N,N''-(methylenedi-4,1-phenylene)bis[N'-(4-methylphenyl)urea]

Endpoint summary

Description of key information

Skin irritation (OECD 404): not irritating

Eye irritation (OECD 405): not irritating

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:

December 1993

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:

1992

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

1992

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

- Source: Broekman Institute, Someren, The Netherlands.
- Age at study initiation: approx. 12 weeks old.
- Weight at study initiation: 2374 - 2772 grams.
- Housing: Animals were housed individually in cages with perforated floors.
- Diet: Free access to pelleted diet for rabbits (LKK-20, pellet diameter 4mm, Hope Farms, Woerden, The Netherlands).
- Water: Free access to tap water.
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
set to maintain:
- Temperature (°C): 21
- Humidity (%): 55
- Air changes (per hr): approx 15
- Photoperiod (hrs dark / hrs light): 12/12.

IN-LIFE DATES: From: 21 December 1993 to 24 December 1993

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 grams

Duration of treatment / exposure:

Single application.

Observation period:

3 days.

Number of animals:

3 males.

Details on study design:

TEST SUBSTANCE PREPARATION
A pre-test revealed that the test substance was hydrophobic. Therefore the skin of the animals was moistened with distilled water, to ensure close contact of the test substance to the skin.

TEST SITE
Approximately 24 hours before treatment, the dorsal fur was clipped with electric clippers, exposing an area of approximately 150 square centimeters (10x15 cm). To facilitate scoring, treated skin areas were re-clipped at least 3 hours before the observations.

The test substance was applied to the skin of one flank, using a patch of 2x3 cm.

REMOVAL OF TEST SUBSTANCE
Four hours after the application, the dressing was removed and the skin cleaned of residual test substance using tap water.

OBSERVATIONS
- Mortality/Viability: Twice daily.
- Toxicity: At least once daily.
- Body Weight: Day of treatment (prior to application).
- Necropsy: \\\tekst onder necropsy overnemen.
- Irritation:
The skin reactions were assessed at approximately 1, 24, 48 and 72 hours after the removal of the dressings and test substance. The irritation scores and a description of all other (local) effects were recorded.

SCORING SYSTEM:
The irritation was assessed according to the numerical scoring system according to OECD 404.

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No skin irritation was caused by KY-AF after a 4 hour exposure. There was no evidence of a corrosive effect on the skin.

Other effects:

No staining of the treated skin by the test substance was observed.

Interpretation of results:

other: Not irritating

Remarks:

According to Regulation (EC) No 1272/2008 and its amendments.

Conclusions:

In an skin irritation study with KY-AF in rabbits, performed according to OECD/EC test guidelines, no irritation was observed.

Executive summary:

An assessment of primary skin irritation/corrosion with KY-AF in the rabbit using a 4 hour semi-occlusive application was performed according to OECD/EC test guidelines and in accordance with GLP principles. No erythema or oedema was observed and there was no evidence of irritation or a corrosive effect on the skin.

Based on these results, KY-AF does not have to be classified and has no obligatory labelling requirement for dermal irritation or corrosion according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2015) (including all amendments) and Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments).

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

Reason / purpose for cross-reference:

data waiving: supporting information

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:

January 1994

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:

1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

1992

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

- Source: Broekman Institute, Someren, The Netherlands.
- Age at study initiation: Animals used withihn the study were approx. 13 weeks old.
- Weight at study initiation: 2510 - 2589 grams.
- Housing: Individually housed in cages with perforated floors.
- Diet: Free access to pelleted diet for rabbits (LKK-20, pellet diameter 4 mm, Hope Farms, Woerden, The Netherlands).
- Water: Free access to tap water.
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
set to maintain:
- Temperature (°C): 21
- Humidity (%): 55
- Air changes (per hr): approx 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 03 January 1994 to 06 January 1994

Vehicle:

unchanged (no vehicle)

Controls:

other: One eye of each animal remained untreated and served as the reference control.

Amount / concentration applied:

TEST MATERIAL- Amount applied: 79 ± 1 mg

Duration of treatment / exposure:

Single instillation on Day 1.

Observation period (in vivo):

The eyes of each animal were examined approximately 1, 24, 48 and 72 hours after instillation of the test substance

Number of animals or in vitro replicates:

3 males

Details on study design:

TREATMENT
On test day 1, the test substance was instilled in the conjunctival sac of one eye of each animal.

REMOVAL OF TEST SUBSTANCE
-Washing (if done): No

OBSERVATIONS (beschrijf beperkt)
- Mortality/Viability: Twice daily.
- Toxicity: At least once daily.
- Body Weight: Day of treatment (prior to instillation).
- Necropsy: No histopathology was performed
- Irritation:
The eyes of each animal were examined approximately 1, 24, 48 and 72 hours after instillation of the test substance.
The irritation scores and a description of all other (local) effects were recorded.The irritation was assessed according to OECD 405.
Immediately after the 24 hour observation, a solution of 2% fluorescein in water (adjusted to pH 7.0) was instilled into both eyes of each animal to quantitatively determine corneal epithelial damage.

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

mean

Time point:

24/48/72 h

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 48 h

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

Irritation
Instillation of KY-AF into one eye of each of the animals resulted in slight redness of the conjunctival tissues, which had resolved within 2 daysafter treatment. Treatment of the eyes with 2% fluorescein, 24 hours after test substance
instillation revealed no corneal epithelial damage ·in any of the animals.

Corrosion
There was no evidence of ocular corrosion.

Other effects:

No staining of peri-ocular tissues by the test substance was observed.

No toxic symptoms were observed in the animals during the test period and no mortality occurred.

Interpretation of results:

other: Not irritating.

Remarks:

According to Regulation (EC) No. 1272/2008 and its amendments.

Conclusions:

In an eye irritation study with rabbits, performed according to OECD/EC test guidelines, no corrosion was observed. Irritation of the conjunctivae was seen as redness which had completely resolved within 48 hours. No corneal opacity, corneal epithelial damage or iridial irritation was observed. Based on these results KY-AF does not have to be classified and has no obligatory labelling requirements.

Executive summary:

Assessment of acute eye irritation/corrosion was performed with KY-AF in the rabbit according to OECD/EC guidelines and in accordance with GLP principles. Installation of single samples of KY-AF into one eye of each of three rabbits resulted in slight redness of the conjunctival tissues, which had resolved within 2 days after treatment. There was no evidence for ocular corrosion. No corneal opacity, corneal epithelial damage or iridial irritation was observed.

Based on these results, KY-AF does not have to be classified and has no obligatory labelling requirement for eye irritation according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2015) (including all amendments) and Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments).

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

Reason / purpose for cross-reference:

data waiving: supporting information

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation:

An assessment of primary skin irritation/corrosion with KY-AF in the rabbit using a 4 hour semi-occlusive application was performed according to OECD/EC test guidelines and in accordance with GLP principles. No erythema or oedema was observed and there was no evidence of irritation or a corrosive effect on the skin.

Eye irritation:

Assessment of acute eye irritation/corrosion was performed with KY-AF in the rabbit according to OECD/EC guidelines and in accordance with GLP principles. Installation of single samples of KY-AF into one eye of each of three rabbits resulted in slight redness of the conjunctival tissues, which had resolved within 2 days after treatment. There was no evidence for ocular corrosion. No corneal opacity, corneal epithelial damage or iridial irritation was observed.

Justification for classification or non-classification

Based on the study results, KY-AF does not have to be classified and has no obligatory labelling requirement for skin and eye irritation according to Regulation (EC) No 1272/2008 and its amendments.