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  Grob and his associates were able to isolate factors that accounted for the fact that parathion was more efficient than Tetraethyl Pyrophosphate (TEPP) as an insecticide even though its anticholinesterase activity and toxicity were lower. These factors also explained the greater danger of parathion to humans and domestic animals in comparison with other organic phosphates. The Johns Hopkins researchers noted that parathion hydrolyzed (broke down into chemical components) more slowly than TEPP, so that once sprayed on trees or fields, parathion remained active for weeks despite contact with moisture, whereas TEPP would hydrolyze within several hours. Another factor they noted was parathion’s higher solubility in lipoid (fat), which meant that it would accumulate in the waxy outer layer of fruit and leaves, where it had been found up to nine days after spraying. Finally, the oxygen analogue of parathion was more toxic and active against cholinesterase than parathion, but Grob and his team could not determine the extent to which exposure to the air (as in spraying), or in plant tissues, or after absorption into the body converted parathion into its oxygen analogue.

  By way of conclusion, the Hopkins researchers suggested a series of precautionary measures to be taken when dealing with parathion. Their recommendations included adequate warning labels, complete protective clothing, respirators, and a change of clothing before eating or smoking. They made specific recommendations regarding the use of parathion on crops for consumption: fruits and vegetables should be sprayed only with very dilute solutions, harvested no less than three weeks after the last spraying, and thoroughly washed prior to use.12 Even within a class of highly toxic chemicals, parathion, as Grob and his team showed, was extremely hazardous to humans in the workplace and probably also as a food residue.

  English physicians also examined the effects of poisoning by organophosphate chemicals. One of them, Lesley Bidstrup, reported only four organophosphate poisonings up to 1950, but each case stood out for the rapidity with which the insecticides wrought havoc on human systems. In one case, a plant foreman and fellow worker were splashed with parathion. Although the foreman made his assistant wash with soap and water and change his clothes at once, the foreman neglected to follow his own advice. After eight hours, he developed nausea, vomiting, abdominal cramps, diarrhea, and constriction of his pupils. By the time the foreman was admitted to the hospital nine hours later, he had developed fibrillary twitching of voluntary muscles and signs of pulmonary edema. Despite treatment with atropine, he died twenty-one hours after the accident.13 With accounts such as this one in mind, Bidstrup bemoaned the lack of knowledge regarding long-term exposure to small amounts of parathion, although he suggested that if the need to leave sufficient time between spraying and harvesting were strictly observed, the food supply would remain safe. The potential exposure of workers was more worrisome, and Bidstrup concluded: “Experience in the United States of America in the 1949 spraying season has demonstrated that, unless all the recommendations made for the safe handling of organic phosphorus insecticides are carried out in detail, serious illness and even death will occur.”14

  Officials at the FDA also studied the new chemicals. From 1946 on, Arnold J. Lehman served as chief of the Division of Pharmacology at FDA. That year, a reorganization of the FDA established specialized sections. Under the new arrangement, the division of toxicology encompassed the acute, chronic, and dermal toxicity sections. Lehman assumed his post at FDA after a distinguished career in research and academia. Before joining the FDA, Lehman served as professor of pharmacology and director of the teaching and research activities in the Pharmacology Department at the University of North Carolina Medical School. In addition, he served as a consultant to the Federal Security Agency and as a member of the Committee on Atomic Research.15 In June 1948 he presented a paper to the Association of Food and Drug Officials of the United States in Portland, Maine, titled “The Toxicology of the Newer Agricultural Chemicals.” Lehman compared the toxicities of about two dozen insecticides including DDT, TEP (or TEPP), parathion, HETP, nicotine, chlordane, and heptachlor. Using DDT as a reference standard for insecticide toxicology, he listed the newer insecticides according to their acute oral toxicities. In this hierarchy, DDT had a median lethal dose of 250 mg/kg. In comparison, TEPP’s LD50 was 2 mg/kg (or 125 times more toxic than DDT), parathion’s LD50 was 3.5 mg/kg (70 times more toxic than DDT), and HETP’s was 7 mg/kg (35 times more toxic than DDT). Lehman’s hierarchy highlighted the relatively low acute toxicity of DDT.

  Lehman also addressed three aspects of dermal toxicity: skin irritation, quantities dangerous upon skin application (single exposure and multiple exposure), and quantities dangerous to man (estimated). In a visually powerful manner, Lehman demonstrated that the organic phosphates were at least one order of magnitude more toxic than DDT. For example, Lehman estimated that it would take a single dermal exposure of 169 grams, and multiple exposures of 9 grams/day of DDT to be harmful to man, whereas for TEPP and parathion, he estimated single exposures of only 0.6 and 3 grams, respectively, of TEPP and parathion, and multiple exposures of 0.3 grams/day, were harmful. Despite their relatively higher dermal toxicity, the two organic phosphates irritated the skin only slightly (compared to no irritation for DDT). Thus an individual could suffer toxic exposure to an organic phosphate without noticing it.

  Lehman also described chronic toxicity in rats in his address, but an accompanying table revealed the paucity of data available from long-term studies. By 1948, few insecticides had undergone toxicity experiments lasting more than 52 weeks. DDT was one of the few insecticides that had been subjected to a two-year study of chronic toxicity to rats (see chapter 2). Thus Lehman could state that the lowest level of DDT producing gross effects was 100 parts per million (ppm), as demonstrated in a study lasting 104 weeks. For parathion, by way of contrast, Lehman listed 25 ppm as the lowest level producing gross effects. He based this claim on a study of only 4 weeks duration. Remarkably, even at levels of 1,000 ppm, HETP produced no effect over the course of a study lasting 12 weeks.16

  Beyond the considerable value of his comparative tables, Lehman anticipated some of the most significant problems associated with the newer chemical insecticides. First, he undercut one of the fundamental beliefs behind the expanding use of pesticides: “It is a fairly safe assumption that chemicals which are toxic to insects are also toxic to man and animals. The great emphasis which has been placed on the specificity of DDT for insects loses its importance when fatal doses are compared on a body-weight basis with warm-blooded animals. On this basis the quantities required are practically identical.”17 Although he was extrapolating from limited data, Lehman’s statement drew on his vast experience in pharmacology. He also expressed concern that the body stored certain insecticides like DDT in fat. Even more disturbing was the secretion of DDT and other chlorinated hydrocarbons in milk: “This is especially important in cases of infants, where the chief diet is milk.”18 Lehman’s concern was not limited to DDT and the chlorinated hydrocarbons. Parathion was known to have a cumulative action, which pointed to its storage in tissues.19 He reserved his most disturbing comment for the end of his paper: no one knew the dangers of using such chemicals in aerosol form. This information was available only for DDT, which had a safety factor several hundred times greater in such conditions. Lehman effectively outlined a comparison of the toxicology of the new agricultural chemicals and from this review identified some of the significant concerns regarding their widespread utilization. Moreover, he anticipated the litany of problems Rachel Carson attributed to pesticides in Silent Spring more than a decade later.

  In 1949 Lehman listed the insecticides in descending order of potential harmfulness to the public health, with emphasis placed on risks other than those related to the spray residue on foods. He arranged the toxicity of insecticides as follows: “TEPP > Parathion > Compound 497 > Nicotine > Compound 118 > Chlordane > Toxaphene > DDT > Rote-none.”20 On the important issue of spray residues (typically small amounts of pesticides that remained on foods), he not
ed that the values established as safe by the current experimental evidence were subject to change, and that they applied only to a single item of food:

  Rotenone

  5 parts per million

  Pyrethrins

  10 parts per million

  TEPP

  rapidly decomposed; known decomposition products not considered as a hazard

  Parathion

  2 parts per million

  Gamma isomer

  3–5 parts per million

  DDT

  less than 1 part per million if all of the food consumed is contaminated; 5 parts per million approaches the upper limit in any single item21

  According to this table, the most toxic of the organic phosphates also decomposed the most rapidly into harmless, nontoxic products. So quickly would TEPP decay that Lehman and other scientists saw no need to set a residue level. Because of its slower rate of decay, the residue limit for parathion was 2 ppm. DDT, the subject of the most extensive scrutiny, received the lowest residue level. Moreover, Lehman cautioned that, because specific chemical methods for the isolation of many of the chlorinated hydrocarbon insecticides had not been developed, the detection of their presence in foods depended on generic organic chloride determinations. Thus food containing any detectable organic chloride residues should be regarded as contaminated.22

  The most notable difference between the organic phosphates and other synthetic insecticides, DuBois and his colleagues at the University of Chicago had found, was that the organic phosphates inhibited cholinesterase in all species, including humans. All of the organic phosphates caused cholinesterase inhibition to some extent, but the new insecticides varied considerably in other aspects, such as persistence.

  The Committee on Pesticides of the Council on Pharmacy and Chemistry of the AMA reviewed the available information on the known organic phosphates in 1950. After a general description of three organic phosphates, DuBois and Grob, members of the committee, summarized their pharmacology and toxicity (both were recapitulations of earlier papers).23 Additional committee members contributed to the review. For example, two doctors from American Cyanamid (one of the chief producers of organic phosphate chemicals) and another from the California Department of Health discussed clinical experience, briefly presenting eight fatal cases, which were mostly occupational exposures of various sorts resulting from lack of protective clothing, but included also a German biologist who attempted to determine the human tolerance for parathion through self-experimentation. Another tragic case involved a ten-year-old child who drank from a whiskey bottle containing TEPP and died in about fifteen minutes, before medical assistance became available.24 Such accounts revealed the greater toxicities of most organic phosphates in comparison with the chlorinated hydrocarbons like DDT.

  The rapid hydrolization of most of the organic phosphates appeared to reduce their risk in soil, but in their contribution to the committee’s review, Lehman, Albert Hartzell, and J. C. Ward noted that the relatively slower rate of hydrolization of parathion posed a health hazard when it was used on turf. They also introduced evidence from animal studies: “Life-time feeding studies in rats at low dietary levels of parathion indicate no detectable cumulative effects below 25 parts per million. Animals fed levels above 25 parts per million and up to 100 parts per million, although they survived, displayed symptoms of nervous system poisoning and possessed an inhibition of blood cholinesterase in proportion to the increase of parathion over 25 parts per million in the diet.”25 Drawing on this information, Lehman extrapolated the risk to humans and recommended a safe residue level on any one item of the diet of approximately 2 parts per million of parathion.26 Even as they proposed a safe residue level, Lehman, Hartzell, and Ward cautioned that only if parathion was applied strictly in accordance with the recommendations of the BEPQ of the USDA, with “particular reference to the time between the last spraying and the harvesting of the fruit,” would normal weathering reduce parathion residues to this level of safety.

  Another question that Lehman and his collaborators raised was whether or not the peel of a fruit would be used in the preparation of a particular foodstuff. Even at the lowest effective spray concentrations, the peel of a fruit taken alone could carry a load of 2 to 3 ppm of parathion; this same concentration constituted 0.16 ppm extended to the entire fruit. This distinction was crucial: peeling the fruit before use, utilizing the whole fruit, or using the peel alone could change the level of exposure to parathion by an order of magnitude. In light of these variables, they concluded by underscoring the importance of adherence to recommended spray schedules: “If spray schedules recommended by qualified entomologists are followed, it is quite unlikely that a parathion spray residue problem will become serious.”27

  Given the composition of the AMA Committee on Pesticides—two industry doctors, two university toxicologists, and two government representatives from the USDA and the FDA—the conclusion probably reflects a compromise among committee members. As an FDA employee, Lehman may have realized that the political climate for the agency was less than favorable. For example, Clarence Cannon, who had shut down FDA’s pesticide research in 1937, had become chairman of the House Appropriations Committee. From this vantage point, which he held from 1947 to 1964, Cannon and like-minded southern and midwestern conservatives wielded considerable influence over the federal government and especially the FDA.28

  In an address before the Chicago Dietetic Association on March 15, 1950, DuBois took up the issue of food residues and food contamination by new insecticides, such as DDT and organic phosphates, as well as by the new systemic insecticides. He succinctly reviewed the state of knowledge in 1950 regarding the acute and chronic toxicity of each of the insecticides. From the practical standpoint of chronic toxicity, the chlorinated hydrocarbons had been a problem of major concern since their introduction: “The chlorinated hydrocarbons are stable toward hydrolysis, and spray residues may remain on fruits and vegetables for a long time. Continued ingestion of these contaminated products may thus produce a health hazard. Furthermore, these materials are fat-soluble, and the ingestion of contaminated forage by dairy cattle results in the appearance of insecticides in the milk where they are concentrated in the fat.”29 All of these factors associated with the chlorinated hydrocarbons contributed to the significant risk of chronic toxicity. DuBois cited one of the few studies of chronic dietary exposure to DDT, which showed that levels of 100 mg/kg DDT in food produced chronic poisoning (in the form of liver damage) in rats during the two-year study. Like Lehman, DuBois urged caution in the face of scientific uncertainty, noting that chronic poisoning by these chemicals was a distinct possibility.30

  In contrast to the chlorinated hydrocarbons, food contamination had not been a problem with organic phosphate chemicals, such as HETP and TEPP, because of their rapid hydrolysis when they came into contact with moisture; spray residues on fruits and vegetables would lose their toxicity before the foods were consumed. Even parathion, DuBois explained, although more stable toward hydrolysis than the other organic phosphates, was rendered nontoxic before foods were harvested. But DuBois drew a sharp distinction between typical organic phosphates and the systemic insecticides, such as OMPA (organic phosphate chemicals applied to the soil and taken up by the plants rendering the plants themselves insecticidal). What did this mean for possible food contamination? DuBois noted that the insecticidal agent formed within plants from OMPA rapidly lost its toxicity rendering plants nontoxic to insects by the time the plants reached maturity. DuBois wondered, however, about the potential risk from plants harvested before they finished growing. Because those plants could be dangerously contaminated, DuBois advised restraint in the application of systemic insecticides, restricting use to non-food crops or food crops that were never harvested before maturity.31

  Thus, DuBois underscored the fundamental differences between chlorinated hydrocarbons and organic phosphates. Chlorinated hydrocarbons like DDT did not cause acute poisoning after a single dose. Resea
rch had demonstrated, however, that animals ingesting the new insecticides for a long time could be poisoned. In contrast, acute toxicity posed the most significant risk with the organic phosphate insecticides, but their rapid hydrolysis greatly limited the threat of chronic toxicity and food contamination. Finally, DuBois noted that organic phosphates used as systemic insecticides presented greater risk than contact with organic phosphates because of their ability to be absorbed by plants. DuBois’s simple taxonomy of the risks associated with the three new classes of insecticides captured their essential differences.