Foreign Compound Metabolism in Mammals Volume 3

By D. E. Hathway

The Royal Society of Chemistry

Copyright © 1975 The Chemical Society
All rights reserved.
ISBN: 978-0-85186-028-2

Contents

Foreword By D. E. Hathway,
General Introduction: Some Environmental and Toxicological Perspectives,
Part I Uses and Abuse of DDT and Dieldrin By D. L. Gunn, 1,
Part II Role of Metabolic Studies in Drug and Biocide Development By D. E. Hathway, 83,
Part III Chronic Toxicity Testing and Metabolic Considerations By D. E. Hathway, 100,
Compound Index, 688,
Author Index, 699,

CHAPTER 1

Part I: Uses and Abuse of DDT and Dieldrin

BY D. L. GUNN

1 Introduction

Most people are aware, perhaps vaguely, of the existence of modern insecticides and have read in newspapers that DDT has been banned in various countries. Some people regard such compounds as the greatest boon of the age, but others think they art dangerous. Both views contain elements of truth. Only a few specialists know the facts, understand the choices to be made, and see that some choices that have already been made are not scientifically secure or wise.

Background. — There has been widespread organized objection in the U.S.A. to the use of DDT, which was selected as the main target by Rachel Carson, and since then there has been sustained propaganda in the Press. This propaganda has affected popular opinion and legislation and also, I consider, the conclusions reached by committees. I therefore quote examples of it from reputable newspapers : ‘inherently dangerous, highly toxic, broad spectrum persistent chemical biocide DDT …’; ‘considered hazardous to birds and marine life …’; ‘Hickel bans 16 pesticides’; quoting C. Wurster, ‘DDT has been shown to be a carcinogen …’; quoting John Thomas of West Virginia ‘Impotence down on the farm’; ‘DDT found in milk of mothers’. Since DDT is in fact found in many foods, the mainsprings of emotive propaganda – birds, food, cancer, babies, and sex – have been tapped. ‘We are dealing with people concerned purely with the profit motive’ said Paul J. Burbach’ and the campaign broke out into stickers on car bumpers inscribed ‘Sue the Bastards’. Burbach continued ‘As soon as we knock out DDT we will go after dieldrin and the rest of the persistent pesticides’.

This sort of propaganda has led to several enquiries in the U.S.A., some of them evidently influenced by untrue emotive propaganda rather than objective wisdom, and finally one ordered by the Administrator of the Environmental Protection Agency (EPA) of the U.S. Government, Mr. William D. Ruckelshaus, with Mr. Edmund M. Sweeney as Hearing Examiner. After a very full hearing of all sides of the matter lasting more than six months with 125 witnesses on 80 working days, Sweeney reported to the Administrator in April 1972. In June, Ruckelshaus ordered the general use of DDT in the U.S.A. to cease from the end of December 1972, and allowed only minor exceptions. In support of this order he made statements contrary to the findings of Sweeney’s report, statements of an unscientific character, and statements at variance with the weight of evidence presented at the Hearing. The almost complete prohibition of the use of DDT in the U.S.A. was not based on the evidence nor on the balance of advantage to the people. Later, Ruckelshaus did almost the same thing by appointing a committee under R. D. O’Brien to report on aldrin and dieldrin and then ignoring the report. He was later appointed Director of the Federal Bureau of Investigation but did not stay long in that office.

On 16th October 1973, Hearings on aldrin and dieldrin began in Washington, D.C., under Judge Herbert L. Perlman, after ‘field hearings’ in August, and were still proceeding in August 1974. It will be interesting to see how Ruckelshaus’s successor, Russell Train (see ref. 217), reacts to Perlman’s report, when it is delivered.

Since 1972, hundreds of thousands of acres of Douglas Fir in Oregon, Washington, and Idaho have been completely defoliated by the tussock moth, formerly controlled by DDT. Some areas have suffered like this for the third year in succession, and are not expected to recover. Similar damage has been done in eastern U.S.A. by the gypsy moth, formerly controlled by DDT (see p. 17). Applications to permit the use of DDT in these cases have failed, and a bill to overcome the EPA ban was placed before Congress later in 1973. Eventually, the public outcry through an organized campaign, led by a vociferous minority, against the damage being done became so great that the EPA Administrator, Russell Train, gave way and allowed the use of DDT against tussock moth just for 1974. It has been stated that he did this lest he be over-ruled by Congress, and lest the EPA be deprived of some of its great powers.

In 1970, the use of cyclamates as sweeteners was prohibited in the U.S.A. on evidence which was regarded by specialists in Britain, and no doubt also in the U.S.A., as totally inadequate and unreliable; nevertheless, Britain followed the U.S.A. in prohibiting its use. It now seems that when the experiments have been repeated in several countries, not one of them has confirmed the results upon which the ban was based. Perhaps the prohibition will shortly be removed, and perhaps some revision of the rules about DDT will ensue.

The decision of Ruckelshaus to forbid most uses of DDT in the U.S.A. was taken to the U.S. Court of Appeal in December 1973. The three judges decided that they need not undertake the ‘time-consuming and difficult task of weighing the evidence’ upon which Ruckelshaus based his decision. The Court said that all that was required was ‘substantial evidence’, ‘to support a conclusion’, apparently irrespective of other information that might completely undermine the original evidence and therefore the conclusion. Thus the judgment quotes that ‘substantial evidence is something less than the weight of evidence and the possibility of drawing two inconsistent conclusions from the evidence does not prevent an administrative agency’s finding from being supported by the evidence’. Further, the Court stated that although other ‘evidence might be sufficient to have allowed the Administrator to have decided the other way and permit DDT to continue’, that possibility did not exclude substantial evidence to support the order to stop the use of DDT.

Amongst the items of ‘substantial evidence’ quoted on p. 12 of the Court Judgment are human hazards from ‘carcinogenicity and mutagenicity of DDT’. No public authority on cancer considers that DDT has this hazard to man (see pp. 27, 63–66, 73) and, as far as I know, no trained scientist considers that it is mutagenic (see p. 67).

Surely this is the sort of judgment that brings the law into disrepute. A revulsion against the improper extrapolation of information and the weighing of fears more heavily than of needs may spread from the recent quick decision to permit the Alaska pipe-line to be laid after years of obstruction by people more concerned about conservation of wild animals than about human beings.

This subordination of scientific conclusions and of the public good to organized propaganda merits fuller discussion, for what happens in the U.S.A. is likely to affect other parts of the world. It is everybody’s business, so a sound basis for forming opinions is required. The present contribution to that purpose is primarily addressed to chemists and biochemists who are familiar with toxicology; but to set the situation into the larger picture, other material has been included.

The Environment. — The surroundings or environment are generally considered in relation to something at the centre, that which is surrounded. Thus we can discuss a man’s environment, the environment of a trout in a Canadian stream, or that of a lion in an African National Park. As a conception one may speak of The Environment in general, meaning the physical and biological conditions of the whole world, as they affect organisms. Sometimes these conditions are thought of in relation to the health or even the survival of man; sometimes the emphasis is on the pleasure that men can take in their surroundings; and sometimes the greatest concern is for the well-being or survival of those wild animals in which people take pleasure. Our fellow creatures, both human and non-human, are part of our environment, and we ought to be concerned about them. But we must be quite clear that at one place and time, the conditions may affect different organisms very differently; no environment is good for every possible inhabitant of it. In a way, then, there are several different environments at one place and time, each one of them related to a special organism. A simple example is a domestic sewage outlet into the sea; this can be very unpleasant and even dangerous to would-be bathers, but attractive and beneficial to many fish. To prevent deterioration of the environment is surely laudable; but what constitutes deterioration and what constitutes improvement may depend on one’s point of view, so that defence of one aspect may result in deterioration of another. This fact is epitomized in the title of an Editorial in Nature, ‘On Which Side are the Angels?’.

Conservation. — Conservation of the environment provides head-line news today. The American Tukey Report of 1965 made 104 recommendations (with a promise of more to follow) for ‘Restoring the Quality of our Environment’. Many of these were either of a general nature or concerned with waste disposal. About one quarter of the specific recommendations referred to pesticides, reflecting the great interest in them in the U.S.A., which is the largest user of pesticides in the world. Popular activities about pesticides reflect diverse attitudes; thus a few people oppose all use of pesticides and of artificial fertilizers as well. If they succeeded, and if agricultural chemicals were banned all over the world, much of the human population would be doomed to early death from starvation. Fortunately, the advocates of such bans can rely on the rest of the community to protect them, and the world, from the consequences of their attitude. Many more people, not so unrealistic, are concerned about possible ill effects of man’s activities, not only on man himself but also on the rest of the world.

Past Reviews. — This review could treat the whole matter as a purely scientific one, could marshall the information available, lay out the conclusions to be drawn, and thus provide a rational basis for decisions. But this has been done already in various degrees, but mainly in official publications, especially those of various committees of the British and American governments and of the United Nations Agencies, the Food and Agriculture Organization (FAO), and the World Health Organization (WHO), The official view has generally been that, in general, pesticides are necessary for the protection of man’s life, and his crops and stock, and in most cases no feasible substitutes exist. In particular, the effectiveness, cheapness, and safety-in-use of certain persistent organochlorine insecticides (which for brevity I shall refer to as pocis) (especially DDT) have generally been indicated. It is also recognized, however, that any pesticide, and indeed very many common chemicals, can cause unwelcome damage, which ought to be prevented. What is at issue is exactly what limitations ought to be placed on the use of each pesticide. Such limitations ought to depend on the biological, economic, and political circumstances in each country, and it would be wrong to impose a ubiquitous set of rules indiscriminately.

Public Opinion. — Although most official reports have recommended that persistent organochlorine insecticides ought to be used for certain purposes, and that their use ought to be somewhat restricted, the effects of these reports have been incomplete. Often they state the case for their recommendations, without full discussion of the arguments for and against using particular compounds. Another kind of publication records the symposium, in which the subject is expounded from the medical, agricultural, fisheries, conservationist, and academic points of view and occasionally from that of the general public. Such publications tend to consist simply of statements and not of attempts to resolve opposing views. In these gentlemanly affairs, nobody makes penetrating remarks or discusses controversial issues. Such publications have generally avoided analyses and have not commented publicly on statements made about ill effects of pesticides. The public is therefore aware of many benefits and is also concerned about dangers. Amongst these are real dangers against which adequate safeguards have long existed and others which are, to say the least, remote and even nonexistent. There is thus an unresolved conflict in the minds of many people. This review aims to help effective decision making.

Misleading Propaganda. — It is well known that sensationalism has greater selling value than sober news and rational conclusions, and for some newspapers, bad news is their stock-in-trade. The alarmist statements put out by Paul Ehrlich, C. Wurster, and others are thus acceptable as news, but the duller real facts and sober judgments are often not. This may explain the banding together of some science correspondents into the Environmental Communicators Organization, which seems to encourage a kind of humanitarianism – namely putting all other interests before those of human beings. Many people who are enthusiastic about conservation thus become caught up in dramatic propaganda. Much information that is untrue is published, and this influences public opinion. I shall document these statements in detail.

Contributions of Scientists. — Scientists who know the facts might be expected to correct erroneous or misleading statements in the Press and in alarm-promoting doomsday books, but in fact, most research workers are disinclined to put the unexciting truth before the public, especially in the USA., where they may then become the target for scurrilous attacks. In any case, most newspapers are disinclined to publish such corrections and even some weekly science journals have been known to refuse articles that put pesticide matters into perspective. Furthermore, many experts work for producers or users of pesticides; their statements have been attacked and discounted, as if they must be not only biased but also unreliable. I shall examine this question of integrity in scientific matters of public interest. What is evident is that serious misconceptions about pesticides have become commonplace and, since these can lead to wrong political decisions and extra losses of human lives, or of wild life, and of human happiness, they should be corrected whenever possible.

Removal of Misconceptions. — An unusual feature of this review is the attempted removal of misconceptions and the exposure of falsehood. Newspaper articles which exaggerate the amount of DDT used in this country, or which suggest that the crime wave and juvenile deliquency are due to insectides, are irrelevant. The examination of statements that are credible enough to affect the views of reasonable people provides an adequate exercise. Accordingly, many blatant falsehoods, petty perversions, and prevarications have been ignored.

A subtle example of the last named comes from an American weekly journal. An editorial article ‘Pollution by Organic Chemicals’ in Science issued a warning to companies producing insecticides such as DDT. It pointed out the very dangerous nature of some of the dioxins; these are not used as pesticides but they have occurred as significant impurities in the herbicide 2,4,5-T from one factory (no longer producing it). However, the dioxins are organic compounds which contain chlorine, and they are therefore organochlorines. Having established in the reader’s mind the horrors of dioxins, the editorial moves on smoothly to DDT, as if they were at all similar in their effects. The smear carries over.

The whole subject is a highly emotive one, and my task is not easy. To take up arms against falsehoods, perversion, and damage is proper; but on the undecided issues, a judicial attitude is commendable. One of the best expositions of this attitude is published by Resources for the Future Inc.

Attitudes. — Although it is necessary to discover the facts of a situation, administrative action is not simply based on an objective assessment of the facts and their implications; it invariably contains a subjective element, viz., what kind of world a man wants. A man’s ideals may be unalterable. This bias should not be applied except at the final stage, after the facts have been discovered and agreed, and it should be explicit. What is to be done then becomes a political matter and can be done fairly, with open eyes. If the bias is applied earlier, the selection of only emotionally or commercially acceptable information hinders the emergence of the truth, and such bias is dangerous to Society. We may have to make such a large allowance for bias that we treat as dubious the evidence or conclusions presented by some individuals or organizations, not because of their declared purposes, but because we have discredited them. Some allowances may have to be made in most cases – even in oneself. Value judgments are made by us all, however objective we may claim to be, and they too require to be identified and evaluated.

(Continues…)Excerpted from Foreign Compound Metabolism in Mammals Volume 3 by D. E. Hathway. Copyright © 1975 The Chemical Society. Excerpted by permission of The Royal Society of Chemistry.
All rights reserved. No part of this excerpt may be reproduced or reprinted without permission in writing from the publisher.
Excerpts are provided by Dial-A-Book Inc. solely for the personal use of visitors to this web site.