Applications of a Job Classification System In Occupational Epidemiology JOHN F. GAMBLE, PHD, ROBERT SPIRTAS, DRPH, AND PEGGY EASTER
Abstract: An occupational preventive medicine program attempts to control exposure so workers experience no detrimental effect on health. In a chemically complex industry, the definition of exposure is difficult because of the many different chemicals used and produced, the many different jobs and processes with qualitatively different exposures, and the movement of workers from job to job. Jobs have therefore been grouped on the basis of process or product into
functionally homogeneous categories called occupational titles (OT's). Work experience can now be quantified independent of exposure (or by the dominant toxicants in each OT) and compared to health outcomes. Examples are discussed of the application of OT's to studies of the mortality and morbidity experience in the rubber industry, and the development of dose-response relations. (Am. J. Public Health 66:768-772, 1976)
Introduction
has been inadequate so that it failed to provide clues to the existence of toxic environmental agents. The difficulties in defining exposure of a worker are compounded by the mobility of the work force, where it is not uncommon for a worker to have 20-30 different jobs during his working lifetime. It is thus not possible to define "exposure" (except on a case-by-case basis), nor to statistically analyze associations between all job and health variables. As a result, relations between work experience and disease(s) have not been known or well-defined in the rubber industry. Similar problems of defining exposure may be found in other chemically complex industries. Since a complete qualitative and quantitative description of "environment" is not possible, how can an objective assessment of work exposure be achieved? The Occupational Health Studies Group (OHSG) at the University of North Carolina has approached the problem of defining work experience in a chemically complex industry by grouping jobs into functionally homogeneous categories called occupational titles (OT's).' An OT is defined not by exposure per se, but by (1) process or function and (2) product (Figure 1, Table 1). OT's form a hierarchical classification, as each major process contains functionally similar subprocesses. For example, in the final inspection OT includes jobs related to finishing and repair (trimming, buffing, repair) and to inspection (sorting, classifying, labeling, inspecting). Depending on the study and the size of the study population, these groupings (e.g. tire inspection, tire repair) may be retained, or classified as one (e.g. final inspection). The level of classification chosen depends on the study design, size of population, and available resources. Just as one knows the
A preventive medicine program for a working population attempts to control toxicants so that exposure does not adversely affect health. To do this requires measurement of health outcomes, and, if there is a detrimental health effect. the measurement of the relevant etiologic agents. In this way. dose-response relations can be determined and safe working environments maintained. In the rubber industry, the job of defining exposure is a difficult one for several reasons. Hundreds of different ingredients are used in making different kinds of tires. tubes, and other rubber products. Little is known of the toxicity and worker exposures to most of these chemicals. The heat and pressure required in the production of rubber products results in the evolution of a myriad of reaction and degradation products whose qualitative and quantitative composition is largely theoretical. Furthermore, there are a large number of different jobs in this complex industry. A typical tire and tube plant has several hundred different jobs, and therefore. exposures. At present. we are unable to fully characterize the exposure of any single job; until recently, information concerning the relationship between jobs and health From the Occupational Health Studies Group. School of Public Health. University of North Carolina. NCNB Plaza, Chapel Hill, NC 27514. Address reprint requests to Dr. Gamble at the above address. This paper. presented at the 103rd Annual Meeting of the American Public Health Association, Chicago 1975. was submitted to the Journal March 1. 1976. revised and accepted for publication April 7. 1976.
768
AJPH August, 1976, Vol. 66, No. 8
OCCUPATIONAL EPIDEMIOLOGY TABLE 1-Description of Occupational Titles in Tire Manufacturing Occupational Titles
Compounding and Mixing Cutting and Milling Milling Extrusion
Calendering Plystock Preparation
Bead Building Tire Building Curing Preparation
Curing Final Inspection
Description
Raw ingredients (rubber, fillers, extender oils, accelerators, antioxidants) are mixed together in a Banbury mixer (BB). This internal mixer breaks down rubber for thorough and uniform dispersion of the other ingredients. The batches from the BB are further mixed on a mill, cooled and coated with talc so they are not tacky. The stock may return to the BB for additional ingredients, or go on to Milling. Final rubber mix is worked between two heavy iron rolls revolving toward each other. These are two kinds of mills feeding stock to a calender or extruder. A breakdown mill softens the rubber. The stock then goes to a feed mill for further working. The softened rubber is forced through a die forming a long, continuous strip in the shape of a tread. This strip is cut in appropriate lengths, and the cut ends are cemented so as to be tacky. The softened rubber from the feed mill is applied to fabric forming continuous sheets of plystock in the calender (a mill with three or more vertical rolls and much greater accuracy and control of thickness). The Plystock from the calender is cut and spliced to the correct size for tire building, and so the strands in the fabric have the proper orientation. Parallel steel wire is insulated with rubber vulcanizable into a semi-hard condition and covered with a special rubberized fabric. The beads maintain the shape of the tire and hold it onto the rim. The tire is built from several sheets of calendered plystock, treads and beads. The assembled tire is inspected, repaired, and coated with agents to keep it from sticking to the mold in vulcanization. Vulcanization changes compounded rubber from a sticky, plastic mass to a dry, elastic material with increased tolerance for temperature changes and increased strength. The tire is placed in a mold and shaped under heat and pressure. The cured tire is trimmed, inspected, repaired and labeled.
genus and species in each phylum of the plant and animal kingdom. so one knows the individual subprocesses and jobs in each OT category. OT's are defined independently of exposure; in fact, the precise environmental profile is not known. Except for short-term samples of solvents, the quantification of chemical species is not complete at any level of classification. Because of the large number of rubber stocks. the exposure profile for jobs and OT's is continually changing. Despite the variable nature of rubber production. however, it is possible to roughly characterize the dominant exposures in each OT
(Table 2). Mortality and morbidity experience can now be assessed in each category. without the diluting effect that oc-
curs when all rubber workers from functionally different jobs. processes. and therefore qualitatively different exposures are observed. If there is an occupationally induced effect on health, the observation of health experience by OT increases the ability to detect such an effect. It increases sensitivity by separating workers into relatively homogeneous categories, and increases specificity by identifying high risk OT's for specific health outcomes. The number of potential and plausible environmental causal agents is also reduced.
Applications Several studies in the rubber industry have indicated an
Figure 1. Production Stages in Manufacture of Tires AJPH August, 1976, Vol. 66, No. 8
769
GAMBLE, ET AL. TABLE 2-Summary of Major Contaminants in Tire Manufacturing Occupational Titles Environmental Exposure
Occupational Titles
Compounding and Mixing
Cutting and Milling Milling Extrusion Calendering Tire Building Curing Preparation Curing Final Inspt -'-n
Accelerators (e.g., thiazoles, guanidines, thiuram sulfides, carbamates). Antioxidants Fillers (carbon black) Extender oils Talc *Emission from Vulcanization Process Solvents *Emission from Vulcanization Process Solvents Variable exposure to solvents, talc *Emission from Vulcanization Products Cured rubber dust, solvents
*Emissions from the hot rubber mix can be of two sorts (based on theoretical considerations), and will not be the same for milling, calendering, and curing. 1. Volatization (1) Residual monomers (probably only milling and calendering)-styrene, acrylonitrile, chloroprene (b) Antioxidants and Antiozonants and Accelerators-higher loss in milling and calendering (c) Processing Aids-oils (d) Miscellaneous Ingredients-special ingredients (amines, esters, organic acids) and impurities (5-40 per cent of main ingredient). 2. Formation of New Compounds-Oxidative products are formed in milling and calendering; reductive products are formed in the mold during curing, oxidative products when the curing press is opened. The compound classes formed include amines and ammonia, organic sulfides, hydrocarbons, acids, esters, water. It has been estimated that 0.50-0.7 per cent volatile material would be released and conceivably 1,000 or more different compounds.
increased risk for a variety of health outcomes.2'7 An operational definition of work experience makes possible the identification of high risk jobs with specific health outcomes. the identification of causal environmental agents. and the establishment of safe levels of environmental exposure. The association of specific OT's with specific health outcomes can be approached as an exercise in hypothesis-generating and hypothesis-testing. The findings raise further questions for investigation as discussed below.
Hypothesis-generating An example of an epidemiologic study in the hypothesis-generating mode is the examination of the ten-year mortality experience of 6.678 male rubber workers.7 All jobs of individuals dying of selected causes of death were classified into OT's and compared with the work experience of a random sample of the total population. Figure 2 summarizes the ratios of time spent in each OT by cases compared to controls. The time periods in each OT are limited to greater than five years during the presumed etiologic period for these chronic diseases. These ratios provide an approximation of increased mortality risk associated with each OT. They also allow one to begin hypothesis testing. For example. the observed association of excess stomach. lung. and bladder cancer with OT's early in the manufacturing process raises questions as to the route of absorption, metabolic transformation. and the carcinogenicity of pigments (accelerators. antioxidants). fillers (carbon black. talc). degradation. and reaction products. There are suggestions in the literature implicating these or related compounds as carcinogens. For example. carbon black has long been known to adsorb carcinogens.8' " but the mortality experience from all kinds of cancer from 1939-1956 of workers producing carbon black was judged to be low when contrasted with comparable populations.'' Talc is a known respiratory carcinogen. "I but heretofore has not generally been consid770
ered as posing a gastrointestinal (GI) threat. Some pigments and products evolved from curing rubber are potential carcinogenic agents. but in curing are thought to not pose a high risk because of the small quantities evolved. These contradictory findings stimulate specific questions such as: Is there a GI insult in these OT's. or operationally. how much particulate is deposited in the upper airways. cleared to the mouth and swallowed? Heretofore. environmental measurements have measured total particulate (e.g. high volume samplers) and respirable particulate (deposited in lower airways with primarily systemic absorption). There is at present no good way to sample for particulate deposited in the upper airways. Thus we may not be measuring the relevant dose for the observed gastrointestinal health effect. Should we be concerned about whether workers are nose or mouth breathers. as this undoubtedly affects lung deposition. if not gastrointestinal insult? The association of stomach and colorectal cancers with the final inspection and repair OT raises similar questions about "rubber dust'". as extracts of automobile tire contain carcinogenic hydrocarbons. 2 Lednar. et al..'3 report on the use of OT's in a case control study of pulmonary disability. This study raises the interesting question as to effects of mobility or selective migration on associations of chronic disease with OT's. Do workers with symptoms tend to move to less symptom-producing jobs? Cross-sectional studies of current health status and exposure indices of workers are also underway. In a study of the effect of a particular rubber adhesive on respiratory function. workers were administered pulmonary function tests before beginning work and again six hours later. and environmental measures were taken concurrently. '4 The workers exposed to the adhesive had. as a group. significant reductions in lung function that were associated with particulate exposure. Only the workers in OT's of milling and calendering. AJPH August, 1976, Vol. 66, No. 8
OCCUPATIONAL EPIDEMIOLOGY Ratio (Cases/Controls) Occupational Title (OT)
St4tomach Cancer
Colorectal Cancer
Respiratory Cancer
Prostate Cancer
Bladder Cancer
0I 1 2
0 1 2
0 1 2
0 1 2
0 1 2
*
1. Receiving and Shipping
1.6
2. Compounding and Mixing
1.9
3. Mill-Mixing, Other Batch Prep
2.0
4. Milling
5. Calendering and Plystock
10. Curing
0.8
.
0.9
U
1.7
E 1.4 U
12. Maintenance
0.7
13. Mechanical Special Products
0.5
14. Reclaim
0.4
E*1.1
0.0
0.5
0.0
0.8
0.3
0.8
1.3
0.1
0.7
0.7
2.4
0.3
0.5
2.3
0.0
2.8
0.4
0.8
0.5 0.0
0.0
0.0
1.0
1.0
2.5
1.4
0.2
1.7
1.0
1.4
0.9
1.0 *
0
0.4
0.0
0.0
1.9
0.0
0.9 0.7
3.1
1.1
0.7
1.1
0.0
0.3
1.1
0.8
0.0
0.9
1.0
1.7
2.2
0.8
1.4
0.6
0.7
1.2
1.0
1.0
0.
1.2
1.5
.0
1.4
0.9 0.0
0.3
0.6
0.7
0.9
0.7
1.1
1.1
2.1
15. Synthetic Plant
.0
0.5
0.0
1.7
00.6
0.6
0.0
0.0
1.3
_
0
2.1
1.2 2.1
0 1 2
1.4
*
0.6
1.2
1.2
*
0.4
Diabetes Mellitus
1.7
2.0
1.5
2.1
2.2
11. Final Inspection
16. Miscellaneous
0.4
1.0
0.7
1.4
0.6
I 0.4
7. Tire Building
9. Tube Building
1.8
1.2
* 1.2
6. Extrusion
8. Curing Preparation
0.6
Ischemic Heart Disease 0 1 2
Lymphatic and Hematopoietic Cancer 0 1 2
1.3
0.6
2.9 0.4
0.0 3.5
FIGURE 2. Ratios of age-adjusted rates of exposure to specific OT's for cases compared to population sample (n = 1402). For example, 8% of stomach than 5 years in Receiving and Shipping, versus 5% of the population sample, giving a ratio of 1.6 (from Reference 7).
cases spent more
however, were observed to have statistically significant reductions in lung function. Although the number of workers in each OT are small, the findings are compatible with the hypothesis of a reaction or degradation product from the adhesive being adsorbed onto particulate, thereby increasing the effective dose. This type of experimental design shows the potential for not only pinpointing high risk OT's, but also determining exposure levels below which there is no measureable effect. In the rubber adhesive study, for example, there was no change in pulmonary function when "respirable" particulate levels were below 0.2 mg/m3. In this type of study, OT is the independent or exposure variable. Changes in pulmonary function (APF) is the dependent variable, or health effect. Response (APF) is used to assess the respiratory hazard of the OT. Cross-sectional environmental data are being systematically gathered in a variety of rubber products plants. Environmental samples are located by OT, providing comparability between plants, and making possible estimates of overall exposure levels and variability of exposures for the measured toxicants in plants and for processes where environmental measurements have not been made.
Hypothesis-testing The initial use of OT's and complete work histories began with the reported finding of an excess of leukemia deaths in a cohort of 6,678 male rubber workers.2 Because of the presumed leukemogenic properties of benzene, OT's were AJPH August, 1976, Vol. 66, No. 8
grouped into solvent and non-solvent exposed categories. When comparing cases and controls, a statistically significant association was observed between lymphatic leukemia and the solvent exposure categories.3 Armed with the epidemiological information of how a particular disease (leukemia) is associated with specific OT's, OHSG initiated in this plant a retrospective reconstruction of solvent use (particularly benzene). Purchasing and production records, quality control specifications, and plant blueprints are being used to construct an estimate of specific solvent exposures over time. Leukemia mortality and retrospective environmental estimates can then be used to determine the association (or lack of it) of leukemia with particular solvents (e.g. benzene, toluene, xylene). The reconstruction of an exposure profile of a handful of agents (solvents in this case) is in itself a large undertaking. Practically, it is not feasible to do this for all chemicals used in the rubber industry. Prospective surveillance of present-day workers has increased as a result of this finding. Sampling of solvents in the cross-sectional environmental survey has been increased. Benzene content of bulk solvents is monitored to ascertain and regulate the content of this agent. Workers in high risk jobs are observed for blood and chromosomal abnormalities. Dose-response The goal in occupational health is to prevent disease and ill-health by controlling causal toxicants. This is done by es771
GAMBLE, ET AL.
tablishing dose-response relations. The response can be as permanent as death, or as temporary as reductions in lung function over a shift. Defining exposure is more difficult. For acute responses such as APF over a shift, dose may be measured as respirable particulate in each OT (where the exposures are similar, and to varying extents known qualitatively). For chronic diseases, dose is a working lifetime of changing exposures. For a chronic disease in an industry with multiple insults. the complete work history must be utilized. The Experience Transformation Algorithm (ETA) computer program has been developed for this purpose.' Input to the program is the sequence ofjobs coded into OT's. Output is a cumulative measure of time spent by each worker in pre-specified groups of OT. Chronic disease characteristically is a progressive disease developing over a long time period. The ETA takes account of this. and can single out certain fractions of a worker's total work history (on the basis of age of the worker. etiologic period prior to disease. or calender period when a causal agent may have had greatest use). Since the exposure profile is largely unknown. OT's have been used as the surrogate measure of exposure. They provide the essential link between 'dose"' (exposure as measured by industrial process or product) and response (as measured by morbidity or mortality). With increased insight into the hazards of this industry, our classification of jobs may begin to look more like categories of different exposures. But however knowledgeable we become. we will be unable to foresee all relevant and hazardous exposures. Classification of jobs. independent of exposure. provide the essential link between environmental and medical information. Without medical data. the precise quantification of the exposure profile is a mammoth task. Without medical data on workers' response. the significance of exposure is difficult. if not impossible to evaluate. Without environmental data, the control of disease causing agents becomes a problematical and costly exercise. Even though the exposure profile is not complete. the association of biological response w ith work experience (OT's) can still be made. Control meas-
772
ures can be initiated in those OT's, and the search goes on for causal agents.
REFERENCES 1. Gamble. J. F. and Spirtas. R. Job classification and utilization of complete work histories in occupational epidemiology. J. Occup. Med.. (in press. 1976). 2. McMichael, A. J., Spirtas. R.. and Kupper. L. L. An epidemiologic study of mortality within a cohort of rubber workers. 1964-72. J. Occup. Med. 16:458-464. 1974. 3. McMichael. A. J., Spirtas. R.. Kupper. L. L.. and Gamble. J. F. Solvent exposure and leukemia among rubber workers: An epidemiologic study. J. Occup. Med. 17:234-239. 1975. 4. Mancuso, T. F.. Ciocco. A.. and El-Altar. A. A. An epidemiological approach to the rubber industry. J. Occup. Med. 10:213232. 1968. 5. Parkes. H. G. Health in the Rubber Industry. A Pilot Study. Manchester. England: A. Megson and Son Ltd.. 1966. 6. Fox. A. J., Lindars. D. C.. Owen R. A survey of occupational cancer in the rubber and cablemaking industries: Results of fiveyear analysis. 1967-71. Brit. J. Ind. Med. 31:140-159. 1974. 7. McMichael, A. J., Spirtas. R. Gamble. J. F.. and Tousey. P. N. Mortality among rubber workers: Relationship to specific jobs. J. Occup. Med. 18:178-185. 1976. 8. Falk, H. L. and Steiner. P. E. The identification of aromatic polycyclic hydrocarbons in carbon black. Cancer Res. 12:3039. 1952. 9. Falk. H. L. and Steiner. P. E. The adsorption of 3.4-benzpyrene and pyrene by carbon blacks. Cancer Res. 12:40-43. 1952. 10. Ingalls. T. H.. Risquez-lribarren. R. Periodic search for cancer in the carbon black industry. Arch. Env. Hlth. 2:429-443. 1961. II. Blejar. H. P. and Arlon. R. Talc: A possible occupational and environmental carcinogen. J. Occup. Med. 15:92-97. 1973. 12. Falk. H. L.. Steiner. P. E.. Goldfein. Breslow. A.. and Hykes. R. Carcinogenic hydrocarbons and related compounds in processed rubber. Cancer Res. 11:318-324. 1951. 13. Lednar. W. M.. Tyroler. H. A.. McMichael. A. J., and Shy. C. M. A study of the occupational determinants of chronic disabling pulmonary disease in rubber workers. Presented at 103rd Annual Meeting of APHA. November 20. 1975. Chicago. IL. 14. Gamble. J. F.. McMichael, A. J., Williams. T. M.. and Battigelli. M. C. Respiratory function and symptoms: An environmental-epidemiologic study of selected rubber workers. Presented to American Industrial Hygiene Conference. Minneapolis. Minn.. June 5. 1975. Am. Industrial Hygiene Assoc. Journal (in press. 1976).
AJPH August, 1976, Vol. 66, No. 8
Abstract: An occupational preventive medicine program attempts to control exposure so workers experience no detrimental effect on health. In a chemically complex industry, the definition of exposure is difficult because of the many different chemicals used and produced, the many different jobs and processes with qualitatively different exposures, and the movement of workers from job to job. Jobs have therefore been grouped on the basis of process or product into
functionally homogeneous categories called occupational titles (OT's). Work experience can now be quantified independent of exposure (or by the dominant toxicants in each OT) and compared to health outcomes. Examples are discussed of the application of OT's to studies of the mortality and morbidity experience in the rubber industry, and the development of dose-response relations. (Am. J. Public Health 66:768-772, 1976)
Introduction
has been inadequate so that it failed to provide clues to the existence of toxic environmental agents. The difficulties in defining exposure of a worker are compounded by the mobility of the work force, where it is not uncommon for a worker to have 20-30 different jobs during his working lifetime. It is thus not possible to define "exposure" (except on a case-by-case basis), nor to statistically analyze associations between all job and health variables. As a result, relations between work experience and disease(s) have not been known or well-defined in the rubber industry. Similar problems of defining exposure may be found in other chemically complex industries. Since a complete qualitative and quantitative description of "environment" is not possible, how can an objective assessment of work exposure be achieved? The Occupational Health Studies Group (OHSG) at the University of North Carolina has approached the problem of defining work experience in a chemically complex industry by grouping jobs into functionally homogeneous categories called occupational titles (OT's).' An OT is defined not by exposure per se, but by (1) process or function and (2) product (Figure 1, Table 1). OT's form a hierarchical classification, as each major process contains functionally similar subprocesses. For example, in the final inspection OT includes jobs related to finishing and repair (trimming, buffing, repair) and to inspection (sorting, classifying, labeling, inspecting). Depending on the study and the size of the study population, these groupings (e.g. tire inspection, tire repair) may be retained, or classified as one (e.g. final inspection). The level of classification chosen depends on the study design, size of population, and available resources. Just as one knows the
A preventive medicine program for a working population attempts to control toxicants so that exposure does not adversely affect health. To do this requires measurement of health outcomes, and, if there is a detrimental health effect. the measurement of the relevant etiologic agents. In this way. dose-response relations can be determined and safe working environments maintained. In the rubber industry, the job of defining exposure is a difficult one for several reasons. Hundreds of different ingredients are used in making different kinds of tires. tubes, and other rubber products. Little is known of the toxicity and worker exposures to most of these chemicals. The heat and pressure required in the production of rubber products results in the evolution of a myriad of reaction and degradation products whose qualitative and quantitative composition is largely theoretical. Furthermore, there are a large number of different jobs in this complex industry. A typical tire and tube plant has several hundred different jobs, and therefore. exposures. At present. we are unable to fully characterize the exposure of any single job; until recently, information concerning the relationship between jobs and health From the Occupational Health Studies Group. School of Public Health. University of North Carolina. NCNB Plaza, Chapel Hill, NC 27514. Address reprint requests to Dr. Gamble at the above address. This paper. presented at the 103rd Annual Meeting of the American Public Health Association, Chicago 1975. was submitted to the Journal March 1. 1976. revised and accepted for publication April 7. 1976.
768
AJPH August, 1976, Vol. 66, No. 8
OCCUPATIONAL EPIDEMIOLOGY TABLE 1-Description of Occupational Titles in Tire Manufacturing Occupational Titles
Compounding and Mixing Cutting and Milling Milling Extrusion
Calendering Plystock Preparation
Bead Building Tire Building Curing Preparation
Curing Final Inspection
Description
Raw ingredients (rubber, fillers, extender oils, accelerators, antioxidants) are mixed together in a Banbury mixer (BB). This internal mixer breaks down rubber for thorough and uniform dispersion of the other ingredients. The batches from the BB are further mixed on a mill, cooled and coated with talc so they are not tacky. The stock may return to the BB for additional ingredients, or go on to Milling. Final rubber mix is worked between two heavy iron rolls revolving toward each other. These are two kinds of mills feeding stock to a calender or extruder. A breakdown mill softens the rubber. The stock then goes to a feed mill for further working. The softened rubber is forced through a die forming a long, continuous strip in the shape of a tread. This strip is cut in appropriate lengths, and the cut ends are cemented so as to be tacky. The softened rubber from the feed mill is applied to fabric forming continuous sheets of plystock in the calender (a mill with three or more vertical rolls and much greater accuracy and control of thickness). The Plystock from the calender is cut and spliced to the correct size for tire building, and so the strands in the fabric have the proper orientation. Parallel steel wire is insulated with rubber vulcanizable into a semi-hard condition and covered with a special rubberized fabric. The beads maintain the shape of the tire and hold it onto the rim. The tire is built from several sheets of calendered plystock, treads and beads. The assembled tire is inspected, repaired, and coated with agents to keep it from sticking to the mold in vulcanization. Vulcanization changes compounded rubber from a sticky, plastic mass to a dry, elastic material with increased tolerance for temperature changes and increased strength. The tire is placed in a mold and shaped under heat and pressure. The cured tire is trimmed, inspected, repaired and labeled.
genus and species in each phylum of the plant and animal kingdom. so one knows the individual subprocesses and jobs in each OT category. OT's are defined independently of exposure; in fact, the precise environmental profile is not known. Except for short-term samples of solvents, the quantification of chemical species is not complete at any level of classification. Because of the large number of rubber stocks. the exposure profile for jobs and OT's is continually changing. Despite the variable nature of rubber production. however, it is possible to roughly characterize the dominant exposures in each OT
(Table 2). Mortality and morbidity experience can now be assessed in each category. without the diluting effect that oc-
curs when all rubber workers from functionally different jobs. processes. and therefore qualitatively different exposures are observed. If there is an occupationally induced effect on health, the observation of health experience by OT increases the ability to detect such an effect. It increases sensitivity by separating workers into relatively homogeneous categories, and increases specificity by identifying high risk OT's for specific health outcomes. The number of potential and plausible environmental causal agents is also reduced.
Applications Several studies in the rubber industry have indicated an
Figure 1. Production Stages in Manufacture of Tires AJPH August, 1976, Vol. 66, No. 8
769
GAMBLE, ET AL. TABLE 2-Summary of Major Contaminants in Tire Manufacturing Occupational Titles Environmental Exposure
Occupational Titles
Compounding and Mixing
Cutting and Milling Milling Extrusion Calendering Tire Building Curing Preparation Curing Final Inspt -'-n
Accelerators (e.g., thiazoles, guanidines, thiuram sulfides, carbamates). Antioxidants Fillers (carbon black) Extender oils Talc *Emission from Vulcanization Process Solvents *Emission from Vulcanization Process Solvents Variable exposure to solvents, talc *Emission from Vulcanization Products Cured rubber dust, solvents
*Emissions from the hot rubber mix can be of two sorts (based on theoretical considerations), and will not be the same for milling, calendering, and curing. 1. Volatization (1) Residual monomers (probably only milling and calendering)-styrene, acrylonitrile, chloroprene (b) Antioxidants and Antiozonants and Accelerators-higher loss in milling and calendering (c) Processing Aids-oils (d) Miscellaneous Ingredients-special ingredients (amines, esters, organic acids) and impurities (5-40 per cent of main ingredient). 2. Formation of New Compounds-Oxidative products are formed in milling and calendering; reductive products are formed in the mold during curing, oxidative products when the curing press is opened. The compound classes formed include amines and ammonia, organic sulfides, hydrocarbons, acids, esters, water. It has been estimated that 0.50-0.7 per cent volatile material would be released and conceivably 1,000 or more different compounds.
increased risk for a variety of health outcomes.2'7 An operational definition of work experience makes possible the identification of high risk jobs with specific health outcomes. the identification of causal environmental agents. and the establishment of safe levels of environmental exposure. The association of specific OT's with specific health outcomes can be approached as an exercise in hypothesis-generating and hypothesis-testing. The findings raise further questions for investigation as discussed below.
Hypothesis-generating An example of an epidemiologic study in the hypothesis-generating mode is the examination of the ten-year mortality experience of 6.678 male rubber workers.7 All jobs of individuals dying of selected causes of death were classified into OT's and compared with the work experience of a random sample of the total population. Figure 2 summarizes the ratios of time spent in each OT by cases compared to controls. The time periods in each OT are limited to greater than five years during the presumed etiologic period for these chronic diseases. These ratios provide an approximation of increased mortality risk associated with each OT. They also allow one to begin hypothesis testing. For example. the observed association of excess stomach. lung. and bladder cancer with OT's early in the manufacturing process raises questions as to the route of absorption, metabolic transformation. and the carcinogenicity of pigments (accelerators. antioxidants). fillers (carbon black. talc). degradation. and reaction products. There are suggestions in the literature implicating these or related compounds as carcinogens. For example. carbon black has long been known to adsorb carcinogens.8' " but the mortality experience from all kinds of cancer from 1939-1956 of workers producing carbon black was judged to be low when contrasted with comparable populations.'' Talc is a known respiratory carcinogen. "I but heretofore has not generally been consid770
ered as posing a gastrointestinal (GI) threat. Some pigments and products evolved from curing rubber are potential carcinogenic agents. but in curing are thought to not pose a high risk because of the small quantities evolved. These contradictory findings stimulate specific questions such as: Is there a GI insult in these OT's. or operationally. how much particulate is deposited in the upper airways. cleared to the mouth and swallowed? Heretofore. environmental measurements have measured total particulate (e.g. high volume samplers) and respirable particulate (deposited in lower airways with primarily systemic absorption). There is at present no good way to sample for particulate deposited in the upper airways. Thus we may not be measuring the relevant dose for the observed gastrointestinal health effect. Should we be concerned about whether workers are nose or mouth breathers. as this undoubtedly affects lung deposition. if not gastrointestinal insult? The association of stomach and colorectal cancers with the final inspection and repair OT raises similar questions about "rubber dust'". as extracts of automobile tire contain carcinogenic hydrocarbons. 2 Lednar. et al..'3 report on the use of OT's in a case control study of pulmonary disability. This study raises the interesting question as to effects of mobility or selective migration on associations of chronic disease with OT's. Do workers with symptoms tend to move to less symptom-producing jobs? Cross-sectional studies of current health status and exposure indices of workers are also underway. In a study of the effect of a particular rubber adhesive on respiratory function. workers were administered pulmonary function tests before beginning work and again six hours later. and environmental measures were taken concurrently. '4 The workers exposed to the adhesive had. as a group. significant reductions in lung function that were associated with particulate exposure. Only the workers in OT's of milling and calendering. AJPH August, 1976, Vol. 66, No. 8
OCCUPATIONAL EPIDEMIOLOGY Ratio (Cases/Controls) Occupational Title (OT)
St4tomach Cancer
Colorectal Cancer
Respiratory Cancer
Prostate Cancer
Bladder Cancer
0I 1 2
0 1 2
0 1 2
0 1 2
0 1 2
*
1. Receiving and Shipping
1.6
2. Compounding and Mixing
1.9
3. Mill-Mixing, Other Batch Prep
2.0
4. Milling
5. Calendering and Plystock
10. Curing
0.8
.
0.9
U
1.7
E 1.4 U
12. Maintenance
0.7
13. Mechanical Special Products
0.5
14. Reclaim
0.4
E*1.1
0.0
0.5
0.0
0.8
0.3
0.8
1.3
0.1
0.7
0.7
2.4
0.3
0.5
2.3
0.0
2.8
0.4
0.8
0.5 0.0
0.0
0.0
1.0
1.0
2.5
1.4
0.2
1.7
1.0
1.4
0.9
1.0 *
0
0.4
0.0
0.0
1.9
0.0
0.9 0.7
3.1
1.1
0.7
1.1
0.0
0.3
1.1
0.8
0.0
0.9
1.0
1.7
2.2
0.8
1.4
0.6
0.7
1.2
1.0
1.0
0.
1.2
1.5
.0
1.4
0.9 0.0
0.3
0.6
0.7
0.9
0.7
1.1
1.1
2.1
15. Synthetic Plant
.0
0.5
0.0
1.7
00.6
0.6
0.0
0.0
1.3
_
0
2.1
1.2 2.1
0 1 2
1.4
*
0.6
1.2
1.2
*
0.4
Diabetes Mellitus
1.7
2.0
1.5
2.1
2.2
11. Final Inspection
16. Miscellaneous
0.4
1.0
0.7
1.4
0.6
I 0.4
7. Tire Building
9. Tube Building
1.8
1.2
* 1.2
6. Extrusion
8. Curing Preparation
0.6
Ischemic Heart Disease 0 1 2
Lymphatic and Hematopoietic Cancer 0 1 2
1.3
0.6
2.9 0.4
0.0 3.5
FIGURE 2. Ratios of age-adjusted rates of exposure to specific OT's for cases compared to population sample (n = 1402). For example, 8% of stomach than 5 years in Receiving and Shipping, versus 5% of the population sample, giving a ratio of 1.6 (from Reference 7).
cases spent more
however, were observed to have statistically significant reductions in lung function. Although the number of workers in each OT are small, the findings are compatible with the hypothesis of a reaction or degradation product from the adhesive being adsorbed onto particulate, thereby increasing the effective dose. This type of experimental design shows the potential for not only pinpointing high risk OT's, but also determining exposure levels below which there is no measureable effect. In the rubber adhesive study, for example, there was no change in pulmonary function when "respirable" particulate levels were below 0.2 mg/m3. In this type of study, OT is the independent or exposure variable. Changes in pulmonary function (APF) is the dependent variable, or health effect. Response (APF) is used to assess the respiratory hazard of the OT. Cross-sectional environmental data are being systematically gathered in a variety of rubber products plants. Environmental samples are located by OT, providing comparability between plants, and making possible estimates of overall exposure levels and variability of exposures for the measured toxicants in plants and for processes where environmental measurements have not been made.
Hypothesis-testing The initial use of OT's and complete work histories began with the reported finding of an excess of leukemia deaths in a cohort of 6,678 male rubber workers.2 Because of the presumed leukemogenic properties of benzene, OT's were AJPH August, 1976, Vol. 66, No. 8
grouped into solvent and non-solvent exposed categories. When comparing cases and controls, a statistically significant association was observed between lymphatic leukemia and the solvent exposure categories.3 Armed with the epidemiological information of how a particular disease (leukemia) is associated with specific OT's, OHSG initiated in this plant a retrospective reconstruction of solvent use (particularly benzene). Purchasing and production records, quality control specifications, and plant blueprints are being used to construct an estimate of specific solvent exposures over time. Leukemia mortality and retrospective environmental estimates can then be used to determine the association (or lack of it) of leukemia with particular solvents (e.g. benzene, toluene, xylene). The reconstruction of an exposure profile of a handful of agents (solvents in this case) is in itself a large undertaking. Practically, it is not feasible to do this for all chemicals used in the rubber industry. Prospective surveillance of present-day workers has increased as a result of this finding. Sampling of solvents in the cross-sectional environmental survey has been increased. Benzene content of bulk solvents is monitored to ascertain and regulate the content of this agent. Workers in high risk jobs are observed for blood and chromosomal abnormalities. Dose-response The goal in occupational health is to prevent disease and ill-health by controlling causal toxicants. This is done by es771
GAMBLE, ET AL.
tablishing dose-response relations. The response can be as permanent as death, or as temporary as reductions in lung function over a shift. Defining exposure is more difficult. For acute responses such as APF over a shift, dose may be measured as respirable particulate in each OT (where the exposures are similar, and to varying extents known qualitatively). For chronic diseases, dose is a working lifetime of changing exposures. For a chronic disease in an industry with multiple insults. the complete work history must be utilized. The Experience Transformation Algorithm (ETA) computer program has been developed for this purpose.' Input to the program is the sequence ofjobs coded into OT's. Output is a cumulative measure of time spent by each worker in pre-specified groups of OT. Chronic disease characteristically is a progressive disease developing over a long time period. The ETA takes account of this. and can single out certain fractions of a worker's total work history (on the basis of age of the worker. etiologic period prior to disease. or calender period when a causal agent may have had greatest use). Since the exposure profile is largely unknown. OT's have been used as the surrogate measure of exposure. They provide the essential link between 'dose"' (exposure as measured by industrial process or product) and response (as measured by morbidity or mortality). With increased insight into the hazards of this industry, our classification of jobs may begin to look more like categories of different exposures. But however knowledgeable we become. we will be unable to foresee all relevant and hazardous exposures. Classification of jobs. independent of exposure. provide the essential link between environmental and medical information. Without medical data. the precise quantification of the exposure profile is a mammoth task. Without medical data on workers' response. the significance of exposure is difficult. if not impossible to evaluate. Without environmental data, the control of disease causing agents becomes a problematical and costly exercise. Even though the exposure profile is not complete. the association of biological response w ith work experience (OT's) can still be made. Control meas-
772
ures can be initiated in those OT's, and the search goes on for causal agents.
REFERENCES 1. Gamble. J. F. and Spirtas. R. Job classification and utilization of complete work histories in occupational epidemiology. J. Occup. Med.. (in press. 1976). 2. McMichael, A. J., Spirtas. R.. and Kupper. L. L. An epidemiologic study of mortality within a cohort of rubber workers. 1964-72. J. Occup. Med. 16:458-464. 1974. 3. McMichael. A. J., Spirtas. R.. Kupper. L. L.. and Gamble. J. F. Solvent exposure and leukemia among rubber workers: An epidemiologic study. J. Occup. Med. 17:234-239. 1975. 4. Mancuso, T. F.. Ciocco. A.. and El-Altar. A. A. An epidemiological approach to the rubber industry. J. Occup. Med. 10:213232. 1968. 5. Parkes. H. G. Health in the Rubber Industry. A Pilot Study. Manchester. England: A. Megson and Son Ltd.. 1966. 6. Fox. A. J., Lindars. D. C.. Owen R. A survey of occupational cancer in the rubber and cablemaking industries: Results of fiveyear analysis. 1967-71. Brit. J. Ind. Med. 31:140-159. 1974. 7. McMichael, A. J., Spirtas. R. Gamble. J. F.. and Tousey. P. N. Mortality among rubber workers: Relationship to specific jobs. J. Occup. Med. 18:178-185. 1976. 8. Falk, H. L. and Steiner. P. E. The identification of aromatic polycyclic hydrocarbons in carbon black. Cancer Res. 12:3039. 1952. 9. Falk. H. L. and Steiner. P. E. The adsorption of 3.4-benzpyrene and pyrene by carbon blacks. Cancer Res. 12:40-43. 1952. 10. Ingalls. T. H.. Risquez-lribarren. R. Periodic search for cancer in the carbon black industry. Arch. Env. Hlth. 2:429-443. 1961. II. Blejar. H. P. and Arlon. R. Talc: A possible occupational and environmental carcinogen. J. Occup. Med. 15:92-97. 1973. 12. Falk. H. L.. Steiner. P. E.. Goldfein. Breslow. A.. and Hykes. R. Carcinogenic hydrocarbons and related compounds in processed rubber. Cancer Res. 11:318-324. 1951. 13. Lednar. W. M.. Tyroler. H. A.. McMichael. A. J., and Shy. C. M. A study of the occupational determinants of chronic disabling pulmonary disease in rubber workers. Presented at 103rd Annual Meeting of APHA. November 20. 1975. Chicago. IL. 14. Gamble. J. F.. McMichael, A. J., Williams. T. M.. and Battigelli. M. C. Respiratory function and symptoms: An environmental-epidemiologic study of selected rubber workers. Presented to American Industrial Hygiene Conference. Minneapolis. Minn.. June 5. 1975. Am. Industrial Hygiene Assoc. Journal (in press. 1976).
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