" DISCLAIMER: The ILO does not take responsibility for content presented on this web portal that is presented in any language other than English, which is the language used for the initial production and peer-review of original content. Certain statistics have not been updated since the production of the 4th edition of the Encyclopaedia (1998)."

Friday, 04 March 2011 18:00

Case Studies Illustrating Methodological Issues in the Surveillance of Occupational Diseases

Written by
Rate this item
(0 votes)

The documentation of occupational diseases in a country like Taiwan is a challenge to an occupational physician. For lack of a system including material safety data sheets (MSDS), workers were usually not aware of the chemicals with which they work. Since many occupational diseases have long latencies and do not show any specific symptoms and signs until clinically evident, recognition and identification of the occupational origin are often very difficult.

To better control occupational diseases, we have accessed databases which provide a relatively complete list of industrial chemicals and a set of specific signs and/or symptoms. Combined with the epidemiological approach of conjectures and refutations (i.e., considering and ruling out all possible alternative explanations), we have documented more than ten kinds of occupational diseases and an outbreak of botulism. We recommend that a similar approach be applied to any other country in a similar situation, and that a system involving an identification sheet (e.g., MSDS) for each chemical be advocated and implemented as one means to enable prompt recognition and hence the prevention of occupational diseases.

Hepatitis in a Colour Printing Factory

Three workers from a colour printing factory were admitted to community hospitals in 1985 with manifestations of acute hepatitis. One of the three had superimposed acute renal failure. Since viral hepatitis has a high prevalence in Taiwan, we should consider a viral origin among the most likely aetiologies. Alcohol and drug use, as well as organic solvents in the workplace, should also be included. Because there was no system of MSDS in Taiwan, neither the employees nor the employer were aware of all the chemicals used in the factory (Wang 1991).

We had to compile a list of hepatotoxic and nephrotoxic agents from several toxicological databases. Then, we deduced all possible inferences from the above hypotheses. For example, if hepatitis A virus (HAV) were the aetiology, we should observe antibodies (HAV-IgM) among the affected workers; if hepatitis B virus were the aetiology, we should observe more hepatitis B surface antigens (HBsAg) carriers among the affected workers as compared with non-affected workers; if alcohol were the main aetiology, we should observe more alcohol abusers or chronic alcoholics among affected workers; if any toxic solvent (e.g., chloroform) were the aetiology, we should find it at the workplace.

We performed a comprehensive medical evaluation for each worker. The viral aetiology was easily refuted, as well as the alcohol hypothesis, because they could not be supported by the evidence.

Instead, 17 of 25 workers from the plant had abnormal liver function tests, and a significant association was found between the presence of abnormal liver function and a history of recently having worked inside any of three rooms in which an interconnecting air-conditioning system had been installed to cool the printing machines. The association remained after stratification by the carrier status of hepatitis B. It was later determined that the incident occurred following inadvertent use of a “cleaning agent” (which was carbon tetrachloride) to clean a pump in the printing machine. Moreover, a simulation test of the pump-cleaning operation revealed ambient air levels of carbon tetrachloride of 115 to 495 ppm, which could produce hepatic damage. In a further refutational attempt, by eliminating the carbon tetrachloride in the workplace, we found that no more new cases occurred, and all affected workers improved after removal from the workplace for 20 days. Therefore, we concluded that the outbreak was from the use of carbon tetrachloride.

Neurological Symptoms in a Colour Printing Factory

In September 1986, an apprentice in a colour printing factory in Chang-Hwa suddenly developed acute bilateral weakness and respiratory paralysis. The victim’s father alleged on the telephone that there were several other workers with similar symptoms. Since colour printing shops were once documented to have occupational diseases resulting from organic solvent exposures, we went to the worksite to determine the aetiology with an hypothesis of possible solvent intoxication in mind (Wang 1991).

Our common practice, however, was to consider all alternative conjectures, including other medical problems including the impaired function of upper motor neurones, lower motor neurones, as well as the neuromuscular junction. Again, we deduced outcome statements from the above hypotheses. For example, if any solvent reported to produce polyneuropathy (e.g., n-hexane, methyl butylketone, acrylamide) were the cause, it would also impair the nerve conduction velocity (NCV); if it were other medical problems involving upper motor neurones, there would be signs of impaired consciousness and/or involuntary movement.

Field observations disclosed that all affected workers had a clear consciousness throughout the clinical course. An NCV study of three affected workers showed intact lower motor neurones. There was no involuntary movement, no history of medication or bites prior to the appearance of symptoms, and the neostigmine test was negative. A significant association between illness and eating breakfast in the factory cafeteria on September 26 or 27 was found; seven of seven affected workers versus seven of 32 unaffected workers ate breakfast in the factory on these two days. A further testing effort showed that type A botulinum toxin was detected in canned peanuts manufactured by an unlicensed company, and its specimen also showed a full growth of Clostridium botulinum. A final refutational trial was the removal of such products from the commercial market, which resulted in no new cases. This investigation documented the first cases of botulism from a commercial food product in Taiwan.

Premalignant Skin Lesions among Paraquat Manufacturers

In June 1983, two workers from a paraquat manufacturing factory visited a dermatology clinic complaining of numerous bilateral hyperpigmented macules with hyperkeratotic changes on parts of their hands, neck and face exposed to the sun. Some skin specimens also showed Bowenoid changes. Since malignant and premalignant skin lesions were reported among bipyridyl manufacturing workers, an occupational cause was strongly suspected. However, we also had to consider other alternative causes (or hypotheses) of skin cancer such as exposure to ionizing radiation, coal tar, pitch, soot or any other polyaromatic hydrocarbons (PAH). To rule out all of these conjectures, we conducted a study in 1985, visiting all of the 28 factories which ever engaged in paraquat manufacturing or packaging and examining the manufacturing processes as well as the workers (Wang et al. 1987; Wang 1993).

We examined 228 workers and none of them had ever been exposed to the aforementioned skin carcinogens except sunlight and 4’-4’-bipyridine and its isomers. After excluding workers with multiple exposures, we found that one out of seven administrators and two out of 82 paraquat packaging workers developed hyperpigmented skin lesions, as compared with three out of three workers involved in only bipyridine crystallization and centrifugation. Moreover, all 17 workers with hyperkeratotic or Bowen’s lesions had a history of direct exposure to bipyridyl and its isomers. The longer the exposure to bipyridyls, the more likely the development of skin lesions, and this trend cannot be explained by sunlight or age as demonstrated by stratification and logistic regression analysis. Hence, the skin lesion was tentatively attributed to a combination of bipyridyl exposures and sunlight. We made further refutational attempts to follow up if any new case occurred after enclosing all processes involving bipyridyls exposure. No new case was found.

Discussion and Conclusions

The above three examples have illustrated the importance of adopting a refutational approach and a database of occupational diseases. The former makes us always consider alternative hypotheses in the same manner as the initial intuitional hypothesis, while the latter provides a detailed list of chemical agents which can guide us toward the true aetiology. One possible limitation of this approach is that we can consider only those alternative explanations which we can imagine. If our list of alternatives is incomplete, we may be left with no answer or a wrong answer. Therefore, a comprehensive database of occupational disease is crucial to the success of this strategy.

We used to construct our own database in a laborious manner. However, the recently published OSH-ROM databases, which contain the NIOSHTIC database of more than 160,000 abstracts, may be one of the most comprehensive for such a purpose, as discussed elsewhere in the Encyclopaedia. Furthermore, if a new occupational disease occurs, we might search such a database and rule out all known aetiological agents, and leave none unrefuted. In such a situation, we may try to identify or define the new agent (or occupational setting) as specifically as possible so that the problem can first be mitigated, and then test further hypotheses. The case of premalignant skin lesions among paraquat manufacturers is a good example of this kind.



Read 2454 times Last modified on Thursday, 13 October 2011 20:24


Part I. The Body
Part II. Health Care
Part III. Management & Policy
Part IV. Tools and Approaches
Biological Monitoring
Epidemiology and Statistics
Occupational Hygiene
Personal Protection
Record Systems and Surveillance
Part V. Psychosocial and Organizational Factors
Part VI. General Hazards
Part VII. The Environment
Part VIII. Accidents and Safety Management
Part IX. Chemicals
Part X. Industries Based on Biological Resources
Part XI. Industries Based on Natural Resources
Part XII. Chemical Industries
Part XIII. Manufacturing Industries
Part XIV. Textile and Apparel Industries
Part XV. Transport Industries
Part XVI. Construction
Part XVII. Services and Trade
Part XVIII. Guides

Epidemiology and Statistics Additional Resources

Click the Button below to view additional resources for this topic.


Epidemiology and Statistics References

Ahlbom, A. 1984. Criteria of causal association in epidemiology. In Health, Disease, and Causal Explanations in Medicine, edited by L Nordenfelt and BIB Lindahl. Dordrecht: D Reidel.

American Conference of Government Industrial Hygienists (ACGIH). 1991. Exposure Assessment for Epidemiology and Hazard Control, edited by SM Rappaport and TJ Smith. Chelsea, Mich.:Lewis.

Armstrong, BK, E White, and R Saracci. 1992. Principles of Exposure Measurement in Epidemiology. Oxford: Oxford Univ. Press.

Ashford, NA, CI Spadafor, DB Hattis, and CC Caldart. 1990. Monitoring the Worker for Exposure and Disease. Baltimore: Johns Hopkins Univ. Press.

Axelson, O. 1978. Aspects on confounding in occupational health epidemiology. Scand J Work Environ Health 4:85-89.

—. 1994. Some recent developments in occupational epidemiology. Scand J Work Environ Health 20 (Special issue):9-18.

Ayrton-Paris, JA. 1822. Pharmacologia.

Babbie, E. 1992. The Practice of Social Research. Belmont, Calif.: Wadsworth.

Beauchamp, TL, RR Cook, WE Fayerweather, GK Raabe, WE Thar, SR Cowles, and GH Spivey. 1991. Ethical Guidelines for Epidemiologists. J Clin Epidemiol 44 Suppl. I:151S-169S.

Bell, B. 1876. Paraffin epithelioma of the scrotum. Edinburgh Med J 22:135.

Blondin, O and C Viau. 1992. Benzo(a)pyrene-blood protein adducts in wild woodchucks used as biological sentinels of environmental polycyclic aromatic hydrocarbons contamination. Arch Environ Contam Toxicol 23:310-315.

Buck, C. 1975. Popper’s philosophy for epidemiologists. Int J Epidemiol 4:159-168.

Case, RAM and ME Hosker. 1954. Tumour on the urinary bladder as an occupational disease in the rubber industry in England and Wales. Brit J Prevent Soc Med 8:39-50.

Checkoway, H, NE Pearce, and DJ Crawford-Brown. 1989. Research Methods in Occupational Epidemiology. New York: Oxford Univ. Press.

Clayson, DB. 1962. Chemical Carcinogenesis. London: JA Churchill.

Clayton, D. 1992. Teaching statistical methods in epidemiology. In Epidemiology. What You Should Know and What You Could Do, edited by J Olsen and D Trichopoulos. Oxford: Oxford Univ. Press.

Clayton, D and M Hills. 1993. Statistical Models in Epidemiology. New York: Oxford Univ. Press.

Cornfield, J. 1954. Statistical relationships and proof in medicine. Am Stat 8:19-21.

Council for International Organizations of Medical Sciences (CIOMS). 1991. International Guidelines for Ethical Review of Epidemiologic Studies. Geneva: CIOMS.

Czaja, R and J Blair. 1996. Designing Surveys. Thousand Oaks, Calif: Pine Forge Press.

Doll, R. 1952. The causes of death among gas-workers with special reference to cancer of the lung. Brit J Ind Med 9:180-185.

—. 1955. Mortality from lung cancer in asbestos workers. Brit J Ind Med 12:81-86.

Droz, PO and MM Wu. 1991. Biological monitoring strategies. In Exposure Assessment for Epidemiology and Hazard Control, edited by SM Rappaport and TJ Smith. Chelsea, Mich.: Lewis.

Gamble, J and R Spirtas. 1976. Job classification and utilization of complete work histories in occupational epidemiology. J Med 18:399-404.

Gardner, MJ and DG Altman. 1989. Statistics With Confidence. Confidence Intervals and Statistical Guidelines. London: BMJ Publishing House.

Garfinkel, L. 1984. Classics in oncology; E. Cuyler Hammond, ScD. Ca-Cancer Journal for Clinicians. 38(1): 23-27

Giere, RN. 1979. Understanding Scientific Reasoning. New York: Holt Rinehart & Winston.

Glickman, LT. 1993. Natural exposure studies in pet animals: Sentinels for environmental carcinogens. Vet Can Soc Newslttr 17:5-7.

Glickman, LT, LM Domanski, TG Maguire, RR Dubielzig, and A Churg. 1983. Mesothelioma in pet dogs associated with exposure of their owners to asbestos. Environmental Research 32:305-313.

Gloyne, SR. 1935. Two cases of squamous carcinoma of the lung occurring in asbestosis. Tubercle 17:5-10.

—. 1951. Pneumoconiosis: Histological survey of necropsy material in 1,205 cases. Lancet 1:810-814.

Greenland, S. 1987. Quantitative methods in the review of epidemiological literature. Epidemiol Rev 9:1-30.

—. 1990. Randomization, statistics, and causal inference. Epidemiology 1:421-429.

Harting, FH and W Hesse. 1879. Der Lungenkrebs, die bergkrankheit in den Schneeberger Gruben. Vierteljahrsschr Gerichtl Med Offentl Gesundheitswesen CAPS 30:296-307.

Hayes, RB, JW Raatgever, A de Bruyn, and M Gerin. 1986. Cancer of the nasal cavity and paranasal sinuses, and formaldehyde exposure. Int J Cancer 37:487-492.

Hayes, HM, RE Tarone, HW Casey, and DL Huxsoll. 1990. Excess of seminomas observed in Vietnam service US military working dogs. J Natl Cancer Inst 82:1042-1046.

Hernberg, S. 1992. Introduction to Occupational Epidemiology. Chelsea, Mich.: Lewis.
Hill, AB. 1965. The environment and disease: Association or causation? Proc Royal Soc Med 58:295-300.

Hume, D. 1978. A Treatise of Human Nature. Oxford: Clarendon Press.

Hungerford, LL, HL Trammel, and JM Clark. 1995. The potential utility of animal poisoning data to identify human exposure to environmental toxins. Vet Hum Toxicol 37:158-162.

Jeyaratnam, J. 1994. Transfer of hazardous industries. In Occupational Cancer in Developing Countries, edited by NE Pearce, E Matos, H Vainio, P Boffetta, and M Kogevinas. Lyon: IARC.

Karhausen, LR. 1995. The poverty of Popperian epidemiology. Int J Epidemiol 24:869-874.

Kogevinas, M, P Boffetta, and N Pearce. 1994. Occupational exposure to carcinogens in developing countries. In Occupational Cancer in Developing Countries, edited by NE Pearce, E Matos, H Vainio, P Boffetta, and M Kogevinas. Lyon: IARC.

LaDou, J. 1991. Deadly migration. Tech Rev 7:47-53.

Laurell, AC, M Noriega, S Martinez, and J Villegas. 1992. Participatory research on workers’ health. Soc Sci Med 34:603-613.

Lilienfeld, AM and DE Lilienfeld. 1979. A century of case-control studies: progress? Chron Dis 32:5-13.

Loewenson, R and M Biocca. 1995. Participatory approaches in occupational health research. Med Lavoro 86:263-271.

Lynch, KM and WA Smith. 1935. Pulmonary asbestosis. III Carcinoma of lung in asbestos-silicosis. Am J Cancer 24:56-64.

Maclure, M. 1985. Popperian refutation in epidemiolgy. Am J Epidemiol 121:343-350.

—. 1988. Refutation in epidemiology: Why else not? In Causal Inference, edited by KJ Rothman. Chestnut Hill, Mass.: Epidemiology Resources.

Martin, SW, AH Meek, and P Willeberg. 1987. Veterinary Epidemiology. Des Moines: Iowa State Univ. Press.

McMichael, AJ. 1994. Invited commentary -"Molecular epidemiology": New pathway or new travelling companion? Am J Epidemiol 140:1-11.

Merletti, F and P Comba. 1992. Occupational epidemiology. In Teaching Epidemiology. What You Should Know and What You Could Do, edited by J Olsen and D Trichopoulos. Oxford: Oxford Univ. Press.

Miettinen, OS. 1985. Theoretical Epidemiology. Principles of Occurrence Research in Medicine. New York: John Wiley & Sons.

Newell, KW, AD Ross, and RM Renner. 1984. Phenoxy and picolinic acid herbicides and small-intestinal adenocarcinoma in sheep. Lancet 2:1301-1305.

Olsen, J, F Merletti, D Snashall, and K Vuylsteek. 1991. Searching for Causes of Work-Related Diseases. An Introduction to Epidemiology At the Work Site. Oxford: Oxford Medical Publications, Oxford Univ. Press.

Pearce, N. 1992. Methodological problems of time-related variables in occupational cohort studies. Rev Epidmiol Med Soc Santé Publ 40 Suppl: 43-54.

—. 1996. Traditional epidemiology, modern epidemiology and public health. Am J Public Health 86(5): 678-683.

Pearce, N, E Matos, H Vainio, P Boffetta, and M Kogevinas. 1994. Occupational cancer in developing countries. IARC Scientific Publications, no. 129. Lyon: IARC.

Pearce, N, S De Sanjose, P Boffetta, M Kogevinas, R Saracci, and D Savitz. 1995. Limitations of biomarkers of exposure in cancer epidemiology. Epidemiology 6:190-194.

Poole, C. 1987. Beyond the confidence interval. Am J Public Health 77:195-199.

Pott, P. 1775. Chirurgical Observations. London: Hawes, Clarke & Collins.

Proceedings of the Conference on Retrospective Assessment of Occupational Exposures in Epidemiology, Lyon, 13-15 April, 1994. 1995. Lyon: IARC .

Ramazzini, B. 1705. De Morbis Artificum Diatriva. Typis Antonii Capponi. Mutinae, MDCC. London: Andrew Bell & Others.

Rappaport, SM, H Kromhout, and E Symanski. 1993. Variation of exposure between workers in homogeneous exposure groups. Am Ind Hyg Assoc J 54(11):654-662.

Reif, JS, KS Lower, and GK Ogilvie. 1995. Residential exposure to magnetic fields and risk of canine lymphoma. Am J Epidemiol 141:3-17.

Reynolds, PM, JS Reif, HS Ramsdell, and JD Tessari. 1994. Canine exposure to herbicide-treated lawns and urinary excretion of 2,4-dichlorophenoxyacetic acid. Canc Epidem, Biomark and Prevention 3:233-237.

Robins, JM, D Blevins, G Ritter, and M Wulfsohn. 1992. G-estimation of the effect of prophylaxis therapy for pneumocystis carinii pneumonia on the survival of Aids patients. Epidemiology 3:319-336.

Rothman, KJ. 1986. Modern Epidemiology. Boston: Little, Brown & Co.

Saracci, R. 1995. Epidemiology: Yesterday, today, tomorrow. In Lectures and Current Topics in Epidemiology. Florence: European Educational Programme in Epidemiology.

Schaffner, KF. 1993. Discovery and Explanation in Biology and Medicine. Chicago: Univ. of Chicago Press.

Schlesselman, JJ. 1987. “Proof” of cause and effect in epidemiologic studies: Criteria for judgement. Prevent Med 16:195-210.

Schulte, P. 1989. Interpretation and communcication of the results of medical field investigations. J Occup Med 31:5889-5894.

Schulte, PA, WL Boal, JM Friedland, JT Walker, LB Connally, LF Mazzuckelli, and LJ Fine. 1993. Methodological issues in risk communications to workers. Am J Ind Med 23:3-9.

Schwabe, CW. 1993. The current epidemiological revolution in veterinary medicine. Part II. Prevent Vet Med 18:3-16.

Seidman, H, IJ Selikoff, and EC Hammond. 1979. Short-term asbestos work exposure and long-term observation. Ann NY Acad Sci 330:61-89.

Selikoff, IJ, EC Hammond, and J Churg. 1968. Asbestos exposure, smoking and neoplasia. JAMA 204:106-112.

—. 1964. Asbestos exposure and neoplasia. JAMA 188, 22-26.

Siemiatycki, J, L Richardson, M Gérin, M Goldberg, R Dewar, M Désy, S Campbell, and S Wacholder. 1986. Associations between several sites of cancer and nine organic dusts: Results from an hypothesis-generating case-control study in Montreal, 1979-1983. Am J Epidemiol 123:235-249.

Simonato, L. 1986. Occupational cancer risk in developing countries and priorities for epidemiological research. Presented at International Symposium On Health and Environment in Developing Countries, Haicco.

Smith, TJ. 1987. Exposure asssessment for occupational epidemiology. Am J Ind Med 12:249-268.

Soskolne, CL. 1985. Epidemiological research, interest groups, and the review process. J Publ Health Policy 6(2):173-184.

—. 1989. Epidemiology: Questions of science, ethics, morality and law. Am J Epidemiol 129(1):1-18.

—. 1993. Introduction to misconduct in science and scientific duties. J Expos Anal Environ Epidemiol 3 Suppl. 1:245-251.

Soskolne, CL, D Lilienfeld, and B Black. 1994. Epidemiology in legal proceedings in the United States. In The Identification and Control of Environmental and Occupational Diseases. Advances in Modern Environmental Toxicology: Part 1, edited by MA Mellman and A Upton. Princeton: Princeton Scientific Publishing.

Stellman, SD. 1987. Confounding. Prevent Med 16:165-182.

Suarez-Almazor, ME, CL Soskolne, K Fung, and GS Jhangri. 1992. Empirical assessment of the effect of different summary worklife exposure measures on the estimation of risk in case-referent studies of occupational cancer. Scand J Work Environ Health 18:233-241.

Thrusfield, MV. 1986. Veterinary Epidemiology. London: Butterworth Heinemann.

Trichopoulos, D. 1995. Accomplishments and prospects of epidemiology. In Lectures and Current Topics in Epidemiology. Florence: European Educational Programme in Epidemiology.

Van Damme, K, L Cateleyn, E Heseltine, A Huici, M Sorsa, N van Larebeke, and P Vineis. 1995. Individual susceptibility and prevention of occupational diseases: scientific and ethical issues. J Exp Med 37:91-99.

Vineis, P. 1991. Causality assessment in epidemiology. Theor Med 12:171-181.

Vineis, P. 1992. Uses of biochemical and biological markers in occupational epidemiology. Rev Epidmiol Med Soc Santé Publ 40 Suppl 1: 63-69.

Vineis, P and T Martone. 1995. Genetic-environmental interactions and low-level exposure to carcinogens. Epidemiology 6:455-457.

Vineis, P and L Simonato. 1991. Proportion of lung and bladder cancers in males resulting from occupation: A systematic approach. Arch Environ Health 46:6-15.

Vineis, P and CL Soskolne. 1993. Cancer risk assessment and management: An ethical perspective. J Occup Med 35(9):902-908.

Vineis, P, H Bartsch, N Caporaso, AM Harrington, FF Kadlubar, MT Landi, C Malaveille, PG Shields, P Skipper, G Talaska, and SR Tannenbaum. 1994. Genetically based N-acetyltransferase metabolic polymorphism and low level environmental exposure to carcinogens. Nature 369:154-156.

Vineis, P, K Cantor, C Gonzales, E Lynge, and V Vallyathan. 1995. Occupational cancer in developed and developing countries. Int J Cancer 62:655-660.

Von Volkmann, R. 1874. Ueber Theer-und Russkrebs. Klinische Wochenschrift 11:218.

Walker, AM and M Blettner. 1985. Comparing imperfect measures of exposure. Am J Epidemiol 121:783-790.

Wang, JD. 1991. From conjectures and refutation to the documentation of occupational diseases in Taiwan. Am J Ind Med 20:557-565.

—. 1993. Use of epidemiologic methods in studying diseases caused by toxic chemicals. J Natl Publ Health Assoc 12:326-334.

Wang, JD, WM Li, FC Hu, and KH Fu. 1987. Occupational risk and the development of premalignant skin lesions among paraquat manufacturers. Brit J Ind Med 44:196-200.

Weed, DL. 1986. On the logic of causal inference. Am J Epidemiol 123:965-979.

—. 1988. Causal criteria and popperian refutation. In Causal Inference, edited by KJ Rothman. Chestnut Hill, Mass.: Epidemiology Resources.

Wood, WB and SR Gloyne. 1930. Pulmonary asbestosis. Lancet 1:445-448.

Wyers, H. 1949. Asbestosis. Postgrad Med J 25:631-638.