Cancer, Reproductive, Cardiovascular, and Other Chronic Disease Prevention Program

engineer

Burden, Need, and Impact

Deaths due to occupational disease are an important source of human suffering and economic cost. It has been estimated that between 32,200 and 78,200 deaths due to occupational disease occur yearly in the United States,1,2 while the Bureau of Labor Statistics has estimated that nearly 300,000 occupational illnesses occurred in 2002.3

Costs of occupational illness in the United States have been estimated to be more than 14 billion dollars yearly.4 Occupational cancers and heart disease among workers are important components of the total burden of occupational disease. Estimates of the range of deaths in the United States due to occupationally-related cancer and heart disease are 12,000–26,000 deaths and 6,000–18,000 deaths per year, respectively,1 with costs being estimated at 9 billion dollars for those two groups of illnesses.Worldwide, occupational exposure to carcinogens is a major cause of death and disability3, with an estimated 666,000 fatal work-related cancers each year.5

The CRC identifies priorities to guide research toward prevention of occupational disease, and base those priorities on the evidence of burden, need and impact. Below are the priority areas for the CRC.

Burden

Many sources of data exist on occupational carcinogens, including single agents, complex mixtures, and occupational groups at high risk for cancer.1 Epidemiologic studies, within specific industries and/or addressing specific exposures, have identified elevated cancer risks among workers. These studies are too numerous to detail here. Among recent examples, a published study of 12,315 workers at eight non-metal mining facilities revealed an excess of lung cancer deaths (standardized mortality ratio=1.26, 95% confidence interval=1.09-1.44).2 This indicates an association between lung cancer mortality and exposure to diesel exhaust, a finding supported by other studies. Surveillance systems are available that provide data addressing potentially occupationally-related cancer. The NIOSH National Occupational Mortality Surveillance System is a database of death certificate data with coded occupation and industry information. Investigators can use these data to explore associations of cause-specific mortality with occupation and/or industry. The measure of association used most often in this system is the proportionate mortality ratio. For example, this database can be used to survey associations of cancer (or other health outcomes such as heart disease) mortality among persons from different occupations. Regarding lung cancer specifically, surveillance information is available from sources including the Work-Related Lung Disease Surveillance System. This surveillance activity provides data, presented in table, chart, and map format, for a variety of work-related respiratory conditions including lung cancer.

Need

There are many known or potential carcinogens that are understudied or have never been studied. One of the goals of CRC research is to follow-up on cohorts of previous studies to continue to increase our knowledge about exposures, interventions, and health effects.  The CRC program also seeks to learn if emerging hazards (e.g., nanomaterials) pose a risk of cancer. Information on exposure and cancer risk derived from studies of high-priority agents should be used to develop quantitative risk assessment models, upon which authoritative recommendations may be based.

Impact

NIOSH research has identified physical and chemical agents in the workplace associated with cancer, including asbestos, benzene, benzidene, 1,3-butadiene, cadmium, chromium, crystalline silica, dioxin, formaldehyde, radon, vinyl chloride, and others. NIOSH studies continue to find links between cancer and workplace exposure to certain chemicals, including most recently beryllium, diesel exhaust, o-toluidine, and 1-bromopropane. A 2015 NIOSH study showed that a population of 30,000 firefighters from three large cities had higher rates of several types of cancers, and of all cancers combined, than the U.S. population as a whole. NIOSH research informs recent guidance to prevent work-related cancer by the World Health Organization and the National Toxicology Program, which frequently cite NIOSH publications documenting the cancer-causing potential of work-related chemical exposures.


1. Ward E [1995]. Overview of preventable industrial causes of occupational cancer. Environ Health Perspect 103(Suppl 8):197-203.

2. Attfield MD, Schleiff PL, Lubin JH, Blair A, Stewart PA, Vermeulen R, Coble JB, Silverman DT [2012]. The Diesel Exhaust in Miners study: a cohort mortality study with emphasis on lung cancer. J Natl Cancer Inst 104(11):869-83.

Burden

Heart disease is the major single cause of mortality in the United States, accounting for 23.4% of deaths in 2016.1 Little is known about occupational risks for heart disease. A few specific toxins encountered occupationally are known to affect the heart, including carbon disulfide, nitroglycerin, carbon monoxide and environmental tobacco smoke. For example, concerning environmental tobacco smoke, a large prospective epidemiologic study by NIOSH CRC investigators and others found approximately 20% higher coronary heart disease death rates among never smokers exposed to environmental tobacco smoke.2 A risk assessment addressing occupational settings has determined that exposure to environmental tobacco smoke is associated with increased risk of death from ischemic heart disease among nonsmoking U.S. workers.3 A recently published study by CRC investigators and others found that low-dose ionizing radiation exposure was associated with heart and cerebrovascular disease among nuclear workers. This suggests another widespread occupational risk factor for circulatory disease4 as 23 million workers globally are estimated to be exposed to low levels of ionizing radiation in the workplace.5

Need

There is a need for increased epidemiologic research into occupational factors contributing to cardiovascular disease among workers.6 Opportunities exist to utilize existing study populations and possibly stored biological specimens to pursue new research questions that would enhance our knowledge concerning the role of occupational exposures in cardiovascular disease. Recent findings suggest that improved monitoring and measures of stress in the work environment could identify key factors that contribute to measurable cardiovascular disease risk.7,8 In addition, recently emerging exposures (e.g. nanomaterials) may require assessment in newly established cohorts and new laboratory-based studies through collaborative research efforts involving NIOSH and its partners. Development of new methods that enable improved detection of exposure and identification of sub-clinical cardiovascular disease should make important contributions.

Impact

The path between the conduct of research and its eventual resulting changes in practice can be long and indirect for epidemiologic and laboratory-based studies, but research leading to a better understanding of the biologic mechanisms underlying cardiovascular disease is vital to achieving reductions in workplace-attributable cardiovascular disease.


1. Heron M [2018]. Deaths: Leading Causes for 2016. National Vital Statistics Reports; vol 67 no 6. Hyattsville, MD: u.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Health Statistics, https://www.cdc.gov/nchs/data/nvsr/nvsr67/nvsr67_06.pdfCdc-pdf .

2. Steenland K, Thun M, Lally C, Heath C[1996]. Environmental tobacco smoke and coronary heart disease in the ACS CPS-II cohort. Circulation 94(4):622-628.

3. Steenland K [1999]. Risk assessment for heart disease and workplace ETS exposure among nonsmokers. Env Health Persp 107(S6):859-863.

4. Gillies M, Richardson DB, Cardis E, et al [2017].Mortality from circulatory diseases and other non-cancer outcomes among nuclear workers in France, the United Kingdom, and the United States (INWORKS). Radiat Res, 188:276–290.

5. United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) [2008]. Report to the General Assembly. Vol 1. Sources and Effects of Ionizing Radiation: Annex B: Exposures of the public and workers from various sources of radiation: 277–322.

6. Steenland K [1996]. Epidemiology of occupation and coronary heart disease: research agenda. Am J Ind Med 30(4):495-499.

7. Violanti JM, Andrew ME, Burchfiel CM, Hartley TA, McCanlies E [2009]. Biosocial synergy: stress, cardiovascular disease, and high risk populations. Psychological factors and cardiovascular disorders. Sher l, ed., New York: Nova Science Publishers, Inc., Jan, p 1-31.

8. Wilson MD, Conroy LM, Dorevitch S {2014]. Occupational stress and subclinical atherosclerosis: a systematic review. Int J Occup Environ Health 20(4):271-280.


Burden

There is significant public health concern about potential effects of occupational exposures on reproductive outcomes. Examples of substances with reported reproductive or developmental effects still in regular commercial use include heavy metals (such as lead), solvents, and pesticides. A recent example includes an evaluation of workplace exposure from a microelectronics and business machines manufacturing facility which suggests an association between paternal exposure to metals (primarily lead) and increased ventricular septal defect risk in infants.1 Estimates of adverse reproductive outcomes demonstrate widespread impact—for example, it is estimated that 10% to 20% of recognized pregnancies end in spontaneous abortion, and that 3% of all live births have major malformations.2 Others have estimated that 3% of major malformations are due to toxicant exposure, 23% are due to multifactorial causes, and 40% are due to unknown causes.3-5 Despite the public health concern and the widespread impact, progress has been limited in identifying occupational reproductive hazards and in separating the contributions of potential occupational hazards from other etiologic factors.

Need

There is significant public health concern about the potential effects of occupational exposure to toxic substances on reproductive outcomes. Several toxicants with reported reproductive and developmental effects are still in regular commercial or therapeutic use and thus present potential exposure to workers. Examples of these include heavy metals, organic solvents, pesticides and herbicides, and sterilants, anesthetic gases, and anticancer drugs used in health care. Many other substances are suspected of producing reproductive or developmental toxicity but lack sufficient data. Progress has been limited in identifying hazards and quantifying their potencies and in separating the contribution of these hazards from other etiologic factors. The pace of laboratory studies to identify hazards and to underpin the biologic plausibility of effects in humans has not matched the pace at which new chemicals are introduced into commerce. Though many research challenges exist today, recent technologic and methodologic advances have been made that allow researchers to overcome some of these obstacles. One of the goals of the NIOSH CRC program, in collaboration with many partners, is to take advantage of recent technologic and methodologic advances in reproductive health research to improve health and reduce adverse reproductive health outcomes.

Impact

Identifying the causative agents, mechanisms by which they act, and any potential target populations will present the opportunity to intervene and better protect the reproductive health of workers.


1. Silver SR, Pinkerton LE, Rocheleau CM, Deddens JA, Michalski AM, Van Zutphen AR [2016]. Birth defects in infants born to employees of a microelectronics and business machine manufacturing facility. Birth Defects Research Part A: Clinical and Molecular Teratology 106(8):696-707.

2. Lawson CC, Schnorr TM, Daston GP, Grajewski B, Marcus M, McDiarmid M, Murono E, Perreault SD, Schrader SM, Shelby M [2003]. An occupational reproductive research agenda for the third millennium. Env Health Perspectives 111(4):584-592.

3. Holmes LB [1997]. Impact of the detection and prevention of developmental abnormalities in human studies. Reprod Toxicol 11(2-3):267-269.

4. Kimmel CA [1997]. Introduction to the symposium. Reprod Toxicol 11(2-3):261-263.

5. Oakley Jr GP [1986]. Frequency of human congenital malformations. Clin Perinatol 13(3):545-554.

Burden

Clinical syndromes associated with neurotoxicity comprise one of the 10 leading occupational disorders in the U.S., and neurotoxic effects are the basis for exposure limit criteria for about 40% of the agents considered hazardous by NIOSH.1 Among the neurologic disorders which may be associated with occupational exposures are neurodegenerative diseases, peripheral neuropathies, and chronic toxic encephalopathies. Neurologic toxicity is one of the most prominent adverse health effects associated with pesticide exposure.2 Pesticides are used extensively throughout the U.S., with more than 18,000 products licensed for use.3 Over 1.1 billion pounds of pesticides are used annually in the U.S., and widespread use results in pervasive occupational exposure.4-6 Separately, welding, a common activity occurring in many industrial sectors (but particularly common in the manufacturing sector), has been associated with neurotoxicity including neurodegenerative disease.7

There is currently an epidemic of chronic kidney disease of unknown etiology (CKDu) around the world. Workers in industries with jobs that occur outdoors and with a high workload, such as agricultural work, seem to be the most affected.8 Among agricultural industries, workers in sugarcane cultivation are among the workers apparently affected to the greatest degree. Currently it is unclear what causes CKDu, however heat stress and exposure to pesticides are thought to be possible contributors. More generally, chronic renal diseases may also be related to occupational exposures. For example, a recent study9 found that exposure to ultrafine particulates in the workplace was associated with risk of CKD, and past studies10 conducted by CRC scientists have found an association between silica dust and CKD. Exposures to dusty conditions are common in the workplace, suggesting that this burden could be high if these relationships are causal.

Need

Poisoning by acute high-level exposure to certain pesticides has well-known neurotoxic effects, but occupational health effects from chronic exposure to more moderate levels of pesticides are an area in need of study. Exposure assessment documenting exposure concentrations both within and among similar and different work tasks in epidemiological studies is needed.11 Some other areas of need may include the role of genetic susceptibility, and more studies of pesticides other than organophosphates. Intervention research is needed to develop and test interventions, programs or strategies aimed at minimizing or preventing pesticide exposure among farmers. Translation research to expand the high-quality implementation of evidence-based interventions, programs and strategies would be beneficial.

Occupational and environmental exposures cause an uncertain proportion of most types of neurodegenerative disease – a type of neurotoxicity that has been associated with welding. For some common neurodegenerative diseases the incidence is higher in men than in women which suggests occupational causes.12 While it is recognized that prolonged exposure to high manganese concentrations in air may lead to a Parkinsonian syndrome known as “manganism,” research is mixed concerning neurological and neurobehavioral deficits occurring when workers are exposed to low levels of manganese in welding fumes over time.

Regarding CKDu, surveillance research is needed to better understand the burden of CKDu among agricultural workers (and perhaps workers in other sectors) and basic/etiologic research is needed to better understand etiologic mechanisms. Most of the NIOSH-funded Centers for Agricultural Disease and Injury Research, Education, and Prevention (Ag Centers) have been involved in research that address pesticide exposure. These centers have already established partners and facilities, and developed methods to approach research in this area. NIOSH has also developed a network of partners through the SENSOR pesticide surveillance initiative to provide pesticide surveillance in cooperating states. Researchers beginning or continuing work in the area of CKDu can potentially tap these networks to address the surveillance and basic/etiologic research needs.

Impact

The impact of CRC work related to neurologic and renal diseases is expected to come from the wide range of types of research described above – ranging from basic work to identify mechanisms and causative agents to intervention and translation research – and lead to decreased morbidity and mortality among workers in the Agriculture and Manufacturing sectors.


1. Pearce N, Kromhout H [2014]. Neurodegenerative disease: The next occupational disease epidemic? Occup Environ Med 71(9):594-595.

2. Keifer MC, Firestone J [2007]. Neurotoxicity of pesticides. J Agromed 12(1):17–25.

3. EPA [2002]. Promoting safety for America’s future. FY 2002 Annual Report. Washington, D.C.: U.S. Environmental Protection Agency, Office of Pesticide Programs.

4. EPA [2011]. Pesticides industry sales and usage. 2008 and 2012 market estimates. Washington, DC: U.S. Environmental Protection Agency, EPA Report No. EPA-733-R-11-001. https://www.epa.gov/sites/production/files/2017-01/documents/pesticides-industry-sales-usage-2016_0.pdfCdc-pdfExternal

5. EPA [1992]. Regulatory impact analysis of worker protection standard for agricultural pesticides. Washington, D.C.: U.S. Environmental Protection Agency.

6. MacFarlane E, Carey R, Keegel T, El-Zaemay S, Fritschi L [2013]. Dermal exposure associated with occupational end use of pesticides and the role of protective measures. Saf Health Work 4(3):136-141.

7. Al-Lozi A, et al [2017]. Cognitive control dysfunction in workers exposed to manganese-containing welding fume. Am J Ind Med 60:181-188.

8. Valcke M, Levasseur ME, da Silva AS, Wesseling C [2017]. Pesticide exposures and chronic kidney disease of unknown etiology: an epidemiologic review. Environ Health 16(1), 49.24.

9. Sponholtz TR, Sandler DP, Parks CG, Applebaum KM [2016]. Occupational exposures and chronic kidney disease: possible associations with endotoxin and ultrafine particles. Am J Ind Med. 59:1-11.

10. Steenland K, Attfield M, Mannejte A [2006]. Pooled analyses of renal disease mortality and crystalline silica exposure in three cohorts. Ann Occup Hyg. 46(Suppl 1):4-9.

11. Gangemi S, Miozzi E, Teodoro M, Briguglio G, De Luca A, Alibrando C, Polito I, Libra M [2016]. Occupational exposure to pesticides as a possible risk factor for the development of chronic diseases in humans (Review). Mol Med Rep. 14(5):4475-4488.

12. Pearce N and Kromhout H [2014]. Neurodegenerative disease: The next occupational disease epidemic? Occup Environ Med 71(9):594-595.

Other examples of peer-reviewed literature that may be sources of information on which to guide future work of the CRC include the following:

Moorman WJ, Ahlers HW, Chapin RE, Daston GP, Foster PM, Kavlock RJ, Morawetz JS, Schnorr TM, Schrader SM [2000]. Prioritization of NTP reproductive toxicants for field studies. Reprod Toxicol 14(4):293-301.
This article describes a systematic method for prioritizing chemicals that may need human reproductive health field studies.

Ward EM, Schulte PA, Bayard S, Blair A, Brandt-Rauf P, Butler MA, Dankovic D, Hubbs AF, Jones C, Karstadt M, Kedderis GL [2003]. Priorities for development of research methods in occupational cancer. Env Health Perspectives111(1):1-12.
This article identifies needs and gaps in occupational cancer research methods in four broad areas: identification of occupational carcinogens, design of epidemiologic studies, risk assessment, and primary and secondary intervention.

Loomis D, Guha N, Hall AL, Straif K. Identifying occupational carcinogens: an update from the IARC Monographs. Occup Environ Med. 2018 Aug;75(8):593-603.
This article provides an updated list of occupational carcinogens and additional information on associated cancer types, exposure scenarios, and trends over time. It also calls for improved epidemiological evidence and quantitative exposure data.

 

References

1. Steenland K, Burnett C, Lalich N, Ward E, Hurrell J [2003]. Dying for work: The magnitude of U.S. mortality from selected causes of death associated with occupation. Am J Ind Med 43(5):461-482.

2.Afshin et al [2017] Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet 390(10100):1345-1422. doi: 10.1016/S0140-6736(17)32366-8. Erratum in: Lancet. 2017 Oct 28;390(10106):e38. Lancet. 2017 Oct 14;390(10104):1736.

3. Schulte PA [2005]. Characterizing the burden of occupational injury and disease. J Environ Occup Med 47(6):607-622.

4. Leigh JP, Yasmeen S, Miller TR [2003]. Medical costs of fourteen occupational illnesses in the United States in 1999. Scand J Work Environ Health 29(4):304-313.

5.Takala J [2015]. Eliminating occupational cancer. Ind Health. 53(4):307-309.

Page last reviewed: November 19, 2018