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

Eye irritation

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1994

Report date:

1994

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

1987

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

1992

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

429-380-1

EC Name:

-

Cas Number:

133336-92-2

Molecular formula:

C29H28N4O2

IUPAC Name:

1-(4-methylphenyl)-3-{4-[(4-{[(4-methylphenyl)carbamoyl]amino}phenyl)methyl]phenyl}urea

Test material form:

solid: particulate/powder

Details on test material:

- Particle size distribution: 10%: < 23.94 µm
- Density: 1.32 g/cm3 (20°C)
- Test substance storage: at room temperature in the dark
- Stability under storage conditions: stable

Test animals / tissue source

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

Test system

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.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 3

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

Results 4

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.

Applicant's summary and conclusion

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).