Registration Dossier

Toxicological information

Eye irritation

Currently viewing:

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
From 22 February 1988 to 14 March, 1988
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
KL2 due to RA
Justification for type of information:
Refer to the Quaternary ammonium salts (QAS) category or section 13 of IUCLID for details on the category justification.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1988
Report Date:
1988

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Type:
Constituent
Type:
Constituent
Type:
Constituent
Type:
Constituent
Test material form:
solid

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Mohican Valley Rabbitry, Loudonville, Ohio
- Age at study initiation: Young adult
- Weight at study initiation: 2,634 to 3,104 g at study initiation
- Housing: Individual suspended wire-mesh cages. The animals were maintained in accordance with the recommendations contained in the "guide for care and use of laboratory animals" NIH publication, No. 8502
- Diet: Purina Certified Rabbit Chow #5322
- Water: Tap water
- Acclimation period: 7 d

ENVIRONMENTAL CONDITIONS
- Temperature : 67-74 °F
- Humidity (%): 40-74%
- Photoperiod (hrs dark / hrs light): 12 h/12 h

IN-LIFE DATES: From 23 February, 1988 to 8 March, 1988

Test system

Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.1 mL
Duration of treatment / exposure:
Single treatment
Observation period (in vivo):
Both eyes were examined at approximately 1, 24, 48 and 72 h after dosing and at 96 h and 7, 14 and 21 d. In addition, both eyes of all rabbits were further examined at 72 h and 7, 14 and 21 d with sodium fluorescein and ultraviolet light.

Number of animals or in vitro replicates:
5 males and 4 females
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): Out of the 9 animals, the eye of the three rabbits were washed with 120 mL of lukewarm tap water for approximately 1 min.
- Time after start of exposure: 30 sec after dosing

SCORING SYSTEM: Draize

TOOL USED TO ASSESS SCORE: Sodium fluorescein and ultraviolet light

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
other: Maximum average score (M.A.S)
Basis:
mean
Time point:
other: 14 d
Score:
96.8
Max. score:
110
Reversibility:
not fully reversible within: 21 d
Remarks on result:
other: This value is for unwashed group
Irritation parameter:
other: Maximum average score
Basis:
mean
Time point:
other: 72 h
Score:
69.7
Max. score:
110
Reversibility:
not fully reversible within: 21 d
Remarks on result:
other: This value is for washed group
Irritation parameter:
other: Maximum average score
Basis:
mean
Time point:
other: 96 h
Score:
69.7
Max. score:
110
Reversibility:
not fully reversible within: 21 d
Remarks on result:
other: This value is for washed group
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
2.5
Max. score:
4
Reversibility:
not fully reversible within: 21 d
Remarks on result:
positive indication of irritation
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 1.03
Max. score:
4
Reversibility:
not fully reversible within: 21 d
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 2.3
Max. score:
4
Reversibility:
not fully reversible within: 21 d
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
(discharge)
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 2.56
Max. score:
4
Reversibility:
not fully reversible within: 21 d
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 3.92
Max. score:
4
Reversibility:
not fully reversible within: 21 d
Remarks on result:
positive indication of irritation
Irritant / corrosive response data:
The test substance was maximally irritating for the unwashed group and extremely irritating for the washed group.
Other effects:
Purulent discharge, clear discharge, petite hemorrhage, blanching, corneal epithelial damage, corneal neovascularization, sodium fluorescein stain retention.

Any other information on results incl. tables

Table 1.                           Results of eye irritation study

 

 

Cornea

Iris

Conjunctiva

redness

chemosis

Score (average of animals investigated)

0 to 4

0 to 2

0 to 3

0 to4

60 min

3.0

1

1

4

24 h

2.8

1

1.7

4

48 h

2.8

1

2.3

4

72 h

2.8

1

2.8

4

21 days

4

0.3

1.8

2.5

Average 24h, 48h, 72h

2.8

1

2.3

4

Area effected

> 75%

Maximum average score (including area affected, max 110)

96.8 on day 14

Reversibility*

n

Average time for reversion

 

Give method of calculation maximum average score.

*          c :       completely reversible
           n c :    not completely reversible
           n :       not reversible

Cornea:   (opacity * area) * 5
Iris:
          Iris * 5
Conjunct.: (redness+chemosis+discharge)*2

Max. score: 80 + 10 + 20 = 110

Applicant's summary and conclusion

Interpretation of results:
other: Category 1 (irreversible effects on the eye) based on CLP criteria
Conclusions:
Based on the results of the read across study, the test substance is considered to cause irreversible effects on the eye.
Executive summary:

A study was conducted to determine the skin irritation potential of the read across substance, Coco TMAC (33% active), in New Zealand White rabbits according to OECD 405 Guideline, in compliance with GLP. Nine rabbits received 0.1 mL of undiluted solution in one eye. The other eye remained untreated. The eyelids were held close for approximately 1 second after instillation. The eyes of three rabbits were washed for approximately 1 minute with 120 mL of lukewarm tap water commencing approximately 30 seconds after dosing. Both eyes were examined at for ocular irritation in accordance with the method of Draize approximately 1, 24, 48 and 72 h after dosing and at 96 h and 7, 14 and 21 d. In addition, both eyes of all rabbits were further examined at 72 h and 7, 14 and 21 d with sodium fluorescein and ultraviolet light. Body weights were obtained and recorded on study day 0 (initiation) and at termination (Day 21). Based on the data obtained, the Maximum Average Scores (according to Kay and Calandra) for the read across substance were calculated to be 96.8 (extremely irritating) at 14 d for the unwashed group and 69.7 (severely irritating) at both 72 and 96 h for the washed group. Purulent discharge, clear discharge, petite haemorrhage, blanching, corneal epithelial damage and peeling, corneal neovascularisation, Sodium fluoresceinstain retention, and vascularised granulation scar tissue was observed in all 6 animals. Same effects were observed in the washed group, except for vascularised granulation scar tissue. There were no deaths or remarkable body weight changes during the study period. Under the study conditions, the read across substance is considered to cause irreversible effects on the eye (Naas, 1988). Based on the results of the read across study, a similar corrosive potential can be expected for the test substance.