4-chlorobenzophenone

Endpoint summary

Description of key information

Skin Irritation/corrosion :

Study 1: No cutaneous reaction was detected. Hence, 4-Tert-butylbenzoic acid was considered to be not irritating to the rabbit’s skin.

Study 2: No cutaneous reaction was detected in any of the animals. Hence, the test substance 4 -Tert-butylbenzoic acid was considered to be not irritating to the rabbit’s skin.

Eye Irritation/serious Eye Damage :

Study 1:  The individual mean score for animal nos. 1, 2 and 3 at 24, 48, 72 hours (at treated site) for corneal opacity, iris, conjunctiva and chemosis were found 0.00, 0.00, 0.33, 0.00; 0.00, 0.00, 0.33, 0.00 and 0.00, 0.00, 0.33, 0.00 respectively. Under the experimental conditions tested, the test chemical was considered to be Non Irritant to New Zealand White male rabbit eyes and is thus Classified as “Category- Not Classified as Eye Irritant” as per CLP criteria for Classification.

Study 2: The test substance 4 -Tert-butylbenzoic acid was considered to be not irritating to the rabbit’s eye.

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

Remarks:

Read across substance

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

Data is from Authoritive database

Qualifier:

according to guideline

Guideline:

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

Principles of method if other than guideline:

Skin irritation study was conducted on 6 New Zealand albino rabbits to assess the irritation potential of 4-tert-Butylbenzoic acid

GLP compliance:

not specified

Specific details on test material used for the study:

Name of the test chemical:4-Tert-Butylbenzoicacid
Molecular formula: C11H14O2
Molecualr Weight:178.23 g/mol
Substance Type: Organic
Physical State: Solid
InChI: 1S/C11H14O2/c1-11(2,3)9-6-4-8(5-7-9)10(12)13/h4-7H,1-3H3,(H,12,13)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

No Data Available

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

water

Controls:

not specified

Amount / concentration applied:

500 mg

Duration of treatment / exposure:

4 hours

Observation period:

72 hours

Number of animals:

6

Details on study design:

No Data Available

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 1, 24, 48, and 72 hours after the removal of the dressing.

Score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No known signs of skin irritation were observed

Interpretation of results:

other: Not irritating

Conclusions:

No cutaneous reaction was detected. Hence, 4-Tert-butylbenzoic acid was considered to be not irritating to the rabbit’s skin.

Executive summary:

Skin irritation study was performed in 6 New Zealand albino rabbits in accordance with EU test guideline B4 to assess the irritation potential of the test substance 4 -Tert-butylbenzoic acid (CAS no.: 98 -73 -7, E.C. no.: 202 -696 -3). Single application of 500 mg of 4 -tert-butylbenzoic acid moistened with water was applied to a clipped area of 6 New Zealand albino rabbits and was held in contact with the skin for 4 hours by a semi-occlusive dressing. The skin reactions were read at 1, 24, 48, and 72 hours after the removal of the dressing. The overall irritation score was noted to be 0. No cutaneous reaction was detected in any of the animals. Hence, the test substance 4 -Tert-butylbenzoic acid was considered to be not irritating to the rabbit’s 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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

data is from experimental reports

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 the test chemical on eye, when exposed by the ocular route in rabbits.

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Sex: Male
- Source: Procured from LIVEON BIOLABS PVT. LTD.
- Age at study initiation: 3.0 to 4.5 Months (Approximately)
- Weight at study initiation: Minimum: 1.822 kg and Maximum: 2.146 kg (Prior to Treatment)
- Health Status : Healthy young adult animals were used for the study.
- Housing: The animals were housed individually in stainless steel cages.
- Room Sanitation: The experimental room floor and work tops were swept and mopped with disinfectant solution every day.
- Cages and water bottle: All the cages and water bottles were changed minimum twice a week.
- Diet (e.g. ad libitum): All animals were provided conventional laboratory rabbit diet, ad libitum.
- Water (e.g. ad libitum): Aqua guard filtered tap water was provided ad libitum.
- Acclimation period: Rabbits were acclimatised to the test conditions for a period of 6 days (Animal No.-1) and 9 days (Animal No. 2 and 3) prior to the application of the test item.

ENVIRONMENTAL CONDITIONS
- Temperature (°C):Minimum: 19.00 °C and Maximum: 20.80 °C
- Humidity (%):Minimum: 45.10 % and Maximum: 65.80 %
- Air changes (per hr): More than 12 changes per hour
- Photoperiod (hrs dark / hrs light): 12:12

Vehicle:

unchanged (no vehicle)

Controls:

yes

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit):0.1 ml
- Concentration (if solution):N/A

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

Duration of treatment / exposure:

24 hrs

Observation period (in vivo):

All the treated animals were observed at 1, 24, 48 and 72 hours after instillation of test item

Duration of post- treatment incubation (in vitro):

no data available

Number of animals or in vitro replicates:

3 male 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 hours

SCORING SYSTEM: Draize Method

TOOL USED TO ASSESS SCORE: Ophthalmoscope and fluorescent strips.

Irritation parameter:

cornea opacity score

Basis:

animal: #1,#2 and #3

Time point:

7 d

Score:

0

Max. score:

3

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:

7 d

Score:

0

Max. score:

3

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:

7 d

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:

7 d

Score:

0

Max. score:

3

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 eyes

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:

For treated eyes

Irritation parameter:

conjunctivae score

Basis:

animal: #1,#2 and #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

not specified

Remarks on result:

no indication of irritation

Remarks:

For treated eyes

Irritation parameter:

chemosis 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 eyes

Irritant / corrosive response data:

The following were observed in treated rabbits.
Observation at 1 hour after instillation of test item revealed: Cornea- No ulceration or opacity in all the animals; Area of Opacity- Zero in all the animals; Iris: Normal in all the animals. Conjunctivae - Some blood vessels definitely hyperaemic (injected) was observed in all the animals; Chemosis: Some swelling above normal (includes nictitating membranes) was observed in all the animals.

Observation at 24 hours after instillation of test item revealed: Cornea- No ulceration or opacity in all the animals; Area of Opacity- Zero in all the animals; Iris: Normal in all the animals. Conjunctivae - Some blood vessels definitely hyperaemic (injected) was observed in all the animals; Chemosis: No swelling (normal) was observed in all the animals.

At 24 hours observation the rabbits were examined for corneal epithelium cell damage using sodium fluorescein strips and noticed 0% damage in all the animals.

Observation at 48 and 72 hours after instillation of test item revealed: Cornea- No ulceration or opacity in all the animals; Area of Opacity- Zero in all the animals; Iris: Normal in all the animals. Conjunctivae - Blood vessels normal in all the animals; Chemosis: No swelling (normal) was observed in all the animals.

The individual mean score for animal nos. 1, 2 and 3 at 24, 48, 72 hours (at treated site) for corneal opacity, iris, conjunctiva and chemosis were found 0.00, 0.00, 0.33, 0.00; 0.00, 0.00, 0.33, 0.00 and 0.00, 0.00, 0.33, 0.00 respectively.

Other effects:

Clinical Observation
No systemic toxicity was observed in treated rabbits during the experimental period

Mortality
No mortality was observed during the experimental period.

Body weight
Increase in body weights in all the treated animals at termination when compared to day 0 was observed.

Table 1: Individual Animal Eye Irritation Scores

In Treated area Dose: 0.1 ml of as such test item                                                 Sex: Male

Animal Numbers	1					2					3
Application Side	Right					Right					Right
Eye Reactions	At hour					At hour					At hour
	*	1	24	48	72	*	1	24	48	72	*	1	24	48	72
Corneal Opacity	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
Iris	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Conjunctiva	0	1	1	0	0	0	1	1	0	0	0	1	1	0	0
Chemosis	0	1	0	0	0	0	1	0	0	0	0	1	0	0	0
Corneal Damage%	0	./.	0			0	./.	0			0	./.	0

In Treated area Dose: Untreated                                                                             Sex: Male

Animal Numbers	1					2					3
Application Side	Right					Right					Right
Eye Reactions	At hour					At hour					At hour
	*	1	24	48	72	*	1	24	48	72	*	1	24	48	72
Corneal Opacity	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
Iris	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
Chemosis	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Corneal Damage%	0	./.	0			0	./.	0			0	./.	0

Key: *= Pre-exposure eye examination.

      ./.= Not Applicable

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	0.33	0.33	0.33
Chemosis	0.00	0.00	0.00

Eye Irritation Scores - Mean Values after 24, 48, 72 Hours (Untreated eye)

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

Formula :

Mean Eye Irritation Score = Sum of the Individual Animal Score for eye reaction at 24, 48 and 72 hours

Number of the Observations (3)

Table 2 : Individual Animal Clinical Signs

Animal No.	Days (Post application observation)
	0	1	2	3
1	1	1	1	1
2	1	1	1	1
3	1	1	1	1

Key: 1 = Normal

Table 3: Individual Animal Body Weight

Animal No.	Animal Body Weight (kg)
	Prior to application	At termination
1	2.146	2.180
2	2.146	2.198
3	1.822	1.886

Key: kg = Kilogram

Interpretation of results:

other: not irritating

Conclusions:

The individual mean score for animal nos. 1, 2 and 3 at 24, 48, 72 hours (at treated site) for corneal opacity, iris, conjunctiva and chemosis were found 0.00, 0.00, 0.33, 0.00; 0.00, 0.00, 0.33, 0.00 and 0.00, 0.00, 0.33, 0.00 respectively. Under the experimental conditions tested, the test chemical was considered to be Non Irritant to New Zealand White male rabbit eyes and is thus Classified as “Category- Not Classified as Eye Irritant” as per CLP criteria for Classification.

Executive summary:

Acute Eye Irritation/Corrosion Study of the test chemical in Rabbits, was performed as per OECD guideline no. 405. 3 male New Zealand White rabbits were used for the study. 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 chemical (as such) was instilled in the other (treated) eye of rabbits. The eye was observed at 1, 24, 48, 72 hours after test chemical instillation. Ophthalmoscope was used for scoring of eye lesions. In the initial test,0.1 ml of as such test chemical was instilled 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 hence a confirmatory test was conducted on additional two rabbits (animal no. 2 and 3);0.1 ml of as such test chemical 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 was normal throughout the experimental period of 72 hours. The following grading scores were observed in treated eye of tested rabbits. Observation at 1 hour after instillation of test chemical revealed: Cornea- No ulceration or opacity in all the animals; Area of Opacity-Zero in all the animals; Iris: Normal in all the animals. Conjunctivae - Some blood vessels definitely hyperaemic (injected) was observed in all the animals; Chemosis: Some swelling above normal (includes nictitating membranes) was observed in all the animals. Observation at 24 hours after instillation of test chemical revealed: Cornea- No ulceration or opacity in all the animals; Area of Opacity-Zero in all the animals; Iris: Normal in all the animals. Conjunctivae - Some blood vessels definitely hyperaemic (injected) was observed in all the animals; Chemosis: No swelling (normal) was observed in all the animals. At 24 hours observation the rabbits were examined for corneal epithelium cell damage using sodium fluorescein strips and noticed 0% damage in all the animals. Observation at 48 and 72 hours after instillation of test chemical revealed: Cornea- No ulceration or opacity in all the animals; Area of Opacity-Zero in all the animals; Iris: Normal in all the animals. Conjunctivae - Blood vessels normal in all the animals; Chemosis: No swelling (normal) was observed in all the animals. The individual mean score for animal nos. 1, 2 and 3 at 24, 48, 72 hours (at treated site) for corneal opacity, iris, conjunctiva and chemosis were found 0.00, 0.00, 0.33, 0.00; 0.00, 0.00, 0.33, 0.00 and 0.00, 0.00, 0.33, 0.00 respectively. Under the experimental conditions tested, the test chemical was considered to be Non Irritant to New Zealand White male rabbit eyes and was thus Classified as "Not Classified ” as per CLP criteria for Classification.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Additional information

Skin Irritation/corrosion :

Study 1: Skin irritation study was performed in 6 New Zealand albino rabbits in accordance with EU test guideline B4 to assess the irritation potential of the test substance 4 -Tert-butylbenzoic acid (CAS no.: 98 -73 -7, E.C. no.: 202 -696 -3). Single application of 500 mg of 4 -tert-butylbenzoic acid moistened with water was applied to a clipped area of 6 New Zealand albino rabbits and was held in contact with the skin for 4 hours by a semi-occlusive dressing. The skin reactions were read at 1, 24, 48, and 72 hours after the removal of the dressing. The overall irritation score was noted to be 0. No cutaneous reaction was detected in any of the animals. Hence, the test substance 4 -Tert-butylbenzoic acid was considered to be not irritating to the rabbit’s skin.

Study 2: Skin irritation study was performed in one male and one female albino rabbits in accordance with Draize test to assess the irritation potential of the test substance 4 -Tert-butylbenzoic acid (CAS no.: 98 -73 -7, E.C. no.: 202 -696 -3). Single application of 800 mg/kg bw of 4 -tert-butylbenzoic acid was applied to the skin and was held in contact with the skin for 8 hours by a occlusive dressing. The overall irritation score was noted to be 0. No cutaneous reaction was detected in any of the animals. Hence, the test substance 4 -Tert-butylbenzoic acid was considered to be not irritating to the rabbit’s skin.

Eye Irritation/serious Eye Damage :

Study 1:  Acute Eye Irritation/Corrosion Study of the test chemical in Rabbits, was performed as per OECD guideline no. 405. 3 male New Zealand White rabbits were used for the study. 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 chemical (as such) was instilled in the other (treated) eye of rabbits. The eye was observed at 1, 24, 48, 72 hours after test chemical instillation. Ophthalmoscope was used for scoring of eye lesions. In the initial test,0.1 ml of as such test chemical was instilled 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 hence a confirmatory test was conducted on additional two rabbits (animal no. 2 and 3);0.1 ml of as such test chemical 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 was normal throughout the experimental period of 72 hours. The following grading scores were observed in treated eye of tested rabbits. Observation at 1 hour after instillation of test chemical revealed: Cornea- No ulceration or opacity in all the animals; Area of Opacity-Zero in all the animals; Iris: Normal in all the animals. Conjunctivae - Some blood vessels definitely hyperaemic (injected) was observed in all the animals; Chemosis: Some swelling above normal (includes nictitating membranes) was observed in all the animals. Observation at 24 hours after instillation of test chemical revealed: Cornea- No ulceration or opacity in all the animals; Area of Opacity-Zero in all the animals; Iris: Normal in all the animals. Conjunctivae - Some blood vessels definitely hyperaemic (injected) was observed in all the animals; Chemosis: No swelling (normal) was observed in all the animals. At 24 hours observation the rabbits were examined for corneal epithelium cell damage using sodium fluorescein strips and noticed 0% damage in all the animals. Observation at 48 and 72 hours after instillation of test chemical revealed: Cornea- No ulceration or opacity in all the animals; Area of Opacity-Zero in all the animals; Iris: Normal in all the animals. Conjunctivae - Blood vessels normal in all the animals; Chemosis: No swelling (normal) was observed in all the animals. The individual mean score for animal nos. 1, 2 and 3 at 24, 48, 72 hours (at treated site) for corneal opacity, iris, conjunctiva and chemosis were found 0.00, 0.00, 0.33, 0.00; 0.00, 0.00, 0.33, 0.00 and 0.00, 0.00, 0.33, 0.00 respectively. Under the experimental conditions tested, the test chemical was considered to be Non Irritant to New Zealand White male rabbit eyes and was thus Classified as "Not Classified ” as per CLP criteria for Classification.

Study 2: Eye irritation study was performed in one male and one female albino rabbits in accordance with Draize test to assess the irritation potential of the test substance 4 -Tert-butylbenzoic acid (CAS no.: 98 -73 -7, E.C. no.: 202 -696 -3). Single administration of 100 mg/kg bw of 4 -tert-butylbenzoic acid, containing 5% of the m-compound (3-tert-butylbenzoic acid. Minimal irritation was noted in one case and  none in the other, but the test substance was conidered to be non-irritating, as the other studies shows that the substance does not have potential to cause eye irritation.. Hence, the test substance 4 -Tert-butylbenzoic acid was considered to be not irritating to the rabbit’s eye.

Justification for classification or non-classification

Based on the above-summarized studies it was concluded that the test substance does not classify as skin irritant and eye irritant.