008 (Chemical in Plastic is Connected to Health Problems in Monkeys). This study and the publicity given it actually show what a problem political toxicology is because the method of applying the substance was via subcutaneous injection, not ingestion. This method of exposure is not relevant to human consumption or health since ingestion results in a small fraction of the exposure achieved by injection and excretion of a substance ingested are very rapid while injection of the substance subcutaneously results in much longer chronic exposure.
[30] For FDA's review of Bisphenol A, see Food and Drug Administration, Bisphenol A (BPA), http://www.fda.gov/oc/opacom/hottopics/bpa.html ("Based on our ongoing review, we believe there is a large body of evidence that indicates that FDA-regulated products containing BPA currently on the market are safe and that exposure levels to BPA from food contact materials, including for infants and children, are below those that may cause health effects.") See also FDA Clearances for Bisphenol A at 21 C.F.R. §§ 175.105, 175.300, 177.1440, 177.1580, 177.1585, 177.2280, 177.2440, and 177.2800 (2008).
For EFSA's review of Bisphenol A, see 428 The EFSA Journal 1 (2006), available at http://www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_1178620772817.htm ("The available studies cover the majority of endpoints considered relevant for assessment of reproductive effects and other toxicities and do not indicate the presence of effects on reproduction or development at doses lower than 50 mg/kg bw/day.") See also a new report of the EFSA AFC Safety Panel, July 24, 2008, stating that the conclusions of the Panel are that "after exposure to BPA the human body rapidly metabolizes and eliminates the substance. This represents an important metabolic difference compared with rats. EFSA will continue to monitor closely scientific findings regarding BPA and any related health effects."
For Health Canada's review of Bisphenol A, see Health Canada, Health Canada Responds to Concerns Raised about Bisphenol A in Canned Food, May 29, 2008, http://www.hc-sc.gc.ca/ahc-asc/media/nr-cp/_2008/2008_84-eng.php ("[T]he average Canadian would need to consume several hundred cans of food per day to reach the tolerable level established by Health Canada").
[31] Among the imputed consumer advocates urging restrictions on Bisphenol A on the basis of the precautionary principle are the Environmental Defense Fund, the Environmental Working Group, and publications such as the Green Guide, Tree Hugger, and Salon.com. A California lawyer, Robert Weiss, acting on behalf of an entity he calls "Rights for America" has filed suit against baby bottle manufacturers for failure to disclose the use of Bisphenol A in their bottles. All of these organizations use their web pages to issue warnings against BPA and/or phthalates.
[32] See, e.g., S.B. 1713, 2008 Leg., Reg. Sess. (Cal. 2008); Sen. Res. 46, 2008 Leg., 213[th] Sess. (N.J. 2008); H.R. 6228, 110[th] Cong. (2008); and S. 2928, 110[th] Cong. (2008).
[33] At a June 10, 2008 hearing held by the House of Representatives Subcommittee on Commerce, Trade and the Consumer, Dr. Michael Babich of the Consumer Product Safety Commission (CPSC) noted that BPA is used in the manufacture of polycarbonate helmets and other protective gear and does not present a health risk. He urged the Subcommittee to consider this beneficial use and not consider a ban since "Such a ban could result in less effective protection of children from head, eye, or bodily injury." Safety of Phthalates and Bisphenol-A in Everyday Consumer Products: Testimony before the Subcomm. on Consumer Affairs, Insurance, and Automotive Safety of the H. Comm. on Energy and Commerce, 110[th] Cong. 4 (2008) (testimony of Dr. Michael Babich, Directorate of Health Services, CPSC), available at http://energycommerce.house.gov/images/stories/Documents/Hearings/PDF/Testimony/CTCP/061008_BPA/061008.ctcp.babich.pdf.
[34] See H.R. 6228, 110th Cong. (2008); S. 2928, 110th Cong. (2008); Leg. Doc. 837, 2008 Leg., 123[rd] Leg. (Me. 2008); H.B. 56, 2008 Leg., Reg. Sess. (Md. 2008); and Assem. B. 6829, 2007 Leg., Reg. Sess. (N.Y. 2007).