Registration Dossier

Diss Factsheets

Toxicological information

Exposure related observations in humans: other data

Currently viewing:

Administrative data

exposure-related observations in humans: other data
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Study of influence of zirconium exposure on radiographic changes or pulmonary function tests. Well described study with some limitations: assessment of dust levels was to a large degree based on judgement rather than actual measurements, however it is reported that such data were correctly ranked. LImited number of study subjects.

Data source

Reference Type:
A study of lung function and chest radiographs in men exposed to zirconium compounds
Marcus RL, Turner S, Cherry NM
Bibliographic source:
Occup. Med. Vol 46, NO. 2, pp 109-113

Materials and methods

Type of study / information:
Study undertaken to examine the effects on chest radiographs and lung function tests of exposure to zirconium compounds over many years.
Principles of method if other than guideline:
Occupational and medical history, chest radiographs, dust exposure and previous dust exposure were assessed and lung function tests were performed.
GLP compliance:

Test material

Constituent 1
Reference substance name:
Automatically generated during migration to IUCLID 6, no data available
Automatically generated during migration to IUCLID 6, no data available
Details on test material:
- Name of test material (as cited in study report): zirconium compounds


Ethical approval:
not applicable
Details on study design:
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 Magnesium Elektron Limited (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.
Exposure assessment:
Details on exposure:
TYPE OF EXPOSURE: exposure to dust of zirconium compounds

TYPE OF EXPOSURE MEASUREMENT: historic data on dustiness of the work site; For the present study company medical and personal records were used to identify specific job titles and work locations within the plant. A list of 34 jobs/locations was drawn up and company safety advisers 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.

EXPOSURE LEVELS: A scale for total dust was constructed consisting of four categories (0-3): no dust (probably less than 1 mg/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 lowdust jobs, 44.8% in medium dust jobs, and 4.1% in high dust jobs. The likelihood of exposure to dust in previous employment was assessed, blind to outcome, by an experienced occupational hygienist, who gave scores to jobs identified on the work history. Pre-employment dust exposure was assessed as non, low or potentially important. 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.

EXPOSURE PERIOD: 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.



Results and discussion

No evidence was found of pulmonary granulomas or of a correlation 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.

Any other information on results incl. tables

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; three were pre-exposure radiographs and one film was unavailable for reading. 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 (t=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, cumulative dust exposure, or age.

Lung function

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 the panel. Dust exposure in previous jobs did not relate to first FEV1 or FVC but did relate to first FEV1/FVC ratio which decreased, from 0.79 -0.73, with increasing prior dust exposure. 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.

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. Analysis of variance for FEV1, FVC, and FEV1/FVC ratio with cumulative zirconium exposure category showed no significant effect of exposure.

Smoking data were available for 159 out of 164 men. In an analysis of variance, both FEV1 and FVC were significantly related to smoking and lung function, but there was no interaction between smoking and zirconium exposure either for FEV1 or for FVC results. No relation was found between FEV1/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 FEV1, and prior dust of FEV1/FVC ratio, but cumulative exposure showed no relation to any of these measures of lung function.

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 finding attributable to zirconium exposure in this population.

Categories Display