N-[3-({[2,2-dimethyl-3-(morpholin-4-yl)propylidene]amino}methyl)-3,5,5-trimethylcyclohexyl]-2,2-dimethyl-3-(morpholin-4-yl)propan-1-imine

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

from 2014-04-14 to 2014-04-23

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Report date:

2014

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

[2,2-dimethyl-3-(morpholin-4-yl)propylidene][(5-{[2,2-dimethyl-3-(morpholin-4-yl)propylidene]amino}-1,3,3-trimethylcyclohexyl)methyl]amine

EC Number:

700-584-3

Cas Number:

1217271-02-7

Molecular formula:

C28H52N4O2

IUPAC Name:

[2,2-dimethyl-3-(morpholin-4-yl)propylidene][(5-{[2,2-dimethyl-3-(morpholin-4-yl)propylidene]amino}-1,3,3-trimethylcyclohexyl)methyl]amine

Test material form:

other: liquid

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 animals
- Sex: male
- Weight at study initiation: 2958 - 3200 g
- Housing: single housing in metal cages
- Diet: CRLT/ny rabbit diet (Szindbád Kft., 2100 Gödöllő, Szárítópuszta, Hungary) ad libitum
- Water: tap water ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature: 20 ± 3 °C
- Humidity: 30 - 70 %
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.1 mL

Duration of treatment / exposure:

The test substance was applied once to each animal (single treatment). The eyes of the test animals were not washed out 24 hours after the application of test item, because the test substance was removed from the eye of the test animal by physiological mechanisms and the test item did not cause immediately severe irritation or corrosion after test item application.

Observation period (in vivo):

The eyes were examined at 1, 24, 48 and 72 hours, then 1 week after the application. The duration of the observation period was sufficient for the statement of reversibility or irreversibility of changes. Any clinical signs of toxicity or signs of pain and/or distress were recorded twice daily, with a minimum of 6 hours between observations.

Number of animals or in vitro replicates:

3 males

Details on study design:

REMOVAL OF TEST SUBSTANCE
The eyes of the test animals were not washed out 24 hours after the application of test item, because the test substance was removed from the eye of the test animal by physiological mechanisms and the test item did not cause immediately severe irritation or corrosion after test item application.

SCORING SYSTEM:
The eye irritation scores were evaluated according to the scoring system by Draize (1977) and OECD 405 (2012-10-02).

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 1 week

Results 2

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 1 week

Results 3

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.66

Max. score:

3

Reversibility:

fully reversible within: 72 h

Results 4

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 h

Results 5

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 h

Results 6

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 h

Results 7

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 1 week

Results 8

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 1 week

Results 9

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.66

Max. score:

4

Reversibility:

fully reversible within: 72 h

Results 10

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 11

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 12

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Other effects:

Signs of pain and distress as discharge were observed in all animals. These symptoms were detected between treatment day and day 2.

Any other information on results incl. tables

Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test

Score at time point / Reversibility	Cornea	Iris	Conjunctivae	Chemosis
	Max. score: 4	Max. score: 2	Max. score: 3	Max. score: 4
60 min	2, 1, 1	0, 0, 0	1, 1, 1	1, 1, 1
24 h	2, 1, 1	0, 0, 0	1, 1, 1	1, 1, 1
48 h	2, 1, 1	0, 0, 0	1, 1, 1	0, 0, 0
72 h	2, 1, 0	0, 0, 0	1, 1, 0	0, 0, 0
Average 24h, 48h, 72h	2.00, 1.00, 0.66	0, 0, 0	1.00, 1.00, 0.66	0.33, 0.33, 0.33
Reversibility*)	c.	-	c.	c.
Average time for reversion	72 h - 1 week	-	1 week	48 h

 

*) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

Applicant's summary and conclusion

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

The test item Sika Hardener MI applied to the rabbits' eye mucosa caused slight to severe conjunctivae and slight to moderate cornea irritant effects, fully reversible within 1 week.

Executive summary:

The acute eye irritation study of the test item Sika Hardener MI 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, 2012). The test item was placed into the conjunctival sac of the left eye of each animal. The untreated right eye served as control. A volume 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 hours, then 1 week after the application.

One hour after the treatment, slight conjunctival redness and chemosis, moderate to severe discharge, as well as slight to moderate cornea opacity were observed. The area of cornea involved was greater than three quarters, up to the whole area in all animals. 72 hours after treatment slight redness and slight to moderate cornea opacity were recorded. The area of cornea involved was greater than three quarters, up to the whole area. One animal became free of symptoms by this time point.

The individual scores (mean over the time points 24, 48 and 72 hours) for animal 1 were determined as: conjunctivae: 1, chemosis: 0.33, cornea: 2 and iris: 0. For animal 2 the following scores were determined: conjunctivae: 0.66, chemosis: 0.33, cornea: 1, iris:0, and for animal 3: conjunctivae: 1, chemosis: 0.33, cornea: 0.66 and iris: 0.

1 week after the treatment, all animals were free of symptoms, so the study was terminated. No systemic toxicity was observed on the day of the treatment and during the 1-week observation period. The body weight of animals corresponded to their species and age. Signs of pain and distress as discharge were observed in all animals. These symptoms were detected between treatment day and day 2.

The test item Sika Hardener MI applied to the rabbits' eye mucosa caused slight to severe conjunctivae and slight to moderate cornea irritant effects, fully reversible within 1 week.