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Description of key information

The substance was not skin sensitizing in the LLNA (OECD 429, GLP).

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of study:
mouse local lymph node assay (LLNA)
Species:
mouse
Strain:
CBA
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Envigo RMS B.V.,lnc ., Postbus 6174, 5960 AD Horst, The Netherlands
- Females (if applicable) nulliparous and non-pregnant:yes
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: Ca. 15 - 25 g
- Housing: single cages
- Diet (e.g. ad libitum): ad libtum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days
- Indication of any skin lesions:

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24°C
- Humidity (%): 30-70%
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12/12
- IN-LIFE DATES: From: 15 Nov 2016 To: 5 Dec 2016 (main study) (Pre-tests for dose-selection and vehicle selection were performed before the main study)
Vehicle:
dimethylformamide
Concentration:
1, 2.5 and 5%
No. of animals per dose:
5
Details on study design:
PRE-SCREEN TESTS:
- Compound solubility: The substance is generally of poor solubility. In DMF, a homogeneous suspension could be achieved.
- Irritation: Concentrations exceeding 5% im DMF were irritating to the skin of mice ears.
- Systemic toxicity:
- Ear thickness measurements:
- Erythema scores:

MAIN STUDY

ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method:3H-Thymidine incorporation
- Criteria used to consider a positive response: SI > 3

TREATMENT PREPARATION AND ADMINISTRATION: Test substance was weighed and mixed with the vehicle shortly before treatment. Homogeneity was achieved by stirring with a magnetic stirrer.
Parameter:
SI
Value:
1.52
Test group / Remarks:
1%
Parameter:
SI
Value:
1.2
Test group / Remarks:
2.5%
Parameter:
SI
Value:
1.41
Test group / Remarks:
5%
Parameter:
EC3
Remarks on result:
not determinable
Cellular proliferation data / Observations:
CELLULAR PROLIFERATION DATA
See table 2

DETAILS ON STIMULATION INDEX CALCULATION

EC3 CALCULATION
An EC3 could not be calculated because there was no dose-dependent increase and no values above 3.

CLINICAL OBSERVATIONS:

BODY WEIGHTS
See table 4

Table 1: 3H-Thymidine incorporation

  DPM / lymph node pair S.D. Stimulation Index
vehicle DMF 982.9 232.8 1.00
1% in DMF 1493.9 331.5 1.52
2.5% in DMF 1184.0 384.2 1.20
5% in DMF 1389.7 167.8 1.41

Table 2: Cell counts

Mean [Counts
/ lymph node pair]
S.D. Stimulation Index
vehicle DMF 11'946'000 1'401'690 1.00
1% in DMF 14'852'400 3'134'248 1.24
2.5% in DMF 13'856'400 2'179'411 1.16
5% in DMF 14'186'400 2'122'103 1.19

Table 3: Lymph node weights

Mean [mg] S.D. Stimulation Index
vehicle DMF 5.2 0.5 1.00
1% in DMF 5.7 0.9 1.08
2.5% in DMF 5.5 0.7 1.06
5% in DMF 5.6 0.9 1.07

Table 4: Body weights

Mean Weight d0 S.D. Mean Weight d5 S.D.
vehicle DMF 19.8 1.1 20.7 1.2
1% in DMF 19.3 0.7 20.2 0.8
2.5% in DMF 19.7 0.5 20.7 0.5
5% in DMF 18.8 1.1 19.8 1.2
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. The stimulation indices in the LLNA (OECD 429) did not show a dose dependent increase. No EC3 could be established. As a result the substance is not considered to be classified for skin sensitization under Regulation (EC) No. 1272/2008,as amended for the seventh time in Regulation (EC) No 2015/1221.