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Toxicological information

Direct observations: clinical cases, poisoning incidents and other

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Administrative data

Endpoint:
direct observations: clinical cases, poisoning incidents and other
Type of information:
other: Human data
Adequacy of study:
weight of evidence
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: The epidemiological data reported was not relevant for risk assessment.

Data source

Reference
Reference Type:
publication
Title:
Human responses to controlled vanadium pentoxide exposure.
Author:
Zenz, C. & Berg, B.
Year:
1967
Bibliographic source:
Arch Environ Health, 14: 709 - 712.

Materials and methods

Study type:
study with volunteers
Endpoint addressed:
acute toxicity: inhalation
repeated dose toxicity: inhalation
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
The primary purpose of the study was to observe clinical responses of human subjects to vanadium pentoxide dust with particular reference to the respiratory system.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: dust
Details on test material:
- Name of test material (as cited in study report): Vanadium pentaoxide
- Physical state: Dust
- Analytical purity: Pure

Method

Type of population:
general
Subjects:
- Number of subjects exposed: Nine healthy volunteer subjects
- Age: Ranged in age from 27 to 44 years
They had no previous history of respiratory disease nor any significant known exposure to pulmonary irritants. Two of the nine subjects smoked less than one pack of cigarettes daily, and the others were nonsmokers.
Ethical approval:
not specified
Route of exposure:
inhalation
Reason of exposure:
intentional
Exposure assessment:
measured
Details on exposure:
The environmental chamber had an internal volume of 660 cu ft (18.5 cu m). It was suitably air-conditioned to maintain constant temperature and humidity. Pure vanadium pentoxide dust was dispersed into this chamber using a dust-feed mechanism (Wright, B.M.: Experimental Studies on the Relative Importance of Concentration and Duration of Exposure to Dust Inhalation, Brit j Industr med 14: 219, 1957). Atmospheric samples were collected on suitable glass fiber filters with a flow calibrated vacuum pump and analyzed by the method described by Hulcher (Hulcher, G.H.: Spectrographic Determination of Vanadium in Biological Materials, Analytical Chemistry 32: 1183 (Aug) 1960). Microscopic size analysis revealed that 98 % of the collected dust was less than 5 µ in diameter.

1.) Two volunteers were exposed to 1 mg/cu m of vanadium pentoxide dust for an eight hour period. Three weeks after the original exposure those same two volunteers were accidentally reexposed for a five minute period to a heavy cloud of vanadium pentoxide dust.

2.) Next, five volunteers were exposed to 0.25 mg/cu m for an eight hour period. Sequential atmospheric samples were taken throughout the test to determine chamber atmospheric vanadium pentoxide concentrations. The average concentration was 0.2 mg/cu m +/- 0.06 SD. Microscopic-size analysis of the dust again revealed that more than 98 % was less than 5µ in diameter.

3.) Two new volunteers not previously exposed to vanadium pentoxide were exposed for eight hours at a concentration of 0.1 mg/cu m.
Examinations:
- Urine analysis: Urinalysis was conducted on each subject.
- Haematology: Complete blood count and microhematocrit were examined in each subject.
- Lung function parameters: Studies of ventilatory parameters of each subject consisted of the forced vital capacity (FVC), the 0.5 second and 1 second forced expiratory volume (FEV), the 0.5 and 1 maximal expiratory flow (MEFT), the 200 to 1,200 cc flow rate (MMF), the maximal midexpiratory time (MMET), and the forced inspiratory vital capacity (FIVC). The two smokers showed no discernible difference in these test results or in the subjective complaints following the vanadium pentoxide inhalation.
- Other: Each subject underwent a complete physical examination as well as 14 X 17 (35 X 43 cm) chest x-ray.
Cystine analysis was made on hair and nail clippings gathered from each subject before exposure and four months after exposure. These were analyzed by the Public Health Service in Cincinnati, Ohio. No discernible differences were detected, probably because of the short duration of exposure.

All subjects were observed clinically for 11 months to 19 months after exposure.

Determinations of vanadium content in the biological samples were also made by the laboratory procedures described by Hulcher (Hulcher, G.H.: Spectrographic Determination of Vanadium in Biological Materials, Analytical Chemistry 32: 1183 (Aug) 1960).
Medical treatment:
The two volunteers (exposed to 1 mg/cu m), who were accidently exposed to vanadium pentoxide three weeks after the original exposure, received a therapeutic dose of 1:2,000 isoproterenol for five minutes under positive pressure inhalation.

Results and discussion

Clinical signs:
Please refer to "Results of examinations" below
Results of examinations:
1.) Two volunteers exposed to 1 mg/cu m:
- Urine analysis: There were no alterations of urinalyses.
- Haematology: There were no alterations of the white blood cell counts.
- Lung function parameters: Prior to exposure, immediately following exposure and once weekly for three weeks, pulmonary function test had been performed. No differences in results were detected.
- Clinical signs: Some sporadic coughing developed after the fifth hour which was believed to be psychologic at the time. Near the end of the seventh hour, more frequent coughing developed in both subjects. By evening, persistent coughing began and remained for eight days. There were no other signs of irritation nor was there fever or increased pulse rate.
- Other: During the post-exposure observation period, chest examinations revealed clear lung fields. Normal physical activities were pursued. There were no alterations of differential cell patterns. Nasal smears made 24 hours, 72 hours, and one week later did not disclose eosinophilia.

After the accidental exposure three weeks after the original exposure, the two volunteers had normal pulmonary functions. The two volunteers developed within 16 hours marked coughing, productive of sputum. The following day, rales and expiratory wheezes were present throughout the entire lung field.


2. ) Five volunteers exposed to 0.25 mg/cu m:
- Urine analysis: The greatest amount of vanadium was found in the urine three days after exposure, namely 0.013 mg/100 ml, and none was detectable one week following exposure.
- Haematology: Differential white blood counts were normal.
- Lung function parameters: On the day of exposure, pulmonary function studies were made immediately before and after the test period without change. Spirometry was repeated at the end of two weeks without detectable changes from preexposure studies.
- Clinical signs: All men developed a loose cough the following morning. Productive coughing was evident without other systemic complaints. Physical examinations were nonrevealing. Daily observation yielded no abnormalities. Several subjects stopped coughing by the tenth day.
- Other:
At the concentrations to which these subjects were exposed, no vanadium was detected in the blood of any subject. Maximum faecal vanadium was 0.003 mg/gm. None was found after two weeks.

3.) Two volunteers exposed to 0.1 mg/cu m:
- Clinical signs: No symptoms occurred during or immediately after exposure. Within 24 hours, however, considerable muscus formed. This mucus was easily cleared by slight coughing which increased after 48 hours, subsided within 72 hours and disappeared completely after four days.
There were no deviations in laboratory studies.
Effectivity of medical treatment:
Two volunteers exposed to 1 mg/cu m: The administration of a therapeutic dose of 1:2,000 isoproterenol relieved the coughing, and adventitious sounds were no longer present. Coughing resumed in about one hour and continued for one week. No other symptoms occurred during this period, and eosinophilia was absent in the blood and in the nasal mucus.
Outcome of incidence:
Please refer to "Effective of medical treatment" above.

Applicant's summary and conclusion

Conclusions:
The acute manifestations of marked pulmonary irritation observed in all subjects demonstrated the prompt reaction of humans to fine vanadium pentoxide dust. Despite the distinct clinical picture of pulmonary irritation presented by all the subjects, the pulmonary function tests remained unaltered. No systemic aberrations were observed in the volunteers.