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Description of key information

- Repeated patch test: no guideline followed, pre-GLP, human, not sensitising


 


In order to confirm the negative result of the human patch test, read-across to a skin sensitisation study with a structural analogue is performed.


- LLNA: read across to CAS 106276-79-3, according to OECD 429, GLP, mouse, not sensitising

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
please refer to the attached read-across justification
Reason / purpose for cross-reference:
read-across source
Parameter:
SI
Value:
0.83
Test group / Remarks:
1% test item concentration
Parameter:
SI
Value:
1.03
Test group / Remarks:
2% test item concentration
Parameter:
SI
Value:
0.96
Test group / Remarks:
5% test item concentration

A statistically significant or biologically relevant increase in DPM values, lymph node weights and lymph node cell counts was not observed in any treated group in comparison to the vehicle control group.

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1974
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
amount of applied substance not reported, no information on test substance
Qualifier:
no guideline followed
Principles of method if other than guideline:
Repeat insult patch test to determine if the test material is capable of irritating the skin of humans under controlled test conditions; and, if so, to classify the test material as a primary irritant, fatiguing agent, and/or sensitizer on the basis of visible clinical responses
GLP compliance:
no
Type of study:
patch test
Justification for non-LLNA method:
An appropriate human patch test is available which would not justify conducting an additional LLNA due to animal welfare.
Specific details on test material used for the study:
Purity: no data
Species:
human
Strain:
other: Test persons were selected from a local population (The study was performed by a company in Pennsylvania, U.S.A.)
Sex:
not specified
Details on test animals and environmental conditions:
The criteria for qualifying as test person were:
1. General well-being.
2. Absence of any skin disease which might be confused with skin reactions from the test material.
3. Willingness to cooperate.
4. Dependability and intelligence in following directions.
5. Reading, understanding, and signing an informed-consent contract, (In the case of minors, parental consent was obtained.)
Route:
epicutaneous, occlusive
Vehicle:
no data
Concentration / amount:
20 %
Route:
epicutaneous, occlusive
Vehicle:
no data
Concentration / amount:
20 %
No. of animals per dose:
200
Details on study design:
TYPE OF TEST(S) USED: repeated patch test (epicutaneous test)

ADMINISTRATION
The test material was applied as 20% dilution under occlusion to a skin size of 3*3 cm for a series of effective contact periods of two days' duration. On Monday, the test material was applied. The participants were instructed to contact the laboratory and inform the investigator immediately if any discomfort was felt at the patch site. On Wednesdays, the patches were removed, the contact sites examined, and the reactions, if any, were graded and recorded.
If no reactions occurred, the test material was re-applied immediately for another forty-eight-hour period. The participants were instructed to call the laboratory on Thursday if any discomfort was felt. On Friday, the covers were removed and the contact sites were again examined and graded. The contact sites were then rested until the following Monday. This cycle was repeated for three more weeks, so that a series of eight forty-eight-hour applications were completed.
On the second Monday following the removal of the last series of applications, the test material was applied to the same contact site. The covers were removed on Wednesday, thereby effecting a challenge contact period of forty-eight hours' duration. The contact sites were examined for visible changes which, if present, were graded and recorded. Sites were re-examined twenty-four and forty-eight hours later for delayed reactions.

EXAMINATIONS
- Grading/Scoring system:
0 = No reactions.
1+ = Slight erythema.
2+ = Marked erythema.
3+ = Marked erythema, edema, with or without a few vesicles.
4+ = Marked erythema, edema, with vesicles and oozing.
Challenge controls:
no
Positive control substance(s):
no
Reading:
1st reading
Hours after challenge:
0
Group:
test chemical
Dose level:
20%
No. with + reactions:
0
Total no. in group:
200
Clinical observations:
no irritating reactions observed
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
24
Group:
test chemical
Dose level:
20%
No. with + reactions:
0
Total no. in group:
200
Remarks on result:
no indication of skin sensitisation
Reading:
other: 3rd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
20%
No. with + reactions:
0
Total no. in group:
200
Remarks on result:
no indication of skin sensitisation
Interpretation of results:
GHS criteria not met
Conclusions:
Under the test conditions, the test item, tested as a 20% dilution, was not capable of eliciting visible skin changes consistent with the criteria deemed characteristic of a primary irritant, fatiguing agent, or sensitizer. In the opinion of the investigator, this material may be considered safe to use in contact with the skin insofar as primary irritation, fatiguing, or sensitization are concerned if the conditions of contact do not exceed those of the test procedure.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

In a human repeated patch test, a group of 200 individuals who qualified were selected from a local population. The test material was applied under occlusion for a series of effective contact periods of two days duration. On Mondays, the test material was applied. The participants were instructed to contact the laboratory and inform the investigator immediately if any discomfort was felt at the patch site. On Wednesdays, the patches were removed, the contact sites examined, and the reactions, if any, were graded and recorded. If no reactions occurred, the test material was re-applied immediately for another forty-eight hour period. The participants were instructed to call the laboratory on Thursday if any discomfort was felt. On Friday, the covers were removed and the contact sites were again examined and graded. The contact sites were then rested until the following Monday. This cycle was repeated for three more weeks, so that a series of eight fortyeight- hour applications were completed. On the second Monday following the removal of the last series of applications, the test material was applied to the same contact site. The covers were removed on Wednesday, thereby effecting a challenge contact period of forty-eight hours' duration. The contact sites were examined for visible changes which, if present, were graded and recorded. Sites were re-examined twenty-four and forty-eight hours later for delayed reactions. No visible skin changes signifying reaction to injury were observed in any of the 200 subjects. Under the test conditions, the compound tested as a 20 % dilution, was not capable of eliciting visible skin changes consistent with the criteria deemed characteristic of a primary irritant, fatiguing agent, or sensitizer.


 


In order to confirm the negative result of the human patch test, read-across to a skin sensitisation study with a structural analogue is performed.


The structural analogue (CAS 106276-79-3) was tested in a Local Lymph Node Assay (LLNA) according to the OECD Guideline 429 (GLP) in mice (CBA/CaOlaHsd). Test item suspensions at different concentrations (1, 2 and 5 % w/w) were prepared using DMSO as a vehicle. The animals did not show any signs of systemic toxicity during the course of the study and no cases of mortality were observed. On day 6, all test item treated animals showed scabby ear skin. A possible erythema of the ear skin could not be evaluated due to the colour of the test item. A statistically significant increase in ear weights was observed in the high dose group in comparison to the vehicle control group (p < 0.05). However, this was considered as not biologically relevant, as the observed increase did not exceed the threshold value of 25 % for excessive local skin irritation mentioned in OECD Guideline 429. Nevertheless, the increase in ear weights indicates a slight irritant property of the test item. In this study Stimulation Indices (S.I.) of 0.83, 1.03 and 0.96 were determined with the test item at concentrations of 1, 2 and 5 %, respectively. A statistically significant or biologically relevant increase in DPM values, lymph node weights and lymph node cell counts was not observed in any treated group in comparison to the vehicle control group. Furthermore, the cut-off value of 1.55 for a positive response regarding the lymph node cell count index reported for BALB/c mice was not exceeded in any dose group. Thus, the test item was not a skin sensitiser under the test conditions of this study.


 


Based on the physico-chemical, structural as well as toxicological similarities, the same outcome is assumed for the actual substance.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008


The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result, the substance is not considered to be classified for skin sensitization under Regulation (EC) No. 1272/2008, as amended for the fourteenth time in Regulation (EC) No. 2020/217.