Comments on "Trouble in paradise".

There are statements I wish to protest in the Focus article "Trouble in Paradise" by John F. Lauerman published in Environmental Health Perspectives [105:914-917 (1997)]. These statements appear to have been attributed to me, but I can assure you I would never have made them. First, there is the suggestion that I included atrazine among a list of agricultural chemicals used in pineapple cultivation. To my knowledge, atrazine was never used on pineapple fields. It does appear in Hawaiian groundwater, however, as a result of widespread use on sugar cane fields. Second, I would never say that "none of these chemicals have been conclusively linked to adverse health effects," as the article appears to paraphrase me having said. I believe that scientific studies conclusively link all these chemicals, and still more, with harmful health effects in exposed populations. What I recall having said to Lauerman is that it is almost impossible to link, with any confidence, the cancer or other health problem of a given individual with exposure to pesticides. Thus, although a population may experience an increase in cancers or other health problems in the aggregate, the likelihood of a person with a cancer being able to prove to the satisfaction of a court of law that his or her disease was the result of exposure to a chemical is vanishingly small. The state of Hawaii has very serious contamination problems as a result of the application of agricultural chemicals and other pesticide products. I do not wish to have my statements be interpreted in any way as minimizing this problem or my own concern for the health risks that this poses.

There are statements I wish to protest in the Focus article "Trouble in Paradise" by John F. Lauerman published in Environmental Health Perspectives [105:914-917 (1997)]. These statements appear to have been attributed to me, but I can assure you I would never have made them.
First, there is the suggestion that I included atrazine among a list of agricultural chemicals used in pineapple cultivation. To my knowledge, atrazine was never used on pineapple fields. It does appear in Hawaiian groundwater, however, as a result ofwidespread use on sugar cane fields.
Second, I would never say that "none of these chemicals have been conclusively linked to adverse health effects," as the article appears to paraphrase me having said. I believe that scientific studies conclusively link all these chemicals, and still more, with harmful health effects in exposed populations. What I recall having said to Lauerman is that it is almost impossible to link, with any confidence, the cancer or other health problem of a given individual with exposure to pesticides. Thus, although a population may experience an increase in cancers or other health problems in the aggregate, the likelihood of a person with a cancer being able to prove to the satisfaction of a court of law that his or her disease was the result of exposure to a chemical is vanishingly small.
The state of Hawaii has very serious contamination problems as a result of the application of agricultural chemicals and other pesticide products. I do not wish to have my statements be interpreted in any way as minimizing this problem or my own concern for the health risks that this poses.

Patricia Tummons Environment Hawaii
Hilo, Hawaii Note: Atrazine was mistakenly included in the list of agricultural chemicals used in pineapple cultivation. EHP regrets the error.

The o2u-Globulin Discussion
One of the most valuable things to emerge from the recent series of letters published in EHP in connection with the proposed a2uglobulin mechanism of male rat renal carcinogenesis was the title of the final letter in the series by Melnick  irretrievably confused in the Discussion section of most papers, certainly in most of mine. It would be useful if all papers had a formal discussion of the data presented, followed by a separate section titled "Speculative Significance of the Data." When an issue assumes an importance in its own right, as with the a2u-globulin controversy, the way forward should be to list the evidence for and against the hypothesis, leading, in turn, to an estimate of its likely validity. Weak points in the hypothesis would thereby be revealed, and these could become the focus of further experiments; alternatively, the hypothesis could be abandoned. This path was not taken in the recent debate and, as a consequence, we are left with opposing speculations and no resolution. I took part in the EPA review of the ax2uglobulin mechanism referred to by several of the discussants in this debate, and most ofthe data recendy discussed were reviewed at that time. However, the trend in that meeting was to hear the opposing arguments and to then draw a condusion-in fact, speculations were weighed, and the balance happened to come out in favor of the probable validity of the hypothesis. What was missing from that exercise was a dissection of each of the component data sets, leading to a decision as to their individual validity. That process was started during the course ofthe EHPdebate.
The a2u-globulin mechanism of renal carcinogenesis is among the richest in data and speculation of all proposed nongenotoxic mechanisms of rodent carcinogenesis. It is therefore critical that advantage is taken of the impetus provided by the recent debate and that this hypothesis is reevaluated according to rigorous scientific criteria. Apart from the obvious need to advance our understanding of the potential carcinogenic hazard implicit in this mechanism, there is the subsidiary question of whether an agent such as limonene is formally required to be active in the TgAC and the p53 mouse abbreviated carcinogenicity bioassays. As things stand at the moment (2), a positive result in both of these assays would define limonene as a genotoxic carcinogen, whereas a positive result in only the TgAC skin painting assay would define it as a nongenotoxic carcinogen. A negative result in both assays would probably be rationalized along the lines that limonene represents the type of nongenotoxic carcinogen that modern methods should not be required to detect, i.e., that it should be classified as 'generally regarded as safe" (2). In fact, the suggested need for such abbreviated carcinogenicity bioassays of limonene would probably flow from a full analysis of the a2u-globulin hypothesis, but that, in turn, would imply that these two assays are already confirmed as giving mechanistically diagnostic data, which they are not. Thus, the importance of resolving the a2u-globulin debate.
Science proceeds by way of informed speculation. However, such speculations should not become personal property to defend at all costs. Rather, they should be vigorously challenged with the aim of either refuting them or transforming them into generally accepted facts. The sooner that happens with the speculations surrounding the ax2u-globulin hypothesis, the better.
John Ashby Zeneca CTL Alderley Park Cheshire, United Kingdom