Reviews of environmental contamination and toxicology

Fd Chem. Toxic. Vol. 28, No. 12, pp. 859-862, 1990 Pergamon Press plc. Printed in Great Britain

REVIEWS OF RECENT PUBLICATIONS

Food Focus. Alar in Perspective--A Literature Survey. By Valerie Sargent. Leatherhead Food RA. 1990. pp. 34. £30.00 Members, £40.00 Non-Members. Alar has been the focus of a powerful media campaign and the subject of intense debate, such that the main issue--is it safe to eat Alar-treated apples--has tended to become lost in a barrage of claims and counter-claims, charges and denials, explanations and fabrications. It was therefore with great expectation that I turned to a " F o o d Focus" report from the Leatherhead Food RA, the very title of which (Alar in Perspective--A Literature Survey) conveyed promises of an informative discussion of the major issues of safety, and clarification of the facts that have inevitably become distorted in the cut and thurst of 'scientific' debate. Certainly the blow-by-blow account of the Alar controversy provides a fascinating insight into the gradual build-up of the affair, demonstrating the ease with which rumblings of concern among government agencies can be whipped up into public hysteria. Unfortunately this saga, which would have made an interesting introduction or appendix, serves instead as the focus of the report and the hoped-for perspective on Alar never materializes. It is difficult to see how Alar can be put into perspective simply by describing its recent history. Surely what is needed is a detailed look at its toxicology and at potential exposure levels, from which some sort of risk assessment can be made. The report does provide some interesting data on residue levels, but little attempt is made to relate these levels to the toxicology of Alar. Sadly, the toxicology seems to be given a bit part in the overall production, summed up under the subheading 'Problems'. This is a disappointing approach, bearing in mind that the only reason Alar became an issue was because of worrying findings in carcinogenicity assays. In the 34 pages of this report, there are only a few paragraphs and a table outlining the carcinogenic status of Alar and its breakdown product--unsymmetrical dimethylhydrazine (UDMH), which can be formed, for example, during the cooking of Alartreated apples. Unfortunately, the information is not only scant, it is also misleading to the point of being factually incorrect. The results of the 1978 National Cancer Institute study, far from failing to produce significant evidence of increased tumour incidence over controls as stated in the Food RA report, did in fact provide clear evidence of carcinogenicity in female rats, and equivocal evidence in male mice. Furthermore, the preliminary results of an unpublished study being conducted by the Uniroyal Chemical Company indicated possible carcinogenic activity in both male and female mice, a finding that the EPA is to investigate further. The Food RA report omitted to mention this study, FCT 28il2--E

although preliminary data on U D M H , published around the same time, were incorporated. In fact, although early accounts of the U D M H studies indicated negative findings (duly cited on the 'Problems' page of the Food RA report), subsequent accounts suggested increased tumour incidences in the liver of female rats, the lungs of female mice, and the blood vessels of both male and female mice. Only the lung tumours in female mice received a brief comment and even this was limited to the section on the Alar controversy, with no mention on the more appropriate 'Problems' page. Having said all this I should emphasize that I agree with the overall message of the report; that the use of Alar on apples did not pose a significant risk to health (see our earlier article, entitled "An alar dose a d a y - - a cause for concern?" (Cited in F.C.T. 1989, 27, 622). My criticism lies not in the conclusion itself, but in the manner in which it was reached, with no clear line of reasoned argument from toxicology and exposure to risk. If the scientific community itself fails to provide a logical explanation of its position, it can hardly condemn the media and pressure groups for similar misdemeanours. What hope is there for the person in the street to put risk into proper perspective? A mother who ordered Californian State Police to stop her daughter's school bus, climb on board and remove the apple from her lunchbox, clearly had a distorted view of the risks of Alar to her daughter's health. It is this type of misconception that needs to be tackled and unfortunately the Food RA report has failed in this respect. Although some will no doubt sympathize with the rather antagonistic approach that the report seems to have adopted towards the pressure groups, this can do little to improve their strained relations with the food industry. The underlying issues of risk assessment of pesticides in general and how to convey an understanding of these risks to the public remain unresolved, awaiting the next media-provoked consumer reaction to whatever 'problem' pesticide or other food chemical is singled out for attack. An authoritative and truly scientific evaluation of the Alar controversy could have made an important contribution to future debates. Unfortunately, it is all too easy to interpret this report as merely reinforcing existing prejudices in the food industry. [Tanya RusselI--BIBRA] Reviews o f Environmental Contamination and Toxicology. Vol. 102. Edited by G. W. Ware. SpringerVerlag, Berlin, 1988. pp. vi + 160. DM 86.00. ISBN 3-540-96830-X. This volume of the Springer-Verlag toxicology reviews is divided into three broad sections covering 859

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Reviews of recent publications--Fd Chem. Toxic. Vol. 28, No. 12

teratological testing, cellular toxicology and bioaccumulation of organic chemicals. The first of these, entitled "Teratologic Testing: Status and Issues after Two Decades of Evolution", by J. L. Schardein, is a comprehensive exposition on the history, regulatory issues and scientific interpretation of an important area of toxicology. The review starts where modern teratology testing really began, with thalidomide, and goes on to follow the various influences that have led to the adoption of the current protocols. Although we would not recommend reading the whole of this chapter in one go, the information therein would most definitely be of benefit to anyone interested in teratology. To the practical scientist, it is useful to have an overview of the various guidelines, protocols, etc., and it is also of interest to see how these have evolved. To manufacturers and users this review provides information not only on what is required but more unusually, whyt Finally, the discussions on interpretive issues and terminology in teratogenicity testing-the term teratogen itself has sadly been misused in toxicology--help to clarify several dilemmas in hazard assessment. In a chapter entitled "Cellular Toxicology", one might reasonably expect to find a broad overview of the usefulness and pitfalls of cell culture methods together with examples drawn from the wide range of investigations conducted on isolated cells. However, M.D. Enger has chosen to ignore such topics as drug metabolism, cell killing, biochemical disturbance and tissue specificity and to concentrate entirely on genetic effects. A title such as "Cellular Genetic Toxicology" would have been less likely to lead to disappointment. The tone of the review is set early on with the contention that risk due to toxicant exposure can only be defined adequately through an understanding of the mechanisms by which toxic agents act: an agreeable proposition for the research scientist but one engendering impatience in those charged with predicting chemical risks. The author clearly defines his field of interest by limiting himself, under the heading "Toxic Mechanisms", to chemical effects on genes and gene expression. Mechanisms of carcinogenesis and promotion are discussed in some detail, concentrating on the contribution of cellular studies to the discovery and investigation of oncogenes. One page each on gene disturbance in teratogenesis and immunotoxicology serve only to show how little progress has been made in these areas. A large section is then devoted to cellular defence mechanisms, particularly on genetic changes, such as gene amplification, which can lead to drug resistance. From the practical toxicologist's point of view, the section on in vitro test systems is the most pertinent, although it is again heavily weighted towards carcinogenicity testing. The shortcomings of current mutagenicity-based tests are discussed with reference to the recent NCI/NTP study of 83 chemicals tested in rodents and in vitro assays. The argument that a better understanding of mechanisms could lead to the deployment of more effective in vitro tests is developed well. It is suggested that the use of endpoints such as D N A demethylation, gene amplification and

aneuploidy is warranted on the basis of our present knowledge of carcinogenic mechanisms. The possible development of cell culture assays for immunotoxicity, neurotoxicity and teratogenicity is mentioned briefly. Overall, this chapter is a useful review of some of the contributions made to toxicology by basic research in cell genetics and it makes a good case in support of more basic research in toxicology. Nevertheless, one is left with the feeling that "Cellular Toxicology" has been undersold by the author concentrating solely on genetic effects. Those seeking guidance on the interpretation of cell culture tests, the prospects for introducing assays for tissue-specific toxicity or the methods used to study drug metabolism or biochemical disturbance in cultured cells may well feel let down--all because of the title! D. W. Connell, in a useful and readable chapter on the distribution of organic compounds in aquatic organisms, identifies the types of chemicals that persist in the environment and the routes of bioaccumulation. The two basic mechanisms for the bioaccumulation of organic compounds are defined. Bioconcentration occurs by uptake of lipophilic compounds directly from the aqueous environment through the gills or other respiratory surfaces and results in the compound being deposited in fatty tissues. Biomagnification results from the transfer of lipophilic compounds from aquatic food to fatty tissues. The latter is a mechanism for the transfer of organic compounds from the aqueous environment for birds and mammals, while micro-organisms, for example, accumulate organic compounds by bioconcentration. The kinetics of bioconcentration are described, together with the usefulness of partition coefficients for the prediction of bioconcentration factors in various species (fish, molluscs and some micro-organisms). [S. Clode, B. Phillips and R. Purchase--BIBRA] Laboratory Animal Handbooks II. Technical Procedures in Reproduction Toxicology. By P. Barrow. Published for Laboratory Animals Ltd by Royal Society of Medicine Services, London, 1990. pp. v + 55. £10.00. ISBN 1-853151-20-3.

As stated in the preface to this handbook, it is aimed at the scientist or technician who is entering the field of reproductive toxicology and wishes to gain basic knowledge of the practicalities of the subject. As such this book is excellent; it sets out clearly all one could wish to know. Beginning with definitions, basic study designs, regulatory requirements and animal species and husbandry, it goes on to describe all the procedures for carrying out the different tests in reproduction toxicology. We are also told that this book will help those having to write Standard Operating Procedures--in fact the book reads rather like an SOP! Accordingly, there is very little advice on data interpretation, and whilst this may be outside the remit of this handbook, there are practical areas that rely solely on the informed judgement of the investigator. Also there are procedures described that appear extremely simple in print, for example handling newborn pups, but are actually very difficult, since great care has to