Health Studies of High Nickel Alloy Workers in the U.S.
#4 -- 1997 Published by the Nickel Development Institute
Summary of Health Studies
Summary Description of the 1994 Redmond Update Study
Description of Work Areas
Exposure Measurements
Comment
References
Five epidemiological reports of workers employed by various U.S. high nickel alloy producers have been published since 1982. All were undertaken by the Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh.
The first study, by Enterline and Marsh, 1982, involved two cohorts of workers at a single U.S. plant and followed their mortality statistics through to 1977.
The second study on these cohorts, followed through to 1982, is found in the report of the International Committee on Nickel Carcinogenesis in Man, 1990. The results of this second report indicated "no strong evidence of excess cancer risk among workers in either cohort."
The third study, by Redmond et al, 1984, evaluated the cause-specific mortality patterns for high nickel alloy workers as a whole and for workers who were employed at jobs in 11 major work area classifications.
For this 1984 study, an industry-wide survey of producers of high nickel alloys was conducted to identify specific plants that had been producing alloys for a period of time sufficient for the development of diseases with long latency periods, i.e. twenty or more years. Based on the results of the survey, twelve plants were selected for inclusion in the study. Work histories and vital status through 1977 were obtained for the 28,261 individuals included in the cohort. Mortality patterns were analysed by job classification and length of employment.
The principal overall finding of the third study was: "no statistically significant increased risk for cancers of the lung, nasal sinuses, larynx, or kidney among workers involved in the production of high nickel alloys."
The fourth study, by Redmond et al, 1994, reexamined the earlier studies referred to above and added 11 years of mortality data from 1977 to 1988. The combined populations of the cohorts, which include 31,165 individuals in 13 plants, provide a unique data set for assessing occupational cancer risks from exposure to nickel. The population represents a significant portion of all workers exposed to nickel in the production and fabrication of high nickel alloys.
The main focus of the 1994 study was to examine the potential health risks of cancers and some non-malignant diseases that are believed to be of most concern regarding exposure to various forms of nickel. Emphasis was placed on the mortality experience from cancers of the nasal sinuses, larynx, lung, colon and kidney, and from cerebrovascular disease, heart disease and non-malignant respiratory disease.
The fourth, 1994, study found "no evidence to support an increased risk due to nasal sinus cancer, laryngeal cancer, cerebrovascular disease, or non-malignant respiratory disease."
It also found that:
"There was an approximately 13% statistically significant excess of lung cancer mortality in the cohort. The risk appeared to be confined to individuals employed in Allocated Services* and a definitive link to occupational exposures was lacking. An assessment of duration of employment data did not support a contention that lung cancer mortality excesses seen in this study were due to occupational exposure. It is possible that some confounding risk factor such as smoking is associated with longer term employment in Allocated Services. What portion of the excess risk may be attributed to differential smoking habits cannot be directly determined since information is not available on smoking history for this cohort."
"A significant excess risk for colon cancer was found in non-white males, predominantly at a single plant but because of the small numbers of deaths, evaluation of a dose-response relationship would not be reliable."
"Kidney cancer for all plants combined did not show any excess although white males ever working in Melting had a significant increase. There was no clear association between nickel exposure and kidney cancer in this cohort, a finding which is consistent with other studies (Shannon et al. 1991; Roberts et al. 1989; International Committee on Nickel Carcinogenesis in Man, 1990; Enterline et al. 1982). There was no evidence of an increased risk from mortality attributed to nephritis and nephrosis. The results were similar to the findings of Shannon et al, 1991."
"A significant increase in risk of ischemic heart disease mortality was found among white, male workers but no occupational link was noted. This was not a finding in the original study and was not identified in previous studies of nickel workers." Again, no dose-response relationship was found.
It was also recognized, however, that "The apparent increased risk (of ischemic heart disease) may be an artifact, reflecting use of the general U.S. population as the control group. It might be that the socioeconomic and demographic characteristics of the study cohort differ from those of the total U.S. population, making the latter an inappropriate control group. A reanalysis of the epidemiological data will examine the influence that the choice of control group has on the study results."
The fifth study, the reanalysis referred to above and reported in 1996, added two new reference groups. One compared the nickel alloy cohort mortality with that of the populations in geographic proximity to each of the nickel alloy plants. This controls for geographic variability observed in many cause-specific mortality rates. The other compared the nickel alloy workers' mortality with that of an industrial population of steelworkers whose socioeconomic status is likely to be similar to that of the nickel alloy workers. The steel workers' comparison also accounted for some selection factors associated with disease risk in working populations.
To quote Dr. Redmond regarding the results of the 1996 reanalysis, "Our findings suggest that the pattern of the risks derived for the various work areas and sex/race subgroups is similar across the three comparison populations, although elevated relative risks tend to be lower when the local population comparisons are used. Mortality from all causes or all malignant neoplasms (tumors) is not increased. There is a 13% increased risk for lung cancer overall among nickel alloys workers when compared with the US population, but this excess is no larger than that which could be explained by some confounding factor such as cigarette smoking. In addition, comparisons made to the local populations show no excess.
Excesses of statistical significance among certain subset populations are found for colon cancer among nonwhite males (primarily from one facility), and kidney cancer among white male workers employed in melting regardless of the comparison. However, there is no strong epidemiologic evidence causally associating occupational exposures with these excess risks."
The fourth, 1994, update study and the fifth, 1996, reanalysis are important for two reasons. Firstly, they represent a very large group of workers, in excess of 31 thousand. Secondly, the mortality observation periods began 21 to 40 years before the end of follow up in 1988, with the majority of workers having 27 or more years of follow up. This is an acceptable time-frame for epidemiological credibility.
The findings of all these studies are clearly of interest to high nickel alloy workers in the United States. They should also be of considerable interest to the nickel alloy industry throughout the world because many of the process operations required to make high nickel alloys are common to all nickel alloys, including both stainless and alloy steels, and because these operations are practised in much the same way wherever nickel alloys are made.
All these studies, individually and collectively, support the notion that nickel alloys, and by association, nickel metal, can be and are produced without undesirable or unacceptable impact on worker mortality.
Summary Description of the 1994 Redmond Update Study
The research entailed four major objectives:
- Update of the vital status of cohort members through 1988
- Review and summarization of available exposure data and work area classifications
- Re-examination of the exposure-response relationships for cause-specific mortality found to be elevated in the first Redmond study
- Examination of the exposure-response relationships for cause-specific mortality found to be elevated in the update or suggested by the literature to be related to nickel exposure.
In many industrial plants, including high nickel alloys, there are commonly dozens or hundreds of names that attach to the various process operations and job titles of the workers doing them. Many of these jobs and operations are quite similar from a function and exposure standpoint, however, and can be grouped into a much smaller and more manageable number of activities or work areas for purposes of analysis. Exposure data and mortality information are therefore grouped and assessed in relation to a practicable number of distinct work areas and determinations are made regarding differences in exposures and mortalities from one work area to another.
Work area classifications were established as part of the project effort in the first Redmond study. Lists of coded job titles were developed by a committee of plant representatives for all study plants. After all job titles across all plants had been identified and coded to a department, an exposure sub-committee developed a general classification scheme of 11 work areas. Each department was assigned to one of the work areas based on the nature of work and exposure associated with the department. The work area of Allocated Services was further divided into four areas: Pattern and Die, Guards and Janitors, Maintenance and Support Services. The types of exposure encountered by workers employed in these areas are shown in Table I.
With inclusion of the additional plant in the 1994 update study, the various departments within this plant had to be classified, using the Work Areas defined for the first Redmond study. Only four departments from this plant contained job titles suggesting activities which would not uniquely classify them into one of the eleven work areas. The decision was made to allocate these departments based on the major activity within the department.
Table I: Types of Exposures
| Work Area | Types of Exposure |
| 1. Cold Working finishing | metal dusts, lubricants; annealing, pickling, cleaning, operations nearby |
| 2. Hot Working | metal dusts, oxides, lubricants; cutting, grinding operations nearby |
| 3. Melting | metal dusts, oxides, fumes |
| 4. Grinding | metal dusts, oxides, abrasives |
| 5. Allocated Services Including Maintenance | welding fumes, dusts, solvents, asbestos, lubricants, cleaning materials, resins, chemicals |
| 6. Foundry | metal dusts, fumes, mold materials, refractories, chemical binders, aldehydes, acidic compounds, amines, creosols, phenols |
| 7. Power Metallurgy | metal powders -- nickel, iron, chromium, titanium, others |
| 8. Administrative and Technical | contaminants from adjacent work areas, including solvents |
| 9. Pickling and Cleaning | acid mists, alkaline aerosols, solvent vapours |
| 10. X-Ray | - |
| 11. All Other Areas | - |
Limited plant-specific data were provided as part of the first Redmond study. Most of these exposure measurements were obtained after 1970 by personal sampling techniques. They are inadequate for use in developing exposure indices to associate with mortality findings but they do provide a crude basis for comparing work areas. These data are presented in Table II.
Table II: Exposures to Airborne Nickel by Work Area
| Work Area | Nickel Concentration, mgNi/m3 | |
| Range | Average | |
| Cold working | 0.001 - 2.3 | 0.0064 |
| Hot working | 0.001 - 4.2 | 0.111 |
| Melting | 0.001 - 4.4 | 0.083 |
| Grinding | 0.001 - 2.3 | 0.298 |
| Allocated Services | 0.001 - 0.350 | 0.071 |
| Foundry | 0.004 - 0.900 | 0.098 |
| Powder Metallurgy | 0.001 - 60.0 | 1.5 |
| Administrative-Technical | 0.001 - 0.015 | 0.008 |
| Pickling & Cleaning | 0.002 - 0.015 | 0.008 |
For the additional plant in the 1994 update study, the company had made estimates of exposure for each department based on limited historic measurements. This information was adjusted for known process changes and environmental controls to estimate historical patterns of exposure. Although there are uncertainties, in most instances it is reasonable to assume that the historical exposures were either the same as or higher than those in more recent periods.
The 1994 update provided eleven years of additional follow-up for the plants originally studied by Redmond and further expanded the cohort by about ten percent by inclusion of the workers studied by Enterline and Marsh. The enhancements to the earlier studies allowed for the inclusion of the causes of an additional 6,500 deaths and substantially increased the number of workers in the cohort with 25 to 30 years since first employment in the high nickel alloys industry. This is particularly important since many of the site-specific cancers of interest have long latency periods. Extended follow-up places many of the cohort members at an age when cancers are more likely to occur.
The results of this 1994 study and the subsequent 1996 reanalysis confirm the lack of epidemiologic evidence for exposure-related excess cancer mortality in workers employed in the high nickel alloys industry.
Enterline, P.E. and Marsh, G.M. Mortality among workers in a nickel refinery and alloy manufacturing plant
in West Virginia.
J NATIONAL CANCER INST 68, p.925-933, 1982.
International Committee on Nickel Carcinogenesis in Man. Report of the International Committee on Nickel
Carcinogenesis in Man.
SCAND J WORK ENVIRON HEALTH 16, p.1-84, 1990.
Redmond, C.K. "Site-specific cancer mortality among workers involved in the production of high nickel
alloys", 1984. In: Sunderman, F.W., Jr. ed., Nickel in the Human Environment.
(IARC Scientific Publications No. 53), Lyon, IARC, p. 73-86, 1989.
Shannon, H.S., et al. Mortality of 11,500 nickel workers - extended follow up and relationship to
environmental conditions.
TOXICOLOGY AND INDUSTRIAL HEALTH 7(4), p.227-294, 1991.
Roberts, R.S., et al. A study of mortality in workers engaged in the mining, smelting and refining of
nickel. II: Mortality from cancer of the respiratory tract and kidney.
TOXICOLOGY AND INDUSTRIAL HEALTH 5, p.975-993, 1989.
