Bis[2-[2-(1-methylethyl)-3-oxazolidinyl]ethyl] hexan-1,2-diylbiscarbamate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

26 September 2012 to 06 December 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

24 April 2002

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Version / remarks:

30 May 2008

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Version / remarks:

August 1998

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Bis[2-[2-(1-methylethyl)-3-oxazolidinyl]ethyl] hexan-1,2-diylbiscarbamate

EC Number:

261-879-6

EC Name:

Bis[2-[2-(1-methylethyl)-3-oxazolidinyl]ethyl] hexan-1,2-diylbiscarbamate

Cas Number:

59719-67-4

Molecular formula:

C24H46N4O6

IUPAC Name:

bis[2-(2-isopropyl-1,3-oxazolidin-3-yl)ethyl] hexane-1,6-diylbiscarbamate

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: S & K LAP Kft. 2173 Kartal, Császár út 135, Hungary
- Age at study initiation: young adult male rabbits
- Weight at study initiation: 2625 - 3356 g
- Housing: Animals were housed individually in metal cages.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 18 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20 ± 3 °C
- Humidity: 30 - 70 %
- Air changes (per hr): 9 - 12
- Photoperiod (hrs dark / hrs light): 12 hours artificial light, from 6 a.m. to 6 p.m.

IN-LIFE DATES: From: 01 October 2012 To: 15 October 2012

Test system

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.1 mL

Duration of treatment / exposure:

The eyes of the test animals were not washed out after the application of test item.

Observation period (in vivo):

The eyes were examined at 1, 24, 48 and 72 hour(s) and then at 1 and 2 weeks after the application.

Number of animals or in vitro replicates:

3

Details on study design:

SCORING SYSTEM: The eye irritation scores were evaluated according to the scoring system by Draize (1979) and OECD 405 (24 April 2002)

TOOL USED TO ASSESS SCORE: hand-slit lamp / biomicroscope

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 2 weeks

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Max. score:

4

Reversibility:

fully reversible within: 2 weeks

Remarks on result:

other: No calculation of score due to severely conjunctivae irritation after 24 and 48 h

Results 3

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 2 weeks

Results 4

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 5

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Max. score:

2

Remarks on result:

other: No calculation of score due to severely conjunctivae irritation after 24 and 48 h.

Results 6

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 7

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.66

Max. score:

4

Reversibility:

fully reversible within: 2 weeks

Results 8

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

3.33

Max. score:

4

Reversibility:

fully reversible within: 2 weeks

Results 9

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 2 weeks

Results 10

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.33

Max. score:

3

Reversibility:

fully reversible within: 2 weeks

Results 11

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Max. score:

3

Reversibility:

fully reversible within: 2 weeks

Remarks on result:

other: No calculation of score due to severely conjunctivae irritation after 24 and 48 hr.

Results 12

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 2 weeks

Irritant / corrosive response data:

One hour after the treatment, moderate conjunctival redness, moderate to severe chemosis and discharge, as well as slight cornea opacity were observed. The area of cornea involved was one quarter in one animal and was greater than half, but less than three quarters in other animal. Redness of conjunctivae, corneal and iris alterations could not be observed in third animal treated due to the swelling the lids were completely closed.

72 hours after the treatment, slight to moderate redness and discharge and moderate chemosis, as well as slight to moderate cornea opacity were detected. The area of cornea involved was greater than one quarter, but less than half or was greater than half, but less than three quarters.

1 week after the treatment, slight to moderate redness, slight chemosis and discharge, as well as slight cornea opacity were found. The area of cornea involved was one quarter. One animal became free of symptoms.

2 weeks after treatment the study was terminated, as all animals were free of symptoms of irritation.

Applicant's summary and conclusion

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

In conclusion, test item applied to the rabbits' eye mucosa, caused slight to severe conjunctival and slight to moderate corneal irritant effects, fully reversible within 2 weeks.

Executive summary:

The acute eye irritation study of the test item was performed in three New Zealand White rabbits. The irritation effect of the test item was evaluated according to the Draize method (OECD No.: 405, 2002).

The test item was placed into the conjunctival sac of the left eye of each animal. The untreated right eye served as control. A weight of 0.1 ml of the test item was used in pure state, as a single dose. The eyes of the test animals were not washed out after the application of test item.

The eyes were examined at 1, 24, 48 and 72 hour(s) and then at 1 and 2 weeks after the application.

One hour after the treatment, moderate conjunctival redness, moderate to severe chemosis and discharge, as well as slight cornea opacity were observed. The area of cornea involved was one quarter in one animal and was greater than half, but less than three quarters in other animal. Redness of conjunctivae, corneal and iris alterations could not be observed in third animal treated due to the swelling the lids were completely closed.

72 hours after the treatment, slight to moderate redness and discharge and moderate chemosis, as well as slight to moderate cornea opacity were detected. The area of cornea involved was greater than one quarter, but less than half or was greater than half, but less than three quarters.

1 week after the treatment, slight to moderate redness, slight chemosis and discharge, as well as slight cornea opacity were found. The area of cornea involved was one quarter. One animal became free of symptoms.

2 weeks after treatment the study was terminated, as all animals were free of symptoms of irritation.

The animals’ individual mean scores (considering readings at 24, 48 and 72 hours after the treatment) were as follows:

cornea opacity: 1.00, n.d., 2.00

iris: 0.00, n.d., 0.00

redness: 1.33, n.d., 2.00

chemosis: 0.66, 3.33, 2.00

 

(n.d.: The respective mean values of redness of conjunctivae, cornea opacity and iris could not be calculated, due to the severe conjunctivae irritation as the swelling the lids were completely closed.)

 

In conclusion, test item applied to the rabbits' eye mucosa, caused slight to severe conjunctival and slight to moderate corneal irritant effects, fully reversible within 2 weeks.

According to Regulation (EC) No 1272/2008, the test item should be classified into “Category 2 (reversible effects on the eye/irritating to eyes)” on basis of corneal and conjunctivae irritation sign as cornea opacity and chemosis.

However, it is to be noted that the test item caused severe conjunctivae irritation sign as chemosis in one animal in 24 and 48 hours after the treatment, so the redness, cornea opacity and iris irritation could not be scored.