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Administrative data

Description of key information

Only minimal irritating effects after prolonged exposure period occured in the key skin irritation study similar to OECD Guideline 404 (Reckers, 1982). No positive reactions were observed in the key eye irritation study according to OECD Guideline 405 (Reckers, 1981).

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:
Jan/Feb 1982
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Guideline study. No GLP compliance is claimed, however, the final report includes an audit and quality assurance inspections. The skin preparation was not exactly performed in accordance to OECD Guideline 404. Furthermore, a 48h observation was not performed.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
The skin preparation was not exactly performed in accordance to OECD Guideline 404. The 48h observation was not performed.
Principles of method if other than guideline:
Detailed description of guideline deviations:
- Skin preparation: At 24 hours prior to study initiation, the fur on the back of each rabbit was clipped from an area approximately 240 cm2, and the skin was examined for abnormalities. On the day of treatment, four test sites (2.5 cm x 2.5 cm each), two on either side of the midline, were designated in the clipped area on the back of each rabbit. The test sites on the right side were abraded in a pattern with a hypodermic needle so as to penetrate the stratum corneum but not the dermis. The test sites on the left side were left intact. The results from the adraded test sites have been excluded from the calculation of the primary irritation index as the use of abraded skin does not follow current OECD test guidelines.
- Exposure: The application was for 24 h rather than the current OECD guideline exposure time of 4 h, and the 48h observation was not performed. Therefore, this represents a worst case.
GLP compliance:
no
Remarks:
Auditation and quality assurance inspections of the final report were performed.
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Dutchland Laboratories, Denver, PA
- Weight at study initiation: 2.0 to 2.7 kg
- Fasting period before study: No
- Housing: Individually housed in stainless steel cages (61.0 x 45.5 x 42.0 cm)
- Diet: Rabbits were fed Purina Lab Rabbit Chow HF (Ralston Purina Co.) ad libitum
- Water: ad libitum
- Acclimation period: approx. 2 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): approx. 20
- Humidity (%): approx. 40 (relative)
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES:
1982-01-26 - 1982-02-09
Type of coverage:
semiocclusive
Preparation of test site:
other: clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL applied to each test site
- Concentration: neat material used
Duration of treatment / exposure:
A 0.5 mL quantity of the test article was applied to each of the four test sites and covered with a 2.5 x 2.5 cm gauze pad which was secured by an adhesive dressing (CoverletR, Beiersdorf Inc., S. Norwalk. Conn.). The mid-section of the rabbit was wrapped in a lint-free cloth towel to prevent removal of the gauze pad while allowing the rabbit free movement. All wrapping materials and gauze pads were removed 24 hours after application and the test sites were washed with a 0.9 % sodium chloride solution to remove any residual test article.
Observation period:
The test sites were examined and scored 1, 3, 7 and 14 days after application for oedema, erythema, and eschar formation.
Each test site was scored for irritation according to the method of Draize.
Number of animals:
3 males and 3 females
Details on study design:
TEST SITE
- Area of exposure: 4 test sites (2.5 x 2.5 cm) on the back of each rabbit
- Type of wrap if used: Gauze pad was secured by an adhesive dressing (CoverletR, Beiersdorf Inc., S. Norwalk. Conn.). The mid-section of the rabbit was wrapped in a lint-free cloth towel to prevent removal of the gauze pad while allowing the rabbit free movement.

REMOVAL OF TEST SUBSTANCE
- Washing: 0.9 % sodium chloride solution
- Time after start of exposure: 24 h

SCORING SYSTEM: Draize
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 1 d
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: 12/12 test sites scored 2
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 3 d
Score:
1.8
Max. score:
2
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: 2/12 test sites scored 1; 10/12 test sites scored 2
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 7 d
Score:
0
Max. score:
0
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 14 d
Score:
0
Max. score:
0
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 1 d
Score:
0
Max. score:
0
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 3 d
Score:
0
Max. score:
0
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 7 d
Score:
0
Max. score:
0
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 14 d
Score:
0
Max. score:
0
Irritant / corrosive response data:
No details available.
Other effects:
No other effects reported.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test report describes a valid guideline study, with auditation and quality assurance inspections of the final report. The test material is not considered to be a primary dermal irritant and does not require classification according to EU CLP.
Executive summary:

A dermal irritation study was conducted using a similar procedure to that described in the current OECD Guideline 404 (Reckers, 1982). The test material (CAS No. 91648-65-6) was applied at a dose of 0.5 mL to the backs of 3 male and 3 female rabbits (strain: New Zealand White). The test article was left in contact with the skin for 24 hours and then the test sites were washed with 0.9 % sodium chloride and the rabbits observed during this time and for 14 days after its removal. The test sites were scored at 1, 3, 7 and 14 days after removal. Erythema was observed in all rabbits at 1 and 3 days following application. Mean scores of 2 (after 1 day) and 1.8 (after 3 days) were reported. After 7 days any effects were fully reversed. Edema did not occur. All rabbits appeared normal 14 days after application. No rabbits died during the study.

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:
Feb/Mar 1981
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study. No GLP compliance is claimed. However, auditation and quality assurance inspections of the final report were performed.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
no
Remarks:
Auditation and quality assurance inspections of the final report were performed.
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Lesser's Rabbitry, Union Grove, WI
- Weight at study initiation: 2.6 to 3.1 kg
- Fasting period before study: No
- Housing: Individually housed in stainless steel cages (61.0 x 45.5 x 42.0 cm)
- Diet: Rabbits were fed Purina Rabbit Chow Complete Blend (Ralston Purina Co.) ad libitum
- Water: ad libitum
- Acclimation period: approx. 25 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): approx. 22
- Humidity (%): approx. 40 (relative)
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES:
1981-02-16 - 1981-03-02
Vehicle:
unchanged (no vehicle)
Controls:
other: Each animal had one treated eye (right eye) and one untreated eye (left eye) which served as the control.
Amount / concentration applied:
0.1 mL
Duration of treatment / exposure:
The test article was instilled into the everted lower lid of the right eye of each rabbit and allowed to remain there.
Observation period (in vivo):
14 days, with ocular examinations on day 1, 2, 3, 4, 7 and 14 following test material administration.
Number of animals or in vitro replicates:
6 rabbits
Details on study design:
SCORING SYSTEM: Draize method
TOOL USED TO ASSESS SCORE: fluorescein and ultraviolet light
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 1, 2, 3, 4, 7, 14 d
Score:
0
Max. score:
0
Irritant / corrosive response data:
Eye irritation was not observed in any animal at any time point.
Other effects:
No other effects described.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test report describes a valid guideline study. Auditation and quality assurance inspections of the final report were performed. The test substance was not irritating to the rabbit eye under the conditions of the study and is thus not classified.
Executive summary:

An eye irritation study was conducted using a similar procedure to that described in the current OECD Guideline 405 (Reckers, 1981). The test material (CAS No. 91648-65-6) was applied at a volume of 0.1 mL to the right eye of six rabbits (strain: New Zealand White). The test article was left in the eye (i.e. no rinsing was performed) and the rabbits were observed during application followed by a 14 -day observation period. The left eye served as control.

The treated eye was scored at day 1, 2, 3, 4, 7 and 14 following instillation. Ocular irritation was not observed in any animal during the study.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

The dermal irritation key study was conducted using a similar procedure to that described in the current OECD Guideline 404 (Reckers, 1982). The target substance (CAS No. 91648-65-6) was applied at a dose of 0.5 mL to the backs of 3 male and 3 female rabbits (strain: New Zealand White). The test article was left in contact with the skin for 24 hours and then the test sites were washed with 0.9 % sodium chloride and the rabbits observed during this time and for 14 days after its removal. The test sites were scored at 1, 3, 7 and 14 days after removal. Erythema was observed in all rabbits at 1 and 3 days following application. Mean scores of 2 (after 1 day) and 1.8 (after 3 days) were reported. After 7 days any effects were fully reversed. Oedema did not occur. All rabbits appeared normal 14 days after application. No rabbits died during the study.

Considering to be a supporting study, a dermal irritation test was conducted using a similar procedure to that described in the current OECD Guideline 404 (Reckers, 1982). The read-across substance (CAS No. 50530-43-3) was applied at a dose of 0.5 mL to the backs of 6 female rabbits (strain: New Zealand White). The test article was left in contact with the skin for 24 hours and then the test sites were washed with 0.9% sodium chloride and the rabbits observed during this time and for 14 days after its removal. The test sites were scored at 1, 3, 7 and 14 days after removal. Oedema and erythema were observed in all rabbits 3 days following application and in the majority of rabbits 7 days following test article application. Mean erythema scores of 0.66 (1-day observation), 2 (3-day observation) and 1.33 (7-day observation) were reported. In addition, mean edema scores of 1.33 (3-day and 7-day observation, respectively) were determined. All effects were fully reversible within 14 days. Besides, all test animals appeared normal 14 days after application. No rabbits died during the study.

In another supporting study according to OECD Guideline 404 (Märtins, 1988), the dermal irritation potential of the read-across substance (1,3,4-Thiadiazolidine-2,5-dithione, reaction products with hydrogen peroxide and tert-dodecanethiol) was tested. In this study, 3 male adult albino-rabbits (strain: New Zealand White) were dermally exposed to 0.5 mL of the test item for 4 hours to ca. 6cm² clipped skin. Afterwards, the exposed skin areas were washed with water and the animals were observed for 7 days.

No erythema, eschar or oedema were observed at any time point. Eye irritation

The key eye irritation study was conducted using a similar procedure to that described in the current OECD Guideline 405 (Reckers, 1981). The target substance (CAS No. 91648-65-6) was applied at a volume of 0.1 mL to the right eye of six rabbits (strain: New Zealand White). The test article was left in the eye (i.e. no rinsing was performed) and the rabbits were observed during application followed by a 14 -day observation period. The left eye served as control. The treated eye was scored at day 1, 2, 3, 4, 7 and 14 following instillation. Ocular irritation was not observed in any animal during the study.

A supporting eye irritation study was conducted using a similar procedure to that described in the current OECD Guideline 405 (Reckers, 1981). The read-across substance (CAS No. 50530-43-3) was applied at a volume of 0.1 mL to the right eye of six female rabbits (strain: New Zealand White). The test article was left in the right eye (i.e. no rinsing was performed) and the rabbits were observed during application followed by a 14 -day observation period. The left eye served as control. The treated eye was scored at day 1, 2, 3, 4, 7 and 14 following instillation. Ocular irritation was not observed in any animal during the study.

In another supporting eye irritation study according to OECD Guideline 405 (Märtins, 1988), 0.1 mL of the read-across substance (1,3,4-Thiadiazolidine-2,5-dithione, reaction products with hydrogen peroxide and tert-dodecanethiol) was instilled into the conjunctival sac of one eye of each 3 male adult albino rabbits (strain: New Zealand White) for 24 hours. The untreated eye served as control. After the exposure period, the treated eye was washed with physiological saline. The animals were then observed for 7 days. Except a slight, fully reversible conjunctivae redness and lacrimation 1 h after exposure in one animal, no other effects were observed.


Justification for selection of skin irritation / corrosion endpoint:
Only one study conducted with the target substance is available (key study).

Justification for selection of eye irritation endpoint:
Only one study conducted with the target substance is available (key study).

Justification for classification or non-classification

Skin irritation

Due to the fact, that the exposure period of the key study amounts to 24 hours, the classification criteria outlined in section 3.2.2.2. (Guidance on the Application of CLP criteria, 2012) cannot be applied. These classification criteria refer to an exposure period of 4 hours. Nevertheless, the substance is not considered as a skin irritant. By increasing the exposure duration, irritating effects would worsen. After prolonged exposure duration, the mean erythema score amounts to 2 (1-day observation) and 1.8 (3 -day observation). Oedema did not occur in any treated test animal. In conclusion, the results only show minimal irritating effects after a prolonged application. Therefore, the performed non-classification is scientifically justified.

Eye irritation

According to the classification criteria outlined in the section 3.3.2.2. (Guidance on the Application of CLP criteria, 2012), if a substance cause positive but reversible reactions such as corneal opacity (score ≥ 1), iritis (score ≥ 1), conjunctival redness (score ≥ 2) or conjunctical oedema (chemosis) (score ≥ 2) in at least 2 of 3 tested animals from gradings at 24, 48 and 72 hours after application, the classification as Eye Irritant (Category 2) is assigned. Eye irritation was not observed in any animal at any time point.

Therefore, this substance does not meet the requirement under EU CLP (Regulation (EC) No. 1272/2008) for classification as irritating to eyes.