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Ribicoff pursued his line of inquiry pointing out that the FDA was reassessing the question of tolerances and that studies should be made, but the products continued to enter the market even though the no-effect level in animals had not been determined. Feichtmeir reiterated that no-effect levels were a matter of opinion and that the products had been reviewed and tolerances established. He underscored a recent advance in the development of analytical methods: “In the last 2 years we developed what we call an electron capture detector cell as an adaptation to gas-liquid chromatography. By this technique, we can measure in the range of a tenth of a part per billion… . I do not know how many of you have an understanding of what this means, but it is about two inches relative to the distance to the moon and back. We have to detect these small differences. With the new tools we can measure blood levels after exposure to the chlorinated materials.”78 Feichtmeir was mistaken in his chronology: James Lovelock invented the electron capture detector in 1957.79
Ribicoff refused to be derailed and again asked if Feichtmeir or his company had found a no-effect level for dieldrin, and again Feichtmeir declined to answer directly, noting that it came down to a matter of opinion to be determined by toxicologists, whether Shell’s medical consultants or FDA’s researchers. Ribicoff reframed the question in light of “good business practice”: “Let us say that the National Academy of Sciences determines that there is no no-effect level for Dieldrin. Now, from a good business standpoint alone, forgetting public policy, is there not a duty more or less on you people to determine this before you market the product?”80 Here Ribicoff introduced the precautionary principle, which, as we have seen, shifted the burden of proof of safety to the pesticide producers from the public and the regulatory network.81 In response, Feichtmeir argued that Shell had “done that sort of thing when the labels were secured”: “In our opinion, there is nothing wrong with these materials at present, based on available data. We think they are safe and can be used, if used properly, without hazard to the public and applied without hazard to the people applying them.”82 Perhaps recognizing the futility of further interrogation, Ribicoff let the subject drop.
Another witness, Ernest J. Jaworski, who was a senior scientist at Monsanto Chemical Company, raised an issue that would later emerge as a topic of considerable contention. Jaworski wondered about the toxicity of natural products. He suggested that toxicologists knew more about the toxicology and pharmacology of pesticides than about many natural products and household products, including food. The Monsanto scientist commented: “We know a tremendous amount about pesticides in general, but I would worry about how little we know in general about food that we eat. What is the chronic effect of eating some given vegetable, say, over a lifetime period?”83 In time, this line of argument would evolve into the “toxicity of natural products” defense, as scientists explored the toxicology and pharmacology of organic products. Jaworski emphasized that scientists knew a great deal about pesticide toxicology and pharmacology and relatively little about natural products: “We really do not know and the plant biochemist knows that there are many naturally occurring organic materials which nobody has ever studied in terms of their pharmacology and toxicology.”84 Within the context of an extended discussion of the importance of a no-effect level as a baseline for toxicological analysis, however, the Monsanto scientist’s implication is clear: if natural products proved to be highly toxic (or at least more toxic than some chemical pesticides), should regulators have devoted greater concern to those risks? In other words, regulators should have expanded the study of toxins and no-effect levels to natural products. The well-known biochemist Bruce Ames revisited and refined this line of argument in 1990.85
Ribicoff’s questions regarding the no-effect level for pesticides like dieldrin scratched the surface of a larger issue in the history of toxicology; namely, the existence of thresholds of effects. The question for regulators was, “Is there a threshold for exposure below which there is no identifiable effect?” Pharmacologists explored a related question: “For a given drug, is there a minimum (measurable) dose below which there is no response?” As we have seen, certain industry representatives accepted the no-effect level as a necessary component for toxicological analysis, whereas others went to great lengths to undermine its significance. The development of technology, in the form of Lovelock’s electron capture detector, facilitated finer analysis and the ability to detect exposure in the parts per billion (and eventually, as the ECD was refined, in the parts per quadrillion). But was it possible to identify and measure the effects of these minute exposures?
The gap between toxicology and pharmacology contributed to a sense of frustration among researchers and regulators. In creating the Institute of Toxicology, some toxicologists hoped to close the distance between the two related fields. As Arnold Lehman related, late in 1962 he met with two other toxicologists and by the end of the year they had established a journal and created a society (see above), but the most important step, in Lehman’s opinion, was the creation of an Institute of Toxicology on February 1, 1963, at Albany Union Medical College in Albany, New York. Lehman reflected: “The purpose of this institute is to help us in our pesticidal work. There is one very large gap in this research on pesticides. Although our protocol has done very well for the human safety, there is still one gap that we must fill, and that is human pharmacology, the testing of pesticides in humans.”86 For the first time, it would be possible to conduct controlled, pharmacological analyses of pesticides in humans using volunteers at prisons. It is not clear whether Lehman did not accept the validity of Wayland Hayes’s research on the effects of pesticides in humans or whether he did not consider the research “pharmacological” (see chapter 2 for analysis of Hayes’s studies of the effects of DDT in humans).
Lehman also addressed questions regarding the phenomenon of potentiation or the interaction of two or more insecticides to create a toxicity level greater than the additive effects of exposure. Lehman’s contention was that potentiation was an extremely rare occurrence; he noted that scientists had documented only five or six cases since the original discovery. When pressed, Lehman quantified his answer: “It has been known to occur, but it is very infrequent. Now, if we were to take the 125 pesticides and test them against the 2,000 drugs, you would have about a quarter of a million tests to do, thousands of animals and years of time. It would be a tedious test. So far these potentiation effects are always discovered accidentally.”87
Kenneth DuBois also testified to the committee regarding potentiation. Drawing on data from drug interactions, DuBois defined potentiation as “greater than additive effects of combinations of drugs.”88 He went on to note that no one really considered the possibility that potentiation of the toxicity of pesticides might occur until 1957 when FDA scientists discovered that two insecticides that were permitted in foods caused potentiation when they were present together at certain levels in the diets of animals. On the basis of this finding, the FDA launched a program to evaluate insecticides that were cholinesterase inhibitors in combinations with one another to determine whether potentiation occurred. DuBois recognized that several pairs of insecticides did cause potentiation of toxicity when given in high doses, but he had not identified potentiation of toxicity in experimental animals when pairs of insecticides were added to the diet at the levels that were permitted in various foods. Thus, he concluded, “This indicates that the tolerance levels selected for these pesticides contain a sufficient margin of safety to take care the unpredictable occurrence of potentiation, at least potentiation caused by a similar type of insecticide.”89
Of greater concern to DuBois, however, was the possibility that other environmental exposures might contribute to potentiation of toxicity (see chapter 4). He cited the case of radiation, which he and his colleagues at the Tox Lab had studied experimentally. When they exposed animals to low doses of radiation, the radiation stopped the development of enzymes in the liver that would normally detoxify some of the organop
hosphate insecticides. As a result, the irradiated young animals became hypersensitive to insecticides and also to certain common drugs. DuBois’s main thesis was that potentiation could be caused by an unrelated substance, which had much broader implications for environmental health than the discovery that two compounds from the same class (like cholinesterase inhibitors) could cause potentiation.90 Such implications prompted DuBois to call for a comprehensive research program, on a much larger scale than previous initiatives, dedicated to the study of potentiation to eliminate exposures to any combination of agents that might endanger public health. The scale of the investigation transcended university capacity and the lack of obvious benefits to industry limited corporate investment, and so DuBois recommended that a national research center tackle the problem.
Frawley further clarified the problem of potentiation. He agreed with Lehman that potentiation was a rare occurrence except in cases when doctors administered a number of drugs at pharmacologically active levels. In contrast, pesticides did not appear in the diet at such levels. Indeed, at levels of less than 1/100 of the no-effect level in experimental animals, the potential exposures from food residues would be far below a pharmacologically active level, according to Frawley. He concluded: “I know of no situation again where any potentiation has been demonstrated at several times above the level that pesticides occur in the diet. Potentiation can, however, be demonstrated at high levels approaching the acute toxic dose, or even maybe a tenth of the acute toxic dose. The potentiation indeed occurs, but that is a pharmacologically active dose.”91 Once again, toxicity hinged on the dosage or exposure, leaving the question of potentiation as a result of exposures to insecticides at the levels of food residues unresolved.
Before and certainly after the publication of the provocatively titled 100,000,000 Guinea Pigs, there was a pervasive notion that pesticides and other toxics arrived at the marketplace with minimal testing for toxicity. In Silent Spring, Carson lent a certain amount of credence to the view that industry and governmental agencies like the USDA were mindfully exposing countless animals and numerous agricultural workers and their families to understudied chemicals across America. Corporations struggled to represent their testing efforts before the public release of a new chemical insecticide. Industry representatives detailed the process of toxicity testing for new pesticides along with the approximate time and cost of such analysis. Frawley noted that the total approximate cost for the development of a new insecticide was two million dollars and the process required approximately five years from initial test tube synthesis to government approval. Other industry representatives were more specific in presenting the steps that led to the development of a new pesticide. For example, Johnson (Dow) presented a detailed chronology of the development of a pesticide. The average time from laboratory synthesis (in the test tube) to the first date of sale typically took six to seven years. Over the course often years, Dow Chemical tested an average of 4,150 compounds per year. To capture the range of biological activity, the compounds were tested on at least 50 different living organisms. Out of more than 4,000 chemicals, a yearly average of 27 passed to stage 2 testing. In stage 2, the studies of metabolism began with compound radioisotope labeling. An average of 2 chemicals (of an original 4,150) passed from stage 2 to stage 3. The cost of testing up to stage 3 amounted to $500,000, approximately. Stage 3 launched the two-year dietary feeding toxicity tests in dogs and rats. It is at this point that Dow Chemical obtained symptomology and treatment information for doctors’ review to protect Dow researchers and later customers. Johnson specified the broad ramifications of this research: “We consider the potential crop application hazards, the drift, the persistence in soil, and leaching to ground waters.”92 Other industry scientists confirmed that they too evaluated these aspects of environmental toxicology. In stage 4, researchers at Dow Chemical worked directly with agricultural experiment stations and the USDA as well as consulting laboratories for specific toxicological investigations. Research on chronic toxicity, analytical methods, and residues (using radiochemical methods) continued through this stage. Moreover, three-generation reproduction studies commenced. Johnson noted that Dow Chemical had been conducting these studies for the previous three to five years. At least in part as a response to Silent Spring, the PSAC had called for incorporation of two-generation reproduction studies. Monsanto’s Jaworski initially bristled at the imposition of three-generation studies but demurred when informed that the PSAC called for two-generation studies, which Monsanto and other companies conducted.
To determine potential for environmental impact, Dow scientists examined effects on snails, fish, Daphnia, and algae, beginning about three years ahead of the projected release. Johnson made explicit reference to food chains: “We hope to help assess the hazards of stream and lake pollution and get this information on effects on biological life chains.”93 The first-year progress report on the two-year toxicology followed with a real chance that 1 of the 2 chemicals that reached stage 4 would not reach market, or, in other words, 1 new insecticide, out of an average of 4,150 per year, actually survived to reach the market. Crops from at least ten experimental studies across the country underwent analysis, and stage 4 also included meat and milk residue studies, if appropriate, as well as human skin sensitization studies and inhalation studies, if mists or dusts were to be employed. After they wrote the label, the Dow scientists prepared the petition to go to the FDA: “In this report are included the performance information, the proposed use and labeling, the dietary feeding toxicology report, the wildlife report, the residue report, the analytical report, any information on symptomology and treatment which should go to a physician, reproduction studies, and toxicology report.”94 The final steps of stage 4 involved education of the salespeople, the resellers, and the applicators. Stage 5 involved shipment, sales, and the launch itself. Johnson concluded his comprehensive review of the development of new pesticide with an overview of the process: “Now, this represents an effort of about 5 to 7 years—if we are lucky it is 5 years—and perhaps between $2 and $3 million if food crops are involved.”95
Jaworski was more succinct in his exposition regarding new pesticide development. After noting that Monsanto was among the first chemical companies to manufacture DDT (a practice later abandoned), he acknowledged that his company was one of the largest manufacturers of herbicides, insecticides, and animal feed additives in the United States as well as one of the five major manufacturers of parathion in the world. Out of 7,000 to 10,000 chemicals screened each year, 50 to 100 received advanced laboratory evaluation and no more than 2 or 3 survived the first year of field study, after which they would be studied in greater detail for efficacy, toxicology, and residues. The entire research department participated in the extensive analysis of chemicals over the course of four to seven years to commercialize a new pesticide at a total cost of between 1.5 and 2.5 million dollars. Jaworski concluded: “We cannot afford to develop poor performing or hazardous materials nor can we afford second-rate research if we are to maintain good relations with the ultimate consumer of our products. Safety, product performance, and confidence by the consumer in our industry demand this high level of professional endeavor.”96
Each of the research scientists from the chemical corporations indicated the considerable scope (in terms of time and cost) of research and development of a new pesticide. The process involved thousands of chemicals, four to seven years of laboratory and field analysis, and from one to three million dollars. If during the course of investigation, scientists identified a problem with an insecticide, development could be abandoned. Johnson cited several examples of promising potential insecticides that Dow removed from the later stages of development as a result of toxicological analysis (see above). Nevertheless, Senator Ribicoff remained skeptical, noting a report from Chemical Week Reports (June 1, 1963) that predicted that pesticides could be a two-billion-dollar market by 1975. He argued, “A $2 billion industry, it would seem, has quite a bit of responsibil
ity to make a thorough study of its products and also look at the side effects or no effects.”97 Ribicoff’s statement placed the claims of industry scientists regarding the costs of pesticide development in broader financial context.
Although five to seven years and two to three million dollars devoted to research and development sounded impressive, the question remained whether such research was sufficient to insure the safety of consumers of chemical insecticides as well as exposed wildlife. The answer to this question arrived through the prolonged process of litigation (see chapter 7).
As Daniel, Langston, Oreskes and Conway, and Rosner and Markowitz and others have brilliantly demonstrated through numerous incisive examples, industry successfully captured regulatory agencies in the U.S. across the twentieth century to the detriment of the health and wellness of millions of Americans and others worldwide.98 In the case of pesticides, Daniel argued: “[USDA’s Agricultural Research Service (ARS)] possessed enormous power, for its label approval function licensed pesticide formulations. It garnered enormous power in its multiple roles as clearinghouse, coordinator, regulator, and research center. To have their way, ARS bureaucrats bullied, plotted, lied, and misled. A culture emerged within the service that justified pesticides at all costs, and staffers bent research, reports, and testimony to serve this mission.”99 As a result, Daniel condemned the ARS as follows: “The ARS was assigned to umpire the debate and assure public protection, yet it had become simply the handmaiden of the chemical companies.”100
Scientific uncertainty played a critical role in the strategies of various industries to evade or delay regulation. By emphasizing uncertainty in toxicological effects other than acute, companies could stymie regulators. But these authors have shown in case after case that regulatory agencies like the USDA and the FDA were “captured” as their designated representatives adopted views entirely compatible with those of industry. Exceptions to this rule—Kelsey at the FDA, Hueper at the NCI, and Clarence Cottam at the FWS, as well as Carson—stand in sharp distinction to a pervasive trend.