Registration Dossier

Toxicological information

Eye irritation

Currently viewing:

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From July 2, 1984 until July 16, 1984, Study report November 4, 1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1984
Report date:
1984

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
OECD guideline No. 405, adopted May 12, 1981
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
(benzothiazol-2-ylthio)succinic acid
EC Number:
401-450-4
EC Name:
(benzothiazol-2-ylthio)succinic acid
Cas Number:
95154-01-1
Molecular formula:
C11H9NO4S2
IUPAC Name:
(benzothiazol-2-ylthio)succinic acid
Test material form:
solid
Details on test material:
(benzothiazol-2-ylthio)succinic acid, Batch: 1

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Remarks:
KFM-NZW
Details on test animals or tissues and environmental conditions:
The albino rabbit is the recommended species for eye irritation / corrosion studies.

Animal Strain: New Zealand white rabbits (KFM-NZW)
Sex: male rabbits
Breeder: Kleintierfarm Maedorin AG, CH-4414 Fuellinsdorf


TEST ANIMALS

- Age at study initiation: approx. 12-14 weeks old
- Weight at study initiation: 2 to 3 kg
- Housing: individually in metal cages, identified with individually numbered ear tags
- Diet (e.g. ad libitum): ad libitum standard rabbit pellet - Nafag No. 814, Gossau, Switzerland
All batches of the diet are assayed for nutritive ingredients and contaminant level by the manufacturer.
- Water (e.g. ad libitum): ad libitum fresh water
The quality of the drinking water was according to the specifications of the "Schweizerisches Lebensmittelbuch" (Edition 1972) .
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): constant room temperature of 20+/-3 °C
- Humidity (%): relative humidity of 30-70 %
- Air changes (per hr): not specified
- Photoperiod (hrs dark / hrs light): 12 hours

IN-LIFE DATES: From: To:

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes
Amount / concentration applied:
0.1 g of the test item was placed into the conjunctival sac of the right eye of each animal, after gently pulling away the lower lid from the eyeball. The lids were then held together for about one second in order to prevent loss of the test material.
Duration of treatment / exposure:
72 hours
Observation period (in vivo):
The ocular reactions were evaluated 1, 24, 48, and 72 hours after the instillation of the test item.
Number of animals or in vitro replicates:
3 male rabbits
Details on study design:
0.1 g of the test item was placed into the conjunctival sac of the right eye of each animal, after gently pulling away the lower lid from the eyeball. The lids were then held together for about one second in order to prevent loss of the test material.
The left eye remained untreated and served as a control.
The animals were checked daily for systemic symptoms and mortality.
The ocular reactions were evaluated 1, 24, 48, and 72 hours after the instillation of the tet item according to the OECD scoring system (Appendix 1) . A slit-lamp was used to facilitate the evaluation. The irritant/corrosive potency of the tet item was classified according to the EEC commission directive No. 83/467, 1983.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal #1
Remarks:
control eye
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #2
Remarks:
control eye
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #3
Remarks:
control eye
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #1
Remarks:
treated eye
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #2
Remarks:
treated eye
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: no effects
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
positive indication of irritation
Irritation parameter:
iris score
Basis:
animal #1
Remarks:
control eye
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: no effects
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #2
Remarks:
control eye
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: no effects
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #3
Remarks:
control eye
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: no effects
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #1
Remarks:
treated eye
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: no effects
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #2
Remarks:
treated eye
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: no effects
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #3
Remarks:
treated eye
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: no effects
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #1
Remarks:
control eye
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
other: no effects
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #2
Remarks:
control eye
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
other: no effects
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #3
Remarks:
control eye
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
other: no effects
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #1
Remarks:
treated eye
Time point:
24/48/72 h
Score:
1.33
Max. score:
3
Reversibility:
fully reversible within: 10 days
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #2
Remarks:
treated eye
Time point:
24/48/72 h
Score:
1.33
Max. score:
3
Reversibility:
fully reversible within: 10 days
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #3
Remarks:
treated eye
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 14 days
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #1
Remarks:
control eye
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #2
Remarks:
control eye
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #3
Remarks:
control eye
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #1
Remarks:
treated eye
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72hrs
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #2
Remarks:
treated eye
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #3
Remarks:
treated eye
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72 hrs
Remarks on result:
positive indication of irritation
Irritant / corrosive response data:
Animal No. 7
Cornea Iris Conjunctiva Chemosis
CE TE CE TE CE TE CE TE
After 1h 0 0 0 0 0 2 0 2

After 24 hrs. 0 0 0 0 0 2 0 2
After 48 hrs. 0 0 0 0 0 1 0 1
After 72 hrs. 0 0 0 0 0 1 0 0
Mean
(24-72 hrs.) 0 0 0 0 0 1.33 0 1

Day 7 0 0 0 0 0 1 0 0
Day 10 0 0 0 0 0 0 0 0
Day 14 0 0 0 0 0 0 0 0


Animal No. 8
Cornea Iris Conjunctiva Chemosis
CE TE CE TE CE TE CE TE
After 1h 0 0 0 0 0 2 0 3

After 24 hrs. 0 0 0 0 0 2 0 2
After 48 hrs. 0 0 0 0 0 1 0 1
After 72 hrs. 0 0 0 0 0 1 0 1
Mean
(24-72 hrs.) 0 0 0 0 0 1.33 0 1.33

Day 7 0 0 0 0 0 1 0 0
Day 10 0 0 0 0 0 0 0 0
Day 14 0 0 0 0 0 0 0 0


Animal No. 9
Cornea Iris Conjunctiva Chemosis
CE TE CE TE CE TE CE TE
After 1h 0 0 0 0 0 2 0 3

After 24 hrs. 0 0 0 0 0 2 0 2
After 48 hrs. 0 0 0 0 0 2 0 1
After 72 hrs. 0 0 0 0 0 2 0 0
Mean
(24-72 hrs.) 0 0 0 0 0 2 0 1

Day 7 0 0 0 0 0 2 0 0
Day 10 0 0 0 0 0 1 0 0
Day 14 0 0 0 0 0 0 0 0

CE= Control Eye
TE = Treated Eye
Other effects:
There are no effects on gain of body weights observed.

Bodyweights (g)
Animal No. 7 (1) 8(2) 9(3)
1 At Start of test 2180 2250 2410
1 Day 3 2180 2290 2510
1 Day 10 2405 2510 2750
1 Day 14 (End of test) 2460 2620 2850

Applicant's summary and conclusion

Conclusions:
Under the experimental conditions employed the test item induced irritation of the conjunctiva when applied into the conjunctival sac of albino rabbits. All effects were reversible after 10 to 14 days.
Executive summary:

The test item (benzothiazol-2-ylthio)succinic acid was tested for its eye irritaion/ corrosion properties in male albino rabbits according to the OECD 405 guideline. 0.1 g of the test item was placed into the conjunctival sac of the right eye of each animal the left eye remained untreated and served as control. The ocular reactions were evaluated 1, 24, 48, and 72 hours after the treatment and animals were observed for 14 days for reversibility of effects.

Under the experimental conditions the test item induced irritation of the conjunctiva. The readings for cornea and iris score were 0 for all animals and time points, the mean conjunctivitis score after 24, 48 and 72 hours was 1.3 for two animals and 2.0 for the third animal. The mean chemosis score after 24, 48 and 72 hours was 1 for two animals and 1.3 respectively. All effects were reversible after 10 to 14 days.