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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:
2012
Report Date:
2012

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1300 (Acute inhalation toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
Deviations:
no
GLP compliance:
yes
Test type:
traditional method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Details on test material:
Purity: 99.4%
Impurities: Not reported

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories, Inc.
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: Young adult (9 weeks)
- Weight at study initiation: males 233-247 grams, females 170-193 grams
- Fasting period before study: not reported
- Housing: animals were individually housed in plastic solid bottom polycarbonate cages. Enrichment was placed in each cage. Corncob bedding was placed in cage and changed once a week.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23°C
- Humidity (%): 61-75%
- Air changes (per hr): 12-13
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
clean air
Mass median aerodynamic diameter (MMAD):
2.8 µm
Geometric standard deviation (GSD):
2.17
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Mini-Nose-Only Inhalation Chamber
- Exposure chamber volume: 6.7 liters
- Method of holding animals in test chamber: individulal polycabronate holding
- Source and rate of air: 30.0 liters per minute supplied by air compressor
- System of generating particulates/aerosols: Wright Dust Generator
- Method of particle size determination: Eight-stage ACFM Andersen Ambient Particle Sizing Sampler
- Temperature, humidity, pressure in air chamber: Temp: 23-24°C, Hum: 28-62%, pressure: slightly negative

TEST ATMOSPHERE
- Samples taken from breathing zone: yes
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
5.04±0.16 mg/L
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 and weighing: Prior to test substance administration, Day 1, Day 3, Day 7, and Day 14 (termination)
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, histopathology
Statistics:
Not Applicable

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.04 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Mortality:
All animals survived
Clinical signs:
other: All animals exhibited irregular respiration after exposure but recovered by Day 3 and appeared healthy and active the remainder of the observation period.
Body weight:
4 males and 4 females failed to gain weight after Day 1 but all animals showed continued weight gain thereafter through the exposure period.
Gross pathology:
No gross abnormalities were observed in any of the animals when necropsied at the conclusion of the observation period.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this study, the single exposure acute inhalation LC50 of the test substance is greater than 5.04 mg/L in male and female rats.
Executive summary:

An acute inhalation toxicity test was conducted in accordace with OECD 403, OPPTS 870.1300, and EU Method B.2 to determine the potential for the test substance to produce toxicity from a single exposure via the inhalation (nose-only exposure) route. The animals were observed for mortality, signs of gross toxicity, and behavioral changes at least once daily for 14 days following exposure. Body weights were recorded prior to exposure and again on Days 1, 3, 7 and 14 (termination). Necropsies were performed on all animals at terminal sacrifice.

The gravimetric chamber concentration was 5.04 ± 0.16 mg/L (mean ± SD). Based upon graphic analysis of the particle size distribution as measured with an ACFM Andersen Ambient Particle Sizing Sampler, the mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD) of the 5.04 mg/L atmosphere was 2.80 μm ± 2.17 (MMAD ± GSD).

All animals survived exposure to the test substance. Following exposure, all animals exhibited irregular respiration. However, the animals recovered from this symptom by Day 3 and appeared active and healthy for the remainder of the 14-day observation period. Although four males and four females lost or failed to gain body weight by Day 1, all animals showed a continued weight gain thereafter through Day 14. No gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14-day recovery period.

Under the conditions of this study, the single 4-hour inhalation medial lethal concentration (LC50) for the test substance is greater than 5.04 mg/L in male and female rats.