Urea

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

29 August to 14 September 1988

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Proprietary guideline compliant study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1988

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Urea

EC Number:

200-315-5

EC Name:

Urea

Cas Number:

57-13-6

Molecular formula:

CH4N2O

IUPAC Name:

urea

Details on test material:

"Harnstoff Techn." (urea)

Test animals / tissue source

Species:

rabbit

Strain:

Vienna White

Details on test animals or tissues and environmental conditions:

The animals were 1 male and 2 female Vienna White rabbits, obtained from Gaukler. The male rabbit weighed 2.45 kg and the mean weight of the females was 2.74 kg. They were housed individually in stainless steel cages with wire mesh floors. Individuals were identified by ear tattoo. The rabbits were housed in air conditioned rooms, the temperature was maintained at 20-24°C and relative humidity was 30-70%. Light was provided on a 12 hour light/dark cycle. The rabbits were fed approximately 130 g/day of Kliba 341. 4 MM (Firma Klingentalmuehle AG, Switzerland), and provided with approximately 250 ml tap water per day. The rabbits were acclimatised for 8 days.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

0.1 mL bulk volume (about 43 mg powdered substance).

Duration of treatment / exposure:

Single application, the substance was not washed out

Observation period (in vivo):

8 days

Number of animals or in vitro replicates:

1 male and 2 females

Details on study design:

0.1 mL bulk volume of the substance was administered in a single application to the conjunctival sac of the right eye of each rabbit, the substance was not washed out. The left eye remained untreated to act as a negative control. Irritation readings were made at 1, 24, 48, 72 hours and 8 days after application. Reactions were scored according to OECD guidelines.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0.9

Max. score:

3

Reversibility:

fully reversible

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.67

Max. score:

3

Reversibility:

fully reversible within: 8 days

Results 3

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 8 days

Results 4

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 8 days

Results 5

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0.4

Max. score:

1

Reversibility:

fully reversible

Results 6

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.33

Max. score:

1

Reversibility:

fully reversible within: 8 days

Results 7

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.67

Max. score:

1

Reversibility:

fully reversible within: 8 days

Results 8

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

1

Reversibility:

fully reversible within: 8 days

Results 9

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

2.2

Max. score:

3

Reversibility:

fully reversible

Results 10

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2.33

Max. score:

3

Reversibility:

fully reversible within: 8 days

Results 11

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 8 days

Results 12

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2.33

Max. score:

3

Reversibility:

fully reversible within: 8 days

Results 13

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible

Results 14

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 8 days

Results 15

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.67

Max. score:

2

Reversibility:

fully reversible within: 8 days

Results 16

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

2

Reversibility:

fully reversible within: 8 days

Irritant / corrosive response data:

At 1 hour after application all irritant effects were limited to the conjunctivae. At 24 hours there were corneal effects in 2 rabbits, and irritation of the iris and conjunctivae in all 3 rabbits; 2 rabbits displayed small retractions of the eyelids, 2 rabbits displayed contracted pupils and 2 rabbits exhibited a loss of corneal tissue. At 48 hours 1 rabbit was also exhibiting suppuration and bloody discharge from the eye. 8 days after treatment all rabbits were given scores of 0 for all irritative parameters, 1 rabbit was still displaying small retractions of the eyelids. Individual data are presented in Table 1.

Other effects:

None reported.

Any other information on results incl. tables

Table 1. Individual animal data.

Time	Rabbit No. Sex	Cornea		Iris	Conjunctivae			Symptoms
		OP	AR		RED	CH	DI
1 h	1 F	0	0	0	2	2	2
	2 M	0	0	0	2	2	1
	3 F	0	0	0	2	2	2
24 h	1 F	0	0	1	3	2	2	RE
	2 M	1	2	1	2	2	2	RE/PC/LC
	3 F	1	3	1	3	1	1	PC/LC
48 h	1 F	1	1	0	2	1	1	RE
	2 M	1	2	1	2	2	2	LC/PC/RE/S/DB
	3 F	1	2	0	2	0	0	LC/PC
72 h	1 F	1	1	0	2	0	0	RE
	2 M	1	1	0	2	1	1	LC/PC/RE
	3 F	1	1	0	2	0	0	LC
8 d	1 F	0	0	0	0	0	0
	2 M	0	0	0	0	0	0	RE
	3 F	0	0	0	0	0	0
Mean	1 F	0.7		0.3	2.3	1.0
	2 M	1.0		0.7	2.0	1.7
	3 F	1.0		0.3	2.3	0.3

OP = Opacity, AR = Area involved

RED = Redness, CH = Chemosis, DI = Discharge

RE = small retractions in eyelids

PC = pupil contracted

LC = loss of corneal tissue

S = suppuration

DB = discharge of blood

Applicant's summary and conclusion

Interpretation of results:

slightly irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Urea is mildly irritating to eyes

Executive summary:

The eye irritation potential of urea was determined in 3 Vienna White rabbits. The substance was administered in a single application to the right conjunctival sac of each rabbit; the substance was not washed out. The degree of corneal opacity, iris irritation and conjunctival irritation (redness, swelling and discharge) were scored at 1, 24, 48, 72 hours and 8 days after application. Well defined to severe redness and slight to well defined swelling of the conjunctivae was seen in all rabbits. Slight opacity of the cornea was seen in 2 rabbits at 24 hours and all rabbits at 48 and 72 hours. Other signs observed included small retractions in eyelids, contracted pupil and loss of corneal tissue. Circumcorneal injection was observed in all rabbits at 24 hours and remained in 1 rabbit at 48 hours. One rabbit (male) also exhibited suppination and bloody discharge 48 hours after application. All signs of irritation had disappeared 8 days after application. The test substance can be classified as mildly irritating to eyes.