Registration Dossier

Toxicological information

Skin sensitisation

Currently viewing:

Administrative data

Endpoint:
skin sensitisation, other
Remarks:
adequate data from an LLNA study is available
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
2011-03-08 to 2011-03-23
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2011
Report Date:
2011

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: OECD Guideline 442B (Skin Sensitisation: Local Lymph Node Assay: BrdU-ELISA
GLP compliance:
yes (incl. certificate)
Type of study:
mouse local lymph node assay (LLNA)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid: viscous

In vivo test system

Test animals

Species:
mouse
Strain:
CBA
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Winkelmann GmbH, Borchen, Germany
- Age at study initiation: approx. 12 weeks at start of the main experiment
- Weight at study initiation: 23.3 ± 1.6 g at start of the main experiment
- Housing: Single housed in Makrolon - cages Type III
- Diet (e.g. ad libitum): Altromin 1324 ad libitum
- Water (e.g. ad libitum): ad libitum, tap water
- Acclimation period: Before the main experiment was started, the animals had an acclimatisation period after delivery of 16 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 30 - 70
- Air changes (per hr): 8 TIMES/HOUR
- Photoperiod (hrs dark / hrs light): 2 hours dimmed Iight, 12 hours dark

IN-LIFE DATES: From: To: 2011-03-01 to 2011-03-23

Results and discussion

Positive control results:
For the reference substance a Stimulation Index of 3.09 was determined indicating the adequate function of the test system.

In vivo (LLNA)

Results
Parameter:
SI
Remarks on result:
other: Test substance: 50 % SI=3.37 75 % SI=6.44 100 % SI=7.11 Negative control: SI=1.0

Any other information on results incl. tables

Pilot Experiment

At the daily clinical observation the animals did not show any visible symptoms of systemic toxicity. Animals showed slightly decreased or nearly unchanged body weights. Only slight local irritation was observed in the highest concentration group but ear thickness values were unaffected by the treatment with the 100 %, 75 % and 50 % (w/w) concentrations of the test substance. As no excessive local irritation and no ear thickness increase was observed in the pilot experiment the same concentrations were selected for the main experiment.

Main Experiment

Visible symptoms of systemic toxicity caused by the test substance were not observed. No unusual finding occurred. The body weight of the animals was slightly decreased. Only slight symptoms of local irritation at the ears of some animals in the 75 % and 100 % test substance concentration groups and the positive control group were observed.

Test substance: 50 % SI=3.37; 75 % SI=6.44; 100 % SI=7.11

Negative control: SI=1.0

Positive control: SI=3.09

Applicant's summary and conclusion

Interpretation of results:
sensitising
Remarks:
Migrated information Criteria used for interpretation of results: other: CLP, EU GHS (Regulation (EC) No 1272/2008)
Conclusions:
In this Local Lymph Node Assay the test substance is a dermal sensitizer.
Executive summary:

In a dermal sensitization study with the test substance hexanoic acid, 3,5,5-trimethyl-, tin (2+)salt (2:1) in acetone/olive oil (4:1, v/v), groups of 4 female CBA mice were tested using the LLNA method according to the OECD Guideline 442B, July 2010. BrdU was measured by ELISA using a commercial kit.

STIMULATION INDICES of 3.37, 6.44 and 7.11 were determined with the test substance at concentrations of 50 %, 75 % and 100 % (w/w) in acetone:olive oil, 4:1 (v/v), respectively.

 

Positive control substance was alpha hexyl cinnamic aldeyde, which gave a positive result (SI = 3.09 at a concentration of 25 % in acetone:olive oil, 4:1 (v/v).

A result is regards as positive when the SI (Stimulation Indes) is ≥ 1.6.

 

Based on these criteria, the test substance was found to be a sensitizer when tested from 50 % up to 100 %.

 

In this study, hexanoic acid, 3,5,5-trimethyl-, tin (2+)salt (2:1) is a dermal sensitizer.

According to the GHS Regulation (EC) No 1272/2008, 2nd ATP, (No 286/2011) sensitizers may be allocated to one of two sub-catogories; sub-category 1A, strong sensitisers, or subcategory 1B for other skin sensitisers. The EC3-values are used for evaluation of data from a standard LLNA, EC3-values of≤2 % are assigned to category 1A, and EC3-values of > 2 % to category 1B, respectively.

For hexanoic acid, 3,5,5-trimethyl-, tin (2+)salt (2:1) the reported SI values were 3.37, 6.44 and 7.11 for test concentrations of 50 %, 75 %, and 100%, respectively. However, no EC3-value was derived in the study report.

Hence, based on the observed dose response curve, it can be assumed that the EC3 will be well beyond the value of > 2 % and thus leading to a classification as moderate sensitizer (category 1B).