- Email: [email protected]
IARC monographs on the evaluation of the carcinogenic risk of chemicals to man. Some aromatic azo compounds
636
Book reviews
Yellow 3, diacetylaminoazotoluene,2,6-diamino-3(phenylazo)pyridine hydrochloride,p-dimethylaminobenzenediazo sodium sulphonate, 4-hydroxyazobenzene,methyl red, Orange G, Sudan III, Sudan Brown RR or Sudan Red 7B. Evidencefor the carcinogenicity of Orange I, scarlet red, Sudan II and Yellow OB was derived only from the dubious bladderimplantation or subcutaneous sarcomatechniques.Conclusiveevidenceof carcinogenicityin animalswasavailablefor p-aminoazobenzene, o-aminoazotoluene, chrysoidine, Citrus Red No. 2, p-dimethylaminoazobenzene, Evansblue, Oil Orange SS, PonceauMX, Ponceau3R, SudanI and trypan blue. Unfortunately, no relevant human studies were known to the Working Group. It was recognized, moreover, that epidemiologicalstudiesin a general population consumingsmall quantities of azo compoundsin food or cosmeticswould be unlikely to demonstratethe isolated effect of a specific compound, in view of the simultaneousexposureto a number of carcinogens.This difficulty adds even greaterurgency to the developmentof more reliable experimentaltechniquesfor predictingthe humanresponseto suchchemicals. Apart from a considerationof inorganic selenium and its compounds,Volume 9 is devotedto aziridines and N-, S- and O-mustards.Thesedirect or indirect alkylating agents have a variety of biological and therapeuticeffects,including cytostatic and immunosuppressiveactivities, and somehave found use in the treatment of neoplasticand non-neoplasticdisordersin man. Compoundsdeemedby the Working Group to be definitely carcinogenicin at least one animal species and by one or more routes of administration were aziridine, aziridyl benzoquinone, bis-(l-aziridinyl)morpholinophosphine sulphide, 2-methylaziridine, tris(aziridinyl)-p-benzoquinone, tris-(l-aziridinyl)phosIARC Monographs on the Evaluation of the Carcinw phine sulphide, 2,4,6-tris-(l-aziridinyl)-sym-triazine, genie Risk of Chemicals to Man. Some Aromatic Azo bis-(2-chloroethyl)ether,chlorambucil, cyclophosphCompounds. Vol. 8. International Agency For amide, mannomustinedihydrochloride, melphalan, Researchon Cancer,Lyon, 1975.pp. 357. Sw.fr.36.00 mustard gas, nitrogen mustard, nitrogen mustard (availablein UK from HMSO). N-oxide hydrochloride,oestradiolmustard,phenoxybenzaminehydrochloride and uracil mustard. The IARC Monographs on the Evaluation of the Carcine evidencefor 2-(I-aziridinyl)ethanol was lessconvincgenie Risk of Chemicals to Man. Some Aziridines, N-, ing, the only incriminatory finding being the producS- & O-Mustards and Selenium. Vol. 9. International tion of sarcomas at the site of repeatedsubcutaneous AgencyFor Research on Cancer,Lyon, 1975.pp. 268. injection. The Working Group waS unable to evaSw.fr.27.00(availablein UK from HMSO). luate, becauseof inadequateor conflicting data, the carcinogenicpotential of apholate,tris-(l-aziridinyl)Of the two publicationsnamedabove,the first con- phosphineoxide, tris-(Zmethyl-I-aziridinyl)phosphine tainsthe IARC Working Group’sdeliberationson the oxide, trichlorotriethylamine hydrochloride and carcinogenicpotential of 32aromaticazo compounds, seleniumand inorganic seleniumcompounds. manyof which have beenor are beingusedas colourInterestingly, evidenceof carcinogenicity in man ingsin food, householdproducts,paper, fabrics, in- wasfound to be convincing only in the casesof meldustrial solvents and lubricants. The inclusion of phalanand mustardgas.Human data on other musmutagenicity data in the monographsfor the first tards and aziridineswereavailablebut wereconfined timereflectsa growinginterestin the useof mutageni- mainly to casereports of cancer patients who had city techniquesin the assessment of carcinogenic beentreated with such drugs (often in combination) potential. and who subsequentlydeveloped second primary The Working Group wassatisfiedthat animaltests turnours, although occasionallytumours had been on can-noisine, D & C RedNo. 9, PonceauSX, Sunset observedfollowing the use of thesecompoundsin Yellow FCF and Yellow AB had failed to provide non-malignantcases.Adequate information is not evidenceof carcinogenicity.Becauseof inadequacies availableon the backgroundincidenceof secondpriin the availabledata,no conclusionscould be reached mary neoplasms in untreatedcancercasesto permit in respectof amaranth, azobenzene,C.I. Disperse a reasonableevaluationof the significanceof second
tions of use are indicated by numerical reference to notes at the end of each table. Each class carries alphabetical indexes of all food products and food additives pertaining to it. The material received for this review presents information on the first four of the 15 classes, published in a ring-binder and reported to reflect the situatiqn at mid-1974. The remaining 11 classes are due to appear by the end of 1976. For practical reasons, individual colourings are not specified in the tables, but appear instead in a separate appendix showing their legal status in each of the 20 countries as well as in the EEC. Flavourings are to be treated in a similar way. Appendix II, which awaits publication, will be a cumulative alphabetical index of all the food additives used in the 15 classes of food products, followed by separate specific lists of flavouring matters, flavour enhancers, enzyme preparations, carrier solvents, aerosol agents and propellants, and release agents. The unacquainted reader may encounter difficulty at first in interpreting the tables and is unlikely to derive much help from the rather laborious and confusing guide provided. It is a pity, moreover, that no attempt has been made to include bibliographic lists of food-additive acts and regulations where practicable. Nevertheless, thanks to the efforts of the late Professor Bigwood and his colleagues at the Food Law Research Centre of the Institute of European Studies at the University of Brussels and to the collaboration of the correspondents representing the 20 countries surveyed, a useful source of reference in the field of food-additive legislation has been compiled. However it will be essential for the tables to be regularly and rapidly updated, if this work is to retain its value.
Book
reviews
primary tumours in cancer patients undergoing chemotherapy. As the excellent series of IARC monographs progresses, it is apparent that published findings are being subjected to increasing scrutiny by the Working Group before a particular effect is accepted as significant, but the Group has made little impression so far on the IARC programme’s ultimate aims to evaluate the data in terms of possible human risk (as the title of each volume of monographs suggests) and to indicate where additional research efforts are needed. of Insecticides. By F. Matsumura. Plenum PublishingCorp., New York, 1975.pp. xvii + 503. $33.10.
Toxicology
It wasestimatedin 1971that food worth some$80 billion wasdestroyedannually through the action of various pests,a third of this damagebeingattributed to insects.To reduce this unacceptableloss, much effort and ingenuity has beendevoted to the design andmanufactureof pesticides,and, in the USA alone, some500million poundsof insecticidesare produced each year. The appearanceof the volume under reviewis timely in view of the debateabout the likely hazardsassociatedwith the accumulationof insecticides, particularly the chlorinated hydrocarbons,in man and the environment. The subjectmatter proceedssystematicallythrough generalprinciplesof insecticidetoxicology, classification, modeof action, metabolismand penetrationinto animal systems,and the dynamics of insecticide movement in the animal and in the environment. Finally, there are two topical and interestingchapters on the effectsof pesticideson wildlife and the potential hazardsthey presentto man and domesticanimals.Thesechaptersare particularly relevant to the environmentaldebate and are written without the emotionalcontent of somesimilar material that has emanatedfrom the USA and elsewhere.The author, however,doesappearto have experiencedsomedifficulty in ordering the hugemassof data that he presentsand this detracts from the urgencyof his argument. The chapterson the modesof action of insecticides, their entry into animal systemsand the dynamicsof insecticideaccumulationare especiallygood. They are written clearly and critically, with the authority of one who hasmadeextensivecontributionsin these fields. An illustration of the use of mathematical modelsfor describinginsecticideaccumulationin the environmentis given, althoughthe difficulty of deriving suchmodelsis stressed. In many chapters,the author hassensiblyrestricted himselfto providing simpleinstructive introductions to important topicsand giving key referencesto authoritative works.This is a usefulmethod of approaching complex subjectssuchas the mode of action of nerve poisonsin the insect and mammal,since the reader is provided with just enough background knowledgeof the relevant nervoussystemsto render the accountmeaningful. The major weaknessof the book lies in the poor quality of the chapter on the genera1principles of
637
insecticidetoxicology. Here the author departsfrom the style that proves so valuable in the rest of the book and includesnumeroustestswith neither adequate descriptionnor usefulreferences.The result is a chapter lacking both clarity and authority, particularly in the sectiondn the toxicology of higher animals.Indeed, this chapter appealsto be an unfortunate mixture of the superficialand the esoteric.A more generalcriticism concernsthe style of writing and the grammaticalpeculiarities,which are extensive even by current standards.These relatively trivial errorstend to be irritating, however,rather than misleading,and the volume hasthree strengths.The first of theseis its comprehensive approachto a complex field, drawing together work from diverse areasof research.Secondly,the author has producedseveral particularly good chaptersin areasinvolving his own researchinterests.And finally, many tables present a massof usefuldata in a form that is easily assimilated, and there are extensivesubjectand author indexes.
Chromatography. A Laboratory Handbook of Chromatographic and Ebrophoretic Methods. 3rd Ed. Edited
by E. Heftmann. Van Nostrand Reinhold Co., London, 1975.pp. xxx + 969. E23.50. This edition of “Chromatography”is a revisedand modified version of the 1967edition. It is a useful and successfuladdition to the limited number of texts which attempt to cover the entire range of the subject from theoretical considerationsto practical and up-to-dateaspectsof all forms of partition, ionexchange,adsorptionand exclusionchromatography and electrophoresis. The basicformat of this necessarilylengthy volume of nearly 1000pagesis similarto that of the previous edition. The book is divided into two sections,in the first of which, 13 chapterson theoretical aspectsof the subjectand practical techniquesfollow a brief historical introduction by the Editor himself.Thus, this sectioncoversthe developmentof the conceptof differential migrationmethodsof analysis,the theory of chromatography,the physicsof the adsorptionprocess,of gelpermeationand of ion-exchangeprocesses, and the techniquesand technologyrelevant to liquid, gas,paper and thin-layer chromatographyand electrophoresis.Most of thesechapters,written by authorities in the field, treat the subjectsin considerable depth and provide extensive bibliographiesof the literature up to the period 1971-1973. The secondand longer sectionpresentsa further 15 chapterson the applicationsof chromatographic methodsto various classesof organic and inorganic compound.The classescovered include amino acids and peptides,proteins,nucleic acids,lipids, steroids, terpenoids,drugs, pesticides,phenolic compounds, carbohydrates,antibiotics,porphyrins, hydrocarbons, non-hydrocarbongasesand inorganic ionsand compounds.Few of thesechaptersare, or claim to be, comprehensive reviewsof the entire field indicatedby the chaptertitle, but eachprovidesa satisfyingsurvey of its topic and an extensiveand valuable bibliography. As in the first section,the literature is covered
Book reviews
Yellow 3, diacetylaminoazotoluene,2,6-diamino-3(phenylazo)pyridine hydrochloride,p-dimethylaminobenzenediazo sodium sulphonate, 4-hydroxyazobenzene,methyl red, Orange G, Sudan III, Sudan Brown RR or Sudan Red 7B. Evidencefor the carcinogenicity of Orange I, scarlet red, Sudan II and Yellow OB was derived only from the dubious bladderimplantation or subcutaneous sarcomatechniques.Conclusiveevidenceof carcinogenicityin animalswasavailablefor p-aminoazobenzene, o-aminoazotoluene, chrysoidine, Citrus Red No. 2, p-dimethylaminoazobenzene, Evansblue, Oil Orange SS, PonceauMX, Ponceau3R, SudanI and trypan blue. Unfortunately, no relevant human studies were known to the Working Group. It was recognized, moreover, that epidemiologicalstudiesin a general population consumingsmall quantities of azo compoundsin food or cosmeticswould be unlikely to demonstratethe isolated effect of a specific compound, in view of the simultaneousexposureto a number of carcinogens.This difficulty adds even greaterurgency to the developmentof more reliable experimentaltechniquesfor predictingthe humanresponseto suchchemicals. Apart from a considerationof inorganic selenium and its compounds,Volume 9 is devotedto aziridines and N-, S- and O-mustards.Thesedirect or indirect alkylating agents have a variety of biological and therapeuticeffects,including cytostatic and immunosuppressiveactivities, and somehave found use in the treatment of neoplasticand non-neoplasticdisordersin man. Compoundsdeemedby the Working Group to be definitely carcinogenicin at least one animal species and by one or more routes of administration were aziridine, aziridyl benzoquinone, bis-(l-aziridinyl)morpholinophosphine sulphide, 2-methylaziridine, tris(aziridinyl)-p-benzoquinone, tris-(l-aziridinyl)phosIARC Monographs on the Evaluation of the Carcinw phine sulphide, 2,4,6-tris-(l-aziridinyl)-sym-triazine, genie Risk of Chemicals to Man. Some Aromatic Azo bis-(2-chloroethyl)ether,chlorambucil, cyclophosphCompounds. Vol. 8. International Agency For amide, mannomustinedihydrochloride, melphalan, Researchon Cancer,Lyon, 1975.pp. 357. Sw.fr.36.00 mustard gas, nitrogen mustard, nitrogen mustard (availablein UK from HMSO). N-oxide hydrochloride,oestradiolmustard,phenoxybenzaminehydrochloride and uracil mustard. The IARC Monographs on the Evaluation of the Carcine evidencefor 2-(I-aziridinyl)ethanol was lessconvincgenie Risk of Chemicals to Man. Some Aziridines, N-, ing, the only incriminatory finding being the producS- & O-Mustards and Selenium. Vol. 9. International tion of sarcomas at the site of repeatedsubcutaneous AgencyFor Research on Cancer,Lyon, 1975.pp. 268. injection. The Working Group waS unable to evaSw.fr.27.00(availablein UK from HMSO). luate, becauseof inadequateor conflicting data, the carcinogenicpotential of apholate,tris-(l-aziridinyl)Of the two publicationsnamedabove,the first con- phosphineoxide, tris-(Zmethyl-I-aziridinyl)phosphine tainsthe IARC Working Group’sdeliberationson the oxide, trichlorotriethylamine hydrochloride and carcinogenicpotential of 32aromaticazo compounds, seleniumand inorganic seleniumcompounds. manyof which have beenor are beingusedas colourInterestingly, evidenceof carcinogenicity in man ingsin food, householdproducts,paper, fabrics, in- wasfound to be convincing only in the casesof meldustrial solvents and lubricants. The inclusion of phalanand mustardgas.Human data on other musmutagenicity data in the monographsfor the first tards and aziridineswereavailablebut wereconfined timereflectsa growinginterestin the useof mutageni- mainly to casereports of cancer patients who had city techniquesin the assessment of carcinogenic beentreated with such drugs (often in combination) potential. and who subsequentlydeveloped second primary The Working Group wassatisfiedthat animaltests turnours, although occasionallytumours had been on can-noisine, D & C RedNo. 9, PonceauSX, Sunset observedfollowing the use of thesecompoundsin Yellow FCF and Yellow AB had failed to provide non-malignantcases.Adequate information is not evidenceof carcinogenicity.Becauseof inadequacies availableon the backgroundincidenceof secondpriin the availabledata,no conclusionscould be reached mary neoplasms in untreatedcancercasesto permit in respectof amaranth, azobenzene,C.I. Disperse a reasonableevaluationof the significanceof second
tions of use are indicated by numerical reference to notes at the end of each table. Each class carries alphabetical indexes of all food products and food additives pertaining to it. The material received for this review presents information on the first four of the 15 classes, published in a ring-binder and reported to reflect the situatiqn at mid-1974. The remaining 11 classes are due to appear by the end of 1976. For practical reasons, individual colourings are not specified in the tables, but appear instead in a separate appendix showing their legal status in each of the 20 countries as well as in the EEC. Flavourings are to be treated in a similar way. Appendix II, which awaits publication, will be a cumulative alphabetical index of all the food additives used in the 15 classes of food products, followed by separate specific lists of flavouring matters, flavour enhancers, enzyme preparations, carrier solvents, aerosol agents and propellants, and release agents. The unacquainted reader may encounter difficulty at first in interpreting the tables and is unlikely to derive much help from the rather laborious and confusing guide provided. It is a pity, moreover, that no attempt has been made to include bibliographic lists of food-additive acts and regulations where practicable. Nevertheless, thanks to the efforts of the late Professor Bigwood and his colleagues at the Food Law Research Centre of the Institute of European Studies at the University of Brussels and to the collaboration of the correspondents representing the 20 countries surveyed, a useful source of reference in the field of food-additive legislation has been compiled. However it will be essential for the tables to be regularly and rapidly updated, if this work is to retain its value.
Book
reviews
primary tumours in cancer patients undergoing chemotherapy. As the excellent series of IARC monographs progresses, it is apparent that published findings are being subjected to increasing scrutiny by the Working Group before a particular effect is accepted as significant, but the Group has made little impression so far on the IARC programme’s ultimate aims to evaluate the data in terms of possible human risk (as the title of each volume of monographs suggests) and to indicate where additional research efforts are needed. of Insecticides. By F. Matsumura. Plenum PublishingCorp., New York, 1975.pp. xvii + 503. $33.10.
Toxicology
It wasestimatedin 1971that food worth some$80 billion wasdestroyedannually through the action of various pests,a third of this damagebeingattributed to insects.To reduce this unacceptableloss, much effort and ingenuity has beendevoted to the design andmanufactureof pesticides,and, in the USA alone, some500million poundsof insecticidesare produced each year. The appearanceof the volume under reviewis timely in view of the debateabout the likely hazardsassociatedwith the accumulationof insecticides, particularly the chlorinated hydrocarbons,in man and the environment. The subjectmatter proceedssystematicallythrough generalprinciplesof insecticidetoxicology, classification, modeof action, metabolismand penetrationinto animal systems,and the dynamics of insecticide movement in the animal and in the environment. Finally, there are two topical and interestingchapters on the effectsof pesticideson wildlife and the potential hazardsthey presentto man and domesticanimals.Thesechaptersare particularly relevant to the environmentaldebate and are written without the emotionalcontent of somesimilar material that has emanatedfrom the USA and elsewhere.The author, however,doesappearto have experiencedsomedifficulty in ordering the hugemassof data that he presentsand this detracts from the urgencyof his argument. The chapterson the modesof action of insecticides, their entry into animal systemsand the dynamicsof insecticideaccumulationare especiallygood. They are written clearly and critically, with the authority of one who hasmadeextensivecontributionsin these fields. An illustration of the use of mathematical modelsfor describinginsecticideaccumulationin the environmentis given, althoughthe difficulty of deriving suchmodelsis stressed. In many chapters,the author hassensiblyrestricted himselfto providing simpleinstructive introductions to important topicsand giving key referencesto authoritative works.This is a usefulmethod of approaching complex subjectssuchas the mode of action of nerve poisonsin the insect and mammal,since the reader is provided with just enough background knowledgeof the relevant nervoussystemsto render the accountmeaningful. The major weaknessof the book lies in the poor quality of the chapter on the genera1principles of
637
insecticidetoxicology. Here the author departsfrom the style that proves so valuable in the rest of the book and includesnumeroustestswith neither adequate descriptionnor usefulreferences.The result is a chapter lacking both clarity and authority, particularly in the sectiondn the toxicology of higher animals.Indeed, this chapter appealsto be an unfortunate mixture of the superficialand the esoteric.A more generalcriticism concernsthe style of writing and the grammaticalpeculiarities,which are extensive even by current standards.These relatively trivial errorstend to be irritating, however,rather than misleading,and the volume hasthree strengths.The first of theseis its comprehensive approachto a complex field, drawing together work from diverse areasof research.Secondly,the author has producedseveral particularly good chaptersin areasinvolving his own researchinterests.And finally, many tables present a massof usefuldata in a form that is easily assimilated, and there are extensivesubjectand author indexes.
Chromatography. A Laboratory Handbook of Chromatographic and Ebrophoretic Methods. 3rd Ed. Edited
by E. Heftmann. Van Nostrand Reinhold Co., London, 1975.pp. xxx + 969. E23.50. This edition of “Chromatography”is a revisedand modified version of the 1967edition. It is a useful and successfuladdition to the limited number of texts which attempt to cover the entire range of the subject from theoretical considerationsto practical and up-to-dateaspectsof all forms of partition, ionexchange,adsorptionand exclusionchromatography and electrophoresis. The basicformat of this necessarilylengthy volume of nearly 1000pagesis similarto that of the previous edition. The book is divided into two sections,in the first of which, 13 chapterson theoretical aspectsof the subjectand practical techniquesfollow a brief historical introduction by the Editor himself.Thus, this sectioncoversthe developmentof the conceptof differential migrationmethodsof analysis,the theory of chromatography,the physicsof the adsorptionprocess,of gelpermeationand of ion-exchangeprocesses, and the techniquesand technologyrelevant to liquid, gas,paper and thin-layer chromatographyand electrophoresis.Most of thesechapters,written by authorities in the field, treat the subjectsin considerable depth and provide extensive bibliographiesof the literature up to the period 1971-1973. The secondand longer sectionpresentsa further 15 chapterson the applicationsof chromatographic methodsto various classesof organic and inorganic compound.The classescovered include amino acids and peptides,proteins,nucleic acids,lipids, steroids, terpenoids,drugs, pesticides,phenolic compounds, carbohydrates,antibiotics,porphyrins, hydrocarbons, non-hydrocarbongasesand inorganic ionsand compounds.Few of thesechaptersare, or claim to be, comprehensive reviewsof the entire field indicatedby the chaptertitle, but eachprovidesa satisfyingsurvey of its topic and an extensiveand valuable bibliography. As in the first section,the literature is covered