Chlorothalonil

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

9 Sep 1977 to 16 Oct 1977

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1977

Report date:

1977

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

A dose of 0.1 mg of test substance was instilled into one eye of each of three male and three female New Zealand White rabbits. The eyes were examined and scored at 24, 48, and 72 hours, and on days 7 and 14 according to a modified Draize system. A sodium fluorescein dye examination was conducted at 72 hours and on days 7 and 14 in order to detect potential corneal lesions.

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Chlorothalonil

EC Number:

217-588-1

EC Name:

Chlorothalonil

Cas Number:

1897-45-6

Molecular formula:

C8Cl4N2

IUPAC Name:

tetrachlorobenzene-1,3-dicarbonitrile

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Age at study initiation: Not reported
- Weight at study initiation: 2002 to 2215 g
- Housing: The rabbits were individually housed in metal metabolism cages in temperature and humidity controlled quarters.
- Diet: Ad libitum
- Water: Ad libitum

IN-LIFE DATES: From: 9 Sep 1977 To: 16 Oct 1977

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 100 mg

Duration of treatment / exposure:

Single treatment

Observation period (in vivo):

24, 48, and 72 hours, and on days 7 and 14

Number of animals or in vitro replicates:

3 males and 3 females

Details on study design:

A dose of 0.1 mg of test substance was instilled into one eye of each of three male and three female New Zealand White rabbits. The left eye served as the untreated control for each rabbit. None of the rabbits received a washout. The eyes were examined and scored at 24, 48, and 72 hours, and on days 7 and 14 according to a modified Draize system. A sodium fluorescein dye examination was conducted at 72 hours and on days 7 and 14 in order to detect potential corneal lesions.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal: 1, 2, 3, 4, 6

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Remarks on result:

other: Marked chemosis precluded observations for corneal and iridal irritation. Maximum score used due to marked chemosis which precluded a definitive score.

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal #5

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Results 3

Irritation parameter:

iris score

Basis:

animal: 1, 2, 3, 4, 6

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

not fully reversible within: 14 days (7 days for animal 3 and 4)

Remarks on result:

other: Marked chemosis precluded observations for corneal and iridal irritation. Maximum score used due to marked chemosis which precluded a definitive score.

Results 4

Irritation parameter:

iris score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0.7

Max. score:

2

Reversibility:

not fully reversible within: 14 days

Results 5

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal: 1, 2, 4

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

not fully reversible within: 14 days

Results 6

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.8

Max. score:

3

Reversibility:

not fully reversible within: 14 days

Results 7

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal: 5, 6

Time point:

24/48/72 h

Score:

1.5

Max. score:

3

Reversibility:

not fully reversible within: 14 days

Results 8

Irritation parameter:

chemosis score

Basis:

animal: 1, 2, 3, 5, 6

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Results 9

Irritation parameter:

chemosis score

Basis:

animal #4

Time point:

24/48/72 h

Score:

3.7

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Irritant / corrosive response data:

The test substance elicited ocular irritation in all six rabbits. Corneal opacities were observed in all eyes at all observation intervals with the exception of five out of six corneas at 24 hours and four out of six corneas at 48 hours which could not be observed due to severe chemosis. Pannus was observed in two out of six eyes at day 7. Vascularization of the corneal surface was noted in five out of six eyes at day 14. Peeling of the corneal epithelium was observed in all rabbits. Dendritic vascularization was noted in two out of six eyes at day 7. The sodium fluorescein dye examination confirmed the occurrence of corneal damage in all rabbits at all observation intervals.

Iritis (iris still reacting to light) was observed in all six eyes. The iris of five eyes at 24 hours, four eyes at 48 hours and one eye at 72 hours could not be observed due to severe chemosis. Iritis was observed in four out of six eyes on day 14.

Conjunctival irritation (redness, chemosis, discharge and blanching) was observed in all rabbits at all observation intervals. Petite conjunctival haemorrhages were observed in all rabbits through day 7 and persisted to day 14 in one rabbit eye.

The maximum mean total Draize score was 99.9 observed at 24 hours. The maximum individual total Draize score was 108.0 observed in three rabbits at 24 hours.

Any other information on results incl. tables

Table 1. results for individual animals

Scores observed after	24 hours	48 hours	72 hours		7 days	14 days
Cornea/opacity	*,2,*,*,*,*	* ,*, 3,*,*,*	2,4,2,3,4,3½		4,4,4,4,4,4	3,4,4,4,4,4
Iris	*,0,*,*,*,*	*,0,1,*,*,*	2,2,1,*,1,*		2,2,1,2,1,2	0,2,1,2,0,2
Conjunctiva redness	2,2,2,2,2,2	1½,1½,1,2,2,2	2,1,1½,2,2,2		1½,1,2,2½,2,2	½,1,1,1½,1,1
Conjunctiva chemosis	4,4,4,4,4,4	4,4,4,4,4,4	4,4,4,4,3,4	1½,4,1½,4,1½,4			1½,2,1½,1½,1½,2
Conjunctiva discharge	3,3,3,2,3,2	3,2,1½,1,1½,2	3,2,2,2,1,2	2,2,2,2,1,2			0,1,2,1,1,1

* Marked chemosis precluded these observations

Applicant's summary and conclusion

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Conclusions:

A dose of 0.1 mg test substance produced corneal opacities, pannus, vascularization of the corneal surface, peeling of the corneal epithelium, dendritic vascularization, iritis, conjunctival irritation and petite conjunctival haemorrhages when instilled into the eyes of albino rabbits, Corneal opacity persisted through day 14 in all six rabbits tested.

Executive summary:

The eye irritation produced by a single application of the test material was assessed in a primary eye irritation study in New Zealand White rabbits (no guideline, GLP). A dose of 0.1 mg of test substance was instilled into one eye of each of three male and three female New Zealand White rabbits. The left eye served as the untreated control for each rabbit. None of the rabbits received a washout. The eyes were examined and scored at 24, 48, and 72 hours, and on days 7 and 14 according to a modified Draize system. A sodium fluorescein dye examination was conducted at 72 hours and on days 7 and 14 in order to detect potential corneal lesions. The test substance elicited ocular irritation in all six rabbits. Corneal opacities were observed in all eyes at all observation intervals with the exception of five out of six corneas at 24 hours and four out of six corneas at 48 hours which could not be observed due to severe chemosis. Pannus was observed in two out of six eyes at day 7. Vascularization of the corneal surface was noted in five out of six eyes at day 14. Peeling of the corneal epithelium was observed in all rabbits. Dendritic vascularization was noted in two out of six eyes at day 7. The sodium fluorescein dye examination confirmed the occurrence of corneal damage in all rabbits at all observation intervals. Iritis (iris still reacting to light) was observed in all six eyes. The iris of five eyes at 24 hours, four eyes at 48 hours and one eye at 72 hours could not be observed due to severe chemosis. Iritis was observed in four out of six eyes on day 14. Conjunctival irritation (redness, chemosis, discharge and blanching) was observed in all rabbits at all observation intervals. Petite conjunctival haemorrhages were observed in all rabbits through day 7 and persisted to day 14 in one rabbit eye.

In conclusion, the test substance produced corneal opacities, pannus, vascularization of the corneal surface, peeling of the corneal epithelium, dendritic vascularization, iritis, conjunctival irritation and petite conjunctival haemorrhages when instilled into the eyes of albino rabbits, Corneal opacity persisted through day 14 in all six rabbits tested.