Pentyl 2-cyano-(3-(6-methoxybenzothiazol-2-ylimino)-2,3-dihydro-1H-isoindol-1-ylidene)acetate

Endpoint summary

Description of key information

The available data suggest that test substance has very low degrees of skin and eye irritation potential. For both skin and eye, the test substance was found to be non-irritating

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 Aug. 22, 2000 to Nov. 28, 2000

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland GmbH, 88353 Kiβlegg
- Weight at study initiation: 3.2 - 3.9 kg
- Diet: ssniff K-H (V2333), ad libitum and hay (approx. 15 g daily)
- Water: water from automatic water dispensers, ad libitum
- Acclimation period: 1 wk

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3 °C
- Humidity (%): 50±20 °C
- Photoperiod (hrs dark / hrs light): 12 h dark/12 h light

IN-LIFE DATES: From: Aug. 22, 2000 To: Aug. 25, 2000

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

other: Tylose H 4000 G4 PHA (0.5 % in deionized water)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.5 g of test substance pasted with 0.5 mL Tylose H 4000 G4 Pha (0.5 % in deion. water)

Duration of treatment / exposure:

4 h

Observation period:

24, 48 and 72 h after removal of the patches

Number of animals:

Three

Details on study design:

TEST SITE
- Area of exposure: Dorsal region of the body
- % coverage: 25 cm2
- Type of wrap if used: Yes, The test substance was evenly distributed over the whole surface of a 2.5 x 2.5 cm cellulose patch on a piece of surgical plaster. The plaster was fixed to the prepared skin area and then covered with a semi-occlusive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes, with warm water
- Time after start of exposure: 4 h

SCORING SYSTEM: Erythema, eschar formation and edema were evaluated numerically according to the score of DRAIZE

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No abnormalities detected in any of the tested animals at time points till 72 h

Other effects:

None

No signs of irritations were observed during the whole observation period

Interpretation of results:

GHS criteria not met

Conclusions:

Under the test conditions, the test substance was considered to be non-irritating to rabbit skin

Executive summary:

A study was conducted to assess the skin irritation potential of test substance to the rabbit skin according to EU Method B.4. and OECD Guideline 404 in compliance with GLP.

Three animals were treated with 0.5 g of the test substance pasted with 0.5 mL Tylose H 4000 G4 Pha (0.5 % in deion. water) using semi-occlusive patches for 4 h. After the exposure period all remnants of the test substance were carefully removed from the skin with warm tap water. The skin was evaluated for erythema, eschar formation and edema numerically according to the score of Draize system for up to 72 h after patch removal.

No signs of irritation were observed during the whole observation period.

Under the test conditions, the test substance was considered to be non-irritating to rabbit skin.

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 Aug. 29, 2000 to Nov. 28, 2000

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland GmbH, 88353 Kiβlegg
- Weight at study initiation: 2.3 - 3.9 kg
- Diet: ssniff K-H (V2333), ad libitum and hay (approx. 15 g daily)
- Water: From automatic water dispensers, ad libitum
- Acclimation period: 1 wk

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20±3 °C
- Humidity (%): 50±20 °C
- Photoperiod (hrs dark / hrs light): 12 h dark/12 h light

IN-LIFE DATES: From: Aug. 29, 2000 To: Sep. 08, 2000

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 mg

Duration of treatment / exposure:

Single treatment

Observation period (in vivo):

72 h

Number of animals or in vitro replicates:

3 rabbits

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes, 24 h after administration the treated eyes were washed out thoroughly with isotonic saline at approx. 37 °C
- Time after start of exposure: 24 h

SCORING SYSTEM: Lesions in cornea, iris or conjunctivae were graded numerically "Scale for scoring ocular reactions"

TOOL USED TO ASSESS SCORE: 0.01 % fluorescein-sodium solution; slit lamp

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

3

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

- 1 h after administration, the conjunctivae of the animals showed sporadically definitely injected blood vessel and a very slight swelling.
- In addition, serous by compound discolored eye discharge was noted, 24 h after administration.
- All signs of irritation had completely reversed

Interpretation of results:

GHS criteria not met

Conclusions:

Under the test conditions, the test substance was considered to be non-irritating to the rabbit eye

Executive summary:

A study was conducted to assess the eye irritation potential of test substance to the rabbit eye according to EU Method B.5. and OECD Guideline 405 in compliance with GLP.

Three animals received 0.1 g of an undiluted test substance into conjunctival sac of the left eye. The other eyes served as untreated control. 24 h after the administration the eyes were washed thoroughly with isotonic saline at 37 °C. The eyes were also washed out at designated examination times at which discharge was observed or a corneal examination with fluorescein was performed.

The eyes were examined 1, 24, 48 and 72 h after administration of the test substance. At 24 and 72 h the eyes were further examined for corneal lesions under UV light after instillation of one drop of a 0.01 % fluorescein-sodium solution. Lesions in cornea, iris or conjunctivae were graded numerically (Scale for scoring ocular reactions). All other changes or toxic effects were recorded when apparent.

One hour after administration the conjunctivae of the animals showed sporadically definitely injected blood vessel and a very slight swelling. In addition, serous by compound discolored eye discharge was noted, 24 h after administration all signs of irritation had completely reversed.

Based on the individual scores after 24, 48 and 72 h, the mean values were calculated to be ‘0’ for opacity of cornea, iris, redness of the conjunctiva and chemosis of conjunctiva.

Under the test conditions, the test substance was considered to be non-irritating to rabbit eye.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Additional information

Skin irritation

A study was conducted to assess the skin irritation potential of test substance to the rabbit skin according to EU Method B.4. and OECD Guideline 404.

Three animals were treated with 0.5 g of the test substance pasted with 0.5 mL Tylose H 4000 G4 Pha (0.5 % in deion. water) using semi-occlusive patches for 4 h. After the exposure period all remnants of the test substance were carefully removed from the skin with warm tap water. The skin was evaluated for erythema, eschar formation and edema numerically according to the score of Draize system for up to 72 h after patch removal. No signs of irritation were observed during the whole observation period. The test substance was considered to be non-irritating to rabbit skin (Dr. Th. Roth, 2000).

 

Eye irritation:

A study was conducted to assess the eye irritation potential of test substance to the rabbit eye according to EU Method B.5. and OECD Guideline 405.

Three animals received 0.1 g of an undiluted test substance into conjunctival sac of the left eye. The other eyes served as untreated control. 24 h after the administration the eyes were washed thoroughly with isotonic saline at 37 °C. The eyes were also washed out at designated examination times at which discharge was observed or a corneal examination with fluorescein was performed. The eyes were examined 1, 24, 48 and 72 h after administration of the test substance. At 24 and 72 h the eyes were further examined for corneal lesions under UV light after instillation of one drop of a 0.01 % fluorescein-sodium solution. Lesions in cornea, iris or conjunctivae were graded numerically (Scale for scoring ocular reactions). All other changes or toxic effects were recorded when apparent. 1 h after administration the conjunctivae of the animals showed sporadically definitely injected blood vessel and a very slight swelling. In addition, serous by compound discolored eye discharge was noted, 24 h after administration all signs of irritation had completely reversed. Based on the individual scores after 24, 48 and 72 h, the mean values were calculated to be ‘0’ for opacity of cornea, iris, redness of the conjunctiva and chemosis of conjunctiva. The test substance was considered to be non-irritating to rabbit eye (Dr. Th. Roth, 2000).

Justification for classification or non-classification

The available data suggest that test substance has very low degrees of skin and eye irritation potential. For both skin and eye, the test substance was found to be non-irritating and does not meet the requirement for classification according to EC criteria (67/548/EEC) and according to CLP criteria (EC 1272/2008).