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Description of key information

The skin sensitization potential of test chemical was assessed in various experimental studies conducted on guinea pigs and humans for test chemical and its structurally similar read across chemicals .The predicted data using the Danish QSAR database has also been compared with the experimental data. Based on the available data for the target and supporting studies, it can be concluded that the test chemical is unable to cause skin sensitization and thus can be 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 journal.
Qualifier:
according to
Guideline:
other: as mentioned below
Principles of method if other than guideline:
The modified repeated insult patch test described by Draize was conducted to assess the skin sensitization potential of test chemical.
GLP compliance:
not specified
Type of study:
patch test
Justification for non-LLNA method:
not specified
Species:
human
Strain:
other: Not applicable
Sex:
male/female
Route:
epicutaneous, occlusive
Vehicle:
other: Cream
Concentration / amount:
0.2 %
Day(s)/duration:
3 weeks
Adequacy of induction:
not specified
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
other: Cream
Concentration / amount:
0.2%
Day(s)/duration:
24 hours
Adequacy of challenge:
not specified
No. of animals per dose:
108 adult panelists (70 females, 38 males)
Details on study design:
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 9
- Exposure period: 24 hours
- Test groups: 108
- Control group: not specified
- Site:upper arm
- Frequency of applications: every other day for 3 weeks (nine induction applications)
- Duration: 3weeks
- Concentrations: 0.2%



B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: after 2 week rest
- Exposure period: 24 hours
- Test groups: 108
- Control group: no data
- Site: no data
- Concentrations: 0.2%
- Evaluation (hr after challenge): after 24 hours
Challenge controls:
Not specified
Positive control substance(s):
not required
Vehicle:
not specified
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
0.2%
No. with + reactions:
108
Total no. in group:
0
Clinical observations:
No skin sensitization was observed.
Remarks on result:
no indication of skin sensitisation
Cellular proliferation data / Observations:
No skin sensitization was observed.
Interpretation of results:
other: not sensitising
Conclusions:
The test chemical at a concentration of 0.02 % in 108 adult panelists for 24-hour in occlusive patch test was considered to be non-sensitizing.
Executive summary:

The modified repeated insult patch test described by Draize was conducted to assess the skin sensitization potential of test chemical. During induction, one hundred eight adult panelists (70 females, 38 males) were tested to determine their skin response to a cream containing 0.2 percent of test chemical. The procedure called for a 24hour occlusive patch to the upper arm every other day for 3 weeks (nine induction applications), a 2-week rest, followed by a 24hour occlusive challenge patch. Since there were no evidence of any contact allergic reaction, the test chemical was considered to be not- sensitizing to the skin of treated panelist.

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

Various studies has 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 performed on guinea pigs and humans for test chemical and its structurally similar read across chemical .The predicted data using the Danish QSAR database has also been compared with the experimental data and summarized as below;

The modified repeated insult patch test described by Draize was conducted to assess the skin sensitization potential of test chemical. During induction, one hundred eight adult panelists (70 females, 38 males) were tested to determine their skin response to a cream containing 0.2 percent of test chemical. The procedure called for a 24hour occlusive patch to the upper arm every other day for 3 weeks (nine induction applications), a 2-week rest, followed by a 24hour occlusive challenge patch. Since there were no evidence of any contact allergic reaction, the test chemical was considered to be not- sensitizing to the skin of treated panelist.

 

In next study, the test chemical was assessed to determine the skin sensitization potential in consecutive patients referred with eczematous dermatitis. When the test chemical was tested at concentration of 2%, only three positive reactions observed from a total 112 patients with eczematous dermatitis. From this test result it is concluded that the test material was not sensitizing to the human skin.

 

Further, a repeated insult patch test was conducted with a skin freshener containing 0.05 percent of test chemical on 104 subjects. Panelists ranged in age from 18 to 65. The test material was applied to the backs of each subject under an occlusive dressing and held in place for 48 hours. Upon removal of the patch, test sites were graded for skin irritation. An identical patch was then applied to the same site and the procedure repeated for a total of 10 induction applications. After a 10-day non-treatment period, a challenge patch containing the skin freshener was applied to a new site on the back of each subject. The challenge patch remained in place for 48 hours, and the test sites were graded 15 minutes and 24 hours after patch removal. None of the panelists showed a positive reaction during the induction or challenge phases. Hence the test chemical was considered to be not sensitizing to the skin of human subjects.

 

According to Danish QSAR database, skin sensitization effects were estimated by using four different models i.e, Battery, Leadscope, SciQSAR and CASE Ultra for test chemical. Based on estimation, no Allergic Contact Dermatitis effects were observed when test chemical was exposed to human and guinea pig skin. Hence, the test chemical can be considered as not sensitizing to skin.

 

The above results were supported by the Mouse Local Lymphnode Assay conducted for similar read across 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.

 

The overall results were further supported by an Open Epicutaneous Test (OET) performed on guinea pigs to assess the skin sensitization potential of another read across chemical. On day 1 during induction, 0.1 ml of the test chemical was applied at concentrations of 100%, 30%, 10%, 3%, 1%, or 0.3% in vehicle to an area measuring 8 cm2 on the clipped flank skin of the guinea pigs. The applications are repeated daily for 3 weeks or done 5 times weekly during 4 weeks, usually on the same skin sites. The application sites were left uncovered and the reactions, if continuous daily applications were performed, can be read 24 h after each application, or at the end of each week. To determine whether or not contact sensitization was induced, all groups of guinea pigs previously treated for 21 days, as well as 10 untreated, or only pretreated with the vehicle, controls are tested on days 21 and 35 on the contralateral flank with the test material. This test was performed by applying with a pipette 0.025 ml of each concentration to skin areas measuring 2 cm2. The reactions were read after 24,48 and/or 72h. It was observed that none of the guinea pigs induced contact sensitization at challenge concentration of 10%.Thus the test chemical was considered to be not sensitizing on skin of guinea pigs at concentration of 10 % in an Open Epicutaneous Test (OET).

All 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”.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

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 test chemical is not likely to cause skin sensitization and hence can be classified as non-skin sensitizer.