Benzoic acid, 2,3,4,5-tetrachloro-6-cyano-, methyl ester, reaction products with 4-[2-(4-aminophenyl)diazenyl]-3-methylbenzenamine and methanol sodium salt (1:1)

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1978

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1978

Report date:

1978

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Principles of method if other than guideline:

In 3 of the 6 rabbits approximately 30 seconds after treatment the treated eye was flushed with 10 mL of lukewarm water.

GLP compliance:

not specified

Remarks:

prior to GLP implementation

Test material

Test material information

Constituent 1

Reference substance name:

(3Z)-4,5,6,7-tetrachloro-3-({3-methyl-4-[(1E)-2-(3-methylphenyl)diazen-1-yl]phenyl}imino)-2,3-dihydro-1H-isoindol-1-one; 4,5,6,7-tetrachloro-3-({3-methyl-4-[(1E)-2-{4-[(4,5,6,7-tetrachloro-1-oxo-1H-isoindol-3-yl)amino]phenyl}diazen-1-yl]phenyl}amino)-1H-isoindol-1-one; 6-acetyl-3-({4-[(1E)-2-{4-[(6-acetyl-4,5,7-trichloro-1-oxo-1H-isoindol-3-yl)amino]phenyl}diazen-1-yl]-3-methylphenyl}amino)-4,5,7-trichloro-1H-isoindol-1-one; 6-acetyl-3-({4-[(1E)-2-{4-[(7-acetyl-4,5,6-trichloro-1-oxo-1H-isoindol-3-yl)amino]phenyl}diazen-1-yl]-3-methylphenyl}amino)-4,5,7-trichloro-1H-isoindol-1-one; 7-acetyl-3-({4-[(1E)-2-{4-[(6-acetyl-4,5,7-trichloro-1-oxo-1H-isoindol-3-yl)amino]phenyl}diazen-1-yl]-3-methylphenyl}amino)-4,5,6-trichloro-1H-isoindol-1-one; 7-acetyl-3-({4-[(1E)-2-{4-[(7-acetyl-4,5,6-trichloro-1-oxo-1H-isoindol-3-yl)amino]phenyl}diazen-1-yl]-3-methylphenyl}amino)-4,5,6-trichloro-1H-isoindol-1-one; N-{4-[(1E)-2-(2-methyl-4-{[(1Z)-4,5,6,7-tetrachloro-3-oxo-2,3-dihydro-1H-isoindol-1-ylidene]amino}phenyl)diazen-1-yl]phenyl}acetamide

EC Number:

600-734-7

Cas Number:

106276-78-2

Molecular formula:

C13H14N.C9H3Cl4NO2.CH4O.Na

IUPAC Name:

(3Z)-4,5,6,7-tetrachloro-3-({3-methyl-4-[(1E)-2-(3-methylphenyl)diazen-1-yl]phenyl}imino)-2,3-dihydro-1H-isoindol-1-one; 4,5,6,7-tetrachloro-3-({3-methyl-4-[(1E)-2-{4-[(4,5,6,7-tetrachloro-1-oxo-1H-isoindol-3-yl)amino]phenyl}diazen-1-yl]phenyl}amino)-1H-isoindol-1-one; 6-acetyl-3-({4-[(1E)-2-{4-[(6-acetyl-4,5,7-trichloro-1-oxo-1H-isoindol-3-yl)amino]phenyl}diazen-1-yl]-3-methylphenyl}amino)-4,5,7-trichloro-1H-isoindol-1-one; 6-acetyl-3-({4-[(1E)-2-{4-[(7-acetyl-4,5,6-trichloro-1-oxo-1H-isoindol-3-yl)amino]phenyl}diazen-1-yl]-3-methylphenyl}amino)-4,5,7-trichloro-1H-isoindol-1-one; 7-acetyl-3-({4-[(1E)-2-{4-[(6-acetyl-4,5,7-trichloro-1-oxo-1H-isoindol-3-yl)amino]phenyl}diazen-1-yl]-3-methylphenyl}amino)-4,5,6-trichloro-1H-isoindol-1-one; 7-acetyl-3-({4-[(1E)-2-{4-[(7-acetyl-4,5,6-trichloro-1-oxo-1H-isoindol-3-yl)amino]phenyl}diazen-1-yl]-3-methylphenyl}amino)-4,5,6-trichloro-1H-isoindol-1-one; N-{4-[(1E)-2-(2-methyl-4-{[(1Z)-4,5,6,7-tetrachloro-3-oxo-2,3-dihydro-1H-isoindol-1-ylidene]amino}phenyl)diazen-1-yl]phenyl}acetamide

Test material form:

solid: nanoform

Test animals / tissue source

Species:

rabbit

Strain:

Himalayan

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 1.5 - 2 kg
- Housing: individually in metal cages
- Diet: standard rabbit food - NAFAG, Gossau SG, ad libitum
- Water: water ad libitum
- Acclimation period: minimum of 4 days
Only rabbits with normal ophthalmic findings were used for these tests.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 1
- Humidity (%): 55 ± 5
- Photoperiod (hrs dark / hrs light): 10 hour light cycle day

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: right untreated eye

Amount / concentration applied:

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

Duration of treatment / exposure:

In 3 of the 6 rabbits approximately 30 seconds after treatment the treated eye was flushed with 10 mL of lukewarm water.
In the other 3 animals the eyes were not rinsed, therefore, they were exposed up to 7 days.

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

6: 3 male, 3 female

Details on study design:

The test material in an amount of 0.1 g was inserted into the conjunctival sac of the left eye of the 6 rabbits and the lids were gently closed for one second. The right eye was not treated and served as an untreated control. In 3 of the 6 rabbits approximately 30 seconds after treatment the treated eye was flushed with 10 mL of lukewarm water. The eye irritation was appraised with a slit-lamp on day 1, 2, 3, 4 and 7 and was scored for each individual rabbit as outlined below. The primary eye irritation index represents the sum of the mean values for cornea, iris and conjunctivae. This procedure was carried out separately for unrinsed and rinsed eyes respectively.

SCORING SYSTEM:
CORNEA:
A Opacity and degree of density (most dense area scored):
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
Maximum possible score = 80

IRIS:
A Values:
Normal, 0
Folds above normal, congestion, swelling, circumcornea 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
Maximum possible score = 10

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
Maximum possible score = 20

The total maximum score was thus 80 for the cornea, 10 for the iris, 20 for the conjunctivae and 110 for the entire eye. The severity of overall eye irritation was rated as:
0 - 10 minimal
11 - 25 slight
26 - 56 moderate
57 - 84 marked
above 84 extreme
The ratio R= unrinsed eyes/rinsed eyes, indicates the effect of rinsing the eyes 30 seconds after instillation of the compound.

<1 = rinsing increased the effect of the compound
1.1 - 1.5 = practically no effect
1.6 - 2 = little but assessable effect
2.1 - 4 = good effect
4.1 - 10 = very good effect
>10 = action of the compound practically abolished

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 1 - 7 days

Score:

0

Max. score:

80

Remarks on result:

other: Unrinsed eyes

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 1 - 7 days

Score:

0

Max. score:

10

Remarks on result:

other: Unrinsed eyes

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 1 - 7 days

Score:

0

Max. score:

20

Remarks on result:

other: Unrinsed eyes

Results 4

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 1 - 7 days

Score:

0

Max. score:

80

Remarks on result:

other: Rinsed eyes

Results 5

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 1 - 7 days

Score:

0

Max. score:

10

Remarks on result:

other: Rinsed eyes

Results 6

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 1 - 7 days

Score:

0

Max. score:

20

Remarks on result:

other: Rinsed eyes

Irritant / corrosive response data:

In the present experiments the irritation index was established as 0 for the cornea, 0 for the iris and 0 for the conjunctivae. The test material caused therefore no eye irritation to rabbits.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The test material was found to cause no irritation.

Executive summary:

A study similar to OECD Guideline 405 was performed. Under the conditions of this experiment the test material was found to cause no irritation when applied to the rabbit eye mucosa.