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Toxicological information

Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
from August 26, 2005 to December 12, 2005
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study was generated according to generally valid and accepted testing guidelines and performed according to GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2006

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
Version / remarks:
(92/69/EEC)
Qualifier:
according to
Guideline:
other: additional examinations performed: clinical signs, gross pathology, histopathological examination of nose, larynx, trachea and lungs (five levels) 24 hours and 14 days after cessation of exposure
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes

Test material

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

Test animals

Species:
rat
Strain:
other: Charles-River rat (strain:CD)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Breeder: Charles River Deutschland GMBH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Age at study initiation: males 49 days; females 60 days
- Weight at study initiation: males 216 - 230 g; females 201 - 218 g
- Fasting period before study: 16 hours
- Housing: granulated textured wood cages; MAKROLON cages (type III) during 14-days observation period
- Diet: ssniff R/M-H V1534 (ssniff Spezialitäten GmbH, 59494 Soest, Germany), discontinued approx. 16 hours before exposure
- Water: ad libitum
- Acclimation period: 5 adaption days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): room temperature of 22°C ± 3°C
- Humidity (%): 55 % ±15 %
- Air changes (per hr): 22.5 changes
- Photoperiod (hrs dark / hrs light): 12 hours each with approx. 150 lux


IN-LIFE DATES: From: August 26, 2005 To: October 4, 2005

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: dynamic inhalation apparatus, nose-only exposure chamber
- Exposure chamber volume: 40 L
- Method of holding animals in test chamber: animals in pyrex tubes at the edge of the chamber in radial position
- Source and rate of air: air from surrounding atmosphere of laboratory room; inflow = 900 L/h
- Method of conditioning air: filtered with an inline disposable gas filter and compressed
- System of generating particulates/aerosols: with a dry , rotating brush dust generator
- Method of particle size determination: cascade impactor
- Treatment of exhaust air: sucked through 3 gas wash-bottles filled with tap water
- Temperature, humidity, pressure in air chamber: 21.7 °C ± 0.6 °C, humidity of 53.1 % ± 3.3 %


TEST ATMOSPHERE
- Brief description of analytical method used: gravimetric analysis with an air sample filter and pump
- Samples taken from breathing zone: yes


TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: geometric standard deviation = 4.27
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 1.664 µm


- no other details on exposure are reported
Analytical verification of test atmosphere concentrations:
yes
Remarks:
Dust concentration was measured gravimetrically with an air sample filter and pump controlled by a rotameter. The particle size distribution was analysed using a cascade impactor accoring to May (1975).
Duration of exposure:
4 h
Concentrations:
5.20 ±0.16 mg Antimony trioxide/L air
No. of animals per sex per dose:
five male and five female rats
In addition, three male and three female satellite animals for histopathological examination 24 hours post exposure
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: once daily for clinical examination until symtoms subsided, thereafter each working day; daily observation on mortality; weights were determined before exposure, weekly after exposure and at the end of observation
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, gross pathology, histopathological examination of nose, larynx, trachea and lungs (five levels) 24 hours and 14 days after cessation of exposure
Statistics:
no calculation as no mortality occurred

Results and discussion

Preliminary study:
no information in study report
Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.2 mg/L air
Exp. duration:
4 h
Remarks on result:
other: LC50 was assigned to a level greater than the limit concentration (5.20 mg/L air) tested since no mortality occurred.
Remarks on result:
other: There were no signs of respiratory irritation, based on an absence of test item-related clinical signs and histopathological effects in the nose, larynx and trachea 24 hours and 14 days after exposure.
Mortality:
no deaths
Clinical signs:
no clinical signs throughout the exposure phase and post-exposure period
Body weight:
all animals gained the expected weight throughout the study period
Gross pathology:
One satellite animal showed multiple red-grey foci (0.1-0.2 mm diameter) as a macroscopic change in the lung.

Other findings:
- Histopathology:
no test item-related changes were noted in the nose (five levels), larynx and trachea

Changes noted in the lungs 24 hours after end of exposure:
∙ all animals revealed an activation of macrophages in the lungs (five levels)
∙ aggregations of foamy alveolar macrophages and macrophages with phagocytic material in the alveolar lumen
∙ inflammatory reactions with granulocytic infiltrations and secretion in the lungs
∙ pigment/substance detected within the secrete and /or mucus
The findings were minimal to mild in severity, and clearly subsided to a large extent after the 14-day observation period.

Changes noted in the lungs 14 days after end of exposure:
∙ all animals revealed an activation of macrophages in the lungs (five levels)
∙ aggregations of foamy alveolar macrophages and macrophages with phagocytic material in the alveolar lumen
∙ the bronchioli contained mucus with pigment/substance
The findings were minimal to mild in severity, and are considered to be test item-related

- no other findings are reported

Any other information on results incl. tables

Table 1: Summerised results

Symptom/

Criteria

5.20 mg Antimony trioxide/L air

males

n = 5

females

n = 5

clinical signs:

none

none

mortality within:

6 h

0

0

24 h

0

0

7 d

0

0

14 d

0

0

mean body

weight (in g)

(excluding satellite

animals):

start

226.0

211.4

( - )

( - )

after 7 days

295.8

229.2

(30.9)

(8.4)

after 14 days

312.4

235.4

(38.2)

(11.4)

inhibition of

body weight

gain

none

none

necropsy findings

none

none

The microscopic changes observed are considered to be test item-related but can be explained with physiological clearance mechanisms to be expected after inhalation exposure to such a high concentration of poorly soluble dust material.

The pathological findings after the 14-day observation period improved by degreasing in incidence and severity compared to the findings noted 24 hours post exposure.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU