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Diss Factsheets

Administrative data

acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
November 14, 2018 to January 17, 2019
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
The study was performed for worker safety requirements.

Data source

Reference Type:
study report
Report date:

Materials and methods

Test guideline
according to guideline
OECD Guideline 436 (Acute Inhalation Toxicity: Acute Toxic Class Method)
Version / remarks:
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:

Test material

Constituent 1
Chemical structure
Reference substance name:
EC Number:
EC Name:
Cas Number:
Molecular formula:
Test material form:
Details on test material:
Specific gravity: 0.928 (20°C)
Appearance: Colorless liquid
Specific details on test material used for the study:
Storage conditions: Room temperature (actual range: 16.5°C to 21.6°C, permissible range: 10°C to 30°C), dark place, airtight container, filled with nitrogen.

Test animals

Details on test animals or test system and environmental conditions:
Rationale for strain selection:
This strain is widely used in toxicity studies using rodents, and there are abundant historical data.

- Source: Charles River Laboratories Japan, Inc.
- Age at study initiation: 8 weeks old.
- Weight at study initiation: Males: 326.3 to 331.5 g, females: 203.6 to 223.3 g.
- Housing: Two to 3 animals (same sex) /cage. Cages: Polycarbonate cages (W 220 x D 380 x H 183 mm).
- Diet: Pellet food provided ad libitum, no food was provided during inhalation exposure.
- Water: Tap water filtered through a 5-µm pore size filter followed by irradiation with ultraviolet light. Provided ad libitum, no water was provided during inhalation exposure.
- Acclimation period: 5 days.
- Method of randomisation in assigning animals to test and control groups: The stratified-by-weight randomization method based on body weight on the allocation day.

- Temperature: 20.9°C to 22.4°C.
- Humidity: 50.0% to 67.3%
- Air changes: Six to 20 times/hr, all fresh air.
- Photoperiod: Twelve hr/day.

Administration / exposure

Route of administration:
inhalation: mist
Type of inhalation exposure:
nose only
Mass median aerodynamic diameter (MMAD):
>= 3.1 - <= 3.5 µm
Geometric standard deviation (GSD):
>= 2.6 - <= 3
Remark on MMAD/GSD:
The MMAD, GSD, and the weight ratio of particles with a diameter = 4 µm, were 3.5 µm, 2.6, and 55.4% at 1 hour after the start of exposure and 3.1 µm, 3.0, and 59.1% at 3 hours after the start of exposure, respectively.
Details on inhalation exposure:
- Exposure apparatus: A flowpast nose-only inhalation exposure chamber (hereinafter referred to as “chamber”). The chamber is constructed from stackable tiers, which have 16 exposure ports per tier.

- Method of holding animals in test chamber: Animals individually held in the restraint tube.

- Rate of air (airflow): The flow rate of the test atmosphere supply to the chamber was set at 1.25 L/min/exposure-port.

- System of generating particulates/aerosols: The test substance was converted into a mist containing the test substance in vapor-form using a double-fluid nebulizer (NB-2N) connected to a glass container of the test substance by supplying pressurized air at a prescribed flow rate.
The test atmosphere was prepared by mixing the mist and pressurized air at a prescribed flow rate. The test atmosphere was continuously supplied to the chamber for exposure to animals. The air from the chamber was a filtered and transported through an exhaust to the outside.

- Method of particle size determination: calculated from the collected weight of the test substance at each stage and effective cutoff diameter.

- Rationale for the selection of the starting concentration:
The information supplied by the sponsor indicated that no rats died and no changes in clinical signs were observed as a result of a 28-day sub-acute inhalation toxicity study of the test substance at an exposure concentration of 500 ppm in vapor-form (approx. 2.4 mg/L). It was expected that no serious acute inhalation toxicity including death of animals would result from exposure to the test atmosphere at 5 mg/L, which is the upper limit of concentration in the guideline.

Analytical verification:
Nominal concentration was calculated from the amount of test substance supplied to the chamber and the air volume passed through the chamber. Analytical verification (concentration and stability) was done using a validated method (gas chromatography). Samples were taken from the exposure port of the chamber at 30 minutes, 2 hours, and 3 hours 30 minutes after the start of exposure.
Analytical verification of test atmosphere concentrations:
See "Details on inhalation exposure" for more information.
Duration of exposure:
4 h
Remarks on duration:
Inhalation exposure was conducted once for 4 hours.
The actual exposure concentration was 5.21 mg/L compared to a target concentration of 5
mg/L. Nominal concentration was 5.6 mg/L.
No. of animals per sex per dose:
Control animals:
Details on study design:
- Duration of observation period following administration: 14 days.
Examinations and observations:
1- Clinical signs:
Daily observations were conducted from the day of exposure to the day of necropsy at the following frequency:
Day 1: Four times a day (pre-exposure, immediately after the end of exposure, and 1 and 2 hours after the end of exposure).
Day 2 and thereafter: Once a day

2- Body weight:
Body weights of all animals were measured according to the following schedule:
Before exposure on Day 1, Day 2, Day 4, Day 8, and Day 15

3- Pathological examination:
a- Necropsy:
After the observation on Day 15, all animals were subjected to necropsy after euthanization by exsanguination from the abdominal aorta after anesthesia by intraperitoneal injection of thiopental sodium (Ravonal).

b- Histopathological examination:
No tissues or organs were collected, preserved, or subjected to histopathological examination, since there were no gross abnormalities.
No statistical analysis was conducted.

Results and discussion

Effect levels
Key result
Dose descriptor:
Effect level:
> 5 mg/L air
Based on:
test mat.
Exp. duration:
4 h
No dead animals were found.
Clinical signs:
bodyweight loss
Body weight:
Body weight loss from Day 1 was observed in 2 males and 1 female on Day 2. Body weight
gain was observed in all males and females from Day 4.
Gross pathology:
There were no gross abnormalities in any male or female.

Any other information on results incl. tables

The actual exposure concentration was 5.21 mg/L. Regarding particle size distribution in the test atmosphere, MMAD's between 1 and 4 μm with a GSD of 1.5 to 3.0 are recommended by the guideline. It was confirmed that the results of this study were within the recommended ranges. There were no changes in temperature or relative humidity which affected the study results.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Based on the results of an acute inhalation study performed according to OECD guideline 436 and GLP principles, the LC50 of 3-Methoxy-3-methyl-1-butanol was concluded to exceed 5 mg/L.
Executive summary:

The acute inhalation toxicity of 3-Methoxy-3-methyl-1-butanol in rats was assessed according to OECD guideline 436 and GLP principles.

Crl:CD (SD) rats (3 males and 3 females per group) were exposed to a target exposure concentration of 5 mg/L (mist) once for 4 hours by nose only inhalation exposure. Exposure was followed by a 14 day observation period. Clinical observations were conducted and body weights were measured during the observation period. The rats were subjected to necropsy after the observation period.

The actual exposure concentration was found to be 5.21 mg/L. The mass median aerodynamic diameters were 3.5 μm and 3.1 μm with geometric standard deviationsof 2.6 and 3.0 at 1 and 4 hours, respectively.

No animals died during the study and no abnormal clinical signs were observed. No unexpected body weight changes were observed during the observation period. No abnormalities were observed at the necropsy of males or females conducted at the end of the observation period.

In conclusion, the acute inhalation toxicity of MMB was considered to be exceed 5 mg/L (mist).