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Description of key information

The skin sensitization potential of test chemical was assessed in various experimental studies conducted on human subjects. The predicted data using the Danish QSAR database has also been compared with the experimental data. Based on the available data for the test chemical and supporting studies, it can be concluded that the test chemical is able to cause skin sensitization and thus can be considered as sensitizing. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Skin Sensitizer”.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
calculation (if not (Q)SAR)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
accepted calculation method
Justification for type of information:
data is from Danish QSAR
Qualifier:
according to
Guideline:
other: Estimated data
Principles of method if other than guideline:
To estimate the allergenic potential of the test chemical in guinea pigs and humans
GLP compliance:
not specified
Justification for non-LLNA method:
Allergic Contact Dermatitis in Guinea Pig and Human
Species:
other: humans and guinea pigs
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
not specified
Route:
other: not specified
Vehicle:
not specified
Adequacy of induction:
not specified
No.:
#1
Route:
other: not specified
Vehicle:
not specified
Adequacy of challenge:
not specified
No. of animals per dose:
not specified
Details on study design:
not specified
Challenge controls:
not specified
Positive control substance(s):
not specified
Reading:
1st reading
Group:
test group
Dose level:
no data available
No. with + reactions:
0
Clinical observations:
no dermal reactions observed
Remarks on result:
no indication of skin sensitisation

Table showing allergic dermatitis estimation by three different models i.e, battery and SciQSAR & CASE Ultra,the average results was given by the fourth model i.e, Battery model.

 

Exp

Battery

CASE Ultra

Leadscope

SciQSAR

Allergic Contact Dermatitis in Guinea Pig and Human

NA

POS_IN

POS_IN

NEG_IN

POS_IN

 

  

                                                                    Where,

IN = inside applicability domain, NEG = Negative; INC = Inconclusive; POS = Positive, OUT = outside applicability domain

 

Interpretation of results:
other: not sensitizing
Conclusions:
According to Danish QSAR database, skin sensitization effects were estimated by using three different models i.e, Battery, 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.
Executive summary:

According to Danish QSAR database, skin sensitization effects were estimated by using three different models i.e, Battery, 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.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (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 in human and guinea pigs for test chemical .The predicted data using the Danish QSAR database has also been compared with the experimental data and summarized as below:

According to Danish QSAR database, skin sensitization effects were estimated by using three different models i.e, Battery, 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.

In second case report, The skin sensitizing potential of the test chemical was assessed by using the Mouse Local Lymphnode Assay. 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 (Dimethylformamide)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 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. The calculated stimulation indices at tested concentrations 1,3, and 10 were 2.3,4.4 and 8.6 respectively. Also the EC3 value of test chemical was calculated to be 1.7 %. Based on the EC3 values, the test chemical was considered to be a moderate skin sensitizer.

Further, the skin sensitization study was conducted on human subjects to assess the skin sensitization potential of test chemical epicutaneously.Out of 28 cases,12 cases showed positive incidation of sensitization. Hence the test material was considered to be sensitizing to the skin of human subjects.

 

The overall results were further supported by Guinea pig maximisation test was conducted in Himalayan white-spotted guinea pigs (male and female) to determine the skin sensitization potential of test chemical. During induction, on day 0the animals were injected intradermally with 0.1 ml of a   5% solution of the compound tested, with 0.1 ml of a 5 % emulsion of the same compound in Freund's complete adjuvant (FCA) and with 0.1 ml of FCA alone. On day 8 the animals were induced epicutaneously with 250 mf of 25% test compound in dissolved in petrolatum on clipped skin area of the neck under occlusion for 2 days. On day 21, animals were challenged with the compound at a subirritant concentration in petrolatum was applied to the flank for 24 h. The reactions were read 24 and 48 h after removing the patch. Since the test chemical showed positive signs of contact sensitization during the observation period, it was considered to be sensitizing to the skin of Himalayan white-spotted guinea pigs.

Thus based on the above studies for test chemical, it can be concluded that the test chemical is able to cause skin sensitization. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Skin Sensitizer”.

Justification for classification or non-classification

The skin sensitization potential of test substance and its read across substances were observed in various studies. From the results obtained from these studies it is concluded that the chemical is likely to cause skin sensitization and hence can be classified as "skin sensitizer".