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Administrative data

Description of key information

The skin sensitization potential of target chemical was assessedin various LLNA and Non- LLNA experimental studies for target and its structurally similar read across substances.Based on the available key data and supporting studies,it can be concluded thatchemical is unable to cause skin sensitization and considered as not sensitizing. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
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 peer reviewed journals
Qualifier:
according to
Guideline:
other: as mentioned below
Principles of method if other than guideline:
The allergenic potential of test chemical was determined in a number of studies using up to 31 patients, 19 males and 12 females, with a history of aspirin intolerance
GLP compliance:
not specified
Type of study:
other: Intradermal Skin test
Justification for non-LLNA method:
not specified
Species:
other: humans
Strain:
not specified
Sex:
male/female
Details on test animals and environmental conditions:
Age: aged between 6 and 64 years
Route:
intradermal
Vehicle:
no data
Concentration / amount:
Induction exposure: 0.02 ml of 0.1 % of test chemical
Day(s)/duration:
20 minutes
Adequacy of induction:
not specified
No.:
#1
Route:
intradermal
Vehicle:
not specified
Concentration / amount:
an intradermal injection of 0.02 ml of 0.1% test chemical
Day(s)/duration:
20 minutes
Adequacy of challenge:
not specified
No. of animals per dose:
19 males and 12 females
Details on study design:
an intradermal injection of 0.02 ml of test chemical (0.1%) were given to human patients and the result were recorded after 20 min
Challenge controls:
no data available
Positive control substance(s):
not specified
Vehicle:
not specified
Reading:
1st reading
Hours after challenge:
20
Group:
test group
Dose level:
0.02 ml of 0.1% of test chemical
No. with + reactions:
1
Total no. in group:
31
Clinical observations:
The test chemical did not develope any skin sensitizing effects on treated animals.
Remarks on result:
no indication of skin sensitisation
Cellular proliferation data / Observations:
The test chemical did not develope any skin sensitizing effects on treated animals.
Interpretation of results:
other: not sensitizing
Conclusions:
There was one positive reaction to test chemical in the skin test was observed out of 31 pateints.Hence, the test chemical can be considered to be not sensitizing to skin.
Executive summary:

The allergenic potential of test chemical was determined in a number of studies using up to 31 patients. 19 males and 12 females, with a history of aspirin intolerance were used for the assay. 31 patients were given an intradermal injection of 0.02 ml of 0.1% test chemical; the results were scored 20 min after dosing. There was one positive reaction to test chemical in the skin test was observed out of 31 patients. Hence, the test material can be considered to be not sensitizing to skin.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Various studieshas been investigated for the test chemical to observe the potential for skin sensitization to a greater or lesser extent. The studies are based on in vivo experiments for target chemicaland its structurally similar read across substance which have summarized as below;

 

The allergenic potential of test chemical was determined in a number of studies using up to 31 patients. 19 males and 12 females, with a history of aspirin intolerance were used for the assay. 31 patients were given an intradermal injection of 0.02 ml of 0.1% test chemical; the results were scored 20 min after dosing. There was one positive reaction to test chemical in the skin test was observed out of 31 patients. Hence, the test material can be considered to be not sensitizing to skin.

 

The next Patch test was conducted on a patient with allergic contact dermatitis to sunscreen for assessing the skin sensitization potential of test chemical. A 48 year old woman with a 12 year history of rosacea was advised to use sunscreen. A sample of Anthelios dermo-pediatrics SPF-50+ was given to the patient. Half year later, the patient developed facial dermatitis. She was tested with the European baseline series using panels 1,2, and 3 of the Thin Layer Rapid Use Epicutaneous Test [T.R.U.E Test] supplemented petrolatum-based allergens in Finn chambers on Scanpor tape and with her own topical products including the Anthelios dermo-pediatrics SPF-50+ lotion. The tests were occluded for 2 days and read according to the ICDRG[International Contact Dermatitis Research Group]scoring scale on day 3 and day 7. The patient was subsequently patch test with individual components of the Anthelios dermo-pediatrics SPF-50+ lotion as provided by the manufacturer. No dermal reactions were observed on day 3 and day 7 of observation when the patient was tested with 2% test chemical in petrolatum. Hence, the test chemical can be considered to be not sensitizing to skin.

 

The above result was supported by the Mouse Local Lymphnode Assay conducted for similar read across chemical. The LLNA was conducted on groups of five female CBA mice (7-12 weeks of age) by mean of topical application of chemical on the dorsum of both ears at a dose of 25µl of 1%, 2.5%, 5%, 10% or 20% in acetone/olive oil (4:1). Treatment was performed daily for 3 consecutive days. Five days after initiation of exposure all mice were injected via the tail vein with 250µl of PBS containing 20µCi of tritiatied thymidine. The mice were sacrificed 5 hours later, and draining the auricular lymph nodes were excised and pooled for each experimental group or each individual animal. The incorporation of tritiated thymidine measured by β-scintillation counting and was reported in disintegrations /minute. An SI was calculated for each chemical group as the ratio of disintegrations/minute of the treated group to the disintegrations/minute of the concurrent vehicle control group. A substance was classified skin sensitizer, if at one or more than one concentrations, it induced a three-fold or greater increase in local lymph node proliferative activity when treated with the concurrent vehicle treated controls (SI ≥3).The approach to estimation of the relative skin sensitization potential is based on the mathematical estimation of the concentration of chemical necessary to obtain a threshold positive response (SI = 3); this is termed as the EC3 value. For each concentration, a stimulation index (SI) relative to the concurrent vehicle-treated control was calculated. The calculated EC3 value for test chemical was >20.0%. Thus based on the relative potency index the test chemical was considered to be not sensitizing in the Mouse Local Lymphnode Assay.

 

The overall results were further supported by the similar LLNA study (mentioned above) for another read across chemical. The relative potency index of test chemical was not calculated since the SI were less than 3. Based on the relative potency, the test chemical was considered to be not sensitizing to mice skin.

Based on the available data for the target chemical, supporting studies and read across substance,it can be concluded thatchemical is unable to cause skin sensitization and considered as not sensitizing. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

Justification for classification or non-classification

The skin sensitization potential of test substance and its structurally similar read across substancewere observed in various studies. From the results obtained from these studies it is concluded that the chemical is not likely to cause skin sensitization and hence can be classified as non-skin sensitizer.