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Toxicity of Pure Foods
Fd Cosmer. ‘hicol.
Vol. 13. pp. 459-464.
Pergamon
Press 1975. Printed
in Great Britain
Review Set tion BOOK
REVIEWS
Natural Flavouring Substances, Their Sources, and have alsostayedlargely unchanged-and still include Added Artificial Flavouring Substances. Partial Agree- 1 July 1973as the date by which data on temporarily ment in the Social and Public Health Field. Council admissibleflavouringsshouldbe madeavailable! of Europe, Strasbourg. Maisonneuve S. A., SainteIt is a great pity that the volume still containsno Ruffine, 1974. pp. 463. 160 Fr. cumulative index, eachcategory of artificial flavourFirst issued in 1970 under the title Natural and ingsbeinglisted separatelyin Englishand French at Artificial Flavouring Substances (Cited in F.C.T. 1971, the end. It may also be remarkedthat someof the 9. 251),this documenthasbeenconsiderablyrevised classificationsof individual flavouring materialsstill and enlarged.A singlevolume now incorporatesboth seemsomewhatarbitrary, perhapsbecausethe relethe French and English versions,and is bound in vant toxicologicaldata existingin the literature have plastic rather than in the flimsy paper used for the not beensubmittedto the Council. However, aslong as it is treated as a guide rather than a bible, this first edition. The broad categoriesof natural and artificial fla- publication shouldfind a deservedplace in the refervourings remain,classifiedin each caseaccordingto ence library of anyone concernedwith the use of whetherthey are considered“admissible”or “tempor- flavouring materials. arily admissible”or have not been fully evaluated, the last subdivisionreplacing the “not admissibleat . present”categoryof the previousversion.Consecutive Toxicitv of Pure Foods.Bv E. M. Boyd. Edited by numberinghasbeenintroduced for artificial flavour- C. E. i)oyd. CRC Press,Ohio, 1973.-pp. iii + 260. ings,with numbersl-2000 reservedfor acceptablefla- $35.00. vourings, 20014000 for those that are temporarily The conceptapparently first propoundedby Paraacceptableand 4001-7000for those not fully eva- celsusmore than four centuries ago that there is luated.There are now 692artificial fltivourings in the nothing without poisonousqualities and it is only first category, 284in the secondand 246 in the third, the dosethat makesa thing a poison is perhapsthe comparedwith the previous totals of 611, 236 and central axiom of contemporarytoxicology. While the 199,respectively.Additions have been made chiefly chief value of this latest book from the CRC Press at the end of each list, rather than according to lies in its final explosionof the myth of ‘non-toxic’ chemicalclass; this preservesthe original order to natural foods,however,it lays little emphasison the a large extent, although deletionsand occasionalin- equally fallaciousconceptof ‘pure’food in the context sertionselsewhere meanthat few compoundshave the of man’sdaily diet. Successive chaptersdescribethe toxicological imsamenumberas before. Notable additionsto the lists of admissible or tem- plicationsof an excessiveintake of carbohydrates,fats porarily admissibleartificial flavourings are someof and oils, proteinsand vitamins in experimentalanithe y- and d-lactones,specifically ones devoid of mals.The studiesreported are almost entirely acute double bonds of the type thought to be associated and short-term investigations,and they demonstrate with carcinogenic potential and those for which convincingly that for certain ‘pure’ foods the doses chronic toxicity data have becomeavailable. Several required to produce toxic or even lethal symptoms of thesewere originally classifiedas of definite toxi- in animalsare well within the limits of conceivable city, a category that now includesonly chloroform, humanconsumption.To illustratehow tenuousis the ethylmethylphenylglycidateand 2-0x0-(5 0; 6)-hexyl- line separatingdefinitionsof food additivesand food itself,the authorshavealso includedchapterson gum 1,4-dioxan. The newedition retainsthe maximumlevelsof use tragacanth,iron, silicatesand tannic acid.The studies and acceptabledaily intakespreviously specifiedfor reported wereprompted by evidencethat while drug acceptable artiticial flavourings, with only a few toxicity in experimentalanimalswas augmentedby changes.It is somewhatodd that similar limitations many vitamin-deficientdiets,the effectwas not overare given for the newcompoundslistedin the tempor- come by vitamin supplementationof the diet; the arily admissible.series and the additional data only commonfeatureof thesedietswas their content required are not specified,in contrast to the pro- of large amounts of purified oi semipurifiedfoodcedure followed for the materialsoriginally listed in stuffs.Taking the question to what may be consithis group. dered,in this context, the ultimate limits, the authors No additions or deletionsappear to have been haveincludeda chapteron the toxic effectsof distilled madeto the list of natural flavourings,but it is good water, which hasbeen shownto produce minor evito find that this list is now printed so that two open denceof toxicity in daily dosesof 20 mg/kg in rats. Overall, this book issuesno threats to reasonably pagesmay be read as one sheet.This dispenses with ihe annoying juggling necessitatedby the previous abstemiousindividuals,but may constitutea cautionversion, in which oppositepagesfaced contrarily in ary tale for those whosevoraciousappetitesrender opposite directions. The preamblesto each section them oblivious to the ‘natural’ food items in their 459
460
Book reviews
diet. At $35.00 the volume may be considered expensive for its mere 260 pages, but its presentation is good and it is easy to read. Datensammhmg zur Toxikologie der Herbizide. Series I. Deutsche Forschungsgemeinschaft-Kommission fur Pflanzenschutz-, Pflanzenbehandlungs- und Verratsschutzmittel. Verlag Chemie GmbH, Weinheim, 1974. pp. 152. DM 58. A toxicological working group of the commission of the Deutsche Forschungsgemeinschaft concerned with plant-protection, plant-treatment and storageprotection agents has produced a series of monographs on important herbicides, considered from the standpoints not only of occupational hazard and the hazard to the consumer from possible crop contamination but also of environmental protection. The data reproduced have been collected both from published literature and from the manufacturers of the materials concerned and the monographs should therefore present a comprehensive picture on the data available and provide some indication of where essential information is lacking. The monographs are all arranged in a standard form which facilitates their use. An introductory section, providing details of identification and physical properties, is followed by a series of sections dealing in turn with range of application, general functional characteristics, toxicity studies in animals, in uitro studies(whereavailable),metabolismin animalsand in plants, breakdown in soils and water, effects in manand in domestic,farm and wild animals,interactions with other materials,and therapy in casesof poisoning,culminatingin a paragraphpresentingan overall toxicologicalassessment and in a list of relevant references. The first set of monographsissuedcovers amitrol, atrazine, barban,chlorbufan, chlorpropham,diallate, diuron, phenmedipham,propham and triallate, and 2-methyl-4chlorophenoxyaceticacid, 4-(2-methyl-4 chlorophenoxy)butyric acid, dichlorprop, mecoprop, 24-D and 4-(2+dichlorophenoxy)butyric acid and their salts and esters.Separateappendicesprovide listsof commercialherbicidalpreparationscontaining thesecompoundstogetherwith their trade-namesand manufacturers,and the addresses of the latter. To enablesubsequent monographsto be incorporated in logical sequence, the first set has been publishedin loose-leafform in a convenientPVC binder. The clearlayout, and the fact that data are tabulated where possible,will help thosewithout a profound knowledgeof German to obtain useful information from thesemonographs. Progressin Toxicology. SpecialTopics.Vol. 1. By G. Zbinden. Springer-Verlag,Berlin, 1973.pp. 88. $4.70. This small volume, comprising a collection of essayson various aspectsof drug toxicology, is the first of a seriesplanned by the author. By dealing with “just a few aspectsof toxicology at one time” and publishing “at frequent intervals”, the author hopesto overcomethe problemsinherent in the production of a comprehensivetextbook in a field as broadand asrapidly expandingas toxicology. Neverthelessthe presentvolume coversa remarkably wide
rangeof topics and doesso with a degreeof insight that may no doubt be attributed to the author’s experience,formerly as a researchdirector of a large American pharmaceuticalcompany and currently as an academicand consultant to various regulatory agencies. The first and longestessayconsidersthe toxicological prerequisitesfor the study and releaseof new drugs. Currently acceptedproceduresare examined critically with referenceto possiblealternative protocolsand the dangersof too rigid an approachto drug testingare emphasized.A usefulinclusionhere is an extensivecheck-list of the type of information that may be required before or during clinical trills or following the releaseof a new drug. The following two essaysdealwith the anticipationof adverseeffects from a considerationof a compound’sknown chemical and biological propertiesand with the problem of assessing whether the effectsof a drug in animal systemsare of significancein relation to its use in man. Particular attention is paid to the influenceon drug action of such factors as microsomalenzyme induction, binding to plasmaproteins,ambient temperatureand speciesand age differences.The importance of information derived from the clinical observation of adversedrug reactionsis illustrated by a discussionof drug-inducedallergic reactionsand of oxalate metabolismin relation to the formation of kidney stones.Recent experiencewith hexachloropheneis usedto emphasizethe need for a continual reappraisalof toxicological data on compoundsin generaluse.An interestinginclusion in this context is a brief review of vitamin toxicology, prompted by the possibilityof hypervitaminosesarisingboth from the increasingtherapeuticuseof vitamins and from their increasedconsumptionas dietary supplements. The final essayis concernedwith the puzzling phenomenonthat toxic reactionsto a drug may occur more frequently in one country or continent than in another. Climate, nutritional practices, racial influencesand prescribinghabitsare amongthe factors that may account for suchdifferences.Theseare discussedwith particular referenceto the casesof subacutemyelooptico-neuropathy(SMON) that occurred in Japanduring the late 1950sand the 1960s. Although set in typescript, the book is well produced,bearing in mind its modestprice. Some230 references are includedand there is an adequatesubject index. The author’s style is informal but eminently readableand the text is ,not marred by linguistic lapses.While in no way a referencework on drug toxicology, this book-and presumablythe subsequent volumes--should provide interesting readingnot only for cliniciansand researchworkers but also for newcomersto the field. Carchmgenesis Testing of Chemicals.Proceedings: Conferenceon Carcinogenesis Testing in the Development of New Drugs, May 23-25, 1973, Washington, D.C. Edited by L. Golberg. CRC Press,Cleveland, Ohio, 1974.pp. xv + 144.$25.00. Among the manyproblemsthat confront all sectors of the chemicalindustry, none is so disturbingas the discoverythat somewidely-usedcompoundpresents a carcinogenichazard to exposed individuals. The problem has becomeparticularly acute in the field
Vol. 13. pp. 459-464.
Pergamon
Press 1975. Printed
in Great Britain
Review Set tion BOOK
REVIEWS
Natural Flavouring Substances, Their Sources, and have alsostayedlargely unchanged-and still include Added Artificial Flavouring Substances. Partial Agree- 1 July 1973as the date by which data on temporarily ment in the Social and Public Health Field. Council admissibleflavouringsshouldbe madeavailable! of Europe, Strasbourg. Maisonneuve S. A., SainteIt is a great pity that the volume still containsno Ruffine, 1974. pp. 463. 160 Fr. cumulative index, eachcategory of artificial flavourFirst issued in 1970 under the title Natural and ingsbeinglisted separatelyin Englishand French at Artificial Flavouring Substances (Cited in F.C.T. 1971, the end. It may also be remarkedthat someof the 9. 251),this documenthasbeenconsiderablyrevised classificationsof individual flavouring materialsstill and enlarged.A singlevolume now incorporatesboth seemsomewhatarbitrary, perhapsbecausethe relethe French and English versions,and is bound in vant toxicologicaldata existingin the literature have plastic rather than in the flimsy paper used for the not beensubmittedto the Council. However, aslong as it is treated as a guide rather than a bible, this first edition. The broad categoriesof natural and artificial fla- publication shouldfind a deservedplace in the refervourings remain,classifiedin each caseaccordingto ence library of anyone concernedwith the use of whetherthey are considered“admissible”or “tempor- flavouring materials. arily admissible”or have not been fully evaluated, the last subdivisionreplacing the “not admissibleat . present”categoryof the previousversion.Consecutive Toxicitv of Pure Foods.Bv E. M. Boyd. Edited by numberinghasbeenintroduced for artificial flavour- C. E. i)oyd. CRC Press,Ohio, 1973.-pp. iii + 260. ings,with numbersl-2000 reservedfor acceptablefla- $35.00. vourings, 20014000 for those that are temporarily The conceptapparently first propoundedby Paraacceptableand 4001-7000for those not fully eva- celsusmore than four centuries ago that there is luated.There are now 692artificial fltivourings in the nothing without poisonousqualities and it is only first category, 284in the secondand 246 in the third, the dosethat makesa thing a poison is perhapsthe comparedwith the previous totals of 611, 236 and central axiom of contemporarytoxicology. While the 199,respectively.Additions have been made chiefly chief value of this latest book from the CRC Press at the end of each list, rather than according to lies in its final explosionof the myth of ‘non-toxic’ chemicalclass; this preservesthe original order to natural foods,however,it lays little emphasison the a large extent, although deletionsand occasionalin- equally fallaciousconceptof ‘pure’food in the context sertionselsewhere meanthat few compoundshave the of man’sdaily diet. Successive chaptersdescribethe toxicological imsamenumberas before. Notable additionsto the lists of admissible or tem- plicationsof an excessiveintake of carbohydrates,fats porarily admissibleartificial flavourings are someof and oils, proteinsand vitamins in experimentalanithe y- and d-lactones,specifically ones devoid of mals.The studiesreported are almost entirely acute double bonds of the type thought to be associated and short-term investigations,and they demonstrate with carcinogenic potential and those for which convincingly that for certain ‘pure’ foods the doses chronic toxicity data have becomeavailable. Several required to produce toxic or even lethal symptoms of thesewere originally classifiedas of definite toxi- in animalsare well within the limits of conceivable city, a category that now includesonly chloroform, humanconsumption.To illustratehow tenuousis the ethylmethylphenylglycidateand 2-0x0-(5 0; 6)-hexyl- line separatingdefinitionsof food additivesand food itself,the authorshavealso includedchapterson gum 1,4-dioxan. The newedition retainsthe maximumlevelsof use tragacanth,iron, silicatesand tannic acid.The studies and acceptabledaily intakespreviously specifiedfor reported wereprompted by evidencethat while drug acceptable artiticial flavourings, with only a few toxicity in experimentalanimalswas augmentedby changes.It is somewhatodd that similar limitations many vitamin-deficientdiets,the effectwas not overare given for the newcompoundslistedin the tempor- come by vitamin supplementationof the diet; the arily admissible.series and the additional data only commonfeatureof thesedietswas their content required are not specified,in contrast to the pro- of large amounts of purified oi semipurifiedfoodcedure followed for the materialsoriginally listed in stuffs.Taking the question to what may be consithis group. dered,in this context, the ultimate limits, the authors No additions or deletionsappear to have been haveincludeda chapteron the toxic effectsof distilled madeto the list of natural flavourings,but it is good water, which hasbeen shownto produce minor evito find that this list is now printed so that two open denceof toxicity in daily dosesof 20 mg/kg in rats. Overall, this book issuesno threats to reasonably pagesmay be read as one sheet.This dispenses with ihe annoying juggling necessitatedby the previous abstemiousindividuals,but may constitutea cautionversion, in which oppositepagesfaced contrarily in ary tale for those whosevoraciousappetitesrender opposite directions. The preamblesto each section them oblivious to the ‘natural’ food items in their 459
460
Book reviews
diet. At $35.00 the volume may be considered expensive for its mere 260 pages, but its presentation is good and it is easy to read. Datensammhmg zur Toxikologie der Herbizide. Series I. Deutsche Forschungsgemeinschaft-Kommission fur Pflanzenschutz-, Pflanzenbehandlungs- und Verratsschutzmittel. Verlag Chemie GmbH, Weinheim, 1974. pp. 152. DM 58. A toxicological working group of the commission of the Deutsche Forschungsgemeinschaft concerned with plant-protection, plant-treatment and storageprotection agents has produced a series of monographs on important herbicides, considered from the standpoints not only of occupational hazard and the hazard to the consumer from possible crop contamination but also of environmental protection. The data reproduced have been collected both from published literature and from the manufacturers of the materials concerned and the monographs should therefore present a comprehensive picture on the data available and provide some indication of where essential information is lacking. The monographs are all arranged in a standard form which facilitates their use. An introductory section, providing details of identification and physical properties, is followed by a series of sections dealing in turn with range of application, general functional characteristics, toxicity studies in animals, in uitro studies(whereavailable),metabolismin animalsand in plants, breakdown in soils and water, effects in manand in domestic,farm and wild animals,interactions with other materials,and therapy in casesof poisoning,culminatingin a paragraphpresentingan overall toxicologicalassessment and in a list of relevant references. The first set of monographsissuedcovers amitrol, atrazine, barban,chlorbufan, chlorpropham,diallate, diuron, phenmedipham,propham and triallate, and 2-methyl-4chlorophenoxyaceticacid, 4-(2-methyl-4 chlorophenoxy)butyric acid, dichlorprop, mecoprop, 24-D and 4-(2+dichlorophenoxy)butyric acid and their salts and esters.Separateappendicesprovide listsof commercialherbicidalpreparationscontaining thesecompoundstogetherwith their trade-namesand manufacturers,and the addresses of the latter. To enablesubsequent monographsto be incorporated in logical sequence, the first set has been publishedin loose-leafform in a convenientPVC binder. The clearlayout, and the fact that data are tabulated where possible,will help thosewithout a profound knowledgeof German to obtain useful information from thesemonographs. Progressin Toxicology. SpecialTopics.Vol. 1. By G. Zbinden. Springer-Verlag,Berlin, 1973.pp. 88. $4.70. This small volume, comprising a collection of essayson various aspectsof drug toxicology, is the first of a seriesplanned by the author. By dealing with “just a few aspectsof toxicology at one time” and publishing “at frequent intervals”, the author hopesto overcomethe problemsinherent in the production of a comprehensivetextbook in a field as broadand asrapidly expandingas toxicology. Neverthelessthe presentvolume coversa remarkably wide
rangeof topics and doesso with a degreeof insight that may no doubt be attributed to the author’s experience,formerly as a researchdirector of a large American pharmaceuticalcompany and currently as an academicand consultant to various regulatory agencies. The first and longestessayconsidersthe toxicological prerequisitesfor the study and releaseof new drugs. Currently acceptedproceduresare examined critically with referenceto possiblealternative protocolsand the dangersof too rigid an approachto drug testingare emphasized.A usefulinclusionhere is an extensivecheck-list of the type of information that may be required before or during clinical trills or following the releaseof a new drug. The following two essaysdealwith the anticipationof adverseeffects from a considerationof a compound’sknown chemical and biological propertiesand with the problem of assessing whether the effectsof a drug in animal systemsare of significancein relation to its use in man. Particular attention is paid to the influenceon drug action of such factors as microsomalenzyme induction, binding to plasmaproteins,ambient temperatureand speciesand age differences.The importance of information derived from the clinical observation of adversedrug reactionsis illustrated by a discussionof drug-inducedallergic reactionsand of oxalate metabolismin relation to the formation of kidney stones.Recent experiencewith hexachloropheneis usedto emphasizethe need for a continual reappraisalof toxicological data on compoundsin generaluse.An interestinginclusion in this context is a brief review of vitamin toxicology, prompted by the possibilityof hypervitaminosesarisingboth from the increasingtherapeuticuseof vitamins and from their increasedconsumptionas dietary supplements. The final essayis concernedwith the puzzling phenomenonthat toxic reactionsto a drug may occur more frequently in one country or continent than in another. Climate, nutritional practices, racial influencesand prescribinghabitsare amongthe factors that may account for suchdifferences.Theseare discussedwith particular referenceto the casesof subacutemyelooptico-neuropathy(SMON) that occurred in Japanduring the late 1950sand the 1960s. Although set in typescript, the book is well produced,bearing in mind its modestprice. Some230 references are includedand there is an adequatesubject index. The author’s style is informal but eminently readableand the text is ,not marred by linguistic lapses.While in no way a referencework on drug toxicology, this book-and presumablythe subsequent volumes--should provide interesting readingnot only for cliniciansand researchworkers but also for newcomersto the field. Carchmgenesis Testing of Chemicals.Proceedings: Conferenceon Carcinogenesis Testing in the Development of New Drugs, May 23-25, 1973, Washington, D.C. Edited by L. Golberg. CRC Press,Cleveland, Ohio, 1974.pp. xv + 144.$25.00. Among the manyproblemsthat confront all sectors of the chemicalindustry, none is so disturbingas the discoverythat somewidely-usedcompoundpresents a carcinogenichazard to exposed individuals. The problem has becomeparticularly acute in the field