Vanadium, oxalate complexes

Epidemiological data

Administrative data

Endpoint:

epidemiological data

Type of information:

other: Human data

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Well-documented publications.

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Effects of vanadium on the upper respiratory tract of workers in a vanadium factory.

Author:

Kiviluoto, M. et al.

Year:

1979

Bibliographic source:

Scand. J. Work Environ. & Health 5: 50 - 58.

Reference 2

Reference Type:

publication

Title:

Observations on the lungs of vanadium workers.

Author:

Kiviluoto, M.

Year:

1980

Bibliographic source:

British Journal of Industrial Medicine, 37: 363 - 366.

Materials and methods

Study type:

other: cross-sectional study and case control study (retrospective)

Endpoint addressed:

repeated dose toxicity: inhalation

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Publication 1 (Kiviluoto, M. et al.(1979):
An epidemiological cross-sectional case history study on the injurious effects of vanadium was carried out among the workers of a V2O5 factory. The upper respiratory tract of 63 male workers exposed to V2O5 dust was examined macroscopically and microscopically, and the findings were compared with those of a reference group of workers who were exposed to inert dust only. The groups compared were of similar ages and had similar smoking habits. Nasal smears and sputum cells were studied microscopically, and biopsies for histological study were taken from the nasal mucosa.

Publication 2 (Kiviluoto, M. (1980):
This case-control study examines the possible effects of V2O5 exposure on ventilatory function, findings in chest radiographs and respiratory symptoms in the workers of the V2O5 factory. Out of a total of 79 employees at the factory making V2O5 from magnetite ore 63 were investigated by respiratory questionnaire, chest radiography, and tests of ventilatory function. The findings were compared with a reference group of 63 men, matched for age (to within two years) and for smoking habit (to within five cigarettes daily) selected from workers at a magnetite ore mine.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Divanadium pentaoxide

EC Number:

215-239-8

EC Name:

Divanadium pentaoxide

Cas Number:

1314-62-1

Molecular formula:

V2O5

IUPAC Name:

divanadium pentaoxide

Details on test material:

- Name of test material (as cited in study report): Vanadium pentoxide

Method

Type of population:

occupational

Ethical approval:

other: Publication 1: no data; Publication 2: confirmed, but no further information available

Details on study design:

PLEASE NOTE: In both publications, the same setting and subjects were investigated. For this reason, the information on setting and subjects were stated together for both publications.

SETTING: V2O5 factory of the Otanmäki Mine of Rautaruukki Company, Finland, which has been manufacturing vanadium pentoxide since 1956.

STUDY POPULATION
- Total number of subjects participating in study: The exposed population consisted of 63 men, who were process workers, repairmen, foremen, and laboratory workers in the V2O5 factory.
- Selection criteria: Every man who had worked in the V2O5 factory for at least four months was selected for examination, but those on holiday or sick leave at that time were not seen.
- Age: 19 - 56 years
- Average height: 170.8 cm (19-39 years of age); 170.0 cm (40 -56 years of age)
- Smoker/nonsmoker: The average smoking time of the smokers within the exposed group was 15.8 years. The average amount in grams of tobacco smoked was 14 g a day.

COMPARISON POPULATION
- Type: Reference group
- Details: The reference group of 63 men was chosen from men living in the same area and thus exposed to similar air pollution. The referents worked in the concentrating plant, the mine, the repair shop, and the office, and they were matched for age within two years and for the number of cigarettes smoked daily within five cigarettes.
- Smoker/nonsmoker: The average smoking time of smokers within the reference group 16.0 years. The average amount in grams of tobacco smoked was 12.5 g a day.
- Age: 19 - 56 years
- Average height: 175.6 cm (19-39 years of age); 171.7 cm (40 -56 years of age) (From the whole sample, the height of the referents was significantly greater (p< 0.01), but there was no difference in the weights of the two groups.)

PUBLICATION 1:
HYPOTHESIS TESTED: No studies on simultaneous macroscopic, cytological, and histological changes have been made on humans exposed to V2O5. The purpose of the present study was to explain these changes.

METHOD OF DATA COLLECTION
The upper respiratory tract of the workers in both groups was examined before they returned to work after their 2- to 4-week summer vacation in June-August 1975; the exposed group was also examined in March-June 1976 after several months of exposure. (The measurements of dust concentration were also made at this time). At the time of the former examination the cytological smears of the nasal mucosa and mucosal biopsies were taken from the middle part of the nasal inferior turbinates for microscopic examination. There was no evidence of epidemic upper respiratory infection in the examined subjects at the time of the study. The subjects took sputum cell specimens for microscopical examinations.. Also, measurements of pulmonary ventilation and some laboratory tests were made.
Nasal secretion smears were made and studied according to the methods of Holopainen (Holopainen, E. Nasal mucous membrane in atropic rhinitis with reference to symptom free nasal mucosa: Histology, histochemistry and exfoliative cytology. Acta oto laryngologica suppl. 227 (1967) 53 p.)
The histological biopsies were fixed in 10 % neutral formalin and embedded in paraffin blocks. They were cut into sections which were 5 µm thick. Different stainings were used to demonstrate overall morphology, ordinary findings, tissue plasma cells, eosinophils, mast cells, and neutrophils.
The metaplastic cells and eosinophils were examined from the sputum.
In smears taken from the nasal inferior turbinates, the columnar epithelial cells, globet cells, metaplastic cells, basal cells squamous epithelial cells, cilia cytophoria cells, neutrophils, eosinophils, mast cells, lymphocytes, plasma cells, and bacteria were examined.
Columnar epithelial cells with or without cilia, possible degeneration, globet cells, metaplastic cells, inflammatory cells (the plasma cells included), eosinophils, and mast cells were examined in the biopsies taken from the nasal inferior turbinates. In addition, the thickness of the connective tissue membrane, changes in the mucous glands and in the vessels, and the stromal fibrosis were examined and a histopathological diagnosis considering a possible acute, subchronic or chronic inflammation was also made.

STUDY PERIOD: A periodic examination in 1973.

PUBLICATION 2:
HYPOTHESIS TESTED: This case-control study examines the possible effects of V2O5 exposure on ventilatory function, findings in chest radiographs and respiratory symptoms in the workers of the V2O5 factory.

METHOD OF DATA COLLECTION
Forced vital capacity (FVC) and forced expiratory volume (FEV1) were determined with a dry bellows spirometer (Vitalograph) and expressed at BTPS. The highest value out of five attempts was used. Investigation of the exposed men took place at the end of their summer holidays in 1975, and at the same time the assisting nurse filled in a standardized questionnaire on respiratory symptoms (Medical Research Council. Committee on Research into Chronic Bronchitis. Questionnaire on respiratory symptoms. London: MRC. 1966). Lung function tests of the reference group were also undertaken in summer 1975. Full-size chest radiographs were taken in April 1976 and read, mixed and "blind" by an experienced radiologist at the Institute of Occupational Health in Finland.

Exposure assessment:

measured

Details on exposure:

PUBLICATION 1:
EXPOSURE LEVELS: Determinations of the concentration of V2O5 dust in the factory air have been carried out since 1970. According to these measurements, 0.2 - 0.5 mg of vanadium per cubic meter can be regarded as the average level of previous exposure (determined from the total dust gathered on a paper filter with the atomic absorption spectrophotometric method, a total of 64 samples between 1970 and 1975).
At the beginning of 1976 the management intensified the flushing of the floors in order to stop the dust from rising. Thereafter the exposure level was about 0.01 - 0.04 mg/m^3 (194 determinations of dust concentration in the spring of 1976, 114 samples of which were taken in the breathing zones of individual workers and the rest at stationary sites). The dust was collected by suction on a paper filter. The concentration of vanadium was determined by an atomic absorption spectrophotometer with the graphite furnace method. The total dust concentrations were very small in the factory. In addition to vanadium, the air contained inert magnetite dust. In ordinary workplaces near sintering furnaces, the concentration of sulfur dioxide was also determined with indicator tubes, the determing limit of which, 0.5 cm^3/m^3, was not exceeded. The samples were taken by methods commonly used by the Institute of Occupational Health in Finland (Suomen Standardisoimisliitto. Measurement of dust concentration in workplace air with filter method (SFS 3860). Helsinki 1976. 6 p.).
Since the subjects had worked an average of 11 years at the factory, attention had to be paid to the previous levels of dust before a reliable picture of the possible chronic effects of V2O5 could be formed.

PUBLICATION 2:
TYPE OF EXPOSURE: In the pocess magnetite is roasted with sodium carbonate. The roasted product is leached, and vanadates are precipitated from the leach liquor. The "red cake" produced is filtered, washed, and smelted to vanadium pentoxide.

TYPE OF EXPOSURE MEASUREMENT:
The concentration of V2O5 dust at various sites in the factory were determined on eight days in March-May 1976. The determination covered two whole shifts. An atomic absorption spectrophotometer using flameless graphite atomiser (Perkin-Elmer 300, HGA 74) was used for these determinations. This could detect vanadium down to 0.002 mg/m^3. The coefficient of variation within run was 6 % at the concentration level of 0.05 mg/m^3. The particle size of the dust samples was determined by a modified Andreasen method from five dust samples, which were taken separately with a high volume sampler (Öhman H. Ödelycke P. Provtagnings-ochanalysförfaranden för silikosfarligt damm (Al-rapport No 3). Stockholm: Arbetsmedicinska Institutet. 1968:20.)

EXPOSURE LEVELS: Workers were exposed to 0.1 to 3.9 mg V/m^3 measured as total dust for 11 years.

Statistical methods:

PUBLICATION 1:
The results were statistically analyzed by means of matched pairs according to the McNemar chi-square test. The changes noticed within the V2O5 group after exposure were also examined according to McNemar's chi-square test. The pathologicoanatomic changes were also analyzed by these means after the 10 persons with the shortest periods of employment at the factory were eliminated from the group.

PUBLICATION 2:
Because the exposed and reference populations were matched for age and smoking habit, the use of Cole's (Cole TJ. Linear and proportional regression models of ventilatory function. Journal of the Royal Statistical Society, Series A 1975: 138:297 - 337) finding that FEV1 = height2 X(c+dX age) simplified the analysis to a paired t-test of the differences FEV1/Height2(exposed) - FEV1/Height2 (referent). The distribution of respiratory symptoms between the exposed and referents was analysed by McNemar's test for paired observations.

Results and discussion

Results:

EXPOSURE (Publication 2:)
The respirable fraction of the dust (particle size 5 µm or less) was 20 %. Concentrations exceeding the TLV of 0.5 mg/m^3 were found only during the grinding process of the laboratory samples. High concentrations of vanadium (V2O5) were also found at the packing of the smelt, but elsewhere in the factory the vanadium concentration was constantly below 0.1 mg/m^3.

FINDINGS OF PUBLICATION 1 AND PUBLICATION 2:
No differences were observed in the anterior and posterior rhinoscopy in the exposed groups after 11 years of exposure to average levels of 0.2-0.5 mg V/m3. Furthermore, there was no difference in the number of blood vessels between the exposed and non-exposed groups. However, the number of neutrophils in the nasal smears and the number of plasma cells in the nasal mucosa were increased indicative of a protective mechanism in the mucosa. Other examined factors of the biopsies and cell findings did not differ between the exposed workers and the controls. Chest radiographs and lung function tests did not reveal any differences. After further 7-11 months of V2O5 exposure to 0.01 to 0.04 mg V/m3 measured as total dust, a subsequent reexamination revealed that the cell findings did not indicate any further significant changes between the studied exposed groups and that there were no significant changes in the number of eosinophils of cytological and histological samples.
Altogether, no pneumoconiosis and no other signs indicative of allergic inflammation, including nasal catarrh, cough, or phlegm, were observed in the exposed subjects working for 11 years under these occupational conditions.

Applicant's summary and conclusion

Conclusions:

No differences were observed in the anterior and posterior rhinoscopy in the V2O5 exposed groups after 11 years of exposure to average levels of 0.2-0.5 mg V/m3. Furthermore, there was no difference in the number of blood vessels between the exposed and non-exposed groups. However, the number of neutrophils in the nasal smears and the number of plasma cells in the nasal mucosa were increased indicative of a protective mechanism in the mucosa. Other examined factors of the biopsies and cell findings did not differ between the exposed workers and the controls. Chest radiographs and lung function tests did not reveal any differences. After further 7-11 months of exposure to 0.01 to 0.04 mg V/m3 measured as total dust, a subsequent reexamination revealed that the cell findings did not indicate any further significant changes between the studied exposed groups and that there were no significant changes in the number of eosinophils of cytological and histological samples.
Altogether, no pneumoconiosis and no other signs indicative of allergic inflammation, including nasal catarrh, cough, or phlegm, were observed in the V2O5 exposed subjects working for 11 years under these occupational conditions.