Registration Dossier

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:
other: Study constructed under GLP conditions.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2007
Report Date:
2007

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))
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1300 (Acute inhalation toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000, including the most recent partial revisions.
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): MTDID 7145
- Molecular weight (if other than submission substance): 399
- Physical state: Clear colorless liquid
- Analytical purity: ~94.5%
- Lot/batch no.: Batch 142072:43
- Expiration date of the lot/batch: 30 December 2007
- Stability under test conditions: Stable
- Storage condition of test material: At room temperature in the dark.
- Other: Vapour pressure: 6.74 +/- 0.40 kPa (at 20 degrees C, determined in Notox project 475177). pH: 7.2. Specific gravity: 1.8

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: 10 weeks
- Weight at study initiation: n.d.; none exceeded +/- 20% of the sex mean.
- Housing:- Diet (e.g. ad libitum): ad libitum (except during exposure to test substance)
- Water (e.g. ad libitum): ad libitum (except during exposure to test substance)
- Acclimation period: at least 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.2-22.7 C
- Humidity (%): 37-69%
- Air changes (per hr):15
- Photoperiod (hrs dark / hrs light): 12 hours dark/12 hours light

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
nose only
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus:vapor generator
- Method of holding animals in test chamber: seperate polycarbonate restraining tubes
- Source and rate of air: 2L/min at animal ports.
- Temperature, humidity, pressure in air chamber: Measured in the pressuriezed air before and after exposure and in the exposure chamber immediately before initiation of exposure with a huminity and temperature indicator. Thermometer mounted
TEST ATMOSPHERE
- Brief description of analytical method used: Animals were exposed to the test material via the inhalatory route. For this purpose the animals were placed in restraining tubes, which were connected to the exposure chamber. The design of the exposure chamber was based on the flow past nose-only inhalation chamber (Am. Ind. Hyg Assoc. J. 44(12): 923-928, 1983). The chamber consisited of animal sections with 8 animal ports each, The number of open animal ports was adapted to the air flow in such a way that at each animal port the theoretical air flow was approximately 2.0 l/min, which ensures an adequate oxygen air supply to the test animals. The inlet of the test atmosphere was located in the top section and the outlet was located in the bottom section. The direction of the flow of the test atmosphere guaranteed a freshly generated atmosphere for each individual animal. All components of the exposure chamber which could come in contact with the test contamination of the laboratory the exposure chamber was placed in a fume hood, which maintained a slight negative pressure.
- Samples taken from breathing zone: Yes
Analytical verification of test atmosphere concentrations:
yes
Remarks:
REES version 1.5, TOXDATA version 8.0, Shimadzu IRsolution software version 1.10
Duration of exposure:
ca. 4 h
Concentrations:
mean actual concentration of 20.6 +/- 1.7 mg/l. The nominal concentration was 21.5 mg/l.
No. of animals per sex per dose:
5 animals/ per sex/per dose. Only one dose level tested.
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 20 mg/L air
Exp. duration:
4 h
Mortality:
No mortality occured.
Clinical signs:
other: During exposure and after exposure, no clinical signs were noted.
Body weight:
Mean body weight gain shown by the animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain. The incidence of slight body weight loss or reduced body weight gain in individual animals were considered not indicative of toxicity, based on the absence of any corrobrative findings in these animals.
Gross pathology:
No gross pathology noted.

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: other: OECD GHS / EU
Conclusions:
The inhalatory LC50, 4hr value of the test article in Wistar rats was established to exceed 20 mg/l.
Executive summary:

The acute inhalation toxicity of this study was done on male and female rats. OECD protocol No 403, “Acute Inhalation Toxicity”, 1996, was followed for this study. The test article was administered by inhalation for 4 hours to one group of five male and five female Wistar rats. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (day 15). The meal actual concentration during the exposure phase of this study was 20.6 mg/L. No mortality occurred during this study and no clinical signs were noted either during or post exposure. The mean body weight gains were similar to control animals and no abnormalities were found at the macroscopic post mortem examination. The inhalation LC50 for the test article in Wistar rats is therefore reported to exceed 20 mg/l. Based on these results, the test article does not have to be classified and has no obligatory labeling requirement for inhalation toxicity according the Globally Harmonized System of Classification and Labeling of Chemicals (GHS) of the United Nations and EC criteria for classification and labeling requirements for dangerous substances and preparation (Council Directive 67/548/EEC).