Benzoic acid, 2,3,4,5-tetrachloro-6-cyano-, methyl ester, reaction products with 2-methyl-1,3-benzenediamine and sodium methoxide

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1975

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Non-GLP non-guideline study, available as unpublished report, predates implementation of GLP and/or development of study guidelines, notable limitations in design and/or reporting. After application eye lids were held open for a few seconds instead of closed.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1975

Report date:

1975

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: The procedure adopted was the technique described in the "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics" (1959) of the US Association of Food and Drug Officials (AFDO).

GLP compliance:

no

Remarks:

prior to GLP implementation

Test material

Test material information

Constituent 1

Reference substance name:

Mixture of octachloro, monomethoxy-heptachloro and bismethoxy-hexachloro derivatives of 3,3'-[(2-methyl-1,3-phenylene)diimino]bis[2,3-dihydro-1H-isoindol-1-one]

EC Number:

600-735-2

Cas Number:

106276-79-3

Molecular formula:

Mixture of C23H8Cl8N4O2, C24H11Cl7N4O3, C25H14Cl6N4O4

IUPAC Name:

Mixture of octachloro, monomethoxy-heptachloro and bismethoxy-hexachloro derivatives of 3,3'-[(2-methyl-1,3-phenylene)diimino]bis[2,3-dihydro-1H-isoindol-1-one]

Test animals / tissue source

Species:

rabbit

Strain:

other: Russion breed

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Housing: single housing in V2A wire cages
- Diet: NAFAG, Gossau SG, rabbit food ad libitum
- Water: water ad libitum
- Only rabbits showing normal ophthalmic findings were included in the test.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated right eye

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g

Duration of treatment / exposure:

Eyes of 3 female animals were rinsed 30 seconds after treatment. Eyes of 3 male animals were not rinsed.

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

6 animals: 3 males, 3 females

Details on study design:

Amounts of 0.1 g of the test substance were introduced into the conjunctival sac of the left eye with a spatula. After application, the eyelids were held open for a few seconds. The right eye served as a control. The treated eyes of three female rabbits were each rinsed with 10 mL lukewarm water about 30 seconds after treatment.

SCORING SYSTEM: The reactions were appraised after 24 hours and after 2, 3, 4 and 7 days on the basis of the "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics" (1959) of the AFDO.

Evaluation of the Eye Reactions:
Cornea:
A. Opacity-degree of density (area most dense taken for reading):
No opacity; 0
Scattered or diffuse area, details of iris clearly visible; 1
Easily discernible translucent areas, details of iris slightly obscured; 2
Opalescent areas, no details of iris visible, size of pupil barely discernible; 3
Opaque, iris invisible; 4

B. Area of cornea involved:
One quarter (or less) but not zero; 1
Greater than one quarter, but less than half; 2
Greater than half, but less than three quarters; 3
Greater than three quarters, up to whole area; 4
A X B X 5
Total maximum = 80

Iris
A. Values
Normal; 0
Folds above normal, congestion, swelling, circumcorneal injection (any or all of these or combination of any thereof) iris still reacting to light (sluggish reaction is positive); 1
No reaction to light, hemorrhage, gross destruction (any or all of these); 2
A x 5

Conjunctivae:
A. Redness (refers to palpebral and bulbar conjunctivae excluding cornea and iris):
Vessels normal; 0
Vessels definitely injected above normal; 1
More diffuse/ deeper crimson red, individual vessels not easily discernible; 2
Diffuse beefy red; 3

B. Chemosis:
No swelling; 0
Any swelling above normal (includes nictitating membrane); 1
Obvious swelling with partial eversion of lids; 2
Swelling with lids about half closed; 3
Swelling with lids about half closed to completely closed; 4

C. Discharge:
No discharge; 0
Any amount different from normal (does not include small amounts observed in inner canthus of normal animals); 1
Discharge with moistening of the lids and hairs just adjacent to lids; 2
Discharge with moistening of the lids and hairs, and considerable area around the eye; 3
(A + B + C) X 2
Total maximum = 20

TOOL USED TO ASSESS SCORE: slit-lamp

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24 hour - 7 days

Score:

0

Max. score:

80

Remarks on result:

other: Rinsed eye

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24 hour - 7 days

Score:

0

Max. score:

10

Remarks on result:

other: Rinsed eye

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 24 hour - 7 days

Score:

0

Max. score:

20

Remarks on result:

other: Rinsed eye

Results 4

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24 hour - 7 days

Score:

0

Max. score:

80

Remarks on result:

other: Eyes not rinsed

Results 5

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24 hour - 7 days

Score:

0

Max. score:

10

Remarks on result:

other: Eyes not rinsed

Results 6

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 24 hour - 7 days

Score:

0

Max. score:

20

Remarks on result:

other: Eyes not rinsed

Irritant / corrosive response data:

The irritation index was found to be 0 for the cornea, 0 for the iris and 0 for the conjunctivae.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met