Bismuth vanadium tetraoxide

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

sub-chronic toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1994

Report date:

1994

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 413 (Subchronic Inhalation Toxicity: 90-Day Study)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Bismuth vanadium tetraoxide

EC Number:

237-898-0

EC Name:

Bismuth vanadium tetraoxide

Cas Number:

14059-33-7

Molecular formula:

Bi O4 V

IUPAC Name:

vanadium(5+) bismuth(3+) tetraoxidandiide

Details on test material:

- Name of test material (as cited in study report): Mix 1:1 Irgacolor Yellow 14247/Sicopal Yellow L 1100
- Physical state: solid
- Analytical purity: 84.8 %, according to certificate of re-analyis in 1993

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Administration / exposure

Route of administration:

inhalation: dust

Type of inhalation exposure:

nose/head only

Vehicle:

other: unchanged (no vehicle)

Remarks on MMAD:

MMAD / GSD: < 1.2 µm

Analytical verification of doses or concentrations:

yes

Duration of treatment / exposure:

90 days

Frequency of treatment:

6 hours/working day

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0.1 mg/m³ air (analytical)

Doses / concentrations 2

Dose / conc.:

0.7 mg/m³ air (analytical)

Doses / concentrations 3

Dose / conc.:

4 mg/m³ air (analytical)

No. of animals per sex per dose:

10

Control animals:

yes, concurrent no treatment

Examinations

Observations and examinations performed and frequency:

Clinical examination was performed once each working day during the pre-flow period and on the day of necropsy. On exposure days, findings were recorded before, during, and after exposure. Body weight of the animals was determined weekly. Ophthalmology was carried out prior to the exposure period in all animals and at the end of exposure in the high concentration group and control.

Sacrifice and pathology:

A complete necropsy including weighing of selected organs and gross-pathological evaluation was performed in all animals. Histopathology of the total respiratory tract was performed in control and high concentration animals in the mid and low concentration. Only lungs and mediastinal lymph nodes were examined. Additionally, all gross lesions were examined. Bismuth and vanadium contents in five left lungs/concentration were determined analytically and lung burdens of CIP were calculated.

Results and discussion

Effect levels

1

Dose descriptor:

NOAEC

Effect level:

0.1 mg/m³ air (analytical)

Sex:

male/female

Basis for effect level:

histopathology: non-neoplastic

2

Dose descriptor:

LOAEC

Effect level:

0.7 mg/m³ air (analytical)

Sex:

male/female

Basis for effect level:

histopathology: non-neoplastic

organ weights and organ / body weight ratios

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

In neither concentration clinical symptoms or an influence on body weight development occurred.

The pigment content of the lungs at the end of the study can be found in the following table:

Pigment content [mg/lung]		Dose Group[mg/m^3]
male	female
--	--	--
0.033	0.021	0.1
0.36	0.28	0.7
1.82	1.51	4.0

The following substance-related findings were detected

during pathological examination:

High concentration (4 mg/m³) and mid concentration

(0.7 mg/m³)

- Significant increase of absolute (222 - 248% or 171 - 175%) and relative (228 - 241% or 171 - 183%) lung weights

- Foci in the lungs mainly due to the alveolar proteinosis and enlarged mediastinal lymph nodes in all or most of the animals

- Aggregates of (partly disintegrated) foamy alveolar macrophages, without substance, multifocal, deep in the lung parenchyma and subpleural in males and females

- Alveolar and septal macrophages containing birefringent test substance in male and female rats

- Birefringent test substance in the Bronchus Associated Lymphoid Tissue (BALT) in male and female rats

- Alveolar proteinosis containing birefringent test substance in male and female animals, more severe at the high concentration (4 mg/m³)

- Hyperplasia of type II pneumocytes, multifocal in males

and females

- collagenization, perivascular and peribronchial, minimal in males and females

- cholesterol crystals (only in one male animal of group 3 and one female animal of group 2) as secondary product of disintegrated alveolar macrophages

- Marked focal squamous cell metaplasia (only in one female animal of group 3)

- residues of birefringent substance intrabronchial in males and females of both groups, intratracheal and in the larynx in males and females of group 3 (without structural organ changes)

- Substance storage in mediastinal lymph nodes and lymphoreticular hyperplasia in males and females

Low concentration (0.1 mg/m³)

- No changes of toxicological significance.

Applicant's summary and conclusion

Conclusions:

The high and mid concentration led to considerable toxic effects exclusively to the lung. No systemic toxicity was observed based on clinical and necropsy findings.
The low concentration of 0.1 mg/m3 is judged to be a "No Observed Adverse Effect Concentration" (NOAEC), because there were no histopathological changes in the target organ.