- Email: [email protected]
European Pharmacopoeia
494
Book reviews
involved in unravelling the complexities of the ecological and biological effects of the organochlorine pesticides will appreciate this paradoxical situation. Fortunately, ‘persistent workers’ abound in this field and we are indebted to the seven contributors to this book not only for bringing us up-to-date but also for indicating those areas requiring further exploration. The major contribution deals with the sublethal effects of organochlorine pesticides in the thyroid. While lethal effects are widely attributed to a neurotoxic mechanism, D. J. Jefferies elaborates on his interesting hypothesis that a variety of pathological and biochemical effects seen at different sites in the body are secondary manifestations of a primary lesion in the thyroid gland. Just how hyper- and hypothyroidism and consequential hypervitaminosis A or avitaminosis A induced by some organochlorine pesticides can account for many of the seemingly unrelated effects elsewhere makes fascinating reading, but how long this hypothesis will stand the test of time is perhaps an even more fascinating question. The other contributors concentrate on less intriguing issues-the monitoring of pesticide residues in the field, the relationship between experimental exposure of organisms and the pesticide concentrations attained in their tissues, the importance of such factors as species, strain, age and sex in determining variations in the intake, distribution, metabolism and excretion of pesticides, the effects on animal populations and, finally, an analysis of the economic considerations in the choice of pesticides and of the systems, both voluntary and statutory, employed in their control. A. V. Holden states (p. 25) that “Chemical, and in particular analytical, science is far ahead of a full biological understanding of the effects of pollution, even though many more pollutants are probably as yet undetectable”. What a daunting prospect lies ahead! Industrial Environmental Health. The Worker and the Community. 2nd Ed. Edited by L. V. Cralley and P. R. Atkins. Academic Press Inc., (London) Ltd., London, 1975. pp. xv + 356. f13.70. Hard on the heels of the first edition of this book, which essentially covered developments spanning 1968-1970, has come a second edition reporting on research activities and experience gained in the field of environmental and occupational health during the period 1971-1973. The word ‘reporting’ is used unashamedly by the reviewer because much of the ground covered in this edition is presented in the form of uncritical accounts and digests of studies published in the literature, occasionally strung together all too loosely. Like its predecessor. the second edition embraces widely divergent topics ranging from epidemiological and toxicological studies on specific chemicals to noise, ionizing and non-ionizing radiation, personal protective devices, standards for hot working environments, the significance of domestic off-job stress and the US approach to environmental chemical control. About one third of the book is devoted to summaries of varying depth on epidemiological studies
of over 50 chemicals, including pesticides. detergents. solvents and heavy metals. and on toxicological studies in animals and man relating to a less ambitious range of chemicals, but nevertheless including many old faithfuls, such as lead. mercury, cadmium, polychlorinated biphenyls. nitrosamines and aflatoxin. But apart from these and cyclamate, saccharin, phthalate esters, ethylene oxide and HC Blue No. 1, there is little to whet the appetite of those engaged in the food, food-packaging and cosmetic industries. Some readers might have derived greater benefit if brief introductory backgrounds and major points of interest had been included for each chemical covered and if the various discussions of analytical methodology, air sampling, toxicology, epidemiology and control measures in respect of a given chemical had been collated under that chemical rather than scattered throughout the book. The latter course tends to encourage unnecessary duplication, as has occurred in the case of carbon tetrachloride decomposition (pp. 94 & 272). Nevertheless. this book provides a useful progress report, lucidly written and well indexed, for workers concerned with the various facets of occupational and environmental health. European Pharmacopoeia. Published under the direction of the Council of Europe (Partial Agreement). European Treaty Series No. 50. Maisonneuve S.A., Sainte-Ruffine. Vol. I (1967): pp. 401. F.fr. 130.00. Vol. II (1971): pp.xxi + 542, F.fr. 130.00. Vol. III (1975): pp. xxii + 464, F.fr. 200.00. Volume I of the first European Pharmacopoeia was published in 1969 in accordance with the terms of the Convention on the Elaboration of a European Pharmacopoeia, under the auspices of the Council of Europe. The preface to this volume traces its background from the inception of the basic idea in 1902 through the difficult intermediate years to its final emergence as a well-produced book presenting the monographs and general methods agreed by the European Pharmacopoeia Commission up to the end of 1968. After the list of the members of the Commission and the various groups of experts, the General Notices explain the nomenclature and abbreviations used. There is then a long and detailed section on methods of analysis, followed by a list of reagents. The actual monographs, 77 in all, commence half-way through the volume. These monographs are arranged alphabetically under their Latin names, so that while gentian root (Gentianae radix), for example, is found under G, potassium chloride must be sought under K (kalii chloridum). In each monograph, the chemical nomenclature and molecular weight, where appropriate, are followed by details of the properties of the material, of methods of identification, testing and assay and of appropriate storage conditions, a format repeated in Volumes II and III and similar to that found in the British Pharmacopoeia. Volume II, published in 1971, includes a revised and expanded General Notices section. Both this volume and the third, published in 1975, present amendments and corrections relating to material published earlier and additional methods of analysis.
Book reviews Notable additions in this connexion include, in Volume II, fluorimetry, amperometry,gaschromatography and the use of infra-red spectrophotometry and thin-layer chromatographyin the identification and purity testing of steroid hormones and, in Volume III, atomic absorption spectrophotometry, electrophoresisand biological assaysfor corticotrophin and insulin.Volume II contains127new monographs,many on antibiotics, steroid hormones,vaccines and immunosera,and a long and valuable chapteron the statisticalanalysisof resultsof biological assaysand tests,while its successor addsa further 111monographs,includingeight on radiopharmaceutical preparationsgrouped together in a separate chapterbecauseof the specialproblemsthey present. The order in which the variouscategoriesof monographs(e.g. chemicalcompounds,biological materials)appearin the Pharmacopoeiadependssolely on the time at which the monographswere completed. For the chemicalcompounds,the nomenclatureand structural formulae usedfollow, where possible,the rules laid down by the International Union of Pure and Applied Chemistry,and stereochemistryis shown whenthis affectsa compound’spharmacologicalactivity or analytical identification. Entries are indexed under various alternative headingsand the indexes in the two later volumesare cumulative.The official texts are in English and French, and these three volumesand a supplementcompletethe first edition of the EuropeanPharmacopoeia. One should not underestimate the immense amountof work involved in the productionof a reference manual compiled on a basisof international agreement. The result in this casemay well be classed as a valuableachievement. Neoplasia. Proceedingsof a Workshop held at the H.T.S. ManagementCentre, Lane End, High Wycombe (Great Britain), 12-17 May 1974.Edited by W. H. Butler and P. M. Newbeme. ElsevierScientific PublishingCompany, Amsterdam, 1975.pp. xi + 195.$31.25. Mouse Hepatic
495
One enlighteningchaptersummarizes the diagnosis madeby 15 pathologists,who were given the same slidesfrom a variety of proliferative hepatic lesions. Only five out of 43 slideswere given the samediagnosisby all the pathologists!Other chaptersdeal at somelength with the factors that affect the production of hepatic tumours. Dietary and geneticfactors are by far the mostimportant, but environmentalfactors can sometimes play a vital role. This point was driven homeby the demonstrationthat oneparticular type of cagebeddingenhancedthe incidenceof mouse hepatoma considerably. One puzzling feature reportedwasa gradualincreasein the percentageincidenceof hepatomain the sameoutbied strain of miceover a periodof 10years,a problemworth bearing in mind whenthe toxicologistcallsfor the “background” incidencein a particular strain. The chemicalinductionof hepatictumoursreceived extensivecoverageat the meeting,their induction by nitrosaminesbeing given particular consideration. Attention was also drawn to the possibility that cancermay develop in the mouseliver as a consequenceof chronic toxic injury, and the tumours inducedby two hepatotoxins,carbon tetrachlorideand chloroform,wereadvancedasan illustration.The role of transplantabilityin the identification of neoplastic lesionswas considered,but it seemedprematureto put too much emphasison this technique because tumours of the same histological type seemedto behavedifferently on transplantation. What were the lessonslearnt from this meeting? They were few but crucial. One may perhapsclaim that as a result of thesediscussions the histological featuresof malignanthepaticneoplasms in the mouse are better understood,the frequencywith which they metastasizeis known with a bit more certainty and the ultrastructural featuresof someof the chemically induced tumours are better defined. The wealth of electron- and light micrographs reproduced with these lectures are of particular value in this connexion.Another important lessonconcernedthe value of mousehepatictumoursasan index of carcinogenic city. In the concluding session,all the participants evaluatedcritically the facts and opinions proferred by the various speakersat the symposiumand concludedthat this particular systemwas not a reliable meansof testing the potential hepatocarcinogenicity of chemicalsof unknown activity. This book is strongly recommended. It is essential readingfor pathologistsand toxicologists,particularly those engagedin making recommendations for carcinogenicity testing.
The toxicological significanceof the induction of tumours in the mouseby chemicalagentshas been a controversialtopic for severalyears. Although the questionhas beenraisedin connexion with tumour induction in mosttissues,the controversyhascentred around the induction of hepatic neoplasia,primarily becauseof a major disagreement amongpathologists about the nature of somenodular lesionsinducedby chemicalagents.A secondreasonwas the suspicion that someexternal influencescausedsignificantfluctuations in the natural incidenceof these tumours. Teratology Trends and Applications Edited by C. L. The book namedabove reproducesthe proceedings Berry and D. E. Poswillo. Springer-Verlag,Berlin, of a workshoparrangedto give a relatively smallin- 1975.pp.x 238.X35.30. ternational group of pathologiststhe opportunity to identify existingareasof agreementand disagreement Sincethe thalidomidedisasterat the beginningof there hasbeengreat concernover the posson the diagnosisof malignant liver tumours in the the 196Os, mouseand on their significance.Theseproceedings ible effectsof existing or novel compoundson the provide not only excellentmorphologicaldescriptions unborn, a situation reflectedin the increasinguseof of a variety of hepatic nodular lesionsbut also some teratogenicity studiesin toxicology. In this monophilosophicaldiscussionon the meaningof malig- graph, an attempt has been made to review recent nancy in the mouse, since some malignant liver advancesin this somewhatdifficult and controversial tumours seemto be well tolerated by this species. field. The text is divided into four sections,eachdeal-
Book reviews
involved in unravelling the complexities of the ecological and biological effects of the organochlorine pesticides will appreciate this paradoxical situation. Fortunately, ‘persistent workers’ abound in this field and we are indebted to the seven contributors to this book not only for bringing us up-to-date but also for indicating those areas requiring further exploration. The major contribution deals with the sublethal effects of organochlorine pesticides in the thyroid. While lethal effects are widely attributed to a neurotoxic mechanism, D. J. Jefferies elaborates on his interesting hypothesis that a variety of pathological and biochemical effects seen at different sites in the body are secondary manifestations of a primary lesion in the thyroid gland. Just how hyper- and hypothyroidism and consequential hypervitaminosis A or avitaminosis A induced by some organochlorine pesticides can account for many of the seemingly unrelated effects elsewhere makes fascinating reading, but how long this hypothesis will stand the test of time is perhaps an even more fascinating question. The other contributors concentrate on less intriguing issues-the monitoring of pesticide residues in the field, the relationship between experimental exposure of organisms and the pesticide concentrations attained in their tissues, the importance of such factors as species, strain, age and sex in determining variations in the intake, distribution, metabolism and excretion of pesticides, the effects on animal populations and, finally, an analysis of the economic considerations in the choice of pesticides and of the systems, both voluntary and statutory, employed in their control. A. V. Holden states (p. 25) that “Chemical, and in particular analytical, science is far ahead of a full biological understanding of the effects of pollution, even though many more pollutants are probably as yet undetectable”. What a daunting prospect lies ahead! Industrial Environmental Health. The Worker and the Community. 2nd Ed. Edited by L. V. Cralley and P. R. Atkins. Academic Press Inc., (London) Ltd., London, 1975. pp. xv + 356. f13.70. Hard on the heels of the first edition of this book, which essentially covered developments spanning 1968-1970, has come a second edition reporting on research activities and experience gained in the field of environmental and occupational health during the period 1971-1973. The word ‘reporting’ is used unashamedly by the reviewer because much of the ground covered in this edition is presented in the form of uncritical accounts and digests of studies published in the literature, occasionally strung together all too loosely. Like its predecessor. the second edition embraces widely divergent topics ranging from epidemiological and toxicological studies on specific chemicals to noise, ionizing and non-ionizing radiation, personal protective devices, standards for hot working environments, the significance of domestic off-job stress and the US approach to environmental chemical control. About one third of the book is devoted to summaries of varying depth on epidemiological studies
of over 50 chemicals, including pesticides. detergents. solvents and heavy metals. and on toxicological studies in animals and man relating to a less ambitious range of chemicals, but nevertheless including many old faithfuls, such as lead. mercury, cadmium, polychlorinated biphenyls. nitrosamines and aflatoxin. But apart from these and cyclamate, saccharin, phthalate esters, ethylene oxide and HC Blue No. 1, there is little to whet the appetite of those engaged in the food, food-packaging and cosmetic industries. Some readers might have derived greater benefit if brief introductory backgrounds and major points of interest had been included for each chemical covered and if the various discussions of analytical methodology, air sampling, toxicology, epidemiology and control measures in respect of a given chemical had been collated under that chemical rather than scattered throughout the book. The latter course tends to encourage unnecessary duplication, as has occurred in the case of carbon tetrachloride decomposition (pp. 94 & 272). Nevertheless. this book provides a useful progress report, lucidly written and well indexed, for workers concerned with the various facets of occupational and environmental health. European Pharmacopoeia. Published under the direction of the Council of Europe (Partial Agreement). European Treaty Series No. 50. Maisonneuve S.A., Sainte-Ruffine. Vol. I (1967): pp. 401. F.fr. 130.00. Vol. II (1971): pp.xxi + 542, F.fr. 130.00. Vol. III (1975): pp. xxii + 464, F.fr. 200.00. Volume I of the first European Pharmacopoeia was published in 1969 in accordance with the terms of the Convention on the Elaboration of a European Pharmacopoeia, under the auspices of the Council of Europe. The preface to this volume traces its background from the inception of the basic idea in 1902 through the difficult intermediate years to its final emergence as a well-produced book presenting the monographs and general methods agreed by the European Pharmacopoeia Commission up to the end of 1968. After the list of the members of the Commission and the various groups of experts, the General Notices explain the nomenclature and abbreviations used. There is then a long and detailed section on methods of analysis, followed by a list of reagents. The actual monographs, 77 in all, commence half-way through the volume. These monographs are arranged alphabetically under their Latin names, so that while gentian root (Gentianae radix), for example, is found under G, potassium chloride must be sought under K (kalii chloridum). In each monograph, the chemical nomenclature and molecular weight, where appropriate, are followed by details of the properties of the material, of methods of identification, testing and assay and of appropriate storage conditions, a format repeated in Volumes II and III and similar to that found in the British Pharmacopoeia. Volume II, published in 1971, includes a revised and expanded General Notices section. Both this volume and the third, published in 1975, present amendments and corrections relating to material published earlier and additional methods of analysis.
Book reviews Notable additions in this connexion include, in Volume II, fluorimetry, amperometry,gaschromatography and the use of infra-red spectrophotometry and thin-layer chromatographyin the identification and purity testing of steroid hormones and, in Volume III, atomic absorption spectrophotometry, electrophoresisand biological assaysfor corticotrophin and insulin.Volume II contains127new monographs,many on antibiotics, steroid hormones,vaccines and immunosera,and a long and valuable chapteron the statisticalanalysisof resultsof biological assaysand tests,while its successor addsa further 111monographs,includingeight on radiopharmaceutical preparationsgrouped together in a separate chapterbecauseof the specialproblemsthey present. The order in which the variouscategoriesof monographs(e.g. chemicalcompounds,biological materials)appearin the Pharmacopoeiadependssolely on the time at which the monographswere completed. For the chemicalcompounds,the nomenclatureand structural formulae usedfollow, where possible,the rules laid down by the International Union of Pure and Applied Chemistry,and stereochemistryis shown whenthis affectsa compound’spharmacologicalactivity or analytical identification. Entries are indexed under various alternative headingsand the indexes in the two later volumesare cumulative.The official texts are in English and French, and these three volumesand a supplementcompletethe first edition of the EuropeanPharmacopoeia. One should not underestimate the immense amountof work involved in the productionof a reference manual compiled on a basisof international agreement. The result in this casemay well be classed as a valuableachievement. Neoplasia. Proceedingsof a Workshop held at the H.T.S. ManagementCentre, Lane End, High Wycombe (Great Britain), 12-17 May 1974.Edited by W. H. Butler and P. M. Newbeme. ElsevierScientific PublishingCompany, Amsterdam, 1975.pp. xi + 195.$31.25. Mouse Hepatic
495
One enlighteningchaptersummarizes the diagnosis madeby 15 pathologists,who were given the same slidesfrom a variety of proliferative hepatic lesions. Only five out of 43 slideswere given the samediagnosisby all the pathologists!Other chaptersdeal at somelength with the factors that affect the production of hepatic tumours. Dietary and geneticfactors are by far the mostimportant, but environmentalfactors can sometimes play a vital role. This point was driven homeby the demonstrationthat oneparticular type of cagebeddingenhancedthe incidenceof mouse hepatoma considerably. One puzzling feature reportedwasa gradualincreasein the percentageincidenceof hepatomain the sameoutbied strain of miceover a periodof 10years,a problemworth bearing in mind whenthe toxicologistcallsfor the “background” incidencein a particular strain. The chemicalinductionof hepatictumoursreceived extensivecoverageat the meeting,their induction by nitrosaminesbeing given particular consideration. Attention was also drawn to the possibility that cancermay develop in the mouseliver as a consequenceof chronic toxic injury, and the tumours inducedby two hepatotoxins,carbon tetrachlorideand chloroform,wereadvancedasan illustration.The role of transplantabilityin the identification of neoplastic lesionswas considered,but it seemedprematureto put too much emphasison this technique because tumours of the same histological type seemedto behavedifferently on transplantation. What were the lessonslearnt from this meeting? They were few but crucial. One may perhapsclaim that as a result of thesediscussions the histological featuresof malignanthepaticneoplasms in the mouse are better understood,the frequencywith which they metastasizeis known with a bit more certainty and the ultrastructural featuresof someof the chemically induced tumours are better defined. The wealth of electron- and light micrographs reproduced with these lectures are of particular value in this connexion.Another important lessonconcernedthe value of mousehepatictumoursasan index of carcinogenic city. In the concluding session,all the participants evaluatedcritically the facts and opinions proferred by the various speakersat the symposiumand concludedthat this particular systemwas not a reliable meansof testing the potential hepatocarcinogenicity of chemicalsof unknown activity. This book is strongly recommended. It is essential readingfor pathologistsand toxicologists,particularly those engagedin making recommendations for carcinogenicity testing.
The toxicological significanceof the induction of tumours in the mouseby chemicalagentshas been a controversialtopic for severalyears. Although the questionhas beenraisedin connexion with tumour induction in mosttissues,the controversyhascentred around the induction of hepatic neoplasia,primarily becauseof a major disagreement amongpathologists about the nature of somenodular lesionsinducedby chemicalagents.A secondreasonwas the suspicion that someexternal influencescausedsignificantfluctuations in the natural incidenceof these tumours. Teratology Trends and Applications Edited by C. L. The book namedabove reproducesthe proceedings Berry and D. E. Poswillo. Springer-Verlag,Berlin, of a workshoparrangedto give a relatively smallin- 1975.pp.x 238.X35.30. ternational group of pathologiststhe opportunity to identify existingareasof agreementand disagreement Sincethe thalidomidedisasterat the beginningof there hasbeengreat concernover the posson the diagnosisof malignant liver tumours in the the 196Os, mouseand on their significance.Theseproceedings ible effectsof existing or novel compoundson the provide not only excellentmorphologicaldescriptions unborn, a situation reflectedin the increasinguseof of a variety of hepatic nodular lesionsbut also some teratogenicity studiesin toxicology. In this monophilosophicaldiscussionon the meaningof malig- graph, an attempt has been made to review recent nancy in the mouse, since some malignant liver advancesin this somewhatdifficult and controversial tumours seemto be well tolerated by this species. field. The text is divided into four sections,eachdeal-