Registration Dossier

Toxicological information

Acute Toxicity: inhalation

Currently viewing:

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
23 July 2012 to 13 August 2012
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study was not conducted in compliance with GLP regulations
Remarks:
A scientifically valid, robust study was conducted on this substance prior to the REACH registration activities associated with this substance. The study is sufficient for hazard classification and in the interest of reducing animal testing, repeating the study under GLP conditions is not warranted.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report Date:
2012

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
not applicable
Principles of method if other than guideline:
Male Sprague-Dawley rats (5/dose) were whole body exposed to 0, 5,000 or 10,000 ppm test article for a single 4 hour exposure on Study Day 1.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: gas
Details on test material:
- Name of test material (as cited in study report: MTDID 28136
- Substance type: Mono-constituent
- Physical state: Gas
- Analytical purity: 99.66%
- Purity test date: 12 July 2012
- Lot/batch no.: N.B.# 159571-114

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan
- Age at study initiation: 6-8 weeks
- Weight at study initiation: 169-197 g
- Fasting period before study: None
- Housing: Group housed in solid bottom cages
- Diet (e.g. ad libitum): Harlan Teklad Rat/Mouse 2018 Diet (Harlan Teklad, Madison, WI) ad libitum
- Water (e.g. ad libitum): Tap water, ad libitum
- Acclimation period: No data
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.6-23.9
- Humidity (%): 30-70
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES: From: 23 July 2012 To: 13 August 2012

Administration / exposure

Route of administration:
inhalation: gas
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: A calculated amount of test material was added to an exposure chamber of known volume
- Exposure chamber volume: No data
- Method of holding animals in test chamber: No data
- Source and rate of air: No data
- Method of conditioning air: No data
- Treatment of exhaust air: No data
- Temperature, humidity, pressure in air chamber: Temp: 20.6-22.2, Humidity: 37-93%
TEST ATMOSPHERE
- Brief description of analytical method used: Nominal concentrations were used
- Samples taken from breathing zone: no
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
ca. 4 h
Concentrations:
0, 5,000, or 10,000 ppm
No. of animals per sex per dose:
5 males per dose
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 3 animals per dose were sacrificed on Study Day 1, all others were observed for 14 days
- Frequency of observations and weighing: Animals were observed for clinical signs throughout the study. Animals were weighed on Days 1, 2-4, 7-11
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology

Results and discussion

Effect levels
Sex:
male
Dose descriptor:
LC50
Effect level:
> 10 000 ppm
Exp. duration:
4 h
Mortality:
No mortality occurred during the study.
Clinical signs:
other: At 10,000 ppm, animals appeared agitated, had sporadic respiratory rates, were gasping, and had a lack of response to noise stimuli. Upon removal from the exposure chamber, all animals were ataxic, had slightly cool appendages and very slow respiratory r
Body weight:
All animals in the 10,000 ppm dose group lost weight on Study Day 1 and either gained weight or remained the same weight from Study Day 2 until the end of the observation period. Four animals in the 5,000 ppm dose group lost weight on Study Day 1, while one remained the same weight. There were sporadic body weight gains and losses in the remaining test animals through Day 3 post exposure. Both animals gained weight on Day 4 and continued to do so through the remainder of the study period.
Gross pathology:
No gross lesions or abnormalities were noted upon necropsy.
Other findings:
Histopathology: There were no test article-related histologic changes in the lungs, livers or kidney's of test group animals.

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the results of the study, the 4-hour LC50 (gas) of the test article was > 10,000 ppm. Together with the results of the supporting study (LC50 < 15,000 ppm), a classification of Toxicity Category 4 was assigned.
Executive summary:

The acute inhalation toxicity of the test article was evaluated in male Sprague Dawley rats. This study was conducted according custom protocol and was not intended to be compliant with GLP guidelines. The test article was administered as received (as a gas). Rats (5/group) were exposed, whole body to the test article at 0, 5000, or 10000 ppm for a single 4-hour exposure. Control rats receiving 0 ppm of the test material were place in a separate chamber and treated in the same manner as the test groups with the exclusion of the addition of the test material. Of each group, 3 animals were euthanized on Day 1 post-dose for organ examination. The remaining 2 animals from each group were observed until Day 14 post-dose. Clinical observations (throughout study) and body weights (prior to exposure, Day 1, Days 2-4, Days 7-11, and Day 14) were recorded. At euthanasia, blood was collected. Following euthanasia, necropsy was performed on all animals, and lungs, liver, and kidneys were collected and weighed. Histopathological evaluation of the lungs and kidneys were also performed. Clinical observation at the 10,000 ppm exposure level included agitated appearance, sporadic respiratory rates, gasping, and a lack of response to noise stimuli. At the end of exposure, all animals were ataxic, had cool appendages, slow respiratory rates and three (3/5) animals had no grip strength. Clinical observations at the 5,000 ppm exposure level included slow, shallow, and sporadic respiratory patterns, gasping, lack of activity, and decreased response to noise stimuli. A decrease in body weight occurred on Days 1-4 in the 10,000 ppm animals and on Days 1-3 in the 5,000 ppm animals. Weights increased on Days 7 and 4 for the 10,000 and 5,000 ppm treated animals respectively. No gross lesions or other abnormalities were noted in any animal at gross necropsy. Average kidney, liver, and lung organ weights were similar between treated and control animals. No histopathological changes associated with the test article were observed (see additional histopathology report). Based on the results of the study, the 4-hour LC50 (gas) of the test article was > 10,000 ppm.