Registration Dossier

Administrative data

Description of key information

The test substance was neither corrosive nor irritating to skin (CIBA GEIGY LTD,1984a) or eye (CIBA GEIGY LTD,1984b).

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From July 3, 1984 until July 6, 1984; report date: October 4, 1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
OECD guideline No. 404, adopted
May 12, 1981
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Remarks:
KFM-NZW
Details on test animals or test system and environmental conditions:
The albino rabbit is the recommended species for skin irritation / corrosion studies.

Animal Strain: New Zealand white rabbits (KFM-NZW)
Sex: female 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: 7 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
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
water
Controls:
yes, concurrent no treatment
Amount / concentration applied:
0.5 g
Duration of treatment / exposure:
4 hours
Observation period:
The skin reactions were evaluated 1, 24, 48, and 72 hours after removing the gauze patches
Number of animals:
3
Details on study design:
An area of about 6 sq.cm was shaved on both flanks of the animals approximately 24 hours before treatment. A gauze patch bearing 0.5 g of the test substance was applied to the flank. A control gauze patch was applied to the contralateral flank. Both gauze patches were moistened before application with distilled water.
The patches were covered with an occlusive membrane and held in place for 4 hours by an adhesive tape (Isoplast, Isoplast AG, CH-5200 Brugg) . The animals were checked daily for systemic symptoms and mortality.
The skin reactions were evaluated 1, 24, 48, and 72 hours after removing the gauze patches according to the OECD scoring system.
The irritant/corrosive potency of the test item was classified according to the EEC commission directive No. 83/467/1983
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
control animal
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no effect observed
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
control animal
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no effect observed
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
control animal
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no effect observed
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
control animal
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no effect observed
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
control animal
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no effect observed
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
control animal
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no effect observed
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
treated animal
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no effect observed
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
treated animal
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no effect observed
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
treated animal
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no effect observed
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
treated animal
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no effect observed
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
treated animal
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no effect observed
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
treated animal
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no effect observed
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
ERYTHEMA
Animal No. 10F 11F 12F
CF TF CF TF CF TF
After 1 hr. 0 0 0 0 0 0
After 24 hrs. 0 0 0 0 0 0
After 48 hrs. 0 0 0 0 0 0
After 72 hrs. 0 0 0 0 0 0
Mean
24-72 hrs. 0 0 0 0 0 0

EDEMA
Animal No. 10F 11F 12F
CF TF CF TF CF TF
After 1 hr. 0 0 0 0 0 0
After 24 hrs. 0 0 0 0 0 0
After 48 hrs. 0 0 0 0 0 0
After 72 hrs. 0 0 0 0 0 0
Mean
24-72 hrs. 0 0 0 0 0 0

CF = Control flank
TF = Test compound treated flank
Other effects:
There are no effects on body weights observed.

Body weights [g]
Animal No. 10F 11F 12F
Start of test 1840 2040 2030
Day 2 1865 2130 2000
Day 3 (End of test) 1910 2110 2070
Conclusions:
Under the present conditions, there were no signs of irritation. Therefore, it can be concluded that the test item has no primary skin irritating potency in albino rabbits.
Executive summary:

The test item (benzothiazol-2-ylthio)succinic acid was tested for its skin irritaion/ corrosion properties in female albino rabbits according to the OECD 404 guideline.

A gauze patch bearing 0.5 g of the test substance was applied to the flank of the rabbit, moistened with distilled water and covered occlusively for 4 hours. The animals were checked daily for systemic symptoms and mortality. The skin reactions were evaluated 1, 24, 48, and 72 hours after removing the gauze patches according to the OECD scoring system. Because no reactions were observed at 24 hours to 72 hours after removing the bandages, the test was ended after the 72 hours evaluation.

It can be concluded that te test item has no primary skin irritating potency in albino rabbits.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
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
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
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:
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.
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
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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Under the present conditions of the OECD 404 study, there were no signs of irritation. Therfore, it can be concluded that the test item has no primary skin irritant potency in albino rabbits.

Under the experimental conditions of the OECD 405 study, the test item induced slight irritation of the conjunctiva when applied into the conjunctival sac of albino rabbits. All effects were reversible after 10 to 14 days.

Justification for classification or non-classification

Based on the available OECD 404 study and according to criteria of EC Regulation 1272/2008 (CLP) the substance is neither corrosive nor irritating to skin and therefore must not be classified.

Based on the available OECD 405 study the substance induced slight and reversible irritation of the conjunctiva., which does not meet the criteria according to EC Regulation 1272/2008 to be classified as "irritating to eyes".