Butyl ethyl ether

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

2017-01-17 to 2017-04-10

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 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

adopted 02 October 2012

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Butyl ethyl ether

EC Number:

211-055-7

EC Name:

Butyl ethyl ether

Cas Number:

628-81-9

Molecular formula:

C6H14O

IUPAC Name:

1-ethoxybutane

Test material form:

liquid

Details on test material:

- Source and batch No.of test material: 60930023
- Expiration date of the batch: 09/2021
- Purity: 98.4%
- Physical State: liquid
- Density: 0.75 g/cm³
- Colour: colourless
- Storage condition of test material: Keep container tightly closed. Store in a dry and cool area

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, 97633 Sulzfeld, Germany
- Age at study initiation: animal 1: approx. 44 weeks old; animal 2: approx. 41 weeks old
- Weight at study initiation: > 2 kg
- Housing: ABS-plastic or Noryl rabbit cages, floor 4200 cm², in an air-conditioned room
- Diet (e.g. ad libitum): ad libitum - Free access to autoclaved hay and to Altromin 2123 maintenance diet for rabbits, rich in crude fibre
- Water (e.g. ad libitum): ad libitum - Free access to tap water (drinking water, municipal residue control, microbiological controls at regular intervals)
- Acclimation period: at least 5 days under laboratory conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3 °C
- Humidity (%): 55 ± 10%
- Air changes (per hr): at least 10 x / hour
- Photoperiod (hrs dark / hrs light): Artificial light, sequence being 12 hours light, 12 hours dark

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL of the test item was applied to the test site

Duration of treatment / exposure:

single treatment

Observation period (in vivo):

The animals were observed for 72 hours after dosing. To determine the reversibility of the observed effects in animal no. 2, the observation period was extended up to 6 days after dosing.

Number of animals or in vitro replicates:

2 rabbits

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The treated eye was not rinsed after application.

SCORING SYSTEM: Grading system for ocular lesions according to OECD 405

TOOL USED TO ASSESS SCORE: At the end of the observation period the treated eyes were examined with the aid of a fluorescein solution. The eyes were rinsed with physiological saline 0.9% NaCl after the examination.

TEST PROCEDURE:
Initial test: The in vivo test was performed initially using one animal.
Confirmatory test: The results of the initial test did not indicate the test item to be corrosive or a severe irritant to the eye using the procedure described. In order to confirm the response, one additional animal was treated in the same manner. According to OECD 405, section 23, treatment of a third animal was omitted as results from the second animal were sufficient to allow for hazard classification determination.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.67

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Results 2

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 3

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 4

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 5

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 6 days

Results 6

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 7

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 8

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

After the application into the eyes of two male NZW rabbits the test item produced slight irritant but not corrosive effects in both animals, which were fully reversible within 72 hours in animal no. 1 and within 6 days in animal no. 2. Upon fluorescein examinations at the end of the observation period of 72 hours no corneal lesions were found in any animal. Conjunctival redness, chemosis and hypersecretion were observed in both animals.

Other effects:

Neither mortality nor significant clinical signs of toxicity but local effects were observed. Moreover, the body weight development of all animals was within the expected range.

Any other information on results incl. tables

Table 1: Eye Irritation Scores - Animal No. 1
Observation	Animal No. 1, Eye Irritation Scores Post-Application After								Average Score (24, 48 and 72 hours)
	1 hour		24 hours		48 hours		72 hours
	Test item	Control	Test item	Control	Test item	Control	Test item	Control
Redness	0	0	1	0	1	0	0	0	0.67
Chemosis	1	0	0	0	0	0	0	0	0
Iris	0	0	0	0	0	0	0	0	0
Cornea	0	0	0	0	0	0	0	0	0

Table 2: Eye Irritation Scores - Animal No. 2
Observation	Animal No. 2, Eye Irritation Scores Post-Application After								Average Score (24, 48 and 72 hours)
	1 hour		24 hours		48 hours		72 hours
	Test item	Control	Test item	Control	Test item	Control	Test item	Control
Redness	1	0	1	0	1	0	1	0	1
Chemosis	1	0	0	0	0	0	0	0	0
Iris	0	0	0	0	0	0	0	0	0
Cornea	0	0	0	0	0	0	0	0	0

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

In an in vivo acute eye irritation/corrosion study in rabbits, butyl ethyl ether was tested negative regarding irritation to the eye.

Executive summary:

In a primary eye irritation study 0.1 mL of butyl ethyl ether (98.4 % purity) was applied into the conjunctival sac of one eye of two male New Zealand White Rabbits, Crl: KBL (NZW). The treated eye was not rinsed after the application. The untreated eye served as control. Control and treated animals were observed for a period of 72 hours.

Under the conditions of the present study, a single ocular application of the test item to rabbits at a dose of 0.1 mL produced slight irritant but not corrosive effects in both animals, which were fully reversible within 72 hours in animal no. 1 and within 6 days in animal no. 2. Neither mortalities nor significant clinical signs of toxicity were observed. Upon fluorescein examinations at the end of the observation period of 72 hours no corneal lesions were found in any animal.

On the basis of the test results and in conformity with the criteria given in Annex I of Regulation (EC) 1272/2008, the substance should be not classified.