Major technological advances in the last few years have increased our knowledge of the role that genetics has in occupational diseases and our understanding of genetic components and the interaction between genetics and environmental factors. The use of genetic information, along with all of the other factors that contribute to occupational morbidity and mortality, will play an increasing role in preventing occupational disease. However, the use of genetic information in occupational safety and health research and practice presents both promise and concerns [McCanlies et al. 2003; Kelada et al. 2003; Henry et al. 2002; Christiani et al. 2001; Schulte et al. 1999]. Use of genetic information raises medical, ethical, legal and social issues [Clayton 2003; Ward et al., 2002; McCunney 2002; Christiani et al 2001; Rothstein 2000a; Schulte et al. 1999; Lemmens 1997; Barrett et al. 1997, Van Damme et al. 1995; Gochfeld 1998; Omenn 1982]. The purpose of this report is to bring together the diverse literature and opinions on genetics in the workplace, to highlight important issues, and to provide some considerations for current and future practice. Occupational safety and health professionals and practitioners may have particular interest in this report as the understanding of gene-environment interactions at the mechanistic and population levels may result in improved prevention and control strategies. This report is divided into topic areas for ease of reading. Specifically, the role of genetic information in occupational disease is discussed in Chapter 2, followed in Chapter 3 by a presentation of how genetics is incorporated into occupational health research. Health records as a source of genetic information are discussed in Chapter 4. The report continues in Chapter 5 with a focus on genetic monitoring, followed in Chapter 6 by a theoretical discussion of genetic screening. The final chapter presents an overview of the most important aspects of this report, which are the ethical, social, and legal implications of genetics in the workplace. In addition, ethical issues specific to health records and genetic testing are discussed in Chapters 4 and 6, respectively. To assist our audience in finding additional sources of information or more in-depth discussion of the issues surrounding genetic information, a list of web sites is provided at the conclusion of this document. Role of Genetic Information in Occupational Disease: The role of genetic information in occupational disease is being explored. The framework for considering genetics in the exposure to disease paradigm arose from a National Academy of Sciences review on biomarkers [NRC 1987]. Biomarkers are measurements using biological tissues that give information about exposure, effect of exposure, or susceptibility. Evaluation of genetic damage can provide information about exposure or effect of exposure. However, the presence of a specific genetic biomarker will not itself result in an occupational disease; exposure to a workplace hazard is necessary. The presence of a disease risk biomarker in the absence of exposure may be innocuous. The study of biomarkers of genetic susceptibility in the context of workplace exposures can provide information about gene-environment interactions. One major emphasis of genetic research in occupational disease has been in the area of response variability. Extensive variability in the human response to workplace exposures has been observed. Genes can have multiple variations known as polymorphisms, which may contribute to some of this variability [Grassman et al. 1998]. Research has been conducted over the last approximately 30 years to identify the role of genetic polymorphisms in a wide range of occupational and environmental diseases, particularly those involving occupational carcinogens [Hornig 1988; Berg 1979]. The risk of biological effects or diseases attributable to an occupational exposure can be decreased, unchanged, or increased among individuals with certain genetic polymorphisms. Incorporating Genetics into Occupational Health Research: The main influence on genetic research with respect to occupational health is the large number of technological advances in molecular biology. Because of these new techniques, it is now feasible to evaluate the relationship of disease with individual genes and their variants or even with the whole genome. These technologies promise to set the stage for new discoveries in understanding mechanisms and the preclinical changes that might serve as early warnings of disease or increased risk [NRC 2007]. They also present difficult challenges in terms of handling large data sets, understanding the normal range, standardizing technologies for comparison and interpretation, and communicating results [King and Sinha 2001; Wittes and Friedman 1999]. As our understanding of the role of specific genes and their variants increases, genetic tests are being developed to look at specific genotypes. One critical issue in genetics is the validity of such genetic tests. Much contemporary genetic research involves the collection of biological specimens (usually DNA in white blood cells) that are then tested either for changes (damage) to genetic material or for genetic polymorphisms. These genetic tests, while useful in occupational health research, are not ready for clinical use; in other words, they are not validated for clinical interpretation. Validation is a process by which a test's performance is measured both in the laboratory and in populations, resulting in the evaluation of the clinical utility or the risks and benefits of the test. Until clinically validated, the information from such tests may be meaningless with regard to an individual's health or risk. In contrast, genetic tests may be validated for assessing exposure or effect modification in research even if they have no clinical utility. Health Records: A Source of Genetic Information: Genetic tests are not the only source of genetic information in the workplace. Genetic information is kept in workers' personnel and workplace health records [Rothenberg et al. 1997]. This information is in the family history of diseases with known strong genetic etiologies as well as in the results of physical examinations and common laboratory tests. This type of information is reported routinely by workers or obtained by employers from workers' job applications, health questionnaires, health and life insurance applications, physicals, and workers' compensation proceedings [Anderlik and Rothstein 2001]. The line between what is and is not genetic information in health records is unclear. States have enacted legislation with widely varying definitions of what constitutes genetic information from an employee's health record. Questions concerning confidentiality, privacy and security remain as the handling of health records may be influenced by various federal and state regulations. Genetic Monitoring and Occupational Research and Health Practice: Genetic information can be a scientific tool to understand mechanisms and pathways in laboratory research and as independent or dependent variables in population research studies of workers. In occupational safety and health practice, genetic tests may be used in a variety of ways. As in other areas of health science, genetic information may be used in the differential diagnosis of disease, allowing clinicians to consider or exclude various diagnoses. Monitoring for the effects of exposure on genetic material, such as chromosomes, genes, and constituent deoxyribonucleic acid (DNA), has been used to evaluate risks and potential health problems for more than 50 years, particularly those from ionizing radiation [Mendelsohn 1995; Langlois et al. 1987; Berg 1979]. Such monitoring is not unlike monitoring for metals in blood, solvents in breath, or dusts in lungs and presents less ethical concern than assessing heritable effects [Schulte and DeBord 2000]. Tests for genetic damage have been advocated as a way to prioritize exposed individuals for more thorough medical monitoring [Albertini 2001]. Genetic monitoring highlights the confusion that exists between individual and group risk assessment. Unlike other monitoring methods, the risks linked to cytogenetic changes are interpretable only for a group, not for an individual [Schulte 2007; Murray 1983; Lappe 1983]. Currently, no U.S. regulations exist that mandate genetic monitoring. Questions arise whether genetic monitoring indicates a potential health problem, an existing health problem, or compensable damage. More research is needed to understand the science before the individual's risk of disease can be interpreted from genetic monitoring results. However, genetic monitoring to determine exposure may be useful for the occupational health practitioner Theoretical Use of Genetic Screening and Occupational Health Practice: Genetic monitoring may have some application in occupational health practice, but perhaps the most controversial use of genetic information would be in making decisions about employment opportunities and health and life insurance coverage [Schill 2000; Bingham 1998; Van Damme et al. 1995; Murray 1983; Lappe 1983]. This would occur primarily as a result of genetic screening, in which a job (and insurance) applicant or a current worker might be asked to undergo genetic testing to determine if he or she has a certain genotype. However, the Genetic Information Nondiscrimination Act of 2008 (GINA) prohibits discrimination on the basis of genetic information with respect to health insurance and employment [U.S. Congress 2008]. Genetic screening which was not strictly prohibited by the Americans With Disabilities Act of 1990 (ADA) is now prohibited. Under ADA an employer may not make medical inquiries about an applicant until a conditional offer has been extended. Once the offer has been tendered, an employer could have obtained medical, including genetic, information about a job applicant. ADA did not prohibit obtaining genetic information or genetic screening, nor did it prohibit an employer from requesting genetic testing once an applicant has been hired provided the testing is job related. and can be used for the purposes of job placement after a conditional job offer is made. Most criteria for genetic screening programs indicate that participation should be voluntary, with informed consent in place. Genetic screening for these purposes cannot be supported at this time because of the current lack of linkage of causation of a given genetic polymorphism with a given occupational disease and its implications with regard to the Occupational Safety and Health Act (OSH Act of 1970) that the workplace be safe for all workers [OSHA 1980b]. Accurate genetic screening information may eventually be useful to workers considering employment options. Obtaining this information for the worker would become appropriate only after the screening tests have been validated regarding risk. Various ethical arguments have been advanced in the discussion of genetic screening, and a broad range of implications of genetic testing has been discussed in the literature and in this document, including the oversight of genetic testing laboratories. The Ethical, Social, and Legal Implications of Genetics in the Workplace: A concern about the use of genetic information in occupational safety and health is that the emphasis in maintaining a safe and healthful workplace could shift from controlling the environment to excluding the vulnerable worker. This would be counter to the spirit and the letter of the OSH Act of 1970 [OSHA 1980b]. Actions that attempt to depart from providing safe and healthful workplaces for all should not be supported. Nevertheless, understanding the role of genetic factors in occupational morbidity, mortality, and injury is important and could lead to further prevention and control efforts. However, occupational safety and health decision- makers, researchers, and practitioners may find that genetic factors do not contribute substantially to some occupational diseases. Environmental risk factors will probably always be more important for developing strategies for prevention and intervention in occupational disease and ultimately for the reduction of morbidity and mortality. The challenge is to identify and apply genetic information in ways that will improve occupational safety and health for workers. The use of genetic information in occupational safety and health research requires careful attention because of the real or perceived opportunities for the misuse of genetic information. Society in general and workers in particular have concerns that discrimination and lack of opportunity will result from the inappropriate use of genetic information [MacDonald and Williams-Jones 2002; Maltby 2000]. While only sparse or anecdotal information supports this contention, a wide range of workers, legislators, scientists, and public health researchers have concern that such discrimination could occur. Thus, GINA and other regulations were passed to prevent the potential misuse and abuse of genetic information in the workplace. Examples of safeguards include rules and practices for maintaining privacy and confidentiality, prohibition of discrimination, and support of a worker's right of self-determination (autonomy) with regard to genetic information. Many of these safeguards have been built into biomedical research in general, and occupational safety and health research in particular, through guidance given in the Nuremberg Code , the Belmont Report , and the Common Rule (45 CFR. 46) [DHHS 2005; CFR 2007], as well as in the National Bioethics Advisory Commission (NBAC) reports , the ADA , Health Insurance Portability and Accountability Act (HIPAA)  and GINA in 2008 [U.S. Congress 2008]. ADA and HIPAA provided some safeguards against the potential misuse of genetic information in the workplace before GINA was signed and in 2000, Executive Order 13145 was signed that prohibits discrimination in federal employment based on genetic information [65 Fed. Reg. 6877 (2000)]. In summary, the use of genetic information in the workplace has the potential to affect every worker in the United States. This NIOSH document provides information on the scientific, legal, and ethical issues with regard to the use of genetics in occupational safety and health research and practice.