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Description of key information

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation
Remarks:
in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Reason / purpose:
reference to same study
Qualifier:
according to
Guideline:
other:
Principles of method if other than guideline:
The contact sensitivity caused by chlorocresol was studied in guinea pigs by the cumulative contact enhancement test
GLP compliance:
not specified
Type of study:
other: cumulative contact enhancement test (CCE T )
Species:
guinea pig
Strain:
other: Ssc:Al
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Statenes serum institute Copenhagen
- Age at study initiation: no data
- Weight at study initiation: 350-450 gm
- Housing: Plastic cages
- Diet (e.g. ad libitum): Rabbit pellet, Supperfos corn ad libitum
- Water (e.g. ad libitum): Vitamin C enriched water ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-30 deg C
- Humidity (%): 45-75%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 hrs

IN-LIFE DATES: From: To:
Route:
epicutaneous, occlusive
Vehicle:
other: 5 different vehicle were used -water containing Carbomer 941 as a gelling agent -water -olive oil / acetone (4:1) -propylene glycol -propylene glycol containing 0.1 5% Carbomer 941
Concentration / amount:
-5% PCMC partly dissolved , mainly suspended in water containing Carbomer 941 as a gelling agent
-a saturated aqueous solution of 0.3 8% PCMC, -5.0% PCMC in olive oil/acetone (4 /1) ,
-5.0% PCMC in propylene glycol
-5 .0% PCMC in propylene glycol containing 0 .1 5%Carbomer 941.
Route:
epicutaneous, occlusive
Vehicle:
other: 5 different vehicle were used -water containing Carbomer 941 as a gelling agent -water -olive oil / acetone (4:1) -propylene glycol -propylene glycol containing 0.1 5% Carbomer 941
Concentration / amount:
-5% PCMC partly dissolved , mainly suspended in water containing Carbomer 941 as a gelling agent
-a saturated aqueous solution of 0.3 8% PCMC, -5.0% PCMC in olive oil/acetone (4 /1) ,
-5.0% PCMC in propylene glycol
-5 .0% PCMC in propylene glycol containing 0 .1 5%Carbomer 941.
No. of animals per dose:
0 , 3 , 7 , and 9 days
Details on study design:
RANGE FINDING TESTS:

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: four exposure
- Exposure period: 0 , 3 , 7 , and 9 days
- Test groups: yes
- Control group: yes
- Site: post nuchal region
- Frequency of applications: no data
- Duration: no data
- Concentrations: -5% PCMC partly dissolved , mainly suspended in water containing Carbomer 941 as a gelling agent
-a saturated aqueous solution of 0.3 8% PCMC,
-5.0% PCMC in olive oil/acetone (4 /1) ,
-5.0% PCMC in propylene glycol
-5 .0% PCMC in propylene glycol containing 0 .1 5%Carbomer 941.


B. CHALLENGE EXPOSURE
- No. of exposures: 1 exposure
- Day(s) of challenge: 21st day
- Exposure period: 1 day
- Test groups: yes
- Control group: yes
- Site: no data
- Concentrations: 0.1% and 1.0% PCMC in petrolatum
- Evaluation (hr after challenge): 48 and 72 hrs

OTHER:
Reading:
1st reading
Hours after challenge:
72
Group:
test group
Dose level:
0.1% and 1.0% PCMC in petrolatum
Clinical observations:
saturated PCMC aqueous solution had marked erythematous and edematous reactions at the patch - test site
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 72.0. Group: test group. Dose level: 0.1% and 1.0% PCMC in petrolatum. Clinical observations: saturated PCMC aqueous solution had marked erythematous and edematous reactions at the patch - test site.
Interpretation of results:
sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
A significant difference was observed between the sensitizing capacities of the preparations. The 5% PCMC suspensions in water and olive oil/acetone solution were the most sensitizing , with 12 of 19 and 11 of 20 animals reacting to 1% PCMC after 48 h , respectively ; the 5% PCMC in propylene glycol solution had the least sensitizing potential , with only 4 of 20 animals reacting o challenge with 1% after 48 h Carbomer 941 had no effect on the sensitization rate .
Executive summary:

The contact sensitivity caused by chlorocresol was studied in guinea pigs by the cumulative contact enhancement test. Female albino guinea pigs were given the cumulative contact enhancement test using topical induction patches on days 0, 3, 7, and 9. Before the third induction patch test an emulsion of Freunds complete adjuvant was injected intradermally as an immune stimulant.

Challenge reactions were read 48 and 72 hours after the last application. A significant difference was observed between the sensitizing capacities of the preparations. The 5% PCMC suspensions in water and olive oil/acetone solution were the most sensitizing , with 12 of 19 and 11 of 20 animals reacting to 1% PCMC after 48 h , respectively ; the 5% PCMC in propylene glycol solution had the least sensitizing potential , with only 4 of 20 animals reacting o challenge with 1%after 48 h Carbomer 941 had no effect on the sensitization rate .

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

Based on studies of target substance CAS NO 59-50-7 reviewed for skin sensitization from reliable sources having Klimisch rating 2considering the weight of evidence approach.

 The summary of the results are presented below

Sr. No

End point

effect

Species

Remark

1

Skin sensitization

sensitizing

guinea pig

Data is from publication for Target chemical

2

Skin sensitization

sensitizing

guinea pig

Data is from publication for Target chemical

3

Skin sensitization

not sensitizing

Humans

Data is from 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 is sensitizing to the skin of guinea pig but not humans.Thus Chlorocresol is considered to be sensitizing to skin as per the criteria of CLP regulation and will be classified as skin sen. category 1.

Migrated from Short description of key information:

The substance chlorocresol was found to be a potent skin sensitizers.

Justification for selection of skin sensitisation endpoint:

The contact sensitivity caused by chlorocresol was studied in guinea pigs by the cumulative contact enhancement test. Female albino guinea pigs were given the cumulative contact enhancement test using topical induction patches on days 0, 3, 7, and 9. Before the third induction patch test an emulsion of Freunds complete adjuvant was injected intradermally as an immune stimulant.

Challenge reactions were read 48 and 72 hours after the last application. A significant difference was observed between the sensitizing capacities of the preparations. The 5% PCMC suspensions in water and olive oil/acetone solution were the most sensitizing , with 12 of 19 and 11 of 20 animals reacting to 1% PCMC after 48 h , respectively ; the 5% PCMC in propylene glycol solution had the least sensitizing potential , with only 4 of 20 animals reacting o challenge with 1%after 48 h Carbomer 941 had no effect on the sensitization rate .

Justification for classification or non-classification

Based on the above studies it can be concluded that the substance chlorocresol was found to sensitizing to skin ans hence classified as Skin sen.1 category.