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Toxicological information

Repeated dose toxicity: inhalation

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Administrative data

Endpoint:
repeated dose toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study does not meet important criteria of current standard methods.
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
other: dissertation
Title:
Chronic inhalation toxicity of antimony trioxide: Validation of the threshold limit value
Author:
Watt, W.D.
Year:
1983
Bibliographic source:
1983; 1, pp 1-133. Wayne State University, Detroit, Michigan

Materials and methods

Test guideline
Guideline:
other: no guideline specified
Principles of method if other than guideline:
The study was an attempt to evaluate the inhalation toxicity of antimony trioxide dust by exposing female rats and miniature swine to concentrations of antimony trioxide at levels relatively close to the threshold limit value. At the same time as the rats (see Chapter 7.7 S_watt_1983_rats) eight female Sinclair S-1 miniature swine that were exposed under similar conditions as the rats and housed in the same exposure chambers. The animals were divided into high dose (n=3), low dose (n=3) and control (n=2) groups.
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
not specified

Test animals

Species:
other: miniature swine
Strain:
other: sinclair S-1
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hormel miniature swine
- Housing:in chambers around the aisle in the same room as the exposure chambers
- Diet: Purina Laboratory Pig Grower Chow
- no other details on test animals and environmental conditions stated

Administration / exposure

Route of administration:
inhalation: dust
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
- dust dissemination: by the use of a modified hammer mill, particles separated and agitated by the
whirling blades were lifted in an air stream
- air changes in exposure room: 7.7 changes /hr (high dose)
25.1 changes /hr (low dose)
16.9 changes /hr (control)

TEST MATERIAL
- aerodynamic particle size: 15 μ diameter or smaller
- no other details on exposure are stated

Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
- air samples were taken during exposure period
Duration of treatment / exposure:
approx. 1 year exposure period
Frequency of treatment:
6 hours per day, 5 days per week
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
4.2 ± 3.2 mg Sb/m³ (high dose chamber)
Basis:
other: analytical conc., corresponding to 5.0 ± 3.8 mg Sb2O3/m³
Remarks:
Doses / Concentrations:
1.6 ± 1.5 mg Sb/m³ (low dose chamber)
Basis:
other: analytical conc., corresponding to 1.9 ± 1.8 mg Sb2O3/m³
No. of animals per sex per dose:
high dose: n= 3
low dose: n= 3
control: n= 2
Control animals:
yes, sham-exposed

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: prior to exposure, after 3, and 6 month of exposure, and at the end of exposure

DETAILED CLINICAL OBSERVATIONS: Yes

BODY WEIGHT: Yes
- Time schedule for examinations:for examinations:periodically before, throughout and after exposure

HAEMATOLOGY: Yes, blood samples from orbital sinus or anterior vena cava
- Anaesthetic used for blood collection: Yes (identity): with V-Pento or with prior tranquilization with Innovar-Vet
- Parameters examined: differential count, red blood cell count, white blood cell count, hemoglobin, hematocrit, mean corpuscular volume,
mean corpuscular hemoglobin, mean corpuscular hemoglobin volume

CLINICAL CHEMISTRY: Yes
- Parameters examined: alkaline phosphatase, glutamate oxalacetate transaminase, glutamate pyrovate transaminase, lactic dehydrogenase, hydroxybutyrate dehydrogenase, creatine phosphokinase, total protein, albumin, globulin, albumin-globulin ratio, blood urea nitrogen, creatine, bilirubin, sodium, potassium, glucose, cholesterol levels

OTHER:
- subjected to roentgenograms and electrocardiograms (prior to exposure, at six month and at the end of exposure)
- radiological studies: lateral and posterior-anterior roentgenograms were taken at pre-exposure, 6 months and at the end of exposure

- no other observations performed
Sacrifice and pathology:
- sacrificed at the end of exposure period by anesthetizing with V-Pento and opening chest cavity
GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Haematological findings:
no effects observed
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Gross pathological findings:
effects observed, treatment-related
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed
Details on results:
BODY WEIGHT AND WEIGHT GAIN
- no differences between the groups

HAEMATOLOGY
- no statistically significant differences in blood values

CLINICAL CHEMISTRY
- no statistically significant difference or consistent pattern of enzyme values
- increase of blood urea nitrogen values in high dose group in contrast to low dose group and in low dose group in contrast to control group (values not statistically significant, but the strong pattern suggest an exposure relationship)

ORGAN WEIGHTS
- no differences between the weights of major organs except the lungs:
- the lungs showed increased weight
- lung weight showed the pattern of high dose group being heavier than the low dose group and the low dose group being heavier than the control group at 3 and 6 months exposure (pattern remains consistent throughout the exposure period for lung weight alone)
- none of the differences in lungs are statistically significant

GROSS PATHOLOGY
- lungs of exposed animals were mottled; the mottling increased with dose level and length of exposure; the mottling is a manifestation of foci of fibrosis

HISTOPATHOLOGY: NON-NEOPLASTIC
- no histopathologic alterations

HISTOPATHOLOGY: NEOPLASTIC (if applicable)
- no histopathologic alterations

OTHER FINDINGS
- no abnormality was detected in roentgenograms and electrocardiograms

- no other findings are reported

Effect levels

Basis for effect level:
other: see 'Remark'
Remarks on result:
not measured/tested
Remarks:
Effect level not specified (migrated information)

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

- the results show evidence of antimony trioxide related toxicity

- in addition to the lung parameters only blood urea nitrogen and body weights show exposure related alteration

- the lung is the main target organ of antimony trioxide inhalation toxicity.No exposure related histopathologic changes were observed in the swine.

Applicant's summary and conclusion