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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:
2006-03-07 to 2006-03-21
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well documented, GLP-compliant study conducted according to OECD Guideline 429. No deviations were recorded.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2006
Report Date:
2006

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 lymphnode assay (LLNA)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): T1310 (chemical name: 4-piperidinecarboxylic acid hydrochloride, CAS number: 005984-56-5)
- Substance type: no data
- Physical state: white solid
- Analytical purity: 100%
- Purity test date: no data
- Lot/batch No.: 00465047 RT001310G4A851
- Expiration date of the lot/batch: 2006-06-30
- Stability under test conditions: Not indicated by the sponsor.
- Storage condition of test material: at room temperature
- Other:
Solubility in water: 320 g/L

In vivo test system

Test animals

Species:
mouse
Strain:
other: CBA/CaOlaHsd
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Netherlands, B.V. Postbus 6174, NL - 5960 AD Horst / The Netherlands
- Age at beginning of acclimatization: 6 - 12 weeks
- Weight at study initiation: 15.6 to 21.7 g (Mean 18.5 g +-1.7)
- Housing: Single caging; Makrolon Type I, with wire mesh top and granulated soft wood bedding
- Diet: pelleted standard diet, ad libitum
- Water: tap water, ad libitum
- Acclimation period: under test conditions after health examination. Only animals without any visible signs of illness were used for the study.


ENVIRONMENTAL CONDITIONS
- Temperature (deg C): 22 +/- 3 °C
- Humidity (%): 30-70%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 2006-03-15 To: 2006-03-21

Study design: in vivo (LLNA)

Vehicle:
other: Ethanol:deionised water, 70:30% (v/v)
Concentration:
concentrations of 1, 5 and 10% (w/v) in Ethanol:deionised water (7+3), respectively.
No. of animals per dose:
2 females (pre-test); 16 females (main study)
4 animals per group
Details on study design:
RANGE FINDING TESTS:
- Compound solubility: concentrations of 1.25, 2.5, 5 and 10% (w/v)
- Irritation: No irritation effects were observed at these concentrations after a single application.
- Lymph node proliferation response: no data

MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: 3HTdR incorporation
- Criteria used to consider a positive response: A test item is regarded as a sensitiser in the LLNA if the following criteria are fulfilled:
First, that exposure to at least one concentration of the test item resulted in an incorporation of 3HTdR at least 3-fold or greater than that recorded in control mice, as indicated by the stimulation index.

Second, that the data are compatible with a conventional dose response, although allowance must be made (especially at high topical concentrations) for either local toxicity or immunological suppression.

TREATMENT PREPARATION AND ADMINISTRATION:
Three groups each of four female mice were treated with different concentrations of the test item by topical application at the dorsum of each ear lobe (left and right) on three consecutive days.
Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)
Statistics:
The mean values and standard deviations were calculated for the body weights.

Results and discussion

Positive control results:
The Disintegrations Per Minute (DPM) :
5% - 6802.45
10 % - 15166.7
25% - 29443.2
DPM per lymph node (Number of lymph nodes: 8) :
5% - 846.4
10% - 1892.0
25% - 3676.5

The stimulation indices
5% - 6.08
10% - 13.59
25% - 26.41

The EC3 value could not be calculated, since all SI's were above 3.

In vivo (LLNA)

Resultsopen allclose all
Parameter:
SI
Remarks on result:
other: The stimulation indices were 1.61, 1.31 and 1.20 for the 1, 5 and 10% w/v groups, respectively.
Parameter:
other: disintegrations per minute (DPM)
Remarks on result:
other: The Disintegrations Per Minute (DPM) 1% - 3561.93 5% - 2902.48 10% - 2646.47 Number of lymph nodes: 8 The DPM per lymph node were 1% - 442.7 5% - 360.2 10% - 328.2

Any other information on results incl. tables

The EC3 value could not be calculated, since all SI's were below 3.

Viability/Mortality:

No deaths occurred during the study period.

Clinical Signs:

No symptoms of local toxicity at the ears of the animals and no systemic findings were observed during the study period.

Body Weights:

The body weight of the animals, recorded prior to the first application and prior to treatment with 3HTdR, was within the range commonly recorded for animals of this strain and age.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The test item T1310 was not a skin sensitiser under the described conditions. Therefore, the test item is considered not to be classified.