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IARC monographs on the evaluation of the carcinogenic risk of chemicals to man. Some miscellaneous pharmaceutical substances
Book reviews indexed works and are a striking example of a felicitous publication policy which has contributed many useful volumes in specialized subjects of wide general interest.
Membrane Toxicity. Advances in Experimental Medicine and Biology. Vol. 84. Edited by M. W. Miller and A. E. Shamoo. Plenum Publishing Corp., New York, 1977. pp. xiv + 553. $54'00. This book contains the proceedings of the Ninth Annual Rochester International Conference on Environmental Toxicity held during May 1976 in Rochester, NY. The volume consists of 23 papers on five topics, together with the discussions and comments of the participants. The first section, on xenobiotics and membrane transport, deals with various aspects of this subject, including the effects of ouabain, p-chloromercuribenzoate and a stilbene derivative on the intestinal transport of glucose, amino acids and sodium, the influence of heavy metals on ion permeability in the lung, and the membrane transport of antifolate drugs in normal and malignant cells. The second section consists of five papers concerned with the modification of membrane function by toxic compounds. This includes an excellent paper on the morphological and biochemical changes produced in the liver by carbon tetrachloride, and also one on membrane damage in radiation-induced cell necrosis. The third section, dealing with cellular responses to toxins, contains a paper on the toxic effects of silica on macrophages and T-lymphocytes and others on the changes in membrane permeability produced by lectins, ionophores and penicillin. The papers in the fourth and fifth sections are concerned with the use of molecular probes for investigating membrane conformation and function, and the interaction of compounds with receptor sites on membranes. This collection of papers will doubtless be useful to workers thoroughly familiar with the subject but it could be of only very limited value to the general reader new tt~ this specialized field.
Directory of On-going Research in Iogy 1977. Edited by C. S. Muir IARC Scientific Publications no. Agency for Research on Cancer, xi + 599. Sw.fr. 25"00 (available in HMSO).
Cancer Epidemioand G. Wagner. 17. International Lyon, 1977. pp. the UK through
The latest directory of cancer epidemiology studies reports on 908 as yet unpublished projects, a considerable escalation on the contents of the 1976 edition. Projects are listed according to their country of origin and encompass a total of 70 countries. The proportion of studies coming from developing countries has increased, although Europe, North America and Australia still play the major role. The content of the directory reflects an increased interest in specific industrial hazards (e.g. vinyl chloride). Efforts are also focused chiefly on cancers of organs such as the lung, breast and uterus, while relatively little attention is given to other common
487
cancers, such as those of the pancreas and prostate gland. An introduction explains the workings of the clearing house for "ongoing research in cancer epidemioIogy" and the use of the directory. In addition to the main list giving details of each project, individual studies can be traced by means of indexes based on principal investigators and collaborators, cancer sites, aetiological factors and other relevant terms or key words, types of study (e.g. immunology, retrospective) and the country in which the study is being conducted. Population-based cancer registries are also listed. Undoubtedly the continuation of this comprehensive directory is invaluable to those involved in the field of cancer epidemiology.
IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Some Miscellaneous Pharmaceutical Substances. Vol. 13. IARC Working Group. International Agency for Research on Cancer, Lyon, 1977. pp. 255 Sw.fr. 30-00. The thirteenth set of monographs in this series is devoted to the evaluation, for the first time, of a group of established drugs (22 in all). It is worth repeating that these monographs summarize the evidence for the carcinogenicity of individual chemicals, but make no recommendations concerning preventive measures or legislation, since these matters depend on riskbenefit evaluation. One of the strengths of these IARC monographs has been the fully comprehensive cumulative index presented in each volume and listing alphabetically all compounds considered to date, together with appropriate synonyms. It is the'refore a little disappointing to note that eleven of the drugs considered by the Working Group at their thirteenth session were disregarded, on the grounds that "available data were inadequate". These drugs were acetylsalicyclic acid, amobarbital, chlorpromazine, diphenylthiohydantoin, LSD, nitroxoline, pentobarbital sodium, prednisone, pyrazinamide, rifampicin and spironolactone. It is to be hoped that some mention will be made of such compounds in the cumulative index of future volumes. As in previous monographs in the series, very little guidance is given on the significance of the animal data presented. Either the limitations of existing information precluded any evaluation of carcinogenic risk, as was the case with acriflavinium chloride, chloroquine, 8-hydroxyquinoline and phenylbutazone, or evidence suggestive of carcinogenicity has been cited. For three of the compounds evaluated, namely oxymetholone, phenacetin and phenytoin, human data suggested that an increased risk of cancer might be associated with administration of the drug. Only in the case of phenytoin, however, was it possible to confirm some of these effects by recourse to data generated in animal experiments. The following compounds were carcinogenic in at least one animal species: aurothioglucose, oxazepam, dithranol (a tumour promoter), ethicmamide, hycanthone mesylate, metronidazole, niridazole, phenobarbital sodium. phenytoin, pronetalol hydrochloride and pyrimelhu-
488
Book reviews
mine. In all these cases, except metronidazole, nirida- A Dictionary of Life Sciences. Edited by E. A. Martin. zole and phenobarbital sodium, for which collateral Macmillan Press Ltd., London, 1976. pp. 374. £5.95. data were obtained in hamsters or rats, the only evidence of carcinogenicity was generated in mouse Elsevier's Dictionary of Food Science and Technology. studies. Even so, no mention is made by the Working Compiled by I. D. Morton and C. Morton. Elsevier Group of reservations that have been expressed in Scientific Publishing Company, Amsterdam, 1977. pp. some quarters about the value of the mouse as a 207. D.fl 73.00. species for carcinogenicity testing. Toxicology is no respecter of disciplines. Not only are those involved directly in toxicological research Side Effects of Drugs Annual 2--1978. A Worldwide or consultancy obliged to view their problems from Yearly Survey of New Data and Trends. Edited by several different scientific angles, but they must be M. I'4. G. Dukes. Excerpta Medica, Amsterdam, 1978. prepared to understand and take into account the pp. xix+ 450. Dfl. 110.00. technological background to many of their investiga. lions. On the other side of the coin, the industrial The appearance of the second annual survey of the chemist or technologist concerned with the safety of adverse effects of drugs presents the opportunity for products or workers will inevitably become involved a few additional comments on this ambitious and far- with biological studies and their terminology. Add to reaching project. Thc volume named above, like its this the international connexions common to any predecessor published in 1977", complements Volume science and dictionaries of one sort and another are VIII of the well-known Meyler's Side Effects of Dru~s likely to come into their own. published in 1975 (Cited in F.C.T. 1977, 15, 241). Two ofthe more recent of a long line of such publiWhile revised editions of the latter, providing an over- cations are named above. The first encompasses the all review of the general situation relating to the major aspects of botany and zoology, fl'om anatomy adverse effects and interactions of drugs, are expected and physiology to genetics and ecology, together with to appear about every 3--4 years, the annual volumes some biochemistry, endocrinology, animal behaviour are intended to give a detailed and critical account and other more specialized branches of animal and of relevant new information that has appeared within plant study. The terminology of the applied biological a specified time. The first 'Annual' covered the field sciences, such as medicine and toxicology, is largely from January 1975, when the coverage of 'Meyler excluded: the seeker of granuloma, sarcoma, LDs0 VIII' terminated, to 31 July 1976. The second covered and Heinz bodies, must, quite rightly, look elsewhere, the period from 1 August 1976 to 31 July 1977, and but endoplasmic reticulum, oxidative phosphorylait is intended that volumes for succeeding years will tion, hyperplasia and autophagy are there, and within present information appearing over this range of its chosen field the book presents a set of generally months. The deadline is not rigid, however, and later clear definitions. These are backed in many cases by papers will be included where possible. explanatory diagrams and formulae, and in each The three indexes follow the same useful pattern explanation the existence of a separate entry for any in all three books, guiding readers to the contents of the terms used is clearly indicated. via the names of drugs or groups of compounds, their Obviously the specialist may disagree with some synonyms or the types of side effect produced. The aspects of the selection or with the extent or content chapters into which the text is divided are largely of individual items--but the book is not intended for the same in both Annuals, and readers familiar with him. Designed for students, teachers and science the 1977 edition will have no difficulty in finding their journalists, among others, it contains much that could way around its successor, since the chapters are be useful to the 'non-biological technologist' who arranged and numbered in the same way in both needs to follow the terminology of the many branches volumes. Two new contributions--on lithium com- of biology on which toxicology impinges. To those pounds and on drugs used in the management of gall- obliged to embark on such unfamiliar seas (perhaps stones--have been added in 1978, however. The help- the "variegated scientists" named in a recent ful system of coding references to indicate the type advertisement) this dictionary can hardly fail to be or extent of the information provided (detailed review, helpful. brief or detailed original clinical evidence and so on) The compilers of the second book named have prohas been continued in the latest volume. Moreover, vided the French, Spanish and German equivalents the cumulative indexing of the Annuals over each for a wide variety of nouns and some verbs used in 4-year period, at the end of which a revised edition the food and food-processing industries. The arrangeof'Meyler' is scheduled to appear, means that all the ment is simple. The first section consists of an alphainformation included on a given topic can be traced betical list of 2087 English words, each numbered and from only two indexes--those in the most recent edi- accompanied by the equivalent terms in the other tion of 'Meyler' and in the latest Annual. three languages, while in the following French, Altogether much thought about the practicalities Spanish and German sections each alphabetically of their use seems to have gone into these compila- listed word carries a number relating it to the English tions, as well as a great deal of information. and other equivalents to be found in the first section. Finally, for good measure, any Latin terms appearing *Side Effecls of Dru.qs Annual 1--1977. A Worldwide in the first (English) section are listed, with the releYearly Survey of New Data and Trends. Edited by vant numbers. While many of the terms included are M. N. G. Dukes. Excerpta Medica, Amsterdam, 1977. no doubt to be found in good French, German or pp. xvii + 420. Dfl. 100.00. Spanish chemical or even general dictionaries, there
Membrane Toxicity. Advances in Experimental Medicine and Biology. Vol. 84. Edited by M. W. Miller and A. E. Shamoo. Plenum Publishing Corp., New York, 1977. pp. xiv + 553. $54'00. This book contains the proceedings of the Ninth Annual Rochester International Conference on Environmental Toxicity held during May 1976 in Rochester, NY. The volume consists of 23 papers on five topics, together with the discussions and comments of the participants. The first section, on xenobiotics and membrane transport, deals with various aspects of this subject, including the effects of ouabain, p-chloromercuribenzoate and a stilbene derivative on the intestinal transport of glucose, amino acids and sodium, the influence of heavy metals on ion permeability in the lung, and the membrane transport of antifolate drugs in normal and malignant cells. The second section consists of five papers concerned with the modification of membrane function by toxic compounds. This includes an excellent paper on the morphological and biochemical changes produced in the liver by carbon tetrachloride, and also one on membrane damage in radiation-induced cell necrosis. The third section, dealing with cellular responses to toxins, contains a paper on the toxic effects of silica on macrophages and T-lymphocytes and others on the changes in membrane permeability produced by lectins, ionophores and penicillin. The papers in the fourth and fifth sections are concerned with the use of molecular probes for investigating membrane conformation and function, and the interaction of compounds with receptor sites on membranes. This collection of papers will doubtless be useful to workers thoroughly familiar with the subject but it could be of only very limited value to the general reader new tt~ this specialized field.
Directory of On-going Research in Iogy 1977. Edited by C. S. Muir IARC Scientific Publications no. Agency for Research on Cancer, xi + 599. Sw.fr. 25"00 (available in HMSO).
Cancer Epidemioand G. Wagner. 17. International Lyon, 1977. pp. the UK through
The latest directory of cancer epidemiology studies reports on 908 as yet unpublished projects, a considerable escalation on the contents of the 1976 edition. Projects are listed according to their country of origin and encompass a total of 70 countries. The proportion of studies coming from developing countries has increased, although Europe, North America and Australia still play the major role. The content of the directory reflects an increased interest in specific industrial hazards (e.g. vinyl chloride). Efforts are also focused chiefly on cancers of organs such as the lung, breast and uterus, while relatively little attention is given to other common
487
cancers, such as those of the pancreas and prostate gland. An introduction explains the workings of the clearing house for "ongoing research in cancer epidemioIogy" and the use of the directory. In addition to the main list giving details of each project, individual studies can be traced by means of indexes based on principal investigators and collaborators, cancer sites, aetiological factors and other relevant terms or key words, types of study (e.g. immunology, retrospective) and the country in which the study is being conducted. Population-based cancer registries are also listed. Undoubtedly the continuation of this comprehensive directory is invaluable to those involved in the field of cancer epidemiology.
IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Some Miscellaneous Pharmaceutical Substances. Vol. 13. IARC Working Group. International Agency for Research on Cancer, Lyon, 1977. pp. 255 Sw.fr. 30-00. The thirteenth set of monographs in this series is devoted to the evaluation, for the first time, of a group of established drugs (22 in all). It is worth repeating that these monographs summarize the evidence for the carcinogenicity of individual chemicals, but make no recommendations concerning preventive measures or legislation, since these matters depend on riskbenefit evaluation. One of the strengths of these IARC monographs has been the fully comprehensive cumulative index presented in each volume and listing alphabetically all compounds considered to date, together with appropriate synonyms. It is the'refore a little disappointing to note that eleven of the drugs considered by the Working Group at their thirteenth session were disregarded, on the grounds that "available data were inadequate". These drugs were acetylsalicyclic acid, amobarbital, chlorpromazine, diphenylthiohydantoin, LSD, nitroxoline, pentobarbital sodium, prednisone, pyrazinamide, rifampicin and spironolactone. It is to be hoped that some mention will be made of such compounds in the cumulative index of future volumes. As in previous monographs in the series, very little guidance is given on the significance of the animal data presented. Either the limitations of existing information precluded any evaluation of carcinogenic risk, as was the case with acriflavinium chloride, chloroquine, 8-hydroxyquinoline and phenylbutazone, or evidence suggestive of carcinogenicity has been cited. For three of the compounds evaluated, namely oxymetholone, phenacetin and phenytoin, human data suggested that an increased risk of cancer might be associated with administration of the drug. Only in the case of phenytoin, however, was it possible to confirm some of these effects by recourse to data generated in animal experiments. The following compounds were carcinogenic in at least one animal species: aurothioglucose, oxazepam, dithranol (a tumour promoter), ethicmamide, hycanthone mesylate, metronidazole, niridazole, phenobarbital sodium. phenytoin, pronetalol hydrochloride and pyrimelhu-
488
Book reviews
mine. In all these cases, except metronidazole, nirida- A Dictionary of Life Sciences. Edited by E. A. Martin. zole and phenobarbital sodium, for which collateral Macmillan Press Ltd., London, 1976. pp. 374. £5.95. data were obtained in hamsters or rats, the only evidence of carcinogenicity was generated in mouse Elsevier's Dictionary of Food Science and Technology. studies. Even so, no mention is made by the Working Compiled by I. D. Morton and C. Morton. Elsevier Group of reservations that have been expressed in Scientific Publishing Company, Amsterdam, 1977. pp. some quarters about the value of the mouse as a 207. D.fl 73.00. species for carcinogenicity testing. Toxicology is no respecter of disciplines. Not only are those involved directly in toxicological research Side Effects of Drugs Annual 2--1978. A Worldwide or consultancy obliged to view their problems from Yearly Survey of New Data and Trends. Edited by several different scientific angles, but they must be M. I'4. G. Dukes. Excerpta Medica, Amsterdam, 1978. prepared to understand and take into account the pp. xix+ 450. Dfl. 110.00. technological background to many of their investiga. lions. On the other side of the coin, the industrial The appearance of the second annual survey of the chemist or technologist concerned with the safety of adverse effects of drugs presents the opportunity for products or workers will inevitably become involved a few additional comments on this ambitious and far- with biological studies and their terminology. Add to reaching project. Thc volume named above, like its this the international connexions common to any predecessor published in 1977", complements Volume science and dictionaries of one sort and another are VIII of the well-known Meyler's Side Effects of Dru~s likely to come into their own. published in 1975 (Cited in F.C.T. 1977, 15, 241). Two ofthe more recent of a long line of such publiWhile revised editions of the latter, providing an over- cations are named above. The first encompasses the all review of the general situation relating to the major aspects of botany and zoology, fl'om anatomy adverse effects and interactions of drugs, are expected and physiology to genetics and ecology, together with to appear about every 3--4 years, the annual volumes some biochemistry, endocrinology, animal behaviour are intended to give a detailed and critical account and other more specialized branches of animal and of relevant new information that has appeared within plant study. The terminology of the applied biological a specified time. The first 'Annual' covered the field sciences, such as medicine and toxicology, is largely from January 1975, when the coverage of 'Meyler excluded: the seeker of granuloma, sarcoma, LDs0 VIII' terminated, to 31 July 1976. The second covered and Heinz bodies, must, quite rightly, look elsewhere, the period from 1 August 1976 to 31 July 1977, and but endoplasmic reticulum, oxidative phosphorylait is intended that volumes for succeeding years will tion, hyperplasia and autophagy are there, and within present information appearing over this range of its chosen field the book presents a set of generally months. The deadline is not rigid, however, and later clear definitions. These are backed in many cases by papers will be included where possible. explanatory diagrams and formulae, and in each The three indexes follow the same useful pattern explanation the existence of a separate entry for any in all three books, guiding readers to the contents of the terms used is clearly indicated. via the names of drugs or groups of compounds, their Obviously the specialist may disagree with some synonyms or the types of side effect produced. The aspects of the selection or with the extent or content chapters into which the text is divided are largely of individual items--but the book is not intended for the same in both Annuals, and readers familiar with him. Designed for students, teachers and science the 1977 edition will have no difficulty in finding their journalists, among others, it contains much that could way around its successor, since the chapters are be useful to the 'non-biological technologist' who arranged and numbered in the same way in both needs to follow the terminology of the many branches volumes. Two new contributions--on lithium com- of biology on which toxicology impinges. To those pounds and on drugs used in the management of gall- obliged to embark on such unfamiliar seas (perhaps stones--have been added in 1978, however. The help- the "variegated scientists" named in a recent ful system of coding references to indicate the type advertisement) this dictionary can hardly fail to be or extent of the information provided (detailed review, helpful. brief or detailed original clinical evidence and so on) The compilers of the second book named have prohas been continued in the latest volume. Moreover, vided the French, Spanish and German equivalents the cumulative indexing of the Annuals over each for a wide variety of nouns and some verbs used in 4-year period, at the end of which a revised edition the food and food-processing industries. The arrangeof'Meyler' is scheduled to appear, means that all the ment is simple. The first section consists of an alphainformation included on a given topic can be traced betical list of 2087 English words, each numbered and from only two indexes--those in the most recent edi- accompanied by the equivalent terms in the other tion of 'Meyler' and in the latest Annual. three languages, while in the following French, Altogether much thought about the practicalities Spanish and German sections each alphabetically of their use seems to have gone into these compila- listed word carries a number relating it to the English tions, as well as a great deal of information. and other equivalents to be found in the first section. Finally, for good measure, any Latin terms appearing *Side Effecls of Dru.qs Annual 1--1977. A Worldwide in the first (English) section are listed, with the releYearly Survey of New Data and Trends. Edited by vant numbers. While many of the terms included are M. N. G. Dukes. Excerpta Medica, Amsterdam, 1977. no doubt to be found in good French, German or pp. xvii + 420. Dfl. 100.00. Spanish chemical or even general dictionaries, there