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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:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2014
Report date:
2014

Materials and methods

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

Test material

Constituent 1
Chemical structure
Reference substance name:
Trimethyl benzene-1,2,4-tricarboxylate
EC Number:
219-547-3
EC Name:
Trimethyl benzene-1,2,4-tricarboxylate
Cas Number:
2459-10-1
Molecular formula:
C12H12O6
IUPAC Name:
trimethyl benzene-1,2,4-tricarboxylate
Test material form:
liquid: viscous
Details on test material:
- Name of test material (as cited in study report): 1,2,4-Trimethylbenzenetricarboxylate
- Physical state: liquid, viscous, amber
- Analytical purity: 100.00 area-% (233 nm); 99.99 area-% (207 nm)
- Lot/batch No.: 3723340
- Homogeneity: The homogeneity of the test substance is assumed by the analytical laboratory
- Stability under test conditions: the stability of the test substance under storage conditions over the test period was guaranteed until 12 Feb 2015 by the sponsor, and the sponsor holds this responsibility
- Storage condition of test material: room temperature

In vivo test system

Test animals

Species:
mouse
Strain:
CBA/Ca
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories B.V., Horst / The Netherlands
- Age at study initiation: Pre-test: 9 - 10 weeks (beginning of treatment); Main study: 8 - 9 weeks (beginning of treatment)
- Housing: group (Maktolon Type II (pre-test) / III (main study)
- Diet (e.g. ad libitum): 2018C Teklad Global 18% protein rodent diet (certified), ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: At least 5 days prior to the start of dosing

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 + 2°C
- Humidity (%): approx. 45 - 65 %
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (LLNA)

Vehicle:
dimethylformamide
Concentration:
10, 25 and 50%
No. of animals per dose:
5
Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)
Statistics:
The mean values and standard deviations were calculated in the body weight tables, for the ear weights, the lymph node weights and lymph node cell count, and for the DPM values (group mean DPM ± standard deviation).
A statistical analysis was conducted on the DPM values, the ear weights, the lymph node weights and the lymph node cell count to assess whether the difference was statistically significant between the test item groups and negative control group. For all statistical calculations SigmaStat for Windows (Version 2.0) was used. A One-Way-Analysis-of-Variance was used as a statistical method. In case of significant results of the One-Way-ANOVA, multiple comparisons were
performed with the Dunnett test. Statistical significance was set at the five per cent level (p < 0.05).
The Dean-Dixon-Test was used for detection of possible outliers (performed with Microsoft Excel 2007). However, both biological and statistical significance were considered together.

Results and discussion

In vivo (LLNA)

Resultsopen allclose all
Remarks on result:
other: The EC3 value could not be calculated, since all S.I.´s are below the threshold value of 3.
Parameter:
SI
Value:
1
Test group / Remarks:
Vehicle control
Parameter:
SI
Value:
1.05
Test group / Remarks:
Test group - 10% concentration
Parameter:
SI
Value:
0.96
Test group / Remarks:
Test group - 25% concentration
Parameter:
SI
Value:
0.69
Test group / Remarks:
Test group - 50% concentration

Any other information on results incl. tables

Test item concentration

Group Calculation

Mean DPM per animal (2 lymph nodes)a)

SD

S.I.

Vehicle Control Group (DMF)

1873.9

758.7

1.00

10% 1,2,4-Trimethylbenzenetricarboxylate

1975.5

541.0

1.05

25% 1,2,4-Trimethylbenzenetricarboxylate

1791.3

482.2

0.96

50% 1,2,4-Trimethylbenzenetricarboxylate

1301.7

391.9

0.69

a)Mean DPM/animal was determined by dividing the sum of the measured values from lymph nodes of all

animals within a group by the number of animals in that group (5 animals)

The EC3 value could not be calculated, since all S.I.´s are below the threshold value of 3.

No deaths occurred during the study period.

No signs of systemic toxicity or any signs of local skin irritation were observed during the study period.

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.

The measured lymph node weights and –cell counts of all animals treated were recorded after sacrifice. A statistically significant or biologically relevant increase in lymph node weights or – cell counts was not observed in any of the test item treated groups in comparison to the vehicle control group. For BALB/c mice, a cut-off value for the lymph node cell count index of 1.55 was reported for a positive response. The indices determined for the lymph node cell count did not exceed this threshold.

The measured ear weight of all animals treated was recorded on test day 6 (after necropsy). A biologically relevant or statistically significant increase in ear weights was not observed. Furthermore, the cut-off value (1.1) of the ear weight index for a positive response regarding ear skin irritation reported for BALB/c mice was not exceeded in any of the treated groups.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The test item 1,2,4-Trimethylbenzenetricarboxylate was not a skin sensitiser under the test conditions of this study.