Search

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.

We exposed 16 healthy human volunteers to air temperatures ranging from 7 to 39 degrees C and measured nasal mucus flow, nasal airflow resistance, forced vital capacity, rectal and body surface temperature, and air temperature within the nasal passage. A moderate fall in nasal mucus flow rate in the anterior and middle parts of the nose was observed with temperature above or below 23 degrees C. The nasal airflow resistance decreased in warm air and tended to increase in cold air. No significant changes in forced vital capacities or rectal temperature were observed. Nasopharyngeal end inspiratory air temperatures at 23 degrees C averaged 32.6 degrees C. At environmental temperatures of 15 and 31 degrees C they average 28.1 and 32.8 degrees C, respectively. Although we found alterations in upper airway function associated with altered inspired air temperature, over the range of 32 degrees C studied these changes were of minor physiological significance.

Nasal mucociliary clearance was measured in healthy young human subjects and tracheal clearance in the experimental animal under a wide variety of conditions. There is a broad range of clearance rates whether at standard ambient conditions (23 degrees C, 50% relative humidity) or in the face of a number of environmental variables. The degree to which those differences are attributable to the effectiveness of ciliary beating or the character of airway secretions is not known. Studies of tracheobronchial secretions simultaneous with clearance measurement in the anaesthetized dog have not yet provided a definite answer. Variations in upper respiratory defence mechanisms may bear some relationship to the aetiology of small airway disease in the lungs.

The nasal mucus flow, lung function, subjective response, and psychometric performance of 16 young healthy subjects was studied during 6-h exposures to clean air and to 10, 40 or 100 ppm of toluene under controlled conditions. The toluene exposures did not affect nasal mucus flow or lung function. At 100 ppm irritation was experienced in the eyes and in the nose. There was a significant deterioration in the perceived air quality and a significant increased odor level during all exposures to toluene. The test battery investigated visual perception, vigilance, psychomotor functions, and higher cortical functions and comprised five-choice, rotary pursuit, screw-plate, Landolt's rings, Bourdon Wiersma, multiplication, sentence comprehension, and word memory tests. In these eight tests measuring 20 parameters, no statistically significant effects of the toluene exposure occurred. For three tests (multiplication errors, Landolt's rings, and the screw plate test) there was a borderline significance (0.05% less than p less than 0.10%). The subjects felt that the tests were more difficult and strenuous during the 100-ppm exposure, for which headache, dizziness, and feeling of intoxication were significantly more often reported. The exposures to 10 and 40 ppm did not result in any adverse effects.

The objective of the present investigation was to study the influence of the occupational nickel exposure on the concentration of nickel in nasal mucosa, plasma and urine. Plasma, urine and biopsy specimens of nasal mucosa from 318 nickel workers, 15 retired nickel workers and 57 non-exposed controls were analyzed for nickel by atomic absorption spectrometry. The results showed that nickel exposure led significantly to raised nickel concentration in nasal mucosa, plasma and urine both in active and retired nickel workers. The average nickel concentration in the nasal mucosa was highest in workers exposed to the highest atmospheric nickel concentration, inhaled as nickel subsulphide and oxide dust. Workers exposed to aerosols of nickel chloride and sulphate at a lower atmospheric nickel concentration had, on the other hand, the highest mean nickel concentration in plasma and urine. The mucosal, plasma and urine nickel concentration were significantly correlated to duration of nickel exposure. The accumulated nickel in the nasal mucosa was retained for years after termination of the nickel exposure, and slowly released with an estimated half-life of 3.5 years.

Biopsy specimens from nasal mucosa of 30 nickel-exposed individuals and 6 controls were analysed by atomic absorption spectrophotometry to determine the content of nickel, copper, cobalt, zinc and iron. Timm's sulphide silver staining method was used for visualizing heavy metals in cryostat sections of biopsy material from each individual. The purpose of the investigation was to study the sulphide silver staining pattern in nasal mucosa of nickel-exposed individuals and controls, and to establish whether variations in heavy metal concentrations, especially nickel, affect the histochemical pattern in the mucosa. No consistent differences were found in the histochemical pattern between biopsies with high and low concentrations of nickel or any of the other metals. Some difference in epithelial types between specimens from the nickel-exposed group and the control group was seen, but the staining pattern was quite similar for corresponding epithelial types in the two groups. Two nasal carcinomas from nickel workers were virtually unstained with the sulphide silver staining method.

We studied nasal mucous flow, airway resistance, and subjective response in 16 young healthy subjects during 5-hour exposures to 2, 10, and 25 mg of inert dust per m3 in an environmental chamber. The dust was a fully polymerized plastic dust containing carbon black. The number of these particles in room air, expressed as a per cent of the total number of particles was 36, 41, 14, 7, and 2, respectively, for the aerodynamic size ranges less than or equal to 1.8, 1.9 to 5.3, 5.4 to 8.9, 9.0 to 12.4, and greater than or equal to 12.5 micron. No significant changes in nasal mucociliary clearance rate or nasal resistance were observed. At all dust concentrations there was a decrease in 1-sec forced expiratory volume, but not in the forced vital capacity or the forced expiratory flow during the middle half of the forced vital capacity. The nasal penetration fraction of particles was approximately 55 per cent for the smallest particles and 20 per cent for the largest particles. Discomfort was proportional to the concentration of dust, but lagged almost 2 hours behind the changes in dust concentration. The discomfort was never excessive; the main complaints were dryness in the nose and pharynx.

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.

Histochemical methods and energy dispersive X-ray micro-analysis (EDX-analysis) were evaluated in model experiments and on tissue sections for their usefulness in detecting traces of metals in biological tissue. The goal for this study was to establish a method for localization of nickel deposits in the nasal mucosa, where it has been found in concentrations between 1 and 40 microgram/g in nickel exposed individuals. The histochemical methods tested were staining with dimethylglyoxime, rubeanic acid and dithizone, the Turnbull and Prussian blue methods and TIMM'S sulphide silver procedure. In model experiments nickel-, cobalt-, copper-, zinc- and ironsalts were applied to thin-layer chromatography sheets (TLC-sheets) and stained by the histochemical methods. Spots containing 500 and 50 ng of these metals represented the smallest amounts that could consistently be detected in these experiments, except for the sulphide silver method which seemed a little more sensitive. With the latter method, moreover, zinc was detected in 40 micrometer thick cryostat sections of gelatine made up with 1 microgram/g of the metal. For nickel the corresponding figure was 10 to 50 microgram/g. On specimens of nasal mucosa from nickel-exposed workers, a faint colour was obtained in 40 micron thick cryostat sections from specimens that had been immersed in dithizone, but the colour was too weak for histological analysis. None of the other coloured chelating agents caused noticeable staining when applied to blocks or to cryostat sections. TIMM'S sulphide silver method caused strong staining of the basal layers of the surface epithelium and of fibroblast-like cells in the underlying connective tissue. This staining pattern is described in more detail in a separate report. Rat liver tissue was analyzed by atomic absorption before and after araldite embedding. Blocks of gelatine made up with nickel, copper, zinc and iron were embedded in epoxy resin and analyzed by atomic absorption. Large changes in the metal concentrations, usually an increase, were found after embedding. Ultrathin sections from this material were used to test the sensitivity of the EDX-equipment. Referring to the concentrations determined by atomic absorption in the embedded material, iron was detected at 1215 microgram/g and 362 microgram/g (gelatine standards) but not at 167 microgram/g (rat liver). Similar values could not be determined for nickel, copper or zinc, because of background radiation resulting from the presence of these metals in the instrument. We did not succeed in establishing a procedure for detecting nickel deposits in nasal mucosa with any of the methods which were tested. The most sensitive but least specific of the tested methods for visualizing heavy metals in the nasal mucosa, was TIMM'S sulphide silver procedure. The preparation of tissue for this method is discussed.