1-Ethyl-3-methylimidazolium Diethyl Phosphate

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Nov 2016

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

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

2009

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.52 (Acute Inhalation Toxicity - Acute Toxic Class Method)

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:

1-Ethyl-3-methylimidazolium Diethyl Phosphate

Cas Number:

848641-69-0

Molecular formula:

C6H11N2 C4H10O4P

IUPAC Name:

1-Ethyl-3-methylimidazolium Diethyl Phosphate

Test material form:

liquid

Details on test material:

Batch No 187-9-113-Y
Expiry date: 2021-1-30

Specific details on test material used for the study:

Batch No.: Batch 1.3
Purity: 80 % (20% water)
Correction factor 1.25
Yellow liquid

Test animals

Species:

rat

Strain:

Sprague-Dawley

Remarks:

Crl:CD(SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories Germany GmbH, Sulzfeld, Germany
- Females (if applicable) nulliparous and non-pregnant: yes
- Rationale for use of males (if applicable) : according to guideline
- Age at study initiation:
Males: approx. 8 weeks, females: approx. 9 weeks
- Weight at study initiation:
Males: 279-288 g, females: 222-232 g
- Fasting period before study: approx. 16 hours before administration
- Housing: During the 14-day observation period the animals were kept by sex in groups of 3 animals in MAKROLON cages (type III plus)
- Diet (e.g. ad libitum): Commercial diet, ssniff® R/M-H V1534 (ssniff Spezialdiäten GmbH, 59494 Soest, Germany), ad libitum
- Water (e.g. ad libitum): Drinking water in bottles was offered ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C ± 3°C
- Humidity (%): 55% ± 15%
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES:
From: 07.11. To: 24.11.2017

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

air

Mass median aerodynamic diameter (MMAD):

2.59 µm

Geometric standard deviation (GSD):

2.98

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus:
The study was carried out using a dynamic inhalation chamber (air changes/h (≥ 12 times)) with a nose-only exposure of the animals according to KIMMERLE & TEPPER. The apparatus consists of a cylindrical exposure chamber (volume 40 L) which holds a maximum of 20 animals in pyrex tubes at the edge of the chamber in a radial position.

- Exposure chamber volume: 40 L

- Method of holding animals in test chamber: in exposure tubes

- Source and rate of air (airflow)/System of generating particulates/aerosols:
The aerosol of the test item was obtained using a spray-jet. At the bottom of the exposure chamber, the air was sucked off at a lower rate than created by the dust generator in order to produce a homogenous distribution and a positive pressure in the exposure chamber (inflow 900 L/h, outflow 800 L/h). A manometer and an air-flow meter were used to control the constant supply of compressed air and the exhaust, respectively. Flow rates were checked hourly and corrected if necessary.

- Method of particle size determination:
An analysis of the particle size distribution was carried out twice during the exposure period using a cascade impactor according to MAY.
The impactor is a device that classifies particles present in a sample of air or gas into known size ranges. It does this by drawing the air sample through a cascade of progressively finer nozzles. The air jets from these nozzles impact on pre-weighed plane sampling surfaces (slides). Each stage represents an aerodynamic size range and collects finer particles than its predecessor. Each successive stage represents a special aerodynamic cut off diameter. The aerosol from the exposure chamber was drawn through the cascade impactor for 5 minutes at a constant flow rate of 5 L/min. The slides were removed from the impactor and weighed on an analytical balance (SARTORIUS, type 1601 004, precision 0.1 mg). The mass median aerodynamic diameter (MMAD) was estimated by means of non-linear regression analysis. The 32 μm particle size range and the filter (particle size range < 0.5 μm) were not included in the determination of the MMAD in order not to give undue weight to these values. The Geometric Standard Deviation (GSD) of the MMAD was calculated from the quotient of the 84.1%- and the 50%-mass fractions, both obtained from the above mentioned non-linear regression analysis.

- Treatment of exhaust air: The exhaust air was sucked through gas wash-bottles.

- Temperature, humidity in air chamber: 22°C ± 3°C; 57.9 - 58.6%



TEST ATMOSPHERE (if not tabulated)
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.):
2.590 µm / 2.98

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

5.27 mg/L

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
A careful clinical examination was made at least once daily until all symptoms subsided, thereafter each working day. Observations on mortality were made at least once daily to minimize loss of animals to the study, e.g. necropsy or refrigeration of those animals found dead and isolation or sacrifice of weak or moribund animals.
Individual body weights of animals were determined 1 day before administration (acclimatisation period), on test day 1 prior to exposure and on test days 2, 4, 8 and 15.
- Necropsy of survivors performed:
yes, necropsy of all animals was carried out and all gross pathological changes were recorded. The weight of the lungs of all animals was determined
- Other examinations performed:
The following organs of all animals were fixed in 10% (nose, i.e. head without brain, eyes, and lower jaw) or 7% (other organs) buffered formalin for a potential histopathological examination (subject to the Sponsor’s consent):
- Nose
- Larynx
- Trachea
- Lungs

Statistics:

none

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.27 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

No animal died prematurely

Clinical signs:

other: slight dyspnoea on test day 1 in all 3 of 3 male and 3 of 3 female animals

Body weight:

2 of 3 female animals appeared to be reduced in body weight gain

Gross pathology:

Necropsy revealed slightly oedematous lungs in all 6 animals.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the present test conditions, the LC50 value for rats following inhalation of CrysCOPlus5100 for 4 hours was determined as follows (actual concentration, mean aerosol concentration):
LC50 males and females combined (14 days):
> 5.27 mg/L air/4 hours (actual concentration).

Executive summary:

The aim of the present study was to assess the acute inhalation toxicity of the test item when administered to rats for a single 4 -hour period.

The test item is a yellow liquid with a water content of 20%. A correction factor of 1.25 was employed. Thus, all information on concentration refers to the waterfree test item. Rats were exposed to the test substance at an actual concentration of 5.27 mg/L air for 4 hours by inhalation using a dynamic nose-only exposure chamber. In the inhalation chamber, close to the animals' noses, the generated aerosol had a mass median aerodynamic diameter (MMAD) of 2.590 µm as determined with a cascade impactor. The Geometric Standard Deviation (GSD) of the MMAD was calculated as 2.98.

A 4 -hour exposure to the test item at the concentration of 5.27 mg/L air revealed slight dyspnoea on test day 1 in all 3 of 3 male and 3 of 3 female animals. No animal died prematurely. Two of 3 female animals appeared to be reduced in body weight gain. Necropsy revealed slightly oedematous lungs in all 6 animals.

LC50 value for males and females combined > 5.27 mg/L air (4 hours).