Reaction mass of Sodium 2-(2 or 3-{[(chloroacetyl)amino]methyl}-4-{[4-(cyclohexylamino)-9,10-dioxo-9,10-dihydroanthracen-1-yl]amino}phenoxy)-5-methylbenzenesulfonate and Sodium 2-(3 or 2-{[(chloroacetyl)amino]methyl}-4-{[4-(cyclohexylamino)-9,10-dioxo-9,10-dihydroanthracen-1-yl]amino}phenoxy)-5-methylbenzenesulfonate

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:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1975

Report date:

1975

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

other: Hazardous substances regulations- USA Federal Hazardous Substances Labelling Act Sect 191.12 (February 1965)

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: "Appraisal of the Safety of Chemicals in Food Drugs and Cosmetics" page 51, published by the Association of Food and Drug Officials of the U.S.A.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Reaction mass of Sodium 2-(2 or 3-{[(chloroacetyl)amino]methyl}-4-{[4-(cyclohexylamino)-9,10-dioxo-9,10-dihydroanthracen-1-yl]amino}phenoxy)-5-methylbenzenesulfonate and Sodium 2-(3 or 2-{[(chloroacetyl)amino]methyl}-4-{[4-(cyclohexylamino)-9,10-dioxo-9,10-dihydroanthracen-1-yl]amino}phenoxy)-5-methylbenzenesulfonate

EC Number:

942-981-6

Molecular formula:

C36H33ClN3NaO7S

IUPAC Name:

Reaction mass of Sodium 2-(2 or 3-{[(chloroacetyl)amino]methyl}-4-{[4-(cyclohexylamino)-9,10-dioxo-9,10-dihydroanthracen-1-yl]amino}phenoxy)-5-methylbenzenesulfonate and Sodium 2-(3 or 2-{[(chloroacetyl)amino]methyl}-4-{[4-(cyclohexylamino)-9,10-dioxo-9,10-dihydroanthracen-1-yl]amino}phenoxy)-5-methylbenzenesulfonate

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

None

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Bred on the premises of the testing laboratory
- Age: 10-11 weeks
- Average body weight: Males: 2.27 kg; Females: 2.07 kg
- Diet: A commercial irradiated diet (Styles-Oxoid), ad libitum
- Water: Sterile filtered water, ad libitum
- Acclimation period: One week

ENVIRONMENTAL CONDITIONS
- Temperature: 20 ± 1 °C
- Humidity: 50-70 %
- Photoperiod: Animals were exposed to artificial light for 10 h daily from 08.00 - 18.00 h

Test system

Vehicle:

not specified

Controls:

other: untreated right eye

Amount / concentration applied:

- Amount(s) applied: 100 mg

Duration of treatment / exposure:

Unwashed eye: unspecified (not rinsed after single instillation)
Washed eye: 30 sec

Observation period (in vivo):

24, 48 and 72 hours after application of the test compound and for any further period that was considered necessary.

Number of animals or in vitro replicates:

Six animals (five males and one females)

Details on study design:

PROCEDURE:
-The test was carried out in accordance with the procedure set out in the Hazardous Substances Regulations" under the U.S.A. Federal Hazardous Substances Labelling Act Sect. 191.12 (February 1965), with slight modification.
-The eyes of the experimental animals were examined and found normal prior to the test. 100 mg of the test substance were instilled into the conjunctival sac of the left eye. The eyelids were then held closed for 1 sec. The right eye served as a control.

REMOVAL OF TEST SUBSTANCE
After 30 seconds the test substance was, as far as possible, flushed out of the eyes of three rabbits with warm water for 1 min.

SCORING SYSTEM: The ocular reactions were scored by the method described in "Appraisal of the Safety of Chemicals in Food Drugs and Cosmetics" page 51, published by the Association of Food and Drug Officials of the U.S.A.
REMOVAL OF TEST SUBSTANCE
- Washing (if done): After 30 seconds the compound was administered, as far as possible, flushed out of the eyes of three of the rabbits with warm water for 1 minute.
- Time after start of exposure: 24, 48 and 72 hours after application of the test compound and for any further period that was considered necessary

SCORING SYSTEM:

The eye reactions were assessed as follows:-
Score Assessment

0 Non-irritant
> 0 - 10 Minimally irritant
11-25 Slightly irritant
26-56 Moderately irritant
57 -84 Markedly irritant
> 84 Extremely irritant

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 24h

Remarks on result:

other: Transient changes at 1 hour

Results 2

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 3

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 6d

Results 4

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72h

Results 5

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 6

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 7

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.33

Max. score:

3

Reversibility:

fully reversible within: 6d

Results 8

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72h

Results 9

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 10

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 11

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.67

Max. score:

3

Reversibility:

fully reversible within: 72h

Results 12

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 13

Irritation parameter:

cornea opacity score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 14

Irritation parameter:

iris score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 15

Irritation parameter:

conjunctivae score

Basis:

animal #4

Time point:

24/48/72 h

Score:

1.33

Max. score:

3

Reversibility:

fully reversible within: 6d

Results 16

Irritation parameter:

chemosis score

Basis:

animal #4

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72h

Results 17

Irritation parameter:

cornea opacity score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 18

Irritation parameter:

iris score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 19

Irritation parameter:

conjunctivae score

Basis:

animal #5

Time point:

24/48/72 h

Score:

1.33

Max. score:

3

Reversibility:

fully reversible within: 6d

Results 20

Irritation parameter:

chemosis score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72h

Results 21

Irritation parameter:

cornea opacity score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 22

Irritation parameter:

iris score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 23

Irritation parameter:

conjunctivae score

Basis:

animal #6

Time point:

24/48/72 h

Score:

1.33

Max. score:

3

Reversibility:

fully reversible within: 6d

Results 24

Irritation parameter:

chemosis score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72h

Irritant / corrosive response data:

A mild to moderate conjunctival reaction was noted in all treated eyes 1 hour after application. A slight reaction was present at 24 hours which slowly regressed until all eyes were normal by day 6. A transient corneal reaction consisting of slight opacity and damage to the surface epithelium was noted in one rabbit at one hour only. There was no significant difference between washed and unwashed eyes.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

FAT 20077/A was considered to be not an eye irritant.

Executive summary:

A study was conducted to assess the eye irritancy potential of the test substance in rabbits according to U.S.A. Federal Hazardous substances Labelling Act Sect. 191.12 (February 1965), with slight modification. A dose of 100 mg of the test compound was instilled into the conjunctival sac of the left eye. The test was carried out in both washed and unwashed eyes with test substance instillation. Ocular reactions were scored at 1, 6, 24, 48 and 72 h post-instillation. A mild to moderate conjunctival reaction was noted in all treated eyes 1 hour after application. A slight reaction was present at 24 hours which slowly regressed until all eyes were normal by day 6. A transient corneal reaction consisting of slight opacity and damage to the surface epithelium was noted in one rabbit at one hour only. There was no significant difference between washed and unwashed eyes. Hence, based on the findings of the study, FAT 20077/A is considered to be not an eye irritant in the albino rabbit.