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  Another concern for toxicologists was the toxicity of insecticides used in combination, or potentiation. A team of FDA pharmacologists led by John P. Frawley analyzed the greater than additive toxicity, or potentiation, resulting from simultaneous administration of two anticholinesterase compounds, which was essentially a study of joint toxicity. After reviewing the rather sparse literature on the toxicity of organophosphate insecticides, Frawley and his colleagues noted: “In all these studies, the observations have been based on the continued administration of a single compound. In practice a worker may be exposed to two or more compounds on the same or alternating days, and the average consumer may ingest at the same meal several different food products each containing a different insecticide.”52 Unlike the joint toxicity of antimalarial drugs as studied at the Toxicity Laboratory, which would have to be prescribed by a physician, individuals could be exposed to two organophosphates inadvertently through occupational exposure and possibly even normal daily consumption.

  Frawley and his team chose two organophosphates, EPN and malathion, because they were each less toxic than other organophosphates. First they determined the acute toxicity (LD50) of each chemical for rats and dogs, and then they established the toxicity of the two chemicals in combination. In dogs, EPN and malathion administered simultaneously caused up to fifty times the potentiation (additive toxic effects) of separate exposures. And they noted potentiation in rats as well. From these findings, Frawley and his team concluded: “However, of broader significance is the conclusion that in some cases the hazard associated with the administration of chemical and drug combinations cannot be evaluated from the toxicity of the individual compounds. The results point out the need for caution in the use of drug combinations in this phase of pharmacology and toxicology which is frequently overlooked.”53 The FDA group also investigated the joint toxicity of malathion and EPN combined in several ratios to house flies, again using Laug’s fly bioassay, but found no indication of potentiation. This finding suggested that potentiation involved complex chemical reactions between the two phosphates and the biological system.

  At the Tox Lab, DuBois also addressed the potentiation of organophosphates. He reasoned that the simplest method for detecting potentiation by acute toxicity tests would be to administer half of the LD50 of each of two organic phosphates. If mortality due to the combination of the two compounds was additive (50 percent) or less than additive, no potentiation had occurred. DuBois used this approach to test for potentiation in several organic phosphates and found that most showed additive or less than additive acute toxic effects. This meant that the combination of half of the LD50 of the two chemicals produced a toxic effect that was equal to or less than the full LD50 dose for either chemical. DuBois anticipated these results when the compounds had the same mode of action, parallel dosage-mortality responses, and a similar time of onset of toxic effects. From the results of the tests of acute toxicity, it became clear to DuBois that he had to clarify the mechanism of toxicity for each organic phosphate involved in potentiation to fully explore subacute effects. Such research revealed that some agents inhibited hydrolytic detoxification reactions. DuBois thought this discovery was potentially valuable for basic research into normal metabolism, but it left unresolved the implications for food residues and occupational exposures.54 He noted, “Our present knowledge of the problem of potentiation of the toxicity of organophosphates does not provide an answer to the question of whether or not this effect constitutes a health hazard in connection with consumption of contaminated food.”55

  The organophosphate insecticides, like DDT and other chlorinated hydrocarbons, demanded novel toxicological techniques and strategies. During World War II, the Toxicity Laboratory at the University of Chicago responded to this considerable need. In particular, Kenneth DuBois and his students and colleagues recognized the major toxicological effects of the organophosphates: cholinesterase inhibition. DuBois and his research group developed toxicological profiles for many of the new insecticides, including OMPA and parathion. In addition to the research conducted at the Tox Lab, David Grob at Johns Hopkins examined the toxicity of parathion to humans, drawing on occupational cases of exposure. Arnold Lehman at the FDA also evaluated the risks of the organophosphates, particularly in comparison to other insecticides like the chlorinated hydrocarbons. Like DuBois, Lehman constructed hierarchies of toxicity for the new chemicals. In general, the organophosphate insecticides had a greater acute toxicity (due to cholinesterase inhibition) but considerably reduced chronic toxicity in comparison with the chlorinated hydrocarbons. One promising exception to this developing rule was malathion, or so American Cyanamid and scientists associated with the company argued. In the mid-1950s, Union Carbide introduced the first of yet another promising class of insecticides: Sevin. The carbamates inhibited cholinesterase like the organophosphates. Like malathion, Sevin had a relatively low mammalian toxicity. Combination of certain organophosphates exacerbated their effects as researchers at the Tox Lab and the FDA independently discovered. As toxicologists at the Tox Lab and the FDA strove to assess the risks associated with exposures to the new organophosphates, legislators held hearings to determine the implications for public health.

  CHAPTER 5

  What’s the Risk?

  Legislators and Scientists Evaluate Pesticides

  In the aftermath of World War II, when DDT and other chemical insecticides became widely available for use in the U.S. for agriculture and public health, legislators began to realize the limits of the Federal Food, Drug, and Cosmetic Act of 1938 to regulate novel synthetic insecticides. Congress held several hearings to discuss further legislation. Industry representatives bridled at the idea of further regulation, and scientific opinion regarding risks of insecticides varied widely. But chlorinated hydrocarbons like DDT and the organophosphate insecticides taxed the regulatory power of the FFDCA, and Congress revisited the mounting challenges of synthetic insecticides by holding hearings, which led to the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) in 1947. Despite wide-ranging hearings and the passage of the FIFRA, lawmakers returned to the subject of pesticides again in 1951 in hearings regarding food additives, with further legislation in the form of the Miller Amendment and the Delaney Clause.

  The FIFRA hearings brought together representatives from government agencies (USDA and FDA), industry (the Agricultural Insecticide and Fungicide Association), and, to a limited extent, consumers. Among those who appeared before the congressional hearing was S. R. Newell, then assistant director, Livestock Branch, Production and Marketing Administration, USDA, who characterized the bill as follows: “The broad objective of this bill is to protect the users of economic poisons by requiring that full and accurate information be provided as to the contents and directions for use and, in the case of poisons toxic to man, a statement of antidote for the poisons contained therein. It is also designed to protect the reputable manufacturer or distributor from those few opportunists who would discredit the industry by attempting to capitalize on situations by false claims for useless or dangerous products.”1 It should be noted that the “users of economic poisons” referenced here were farmers not consumers or the public at large. Newell noted unanimous agreement on the need for such a bill and general agreement that the Insecticide Act of 1910 no longer met the needs for effective regulation, largely as a result of the emergence of new pests, new insecticides, and new controls that had emerged over the course of the previous thirty-five years. New insecticides, such as DDT, inspired questions. It is worth noting, however, that the Insecticide Act of 1910, like the Pure Food and Drug Act, served primarily as a labeling law (see chapter 1). Newell suggested that the insecticides industry would react favorably to registration: “Experience over many years indicates that many manufacturers would welcome the opportunity to check their products and the claims made for them with the administrative body. Recent experience in the examination of labels applying to DDT amply demonstrates this fact.”2


  Newell’s optimism regarding industry cooperation with pesticide registration was not shared by all. L. S. Hitchner, executive secretary of the Agricultural Insecticide and Fungicide Association (the national pesticide trade organization), stated his preference for free market competition over federal regulation: “Let us take DDT. I do not think the Bureau of Entomology or any government department or agency today is in position to set and freeze standards. Normal competition has given the American farmer the highest quality of goods in a highly competitive industry, and setting of standards, in my opinion, would be impossible.”3 Note that like Newell, Hitchner made specific reference to DDT. But Hitchner restricted his statement to the “quality” of insecticides, which presumably referred to their efficacy against target organisms rather than their potential toxicity to nontarget organisms, including humans. Moreover, Hitchner questioned the ability of government or industry to standardize insecticides, though he acknowledged that two older insecticides, arsenate of lead and calcium arsenate, were in fact standardized. He argued that state experimental stations could educate consumers in the use of pesticides, while dismissing standards: “For example, New York State today is having dealer conferences all over New York to educate buyers on insecticides. There is no simple way of arriving at a standard on two or three thousand chemicals. I wish we could, but it just seems to me to be impossible.”4 Hitchner argued that education provided by the state experimental stations obviated the need for federal standards, which would be impossible to develop anyway.

  Hitchner returned the theme of state sovereignty later in his testimony when he challenged the consolidation of regulatory authority in the office of the secretary of agriculture by citing slow acceptance of oil sprays: “When oil sprays were first introduced, they were vigorously opposed by several of the state agricultural colleges and official workers of the government. The companies that introduced those hired their own entomologists, their own pathologists, and went from farm to farm getting the material used over the vigorous objection of the experimentstation people, who were in a rut on new development. Today there are millions of gallons of those oil sprays in commercial operation.”5 Once again, Hitchner assumed that reticence to adopt oil sprays stemmed from fear of new technology rather than safety concerns. But concentration of authority troubled the industry representative most: “You are definitely giving a man a right to say ‘You cannot use cryolite; you have to use arsenate of lead’; or ‘You can’t use arsenate of lead, you have to use DDT.’” He continued: “The best example on that is where we made a survey on DDT, where we got 48 States to send their directions for use, and if you read the 48 reports there is hardly one State that agrees with any other at the present time. Under this power, if they had the right to refuse registration, we would not be able to sell in a lot of those States our materials. It is a very dangerous precedent.”6 Again, Hitchner used state sovereignty to set independent directions for use (and the ability of companies to market insecticides accordingly) to undercut registration and centralized authority.

  Representative Walter K. Granger of Utah turned this argument on its head, when he commented on Hitchner’s statement: “It seems to me there is another horn to that dilemma, too. I assume that the Secretary Agriculture, before he would disapprove the registration, would have competent chemists—I assume he would—to ascertain what it was, and instead of taking the bureau’s idea and their chemists, the public would be forced to take what your chemists said; would they not? That would be the case of another individual saying what the situation should be.”7 Hitchner continued to resist central authority: “There you have an awfully concentrated amount of authority in one man.”8 But not all organizations were so resistant to further regulation of insecticides. Russell Smith of the National Farmers Union urged the committee to report the bill without substantial amendment, and he praised the extension of the bill to cover rodenticides and for the secretary of agriculture to provide a definition of what constituted “pests.” Finally, he appreciated additional labeling safeguards, particularly the designation “highly toxic to man.”9

  Several speakers attributed the need for new legislation to the increasingly “scientific” nature of new insecticides. Dr. E. L. Griffin, who was assistant chief of the Insecticide Division, Livestock Branch at the USDA, referred to technical (or scientific) challenges in voicing his support for the new act: “The insecticide, fungicide, and rodenticide business has changed very markedly since 1910. It is now a highly scientific business. The products coming on the market are new and unknown products in a good many cases, and in our opinion they need a lot more careful supervision than is possible under the present act. We believe that this act should be brought up to date, and we believe that this is a good act.”10

  When the new insecticide bill (H.R. 1237) came up for debate in the House in May 1947, August Andresen (Republican, Michigan) introduced the bill and noted that it had the support of the insecticide industry, distributors, USDA, and farmer’s organizations. Some of the manufacturers were resistant to registration, but for the protection of the public, this was a necessary part of H.R. 1237.11 The only interchange of note occurred when Representative Frank B. Keefe (Wisconsin) asked why administration of the act would fall to the USDA rather than the FDA, which already administered the FFDCA. Andresen deflected Keefe’s question by pointing out that the USDA administered the Insecticide Act of 1910. Keefe pressed his point noting that the new act would require separate testing facilities in two agencies. The chairman of the Agriculture Committee, John W. Flannagan, Jr. (Virginia), suggested that the act would primarily affect farmers and that it was currently administered by the USDA in the form of the Insecticide Act; the new act only amended the old one. Without further debate, H.R. 1237 passed the House and went on to the Senate, where it passed without further debate.12

  The Federal Insecticide, Fungicide, and Rodenticide Act, signed into law in 1947, dictated the licensing of the so-called economic poisons prior to their sale in interstate or international commerce. The law also stipulated that prominent warning labels detailing instructions for use be included on highly toxic pesticides. Furthermore, FIFRA required manufacturers to color powdered insecticides to prevent confusion with other household products, for example, flour, sugar, baking soda, and salt. Adelynne Whitaker emphasized that FIFRA assured consumers of quality pesticides while protecting them from accidental poisonings. Registration required manufacturers to test insecticides to determine efficacy before marketing their products. Yet public health officials were disappointed that FIFRA’s registration clause did not reinforce the FFDCA and control pesticide residues. In his critique of an earlier version of the bill, Paul A. Neal of the PHS recommended a consideration of public health aspects and called for coordinating toxicity testing between PHS, FDA, and USDA.13 FIFRA in its final form did not incorporate Neal’s recommendations.

  Though federal officials, consumers, and even manufacturers questioned the efficacy of FIFRA in addressing potential damage to the environment and health, like the Federal Food, Drug, and Cosmetic Act of 1938, FIFRA served as a critical initial step in the development of more comprehensive regulation. Nevertheless, according to environmental scientist John Wargo, the primary risk-management strategy reinforced by FIFRA after World War II was simply labeling. By requiring labels with instructions for use, the law implied that those who used pesticides could avoid adverse effects by following the directions. Despite the clear notes of concern regarding DDT and other new pesticides sounded during the FIFRA hearings, the law failed to address potential risks to health and the environment.14 Wargo criticized the legislation as preferential to pesticides manufacturers: “This approach may have done far more to protect the entitlements of the pesticide manufacturers rather than either public health or environmental quality. It sheltered manufacturers from uncoordinated state regulations, and may simply have served to provide the public with a false sense of security that pesticide risks were being well contained by USDA. The realit
y was that USDA registered pesticides whenever asked.”15

  By 1951, concern regarding possible risks associated with insecticides and other chemicals that were finding their way into the food supply inspired a new round of congressional hearings before the House Select Committee to Investigate the Use of Chemicals in Food Products, which took place in the nation’s capital and around the country from April 1951 to March 1952. Congressman James J. Delaney of New York chaired the hearings, which became known as the “Chemicals in Food Products” or the “Delaney Hearings.” Another key member of the committee was Nebraska Congressman A. I. Miller. Yet it was the committee’s chief counsel, Vincent A. Kleinfeld, who examined witnesses utilizing his comprehensive and encyclopedic knowledge of the FFDCA and its amendments as well as the prepared statements and exhibits.

  Over the course of many days of hearings in several venues, including Washington, DC, Washington state, and California, with a transcript of more than 2,700 pages, several critical issues emerged. Congressmen repeatedly returned to their concerns regarding the widespread use of DDT and its potential health effects. Nevertheless, scientific uncertainty permeated the hearings. The views of scientists and public health officials on DDT and other synthetic insecticides ranged widely. Some scientists noted the lack of concrete evidence of harmful effects associated with DDT, and others cited anecdotal evidence of effects from mild to profound in connection with DDT and other chemical insecticides. Yet most participants agreed that the new insecticides had significantly boosted crop yields and contributed to public health since their introduction in the years following World War II. Thus the Delaney Hearings provide a useful index to congressional interest in pesticides, broad-based uncertainty among scientists, and a sense that such chemicals had quickly emerged as critical to American food production and public health. There was, however, general recognition, particularly among state health officials, that the Insecticide Act of 1910 and the FFDCA of 1938 required revision.