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Diss Factsheets

Administrative data

epidemiological data
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
supporting study
Study period:
1975 to 1982
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Study well documented in the publication but with main deficiencies: no identification of the Zirconium compounds present, exposure estimations used, employees with radiological changes or poor lung function could have chose to leave employment and so were not taken into account, exposure duration not sufficiently long to detect frequently occurring chronic effects, limited population unlikely to detect a rare even

Data source

Reference Type:
A study of lung function and chest radiographs in men exposed to zirconium compounds
Marcus, R.L., Turner, S., Cherry, N.M.
Bibliographic source:
Occupational Medecine, 46(2): 109-113

Materials and methods

Study type:
cohort study (retrospective)
Endpoint addressed:
repeated dose toxicity: inhalation
Principles of method if other than guideline:
GLP compliance:

Test material

Constituent 1
Reference substance name:
Zirconium compounds
Zirconium compounds
Details on test material:
Zirconium compounds not identified
Form: dust


Type of population:
Ethical approval:
not specified
Details on study design:
male employees was set up at Magnesium Elektron Limited (MEL), Manchester, England. The target population was all men identified by the safety adviser as exposed, on a day to day basis, to zirconium compounds. Men who continued in employment were re-examinedin 1978 and 1982, and men who joined the company subsequent to 1975 and who took up work with exposure were also examined at these later dates.
A total of 178 men participated in the study. Of these 144 entered in 1975, 24 in 1978, and a further 10 in 1982. The mean age of the 144 men
joining the study in 1975 was 37.6 years (range= 17-61). They had, on average, been employed by MEL for 10.0 years (range=0-38) with 58.0% having worked for the company for less than 10 years, 21.7% for 11-20 years, 16.1% for 21-30 years, and 4.2% for more than 30 years. The 34 men who joined after 1975 had a mean age at joining of 27.2 years and a mean duration of employment of 5.2 years at the end of the study.
The occupational physician interviewed each man to obtain a general medical history, work history, summary of current symptoms and smoking habits. Specific attention was paid to eliciting information on exposure to dusts in any job prior to joining MEL (assessed byoccupational hygienist, who gave scores to jobs identified on the work history; pre-employment dust exposure was assessed as none, low or potentially important).

Chest radiographs
The first set of chest radiographs was taken in 1975, with subsequent radiographs in 1978 and 1982. At least one chest radiograph was obtained from each man within the study period, although not all men had a radiograph on each occasion. Report films were read independently in
randomized order by three experienced readers following the ILO guidelines for classification of radiographs for pneumoconiosis. A subset of films from men who had not been exposed to zirconium compounds was also included in the reading exercise, so that the panel could not presume that all films originated from exposed workers. Readers had no information on degree or duration of exposure. The median rating of the three readers was taken in each case. Side by side readings were also made of films from the same individual in temporal order for those men who had more than one radiograph. A subset of 60 films was also re-read by the three readers independently after the main reading.

Lung function tests
FEVi and FVC measurements were carried out at the medical centre at MEL at regular intervals throughout the study period. Measurements were recorded for 168 out of the 178 employees, and results on two or more occasions obtained for 136 (76.4%) men. A wedge bellows spirometer was used (Vitalograph, Buckingham, UK) and measurements were supervised by either the occupational physician or nurse. Workers were asked to perform three forced expirations, and the best result was recorded. All measurements were taken with the operative standing. The measurements were expressed as a percentage of expected values, adjusted for height and age, using the standard prediction nomogram in use at the beginning of the study. The FEVi/FVC ratio was also calculated for each result.
Exposure assessment:
Details on exposure:
Medical and personnel records were used to identify specific job titles and work locations within the plant. A list of 34 jobs/locations was drawn up and two company safety advisers, one currently employed and one retired, were asked to assess the dustiness of each job. Consideration was given to any change in process which had altered dust levels for the workforce over the period of employment.
A scale for total dust was constructed consisting of four categories (0-3):
no dust (probably less than lmg/m3),
low dust (probably 1-2.5 mg/m3),
medium dust (probably 2.5 to 10 mg/m3), and
high dust (probably greater than 10 mg/m3).
The number of years spent in each job was multiplied by the score on the dust scale and a cumulative dust exposure score calculated for each man. At the start of the study 51.1% were in low dust jobs, 44.8% in medium dust jobs, and 4.1% in high dust jobs. The mean cumulative exposure (years x dust level) was 12.9 'dust years' at the start and 22.3 at the end of the study.

Previous dust exposure:
Of the 178 men, 144 (80.9%) had codable information on prior occupational exposure to dust. Substantial dust exposure was found for 52 men who
had been in jobs such as coal mining, foundry work, and cotton milling.
Statistical methods:
Cumulative exposures were calculated to the date of the last chest radiograph and last lung function for each worker. ILO readings were converted to a numeric scale (0/0=0; 0/1 = 1; 3/3=9) and Spearman rank correlations computed with cumulative and prior dust exposures. Analyses of variance and multiple regression were used to investigate the relationship between lung function and exposure.

Results and discussion

Chest radiographs
The last available chest radiograph was considered to be of acceptable technical quality for 167 of the 178 men. Of these, 163 were used in the analysis. The median ILO classification was greater than 0/1 for three (of 163) films. The mean cumulative exposure to last radiograph of these three men was 18.67 (SD=16.26) compared with 16.79 (SD =12.84) for those with 0/0 or 0/1 (i=1.60, p=0.41).
The Spearman rank correlation between zirconium exposure and ILO classification was 0.08 (p=0.28).
The study was set up with particular concern for the appearance of pulmonary granulomas. No granuloma was seen but a calcified nodule was read in the films of 12/175 (6.9%) men exposed to zirconium compounds prior to their final chest radiograph. No correlation was found between the presence of nodules on chest radiographs and duration of exposure to zirconium compounds (R=0.04, p=0.61), cumulative dust exposure (R=0.05, p=0.53), or age (R=0.ll, p=0.14).
Chest radiograph readings were also related to previous dust exposure. All 38 films for those with no history of dusty jobs were classed as 0/0 or 0/1 but this reading was recorded for only 46/48 with low prior exposure and 45/49 with substantial prior exposure.

Lung functions
For each man, first and last lung function measurements within the study period were identified. Ten subjects had no lung function test, and four had no exposure to zirconium prior to their last available test, leaving 164 men available for inclusion in the analysis.
Information on dust exposure in previous jobs was available for 140 of the men with lung function scores.
Of these 135 had acceptable chest radiographs when read by t e panel. Dust exposure in previous jobs did not relate to first FEVi or FVC but did relate to first FEVi/FVC ratio which decreased, from 0.79-0.73, with increasing prior dust exposure.
Inspection of results of the last lung function test available suggested no trend between grouped cumulative exposure and any of the measures of lung function. Analyses of variance for FEVi,FVC, and FEVi/FVC ratio with cumulative zirconium exposure category showed no significant effect of exposure.
Smoking data were available for 159 out of the 164 men. In an analysis of variance, also shown both FEVi and FVC were significantly related to smoking and lung function, but there was no interaction between smoking and zirconium exposure either for FEV, (F=1.62,p=0.19) or for FVC results (F=0.32,
p=0.81). No relation was found between FEVi/FVC ratio and either exposure, smoking or their interaction. The most recent lung function test results were examined in a regression analysis with cumulative zirconium exposure as a continuous scale, adjusted for binary factors reflecting prior dust exposure, radiographic reading and cigarette smoking. Cigarette smoking and prior dust exposure were both predictive of FEVi, and prior dust of FEVi/FVC ratio, but cumulative exposure showed no relation to any of these measures of lung function.
Confounding factors:
Smoking habits, previous dust exposure
Strengths and weaknesses:
Zirconium compounds not identified and exposure estimated instead of measured
Employees with radiological changes or poor lung function could have chose to leave employment.
Workers with sufficiently long duration (37/178 exposed for more than 20 years) to detect frequently occurring chronic effects were not include in this study, and no such effect has been found. The limited population would be unlikely to detect a rare event.

Applicant's summary and conclusion

No evidence was found of pulmonary granulomas or of a relation between cumulative exposure to dust and ILO classification of radiographs, presence of calcified nodules or lung function. The results presented do not support either non-specific pulmonary function changes or specific radiological findings attributable to zirconium exposure in this population.