Ethical, Social, and Legal Issues SurroundingStudies of Susceptible Populationsand IndividualsColin L. SoskolneDepartment of Public Health Sciences, University of Alberta,Edmonton, Alberta, CanadaCalls for professional accountability have resulted in the development of ethics guidelines bynumerous specialty and subspecialty groups of scientists. Indeed, guidelines among some healthprofessions now address vulnerable and dependent groups; but these are silent on issues relatedto biomarkers. In parallel, attention has been drawn to human rights concerns associated withattempts to detect hypersusceptible workers, especially in democratic countries. Despite this,concern for vulnerable populations grows as advances in biomarker technology make theidentification of genetic predisposition and susceptibility markers of both exposure and outcomemore attainable. In this article, the principles derived from the ethical theory of utilitarianismprovide the basis for principle-based ethical analysis. In addition, the four principles of biomedicalethics-respect for autonomy, beneficence, nonmaleficence, and social justice are consideredfor biomarker studies. The need for a context in which ethical analysis is conducted and fromwhich prevailing social values are shown to drive decisions of an ethical nature is emphasized;these include statutory regulation and law. Because biomarker studies can result in more harmthan good, special precautions to inform research participants prior to any involvement in the useof biomarkers are needed. In addition, safeguards to maintain the privacy of data derived frombiomarker studies must be developed and implemented prior to the application of these newtechnologies. Guidelines must be expanded to incorporate ethical, social, and legal considerationssurrounding the introduction of new technologies for studying susceptible populations andindividuals who may be vulnerable to environmental exposures. Environ Health Perspect1 05(Suppl 4):837-841 (1997)

Key words: applied ethics, biomonitoring, genetics, guidelines, health risks, human rights,industrial toxicology, law, political ideology, privacy, technology

Introduction to ProfessionalConductThe need, among others, to be publiclyaccountable has led many professions to

develop guidelines, declarations, or codesof ethics and, in some instances, standardsof practice. These statements on appro-priate professional conduct document thenormative practices against which theprofession can be held accountable for its

actions, both collectively and by itsindividual practitioners (1).

The phenomenon of developingcodes/guidelines is relatively recent, havingbecome common practice within only thepast decade. Hence, many of the codes arevery recent, e.g., those promulgated by theInternational Commission on OccupationalHealth (ICOH) (2) and the Council forInternational Organizations of MedicalSciences (CIOMS) (3,4). It is therefore

This paper was prepared as background for the Workshop on Susceptibility to Environmental Hazardsconvened by the Scientific Group on Methodologies for the Safety Evaluation of Chemicals (SGOMSEC) held17-22 March 1996 in Espoo, Finland. Manuscript received at EHP 5 November 1996; accepted 18 November1996.

In preparing this paper, have drawn heavily on material published by the International Commission onOccupational Health, Council for International Organizations of Medical Sciences, and, in particular, papers ofPaolo Vineis, among others, contained in the bibliography.

Address correspondence to Dr. C. Soskolne, Department of Public Health Sciences, Faculty of Medicine, 13-103 Clinical Sciences Building, University of Alberta, Edmonton, Alberta, Canada T6G 2G3. Telephone: (403)492-6013. Fax: (403) 492-0364. E-mail: colin.soskolne@ualberta.ca

Abbreviations used: CIOMS, Council for International Organizations of Medical Sciences; ICOH, InternationalCommission on Occupational Health

useful to examine them to see whatguidance has been incorporated on issuesdealing with susceptible groups of peopleand/or individuals. Of particular note is theattention given in these recent documentsto vulnerable populations.

Advances in professional (or, applied)ethics are made by thoughtful and in-novative thinkers (or, visionaries) in anyactivity area within the broad array ofprofessional endeavor. However, it is onlyonce the deliberations of these so-calledvisionaries are ultimately integrated intothe profession's codes/guidelines, that theywill be deemed "common practice," ornormative. Hence, this article also exam-ines the more recent published and pre-sented works by leading contributors tothe philosophy of biomarkers for thescreening of populations (5-66). The lat-ter exercise is intended to identify futureethical, social, and legal directions in thearea of studies of susceptible populationsand individuals. Matters that focusdirectly on the science and/or technologyof biomarkers do not fall within the scopeof this article.

Extant GuidelinesThe four principles upon which muchhealth-related ethical analysis is conductedare respect for autonomy (respect for per-sons, embracing the need for prior, volun-tary, fully informed consent), beneficence(doing good), nonmaleficence (doing noharm), and distributive justice (social jus-tice or equity vis i vis the equal allocationof risks and benefits).

While recent international guidelinesare silent on the issue of biomarker studiesper se, the CIOMS (1991) guidelines dostate, consistent with the principle of non-maleficence, that harm to the individualshould be minimized (3). Specifically (andof relevance to genetic testing), "Ethicalreview must always assess the risk of sub-jects or groups suffering stigmatization,prejudice, loss of prestige or self-esteem, oreconomic loss as a result of taking part in astudy..." (principle 19). With regard togroups (principle 21), "Epidemiologicalstudies may inadvertently expose groups aswell as individuals to harm, such as eco-nomic loss, stigmatization, blame, or with-drawal of services. Investigators who findsensitive information that may put a groupat risk of adverse criticism or treatmentshould be discreet in communicating andexplaining their findings...."

Environmental Health Perspectives - Vol 105, Supplement 4 * June 1997 837

C.L. SOSKOLNE

Concerning "vulnerable and dependentgroups," the CIOMS (1991) guidelinesstate:

Ethical review committees should beparticularly vigilant in the case of pro-posals involving populations primarily ofchildren, pregnant and nursing women,persons with mental illness or handicap,members of communities unfamiliarwith medical concepts, and persons withrestricted freedom to make truly inde-pendent choices, such as prisoners andmedical students. Similar vigilance iscalled for in the case of proposals forinvasive research with no direct benefitto its subjects (principle 43) (4).

It is only the latter portion of thisprinciple that could be seen to be of partic-ular relevance to biomarker research and itsapplications. CIOMS (1993) addresses thisissue under its guideline no. 10, "Selectionof research subjects: equitable distributionof burdens and benefits." It states, " ...

Special justification is required for invitingvulnerable individuals and, if they areselected, the means of protecting theirrights and welfare must be particularlystrictly applied."

On the subject of "biological monitor-ing and investigations," (principle 12) themost relevant guidelines for professionalsengaged in occupational health and safety(ICOH, 1996) states:

Biological tests and other investigationsmust be chosen from the point ofview oftheir validity for protection of the healthof the worker concerned, with due regardto their sensitivity, their specificity andtheir predictive value. Occupational (andenvironmental) health professionals mustnot use screening tests or investigationswhich are not reliable or which do nothave a sufficient predictive value in rela-tion to the requirements of the workassignment. Where a choice is possibleand appropriate, preference must alwaysbe given to noninvasive methods and toexaminations which do not involve anydanger to the health of the worker con-cerned. An invasive investigation or anexamination which involves a risk to thehealth of the worker concerned may onlybe advised after an evaluation of thebenefits and the risks involved and can-not be justified in relation to insuranceclaims. Such an investigation is subject tothe worker's informed consent and mustbe performed according to the highestprofessional standards.

[Note: Because the ICOH documentconfines itself to occupationally exposedgroups, all quoted statements from this

document will be expanded to incorporateenvironmental health where appropriate, inparentheses within any quotation.]

Guidelines are not an end in themselves;they are expected to be reviewed andrevised from time to time to reflect chang-ing values and to rise to the challenge pre-sented from advances in technology that sooften precipitate the need for concernabout ethical conduct. With biomarkertechnology gaining prominence, a lag ofsome years can be anticipated before theethics guidelines/codes of conduct are seento address related issues.

Social and Legal PerspectivesThe context for considering ethical issues isimportant for the analysis of an ethicaldilemma. Context can shed light on whichethical principles ought to take precedenceover others. Hence, the context of occupa-tional and environmental health will beaddressed first.

The aim of occupational and environ-mental health practice is to protect healthand to promote the establishment andmaintenance of a safe and healthy environ-ment. In addition, in the occupationalhealth context in particular, the aim is topromote the adaptation of work to thecapabilities of workers, taking into accounttheir state of health. Attention in guide-lines thus should be given to vulnerablegroups and to underserved working popu-lations (43). Occupational health is essen-tially preventive and should help theworkers, individually and collectively, tosafeguard their health in their employment.It should thereby help the enterprise toensure healthy and safe working conditionsand environment, which are criteria of effi-cient management and are to be found inwell-run enterprises.

The field of occupational health iscomprehensive and covers the preventionof all impairments arising out of employ-ment, work injuries, and work-related dis-eases as well as all aspects relating to theinteractions between work and health.Occupational health professionals shouldbe involved, whenever possible, in thedesign of health and safety equipment,methods, and procedures and they shouldencourage workers' participation in thisfield. Occupational health professionalshave a role to play in the promotion ofworkers' health and should assist workersin obtaining and maintaining employmentnotwithstanding their health deficienciesor their handicap. The word "workers" isused here in a broad sense and covers all

employees, including management and theself-employed.

The approach in both occupational andenvironmental health is multidisciplinaryand intersectoral. There is a wide range ofobligations and complex relationshipsamong those concerned (2). It is thereforeimportant to define the role of profession-als and their relationships with other pro-fessionals, with other health professionalsand with social partners in the purview ofeconomic, social, and health policies devel-opment. This calls for a clear view aboutthe ethics of occupational and/or environ-mental health professionals and standardsin their professional conduct.

In occupational settings in general,duties and obligations are defined by statu-tory regulations. Each employer has theresponsibility for the health and safety ofthe workers in his or her employment. Inparticular, in the United States it is theobligation of the employer to provide asafe and healthful workplace (67). Morerecent interpretation of this legislationpoints to environmental control asopposed to worker exclusion for meetingthis obligation.

Each profession has its responsibilitiesthat are related to the nature of its duties.When specialists of several professions areworking together within a multidiscipli-nary approach, it is important that theybase their action on some common princi-ples of ethics and that they have an under-standing of each others' obligations,responsibilities and professional standards.Special care should be taken with respect toethical aspects, in particular when there areconflicting rights such as the right to theprotection of employment and the right tothe protection of health, the right to infor-mation and the right to confidentiality, aswell as individual rights and collectiverights (2).

Some of the conditions of execution ofthe functions of occupational health pro-fessionals and the conditions of operationof occupational health services are oftendefined in statutory regulations. One of thebasic requirements for a sound occupationalhealth practice is full professional indepen-dence, i.e., that occupational health profes-sionals must enjoy independence in theexercise of their functions that shouldenable them to make judgments and giveadvice for the protection of the workers'health and for their safety within the under-taking in accordance with their knowledgeand conscience (2). The analogous argu-ments could be made in support of the

Environmental Health Perspectives * Vol 105, Supplement 4 * June 1997838

ETHICS IN STUDIES OF SUSCEPTIBLE POPULATIONS

independence of the environmental healthpractitioner in protecting the interests ofpublic health.

There are basic requirements foracceptable occupational health practice.These conditions of operation are some-times specified by national regulations andinclude, in particular, free access to thework place, the possibility of takingsamples and assessing the working envi-ronment, making job analyses and partici-pating in inquiries after an accident, andthe possibility to consult the competentauthority on the implementation ofoccupational safety and health standards inthe undertaking. Occupational healthprofessionals should be allocated a budgetthat will enable them to carry out theirfunctions according to good practice and tothe highest professional standards. Thisshould include adequate staffing, training,and retraining; support, and access torelevant information and to an appropriatelevel of senior management (2). Thesearguments can be extended to environmentalhealth professionals.

Ethical ConsiderationsEthical analysis often points to tensionsbetween two or more principles. Forexample, the need for individual privacycan conflict with the need to protect thepublic interest; and, the need to do goodhas to be balanced against the potential alsoto cause harm. Because of this, a review ofthe strengths and weaknesses of theadvances that biomarker technology bringsmust be considered.

Epidemiology has relied on hard endpoints such as death in most cohortstudies. However, workers might prefer tosee something different from body countswhen the potential health effects of occu-pational exposures are studied (31,57).Likewise, the public might prefer to seesomething different from body countswhen the potential health effects fromenvironmental exposures are studied.Therefore, more direct indicators of bothexposure and early response (or outcome)would have some advantages. Biologicalmarkers provide just such a tool.

The use of biological markers, such aslead levels in blood or liver function tests,is not new in occupational or environmen-tal epidemiology. However, the use ofmolecular techniques in epidemiologicalstudies has made possible the use ofbiomarkers to assess target organ exposurefor determining susceptibility and forestablishing early disease.

Potential uses of biomarkers in thecontext of occupational and environmentalepidemiology include the following (31,57):* exposure assessment in cases in which

traditional epidemiologic tools areinsufficient (particularly for low dosesand low risks)

* multiple exposures or mixtures, inwhich the aim is to disentangle thecausative role of single chemical agentsor substances

* estimation of the total burden of expo-sure to chemicals that have the samemechanistic target

* investigation of pathogenetic mecha-nisms

* study of individual susceptibility (e.g.,metabolic polymorphisms, DNArepair)

* an increase in statistical power owing tomore accurate classification of exposureand/or disease.In reference to the latter point,

biomarkers can be highly specific indica-tors of a cause of a disease that otherwisehas multiple causes. For example, determi-nation of the relationship among specificpatterns of chromosomal abnormalities inchemical-induced leukemia can improvethe likelihood of determining a cause-andeffect-relationship in a cluster of leukemiasor, as another example, study of the codonsinvolved in p53 mutations could lead todistinguishing between those lung cancersfrom radon and those from cigarette smok-ing, a point of much value in determiningradon risk.

Great enthusiasm has arisen in thescientific community about these uses but,as noted above, methodological complexityshould serve to caution against excessiveoptimism. Biomarkers of chemical expo-sures (such as DNA adducts) have severalshortcomings (31,35,57).

a) They usually reflect recent exposuresand, therefore, are of limited use incase-control studies, whereas they requirerepeated samplings over prolonged periodsfor use in cohort investigations. b) Whilethey can be highly specific and thus improveexposure classification, findings oftenremain difficult to interpret. c) When com-plex chemical exposures, e.g., air pollutionor environmental tobacco smoke are investi-gated, it is possible that the biomarkerwould reflect one particular component ofthe mixture, whereas the biological effect, infact, could have arisen from another compo-nent of the mixture. d) In many situations,it is not clear whether a biomarker reflects arelevant exposure, a correlate of the relevant

exposure, individual susceptibility, or anearly disease stage, thus limiting causal infer-ence. e) The determination of most bio-markers requires an expensive test or aninvasive procedure or both, thus creatingconstraints for adequate study size and sta-tistical power. f) A biomarker of exposureis no more than a proxy for the real objec-tive of an epidemiological investigationwhich, as a rule, focuses on an avoidableenvironmental exposure (31,56,57).

Even more important than themethodological shortcomings is the con-sideration that molecular techniques mightcause us to redirect our focus from identi-fying risks in the exogenous environmentto identifying high-risk individuals andthen making personalized risk assessmentsby measuring phenotype, adduct load, andacquired mutations. This would direct ourfocus to a form of clinical evaluationrather than one of public health epidemi-ology. Focusing on individuals could dis-tract us from the important public healthgoal of creating a less hazardous environ-ment. Clearly, there are both potentialbenefits and potential harms from the useof biomarker technology.

At least two early critiques of the viewthat supported the advancement of tech-nologies whose goal it was to detect hyper-susceptible workers have pointed to thesociopolitical context of such technologies(10,16). In fact, Green (16) examined theearlier concept of the hypersusceptibleworker, arguing that the "concept enabledindustrial toxicologists to organize knowl-edge about workers' reactions to toxicity soas to sustain a professional and method-ological ideology which reflects the rela-tionship between industrial toxicology andcapitalist industry." Atherley (10) presentsan example (i.e., lead) of the erosion ofhuman rights by certain legislated activitiesin occupational medicine, concluding thatissues relating to medical monitoring com-prise political and ethical issues, not merelytechnical ones, that should be debatedpublicly. Both Green and Atherley,whether invoking examples from audiome-try and radiographs (X-rays) of the back toglucose 6-phosphate dehydrogenase andserum-a-1-antitrypsin deficiency, concludethat none of these markers satisfy eventhose criteria specified by the proponentsof such tests (10,16); this view also hasmore recent support (56,57).

Ethical DirectionsTwo further important issues emergeregarding the use of biomarkers (31). First,

Environmental Health Perspectives * Vol 105, Supplement 4 * June 1997 839

C.L. SOSKOLNE

the use of biomarkers in both occupationaland environmental epidemiology must beaccompanied by a clear policy as far asinformed consent is concerned. In theoccupational setting, the worker may haveseveral reasons to refuse cooperation. Onevery practical reason is that the identifica-tion of, say, an alteration in an earlyresponse marker (such as sister chromatidexchange) is not recognized by insurancecompanies as an occupational disease, butprivate insurers might shun the workerbecause he/she may be more prone todisease. A second reason concerns geneticscreening: since the distributions of geno-types and phenotypes vary according toethnic group, occupational opportunitiesfor minorities might be hampered bygenetic screening. Third, doubts can beraised about the predictability of genetictests: since the predictive value depends onthe prevalence of the condition that thetest aims to identify, if the latter is rare, thepredictive value will be low and the prac-tical use of the screening test will bequestionable, with a high rate of false

positives (12). To date, none of the geneticscreening tests have been judged applicablein the field (6,10,11,16,35,56).

The second issue that emerges concern-ing use of biomarkers is that ethical princi-ples must be applied prior to the use ofbiomarkers. Recently, these principles wereconsidered for biomarkers used for identify-ing individual susceptibility to disease. Aninterdisciplinary Working Group of theTechnical Office of the European TradeUnions with the support of the Com-mission of the European Communities hasreinforced the view that tests can be con-ducted only with the objective of preventingdisease in a workforce (68). Among otherconsiderations, the use of tests must nevera) serve as a means for selection of thefittest; b) be used to avoid implementingeffective preventive measures, notably theneed to eliminate or reduce hazardous con-ditions in the workplace or in the environ-ment; c) create, confirm, or reinforce socialinequality; d) create a gap between the ethi-cal principles followed in the workplace or inthe environment and the ethical principles

that must be upheld in a democratic society;or e) oblige a person seeking employment todisclose personal details other than thosestrictly necessary for obtaining the job (57).

Finally, evidence is accumulating thatthe metabolic activation or inactivation ofhazardous substances (and of carcinogensin particular) varies considerably in humanpopulations and is partly genetically deter-mined. Furthermore, interindividual vari-ability in susceptibility to carcinogens maybe particularly important at low levels ofoccupational and environmental exposure(59). The implications of these findings forregulatory decisions that focus the riskassessment process on the most susceptibleare obvious (61).

Where professional groups are slow orreluctant to exercise due restraint in theapplication of new technologies (such asbiomarkers), governments are likely tointervene with legislation in the publicinterest. It therefore behooves thoughtfulprofessionals to consider the application ofbiomarkers in their professional interestsand to develop guidelines for their use.

REFERENCES

1. Frankel MS. Guidelines/codes of ethics: merging process andcontent. Sci Total Environ 184:13-16 (1996).

2. ICOH. International Code of Ethics for Occupational HealthProfessionals. Singapore:International Commission onOccupational Health, 1996.

3. CIOMS. International Guidelines for Ethical Review ofEpidemiological Studies. Geneva:Council for InternationalOrganizations of Medical Sciences, 1991.

4. CIOMS. International Ethical Guidelines for BiomedicalResearch Involving Human Subjects. Geneva:Council forInternational Organizations of Medical Sciences, 1993.

5. Annas G. The bioethics of biomonitoring people for exposureto carcinogens. In: Molecular Dosimetry and Human Cancer:Analytical, Epidemiological, and Social Considerations(Groopman JD, Skipper PL, eds). Caldwell, NJ:Telford Press,1991;385-399.

6. Ashford NA, Spadafor CJ, Hattis DB, Caldart CC, eds.Monitoring the Worker for Exposure and Disease. Scientific,Legal, and Ethical Considerations in the Use of Biomarkers.Johns Hopkins Series in Environmental Toxicology. Baltimore,MD:Johns Hopkins University Press, 1990.

7. Ashford NA. Policy considerations for human monitoring inthe workplace. J Occup Med 28:563-568 (1986).

8. Ashford NA. Medical screening in the workplace: legal and eth-ical considerations. Semin Occup Med 1:67-79 (1986).

9. Ashford NA. Monitoring the worker and the community forchemical exposure and disease: legal and ethical considerationswithin the context of the United States. Clin Chem41:1426-1437 (1994).

10. Atherley G. Human rights versus occupational medicine. Int JHealth Serv 13:265-275 (1983).

11. Atherley G, Johnston N, Tannassee M. Biological surveillance:rights conflict with rights. J Occup Med 8:958-965 (1986).

12. Boden L. Genetic testing in the workplace: costs and benefits.In: Molecular Dosimetry and Human Cancer: Analytical,

Epidemiological, and Social Considerations (Groopman JD,Skipper PL, eds). Caldwell, NJ:Telford Press, 1991;401-415.

13. Correa P. Molecular and biochemical methods in cancer epi-demiology and prevention: the path between the laboratory andthe population. Cancer Epidemiol Biomarkers Prev 2:85-88(1993).

14. Friend SH. Genetic models for studying cancer susceptibility.Science 259:774-775 (1993).

15. Grandjean P, Sorsa M. Ethical aspects of genetic predispositionto environmentally-related disease. Sci Total Environ184:37-43 (1996).

16. Green J. Detecting the hypersusceptible worker: genetics andpolitics in industrial medicine. Int J Health Serv 13:247-264(1983).

17. Hatchwell PK. Genetic research: implications for workplacescreening. Occup Health Rev April/May:8-11 (1992).

18. Higginson J, Chu F. Ethical considerations and responsibilitiesin communicating health risk information. J Clin Epidemiol44(Suppl 1):51S-56S (1991).

19. Hulka BS, Wilcosky TC, Griffith JD, eds. Biological Markersin Epidemiology. New York:Oxford University Press, 1990.

20. Hulka BS. Overview of biological markers. In: BiologicalMarkers in Epidemiology (Hulka BS, Wilcosky TC, GriffithJD, eds). New York:Oxford University Press, 1990;3-15.

21. Hulka BS. Methodologic issues in molecular epidemiology. In:Biological Markers in Epidemiology (Hulka BS, Wilcosky TC,Griffith JD, eds). New York:Oxford University Press,1990;214-226.

22. Hulka BS. Epidemiological studies using biological markers:issues for epidemiologists. Cancer Epidemiol Biomarkers Prev1:13-19 (1991).

23. International Labour Office, Geneva. Workers' Privacy. PartIII: Testing in the Workplace. Conditions of Work Digest.Geneva:International Labour Office, 1993; 12(2).

24. Jonsen AR. Ethical considerations and responsibilities when

840 Environmental Health Perspectives - Vol 105, Supplement 4 * June 1997

ETHICS IN STUDIES OF SUSCEPTIBLE POPULATIONS

communicating health risk information. J Clin Epidemiol44( Suppl 1):69S-72S (1991).

25. Knoppers BM, Chadwick R. The human genome project:under an international ethical microscope. Science265:2035-2036 (1994).

26. Lappe M. Ethical issues in testing for differential sensitivity tooccupational hazards. J Occup Med 25:797-808 (1983).

27. Lappe M, Gustafson J, Robin R. Ethical and social aspects ofscreening for genetic disease. N Engl J Med 206:1129-1132(1972).

28. Lappe M. Ethical concerns in occupational screening programs.J Occup Med 28:572-577 (1986).

29. Loomis D, Wing S. Is molecular epidemiology a germ theoryfor the end of the twentieth century? Int J Epidemiol 19:1-3(1991).

30. McMichael AJ. Invited commentary-"Molecular epidemiol-ogy': new pathway or new traveling companion? Am JEpidemiol 140:1-11 (1994).

31. Merletti F, Soskolne CL, Vineis P. Epidemiological methodapplied to occupational health and safety. In: ILOEncyclopedia of Occupational Health and Safety, 4th ed.Geneva:International Labour Office, 1997:28.2-28.6.

32. Neutra RR. What the public can reasonably expect from bio-markers. Health Environ Dig (Freshwater Foundation) 2:3-4(1988).

33. NRC Committee on Biological Markers. Biological markers inhealth research. Environ Health Perspect 74:3-9 (1987).

34. Omenn GS. Predictive identification of hypersusceptible indi-viduals. J Occup Med 24:369-374 (1982).

35. Pearce N, de Sanjose S, Boffetta P, Kogevinas M, Saracci R,Savitz D. Limitations of biomarkers of exposure in cancer epi-demiology. Epidemiology 6:190-194 (1995).

36. Perera F, Weinstein IB. Molecular epidemiology and carcino-gen-DNA adduct detection: new approaches to studies ofhuman cancer causation. J Chron Dis 35:581-600 (1982).

37. Perera FP. Molecular cancer epidemiology: a new tool in cancerprevention. J Natl Cancer Inst 78:887-898 (1987).

38. Perera FP, Hemminki K, Gryzbowska E, Motykiewicz G,Michalska J, Santella RM, Young T-L, Dickey C, Brandt-RaufP, DeVivo I et al. Molecular and genetic damage in humansfrom environmental pollution in Poland. Nature 360:256-258(1992).

39. Perera FP, Santella R. Carcinogenesis. In: MolecularEpidemiology: Principles and Practices (Schulte P, Perera FP,eds). New York:Academic Press, 1993;277-300.

40. Perera FP. Biomarkers: new tools for studying environmentalexposures. Health Environ Dig (Freshwater Foundation) 2:1-3(1988).

41. Privacy Commissioner of Canada. Genetic Testing and Privacy.Ottawa:Minister of Supply and Services, 1992.

42. Rothman N, Stewart WF, Caporaso NE, Hayes RB.Misclassification of genetic susceptibility biomarkers: implica-tions for case-control studies and cross-population compar-isons. Cancer Epidemiol Biomarkers Prev 2:299-303 (1993).

43. Rothstein MA. Medical Screening of Workers. Washington:Bureau of National Affairs, 1984.

44. Sandman PM. Emerging communication responsibilities ofepidemiologists. J Clin Epidemiol 44(Suppl 1):41S-50S(1991).

45. Schulte PA. Methodologic issues in the use of biologic markersin epidemiologic research. Am J Epidemiol 126:1006-1016(1987).

46. Schulte PA, Perera FP, eds. Molecular Epidemiology:Principles and Practices. San Diego, CA:Academic Press, 1993.

47. Schulte PA. Contribution of biological markers to occupational

health. Am J Ind Med 20:435-446 (1991).48. Schulte PA. Ethical issues in the communication of results. J

Clin Epidemiol 44(suppl 1):57S-61S (1991).49. Schulte PA. A conceptual and historical framework for molecu-

lar epidemiology. In: Molecular Epidemiology: Principles andPractices (Schulte P, Perera FP, eds). New York:AcademicPress, 1993;3-44.

50. Schulte PA, Ringen K. Notification of workers at high risk: anemerging pub[ic health problem. Am J Public Health74:485-490 (1984).

51. Schulte PA, Ringen K, Altekruse EB, Gullen WH, DavidsonK, Anderson SS, Patton MG. Notification of a cohort of work-ers at risk of bladder cancer. J Occup Med 27:19-28 (1985).

52. Shields PG, Harris CC. Molecular epidemiology and the genet-ics of environmental cancer. JAMA 266:681-687 (1991).

53. Smith PJ. Molecular genetics and human cancer. Med J Aust158:851-853 (1993).

54. Spivey GH. Health risk communication-a view from withinindustry. J Clin Epidemiol 44(suppl 1):63S-67S (1991).

55. U.S. Congress. Genetic Monitoring and Screening in theWorkplace. OTA-BA-455. Washington:U.S. GovernmentPrinting Office, 1990.

56. Vainio H, Husgafvel-Pursiainen K. Editorial: Elimination ofenvironmental actors or elimination of individuals: biomarkersand prevention. J Occup Environ Med 37:12-13 (1995).

57. Van Damme K, Casteleyn L, Heseltine E, Huici A, Sorsa M,van Larebeke N, Vineis P. Individual susceptibility and preven-tion of occupational diseases: scientific and ethical issues. JOccup Environ Med 37:91-99 (1995).

58. Vineis P. Uses of biochemical and biological markers in occu-pational epidemiology. Rev Epidemiol Sante Publique40:S63-S69 (1992).

59. Vineis P, Schulte PA. Scientific and ethical aspects of geneticscreening of workers for cancer risk: the case of the N-acetyl-transferase phenotype. J Clin Epidemiol 48:189-197 (1995).

60. Vineis P. Use of biomarkers in epidemiology. The example ofmetabolic susceptibility to cancer. Toxicol Lett 77:163-168(1995).

61. Vineis P. Ethical issues in genetic screening of workers. Paperpresented at the Collegium Ramazzini, 3-5 November 1995,Washington, DC.

62. Vineis P. Use of biochemical markers in environmental epi-demiology. In: Environmental Epidemiology: Exposure andDisease (Bertollini R, Lebowitz MD, Saracci R, Savitz DA,eds). Boca Raton, FL:CRC Lewis, 1996;201-206.

63. Vineis P, Soskolne CL. Cancer risk assessment and manage-ment: an ethical perspective. J Occup Med 35:902-908 (1993).

64. Weinstein IB. Molecular cancer epidemiology: the use of newlaboratory methods in studies on human cancer causation. In:Epidemiology and Health Risk Assessment (Gordis L, ed).New York:Oxford University Press, 1988; 1 59-165.

65. Wilcosky TC, Griffith JD. Applications of biological markers.In: Biological Markers in Epidemiology (Hulka BS, WilcoskyTC, Griffith JD, eds). New York:Oxford University Press,1990;16-27.

66. Wyrobek AJ. Male biomarkers of abnormal reproductive out-come. Health Environ Dig 4:1-4 (1990).

67. Occupational Safety and Health Act, July 9, 1970: 91stCongress, 2nd Session. U.S. House of Representatives Report91-1291:62 pp.

68. Council of Europe. Draft Convention for the Protection ofHuman Rights and Dignity of the Human Being with Regardto the Application of Biology and Medicine: BioethicsConvention, and Explanatory Report. Strasbourg:Directorateof Legal Affairs, 1994.

Environmental Health Perspectives - Vol 105, Supplement 4 * June 1997 841