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Administrative data

Description of key information

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Klimisch reliability of study is 1 (GLP guideline study); according to ECHA Practical Guide 6 rel. 2 is selected from the IUCLID pick-list as this should be the maximum score for read-across.
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
(2002)
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Strain: New Zealand White A1077 INRA (SPF)
- Source: Centre Lago S.A., 01540 Vonnas, France
- Age at study initiation: About 5 months
- Weight at study initiation: 3.08 - 3.39 kg
- Housing: Single housing in stainless steel wire mesh cages with grating, floor area: 3000 cm²
- Diet: Kliba-Labordiät, Provimi Kliba SA, Kaiseraugst, Switzerland (about 130 g/animal per day)
- Water: Tap water ad libitum
- Acclimation period: At least 5 days before the beginning of the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12 / 12
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
other: Untreated skin sites of the same animal.
Amount / concentration applied:
0.5 ml
Duration of treatment / exposure:
4 hours
Observation period:
14 days
Number of animals:
3
Details on study design:
- Clipping of the fur: At least 24 hours before the beginning of the study clipping of the dorsolateral part of the trunk of the animal(s).
- Body weight determination: Just before application of the test substance and after the last reading.
- Route of application: The test substance was applied in a single dose to the intact untreated skin The test patch was secured in position with a semiocclusive dressing. The test substance was removed at the end of the exposure period with Lutrol and Lutrol/water (1 : 1).
- Readings: lmmediately after removal of the patch, approx. 1, 24, 48 and 72 h after removal of the patch and then in weekly intervals up to day 14.
- Illumination used for reading: Daylight tubes "Lumilux" (L 58W/860 PLUS ECO 25X1, Osram, Germany)
- Check for dead animals or moribund: Twice each workday (beginning and end) and once on Saturdays, Sundays and on public holidays.
- Evaluation of results: For evaluation, the calculation of the mean values of erythema and edema for readings 24, 48 and 72 hours were quoted. Additionally, the reversibility of the observed findings was taken into account.
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 24, 48, 72 hours
Score:
>= 2 - <= 3
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: mean score after 72h: 2.3
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 24, 48, 72 hours
Score:
>= 1 - <= 3
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: mean score after 72 h: 2
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 24, 48, 72 hours
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
animal: #1, #2, #3
Time point:
other: 24, 48, 72 hours
Score:
>= 0 - <= 1
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: mean score after 72 h: 0.3
Irritant / corrosive response data:
- Moderate erythema (grade 2), observed in all animals immediately and 1 hour after removal of the patch, increased to marked (grade 3) in all animals after 24 hours and decreased to slight or moderate (grade 1 or 2) in one or two animals after 48 and 72 hours. In one animal marked erythema persisted up to 72 hours, decreased to slight after day 7 and persisted up to study termination on day 14.
- Slight edema (grade 1) was noted in all animals immediately after removal of the patch up to 24 hours.
- Additionally erythema was extended beyond the area of exposure in all animals after 24 hours up to 72 hours. Moreover scaling and dryness of the skin was noted. The cutaneous reactions were reversible in two animals within 7 days, while in one animal slight erythema and scaling was still present up to study termination on day 14. Mean scores over 24, 48 and 72 hours for each animal were 2.3, 2.0 and 3.0 for erythema and 0.3 for edema.

For assessing skin irritation in vivo a read across to a substance with a very similar chemical composition (EC No. 900 -066 -9; comparable allophanate-type HDI oligomerisation product) is applied.The read across is based on physicochemical and toxicological similarity of the two substances. Especially a comparative pulmonary irritant potency study according to TRGS 430 (Technical Rule for Hazardous Substances 430; published by the German Federal Ministry of Labour and Social Affairs, 2009), as the key study for justification of read-across, confirmed for both substances the same toxicological mode of action and nearly identical potency. For further justification of the grouping and read-across according to regulation (EC) No 1907/2006, Annex XI, 1.5 see document attached to chapter "Assessment Reports".

 

Executive summary:

An Acute Skin Irritation/Corrosion test according to OECD 404 was conducted with the test substance. Slight to marked erythema, partly extending beyond the area of exposure and slight edema were observed in the animals during the course of the study. Additionally dryness of the skin and scaling were noted during the observation period. The cutaneous reactions were reversible in two animals within 7 days, while in one animal slight erythema and scaling was still present up to study termination on day 14. The average scores for erythema (24, 48 and 72 hours) were 2, 2.3, 3 and for edema 0.3, 0.3, 0.3.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Klimisch reliability of study is 1 (GLP guideline study); according to ECHA Practical Guide 6 rel. 2 is selected from the IUCLID pick-list as this should be the maximum score for read-across.
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
(2002)
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Strain: New Zealand White A1077 INRA (SPF)
- Source: Centre Lago S.A., 01540 Vonnas, France
- Age at study initiation: About 6 - 7 months
- Weight at study initiation: 3.52 - 3.82 kg
- Housing: Single housing in stainless steel wire mesh cages with grating, floor area: 3000 cm²
- Diet: Kliba-Labordiät, Provimi Kuba SA, Kaiseraugst, Switzerland (about 130 g/animal per day)
- Water: Tap water ad libitum
- Acclimation period: At least 5 days before the beginning of the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12 / 12
Vehicle:
unchanged (no vehicle)
Controls:
other: Untreated left eye
Amount / concentration applied:
0.1 mL
Duration of treatment / exposure:
24 hours. The test substance was applied in a single dose to the conjunctival sac of the right eyelid. About 24 hours after application of the liquid test substance the treated eye of the animal(s) was rinsed with 3 to 6 ml of hand warm tap water tor 1 to 2 minutes using a syringe with a blunt probe.
Observation period (in vivo):
Animals were monitored approx. 1, 24, 48 and 72 h after application and then in weekly intervals maximally up to day 28.
Number of animals or in vitro replicates:
1 female, 2 males
Details on study design:
- Body weight determination: Just before application of the test substance and after the last reading.
- Route of application: The test substance 0.1 mL (undiluted) was applied in a single dose to the conjunctival sac of the right eyelid.
- Rinsing of the eye: About 24 hours after application of the liquid test substance the treated eye of the animal(s) was rinsed with 3 to 6 mL of hand warm tap water tor 1 to 2 minutes using a syringe with a blunt probe.
- Readings: Approx. 1, 24, 48 and 72 h after application.
- Illumination used tor reading: Daylight tubes ‹Lumilux" (L 58W/860 PLUS ECO 25X1, Osram, Germany)
- Check for dead or moribund Twice each workday (beginning and end) and once animais: on Saturdays, Sundays and on public holidays.
Irritation parameter:
cornea opacity score
Basis:
animal: #1, #2, #3
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
animal: #1, #2, #3
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #1
Time point:
other: 24, 48, 72 hours
Score:
>= 0 - <= 1
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: mean score after 72h: 0.3
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal: #2, #3
Time point:
other: 24, 48, 72 hours
Score:
>= 0 - <= 2
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: mean score after 72h: 1.3
Irritation parameter:
chemosis score
Basis:
animal: #1, #3
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: 24, 48, 72 hours
Score:
>= 0 - <= 1
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: mean score after 72h: 0.3
Irritant / corrosive response data:
- Slight conjunctival redness (grade 1) was observed in one animal 1 hour after application up to 24 hours. Two animals showed moderate conjunctival redness (grade 2) from 1 hour until 48 hours after application. Slight conjunctival chemosis (grade 1) was noted in one animal 24 hours after application only. Slight discharge (grade 1) was observed in two animals 1 hour after application. Severe discharge (grade 3), noted in one animal after 1 hour, decreased to slight at the 24 hour-reading.
- No other ocular reactions were observed during the study.
- The ocular reactions were reversible in one animal within 48 hours and in two animals within 72 hours after application.
- Mean scores calculated for each animal over 24, 48 and 72 hours were 0.0 for corneal opacity and for iris lesions, 0.3, 1.3 and 1.3 for redness of the conjunctiva and 0.0, 0.3 and 0.0 for chemosis.

For assessing skin irritation in vivo a read across to a substance with a very similar chemical composition (EC No. 900 -066 -9; comparable allophanate-type HDI oligomerisation product) is applied.The read across is based on physicochemical and toxicological similarity of the two substances. Especially a comparative pulmonary irritant potency study according to TRGS 430 (Technical Rule for Hazardous Substances 430; published by the German Federal Ministry of Labour and Social Affairs, 2009), as the key study for justification of read-across, confirmed for both substances the same toxicological mode of action and nearly identical potency. For further justification of the grouping and read-across according to regulation (EC) No 1907/2006, Annex XI, 1.5 see document attached to chapter "Assessment Reports".

 

Executive summary:

An Eye Irritation/ Corrosion test according to OECD TG 405 was conducted with the test substance. Slight or moderate conjunctival redness and slight or severe discharge were observed in the animals during the course of the study. Slight conjunctival chemosis was noted in one animal 24 hours after application only.

The ocular reactions were reversible in all animals within 72 hours after application at the latest. The average scores (24, 48 and 72 hours) were for conjunctivae (redness) 0.3, 1.3, 1.3 and for chemosis 0.0, 0.3 and 0.0. No effects were observed on corneal opacity or iris.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Validated in vitro assays (OECD 431 and 439) reveal for the substance no corrosive and no irritant property to the skin. For investigating the ocular irritant property an in vitro human corneal epithelium (HCE) test, as prevalidated in 2004 (van Goethem et. al., Tox in Vitro 20, 2006, 1-17) was conducted. On the basis of this test the substance was considered to be non-irritant to the eye.

For assessing skin and eye irritation in vivo a read across to a substance with a very similar chemical composition (EC No. 900 -066 -9; comparable allophanate-type HDI oligomerisation product) is applied. The read across is based on physicochemical and toxicological similarity of the two substances. Especially a comparative pulmonary irritant potency study according to TRGS 430, as the key study for justification of read-across, confirmed for both substances the same toxicological mode of action and nearly identical potency. For further justification of the grouping and read-across according to regulation (EC) No 1907/2006, Annex XI, 1.5 see document attached to chapter "Assessment Reports".

The Skin Irritation/Corrosion test with the read-across substance (EC No. 900 -066 -9) was conducted according to OECD 404. Slight to marked erythema, partly extending beyond the area of exposure and slight edema were observed in the animals during the course of the study. Additionally dryness of the skin and scaling were noted during the observation period. The cutaneous reactions were reversible in two animals within 7 days, while in one animal slight erythema and scaling was still present up to study termination on day 14. The average scores for erythema (24, 48 and 72 hours) were 2, 2.3, 3 and for edema 0.3, 0.3, 0.3.

The Eye Irritation/ Corrosion test with the read-across substance (EC No. 900 -066 -9) was conducted according to OECD TG 405. Slight or moderate conjunctival redness and slight or severe discharge were observed in the animals during the course of the study. Slight conjunctival chemosis was noted in one animal 24 hours after application only. The ocular reactions were reversible in all animals within 72 hours after application at the latest. The average scores (24, 48 and 72 hours) were for conjunctivae (redness) 0.3, 1.3, 1.3 and for chemosis 0.0, 0.3 and 0.0. No effects were observed on corneal opacity or iris.

For respiratory irritation see chapter Acute Toxicity.


Justification for selection of skin irritation / corrosion endpoint:
Only one in vivo study available.

Justification for selection of eye irritation endpoint:
Only one in vivo study available.

Effects on skin irritation/corrosion: irritating

Effects on respiratory irritation: irritating

Justification for classification or non-classification

According to Regulation (EC) No 1272/2008, Annex I, the substance has to be classified as Skin Irrit. 2 (H315: Causes skin irritation).

No classification required for eye irritation according to Regulation (EC) No 1272/2008, Annex I.

As the studies on Acute Inhalation Toxicity show for the substance evidence for lower respiratory tract sensory irritation the substance has to be classified as STOT SE 3 (H335: May cause respiratory irritation) according to Regulation (EC) No 1272/2008, Annex I.