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Description of key information

RA OECD 429: negative

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2007-05-15 to 2007-05-30
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Version / remarks:
04-2002
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of study:
mouse local lymph node assay (LLNA)
Species:
mouse
Strain:
CBA
Remarks:
CBA/CaOlaHsd
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Netherlands B.V., NL 5960 AD Horst
- Age: 7-8 weeks at beginning of acclimatisation
- Weight at study initiation: 17.4 - 20 g
- Housing: single in Makrolon type-1 cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: not further specified

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 30-88
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: Days 1 - 5
Vehicle:
dimethylformamide
Concentration:
pre test for signs of irritation: 2.5, 5, 10 and 25 %
main test: 5, 10 and 25 %
No. of animals per dose:
pre test: 2 f
main test: 5 f per group (3 test groups, 1 control group)
Details on study design:
RANGE FINDING TESTS
To determine the highest non-irritant test concentration or the highest technically applicable concentration, a pretest was performed in two mice with test item concentrations of 2.5, 5, 10 and 25 % on one ear each. No irritation effects were observed at these concentrations after a single application.

MAIN STUDY
Criteria used to consider a positive response: 3-fold greater response at one concentration in SI than control animals

TREATMENT PREPARATION AND ADMINISTRATION
Each test group of mice was treated by topical (epidermal) application to the dorsal surface of each ear lobe (left and right) with different test item concentrations of 5, 10 and 25% (w/v) in dimethylformamide. The application volume of 25 uL was spread over the entire dorsal surface (0 - 8 mm) of each ear lobe once daily for three consecutive days. A further group of mice was treated with an equivalent volume of the relevant vehicle alone (control animals).
Five days after the first topical application, all mice were administered with 250 uL of 78.8 uCi/mL 3H-methyl thymidine (3HTdR) by intravenous injection via a tail vein. Prior to the first application of the test item and prior to treatment with 3HTdR the ear thickness was determined using a micrometre.
The level of 3HTdR incorporation was then measured on a ß-scintillation counter. Similarly, background 3HTdR levels were also measured in two 1 mL-aliquots of 5 % trichloroacetic acid. The ß-scintillation counter expresses 3HTdR incorporation as the number of radioactive disintegrations per minute (DPM).
The validation/positive control experiment was performed with alpha-Hexylcinnamaldehyde in acetone:olive oil (4+1) in mice.
Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)
Statistics:
Mean values and standard deviations were calculated in the body weight tables. A statistical analysis was conducted for assessment of the dose-response relationship, and the EC3 value was calculated according to the equation EC3 = (a-c) [(3-d)/(b-d)] + c, where EC3 is the estimated concentration of the test item required to produce a 3-fold
increase in draining lymph node cell proliferative activity; (a, b) and (c, d) are respectively the co-ordinates of the two pair of data lying immediately above and below the S.I. value of 3 on the local lymph node assay dose response plot.
Positive control results:
Conc. (%, w/v) SI
5 1.03
10 1.59
25 1.68
Key result
Parameter:
SI
Value:
1.03
Test group / Remarks:
5%
Key result
Parameter:
SI
Value:
1.59
Test group / Remarks:
10%
Key result
Parameter:
SI
Value:
1.68
Test group / Remarks:
25%
Key result
Parameter:
EC3
Remarks:
% (w/v)
Remarks on result:
not determinable
Remarks:
All SI were < 3
Interpretation of results:
GHS criteria not met
Conclusions:
The test item was not a skin sensitiser in this assay.
Endpoint:
skin sensitisation: in vitro
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin sensitisation study does not need to be conducted because adequate data from an in vivo skin sensitisation study are available
Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
For this endpoint information from structural similar compounds is available. The studies for these similar compounds were performed according to GLP and the methods applied are fully compliant with OECD TG 429. See chapter 13 report for a more detailed justification.
Reason / purpose:
read-across source
Key result
Parameter:
SI
Value:
1.03
Test group / Remarks:
5 %
Key result
Parameter:
SI
Value:
1.59
Test group / Remarks:
10 %
Key result
Parameter:
SI
Value:
1.68
Test group / Remarks:
25 %
Key result
Parameter:
EC3
Remarks on result:
not determinable
Remarks:
All SI were < 3
Interpretation of results:
GHS criteria not met
Conclusions:
For this endpoint a one-to-one read across was performed to a chemical similar compound of the same chemical class with a comparable phys. chem. profile and similar response in biological assays. The relevant study was performed according to GLP and the methods applied are fully compliant with OECD TG 429. The chemical analogue was not sensitising in this in vivo assay.
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

Based on the provided information there is no need to classified for skin sensitization according to the EU Regulation (EC) No 1272/2008 on Classification, Labelling and Packaging of Substances and Mixtures.