Rates of regression and progression of dysplastic lesions in the nasal mucosa in nickel workers: a Markov model approach.

Nasal epithelial dysplasia is considered a precancerous state. From 1976 through 1989, regular screening for such lesions has been performed among workers at the Falconbridge nickel refinery in Kristiansand. The longitudinal data thus obtained have been evaluated to ascertain to what extent, if any, pre-existing dysplasia can regress when exposure to nickel is reduced. A total of 418 pairs of observations were available from 243 workers. Interpretation of the data is complicated by the fact that dysplasia may remain undetected in small biopsies and the probability of detection of existing dysplasia was, therefore, incorporated into the two-state Markov model. Transition probability rates were estimated by maximum likelihood. The results suggest that regression of dysplasia has taken place and that regression rates increased with time. This finding probably reflects a decreased exposure resulting from a combination of a reduction in airborne nickel, improved personal hygiene and allocation of workers with dysplasia to work in areas with lower nickel exposure. Our results indicate that the chance of developing carcinomas related to nickel exposure is reduced. There are, however, indications that dysplasias continue to develop at a low rate.

Increased incidence of chromosomal aberrations in peripheral lymphocytes of retired nickel workers.

Chromosomal aberrations and sister chromatid exchanges were analysed in the peripheral lymphocytes of nine retired nickel refinery workers 4-15 years after the retirement and compared with 11 matched non-nickel exposed controls. None of the controls had previous occupations with known relation to induction of chromosomal aberrations nor sister chromatid exchanges. The groups were equal as to socioeconomic status and environmental factors other than the occupational ones, which could influence the chromosome parameters, were to the largest possible extent excluded. The nickel workers' previous occupational employment involved exposure to inhalation of furnace dust of Ni3S2 and NiO or aerosols of NiCl2 and NiSO4. The concentration of nickel in the working atmospheres has been higher than 1.0 mg/m3 air and the exposure time more than 25 years. The retired nickel workers showed an increased incidence of breaks (p less than 0.001) and gaps (p less than 0.05) but no difference in the incidence of sister chromatid exchanges when compared with the controls.

Histological changes, rhinoscopical findings and nickel concentration in plasma and urine in retired nickel workers.

Histological examination of nasal biopsy specimens, rhinoscopical evaluation and nickel analysis in plasma and urine were performed on 59 retired nickel workers. The histological characteristics were graded according to a numerical classification table. Workers with short employment and short retirement time had a significantly lower mean histological scores than those with long employment and long retirement. Thirteen persons (22%) showed epithelial dysplasia, possibly representing precancerous lesions. Also included in the material were four cases of nasal carcinoma. Presence of hyperplastic/polypoid nasal mucosa was inversely related to the duration of retirement, possibly reflecting gradual regression of the mucosal swelling after termination of the irritation. The nickel concentration in plasma and urine was significantly higher among former roasting/smelting workers than in former electrolysis and non-process workers. This is probably a consequence of the slow release of heavy soluble nickel compounds that have accumulated in the organism at the former place of work.

Cancer of respiratory organs among workers at a nickel refinery in Norway.

In a previous report (Pedersen et al., 1973) an excess risk of respiratory cancer among Norwegian nickel workers was demonstrated. The number of cancer cases was relatively small for the study of temporal changes in exposure. In this report the number of cancer cases increased by 70% through an extended follow-up to 1979, and the results published previously were confirmed. Data on smoking habits of the employees at the nickel refinery have now become available. The interaction between smoking and occupational nickel exposure is assessed by comparing the excess risk of lung cancer caused by smoking in the study group and in a sample of the general population. It is shown that the interaction is closer to being additive than multiplicative. This observation has methodological implications for studying temporal changes in occupational exposure. These implications are discussed. No substantial reduction in occupational exposure at the nickel refinery can be observed as far as lung cancer is concerned. For nasal cancer, however, the risk is much smaller among those employed around 1960 than among those employed around 1930. The difference in trend of occupational risk for the two types of cancer cannot be explained by the data presented.

Nasal histology and nickel concentration in plasma and urine after improvements in the work environment at a nickel refinery in Norway.

Nasal histology and nickel concentration in the plasma and urine of nickel workers were reexamined after 4 a for an evaluation of the effect of improvements in the refining process and work conditions. Ninety-eight (31%) nickel workers who were part of a previous study were reexamined. In addition, 33 of the original 38 workers with nasal epithelial dysplasia were studied for possible regression of the histological changes. Reduction in the atmospheric content of nickel and improved hygienic conditions lowered the concentration of nickel in plasma and urine by approximately 50%. The mean histological score and frequency of dysplasia was virtually the same in the two investigations, 12 and 13%, respectively. Nasal biopsies are of limited diagnostic value in the examination of individual cases. However, the method seems to be of value in identifying and monitoring groups of persons with increased risk of developing nasal carcinoma.

Variations of nickel in plasma and urine during the work period.

One of the basic problems in monitoring exposure of nickel refining workers has been the unclear correlation between plasma nickel, urine nickel, and airborne nickel during the eight-hour work period or throughout the 24-hour day. In previous studies the authors have demonstrated the value of biological sampling in an occupational health program in the nickel processing industry. Whether a single plasma or single urine sample is an adequate gauge of exposure or whether 24-hour urine specimens or a three-day average plasma level are more accurate indices remained to be determined. The purpose of this paper is to report the results of studies of diurnal variations which affect the significance of single biological samples. In addition, data gathered on the correlation of plasma and urine nickel levels with soluble and insoluble nickel compounds in the atmosphere are presented.

Nickel-related cancers of the respiratory tract.

Nickel-related cancers of the respiratory tract have been recognized for nearly 50 years and represent a unique opportunity for prevention among refinery workers. Studies of exposed employees have been conducted in which evaluations were made of the histopathologic changes in the respiratory mucosa and the body burden of nickel was measured by regular plasma nickel determinations. The sites of tumor predilection are related to airflow patterns of the nose and tracheobronchial tree. The metaplastic changes in these areas are accompanied by increased tissue concentrations of nickel. Close monitoring of nickel workers has led to a lower incidence of respiratory cancers and earlier diagnosis.

Histopathological changes of the nasal mucosa in active and retired nickel workers.

Histological examinations were made on nasal biopsy specimens from the middle turbinate in 318 active and 15 retired nickel workers and in 57 controls, to study the prevalence of nasal carcinoma or possible precancerous mucosal changes in nickel-exposed individuals. The histopathological changes were evaluated according to a point-score scale, and the results were correlated to age, smoking habits, duration and type of nickel exposure and to nickel concentrations in nasal mucosa, plasma and urine. The explanatory values of these factors on the histopathology were estimated by stepwise multiple regression analysis. Two nickel workers from the roasting/smelting department (0.6%), both employed 28 years at the plant, had nasal carcinoma. Epithelial dysplasia was found in about 12% of active and 47% of retired nickel workers. One of the controls, a male carpenter, had dysplasia. These histopathological changes may be precancerous lesions, as they are almost exclusively found in active and retired nickel workers with enhanced risk of nasal carcinoma. Loss of respiratory epithelium and development of squamous epithelium were regarded as unspecific histopathological changes. These changes were seen in all groups, even though in significantly higher incidence in the nickel-exposed groups. Duration of nickel exposure, type of nickel-refining work and tobacco consumption were the independent variable that, taken altogether, had the highest explanatory values for the histopathological changes.

Histopathologic changes of nasal mucosa in nickel workers: a pilot study.

Histologic examination of standard biopsy specimens from nasal mucosa were performed on 98 former and present employees at a nickel refinery and 61 controls. Histologic characteristics of the epithelium were graded blindly according to a point score table. The histologic scores were compared to certain epidemiologic data, such as the degree and duration of nickel exposure, duration of industrial work without nickel exposure, age, and smoking habits. High histologic scores were correlated to high nickel exposure, to the duration of this exposure, to age, and to industrial work not involved with nickel. One person with nasal carcinoma was detected in the nickel-exposed group. During the investigation period, three additional nasal carcinomas in former nickel workers were discovered and later included in the study. Furthermore, 18 cases of epithelial dysplasia were found in the nickelexposed group, but none among the controls. The cases with nasal carcinomas were or had been working with processes that gave an estimated high nickel dust exposure. All the individuals with epithelial dysplasia were nickel process workers.

Preventive health program for nickel workers.

The possible hazards of exposure to certain nickel compounds during nickel refining have been recognized for over 40 years. Much progress has been made in worker protection by cleaning up the process and by other protective means, and improved personal hygiene. The problem in the past has been determining those employees who are most exposed. This has been accomplished in this project by regular plasma and urine nickel determinations, demonstrating that nickel process workers absorb nickel which can be measured in plasma and urine. It was found that the highest plasma and urine nickel levels were seen in workers in those departments in which the greatest incidence of respiratory cancer occurs. Whether persistently elevated plasma nickel can be correlated with the eventual development of respiratory tract cancer is the subject for continued years of follow-up. It is not possible to conclude at this time that there is any association between the raised plasma and urine nickel and the incidence of cancer.