6-Amino-5-chloro-2-cyclopyrimidine-4-carboxylic acid

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

19 - 29 March 2007

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2011

Report date:

2011

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

adopted: 2002

Deviations:

yes

Remarks:

no use of topical anesthetics and systemic analgesics

GLP compliance:

yes

Test material

Test material information

1

Reference substance name:

6-amino-5-chloro-2-cyclopropylpyrimidine-4-carboxylic acid

EC Number:

617-769-9

Cas Number:

858956-08-8

Molecular formula:

C8H8ClN3O2

IUPAC Name:

6-amino-5-chloro-2-cyclopropylpyrimidine-4-carboxylic acid

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Covance Research Products, Denver, Pennsylvania, USA
- Age at study initiation: adult
- Weight at study initiation: 3267 g, 3524 g and 3610 g
- Housing: individual housed in stainless steel wire-mesh cages suspended above cage boards
- Diet: approximately 125 g of PMI® Nutrition International, LLC Certified Rabbit LabDiet® 5322 daily during the study
- Water: ad libitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 - 22
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount applied: approximately 86 mg (a weight equal to a 0.1 mL volume)

Duration of treatment / exposure:

The treated and control eyes of all rabbits remained unwashed.

Observation period (in vivo):

1, 24, 48 and 72 h

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: unwashed

SCORING SYSTEM: Draize Scale

TOOL USED TO ASSESS SCORE: illumination, magnification, fluorescein

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

of 3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other:

Remarks:

reversibility: not applicable

Results 2

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other:

Remarks:

reversibility: not applicable

Results 3

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.67

Max. score:

2

Reversibility:

fully reversible within:

Remarks:

72 h

Results 4

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other:

Remarks:

reversibility: not applicable

Results 5

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within:

Remarks:

72 h

Results 6

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.67

Max. score:

3

Reversibility:

fully reversible within: 72 h

Results 7

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.67

Max. score:

3

Reversibility:

fully reversible within:

Remarks:

72 h

Results 8

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within:

Remarks:

48 h

Results 9

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other:

Remarks:

reversibility: not applicable

Results 10

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other:

Remarks:

reversibility: not applicable

Irritant / corrosive response data:

Additional time point 1h (for further details please refer to table 1 in the "Any other information on results incl. tables):
Cornea opacity: mean / of 3 animals was 0.
Iris score: mean / of 3 animals was 0.33.
Conjuctivae score: mean / of 3 animals 2.
Chemosis score: mean / of 3 animals 1.33.

Other effects:

- Lesions and clinical observations: Fluorescein stain examinations were negative for corneal injury in the treated eyes of all rabbits. No clinical signs of toxicity were observed, and no body weight loss occurred.
- Other observations: One of the rabbits pawed the treated eye after instillation of the test substance.

Any other information on results incl. tables

Table 1: Summary Occular Irritation Scores

	Rabbitt	Corneal			Conjunctiva			Fluorescein
Reading	Number	Opacity	Area	Iritis	Redness	Chemosis	Discharge	Stain
1 h	44a	0	0	0	2	2	0	NA
	169	0	0	1	2	1	0	NA
	170	0	0	0	2	1	0	NA
24 h	144a	0	0	0	2	1	0	Negative
	169	0	0	1	2	0	0	Negative
	170	0	0	0	1	0	0	Negative
48 h	144a	0	0	0	1	0	0	Negative
	169	0	0	1	0	0	0	Negative
	170	0	0	0	1	0	0	Negative
72 h	144a	0	0	0	0	0	0	Negative
	169	0	0	0	0	0	0	Negative
	170	0	0	0	0	0	0	Negative

NA = not applicable

a)    Initial animal tested

 

Table 2: Mean Scores for Ocular Responses for Individual Rabbits (24/48/72 h)

Rabbit number	Corneal opacity	Iritis	Conjunctival redness	Conjunctival chemosis
144	0	0	1	0.33
169	0	0.67	0.67	0
170	0	0	0.67	0

 

Table 3: Body weight

Rabbit number	sex	Initial weight (g)	Final weight (g)
144	male	3167	3260
169	male	3524	3560
170	male	3610	3658

Applicant's summary and conclusion

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation(EC) No. 1272/2008

Conclusions:

Under the conditions of the acute eye irritation/corrosion test, the test substance did not show irritant properties towards the eyes.
CLP: not classified