Sucker Control Agents: MH-30 And Penar

To promote optimal leaf growth, farmers remove the terminal buds from tobacco plants about two months after transplantation from the seed bed into the field (3, 4). This procedure prevents flowering, which results in increased nicotine content in the leaves (4). Removing the terminal bud also controls the total number of leaves the plant will bear. In the absence of the terminal bud, new shoots arise from the axils of the leaves. These "suckers" must be removed by hand, or their growth must be inhibited by chemicals, to avoid sapping nourishment from (and lowering nicotine levels in) the developing leaf. Sucker control agents are chemicals that are sprayed on tobacco plants to slow the growth of suckers and thereby enhance crop yield. These agents—such as MH-30 (maleic hydrazide) and Penar (dimethyldodecylamine acetate)—eliminate the laborious task of removing suckers by hand and therefore lower the labor costs of growing tobacco.

In the mid-1960s the toxicology of sucker control agents was a matter of concern to the Sucker Control Committee, a committee composed of representatives from the tobacco industry and the US Department of Agriculture (USDA). Dr. R. B. Griffith wrote an extensive summary of an April 1967 meeting of this group, in which he had participated {1302.01}. At that time emerging data were suggesting that a commonly used sucker control agent, MH-30, was toxic. Experiments had exposed selected strains of mice to high doses of MH-30, and the significant toxicity that resulted called into question the safety of this agricultural chemical. In his memo Dr. Griffith notes that the USDA has very limited authority to act in such a situation:

Although they [the USDA Pesticide Regulation Division] are greatly concerned, the law requires that others must demonstrate a potential effect on health which is irrefutable. However, they are prepared to act when such knowledge indicates that they should move. {1302.01, p. 1}

The committee members then compared the expected dose of MH-30 to human smokers with the dose administered to the mice; they concluded that the mice had been exposed to two million times the dose that a human smoker consuming two packs of cigarettes daily would ingest.

The committee discussion moved from MH-30 to a consideration of studies on Penar as a possible cause of chromosomal aberrations in plants:

At this point in the discussion, I pointed out that the tobacco problem was unique. If one applies a given material to tobacco, three things are important:

I went on to point out that unusual chemical effects had been noted for each of the new sucker control materials now being considered and that there was no way of predicting the effect that these chemical changes might have on the biological effects of the smoke produced by the treated tobacco. I expressed the opinion that this was a very serious problem and that it was highly desirable for some way to be found to subject treated material to biological tests. In this connection mouse skin painting was not enough since it does not measure whole smoke. Present problems facing the industry certainly indicate the need for assurance that any material used will not result in any detrimental biological effects [emphasis added]. {1302.01, p. 2}

Dr. Griffith's comments reveal a concern with the toxicity of combustion products of additives and of the residues of agricultural chemicals. Although mouse skin painting is an important test for "biological effects" (i.e., carcinogenicity; see chapter 4), it might miss important effects because, as Dr. Griffith pointed out, it relies on painting smoke condensate, rather than whole smoke, onto the experimental animal. In other words, materials in the vapor phase, which are too volatile to be part of the "tar," are not tested in skin-painting experiments. Mouse skin might show no damage from a particular preparation of tobacco smoke condensate, but the smoke might still be highly carcinogenic.

A participant at the meeting indicated that a committee formed by British tobacco companies was "contemplating a series of biological tests" of the new sucker control agents, and that these tests could be replicated in the United States. The memo concludes:

Although everyone there [i.e., in Britain] seemed to recognize the magnitude of the problem, no one seemed to know what, if any, actions could be taken. It was agreed that none of this information would be discussed with the chemical suppliers of any of the sucker control materials, and that no public discussions of this subject could take place until after ... [the] papers [describing the toxicity of MH-30 in mice] have been published [emphasis added]. {1302.01, p. 3}

A year later, Penar was the subject of correspondence between scientists at BAT and B&W. Dr. S. J. Green, a senior R&D scientist at BAT in London, transmitted a Tobacco Research Council (TRC) report on

Penar to Dr. Griffith in mid-April 1968. Griffith, in turn, sent copies to Addison Yeaman, B&W's general counsel, and Dr. R. A. Sanford, a fellow scientist at B&W {1303.01}. The report gave preliminary results suggesting that Penar is toxic. The authors recommended additional testing of Penar-treated tobacco, and they urged B&W to report the alarming initial results to regulatory authorities in the United States and Canada:

The tests on [Penar-]spiked tobacco have now been going for 31 weeks and results reported from Huntingdon [Imperial Tobacco's laboratory in England] at this stage are so disquieting that we consider that they should be reported to the U.S.D.A. and Canadian Department of Agriculture [emphasis added]. {1303.02, p. 1}

We found no indication in the documents whether the data were, in fact, reported to the appropriate government authorities.

Shortly after this report was received in Louisville, on May 1, 1968, Dr. Griffith sent Yeaman a status report along with some background documents on the growing evidence of toxicity from sucker control agents {1317.09}. The report conveys a tone of urgency and helplessness. Griffith recognizes that, although Penar appears to be carcinogenic, he and the cigarette manufacturers have limited power to do anything about it, because Penar is produced by an independent company and is applied to tobacco in the field, months before the tobacco is bought by the cigarette makers.

The tobacco manufacturer is completely at the mercy of the people who use various chemicals on tobacco. Of the chemicals used, MH-30 and Penar have probably been investigated most extensively, and there are certainly indications that these could have detrimental biological effects from smoke. As you know, we have been sitting on the MH-30 "powder keg" for three years and no positive steps have been taken by the government agencies to provide any relief. We now have, as a result of Dr. Green's letter of April 16 [{1303.01; 1303.02}], information which suggests that Penar could be even more of a problem than MH-30. In Dr. Smith's report of April 18, he pointed out that there is a possibility that as much as 25% of the crop in North Carolina will be produced using a combination of MH-30 and Penar. It would seem that something must be done, and since this is an industry problem, we must consider every possible avenue, including bringing this to the attention of the "Less Hazardous Cigarette" Committee [discussed in chapter 4].

If you and your opposite numbers [i.e., attorneys at the other tobacco companies] can agree that this is an industry problem which must be handled on an industry basis, it might be helpful to solicit specific suggestions from the Industry Research Directors [emphasis added]. {1317.09}

Griffith's proposal to deal with the problem directly on an industry-wide basis is in line with the general policy of the R&D establishments

throughout BAT in the 1960s: they were earnestly seeking to lower toxicity in ways that did not fundamentally threaten the product itself (see chapter 4). Thus, the B&W general counsel could be asked to confer with his opposite numbers at competing companies about this "industry problem," because the problem was potentially soluble without threatening B&W's core business. Government could regulate these agricultural chemicals if necessary, and tobacco production would go on.

J. E. Kennedy and R. P. Newton of B&W R&D wrote a "private and confidential" file note in mid-1968 titled "The Relative Carcinogenicity of Sucker Control Agents Maleic Hydrazide (MH) and Dimethyldodecylamine Acetate (Penar)" {1303.03}. It was circulated to Ed Finch, B&W's CEO, Yeaman, and Griffith. The note analyzes two published studies on maleic hydrazide and the unpublished Huntingdon study on Penar. It emphasizes the relatively huge doses of both agents involved in these experiments and describes the combustion behavior of the compounds. According to the report, maleic hydrazide was not changed at high temperature and was therefore not expected to contribute other compounds to cigarette smoke. Penar, on the other hand, decomposed to dimethylamine, dodecaene, and acetic acid. Dimethylamine, in turn, was expected to produce dimethylnitrosamine, which Kennedy and Newton describe as "a strong carcinogen" {1303.03, p. 2}.

In August 1968 Imperial scientists shared their data on the carcinogenicity of Penar with Dr. T. C. Tso, a senior scientist at the US Department of Agriculture, while Dr. Tso was visiting England. This interchange is discussed prominently in a September 13, 1968, file note by Dr. Griffith, which tells of his visits earlier in the month to USDA offices in Beltsville, Maryland. He had meetings there with Dr. Tso and with Dr. Leon Moore, who was in charge of the USDA's tobacco program {1303.04}. After summarizing the data on Penar, Dr. Griffith notes:

Dr. Tso and the people in England consider that these results indicate a very serious potential problem with Penar. This information is being given to the Penar manufacturers and a summary statement has been sent to Dr. T. W. Edminster, Deputy Administrator of ARS [Agricultural Research Service], with a request that he pass this information on through normal channels to the Pesticide Division of the USDA [emphasis added]. {1303.04, pp. 1-2}

Dr. Griffith had thought from a telephone conversation with Dr. Tso on August 28 that Dr. Tso might want additional toxicology work to be done on Penar, but "this impression is erroneous. He intends to accept the English results as definitive for Penar" {1303.04, p. 2}. The additional work was to be done on other sucker control agents.

Dr. Tso is obviously impressed with the procedures being used in England and fully recognizes that valid work should not be repeated. On the other hand, the results obtained on Penar definitely indicate the need for such tests on other compounds used on tobacco. {1303.04, p. 2}

During this same September 1968 visit, Dr. Tso also talked with Dr. Griffith about the work of the Tobacco Working Group and the "Less Hazardous Cigarette Committee" in the United States. The discussion centered on cooperation and collaboration on the production of a standardized cigarette for testing.

The notes of Dr. Griffith's visit to Beltsville also summarize his meeting with Dr. Moore. Dr. Moore and Dr. Griffith agreed "that Penar was a very serious potential problem, but that this was only a specific example of a general problem" {1303.04, p. 3}. At the time, only MH-30 and Penar had been tested, and both had been found toxic. Griffith suggested that a general framework for approaching questions regarding agricultural chemicals should be developed to "prevent the feeling on the part of anyone that the USDA or Industry was attacking any individual company" {1303.04, p. 4}. The exchange indicates that Griffith was interested in developing a systematic approach to dealing with the potential toxicity of agricultural chemicals, and he clearly felt that government regulators had a major role to play. His view on pesticides sharply contrasts with B&W's position on cigarettes—that the government should play no role in regulating toxicity of cigarettes. Griffith endorsed government regulation of potentially toxic agricultural chemicals, but B&W has never wanted the government to regulate its manufactured tobacco products.

Griffith's file note concludes with his encouraging Dr. Moore to share the Penar results from England with other US tobacco product manufacturers. Griffith had known of the results because of the free exchange of research results between BAT and B&W. Other US manufacturers did not enjoy this access to the UK industry's joint research results. Moore indicated that his contact at Imperial Tobacco (John Campbell) had not given him permission to share the data. Griffith encouraged him to try to obtain that permission.

I expressed the opinion that if I were a company who did not have access to the information, I would be very disturbed. The Penar situation could explode at any minute and a company without prior knowledge could be caught in a very embarrassing position. Dr. Moore recognized this and promised to try and obtain permission from Mr. Campbell to pass this information on to the total American Tobacco Industry [emphasis added]. {1303.04, p. 4}

The carcinogenicity of Penar was later confirmed through long-term mouse skin–painting experiments conducted within the BAT system. A report two years later, dated May 18, 1970, from C. I. Ayres, a scientist in R&D at BAT in Southampton, describes the results of a 72-week-long experiment in which tobacco smoke condensates derived from tobaccos treated with two different concentrations of Penar were painted on the skins of mice {1308.01}. The report was sent to the R&D department at B&W as well as to BAT officials in Australia and Montreal. It seems to have originated at BAT's laboratory in Southampton. It refers to the experiment as the "remaining" Penar experiment, suggesting that its long-term results may have complemented short-term assays completed earlier. The experiment would have begun no later than sometime in 1968. In his report Dr. Ayres summarizes the experiments on 1,056 mice:

I am enclosing the latest results (H 685) from the remaining PENAR experiment. The position is unchanged, i.e., there is the indication that the addition ofPENAR to cut tobacco leads to an increase in the tumorigenicity of the condensate [emphasis added]. {1308.01, p. 1}

Thus, by 1970 BAT had demonstrated that an agricultural chemical could detectably increase the already high toxicity of tobacco.

Penar was finally reformulated at some time in the 1970s—years after the initial data which indicated that the original formula was carcinogenic had been developed.

Maleic hydrazide, another sucker control agent, was also reformulated. The diethanolamine salt was replaced with the potassium salt because of concerns that nitrosamines might be produced when tobacco treated with diethanolamine salt was burned (4, 5). Maleic hydrazide has continued in widespread use: in the mid-1970s about 3 million pounds were used on tobacco in the United States (4). The B&W Leaf Division reported that it was having difficulty meeting the standards set by the West German government for permissible levels of maleic hydrazide in tobacco in the 1971 tobacco crop {1317.07}. The report notes, "there is no systemic alternative to maleic hydrazide, but contact suckering formulations based on the long-chain alcohols octanol and decanol are coming into favour, especially in Canada" {1317.07}.

An April 12, 1984, memorandum from K. J. Brotzge, associate research biologist, to E. E. Kohnhorst, vice president for research, development, and engineering (RD&E) at B&W (with copies to Ivor Wallace Hughes, chairman and CEO; Thomas Sandefur, executive vice president; Ernest Pepples, senior vice president and general counsel; and others

{1003.01}), describes the "annual pesticide residue meetings" held at North Carolina State University the previous week {1318.01}. The meeting reviewed an ongoing monitoring program that analyzed levels of residues of agricultural chemicals in various brands of cigarettes. The work was supported by grants from the North Carolina Tobacco Foundation, American Tobacco, B&W, Liggett & Myers, Lorillard, Philip Morris, R. J. Reynolds, and the Tobacco Advisory Committee (UK). The program had supported a graduate student's master's degree work in toxicology. Maleic hydrazide, the sucker control agent, was still evident in cigarettes.