Reaction products of 3-aminomethyl-3,5,5-trimethylcyclohexylamine with 2,2'-[(1-methylethylidene)bis(4,1-phenyleneoxymethylene)]bisoxirane

Endpoint summary

Description of key information

Skin irritation:

The test item was tested for skin irritation in albino New Zealand white rabbits according to EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion). The results showed very slight to well defined erythema. No edema was observed during the study. The irritation signs decreased completely during the observation period and were evaluated as fully reversible alterations.

Eye irritation:

The test item was tested for eye irritation properties in albino New Zealand white rabbits according to EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion). The results showed moderate conjunctival redness, slight to moderate chemosis and moderate to severely increased discharge excretion in all animals. All signs of irritation decreased during the observation period.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

from 2007-10-03 to 2007-12-03

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

2002

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Version / remarks:

2004/73/EC

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Version / remarks:

August 1988

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: TETRABBIT Kft. 2173 Kartal, Császár út 135, HUNGARY
- Age at study initiation: Young adult rabbits, 10 weeks old
- Weight at study initiation: 2834 - 3389 g
- Housing: Animals were housed individually in metal cages
- Diet: The animals received PURINA Base – Lap gr. diet for rabbits produced by AGRIBRANDS Europe Hungary PLC, H-5300 Karcag, Madarasi road, Hungary, ad libitum
- Water: The animals received as tap water from self-service water system ad libitum
- Acclimation period: 15 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3 °C
- Humidity (%): 30 - 70 %
- Air changes (per hr): 8 - 12 air exchange/hour by central air-condition system
- Photoperiod: 12 hours daily, from 6.00 a.m. to 6.00 p.m.

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.5 g
- Concentration: None

VEHICLE
- Amount(s): None

Duration of treatment / exposure:

4 hr

Observation period:

Animals were examined for signs of erythema and oedema, and the responses scored at 60 minutes, and then at 24, 48, 72 hours, then one week after the patch removal.

Number of animals:

3 Male

Details on study design:

TEST SITE
- Area of exposure: approximately 6 cm² of intact skin
- % coverage: Not estimated
- Type of wrap if used: Plastic wrap for 4 hrs

REMOVAL OF TEST SUBSTANCE
- Washing: Water of body temperature
- Time after start of exposure: 4 hrs

SCORING SYSTEM: Draize (1959)

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

9143/M

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

9135/M

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

9139/M

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

1.1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

9143/M

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

9135/M

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

9139/M

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

Very slight erythema in two animals (score 1), well defined erythema (score 2) in one animal. No oedema in all animals. No irritation symptoms /erythema, oedema, and/or other signs)) were observed after 1 week. Study was terminated one week after treatment.

Other effects:

no other effects observed

Interpretation of results:

GHS criteria not met

Conclusions:

The test item was tested for skin irritation in rabbits. The observed symptoms were evaluated as fully reversible alterations.

Executive summary:

In this skin irritation study albino New Zealand White rabbits were treated with the test item. The test item was applied to the intact skin of rabbits as a single dose of 0.5 g. The irritation symptoms were examined at 1, 24, 48 and 72 hours, then one week after the patch removal.

One hour after the patch removal in two animals very slight erythema (scores 1-1) and in one animal well defined erythema (score 2) was observed on the treated skin surfaces. There was no oedema observed during the study.

24 hours after the patch removal the degree of erythema did not change compared to the previous observation.

48 hours after the patch removal very slight erythema (scores 1-1-1) was found in all animals.

72 hours after the patch removal the irritation symptoms did not change compared to the previous observation.

1 week after the patch removal, no irritation symptoms (erythema, oedema and/or other signs) were observed in any of the animals. Thus, one week after the treatment the study was terminated.

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

- erythema: 1.00, 1.00, 1.33

- oedema: 0.00, 0.00, 0.00

During the study the control areas of all animals were symptom-free. During the study the general state and behaviour of all animals were normal. There were no notable body weight changes during the contact and observation period.

Reference 2

Endpoint:

skin irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

from 2007-10-03 to 2007-12-03

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

2002

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

2004/73/EC

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Version / remarks:

August 1998

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: TETRABBIT Kft. 2173 Kartal, Császár út 135, HUNGARY
- Age at study initiation: Young adult rabbits, 10 weeks old
- Weight at study initiation: 3126 - 3240 g
- Housing: Animals were housed individually in metal cages
- Diet: The animals received PURINA Base – Lap gr. diet for rabbits produced by AGRIBRANDS Europe Hungary PLC, H-5300 Karcag, Madarasi road, Hungary, ad libitum
- Water: The animals received tap water from self-service water system ad libitum
- Acclimation period: 16 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 30 - 70
- Air changes: 8 - 12 air exchange/hour by central air-condition system
- Photoperiod: 12 hours daily, from 6.00 a.m. to 6.00 p.m.

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.1 g

VEHICLE
- None

Duration of treatment / exposure:

1 h

Observation period (in vivo):

1, 24, 48, 72 hrs, one week

Number of animals or in vitro replicates:

3 males

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: Not applied

SCORING SYSTEM: Draize 1959

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

Irritation parameter:

cornea opacity score

Basis:

animal #1

Remarks:

9103/M

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

cornea opacity score

Basis:

animal #2

Remarks:

9111/M

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

cornea opacity score

Basis:

animal #3

Remarks:

9175/M

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

iris score

Basis:

animal #1

Remarks:

9103/M

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

fully reversible

Irritation parameter:

iris score

Basis:

animal #2

Remarks:

9111/M

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

fully reversible

Irritation parameter:

iris score

Basis:

animal #3

Remarks:

9175/M

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

fully reversible

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #1

Remarks:

9103/M

Time point:

24/48/72 h

Score:

1.67

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #2

Remarks:

9111/M

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #3

Remarks:

9175/M

Time point:

24/48/72 h

Score:

1.33

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

mean

Time point:

24/48/72 h

Score:

1.31

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

animal #1

Remarks:

9103/M

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

animal #2

Remarks:

9111/M

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

animal #3

Remarks:

9175/M

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

conjunctivae score

Remarks:

(discharge)

Basis:

animal #1

Remarks:

9103/M

Time point:

24/48/72 h

Score:

0.67

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

conjunctivae score

Remarks:

(discharge)

Basis:

animal #2

Remarks:

9111/M

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

conjunctivae score

Remarks:

(discharge)

Basis:

animal #3

Remarks:

9175/M

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

conjunctivae score

Remarks:

(discharge)

Basis:

mean

Time point:

24/48/72 h

Score:

0.22

Max. score:

3

Reversibility:

fully reversible within: 7 days

Other effects:

No other effects

Interpretation of results:

GHS criteria not met

Conclusions:

The test item, applied to the rabbits' eye mucosa, caused slight to severe conjunctival irritant effects and in one case slight corneal alteration, which were fully reversible within one week.

Executive summary:

The acute eye irritation study of the test item was performed in three albino 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. The treated eyes of the test animals were not washed out following the instillation of 0.1 g of the test item, administered in pure state, in single dose. The eyes were examined at 1, 24, 48, 72 hours and one week after application.

One hour after the application of the test item into the eyes of rabbits moderate conjunctival redness, slight to moderate chemosis and moderate to severely increased discharge excretion. In one animal diffuse areas of opacity were observed on whole surface of cornea. Iris alterations were not recorded throughout the study.

72 hours after the application in two cases slight redness was found. In above mentioned animal the degree and extension of opacity density did not change to the previous observations. One animal became symptom-free at this time.

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

The general state and the behaviour of animals were normal throughout the study period. There were no notable body weight changes during the contact and observation period.

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

- cornea opacity: 1.00, 0.00, 0.00

- iris: 0.00, 0.00, 0.00

- conjunctival redness: 1.67, 1.00, 1.33

- conjunctival chemosis: 1.00, 0.00, 0.00

- conjunctival discharge: 0.67, 0.00, 0.00

The test item, applied to the rabbits' eye mucosa, caused slight to severe conjunctival irritant effects and in one case slight corneal alteration, which were fully reversible within one week.

Reference 2

Endpoint:

eye irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

In a skin irritation study albino New Zealand White rabbits were treated with the test item. The test item was applied to the intact skin of rabbits as a single dose of 0.5 g. The irritation symptoms were examined at 1, 24, 48 and 72 hours, then one week after the patch removal. One hour after the patch removal in two animals very slight erythema (scores 1-1) and in one animal well defined erythema (score 2) was observed on the treated skin surfaces. There was no edema observed during the study. 24 hours after the patch removal the degree of erythema did not change compared to the previous observation. 48 hours after the patch removal very slight erythema (scores 1-1-1) was found in all animals. 72 hours after the patch removal the irritation symptoms did not change compared to the previous observation. 1 week after the patch removal, no irritation symptoms (erythema, edema and/or other signs) were observed in any of the animals. Thus, one week after the treatment the study was terminated. The animals’ individual mean scores (considering readings at 24, 48 and 72 hours after patch removal) were as follows:

- erythema: 1, 1, 1.33

- edema: 0, 0, 0

During the study the control areas of all animals were symptom-free. During the study the general state and behaviour of all animals were normal. There were no notable body weight changes during the contact and observation period.

Eye irritation

The acute eye irritation study of the test item was performed in three albino 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. The treated eyes of the test animals were not washed out following the instillation of 0.1 g of the test item, administered in pure state, in single dose. The eyes were examined at 1, 24, 48, 72 hours and one week after application. One hour after the application of the test item into the eyes of rabbits moderate conjunctival redness, slight to moderate chemosis and moderate to severely increased discharge excretion. In one animal diffuse areas of opacity were observed on whole surface of cornea. Iris alterations were not recorded throughout the study. 72 hours after the application in two cases slight redness was found. In above mentioned animal the degree and extension of opacity density did not change to the previous observations. One animal became symptom-free at this time. One week after treatment the study was terminated, as all animals were free of symptoms of irritation. The general state and the behaviour of animals were normal throughout the study period. There were no notable body weight changes during the contact and observation period. The animals’ individual mean scores (considering readings at 24, 48 and 72 hours after the treatment) were as follows:

- cornea opacity: 1, 0, 0

- iris: 0, 0, 0

- conjunctival redness: 1.67, 1.00, 1.33

- conjunctival chemosis: 1.00, 0, 0

- conjunctival discharge: 0.67, 0, 0

The test item, applied to the rabbits' eye mucosa, caused slight to severe conjunctival irritant effects and in one case slight corneal alteration, which were fully reversible within one week. According to the EC criteria for classification and labelling requirements for dangerous substances and preparations the test item does not have to be classified and has no obligatory labelling requirement for eye irritation.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. As a result the substance is not considered to be classified for skin and eye irritation under Regulation (EC) No 1272/2008, as amended for the tenth time in Regulation (EU) No 2017/776.