3-(5,5,6-trimethylbicyclo[2.2.1]hept-2-yl)cyclohexan-1-ol

Endpoint summary

Description of key information

Skin Irritation:

Acute Dermal Irritation/corrosion Study of test chemical in Rabbits, was performed as per OECD guideline No. 404. A volume of 0.5 ml of test item (as such) was applied to the skin for 4 hours and rabbits were observed for erythema and oedema at 1, 24, 48 and 72 hours and on day 7 post patch removal, evaluated and graded as per Draize method. The individual mean score at 24, 48 and 72 hours for Animal Nos. 1, 2 and 3 were 0.00, 0.00, 0.00 and 0.00, 0.00, 0.00, for erythema and oedema formation, respectively Hence, it was concluded that the test chemical was Non-Irritating to the skin of male New Zealand White rabbits under the experimental conditions tested. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

 

Eye Irritation:

Acute Eye Irritation/Corrosion Study of Test chemical in Rabbits, was performed as per OECD guideline No. 405. The. 0.1 ml of test item was instilled in the other (treated) eye of each rabbit. The eye was observed at 1, 24, 48, 72 hour, day 7, day 14 and day 21 for animal no. 1 and 3 whereas at 1, 24, 48 and 72 hour after test item instillation. Ophthalmoscope was used for scoring of eye lesions. The individual mean score for animal nos. 1, 2 and 3 at 24, 48, 72 hours for corneal opacity, iris, conjunctiva and chemosis were found 0.00, 0.00, 1.67, 0.00; 0.00, 0.00, 1.00, 1.00 and 0.00, 0.00, 2.00, 1.00, respectively. Under the experimental conditions tested, eye irritation and reversibility of effects on eyes of all 3 animals was observed at day 7. Hence, the test chemical is considered as mildly irritating to the eyes of female New Zealand White rabbits, and thus comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Category 2”.

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

Data is from experimental study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Principles of method if other than guideline:

The objective of the study was to assess the irritant and/or corrosive effects of test chemical after dermal application on the intact skin of rabbits.

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS

- Source:Procured from RABBI ROOF, Hyderabad
.- Age at study initiation:4 to 5 Months (Approximately)
- Weight at study initiation: 1.874-2.272 kg
- Housing:The animals were housed individually in stainless steel cages in a controlled environment.
- Diet (e.g. ad libitum): Conventional laboratory rabbit diet (Nutrivet Life Sciences, Pune), ad libitum
- Water (e.g. ad libitum):Aqua guard filtered tap water, ad libitum-
Acclimatization period: Rabbits were acclimatized to the test conditions for a period of 5 days (Animal No. 1) and 9 days (Animal No. 2 and 3) prior to the application of the test item.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.30-22.50 °C
- Humidity (%): 45.00-68.40 %
- Air changes (per hr):More than 12 changes per hour
- Photoperiod (hrs dark / hrs light):12-hrs light/12-hrs dark

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

other: distilled water

Controls:

yes, concurrent vehicle

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit):0.5 ml
- Concentration (if solution): No data available

VEHICLE
- Amount(s) applied (volume or weight with unit):0.5 ml distilled water
- Concentration (if solution): No data available
- Lot/batch no. (if required): No data available- Purity: No data available

Duration of treatment / exposure:

4 hours

Observation period:

72 hours

Number of animals:

3 male rabbits

Details on study design:

TEST SITE
- Area of exposure: approximately 6 X 6 cm at contralateral sites
- Type of wrap if used: porous gauze dressing and non-irritating tape (Micropore 3”)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): residual test item was removed by using cotton soaked in distilled water
- Time after start of exposure: 4hr

Control site: 0.5 ml distilled water was applied at control site.

Irritation parameter:

erythema score

Basis:

animal: #1 ,#2 and #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal: #1 ,#2 and #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

The patch was removed after 4 hours and rabbits were observed for erythema and oedema at 1, 24, 48 and 72 hours after patch removal, evaluated and graded as per draize method. In Animal Nos. 1, 2 and 3 at 1 hour observation after post patch removal, revealed no erythema and oedema at 1, 24, 48 and 72 hour observation. The individual mean score at 24, 48 and 72 hours for Animal Nos. 1, 2 and 3 were 0.00, 0.00, 0.00 and 0.00, 0.00, 0.00, for erythema and oedema formation, respectively.

Other effects:

Clinical Observation
No systemic toxicity was observed at treated rabbits during the experimental period.
Mortality
No mortality was observed during the observation period.
Body weight
Body weight of all animals was comparable with pre-treatment body weight.

Table 1

Skin Reaction

 

In Treated area Dose:0.5 ml of test item                                                                                             Sex:Male

 

Animal No.	Test	Treated  area*	Erythema score				Oedema score
			1h	24h	48h	72h	1h	24h	48h	72h
1	Initial	Right	0	0	0	0	0	0	0	0
2	Confirmatory	Right	0	0	0	0	0	0	0	0
3		Left	0	0	0	0	0	0	0	0

 

In Control areaDose:0.5 ml of distilled water                                                Sex:Male

 

Animal No.	Test	Treated area*	Erythema score				Oedema score
			1h	24h	48h	72h	1h	24h	48h	72h
1	Initial	Left	0	0	0	0	0	0	0	0
2	Confirmatory	Left	0	0	0	0	0	0	0	0
3		Right	0	0	0	0	0	0	0	0

Key: h = Hour.

Erythema                                                                                                                                           Oedema

0 = No erythema                                                                                                                            0 = No oedema

Table 1 Continued…

Mean Individual Animal Score at 24, 48 and 72 hours

 

Animal Number                   Observations	1	2	3
Erythema	0.00	0.00	0.00
Oedema	0.00	0.00	0.00

 

  

Table 2

Individual Animal BodyWeight

Sex:Male

Animal No.	Body Weight (kg)
	Prior to Dosing	At termination
1	2.272	2.330
2	1.874	1.912
3	1.938	1.948

Table 3

Individual AnimalClinicalSigns

Sex:Male

Animal No.	Days (Post dosing Observation)
	0	1	2	3
1	1	1	1	1
2	1	1	1	1
3	1	1	1	1

Key: 1 = Normal.

Interpretation of results:

other: Not irritating

Conclusions:

The individual mean score at 24, 48 and 72 hours for Animal Nos. 1, 2 and 3 were 0.00, 0.00, 0.00 and 0.00, 0.00, 0.00, for erythema and oedema formation, respectively.Hence, the test chemical was regarded as non-Irritating to the skin of male New Zealand White rabbits under the experimental conditions tested and is thus not classified as a skin irritant.

Executive summary:

Acute Dermal Irritation/corrosion Study of test chemical was performed as per OECD guideline No. 404 using three healthy young adult male New Zealand White rabbits.The hairs of all the rabbits were clipped at contralateral sites, approximately 24 hours prior to treatment. A dose of 0.5 g of test item(moistened with 0.5 ml distilled water) was applied to the skin, over an area of approximately 6 x 6 cm clipped of hair on one side of rabbits. The other untreated side was kept as control area and0.5 ml of distilled water was applied at this site. At the end of 4 hours, the gauze patch was removed and test item application site was wiped with water without altering the integrity of the epidermis. Initially, the test item was applied to the clipped area of skin of one rabbit. The test site was covered with gauze patch. After 4 hours of exposure in animal no. 1, no erythema and no oedema observed at 1, 24 and 48 hour of observation hence a confirmatory test was conducted on additional two rabbits (No. 2 and 3) to confirm the non-irritant nature of the test item. The patch was removed after 4 hours and rabbits were observed for erythema and oedema at 1, 24, 48 and 72 hours post patch removal, evaluated and graded as per Draize method. In animal no. 2 and 3 at 1 hour observation post patch removal, revealed no erythema and no oedema. At 24, 48 and 72 hour post patch removal, animals showed no erythema and no oedema.The individual mean score at 24, 48 and 72 hours for Animal Nos. 1, 2 and 3 were 0.00, 0.00, 0.00 and 0.00, 0.00, 0.00, for erythema and oedema formation, respectively Hence, it was concluded that the test chemical was Non-Irritating to the skin of male New Zealand White rabbits under the experimental conditions tested.

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

Data is from experimental study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Principles of method if other than guideline:

The objective of the study was to assess the irritant and/or corrosive effects of test chemical on eye when exposed by an ocular route in rabbits.

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS- Source:Procured from RABBI ROOF, Hyderabad
.- Age at study initiation:4 to 5 Months (Approximately)
- Weight at study initiation: 1.999-2.268 kg
- Housing:The animals were housed individually in stainless steel cages in a controlled environment.
- Diet (e.g. ad libitum): Conventional laboratory rabbit diet (Nutrivet Life Sciences, Pune), ad libitum
- Water (e.g. ad libitum):Aqua guard filtered tap water, ad libitum-
Acclimatization period: Rabbits were acclimatized to the test conditions for a period of 5 days (Animal No. 1) and 9 days (Animal No. 2 and 3) prior to the application of the test item.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.20-22.60°C
- Humidity (%): 42.00-74.70%
- Air changes (per hr):More than 12 changes per hour
- Photoperiod (hrs dark / hrs light):12-hrs light/12-hrs dark

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml
- Concentration (if solution): No data available

VEHICLE
- Amount(s) applied (volume or weight with unit): No data available
- Concentration (if solution): No data available
- Lot/batch no. (if required): No data available
- Purity: No data available

Duration of treatment / exposure:

24 hours

Observation period (in vivo):

All the animals were observed at 1, 24, 48, 72 hours and on day 7 after instillation of test item.

Duration of post- treatment incubation (in vitro):

no data available

Number of animals or in vitro replicates:

3 female rabbits

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The treated eye of rabbit was washed with normal saline
- Time after start of exposure: 24 hrs

SCORING SYSTEM: Grading of irritation lesions was carried out as per Draize Method

TOOL USED TO ASSESS SCORE: Ophthalmoscope and fluorescein strips.

Irritation parameter:

cornea opacity score

Basis:

animal: #1,#2 and #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

not specified

Remarks on result:

no indication of irritation

Remarks:

Untreated (Control Eye)

Irritation parameter:

iris score

Basis:

animal: #1,#2 and #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

not specified

Remarks on result:

no indication of irritation

Remarks:

Untreated (Control Eye)

Irritation parameter:

conjunctivae score

Basis:

animal: #1,#2 and #3

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

not specified

Remarks on result:

no indication of irritation

Remarks:

Untreated (Control Eye)

Irritation parameter:

chemosis score

Basis:

animal: #1,#2 and #3

Time point:

other: 24,48,72 hrs and 7 days

Score:

0

Max. score:

4

Reversibility:

not specified

Remarks on result:

no indication of irritation

Remarks:

Untreated (Control Eye)

Irritation parameter:

cornea opacity score

Basis:

animal: #1,#2 and #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

not specified

Remarks on result:

no indication of irritation

Remarks:

For treated eye

Irritation parameter:

iris score

Basis:

animal: #1,#2 and #3

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

not specified

Remarks on result:

no indication of irritation

Remarks:

For treated eye

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24 h

Score:

1.67

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

positive indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

48 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

positive indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

72 h

Score:

4

Max. score:

3

Reversibility:

fully reversible within: 7 days

Remarks on result:

positive indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24 h

Score:

0

Max. score:

3

Reversibility:

not specified

Remarks on result:

other: For treated eye

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

48 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 7 days

Remarks on result:

positive indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 7 days

Remarks on result:

positive indication of irritation

Irritant / corrosive response data:

The following were observed in treated rabbits.In the initial test, 0.1 ml of test item was applied into the conjunctival sac of the right eye of animal no.1 whereas the left eye of the rabbit served as the control. As animal no. 1 showed no severe ocular lesions a confirmatory test was conducted on additional two rabbits (animal no. 2 and 3); 0.1 ml of test item was instilled into the conjunctival sac of right eye of both the rabbits and left eye served as the control. Ocular lesions were seen in animal no. 2 and 3 at till 72 hour observation which recovered at day 7.Untreated eye of all the three rabbits was normal throughout the experimental period of 7 days.The following grading scores were observed in treated eye of tested rabbits.Observation at 1 hour after instillation of test item revealed:Cornea: No ulceration or opacity in all 3 animals; Area of Opacity: Zero in all 3 animals; Iris: Normal in all 3 animals. Conjunctivae: Blood vessels normal was seen in all 3 animals; Chemosis: No swelling (Normal) was seen in animal no. 1 whereas some swelling above normal (includes nictitating membranes) was seen in animal no. 2 and 3.Observation at 24 hours after instillation of test item revealed: Cornea: No ulceration or opacity in all 3 animals; Area of Opacity: Zero in all 3 animals; Iris: Normal in all 3 animals; Conjunctivae: Some blood vessels definitely hyperaemic (injected) was seen in animal no. 1 and 2 whereas obvious swelling with partial eversion of lids was seen in animal no. 3; Chemosis: No swelling (Normal) was seen in animal no. 1 whereas some swelling above normal (includes nictitating membranes) was seen in animal no. 2 and 3.At 24 hours observation the rabbits were examined for corneal epithelium cell damage using sodium fluorescein strips and noticed 0 %, 15 % and 20 % damage in animal no. 1, 2 and 3 resectively. Observation at 48 and 72 hours after instillation of test item revealed: Cornea: No ulceration or opacity in all 3 animals; Area of Opacity: Zero in all 3 animals; Iris: Normal in all 3 animals; Conjunctivae: Some blood vessels definitely hyperaemic (injected) was seen in animal no. 2 whereas obvious swelling with partial eversion of lids was seen in animal no. 1 and 3; Chemosis: No swelling (Normal) was seen in animal no. 1 whereas some swelling above normal (includes nictitating membranes) was seen in animal no. 2 and 3.Observation at day 7 after instillation of test item revealed: Cornea: No ulceration or opacity in all 3 animals; Area of Opacity: No opacity was seen in all 3 animals; Iris: Normal in all 3 animals. Conjunctivae: Blood vessels normal was seen in all 3 animals; Chemosis: No swelling (Normal) was seen in all 3 animals.

Other effects:

No systemic toxicity or mortality was observed in treated rabbits during the experimental period. All the rabbits were observed with a body weight gain on day 7 as compared to day 0.

Table 1 : Individual Animal Eye Irritation Scores

 

In Treated area Dose:0.1 ml of test item  Sex:Female

Animal Numbers	1						2						3
Application Side	Right						Right						Right
Eye Reactions	At hour						At hour						At hour
	*	1	24	48	72	7 days	*	1	24	48	72	7 days	*	1	24	48	72	7 days
Corneal Opacity	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Area of Opacity	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Iris	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Conjunctiva	0	1	1	2	2	0	0	1	1	1	1	0	0	1	2	2	2	0
Chemosis	0	0	0	0	0	0	0	1	1	1	1	0	0	1	1	1	1	0
Corneal Damage%	0						15						20

 

 

Dose:Untreated (Control Eye)                                                                         Sex:Female

Animal Numbers	1						2						3
Application Side	Left						Left						Left
Eye Reactions	At hour						At hour						At hour
	*	1	24	48	72	Day 7	*	1	24	48	72	Day 7	*	1	24	48	72	Day 7
Corneal Opacity	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Area of Opacity	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Iris	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Conjunctiva	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Chemosis	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Corneal Damage%	0						0						0

Key:*= Pre-exposure eye examination.

 

 

 

Table 1 (Continued):Eye Irritation Scores - Mean Values after 24, 48, 72 Hours (Treated eye)

Animal No.  Eye Reaction	1	2	3
Corneal Opacity	0.00	0.00	0.00
Iris	0.00	0.00	0.00
Conjunctiva	1.67	1.00	2.00
Chemosis	0.00	1.00	1.00

 

 

Formula :

 

Mean Eye Irritation Score =

                          

Sum of the Individual Animal Score for eye reactionat24, 48 and 72 hours

Number of the Observations (3)

 

Table 2: Individual AnimalClinicalSigns

 

Sex:Female

Animal No.	Days (Post application observation)
	0	1	2	3	4	5	6	7
1	1	1	1	1	1	1	1	1
2	1	1	1	1	1	1	1	1
3	1	1	1	1	1	1	1	1

Key:1 = Normal

 

  

Table 3: Individual Animal Body Weight

Sex :Female

Animal No.	Animal Body Weight (kg)
	Prior to application	At termination
1	2.268	2.361
2	1.999	2.201
3	2.092	2.213

Key:kg = Kilogram

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

The individual mean score for animal nos. 1, 2 and 3 at 24, 48, 72 hours for corneal opacity, iris, conjunctiva and chemosis were found 0.00, 0.00, 1.67, 0.00; 0.00, 0.00, 1.00, 1.00 and 0.00, 0.00, 2.00, 1.00, respectively.Under the experimental conditions tested, eye irritation and reversibility of effects on eyes of all 3 animals was observed at day 7. Hence, the test chemical was considered as mildly irritating to the eyes of female New Zealand White rabbits, and thus the substance was classified as an eye irritant in Category 2 as per the CLP regulation.

Executive summary:

Acute eye irritation/corrosion study was conducted in rabbits to evaluate the eye irritant nature of the test chemical. The study was performed as per OECD 405 Guidelines using 3 female New Zealand White rabbits. Rabbits free from injury of eye were selected for the study. The eyes of all the rabbits were examined 24 hours prior to treatment. One eye of each rabbit served as control and other as treated. Control eye was left untreated whereas; 0.1 ml of test item was instilled in the other (treated) eye of each rabbit. The eye was observed at 1, 24, 48, 72 hour, day 7, day 14 and day 21 for animal no. 1 and 3 whereas at 1, 24, 48 and 72 hour after test item instillation. Ophthalmoscope was used for scoring of eye lesions. In the initial test, 0.1 ml of test item (as such) was applied into the conjunctival sac of the right eye of animal no.1 whereas the left eye of the rabbit served as the control. As animal no. 1 showed no severe ocular lesions a confirmatory test was conducted on additional two rabbits (animal no. 2 and 3); 0.1g of test item (in pulverized form) was instilled into the conjunctival sac of right eye of both the rabbits and left eye served as the control. Untreated eye of all the three rabbits were normal throughout the experimental period of 7 days. The following grading scores were observed in treated eye of tested rabbits. Observation at 1 hour after instillation of test item revealed: Cornea: No ulceration or opacity in all 3 animals; Area of Opacity: Zero in all 3 animals; Iris: Normal in all 3 animals. Conjunctivae: Blood vessels normal was seen in all 3 animals; Chemosis: No swelling (Normal) was seen in animal no. 1 whereas some swelling above normal (includes nictitating membranes) was seen in animal no. 2 and 3. Observation at 24 hours after instillation of test item revealed: Cornea: No ulceration or opacity in all 3 animals; Area of Opacity: Zero in all 3 animals; Iris: Normal in all 3 animals; Conjunctivae: Some blood vessels definitely hyperaemic (injected) was seen in animal no. 1 and 2 whereas obvious swelling with partial eversion of lids was seen in animal no. 3; Chemosis: No swelling (Normal) was seen in animal no. 1 whereas some swelling above normal (includes nictitating membranes) was seen in animal no. 2 and 3.At 24 hours observation the rabbits were examined for corneal epithelium cell damage using sodium fluorescein strips and noticed 0 %, 15 % and 20 % damage in animal no. 1, 2 and 3 respectively. Observation at 48 and 72 hours after instillation of test item revealed: Cornea: No ulceration or opacity in all 3 animals; Area of Opacity: Zero in all 3 animals; Iris: Normal in all 3 animals; Conjunctivae: Some blood vessels definitely hyperaemic (injected) was seen in animal no. 2 whereas obvious swelling with partial eversion of lids was seen in animal no. 1 and 3; Chemosis: No swelling (Normal) was seen in animal no. 1 whereas some swelling above normal (includes nictitating membranes) was seen in animal no. 2 and 3. Observation at day 7 after instillation of test item revealed: Cornea: No ulceration or opacity in all 3 animals; Area of Opacity: No opacity was seen in all 3 animals; Iris: Normal in all 3 animals. Conjunctivae: Blood vessels normal was seen in all 3 animals; Chemosis: No swelling (Normal) was seen in all 3 animals. The individual mean score for animal nos. 1, 2 and 3 at 24, 48, 72 hours for corneal opacity, iris, conjunctiva and chemosis were found 0.00, 0.00, 1.67, 0.00; 0.00, 0.00, 1.00, 1.00 and 0.00, 0.00, 2.00, 1.00, respectively. Under the experimental conditions tested, eye irritation and reversibility of effects on eyes of all 3 animals was observed at day 7. Hence, the test chemical was considered as mildly irritating to the eyes of female New Zealand White rabbits, and thus the substance was classified as an eye irritant in Category 2 as per the CLP regulation.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

 

Acute Dermal Irritation/corrosion Study of test chemical was performed as per OECD guideline No. 404 using three healthy young adult male. The hairs of all the rabbits were clipped at contralateral sites, approximately 24 hours prior to treatment. A dose of 0.5 g of test item (moistened with 0.5 ml distilled water) was applied to the skin, over an area of approximately 6 x 6 cm clipped of hair on one side of rabbits. The other untreated side was kept as control area and0.5 ml of distilled water was applied at this site. At the end of 4 hours, the gauze patch was removed and test item application site was wiped with water without altering the integrity of the epidermis. Initially, the test item was applied to the clipped area of skin of one rabbit. The test site was covered with gauze patch. After 4 hours of exposure in animal no. 1, no erythema and no oedema observed at 1, 24 and 48 hour of observation hence a confirmatory test was conducted on additional two rabbits (No. 2 and 3) to confirm the non-irritant nature of the test chemical.The patch was removed after 4 hours and rabbits were observed for erythema and oedema at 1, 24, 48 and 72 hours post patch removal, evaluated and graded as per Draize method. In animal no. 2 and 3 at 1 hour observation post patch removal, revealed no erythema and no oedema. At 24, 48 and 72 hour post patch removal, animals showed no erythema and no oedema.The individual mean score at 24, 48 and 72 hours for Animal Nos. 1, 2 and 3 were 0.00, 0.00, 0.00 and 0.00, 0.00, 0.00, for erythema and oedema formation, respectively Hence, it was concluded that the test chemical was Non-Irritating to the skin of male New Zealand White rabbits under the experimental conditions tested.

 

Eye Irritation:

Acute eye irritation/corrosion study was conducted in rabbits to evaluate the eye irritant nature of the test chemical. The study was performed as per OECD 405 Guidelines using 3 female New Zealand White rabbits.Rabbits free from injury of eye were selected for the study. The eyes of all the rabbits were examined 24 hours prior to treatment. One eye of each rabbit served as control and other as treated. Control eye was left untreated whereas; 0.1 ml of test item was instilled in the other (treated) eye of each rabbit. The eye was observed at 1, 24, 48, 72 hour, day 7, day 14 and day 21 for animal no. 1 and 3 whereas at 1, 24, 48 and 72 hour after test item instillation. Ophthalmoscope was used for scoring of eye lesions.In the initial test, 0.1 ml of test item (as such) was applied into the conjunctival sac of the right eye of animal no.1 whereas the left eye of the rabbit served as the control. As animal no. 1 showed no severe ocular lesions a confirmatory test was conducted on additional two rabbits (animal no. 2 and 3); 0.1g of test item (in pulverized form) was instilled into the conjunctival sac of right eye of both the rabbits and left eye served as the control.Untreated eye of all the three rabbits were normal throughout the experimental period of 7 days.The following grading scores were observed in treated eye of tested rabbits.Observation at 1 hour after instillation of test item revealed: Cornea: No ulceration or opacity in all 3 animals; Area of Opacity: Zero in all 3 animals; Iris: Normal in all 3 animals. Conjunctivae: Blood vessels normal was seen in all 3 animals; Chemosis: No swelling (Normal) was seen in animal no. 1 whereas some swelling above normal (includes nictitating membranes) was seen in animal no. 2 and 3.Observation at 24 hours after instillation of test item revealed: Cornea: No ulceration or opacity in all 3 animals; Area of Opacity: Zero in all 3 animals; Iris: Normal in all 3 animals; Conjunctivae: Some blood vessels definitely hyperaemic (injected) was seen in animal no. 1 and 2 whereas obvious swelling with partial eversion of lids was seen in animal no. 3; Chemosis: No swelling (Normal) was seen in animal no. 1 whereas some swelling above normal (includes nictitating membranes) was seen in animal no. 2 and 3.At 24 hours observation the rabbits were examined for corneal epithelium cell damage using sodium fluorescein strips and noticed 0 %, 15 % and 20 % damage in animal no. 1, 2 and 3 respectively.Observation at 48 and 72 hours after instillation of test item revealed: Cornea: No ulceration or opacity in all 3 animals; Area of Opacity: Zero in all 3 animals; Iris: Normal in all 3 animals; Conjunctivae: Some blood vessels definitely hyperaemic (injected) was seen in animal no. 2 whereas obvious swelling with partial eversion of lids was seen in animal no. 1 and 3; Chemosis: No swelling (Normal) was seen in animal no. 1 whereas some swelling above normal (includes nictitating membranes) was seen in animal no. 2 and 3.Observation at day 7 after instillation of test item revealed: Cornea: No ulceration or opacity in all 3 animals; Area of Opacity: No opacity was seen in all 3 animals; Iris: Normal in all 3 animals. Conjunctivae: Blood vessels normal was seen in all 3 animals; Chemosis: No swelling (Normal) was seen in all 3 animals. The individual mean score for animal nos. 1, 2 and 3 at 24, 48, 72 hours for corneal opacity, iris, conjunctiva and chemosis were found 0.00, 0.00, 1.67, 0.00; 0.00, 0.00, 1.00, 1.00 and 0.00, 0.00, 2.00, 1.00, respectively.Under the experimental conditions tested, eye irritation and reversibility of effects on eyes of all 3 animals was observed at day 7. Hence, the test chemical is considered as mildly irritating to the eyes of female New Zealand White rabbits, and thus the substance is classified as an eye irritant in Category 2 as per the CLP regulation.

 

Justification for classification or non-classification

The Guideline study results indicate that the chemical is not likely to cause skin irritation but can cause mild eye damage. Hence the test chemical can be classified under the category for “Not Classified” for skin irritation and “Category 2” for eye irritation as per CLP.