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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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP-compliant guideline study, available as unpublished report, no restrictions, fully adequate for assessment.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Qualifier:
according to
Guideline:
EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)
Qualifier:
according to
Guideline:
EPA OPPTS 870.2600 (Skin Sensitisation)
GLP compliance:
yes (incl. certificate)
Type of study:
mouse local lymph node assay (LLNA)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Tetraoctyltin, TOT
- Substance type: organometallic
- Physical state: slightly yellowish liquid
- Analytical purity: 86.0%
- Lot/batch No.: UAKW060
- Expiration date of the lot/batch: 31 October 2011
- Storage condition of test material: ambient temperature

In vivo test system

Test animals

Species:
mouse
Strain:
other: CBA/J
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories
- Age at study initiation: 8-12 weeks
- Housing: group housing in macrolon cages (maximally 5/cage), from the start of treatment animals were housed individually (macrolon cages)
- Diet: standard diet ad libitum (Rat and Mouse no.3 breeding diet RM3).
- Water: Domestic mains tap water, ad libitum.
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 45-65
- Air changes (per hr): ca. 10
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (LLNA)

Vehicle:
acetone/olive oil (4:1 v/v)
Concentration:
0%, 25%, 50% and 100%
No. of animals per dose:
5 females/dose
Details on study design:
RANGE FINDING TESTS:
In a dose range finding test two mice were treated with a 50% or 10% concentration of the substance in vehicle for three consecutive days in a similar manner as described for the main test. These mice were observed for signs of toxicity and/or skin irritation as a result of this treatment. Based on the dose range finding test, concentrations of 100% (undiluted), 50% and 25% were selected for the main study.
Balb/c mice were used in the dose range finding test, because spare mice of the CBA/J strain were not available. It was assumed that skin irritation and dermal absorption and/or toxicity should be similar between strains of the same species, and the results obtained in Balb/c mice should be suitable for extrapolation to CBA/J mice. As a consequence of the decision to use mice of another strain for the dose range finding test, two different mice strains were present in the animal room during (a part of) the acclimatisation period until the start of the main study.

MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: LLNA
- Criteria used to consider a positive response: The present Local Lymph Node Assay was conducted simultaneously with a LLNA reliability study. The results of the vehicle control group that is part of the reliability check was used for evaluation of the data of test groups. The 3H-thymidine incorporation was compared between the different treatment groups. Changes in 3H-thymidine incorporation in the test substance treatment groups were evaluated and expressed as stimulation index (SI) relative to the vehicle control group. The SI is obtained by dividing the individual values of the 3H-thymidine incorporation, expressed as DPM (corrected for background), with the mean proliferation of the vehicle control group. Since also the DPM-data of the vehicle-treated group are divided with its own mean DPM-data, this results in an average SI for vehicle-treated controls of 1. The decision process with regard to a positive response includes a stimulation index ≥3 together with consideration of dose response and statistical analyses based on the test guideline and the recommendations done by ICCVAM.

TREATMENT PREPARATION AND ADMINISTRATION:
The test substance was applied topically once daily for three consecutive days on the dorsum of both ears (by means of a pipette 25 µl on each ear). Immediately after application, the test substance was spread over the dorsum of the ear with the tip of the pipette. Each animal received a total amount of 50 µL per dosing.
Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)
Statistics:
Statistical evaluation of the data (body weights and 3H-thymidine incorporation) was performed by one-way ANOVA, followed by Dunnett’s multiple comparison tests. Probability values of p<0.05 were considered significant.

Results and discussion

In vivo (LLNA)

Resultsopen allclose all
Parameter:
SI
Value:
1
Test group / Remarks:
0%
Parameter:
SI
Value:
1.96
Test group / Remarks:
25%
Parameter:
SI
Value:
4.32
Test group / Remarks:
50%
Parameter:
SI
Value:
7.9
Test group / Remarks:
100%
Parameter:
other: disintegrations per minute (DPM)
Remarks on result:
other: 1400, 2740, 6048 and 11060 DPM for 0%, 25%, 50% and 100% groups, respectively

Any other information on results incl. tables

No signs of local irritation or other clinical signs were observed in any of the animals during the study period. No aberrant body weights or body weight gains were observed, and no statistical significant difference was found between the vehicle and the positive control group.

Applicant's summary and conclusion

Interpretation of results:
sensitising
Remarks:
Migrated information
Conclusions:
Since the SI was > 3 after 50% tetraocyltin treatment, the limiting value required for classification as a skin sensitiser, it was concluded that tetraocyltin should be regarded as a skin sensitiser when applied at concentrations of 50% (v/v) and higher.