Registration Dossier

Administrative data

Description of key information

Data available for the closely related read across chemicals has been reviewed to determine the skin sensitization potential of the test chemical. Based on the summarized studies,it can be concluded that the testchemical 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)
Remarks:
LLNA and 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 of read across substances
Justification for type of information:
Data for the target chemical is summarized based on the closely related read across chemicals
Reason / purpose:
read-across source
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 3 skin sensitization studies as- WoE-2, WoE-3 and WoE-4.
Skin sensitization of test chemical was determined by performing LLNA and Non-LLNA sensitization tests on humans, guinea pigs and mice.
GLP compliance:
not specified
Type of study:
other: 1.patch test 2.Guinea pig maximization test 3.mouse local lymphnode assay (LLNA)
Species:
other: 1.Human 2.guinea pigs 3.mouse
Strain:
other: 1.Not applicable 2.No data available 3.CBA
Sex:
male/female
Details on test animals and environmental conditions:
1,2.No data available.
3.Age at study initiation: 7-12 weeks
Route:
other: 1.epicutaneous, occlusive
Vehicle:
not specified
Concentration / amount:
0.2%
Day(s)/duration:
3 weeks
Adequacy of induction:
not specified
Route:
other: 2.intradermal and epicutaneous
Vehicle:
other: Acetone
Concentration / amount:
Intradermal – 2.5%,
topical – 5%,
Day(s)/duration:
not specified
Adequacy of induction:
not specified
No.:
#1
Route:
other: 2.epicutaneous, occlusive
Vehicle:
not specified
Concentration / amount:
0.2%
Day(s)/duration:
24 hours
Adequacy of challenge:
not specified
No.:
#1
Route:
other: 2.epicutaneous, occlusive
Vehicle:
other: Acetone
Concentration / amount:
0.5% w/v in acetone
Day(s)/duration:
not specified
Adequacy of challenge:
not specified
No. of animals per dose:
1.108 adult panelists (70 females, 38 males)
2. 15 animals
3.No data
Details on study design:
1.
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 9
- Exposure period: 24 hour
- Test groups: yes
- Control group: No data available
- Site: upper arm
- Frequency of applications: every other day for continuous 3 weeks
- Duration: 3 weeks
- Concentrations: 0.2%

B. CHALLENGE EXPOSURE
- No. of exposures:Single
- Day(s) of challenge: 2 weeks
- Exposure period: 24 hour
- Test groups: Yes
- Control group: No data available
- Site: No data available
- Concentrations: 0.2%
- Evaluation (hr after challenge): 24 hour

2. No data available

3. LLNA study
vehicle: acetone/olive oil (4:1 v/v)

concentration :25 µl

study design: 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)

statistics: 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

Refer Table 1 and 2 for more information
Reading:
other: 1.1st reading
Hours after challenge:
24
Group:
test group
Dose level:
0.2%
No. with + reactions:
0
Total no. in group:
108
Clinical observations:
No sensitization observed.
Remarks on result:
no indication of skin sensitisation
Reading:
other: 2.1st reading
Group:
test group
Dose level:
0.5% w/v acetone
No. with + reactions:
0
Total no. in group:
15
Clinical observations:
No skin reactions were observed
Remarks on result:
no indication of skin sensitisation
Reading:
other: 3.EC3
Group:
test group
Dose level:
25 µl
Remarks on result:
other: The relative potency index of test chemical was not calculated but on the basis of classification system it was considered to be >100.
Remarks:
For LLNA study

1,2. No data available

3.

Table 1:Classification of relative skin sensitization potency by local lymphnode assay (LLNA) EC3 values

EC3 values (%)

Potency classification

≥10 to ≤100

Weak

≥1 to <10

Moderate

≥0.1 to <1

Strong

<0.1

Extreme

Interpretation of results:
other: Not sensitizing
Conclusions:
Since no adverse effects were observed in treated subjects and animals. Hence the test material was considered to be not sensitizing to the skin.
Executive summary:

Data available for the closely related read across chemicals has been reviewed to determine the skin sensitization potential of the test chemical. The studies are as mentioned below:

 

A skin sensitization study was conducted in 108 (70 females, 38 males) to determine their skin response to a cream containing 0.2 percent test chemical. The method used was a modification of the repeated insult patch test. A 24-hour occlusive patch to the upper arm was applied every other day for 3 weeks (nine induction applications), a 2-week rest, followed by a 24-hour occlusive challenge patch. After the challenge exposure no sensitization was observed in any subject. Therefore the test chemical was considered to be non-sensitizing to human skin.

 

The above result was supported by the guinea pig maximization test conducted to assess the dermal sensitization potential of the test chemical. 15 guinea pigs were used for the study. Guinea pigs were intradermally induced with 2.5% of the test chemical and then subjected to topically induction with 5% test chemical. After a suitable rest period, the guinea pigs were challenged with 0.5%w/v in acetone and observed for effects. No reactions were observed in 15 guinea pigs tested. Hence, the test chemical can be considered to be not sensitizing to skin.

 

The above results were further supported by the Mouse Local Lymphnode Assay conducted for test chemical. The LLNA was conducted on groups of 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 or to an equal volume of relevant vehicle (Acetic acid in olive oil (4:1))only. 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 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. The relative potency index of test chemical was not calculated but on the basis of classification system it was considered to be >100. Thus the test chemical was considered as non-skin sensitizer.

 

Based on the above summarized studies for target chemical and itsclosely related read across chemicals,it can be concluded that the testchemical is unable to cause skin sensitization and considered as non-skin sensitizer. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

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

Data available for the closely related read across chemicals has been reviewed to determine the skin sensitization potential of the test chemical. The studies are as mentioned below:

 

A skin sensitization study was conducted in 108 (70 females, 38 males) to determine their skin response to a cream containing 0.2 percent test chemical. The method used was a modification of the repeated insult patch test. A 24-hour occlusive patch to the upper arm was applied every other day for 3 weeks (nine induction applications), a 2-week rest, followed by a 24-hour occlusive challenge patch. After the challenge exposure no sensitization was observed in any subject. Therefore the test chemical was considered to be non-sensitizing to human skin.

 

The above result was supported by the guinea pig maximization test conducted to assess the dermal sensitization potential of the test chemical. 15 guinea pigs were used for the study. Guinea pigs were intradermally induced with 2.5% of the test chemical and then subjected to topically induction with 5% test chemical. After a suitable rest period, the guinea pigs were challenged with 0.5%w/v in acetone and observed for effects. No reactions were observed in 15 guinea pigs tested. Hence, the test chemical can be considered to be not sensitizing to skin.

 

The above results were further supported by the Mouse Local Lymphnode Assay conducted for test chemical. The LLNA was conducted on groups of 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 or to an equal volume of relevant vehicle (Acetic acid in olive oil (4:1))only. 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 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. The relative potency index of test chemical was not calculated but on the basis of classification system it was considered to be >100. Thus the test chemical was considered as non-skin sensitizer.

 

Based on the above summarized studies for target chemical and itsclosely related read across chemicals,it can be concluded that the testchemical is unable to cause skin sensitization and considered as non-skin sensitizer. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

The skin sensitization potential of test substance anditsclosely related read across chemicals were 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.