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Administrative data

Description of key information

The substance chlorocresol was found to be a eye irritant as well as skin irritant

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:
weight of evidence
Reliability:
1 (reliable without restriction)
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Institute for Industrial Research & Toxicology
- Sex: Female
- Age at study initiation: 10 to 12 weeks
- Weight at study initiation: 2.15 kg
- Housing: Animal was housed individually in stainless steel cages provided with stainless steel mesh bottom and facilities for food and water bottle
- Diet (e.g. ad libitum): Pelleted feed supplied by Pranav agro Industries Ltd., B7/6 Ramesh Nagar, Delhi
- Water (e.g. ad libitum): Pelleted feed supplied by Pranav agro Industries Ltd., B7/6 Ramesh Nagar, Delhi
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-25°C
- Humidity (%): 40-60%
- Air changes (per hr): 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light): illumination cycle set to 12 hours artificial fluorescent light and 12 hours dark
Type of coverage:
occlusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
yes
Amount / concentration applied:
0.5 gm
Duration of treatment / exposure:
no data
Observation period:
72 hours
Number of animals:
1
Details on study design:
EXPERIMENTAL PROCEDURE
Preparation of Animals:
The animal was prepared 24 hrs prior to application of test product. The furs from the dorsal area of trunk of animal were removed with electric clippers exposing an area measuring approximately 6 cm2 of body surface area of animal. The care was taken such that abrasion penetrated the Stratum corneum only and not dermis.

Application of test product:
The 0.5 gm of test compound was applied on a small area (approximately 6 cm2) of intact skin site. Each site of application was covered with impervious dressing which was secured in position with adhesive tape. The treated animal was then housed individually and plastic collar was put around their necks in order to prevent access by the animal to the patch and resultant ingestion of the test product. After patch removal, the dressing and unabsorbed test product was removed and the site of application was cleaned with lukewarm water.
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 4 hrs
Max. score:
8
Reversibility:
fully reversible within: 1 week
Remarks on result:
other: severe necrosis at the site of application
Irritant / corrosive response data:
Skin reaction
The test compound Chlorocresol (CAS No.: 59-50-7) when applied at the dose level of 0.5 gm on shaven back skin of rabbit produced severe necrosis at the site of application of test compound after four hours of patch removal. The test compound produced necrosis to epidermal layer and complete layer of necrotic tissue was removed after one week.

Clinical Signs
The test compound Chlorocresol (CAS No.: 59-50-7) applied on the shaven back skin of rabbit did not produce any clinical signs of toxicity during the entire observation period

CLINICAL SIGNS

SEX

ANIMAL NO.

Time (Min.)

Time (Hours)

3

1

4

24

FEMALE

01

N

N

N

N

N: No Clinical Signs

C: Clinical Signs Observed

Interpretation of results:
Category 1 (corrosive)
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test compound Chlorocresol when applied at the dose level of 0.5 gm on shaven back skin of rabbit produced severe necrosis at the site of application of test compound after four hours of patch removal. The test compound produced necrosis to epidermal layer and complete layer of necrotic tissue was removed after one week
Executive summary:

The test compound Chlorocresol when applied at the dose level of 0.5 gm on shaven back skin of rabbit produced severe necrosis at the site of application of test compound after four hours of patch removal. The test compound produced necrosis to epidermal layer and complete layer of necrotic tissue was removed after one week.

Based on the results obtained from present study, it can be concluded that the test compound Chlorocresol produced corrosive effect to skin of the New Zealand white rabbits when applied dermally under test condition

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
1 (reliable without restriction)
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Institute for Industrial Research & Toxicology
- Sex: Female
- Age at study initiation: 10 to 12 weeks
- Weight at study initiation: 2.0kg ±200g
- Housing: Rabbit was housed in stainless steel cages provided with stainless steel mesh bottom and facilities for food and water bottle
- Diet (e.g. ad libitum): Pelleted feed supplied by Pranav agro Industries Ltd., B7/6 Ramesh Nagar, Delhi, India
- Water (e.g. ad libitum): Community tap water passed through ‘Aqua Guard on line water filter’ was kept in bottles, ad libitum
- Acclimation period: 24 hours

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-25°C
- Humidity (%): 40-60%
- Air changes (per hr): 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light): illumination cycle set to 12 hours artificial fluorescent light and 12 hours dark
Vehicle:
water
Controls:
yes
Amount / concentration applied:
0.1 gm moistened with distilled water
Duration of treatment / exposure:
24 hours
Observation period (in vivo):
upto 21 days after exposure
Number of animals or in vitro replicates:
3
Details on study design:
PREPARATION AND TREATMENT OF ANIMALS
Selection of species:
The albino rabbit is the preferable laboratory animal and only healthy young adult animals are used.
Preparation of animals:
Both eyes of each experimental animal provisionally selected and examined for any eye irritation, ocular defects and pre-existing corneal injury within 24 hours before testing of compound.
TEST PROCEDURE:
The test compound Chlorocresol (CAS No.-59-50-7) in the amount of 0.1 gm moistened with distilled water and then placed in the conjunctival sac of one eye of each animal after gentle pulling the lower eye lid away from the eye ball. The eye lids were then gently held together for about one second to prevent the loss of the material. The other eyes which remains untreated, served as control.
Eye Irrigation:
The eyes of the test animal did not washed for at least 24 hours following instillation of the test compound. At 24 hours a washout may be used if considered appropriate.
Dose level:
A dose of 0.1gm of test substance was applied into the one eye of the rabbits. The other eye, which remains untreated, serves as a control.
OBSERVATION:
The eyes were examined at 1, 24, 48 and 72 hours after test substance application. The grades of ocular reaction (conjunctiva, cornea and iris) were recorded at each observation. To determine the reversibility of the effect the animal was observed normally for 21 days. Any other lesions in the eye viz pannus, staining were observed and scored accordingly. Examination of reactions was facilitated by use of biomicroscope and hand slit lamp. After recording the observations at 24 hours, the eyes were further examined with the aid of fluorescein. Individual animal weight before and during the study was also observed
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 72 hours
Score:
58
Max. score:
110
Reversibility:
fully reversible
Remarks on result:
other: Severely irritating
Irritant / corrosive response data:
Irritation Scoring
The test compound Chlorocresol (CAS No.: 59-50-7) when applied to the eye of New Zealand white rabbit at the dose level of 0.1 gm showed cornea discernible translucent area, details of iris slightly obscured, iris showed sluggish reaction to light, conjunctiva observed crimson red colour, half closed of eye lid and eye discharge moistening eye lids and hairs just adjacent to the lids.
Clinical Signs
The test compound Chlorocresol (CAS No.: 59-50-7) applied in conjunctival sac of rabbits did not show any observable clinical signs throughout the observation period of 21 days.

GRADING OF OCULAR LESIONS

 

S.No/

Sex

 

OBSERVATION

Score

Total

Total Score

1/F

 

1 hr

24hrs

48 hrs

72 hrs

Cornea

A.       Opacity-Degree of Density

1

2

2

2

7

 

7×12×5=420

B.       Area of Cornea Involved

3

3

3

3

12

Iris

A.       Values

1

1

2

2

6

6×5=30

Conjunctivae

A.       Redness

3

3

3

3

12

 

12+12+11×5=175

B.       Chemosis

3

3

3

3

12

C.       Discharge 

2

3

3

3

11

 

 

Total

625

 

 

Mean

156.3

At 72 hours,

Cornea score: 3x2x5= 30

Iris Score: 2x5= 10

Conjunctivae score: (3 +3 +3)x2 = 18

Total Score: 30 +10 +18= 58

Interpretation of results:
Category 1 (irreversible effects on the eye)
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test compound Chlorocresol when applied to the eye of New Zealand white rabbit at the dose level of 0.1 gm showed cornea discernible translucent area, details of iris slightly obscured, iris showed sluggish reaction to light, conjunctiva observed crimson red colour, half closed of eye lid and eye discharge moistening eye lids and hairs just adjacent to the lids.
Executive summary:

The test compound Chlorocresol when applied to the eye of New Zealand white rabbit at the dose level of 0.1 gm showed cornea discernible translucent area, details of iris slightly obscured, iris showed sluggish reaction to light, conjunctiva observed crimson red colour, half closed of eye lid and eye discharge moistening eye lids and hairs just adjacent to the lids.

Based on the result obtained from present study, it can be concluded that the test compound Chlorocresol is maximally irritant to the eyes of New Zealand white rabbit under test condition.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Skin irritation:

Based on studies of target substance CAS NO 59-50-7 reviewed for skin irritation from reliable sources having Klimisch rating 1 and 4 considering weight of evidence approach.

The summary of the results are presented below

 

Sr. No

End point

effect

Species

Remark

1

Overall irritation score

not irritating

Human

Publication for target chemical

2

Overall irritation score

irritating

Rabbits

Study report for target chemical

3

Overall irritation score

irritating

Human

Publication for target chemical

 

Based on results summarized in above table for the target chemical CAS NO 59-50-7, it can be concluded that the substance chlorocresol is irritating to the skin of Rabbit and Human.Since the substance has harmonized classification and as per classification, it is not a skin irritant. Hence it can be concluded that the substance is not a skin irritantfor the pupose of chemical safety assessment

Eye irritation:

Based on studies of target substance CAS NO 59-50-7 reviewed for eye irritation from reliable sources having Klimisch rating 1 and 4considering weight of evidence approach

 

The summary of the results are presented below

 

Sr. No

End point

effect

Species

Remark

1

Overall irritation score

 

irritating

Rabbit

Data from Study report for target chemical

2

Overall irritation score

 

irritating

Rabbit

Data from publication for target chemical

3

Overall irritation score

irritating

Rabbit

Data from publication for target chemical

 

Based on the results summarized in above tables for the target chemical CAS NO 59-50-7, it can be concluded that the substance is irritating to the eye of.Thus based on this results chlorocresol is considered to be eye irritant as the criteria for CLP regulation and classified as eye damage 1 category.

Justification for selection of skin irritation / corrosion endpoint:

The test compound Chlorocresol when applied at the dose level of 0.5 gm on shaven back skin of rabbit produced severe necrosis at the site of application of test compound after four hours of patch removal. The test compound produced necrosis to epidermal layer and complete layer of necrotic tissue was removed after one week.

Based on the results obtained from present study, it can be concluded that the test compound Chlorocresol produced corrosive effect to skin of the New Zealand white rabbits when applied dermally under test condition

Justification for selection of eye irritation endpoint:

The test compound Chlorocresol when applied to the eye of New Zealand white rabbit at the dose level of 0.1 gm showed cornea discernible translucent area, details of iris slightly obscured, iris showed sluggish reaction to light, conjunctiva observed crimson red colour, half closed of eye lid and eye discharge moistening eye lids and hairs just adjacent to the lids.

Based on the result obtained from present study, it can be concluded that the test compound Chlorocresol is maximally irritant to the eyes of New Zealand white rabbit under test condition.

Effects on skin irritation/corrosion: highly irritating

Effects on eye irritation: highly irritating

Justification for classification or non-classification

Based on the above studies it can be concluded that the substance Chlorocresol is irritant to skin and irritating to eye. Since the substance has harmonized classification and as per classification, chlorocresol is not a skin irritant but cause eye damage . Hence it can be concluded that the substance is not a skin irritant but cause eye irritation and hence classified as eye damage 1 category for the pupose of chemical safety assessment