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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
From 02 May 2007 to 23 May 2007
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study (OECD TG 429)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2007
Report Date:
2007

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent

In vivo test system

Test animals

Species:
mouse
Strain:
CBA
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
-strain: CBA/CaOlaHsd
- Source: Harlan Netherlands, Horst, The Netherlands
- Age at study initiation: 7-12 weeks (beginning of acclimatisation)
- Weight at study initiation: 18.9 g (18.0 g - 21.0 g)
- Housing: individually, Makrolon Type I with mesh top
- Diet: pelleted standard diet, ad libitum
- Water: tap water (ad libitum)
- Acclimation period: yes (acclimatization period not given)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 30-96 % (this deviation from the study plan did not affect the validity of the study)
- Photoperiod (hrs dark / hrs light): 12 hrs/ 12 hrs

Study design: in vivo (LLNA)

Vehicle:
propylene glycol
Concentration:
0 %, 2.5 %, 5 %, 10 %
No. of animals per dose:
4 females per dose group,
2 females in the pre-test
Details on study design:
RANGE FINDING TESTS:
- non GLP
- Compound solubility: 10 % (w/v) was the highest concentration at which the test item could be suspended in propylene glycol so that an applicable test item formulation was obtained. Higher concentrations could also not be achieved with other vehicles.
- Irritation: Due to the intense red colour of the test item local irritation reactions such as ear redness could not be detected.
- Lymph node proliferation response: no data

MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: LLNA
- Criteria used to consider a positive response: 1: exposure to at least one concentration of the test item resulted in an incorporation of 3H-methyl thymidine at least 3-fold or greater than that recorded in control mice as indicated by the stimulation index
2: data are compatible with a conventional dose response, although allowance must be made for either local toxicity or immunological suppression

TREATMENT PREPARATION AND ADMINISTRATION:
- individual preparation of weight volume dilutions using a magnetic stirrer as homogenizer
- test item preparations were made freshly before each dosing occasion
- 25 µl were spread over the entire dorsal surface of each ear lobe once daily for three consecutive days
Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)
Statistics:
- calculation of mean values and standard deviations for body weight .

Results and discussion

Positive control results:
Stimulation indices of 2.43, 4.07 and 4.88 were determined with the positive control substance at concentrations of 5%, 10% and 25% (w/v), respectively, in acetone:olive oil (4+1). An EC3 value of 6.7% (w/v) was calculated.

In vivo (LLNA)

Resultsopen allclose all
Parameter:
SI
Remarks on result:
other: Stimulation indices were all below 3. The following SI were calculated: 2.5 % test item: 1.28 5 % test item: 1.30 10 % test item: 0.78
Parameter:
other: disintegrations per minute (DPM)
Remarks on result:
other: see Remark
Remarks:
The DPM were measured for the pooled lymph nodes of each treatment group (8 lymph nodes per dose group): Background I: 21.62 dpm Background II: 33.29 dpm Control group: 1430.00 dpm 2.5 % test item: 1824.51 dpm 5 % test item: 1850.46 dpm 10 % test item: 1119.37 dpm

Any other information on results incl. tables

The animals did not show any clinical signs during the course of the study and no cases of mortality were observed. The body weight of the animals was within the normal range. Due to the intense red colour of the test item local irritation reactions such as ear redness could not be detected. Calculation of the EC3 value was not performed, because no test concentration produced a SI of 3 or higher.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test substance was not sensitising in this LLNA in concentrations up to 10 % (w/v) in propylene glycol, the highest technically achievable concentration.
Executive summary:

In the study the test item suspended in propylene glycol was assessed for its possible contact allergenic potential.

For this purpose a local lymph node assay was performed using test item concentrations of 2.5 %, 5 %, and 10 % (w/v).

The animals (4 female mice/dose grouop) did not show any clinical signs during the course of the study and no cases of mortality were observed. In this study Stimulation Indices (S.I.) of 1.28, 1.30 and 0.78 were determined with the test item at concentrations of 2.5 %, 5 % and 10 % (w/v) in propylene glycol, respectively. The results obtained with the positive control confirmed the validity of the test.

The test item was not a skin sensitiser in this assay.