Registration Dossier

Administrative data

Description of key information

The skin sensitization potential of test chemical was assessed in various experimental studies conducted on mose lymphoma. Based on the available data for the target studies, it can be concluded that the test chemical is not able to cause skin sensitization and thus cannot be considered as sensitizing. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not sensitizing”.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Remarks:
experimental data from various test chemicals
Justification for type of information:
Data is summarized based on the available information from various read across test chemicals.
Reason / purpose:
read-across source
Reason / purpose:
read-across source
Qualifier:
according to
Guideline:
other: As mentioned below
Principles of method if other than guideline:
WoE report is based on 2 skin sensitization studies as - WoE 2 and WoE 3.
Skin sensitization test was carried out to study the effects of the test chemicals on rodents.
GLP compliance:
not specified
Type of study:
other: 2. sensitive mouse lymph node assay (SLNA) 3.patch test
Justification for non-LLNA method:
No data available
Species:
other: 2.mouse 3.human
Strain:
other: 2.Balb/c 3.not applicable
Sex:
male/female
Details on test animals and environmental conditions:
2. TEST ANIMALS
- Source: Japan SLC Inc, Shizuoka,Japan
- Age at study initiation: 6-8 weeks old
- Weight at study initiation: No data available
- Housing: No data available
- Diet (e.g. ad libitum): No data available
- Water (e.g. ad libitum): No data available
- Acclimation period: No data available

ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data available
- Humidity (%):No data available
- Air changes (per hr): No data available
- Photoperiod (hrs dark / hrs light): No data available

IN-LIFE DATES: From: To: No data available
3. No data available
Route:
intradermal
Vehicle:
other: For intra-dermal injection: saline and For topical injection : Dimethyl sulphoxide
Remarks:
2
Route:
epicutaneous, occlusive
Vehicle:
petrolatum
Remarks:
3
Concentration / amount:
2% in petrolatum
Route:
other: Topical application
Vehicle:
other: For intra-dermal injection: saline and For topical injection : Dimethyl sulphoxide
Remarks:
2
No.:
#1
Route:
other: No data
Vehicle:
petrolatum
Remarks:
3
Concentration / amount:
2% in petrolatum
No. of animals per dose:
2.3 mice
3.9 patients
Details on study design:
2.RANGE FINDING TESTS: No data available

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 1
- Exposure period: No data available
- Test groups: 3
- Control group: No detailed data available
- Site: Two sites of the abdominal skin at both sides of the ventral midline
- Frequency of applications: 1
- Duration: 5 days
- Concentrations: 50 µl of test chemical-FCA emulsion; Maximum injection concentration was 2%

B. CHALLENGE EXPOSURE
- No. of exposures: Thrice (on three consecutive days)
- Day(s) of challenge: three consecutive days
- Exposure period: 3 consecutive days
- Test groups: 3
- Control group: No detailed data available - Site: applied to both sides of each ear
- Concentrations: 25 µl of test chemical-FCA emulsion;Topical concentrations for the chemical was selected based on solubility limit to vehicles
- Evaluation (hr after challenge): the day following the last topical application

OTHER: After the topical exposure auricular lymph nodes were excised and pooled for each experimental group. A single cell suspension of LNC was prepared by mechanical disaggregation through a sterile 200-mesh gauge and washed once with Hanks' balanced salt solution. The LNCs were resuspended in RPMI- 1640 culture medium supplemented with 25 mM N-2-hydroxyethylpiperazine-N'- 2-ethanesulphonic acid (HEPES), penicillin, streptomycin and fetal calf serum, and the total LNC number were determined using an automated cell counter. The LNC suspensions (1 x 106 cells) were seeded into 96-well culture plates (five wells per group) and cultured with 0.5 pCi [3H] methyl thymidine (3HTdR) for 24 h at 37°C in a humidified atmosphere of 5% CO, in air. Culture was terminated by a semiautomatic cell harvester, and the 3HTdR incorporation was determined by liquid scintillation counting. The increases in LNC number and 3HTdR incorporation relative to controls were derived for each experimental group and the total lymph node activation induced by the test chemicals was calculated.

3.OTHER: The dye was applied in Finn Chambers and read first at 2 or (more commonly) 3 days and again at 4–7 days.
The reactions of the patients were graded as ?+. + and ++ categories.
Challenge controls:
No data available
Positive control substance(s):
not specified
Positive control results:
No data available
Reading:
other: induction exposure phase /2
Hours after challenge:
24
Group:
test group
Dose level:
50 µl
No. with + reactions:
0
Total no. in group:
3
Clinical observations:
non- sensitizing during sensitive mouse lymph node assay (SLNA)
Remarks on result:
other: see Remark
Remarks:
Reading: other: induction exposure phase. . Hours after challenge: 24.0. Group: test group. Dose level: 50 µl . No with. + reactions: 0.0. Total no. in groups: 3.0. Clinical observations: non- sensitizing during sensitive mouse lymph node assay (SLNA) .
Reading:
other: challenge exposure phase/2
Hours after challenge:
24
Group:
test group
Dose level:
25 µl
No. with + reactions:
0
Total no. in group:
3
Clinical observations:
non- sensitizing during sensitive mouse lymph node assay (SLNA)
Remarks on result:
other: see Remark
Remarks:
Reading: other: challenge exposure phase. . Hours after challenge: 24.0. Group: test group. Dose level: 25 µl . No with. + reactions: 0.0. Total no. in groups: 3.0. Clinical observations: non- sensitizing during sensitive mouse lymph node assay (SLNA) .
Reading:
1st reading
Group:
test group
Dose level:
2%
No. with + reactions:
0
Total no. in group:
9
Clinical observations:
non sensitising
Remarks on result:
other: Reading: 1st reading. Group: test group. Dose level: 2%. No with. + reactions: 0.0. Total no. in groups: 9.0. Clinical observations: non sensitising.
Remarks:
3
Interpretation of results:
other: Not sensitizing
Conclusions:
The sensitization potential of test chemical was considered to be a non- sensitizing in humans and animals.
Executive summary:

Various studies were performed on test animals to assess the skin sensitization potential of test chemical which have been summarized as follows:

Sensitive mouse lymph node assay skin sensitization assay was performed on female BALB/c strain mice. They were intradermally injected with 50 µl of test chemical –FCA emulsion into two sites of the abdominal skin at both sides of the ventral line. After 5 days 25 µl of test chemical in vehicle was applied to both sides of each ear for three consecutive days.Control mice were treated by intradermal injection of vehicle-FCA emulsion into the abdomen and then after 5 days they were exposed to vehicle alone on the ears for three consecutive days.The increases in LNC number and3HTdR incorporation relative to controls were derived for each experimental group and expressed as SInand SIP, respectively; SI total as obtained from SInx SIP, which indicates the total lymph node activation induced by the test chemical.A chemical was regarded as positive if it showed an SItotalvalue of 3 or more. The SItotalvalue of test chemical was found to be 1.55 at 5% DMSO concentration. Hence,the test chemical was considered to be not sensitizing to the skin of BALB/c strain mice in the sensitive mouse lymph node assay.

In another study, the sensitization potential of test chemical was determined by performing patch tests on humans. The dye was applied in Finn Chambers and read first at 2 or (more commonly) 3 days and again at 4–7 days.The reactions of the patients were graded as ‘?+ ‘ , ‘+’ and ‘++’ categories 9 patients were tested with the dye.No reactions were reported by all the patients.Hence the test chemical can be considered as a non- sensitizer in humans.

The results obtained from these studies lead to a conclusion that Test chemical is indeed not sensitizing to skin. Hence, comparing the above annotations with the criteria of CLP regulation, Test chemical can be classified under the category “ Not classified based on GHS criteria”.

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

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available (further information necessary)
Additional information:

Various studies were performed on test animals to assess the skin sensitization potential of test chemical which have been summarized as follows:

Sensitive mouse lymph node assay skin sensitization assay was performed on female BALB/c strain mice. They were intradermally injected with 50 µl of test chemical –FCA emulsion into two sites of the abdominal skin at both sides of the ventral line. After 5 days 25 µl of test chemical in vehicle was applied to both sides of each ear for three consecutive days.Control mice were treated by intradermal injection of vehicle-FCA emulsion into the abdomen and then after 5 days they were exposed to vehicle alone on the ears for three consecutive days.The increases in LNC number and3HTdR incorporation relative to controls were derived for each experimental group and expressed as SInand SIP, respectively; SI total as obtained from SInx SIP, which indicates the total lymph node activation induced by the test chemical.A chemical was regarded as positive if it showed an SItotalvalue of 3 or more. The SItotalvalue of test chemical was found to be 1.55 at 5% DMSO concentration. Hence,the test chemical was considered to be not sensitizing to the skin of BALB/c strain mice in the sensitive mouse lymph node assay.

In another study, the sensitization potential of test chemical was determined by performing patch tests on humans. The dye was applied in Finn Chambers and read first at 2 or (more commonly) 3 days and again at 4–7 days.The reactions of the patients were graded as ‘?+ ‘ , ‘+’ and ‘++’ categories 9 patients were tested with the dye.No reactions were reported by all the patients.Hence the test chemical can be considered as a non- sensitizer in humans.

The results obtained from these studies lead to a conclusion that Test chemical is indeed not sensitizing to skin. Hence, comparing the above annotations with the criteria of CLP regulation, Test chemical can be classified under the category “ Not classified based on GHS criteria”.

Justification for classification or non-classification

The skin sensitization potential of test substance were observed in various studies. From the results obtained from these studies it is concluded that the test chemical is not likely to cause skin sensitization and hence can be classified as “Not sensitizing”.