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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
September 18, 2018 -October 09, 2018
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
OECD 429

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2018
Report Date:
2018

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of study:
mouse local lymph node assay (LLNA)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Test material form:
solid: particulate/powder

In vivo test system

Test animals

Species:
mouse
Strain:
CBA:J
Sex:
female

Study design: in vivo (LLNA)

Vehicle:
dimethylformamide
Concentration:
1%, 10% and 25% (w/v) test item in dimethylformamide
No. of animals per dose:
5 mice/group
Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)

Results and discussion

Positive control results:
The SI of 5.49 obtained for the positive control, α-Hexylcinnamaldehyde, showed greater than a three-fold increase over the control value indicating a positive response in agreement with the historical control for this known weak sensitiser. This confirmed the reliability of this test procedure.

In vivo (LLNA)

Resultsopen allclose all
Key result
Parameter:
SI
Value:
1
Test group / Remarks:
G1Vehicle [DMF]
Key result
Parameter:
SI
Value:
1.18
Test group / Remarks:
G2 1% (w/v) test item in DMF
Key result
Parameter:
SI
Value:
2.03
Test group / Remarks:
G3 10% (w/v) test item in DMF
Key result
Parameter:
SI
Value:
2.38
Test group / Remarks:
G4 25% (w/v) test item in DMF
Key result
Parameter:
SI
Value:
5.49
Test group / Remarks:
G5 25% (v/v) HCA in DMF

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Based on the results of this study, an indication of the classification for the substance is as follows:
Globally Harmonized System of Classification and Labelling of Chemicals (GHS 2017): Not Classified as a Skin Sensitiser
Executive summary:

The Local Lymph Node Assay was conducted to evaluate the skin sensitisation potential of the reaction mass in CBA/J strain mice in compliance with the OECD 429 test guideline.

A preliminary assay was conducted to identify the appropriate test concentrations for the Local Lymph Node Assay for main study.

In the main assay, five groups of mice comprising 5 females per group were selected. Based on the results of the preliminary assay, three groups were treated at dose concentrations of 1%, 10% and 25% (w/v) test item in dimethylformamide for three consecutive days (days 0, 1 and 2) on the dorsum of both ears (25mL per ear). In addition, one group served as the vehicle control and was treated with dimethylformamide and another group served as the positive control and was treated at a concentration of 25% (v/v) HCA (a-hexylcinnamaldehyde) in dimethylformamide.

Animals were observed for clinical reactions. Animals were weighed at the beginning and at the end of treatment. On day 5, the uptake of intravenously injected3H-methyl thymidine into the auricular (local) lymph nodes draining at the site of chemical application was measured (5 hours post-administration) to assess the lymph node proliferative response.

There were no indications of local irritation or systemic toxicity in the test item treated animals. In all mice treated with 25% (v/v) HCA, a local reaction consisting of very slight erythema (score of 1) was observed from days 1 to 4. Group mean body weight of treated animals and positive control group animals were comparable with the mean body weight of the vehicle control group.

Stimulation indices (SI) for the1%, 10% and 25% (w/v)CZ-HABIindimethylformamidetreated groups were 1.18, 2.03 and 2.38, respectively (i.e., less than three-fold increase over mean vehicle control group). Therefore, the test item did not demonstrate dermal sensitisation potential in the local lymph node assay. All criteria for a valid study were met as described in the study plan. The vehicle control and positive control in the definitive LLNA were within the acceptable ranges and fulfilled the requirements for a valid assay.

A positive response for HCA (SI = 5.49) confirmed the reliability of the test procedure.


Based on the results of this study, an indication of the classification for the reaction mass is as follows:

Globally Harmonized System of Classification and Labeling of Chemicals (GHS 2017):        

Not Classified as a Skin Sensitiser