3-ethyloxetane-3-methanol

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

15 Jun 2017- 10 Jul 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 436 (Acute Inhalation Toxicity: Acute Toxic Class Method)

Version / remarks:

2009

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

3-ethyloxetane-3-methanol

EC Number:

221-254-0

EC Name:

3-ethyloxetane-3-methanol

Cas Number:

3047-32-3

Molecular formula:

C6H12O2

IUPAC Name:

(3-ethyloxetan-3-yl)methanol

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Cited as 3-Oxetanemethanol, 3-ethyl- (EC 221-254-0, CAS 3047-32-3) in the report
- Source and /batch No. of test material: Perstorp Holding AB/ 170100433
- Expiration date of the lot/batch: 31 Jan 2018
- Purity 99.6%

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature and protected from light

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Envigo RMS Spain S.L.
- Females nulliparous and non-pregnant: Yes
- Age at study initiation: 8 weeks
- Weight at study initiation: 181.90- 260.80 g
- Housing:Cageswith Sodispan (SR-CHOPO-T)bedding material
- Diet : (Global diet) Ad libitum (animals were deprived of food during exposure)
- Water : (Tap water) Ad libitum (animals were deprived of water during exposure)
- Acclimation period: 6 days prior to exposure to housing facility and 30 minutes to nose only restraining tubes on day of exposure

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.2 - 24.6 °C
- Humidity (%): 28- 63%
- Photoperiod (hrs dark / hrs light): 12h light: 12h dark

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

air

Mass median aerodynamic diameter (MMAD):

>= 1.489 - <= 1.629 µm

Geometric standard deviation (GSD):

>= 1.55 - <= 1.81

Remark on MMAD/GSD:

Target MMAD range was (1 - 4 µm) and the Target GSD range was (1.5 - 3.0). Mean MMAD during exposure was 1.56 µm. The particle size distributions obtained were considered a respirable range to rats and appropriate for acute inhlation toxicity testing. The general aerosol was considered stable during the whole exposure period

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus:Nose only flow past exposure system. Exposure chambers type- EC-FPC-232 (anodized aluminium) equipped with glass exposure tubes
- Exposure chamber volume: Approximately 3 L
- Method of holding animals in test chamber: Animals were confined separately in restraint tubes which were positioned radially around the exposure chamber.
- Source and rate of air: Approximately 1.07 L/min
- System of generating particulates/aerosols: Nebulizer
- Method of particle size determination: PIXE cascade impactor. The particle size distribution of the test item in the generated aerosol was measured by gravimetry analyzing the test item deposited on each stage of the cascade impactor. MMAD and GSD were determined at the target concentration and calculated on the basis of the results from the cascade impactor, using Microsoft Excel® software (Microsoft Corporation, USA).
- Temperature, humidity, pressure in air chamber: 19-25ºC, 30-70%, 1.0 ± 0.5 L/min

TEST ATMOSPHERE
- Brief description of analytical method used: Gravimetric determination of the aerosol concentration was performed at least once during each hour of exposure and samples were collected onto a Whatman filter (grade F319.04) using a filter sampling device
- Samples taken from breathing zone: Yes

CLASS METHOD
- Rationale for the selection of the starting concentration: A respirable aerosol (MMAD in the range of 1-4 µm) could be achieved at approximately 5 mg/L air with a nebulizer therefore the starting dose was set at 5 mg/L; the limit dose recommended by the guideline.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

Gravimetric analysis

Duration of exposure:

ca. 4 h

Concentrations:

4.93 mg/L (gravimetric concentration) 9.11mg/L air (nominal aerosol concentration)

No. of animals per sex per dose:

3/sex/dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Once during the acclimatization period, on the day of treatment just before starting the inhalation period (day 1 of study), on study days 2, 4, 8 and immediately before sacrifice on study day 15.
- Necropsy of survivors performed: Yes
- Other examinations performed: clinical signs, body weight and gross necropsy consisting of the abdominal and thoracic cavities and special attention was paid to any change in the respiratory tract.

Statistics:

No statistical analysis was required

Results and discussion

Preliminary study:

None performed. Technical trials were however performed without animals and conducted before the in life phase of the study to establish the conditions for aerosol generation.

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 4.93 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Mortality:

No mortalities observed for the duration of the study

Clinical signs:

other: No grossly abnormal signs were observed during the 4 hour exposure period. The main clinical signs present after exposure were transient piloerection, chromodacryorrhea and dirty fur. These clinical signs were said to be due to the stress of the procedur

Body weight:

A decrease in body weight, ranging from 1 to 3 % approximately with respect to body weight on day 1, was observed in all males and 3 % for all but one female from day 1 to day 2 of study. From study day 2 to the end of the observation period (day 15), body weight increased gradually in all three male animals and in two females. In the female ID4 a body weight decrease was recorded until study day 4 (~ 7 %) and thereafter a body weight increase of approximately 9.6 % with respect to day 4, was observed until the end of the observation period.
Mean body weight gains of approximately 20 % and 10 % were recorded for males and two out of three females respectively, during the 14 day observation period (study day 1 to study day 15).

Gross pathology:

No macroscopical findings were observed in any of the animals at necropsy.

Any other information on results incl. tables

Table 1: Individual Bodyweight throughout the study period (Individual values)

Bodyweight (g)
		Day numbers relative to Start date
Sex	Animal	1	2	4	8	15
Male	ID1	252.40	244.00	256.70	279.30	296.40
	ID2	258.50	255.60	268.40	292.60	316.10
	ID3	260.80	252.00	264.60	286.90	312.20
Female	ID4	199.50	194.30	184.80	201.10	202.60
	ID5	184.30	184.40	188.10	197.60	206.90
	ID6	181.90	176.10	185.10	192.10	197.70

 

Table 2: Individual Bodyweight gain throughout the study period (Individual values)

Bodyweight Gain (g)
	Animal	From:	1	2	4	8
Sex		To:	2	4	8	15
Male	ID1		-8.40	12.70	22.60	17.10
	ID2		-2.90	12.80	24.20	23.50
	ID3		-8.80	12.60	22.30	25.30
Female	ID4		-5.20	-9.50	16.30	1.50
	ID5		0.10	3.70	9.50	9.30
	ID6		-5.80	9.00	7.00	5.60

 

 

 

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The LC50 of 3-Oxetanemethanol, 3-ethyl- (EC 221-254-0, CAS 3047-32-3) was found to be greater than 4.93 mg/L air (gravimetric aerosol concentration).

Executive summary:

The acute inhalation toxicity of 3 -Oxetanemethanol, 3-ethyl-(EC 221-254-0, CAS 3047-32-3) was determined in male and female Sprague Dawley rats by the acute toxic class (ATC) method (OECD test guideline No 436). A group of three male and three female Sprague Dawley rats was exposed by nose-only, flow-past inhalation to 3-Oxetanemethanol, 3-ethyl-(EC 221-254-0, CAS 3047-32-3)at a mean concentration of 4.93 mg/L air during 4 hours. All animals were observed for clinical signs and mortality during the exposure and the subsequent 14-day observation period. Body weight was recorded just before starting exposure (study day 1), on study days 2, 4, 8 and immediately before sacrifice and gross necropsy on study day 15. The ranges of aerosol concentration, temperature, relative humidity and air flow rate were considered satisfactory for a study of this type. In addition, the test item was considered to be respirable to rats. No mortality was recorded during the study period. The main clinical signs observed after finishing exposure were chromodacryorrhea, dirty fur and piloerection. All these signs were transient and most of them were not present 1 h after exposure. From study day 2 to the end of the 14 day observation period the animals exhibited a normal behaviour and no clinical signs were recorded. A transient and marginal body weight loss (ranging between 1 % and 3.4 %) was observed in the majority of animals from exposure day to day 2 of the study. Thereafter, body weight increased gradually in all animals except for the female ID4 in which a body weight decrease of ~7 % was observed until study day 4. Mean body weight gains over the 14 day observation period of approximately 20 % and 10 % were recorded for males and two out of three females, respectively. Upon terminal necropsy, no macroscopical findings were observed in any of the animals. It was concluded that, under these experimental conditions, the LC50 of 3-Oxetanemethanol, 3-ethyl-(EC 221-254-0, CAS 3047-32-3) was greater than 4.93 mg/L air (gravimetric aerosol concentration) which is the maximum achieved concentration.