Occupational and

Environmental MedicineAdopted as the Journal of the Faculty of

Occupational Medicine of the Royal College ofPhysicians of London

Editor: Anne Cockcroft (United Kingdom)Technical Editor: Judith HaynesEditorial Assistant: Rachel HarveyEditorial Board:T C Aw (United Kingdom) R McNamee (United Kingdom) D C Snashall (United Kingdom)F J H Van Dijk (Holland) J Myers (South Africa) 0 Svane (Denmark)

J S Evans (United States) B Nemery (Belgium) G Theriault (Canada)RM Harrison (United Kingdom) T Okubo (Japan) KM Venables (United Kingdom)J Jeyaratnam (Singapore) L Rosenstock (United States) Editor, British MedicalJournalF Kauffmann (France) M Sim (Australia)R L Maynard (United Kingdom) M Singal (United States)

NOTICE TO CONTRIBUTORS Occupational and EnvironmentalMedicine is intended for the publication of original contribu-tions relevant to occupational and environmental medicine,including toxicological studies of chemicals of industrial, agri-cultural, and environmental importance, and epidemiologicalstudies. As well as full papers, short papers dealing with briefor preliminary observations relevant to occupational and envi-ronmental medicine will also be considered. Case reportsshould cover substantial new ground to merit publication.Other articles, including review or position papers, will be con-sidered but should not be submitted without first approachingthe Editor to discuss their suitability for the Journal. Letters tothe Editor are always welcome. The website address for theJournal is:- http://www.bmj.com/bmj/INSTRUCTIONS TO AUTHORS Three copies of all submissionsshould be sent to: The Editor, Occupational and EnvironmentalMedicine, BMJ Publishing Group, BMA House, TavistockSquare, London WC1H 9JR, UK. All authors should sign thecovering letter as evidence of consent to publication. Papersreporting results of studies on human subjects must be accom-panied by a statement that the subjects gave written, informedconsent and by evidence of approval from the appropriateethics committee. These papers should conform to theprinciples outlined in the Declaration of Helsinki (BMJ1964;ii: 177).

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lished by the first identification in the text of a particular tableor illustration. Include only references essential to the argu-ment being developed in the paper or to the discussion ofresults, or to describe methods which are being used when theoriginal description is too long for inclusion. Information frommanuscripts not yet in press or personal communicationsshould be cited in the text, not as formal references.Use the Vancouver style, as in this issue for instance, for a

standard journal article: authors (list all authors when seven orfewer, when eight or more, list only six and add et al), title,abbreviated title of journal as given in Index Medicus (if notin Index Medicus give in full), year of publication, volumenumber, and first and last page numbers.

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Reprints Reprints will be charged for. The number ofreprints required should be stated on the form provided withthe proofs.Copyright C 1996 Occupational and Environmental Medicine.This publication is copyright under the Berne Convention andthe International Copyright Convention. All rights reserved.Apart from any relaxations permitted under national copyrightlaws, no part of this publication may be reproduced, stored ina retrieval system, or transmitted in any form or by any meanswithout the prior permission of the copyright owners.Permission is not, however, required to copy abstracts ofpapers or of articles on condition that a full reference to thesource is shown. Multiple copying of the contents of the publi-cation without permission is always illegal.NOTICE TO ADVERTISERS Applications for advertisementspace and for rates should be addressed to the AdvertisementManager, Occupational and Environmental Medicine, BMJPublishing Group, BMA House, Tavistock Square, LondonWC1H 9JR.NOTICE TO SUBSCRIBERS Occupational and EnvironmentalMedicine is published monthly. The annual subscription rate(for 1996) is £146 (US $229). Orders should be sent to theSubscription Manager, Occupational and EnvironmentalMedicine, BMJ Publishing Group, BMA House, TavistockSquare, London WC1H 9JR. Orders may also' be placed withany leading subscription agent or bookseller. (For the conve-nience of readers in the USA subscription orders with or with-out payment may also be sent to British Medical Journal, POBox 408, Franklin, MA 02038, USA. All inquiries, however,must be addressed to the publisher in London). All inquiriesregarding air mail rates and single copies already publishedshould be addressed to the publisher in London.

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ISSN 1351-0711.

Published by BMJPublishing Group andprinted in England byThanet Press IUmited,Margate, Kent

Respiratory health of workers exposed to low levels of chromium in stainless steel production

these workers can be explained partly, but nottotally, by the differences in age and smokinghabits between the groups. It is also probablethat there is a causal correlation between our

findings and both the higher dust exposures

during the first years of mine operation andthe fibrous minerals in the waste rock of themine.

Radiological parenchymal abnormalitiesand plaques classified according to ILO rec-

ommendations were not common in our

study. Small opacities were more frequentlyobserved in the radiographs of the workersexposed to chromite than in the radiographs ofthe other groups. This finding agrees with theidea that early exposure to fibrous materials is a

factor contributing to the pulmonary effects.An increased risk of lung cancer has been

found among workers in the production ofchromates and chromate pigments, as well as

in chromium plating, although no conclusivedata are available on lung cancer in fer-rochromium production.202' No cases of lungcancer were found in this study. However, riskof cancer could not be excluded because thefollow up time was short and the exposedgroup young and small.No cases of chromium asthma were found

in this study. It was recently reported thatmortality from non-malignant diseases of therespiratory system was not increased (stan-dardised mortality ratio (SMR 0O88)) among

production workers in stainless steel produc-tion.2'

ConclusionsAn average exposure time of 18 years in mod-ern ferrochromium and stainless steel produc-tion and low exposure to dusts containing Cr+6or Cr+3 does not lead to any respiratorychanges detectable by lung function tests or

radiography or to any increase in symptoms ofrespiratory diseases. The process chain understudy is unique; however, the results are alsoapplicable to other production facilities wherethe exposures to different chromium com-

pounds are equally low.The lung function test results were lower

and the occurrence of radiological findingswas more frequent among the workers fromthe chromium mine than among the controls.The difference was partly caused by differ-ences in age and smoking habits, but evidentlyalso partly by higher exposures more than twodecades ago, when the mine operations were

started, and by the fibrous components of thedust.

Because the follow up time was limited, we

are planning a reinvestigation after five years,

although there are no personal needs or

expected benefits to individual workers. Themain reason is to collect new information andto confirm the present results.

This study was conducted with financial support from theFinnish Work Environment Fund.

1 Meyers JB. Acute pulmonary complications followinginhalations of chromic acid mist. Arch Ind Hyg OccupMed 1950:2:742-7.

2 Haines AT, Nieboer E. Chromium hypersensitivity. In:Nriagu JO, Nieboer E, eds. Chromium in the natural andhuman environments. New York: John Wiley, 1988:497-532.

3 Ballal SG. Respiratory symptoms and occupational bron-chitis in chromite ore miners, Sudan. Journal of TropicalMedicine and Hygiene 1986;5:223-8.

4 Reggiani A, Lotti M, De Rosa E, Saia B. Impairments ofrespiratory functions in subjects exposed to chromium:Note 1. Spirographic changes. Lavoro Umano 1973;25:23-7.

5 Bovet P, Lob M, Grandjean M. Spirometric alterations inworkers in the chromium electroplating industry. IntArchOccup Environ Health 1977;40:25-32.

6 Lindberg E, Hedenstierna G. Chrome plating: symptoms,findings in the upper airways, and effects on lung func-tion. Arch Environ Health 1983;38:367-74.

7 Langird S. A survey of respiratory symptoms and lungfunction in ferrochromium and ferrosilicon workers. IntArch Occup Environ Health 1980;46:1-9.

8 Mancuso TF, Hueper WC. Occupational cancer and otherhealth hazards in a chromate plant: a medical appraisal. I.

Lung cancer in chromate workers. Ind Med Surg 1951;20:358-63.

9 Zober A. Possible dangers to the respiratory tract fromwelding fumes: methods of approach in an industrialhealth care context and results. Schweissen Schneiden1982;34:77-81.

10 US Public Health Service. Health of workers in chromate pro-ducing industry. Washington, DC: US Department ofHealth, Education, and Welfare, US Public HealthService 1953;192:131.

11 Swensson A. Experimental research on thefibrogenetic effect ofchromite. Stockholm: Arbetarskyddsverket 1977. Arbeteoch Hilsa 1977;2:1-14.

12 Huvinen M, Kiilunen M, Oksanen L, Koponen M, Aitio A.Exposure to chromium and its evaluation by biologicalmonitoring in the production of stainless steel. OccupMed Toxicol 1993;3:205-16.

13 Love RG, Smith TA, Gurr D, Soutar CA, Scarisbrick DA,Seaton A. Respiratory and allergic symptoms in wool tex-tile workers. BrJ Ind Med 1988;45:727-41.

14 Medical Research Council (MRC). Questionnaire on respira-tory symptoms, instructions to interviewers. London: MRC,1986.

15 American Thoracic Society. Standardization of spirometry(1987) update. Am Rev Respir Dis 1987;136:1285-98.

16 Viljanen AA, Halttunen PK, Kreus K-E, Viljanen BC.Reference values for spirometric, pulmonary diffusingcapacity and body plethysmographic studies. ScandJ ClinLab Invest 1982;42(suppl 159):1-50.

17 Make B, Miller A, Epler G, Gee JBL. Single breath diffusingcapacity in the industrial setting. Chest 1982;82:351-6.

18 Cotes JE. Lung function. Assessment and application in medi-cine. 3rd ed. Oxford: Blackwell, 1975.

19 International Labour Office. International classification ofradiographs ofpneumoconioses. Geneva: ILO, 1980.

20 International Agency for Research on Cancer. IARC mono-graphs on the evaluation of carcinogenic risks to humans. Vol49. Lyon: IARC, 1990.

21 Moulin JJ, Wild P, Mantout B, Fournier-Betz M, Mur JM,Smagghe G. Mortality from lung cancer and cardiovas-cular diseases among stainless-steel producing workers.Cancer Causes Control. 1993;4:75-81.

Rejected manuscriptsFrom February 1994, authors whose sub- be returned to them.The Joumnal will destroymitted articles are rejected will be advised of remaining copies of the article but corres-the decision and one copy of the article, pondence and reviewers' comments will betogether with any reviewers' comments, will kept.

747

Lin, Dimich-Ward, Chan-Yeung

lower in patients with RCA than in sawmillworkers. The prevalence of smokers amongasthmatic patients has been reported to be lowat 20%.3 This is not an unusual finding inasthmatic patients as they are characterized bynon-specific bronchial hyperresponsivenessand may not take up smoking or may have hadto give up smoking when they developedasthma. As expected, we found that smokingwas associated with a higher rate of decline inFEVI as in the study by Peat and Frew.219However, Ulrik et a13 were unable to show theeffect of smoking on lung function in 180adult asthmatic patients over 10 years of fol-low up. They attributed the negative finding toa small number of smokers in their series.The limitations of this study are that many

subjects were lost to follow up. There werealso differences in the duration and of followup among the groups. Subjects who wereexcluded were younger and had better initialFEV, otherwise they were similar in bothgroups. It is likely that there is a selection biasand that healthier subjects were excluded fromthis study among both patients and controls.

In conclusion, we found that patients withRCA who continued to be exposed to cedardust had a greater rate of decline in FEV1 andpatients with RCA who avoided the exposureafter the diagnosis showed a similar rate ofdecline in FEV, compared with sawmill work-ers. Removal of patients with asthma from thespecific sensitiser that caused their symptomsis important in the prevention of excessivedecline in lung function and development ofchronic airflow limitation.

1 Schachter EN, Doyle CA, Beck GJ. A Prospective study ofasthma in a rural community. Chest 1984;85:623-30.

2 Peat JK, Woolcock AJ, Cullen K. Rate of decline of lungfunction in subjects with asthma. Eur J Respir Dis1987;70:171-9.

3 Ulrik CS, Backer V, Dirksen A. A 10 year follow up of 180adults with bronchial asthma: factors important fordecline in lung function. Thorax 1992;47: 14-8.

4 Brown PJ, Greville HW, Finucane KE. Asthma and irre-versible airflow obstruction. Thorax 1984;39: 131-6.

5 Blanc P. Occupational asthma in a national disability sur-vey. Chest 1987;92:613-7.

6 Malo J. Compensation for occupational asthma in Quebec.Chest 1990;98(suppl 5):236S-9.

7 Meredith S, Taylor V, McDonald J. Occupational respira-tory disease in the United Kingdom 1989: a report to theBritish Thoracic Society and the Society of OccupationalMedicine by the SWORD project group. Br J Ind Med1991;48:292-8.

8 Chan-Yeung M, MacLean L, Paggiaro P. Follow-up studyof 232 patients with occupational asthma caused by west-ern red cedar (Thuja plicata). J Allergy Clin Immunol1987;79:792-6.

9 Chan-Yeung M, Lam S, Koerner S. Clinical features andnatural history of occupational asthma due to western redcedar (Thuja plicata). Am JMed 1982;72:411-5.

10 Mapp C, Corona P, Marzo N, Fabbri L. Persistent asthmadue to isocyanates. A follow-up study of subjects withoccupational asthma due to toluene diisocyanate. AmRev Respir Dis 1988;137:1326-9.

11 Cote J, Kennedy S, Chan-Yeung M. Outcome of patientswith cedar asthma with continuous exposure. Am RevRespirDis 1990;141:373-6.

12 American Thoracic Society. Lung function testing: selec-tion of reference values and interpretative strategies. AmRev Respir Dis 1991;144:1202-18.

13 Crapo RO, Morris AH, Gardner RM. Reference spirometricvalues using techniques and equipment that meet ATSrecommendations. Am Rev Respir Dis 1981;123:659-64.

14 Dreborg S. Skin tests used in type I allergy testing: positionpaper. Allergy 1989;44(suppl 10):36.

15 Bernstein L. Proceedings of the task force on guidelines forstandardizing old and new technologies used for the diag-nosis and treatment of allergic diseases. Jf Allergy ClinImmunol 1988;82:487-526.

16 Ulrik CS, Lange P. Decline of lung function in adults withbronchial asthma. Am J Respir Crit Care Med 1994;150:629-34.

17 Dodge RR, Burrows B. The prevalence and incidence ofasthma-like symptoms in a general population sample.Am Rev Respir Dis 1980;122:567-75.

18 Burrows B, Knudson RJ, Camilli AE, Lyle SK, LebowitzMD. The "horse-racing effect" and predicting decline inforced expiratory volume in one second from screeningspirometry. Am Rev Respir Dis 1987;135:788-93.

19 Frew AJ, Kennedy SM, Chan-Yeung M. Methacholineresponsiveness, smoking, and atopy as risk factors foraccelerated FEV, decline in the male working population.Am Rev RespirDis 1992;146:878-83.

Vancouver styleAll manuscripts submitted to Occup EnvironMed should conform to the uniformrequirements for manuscripts submitted tobiomedical journals (known as theVancouver style.)

Occup Environ Med, together with manyother international biomedical journals, hasagreed to accept articles prepared in accor-dance with the Vancouver style. The style(described in full in the BMJ, 24 February1979, p 532) is intended to standardizerequirements for authors.

References should be numbered consec-utively in the order in which they are firstmentioned in the text by Arabic numeralsabove the line on each occasion the refer-ence is cited (Manson' confirmed otherreports2 5. . .). In future references topapers submitted to Occup Environ Med

should include: the names of all authors ifthere are seven or less or, if there are more,the first six followed by et al; the title ofjournal articles or book chapters; the titlesof journals abbreviated according to thestyle of Index Medicus; and the first and finalpage numbers of the article or chapter.Titles not in Index Medicus should be givenin full.

Examples of common forms of refer-ences are:

1 International Steering Committee of Medical Editors,Uniform requirements for manuscripts submitted tobiomedical journals. BrMedJ 1979;1:532-5.

2 Soter NA, Wasserman SI, Austen KF. Cold urticaria:release into the circulation of histamine and eosino-phil chemotactic factor of anaphylaxis during coldchallenge. N EnglJ Med 1976;294:687-90.

3 Weinstein L, Swartz MN. Pathogenic properties ofinvading micro-organisms. In: Sodeman WA Jr,Sodeman WA, eds. Pathologic physiology, mechanismsof disease. Philadelphia: W B Saunders, 1974:457-72.

756

Fakhi, Paoletti, Mariotta, Giosue, Guidi, Biondo, et al

and smoking on bronchoalveolar lavage measurements oflung dust in Vermont granite workers. Am Rev Respir Dis1991;144: 1307-13.

6 Begin RO, Cantin AM, Boileau RD, Bisson GY. Spectrumof alveolitis in quartz-exposed human subjects. Chest1987;92:1061-7.

7 Bernstein M, Pairon JC, Morabia A, Gaudichet A, JansonX, Brochard P. Non-fibrous dust load and smoking indental technicians: a study using bronchoalveolar lavage.Occup Environ Med 1994;51:23-7.

8 American Conference of Governmental IndustrialHygienists. Documentation of the threshold limit values andbiological exposures indices, 5th ed. Cincinnati, US:ACGIH, 1986.

9 Falchi M, Donelli G, Paoletti L. Influence of particle sizeand chemical composition on efficiency of clearancemechanisms: electron microscopy studies in humans.Environ Health Perspect 1994;102:241-3.

10 Falchi M, Biondo L, Conti C, Cipri A, De Marinis F, GigliB, Paoletti L. Inorganic particles in BAL fluids from non-occupationally exposed subjects. Arch Environ Health1996;51:157-61.

11 Chariot P, Couste B, Guillon F, Gaudichet A, Bignon J,Brochard P. Non fibrous mineral particles in bron-choalveolar lavage fluid and lung parenchyma from thegeneral population. Am Rev RespirDis 1992;146:61-5.

12 De Vuyst P. Van de Weyer R, De Coster A, MarchandiseFX, Dumortier P, Ketelbant P, Jedwab J, Yernault JC.Dental technician's pneumoconiosis. Am Rev Respir Dis1986;133:316-20.

13 Johnson NF, Haslam PL, Dewar A, Newman-Taylor AJ,Turner-Warwick M. Identification of inorganic dust par-ticles in bronchoalveolar lavage macrophages by energydispersive x ray microanalysis. Archiv Environ Health1986;41:133-44.

14 European Society of Pneumology Task Group on BAL.Technical recommendations and guidelines for bron-choalveolar lavage (BAL). Eur RespirJ 1989;2:561-85.

15 Pairon JC, Roos F, Iwatsubo Y, Janson X, Brochard P.Lung retention of cerium in humans. Occup Environ Med1994;51: 195-9.

16 Dumortier P, De Vuyst P, Yernault JC. Non-fibrous inor-

ganic particles in human bronchoalveolar lavage fluids.Scann Microscop 1989;3:1207-18.

17 Dodson RF, Garcia JGN, O'Sullivan M, Corn C, Levin JL,Griffith DE, Kronenberg RS. The usefulness of bron-choalveolar savage in identifying past occupational expo-sure to asbestos: a light and electron microscopy study.AmJ'IndMed 1991;19:619-28.

18 Tuomi T, Oksa P. Antilla S, Taikina-aho 0, Taskinen E,Karjalainen A, Tukiainen P. Fibres and asbestos bodiesin bronchoalveolar lavage fluids of asbestos sprayers. BrJIndMed 1992;49:480-5.

19 Teschler H, Konietzko N, Schonfeld B, Ramin C, SchrapsT, Costabel U. Distribution of asbestos bodies in thehuman lung as determined by bronchoalveolar lavage:Am Rev RespirDis 1993;147:1212-5.

20 Teschesler H, Friedrichs KH, Hoheisel GB, Wick G,Soltner U, Thompson AB, Konietzko N, Costabel U.Asbestos fibers in bronchoalveolar lavage and lung tissueof farmer asbestos workers. Am J Respir Crit Care Med1994;149:641-5.

21 Funahashi A, Schlueter DP, Pintar K, Siegesmund AK.Value in situ elemental microanalysis in the histologicdiagnosis of silicosis. Chest 1984;85:506-9.

22 Gaudichet A, Pairon JC, Malandain 0, Couste B,Brochard P, Bignon J. Etude mineralogique des partic-ules non fibreuses du liquide de ravage broncho-alveo-laire. Rev Mal Respir 1987;4:237-43.

23 Ziskind M, Jones RN, Weill H. State of the art. Silicosis.Am Rev RespirDis 1976;113:643-65.

24 Lusuardi M, Capelli A, Carli S, Donner CF. Inflammatoryand immune reactions associated with inorganic dustexposure: comparison between patients with and withoutclinical lung involvement. Eur RespirJ 1990;3:365-7.

25 Rom NW, Bitterman BP, Rennard IS, Cantin A, CrystalGR. Characterization of lower respiratory tract inflam-mation of nonsmoking individuals with interstitial lungdisease associated with chronic inhalation of inorganicdusts. Am Rev RespirDis 1987;136:1429-34.

26 Liippo KK, Anttila SL, Taikina-Aho 0, Ruokonen E-L,Toivonen ST, Tuomi T. Hypersensitivity pneumonitisand exposure to zirconium silicate in a young ceramic tileworker. Am Rev RespirDis 1993;148:1089-92.

Occupational and Environmental Medicine and theelectronic age

OEM has an Email address which is100632.3615@compuserve.com. We wel-come contact by Email, including letters tothe editor. Some of our reviewers alreadysend us their reports by Email, helping tospeed up the peer review process.We are moving towards electronic pub-

lishing and for some months now we havebeen asking authors to send us their revisedpapers on disk as well as a hard copy. I amdelighted to report that nearly all ourauthors are managing to comply with this

request; far more than for other specialistjournals in the BMJ Publishing group.Oddly enough, the few authors who havenot sent us a disk version of their revisedpapers have been almost exclusively fromthe United Kingdom. I would be interestedin suggestions for why this might be.Perhaps United Kingdom based authorsread our correspondence and instructionsless assiduously? Watch for revisedInstructions to Authors.

The Editor

766

Lymphohaematopoietic malignancies and quantitative estimates of exposure to benzene in Canadian petroleum distribution workers

17 Paxton MB, Chinchilli VM, Brett SM, Rodricks JV.Leukemia risk associated with benzene exposure in thepliofilm cohort: II. Risk estimates. Risk Anal 1994;14:155-7.

18 Wong 0. An industry wide mortality study of chemicalworkers occupationally exposed to benzene. II. Doseresponse analyses. BrJ Ind Med 1987;44:382-95.

19 Bond GG, McLaren EA, Baldwin CL, Cook RR. Anupdate of mortality among chemical workers exposed tobenzene. BrJ Ind Med 1986;43:685-91.

20 Paci E, Buiatti E, Seniori Costantini AR, Miligi L, Quinn M,Kaldor J, et al. Leukemia and aplastic anaemia in a

shoeworker cohort exposed to benzene. In: C Hogstedt,C Reuterwall, eds. Progress in occupational epidemiology.Amsterdam: Elsevier, BV Biomedical Division,1988:133-6.

21 Vigliani EC, Saita G. Benzene and leukemia. NEnglJ7Med1964;271:872-6.

22 Rushton L. Further follow up of mortality in a UnitedKingdom oil distribution centre cohort. Br _7 Ind Med1993;50:561-9.

23 Schnatter AR, Katz AM, Nicolich MJ, Theriault G. A ret-rospective mortality study among Canadian petroleummarketing and distribution workers. Environ HealthPerspect 1993;1O1(suppl 6):85-99.

24 Wong 0, Harris F, Smith TJ. Health effects of gasolineexposure. II. Mortality patterns of distribution workers inthe United States. Environ Health Perspect 1993;101(suppl 6):63-76.

25 Christie D, Robinson K, Gordon I, Bisby J. A prospectivestudy in the Australian petroleum industry. I. Mortality.BrJ7IndMed 1991;48:507-10.

26 Schnatter AR, Theriault G, Katz AM, Thompson FS,Donaleski D, Murray N. A retrospective mortality studywithin operating segments of a petroleum company. AmJIndMed 1992;22:209-29.

27 Armstrong TW, Pearlman ED, Schnatter AR, Bowes SM,Murray N, Nicolich MJ. Retrospective benzene exposureassessment for petroleum marketing and distribution epi-demiology. Am Ind HygAssocJr 1996;57:333-43.

28 Checkoway H, Pearce N, Hickey JLS, Dement JM.Latency analysis in occupational epidemiology. ArchEnviron Health 1990;45:95-100.

29 Mantel N, Haenszel W. Statistical aspects of the analysis ofdata from retrospective studies of disease. Nad CancerInst 1959;22:719-48.

30 Breslow NE, Day NE. Statistical methods in cancer research,vol I-the analysis of case-control studies. Lyon, France:International Agency for Research on Cancer, 1980.

31 Statistics and epidemiology research corporation EGRET

manual addendum, revision 2. Seattle, WA: SERC,1991.32 Mehta CR, Patel NR, Grey R. Computing an exact confi-

dence interval for the common odds ratio in several 2x2

contingency tables. Journal of the American StatisticalAssociation 1986;80:392, and 969-73.

33 Wartenberg D, Northridge M. Defining exposure in casecontrol studies: a new approach. Am Epidemiol 1991;133:1058-71.

34 SAS Institute. SASISTAT software: changes and enhance-ments, release 6-07. Cary, NC: SAS, 1992. (SAS technicalreport P-229.)

35 Kinlen L, Rogot E. Leukemia and smoking habits amongUnited States veterans. BMJ 1988;297:657-9.

36 Mills PK, Nowell GR, Beeson WL, Fraser GE, Phillips RL.History of cigarette smoking and risk of leukemia andmyeloma: results from the adventist health study. J7 NatlCancer Inst 1990;82:1832-6.

37 Siegel M. Smoking and leukemia: evaluation of a causalhypothesis. Am Epidemiol 1993; 138:1-9.

38 Linet MS, McLaughlin JK, Hsing AW, Wacholder S, Co-Chien HT, Schuman LM, et al. Cigarette smoking andleukemia results from the Lutheran brotherhood cohortstudy. Cancer Causes Control 1991;2:413-7.

39 Linet MS, McLaughlin JK, Hsing AW, Wacholder S,CoChien HT, Schuman LM, et al. Is cigarette smoking arisk factor for non-Hodgkin's lymphoma or multiplemyeloma? Results from the Lutheran brotherhood cohortstudy. Leuk Res 1992;16:621-4.

40 Brown LM, Everett GD, Gibson R, Burmeister LF,Schuman LM, Blair A. Smoking and risk of non-Hodgkin's lymphoma and multiple myeloma. CancerCauses Control 1992;3:49-55.

41 Franceschi S, Serraino D, Bidoli E, Talamini R, Tirelli U,Carbone A, et al. The epidemiology of non-Hodgkin'slymphoma in the north-east of Italy: a hospital-basedcase control study. Leuk Res 1989;13:465-72.

42 Persson B, Frederksson M, Olsen K, Boeryd B. Axelson 0.Some occupational exposures as risk factors for malig-nant lymphomas. Cancer 1993;72:1773-8.

43 Heineman EF, Zahm SH, McLaughlin JK, Vaught JB,Hrubec Z. A prospective study of tobacco use and multi-ple myeloma: evidence against an association. CancerCauses Control 1992;3:391-2.

44 Tajima K. The 4th nationwide study of adult T-cellleukemia/lymphoma in Japan: estimates of risk of ATLand its geographic and clinical features. Int Cancer1990;45:237-43.

45 Bourguet CC, Grufferman S, Delzell E, DeLong ER,Cohen HJ. Multiple myeloma and family history of can-cer. Cancer 1985;56:2133-9.

Correspondence and editorialsOccupational and Environmental Medicine wel- minimum. Letters are accepted on thecomes correspondence relating to any of the understanding that they may be subject tomaterial appearing in the journal. Results editorial revision and shortening.from preliminary or small scale studies may The journal also publishes editorials whichalso be published in the correspondence are normally specially commissioned. Thecolumn if this seems appropriate. Letters Editor welcomes suggestions regardingshould be not more than 500 words in length suitable topics; those wishing to submit anand contain a minimum of references. Tables editorial, however, should do so only afterand figures should be kept to an absolute discussion with the Editor.

781

Book reviews

regarded as its originator, that the dose-response curve need not always be monoto-nic. In other words, the one way relation,apart from instances of threshold, usuallythought to show that an increase in doseleads to an increased effect in the samedirection, may not be correct and that morecomplex patterns may occur in practice.We are treated to many attempts to show

non-monotonic-that is, U, J and B or bellshaped relations, in which a very low to lowdose of a chemical toxicant or radiation pro-duces a beneficial effect on cells (enhancedresistance), animals (better survival thanuntreated controls in long term toxicitytests), and people (less neoplasia induced byradiation), whereas higher doses produceharmful effects. There is a wordy attempt tobolster this by philosophising about breach-ing the conventional Kuhnian paradigm (aharmful heuristic in this instance).The basic concept is very important scien-

tifically, because of what it can show aboutresponses to injury-for example, activatedrepair enzymes, heat shock proteins, changesin cell kinetics-and, as well shown here, thedifferent ways of analysing and modellinglaboratory and epidemiological data do showup misleading assumptions and hiddenerrors in many conventional and superficialevaluations. There is also a strong themethat United States Government style quanti-tative dose-response calculations for chemi-cal toxicity, which ignore the complex shapeof low dose responses, are liable to givequite erroneous risk predictions, even beforeignoring the biological barriers involved inextrapolation between species. That shouldnot be news in Europe, where we have longdistrusted those who, like Trollope'sMr Minusex "never thought but alwayscounted".The general standard of presentation and

dialectic is high, but some contributors seemignorant of modern receptor pharmacology,especially the concept of the partial agonist,and others overlook the dangers of uncon-trolled molecular and cellular reactionmechanisms when arguing for the seeming"stimulation" of health by very low doses ofchemicals and radiation.

There are many examples here of thediverse shapes of quantal and quantitativedose-response relations in the laboratory,the clinic, and the factory. In this way itaffords an excellent training in the problemsof analysing and interpreting results. Thatalone would be a good reason for buying thebook, and another is its exemplification ofthe need to look hard at the complexity ofbiological findings. It also shows the stupid-ity of trying to force all toxicological datainto the legislative convenience of a uniformmodel. However, it does so with a solemnityand persistence that should be unnecessaryfor any rational biologist. Perhaps theBELLE has had her ball and now can seek abetter balance?

A D DAYAN

Advances in Occupational Medicine andRehabilitation, Vol 1, No 2. Update onBenzene. Edited by M IMBRIANI, SGHITTORI, G PEZZAGNO, E CAPODAGLIO. (Pp265.) 1995. Pavia 27100, Italy: FondazioneSalvatore Maugeri Edizioni and PI-MEPress. ISBN: 88-7963-038-5.

This is the second publication of a quarterlyseries. The issue of setting limits for benzeneexposure in the workplace and the environ-

ment is both topical and controversial, sothe timing of this volume is appropriate. Thebook consists of 22 chapters, all written bydifferent contributors, with the aim of pro-viding an update on the current state ofknowledge about the effects of benzene. Thefirst four chapters review exposures in theworkplace, in ambient and in indoor air, andthrough environmental tobacco smoke, andthe factors which affect the biological levelsof benzene in humans. Chapter 5, thelongest in the volume, surveys studies onhuman leukaemogenesis induced by ben-zene, and includes descriptions of the patho-physiology, human studies, the controversialrisk assessments carried out on data fromrubber manufacturing workers, animal stud-ies, metabolism, and a long section of cyto-genetic changes. Several of the later chapterscontain material which overlap with chapter5 although Paustenbach's contribution onthe acute and chronic effects in humans is agood summary of the epidemiological workto date.

Other chapters cover experimental stud-ies, and haematological changes and 11chapters report various aspects of biologicalmonitoring and biomarkers. The topics ofrisk assessment and pharmacokinetics arebarely touched upon in this book, and yetthese are the areas of research in which thereis much work being currently carried out.The volume begins well with an attempt tocoordinate the chapters. However, by themiddle of the book there has begun to beobvious repetition and overlap and the sec-ond half consists of a series of papers onmore specialist topics. The volume would beof more use to the reader if it had beenstructured more formally and the articlesgrouped under definite headings. It is notclear whether the editors intended it to beliterally an update in that they assume thereader to have considerable knowledge ofthe topic or whether they wished it to be athorough review. The chapters vary in theirachievements towards these two differentaims. Someone with little knowledge of theeffects of benzene would obtain a ratherpatchy picture from this book. However,there is no doubt that sections of it would beuseful to those with an interest in this spe-cialist area. The reader would also need tobe aware that this volume is probablyalready out of date and likely to becomeeven more so very quickly. There are alreadyseveral new studies reported in the scientificliterature and in particular, the recentlycommissioned European Union risk charac-terisation will soon be available.

LESLEY RUSHTON

NOTICES

Diagnostic approaches to lymphoprolif-erative disorders. 24-28 March 1997.The Grand Wailea Resort and Spa,Maui, Hawaii

This continuing medical education course issponsored by Scripps Clinic and ResearchFoundation and designed for haematologists,oncologists and pathologists who are involvedin the histological diagnosis or clinical evalua-tion of patients with malignancies of the lym-phopoietic system. The course will offer 26credit hours of category 1 CME credit.

For further information contact:Department of Academic Affairs, 403C,Scripps Clinic and Research Foundation,10666 N Torrey Pines Road, La Jolla, CA92037, USA. Tel (619) 554-8556; Fax(619) 554-6310.

12th International Symposium:Epidemiology in Occupational HealthISEOH 1997. 16-19 September 1997.Harare, Zimbabwe

This symposium is organised by theNational Social Security Authority ofZimbabwe, and the National Centre forOccupational Health, South Africa, onbehalf of The Scientific Committee onOccupational Epidemiology (ICOH).The conference aims to bring together

people working in occupational epidemiolo-gy globally and to discuss methodologicalissues and practical applications of theirresearch. The programme will includekeynote lectures, oral presentations andposters. The conference will be held insouthern Africa, where new developmentand social challenges provide fertile groundfor advances in occupational health. Welook forward to seeing you in the warm andfriendly city of Harare in Zimbabwe!

For further information, contact: Ms MMashingaidze, Att: ISEOH, National SocialSecurity Authority, Box CY 1387,Causeway, Harare, Zimbabwe. Tel 263-4-728 931/722 047-9/723 822-4, Fax 263-4-796 320.

Sixth International Symposium onNeurobehavioural Methods and EffectsIn Occupational and EnvironmentalHealth. 15-18 October, 1997. Shanghai,China.

The symposium is organised by the SanlianAccident Prevention Institute and theShanghai Medical University.

For further information send a fax to: TheSecretariat, 6th International Symposium onNeurobehavioural Methods and Effects inOccupational and Environmental Health,Sanlian Accident Prevention Institute,Hefei, Anhui province, PR China. Fax: +86-5515319266.

International Course on ModernEpidemiology, 12-15 May, 1997.Lunteren, The Netherlands.

This advanced course is about the principlesof epidemiological research. The lecturer isKJ Rothman. Among others, the topics willbe: case-control research principles, interac-tion in aetiology, statistics v epidemiologicalanalyses. Enrolment is open to researcherswith a basic knowledge of epidemiology andbiostatistics and at least some work experi-ence. Closing date for enrollment is 13January 1997. Course fee is DFL 1895,including a single room with shower and toi-let, breakfast, lunches, dinner, coffee or teaduring breaks, the textbook ModemEpidemiology, and other course materials.

For further information please contact:Mrs Astrid van Alst, course secretary,Department of Epidemiology, University ofNijmegen, PO Box 9101, NL-6500 HBNijmegen, The Netherlands. Tel.+31-24-3619132; Fax. +31-24-3613505;E-mail: A.vanAlstgmie.kun.nl

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