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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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

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

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Version / remarks:
(1981) Method B2, Commission Directive 92/69/EEC
Deviations:
no
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS: Sprague-Dawley Crl:CD® (SD) IGS BR
- Source:Charles River (UK) Ltd, Margate, Kent
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 200g - 350g
- Fasting period before study: none
- Housing:in groups of five by sex in solid-floor polypropylene cages with stainless steel lids, furnished with softwood flakes and provided with environmental enrichment items: wooden chew blocks
- Diet (e.g. ad libitum): ad libidtum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: min. 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25°C
- Humidity (%): 30-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
inhalation: dust
Type of inhalation exposure:
nose only
Vehicle:
clean air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: SAG 410 Solid Aerosol Generator (TOPAS GmbH, Dresden, Germany)
- Exposure chamber volume: 30 l
- Method of holding animals in test chamber: tapered, polycarbonate restraining tube fitted onto a single tier of the exposure chamber
- Source of air: Compressed air, passed through a water trap and respiratory quality filters
- Method of particle size determination: Marple Personal Cascade Impactor, (Westech IS Ltd, Beds., UK); six impactor stages (9.6, 6.6, 3.5, 1.8, 0.87
and 0.33 μm cut points
- Treatment of exhaust air: passed through a scrubber trap, connected with a filter

- Samples taken from breathing zone: yes

TEST ATMOSPHERE (see Any other information on materials and methods incl. tables, table 1)
Analytical verification of test atmosphere concentrations:
yes
Remarks:
gravimetric method
Duration of exposure:
4 h
Concentrations:
see Any other information on materials and methods incl. tables, table 1
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: hourly during exposure, at the end of exposure and 1h later. Once daily up to 14 days.
and weighing: prior to exposure on the day of treatment, days 7 and 14.
- Necropsy performed: yes (all animal, surviving, died, killed)
- Other examinations performed: clinical signs, body weight, macroscopic examination, esp. of the respiratory tract, behavioural observations
Statistics:
LC50’s estimated by Linear Interpolation (US EPA, 1989)

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
3.11 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
see Any other information on results incl. tables, table 2
Clinical signs:
Common abnormalities:increased respiratory rate, hunched posture, pilo-erection and wet fur.
Frequent instances of decreased respiratory rate, laboured respiration, noisy respiration, ataxia and red/brown staining around the head.
Occasional instances of red/brown staining around the snout, gasping respiration.
Isolated occurrences of prostration, red/brown staining around the eyes, sneezing and fur loss.

Animals from Group 1 recovered to appear normal from Days 4 to 6 post-exposure.
Surviving animals from Group 2 recovered to appear normal from Days 8 to 10.
None of the animals from Group 3 survived until Day 1.
Body weight:
Normal bodyweight development for all surviving animals during the study with the following exeptions:
Group 1: 1 male and 1 female showed reduced bodyweight gain or slight bodyweight loss during Week 1 but recovered to show normal development during Week 2. A further female from Group 1 showed slight bodyweight loss during Week 2.
Group 2: 5 females exhibited a reduced bodyweight gain or slight bodyweight loss during Week 1 but recovered to show normal development during Week 2.
Gross pathology:
Macroscopic abnormalities detected amongst
- animals that survived until Day 14 at necropsy:
Lungs – enlarged, fluid filled, abnormally dark, pale patches, dark patches (in all animals of the low and mid dose groups);
- animals that died or were humanely killed during the course of the study at necropsy:
Lungs – haemorrhagic, fluid filled, abnormally dark, pale patches;
Liver – dark;
Kidneys – dark or pale;
Stomach – gaseous distension; Small Intestine – gaseous distension; Large Intestine – gaseous distension.

Any other information on results incl. tables

Table 2: Mortality data

Group Number

Mean Achieved

Atmosphere Concentration (mg/L)

 

Deaths

 

Male

Female

Total

1

1.00

0/5

0/5

0/10

2

1.96

2/5

0/5

2/10

3

5.03

5/5

5/5

10/10

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
Acute Toxicity Inhalation Category 4, H332: [Regulation (EC) No 1272/2008]