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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:
25/10/2006 - 20/11/2006
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

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

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Version / remarks:
OECD Guidelines for Testing of Chemicals, Section 4, Health Effects, No. 429, "Skin Sensitisation: Local Lymph Node Assay", Paris Cedex, April 2002.
Qualifier:
according to
Guideline:
EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)
Version / remarks:
European Community (EC), Council Directive 67/548/EEC, Annex V, Part B, Methods for the Determination of Toxicity, as last amended by Commission Directive 2004/73/EC, B.42: "Skin Sensitisation: Local Lymph Node Assay", April 2004.
Qualifier:
according to
Guideline:
EPA OPPTS 870.2600 (Skin Sensitisation)
Version / remarks:
Environmental Protection Agency (EPA): Health Effects Guidelines OPPTS 870.2600. "Skin Sensitisation", March 2003
GLP compliance:
yes (incl. certificate)
Type of study:
mouse local lymph node assay (LLNA)

Test material

Reference
Name:
Unnamed
Test material form:
solid: particulate/powder
Details on test material:
- Description: dark purple powder
- Solubility in the water: <= 0.412 g/L
- Melting point: > 250 °C
- Boiling point: > 250 °C
- Explosion: not explosion
- Log Pow: >= 3.3
- Test substance storage: at room temperature in the dark, 20°C, dry store
- Stability under storage conditions: stable
Specific details on test material used for the study:
pH (1% in water, indicative range) 8.1-8.3 (determined at NOTOX)
Stability at higher temperatures Maximum temperature 75°C, maximum duration 48 hours

In vivo test system

Test animals

Species:
mouse
Strain:
CBA
Sex:
female
Details on test animals and environmental conditions:
Species:
Mouse, CBA strain, inbred, SPF-quality. Recognized by the international guideline as the recommended test system (e.g. OECD, EC, EPA). Source: Charles River France, L'Arbresle Cedex, France

Number of animals:
20 females (nulliparous and non-pregnant), five females per group

Age and bodyweight:
Yound adult animals (approx. 11 weeks old) were selected. Body weight variation was within +- 20% of the sex mean.

Identification:
tail mark with marker pen

Health inspection:
A health inspection was performed prior to treatment, to ensure that the animals are in a good state of health. Special attention was paid to the ears, which were intact and free from any abnormality.

Reliability check:
the results of a reliability test with Hexylcinnamic aldehyde, performed not more than 6 months previously or 2 month afterwards, are summarized in the Appendix. Similar procedures were used in the reliability tests and in the study

Study design: in vivo (LLNA)

Vehicle:
dimethylformamide
Remarks:
Merck, Darmstadt, Germany
Concentration:
The results of the epidermal exposures for the selection of highest test substance concentration to be tested in the main studey are described in the table. Based on the results, the highest test substance concentration selected for the main study was a 10% concentration.
No. of animals per dose:
Three groups of five animals were treated with one test substance concentration per group. The highest test substance concentration was selected from the preliminary irritation study. One group of five animals was treated with vehicle.

Results and discussion

In vivo (LLNA)

Results
Key result
Parameter:
EC3
Value:
ca. 13.1
Variability:
An EC3 value of 13.1% was calculated using the linear interpolation
Cellular proliferation data / Observations:
DETAILS ON STIMULATION INDEX CALCULATION
The SI values calculated for the substance concentrations 2.5, 5 and 10% were 1.2, 2.7 and 2.4 respectively.

EC3 CALCULATION
Since there was no indication that the test substance could elicit an SI >= 3 when tested up to 10%, it was established that the EC3 value (if any) exceeds 10%.

CLINICAL OBSERVATIONS:

BODY WEIGHTS
Body weights and body weight gain of experimental animals remained in the same range as controls over the study period. The slight body weight loss, noted in some animals, was considered not toxicologically significant.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The SI values calculated for the substance concentrations 2.5, 5 and 10% were 1.2, 2.7 and 2.4 respectively.
Since there was no indication that the test substance could elicit an SI >= 3 when tested up to 10%, it was established that the EC3 value (if any) exceeds 10%.

The six month reliability check with Hexylcinnamic aldehyde indicates that the Local Lymph Node Assay as performed at NOTOX is an appropriate model for testing for contact hypersensitivity.
Executive summary:

Based on the results:

- according to the recommendations made in the test guidelines, SXJUL2006 would not be regarded as skin sensitizer.

- according to the Globally Harmonized System of Classification and Labeling of Chemicals (GHS) of the United Nations (New York and Geneva, 2003), SXJUL2006 does not have to be classified for sensitization by skin contact

- according to the EC criteria for classification and labeling requirements for dangerous substances and preparations (Council Directive 67/548/EEC), SXJUL2006 does not have to be classified and has no obligatory labeling requirement for sensitization by skin contact.