reaction product of diphenylmethanediisocyanate, toluenediisocyanate ( reaction mass of isomers: 65 % 2,4- and 35 % 2,6-diisocyanate), octylamine, oleylamine and 4-ethoxyaniline (molar ratio 3.88:1:6.38:0.47:2.91)

Endpoint summary

Description of key information

In the available skin and eye irritation/ corrosion studies in rabbits performed according to OECD Guidelines 404 and 405 respectively, the test substance showed no irritation/ corrosion effects. 

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:

1999-02-16 until 1999-02-20

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

adopted 17 July 1992

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Version / remarks:

EPA 712-C-96-196, June 1996

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: Charles River Deutschland GmbH, D-88353 Kißlegg, Germany
- Weight at study initiation: 2.6 - 2.7 kg
- Housing: individually housed in ABS - plastic rabbit cages, floor 4200 cm²
- Diet: Altromin 2123 maintenance diet for rabbits, rich in crude fibre, totally pathogen free-TPF
- Water: tap water
- Acclimatisation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature: 18 ± 3°C
- Humidity: 55 ± 10%
- Air changes: at least 10 x / hour
- Photoperiod: artificial light, lighting regime 12 : 12 hours, light 6.30 -18.30

Type of coverage:

semiocclusive

Preparation of test site:

abraded

Vehicle:

other: CMC (drop down)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

Single dose of 0.5 g

Duration of treatment / exposure:

4 hours

Observation period:

72 hours (14 days observation period was not required as no indications which had to be examined for reversibility were observed).

Number of animals:

3 female animals

Details on study design:

TEST SITE
- Area of exposure: 6 cm² on one side of the dorsal area
- Type of wrap if used: the test item was applied to the patch first (gauze patch), and then applied to the skin. The patch was fixed with a semi-occlusive dressing with non-irritating tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with water
- Time after start of exposure: 4 hours

SCORING SYSTEM: as indicated in the OECD guideline 404

Irritation parameter:

erythema score

Basis:

mean

Remarks:

mean score animal 1, 2, 3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

mean

Remarks:

mean score animal 1, 2, 3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

The test item showed no irritant effects on the intact skin after a contact time of 4 hours. No skin reactions (erythema, oedema) were recorded throughout the observation period of 72 hours as compared to untreated control sites. There were no significant body weight changes during the contact and observation period.

Other effects:

No other effects

There were no significant body weight changes during the contact and observation period.

Interpretation of results:

not classified

Conclusions:

Under the conditions of this study, the test substance was considered to have no skin irritation/corrosive effects.

Executive summary:

The test substance was tested for its skin irritation/ corrosion properties in a study performed according to EU Method B.4, OECD Guideline 404 and EPA OPPTS 870.2500. The test substance was applied to one site of the clipped back of 3 rabbits at a dose of 0.5 g per application site while the untreated side served as control. The application site was covered with a semi-occlusive bandage for a 4 hour - contact/ exposure time. Observations were recorded and compared to the control sites, 1, 24, 48 and 72 hours after removal of the patch. The test item showed no irritant/ corrosive effects on the intact skin within 72 hours after removal of the test item. No other clinical signs of toxicity were observed. Under the conditions of the study, the test substance was considered to have no irritation/corrosive properties.

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:

1999-02-22 until 1999-02-26

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:

adopted 24 Feb., 1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Version / remarks:

EPA 712-C-96-195, June 1996

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: Charles River Deutschland GmbH, D-88353 Kißlegg, Germany
- Weight at study initiation: 2.6 - 2.9 kg
- Housing: individually housed in ABS - plastic rabbit cages, floor 4200 cm²
- Diet: Altromin 2123 maintenance diet rabbit, rich in crude fibre, totally pathogen free-TPF
- Water: tap water (drinking water, municipal residue control, microbiol. controlled periodically)
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature: 18 ± 3°C
- Humidity: 55+ 10%
- Air changes: :at least 10 x / hour
- Photoperiod: artificial light, lighting regime 12 : 12 hours, light 6.30 -18.30

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

0.1 g of the test substance

Duration of treatment / exposure:

72 hours (same as the observation period as the test substance was not washed away)

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

3 female animals

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: the test substance was not washed

SCORING SYSTEM: as indicated in the OECD Guideline 405

TOOL USED TO ASSESS SCORE: fluorescein

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

mean score animal 1, 2, 3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

mean

Remarks:

mean score animal 1, 2, 3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

mean

Remarks:

mean score animal 1, 2, 3

Time point:

24/48/72 h

Score:

0

Max. score:

3

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

mean score animal 1, 2, 3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

The application of the test item at a dose of 0.1 g caused minimal blepharospasm in all animals immediately after the application.
1 hour after application a slight erythema of the conjunctivae was visible two of three animals.
No signs of irritation were visible at the 24 h reading in all of the 3 test animals.
No Cornea lesions were found upon fluorescein examination at the 72 h reading.
The test item produced no corrosion or irreversible effects in any of the animals.
No other toxic effects were observed.

Interpretation of results:

not classified

Conclusions:

Under the study conditions it was concluded that the test item caused no irritation and no corrosive effects to the eyes of rabbits.

Executive summary:

The test item was tested for its eye irritation/ corrosion properties according to EU Method B.5, OECD Guideline 405 and EPA OPPTS 870.2400. In the available study the test item was applied to the lower conjunctival sac of one eye of 3 rabbits at a dose of 0.1 g per application site and it was not rinsed thereafter. The untreated eye served as control. Observations were calculated and compared to controls 1, 24, 48 and 72 hours after application of the test item. Application of the test item caused minimal blepharospasm in all animals immediately after application and 1 hour after application a slight erythema of the conjunctivae was visible. No signs of irritation were visible at the 24 hours reading in all of the 3 test animals. No corneal lesions were found upon fluorescein examination at the 72 h reading. Thus, the mean cornea, iris, conjunctivae score redness and chemosis for all 3 animals was 0. No corrosion effect were observed. Under the study conditions the test item was considered to have no irritation and no corrosive effects to eyes of rabbits.

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)

Additional information

Skin:

The test substance was tested for its irritation/ corrosion properties in a study performed according to EU Method B.4, OECD Guideline 404 and EPA OPPTS 870.2500. The test substance was applied to one site of the clipped back of 3 rabbits at a dose of 0.5 g per application site while the untreated side served as control. The application site was covered with a semi-occlusive bandage for a 4 hour - contact/ exposure time. Observations were recorded and compared to the control sites, 1, 24, 48 and 72 hours after removal of the patch. The test item showed no irritant/ corrosive effects on the intact skin within 72 hours after removal of the test item. No other clinical signs of toxicity were observed. Under the conditions of the study, the test substance was considered to have no irritation/corrosive properties.

Eye:

The test item was tested for its eye irritation/ corrosion properties according to EU Method B.5, OECD Guideline 405 and EPA OPPTS 870.2400. In the available study the test item was applied to the lower conjunctival sac of one eye of 3 rabbits at a dose of 0.1 g per application site and it was not rinsed thereafter. The untreated eye served as control. Observations were calculated and compared to controls 1, 24, 48 and 72 hours after application of the test item. Application of the test item caused minimal blepharospasm in all animals immediately after application and 1 hour after application a slight erythema of the conjunctivae was visible. No signs of irritation were visible at the 24 hours reading in all of the 3 test animals. No corneal lesions were found upon fluorescein examination at the 72 h reading. Thus, the mean cornea, iris, conjunctivae score redness and chemosis for all 3 animals was 0. No corrosion effect were observed. Under the study conditions the test item was considered to have no irritation and no corrosive effects to eyes of rabbits.

Justification for classification or non-classification

Based on the results obtained, the test substance was not classified and labelled for skin and eye irritation/ corrosion according to Regulation No (EC) 1272/2008 (CLP).