Registration Dossier

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline-conform study performed under GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2001
Report Date:
2001

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Deviations:
no
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): EXP 3982 N-2-hydroxyethylurea
- Physical state: clear yellow liquid
- Analytical purity: aqueous solution containing 57.58 % hydroxyethyl urea
- Impurities (identity and concentrations): not reported
- Composition: aequeous solution containing 57.58 % hydroxyethyl urea
- Purity test date: not reported
- Lot/batch No.: 84714
- Expiration date of the lot/batch: 15 July 2001
- Storage condition of test material: at room temperature

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Myrtle's Rabbitry, Thompson Station, TN
- Age at study initiation: males: 14-15 weeks, females: 15 weeks
- Weight at study initiation: males: 3.0 - 3.2 kg, females: 3.1 - 3.5 kg
- Housing: individually in suspended stainless steel cages
- Diet (e.g. ad libitum): PMI Certified Rabbit Chow #5322 (Purina Mills, Inc.) ad libitum
- Water (e.g. ad libitum): municipal tap water treated by reverse osmosis ad libitum
- Acclimation period: acclimated to the laboratory conditions for a minimum of five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-22
- Humidity (%): 26-56
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: One eye of each rabbit remained untreated and served as a control.
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
Duration of treatment / exposure:
single application
Observation period (in vivo):
1, 24, 48 and 72 h and up to 7 days after dosing
Number of animals or in vitro replicates:
3 males, 3 females
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): Following macroscopic observations at the 24-h scoring interval, any residual test article was gently rinsed from the eye using physiological saline.
- Time after start of exposure: 24 h

SCORING SYSTEM:
CORNEAL OPACITY-DEGREE OF DENSITY (AREA MOST DENSE TAKEN INTO ACCOUNT)
0: No ulceration or opacity
1: Scattered or diffuse areas of opacity (other than slight dulling of normal luster), details of iris clearly visible
2: Easily discernible translucent area,, details of iris slightly obscured
3: Nacreous (opalescent) area, no details of iris visible, size of pupil barely discernible
4: Opaque cornea, iris not discernible through opacity

AREA OF CORNEA INVOLVED (TOTAL AREA EXHIBITING ANY OPACITY, REGARDLESS OF DEGREE)
0: No ulceration or opacity
1: One quarter (or less) but not zero
2: Greater than one quarter, but less than half
3: Greater than half, but less than three quarters
4: Greater than three quarters, up to whole area

IRITS
0: Normal
1: Markedly deepened rugae (folds above normal), congestion, swelling, modarate circumcorneal hyperemia or injection, any or all of these or combination of any thereof, iris is still reacting to light (sluggish reaction is positive)
2: No reaction to light, hemorrhage, gross destruction (any or all of these)

CONJUNCTIVAL REDNESS (REFERS TO PALPEBRAL AND BULBAR CONJUNCTIVAE EXCLUDING CORNEA AND IRIS
0: Blood vessels normal
1: Some blood vessels definitely hyperemic (injected) above normal (slight erythema)
2: Diffuse, crimson color, individual vessels not easily discernible (moderate erythema)
3: Diffuse beefy red (marked erythema)

CONJUNTIVAL SWELLING (LIDS AND/OR NICTITATING MEMBRANE)
0: No swelling
1: Any sweliing above normal (includes nictitating membrane, slightly swollen)
2: Obvious sewlling with partial eversion of lids
3: Swelling with lids about half closed
4: Swelling with lids more than half closed

CONJUNCTVAL DISCHARGE
0: No discharge
1: Any amount different from normal (does not include small amounts observed in inner canthus of normal animals)
2: Discharge with moistening of the lids and hairs just adjacent to lids
3: Discharge with moistening of the lids and hairs and considerable area around the eye


TOOL USED TO ASSESS SCORE: auxiliary light source/ fluorescein (before start of test and after 24 h)

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: mean of scores at 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
iris score
Basis:
mean
Time point:
other: mean of scores at 24, 48 and 72 h
Score:
0.056
Max. score:
2
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: mean of scores at 24, 48 and 72 h
Score:
0.56
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: mean of scores at 24, 48 and 72 h
Score:
0.22
Max. score:
4
Reversibility:
fully reversible within: 48 h

Any other information on results incl. tables

Individual scores at 1 h

Cornea score: 0 for all animals

Iris score: 0 in three males, 1 in three females

Conjunctivae score: 1 in all animals

Chemosis score: 1 in all animals

Individal mean scores at 24, 48 and 72 h

Cornea score: 0 for all animals

Iris score: 0 in three males and two females, 1/3 in one female

Conjunctivae score: 1/3 in two males and one female, 2/3 in two females, 1 in one male

Chemosis score: 0 in one male and one female, 1/3 in two males and two females

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the results of the test, the test item is considered to be a mild irritant to the ocular tissure of the rabbit. EXP 3982 N-2-hydroxyethylurea does not have to be classified for eye irritation according to Regulation (EC) 1272/2008 (CLP).
Executive summary:

The potential irritant and/or corrosive effects of the aqueous solution EXP 3982 N-2-hydroxyethylurea containing 57.58 % of the active ingredient hydroxyethyl urea were evaluated under GLP on the eyes of New Zealand White rabbits in accordance with OECD TG 405. Each of six rabbits received a 0.1 mL dose of the aqueous solution in the conjunctival sac of the right eye. The contralateral eye of each animal remained untreated and served as a control. Test and control eyes were examined for signs of irritation for up to 7 days following dosing.

Exposure to the test article produced iritis in 3/6 test eyes at the 1-hour socring interval which resolved completely in all test eyes by the 48-hour scoring interval. Effects on the conjunctivae (redness, swelling and/or discharge) were noted in 6/6 test eyes at the 1-hour scoring interval. The conjunctival irritation resolved completely in all test eyes by study day 7.

EXP 3982 N-2-hydroxyethylurea is considered to be a mild irritant to the ocular tissue of the rabbit. It does not have to be classified for eye irritation according to Regulation (EC) 1272/2008 (CLP) /GHS.