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Administrative data

Description of key information

A LLNA is available on Tricyclodecane dimethanol dimethacrylate and showed positive results.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
21 May 2015 - 06 July 2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Reference:
Composition 1
Qualifier:
according to
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of study:
mouse local lymphnode assay (LLNA)
Test material information:
Composition 1
Species:
mouse
Strain:
CBA
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: breeder: Janvier, Le Genest-Saint-Isle, France.
- Age at study initiation: at the beginning of the treatment period, the animals of the preliminary test were approximately 12 weeks old and the animals of the main test were approximately 8 weeks old.
- Mean body weight at study initiation: at the beginning of the treatment period, the animals of the preliminary test had a mean body weight of 22.4 g (range: 21.3 g to 23.9 g) and the animals of the main test had a mean body weight of 20.5 g (range: 17.3 g to 23.1 g).
- Fasting period before study: no
- Housing: the animals were housed by group of two (preliminary test) or four (main test) in polycarbonate cages (Tecniplast 1145T, 435 cm2) .
- Diet: SSNIFF R/M-H pelleted diet (free access)
- Water: tap water filtered with a 0.22 µm filter (free access)
- Acclimation period: 6 days before the beginning of the treatment period.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2°C
- Humidity (%): 50 ± 20%
- Air changes (per hr): approximately 12 cycles/hour of filtered, non-recycled air
- Photoperiod (hrs dark / hrs light): 12 h/12 h.

IN-LIFE DATES: 16 June 2015 to 06 July 2015.
Vehicle:
acetone/olive oil (4:1 v/v)
Concentration:
0, 5, 10, 25, 50, 100%.
No. of animals per dose:
4 females per dose.
Details on study design:
RANGE FINDING TESTS:
The maximum concentration tested in the main test was selected according to the criteria specified in the OECD Guidelines and on the basis of the data that was obtained in the preliminary test:
- the vehicle was selected on the basis of producing a homogeneous preparation suitable for application of the test item,
- the concentrations were selected from the concentration series 100%, 50%, 25%, 10%, 5%, 2.5%, 1%, 0.5%, etc,
- the maximum concentration of the test item was selected to avoid overt systemic toxicity and excessive local skin irritation the latter being defined by an increase of the ear thickness = 25%.

MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: murine Local Lymph Node Assay
- Criteria used to consider a positive response: stimulation Index SI >= 3 and dose-relationship; additional consideration of ear thickness.

TREATMENT PREPARATION AND ADMINISTRATION:
- Treatment preparation: The test item was prepared at the chosen concentrations in the vehicle.
The positive control was dissolved in AOO at the concentration of 25% (v/v).
- Administration:
On Days 1, 2 and 3, a dose-volume of 25 µL of the control or dosage form preparations was applied to the dorsal surface of both ears, using an adjustable pipette fitted with a plastic tip.
In order to avoid licking and to ensure an optimized application of the test materials, the animals were placed under light isoflurane anesthezia during the administration.
No massage was performed but the tip was used to spread the preparation over the application sites. No rinsing was performed between each application.
Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)
Statistics:
no
Positive control results:
The threshold positive value of 3 for the SI was reached in the positive control group.

Key result
Parameter:
EC3
Value:
47
Parameter:
SI
Value:
0.82
Test group / Remarks:
5%
Parameter:
SI
Value:
0.77
Test group / Remarks:
10%
Parameter:
SI
Value:
1.18
Test group / Remarks:
25%
Parameter:
SI
Value:
3.27
Test group / Remarks:
50%
Parameter:
SI
Value:
3.97
Test group / Remarks:
100%

Preliminary test:

Mortality and clinical signs: No unscheduled deaths and no clinical signs were observed during the observation period. Body weights

were unaffected by the test item treatment.

Ear thickness measurements and local irritation :

No local reactions on the ears were observed in any animals.

At the concentrations of 25, 50 and 100%, increases in ear thickness were noted. These slight increases in ear thickness ranged from 10% to 25% and suggested of a slight irritancy of the test item at these concentrations. However, as the acceptance limit of 25% was not reached, these concentrations were not rejected for testing on the main test.

Increase in ear thickness at the lowest tested concentration (i.e. 10%) was below 10%.

The highest concentration retained for the main test was therefore 100%.

Results of the main test:

The results are presented in the following table:

 

Treatment

Concentration

(%)

Irritation level

Stimulation Index

(SI)

Test item

5

I

0.82

Test item

10

I

0.77

Test item

25

I

1.18

Test item

50

I

3.27

Test item

100

I

3.97

HCA

25

-

8.59

-: not recorded.

I: non irritant (increase in ear thickness < 10%).

HCA: a-hexyl cinnamaldehyde. 

Interpretation of results:
Category 1B (indication of skin sensitising potential) based on GHS criteria
Conclusions:
The test item was tested as a solution after preparation at concentrations of 5, 10, 25, 50 and 100% in Acetone/Olive Oil (4/1; v/v).
The test item gave a positive result in the murine Local Lymph Node Assay, indicative of skin sensitization properties.
According to the EC3 value obtained (47%), the test item should be considered as a weak sensitizer.
Executive summary:

The objective of this study was to evaluate the potential of the test item to induce contact hypersensitivity, using the murine Local Lymph Node Assay (LLNA). This study was conducted in compliance with the principles of Good Laboratory Practice.

A solution was obtained at the highest concentration of 50% in Acetone/Olive Oil (4/1; v/v).

In the main test, no unscheduled deaths and no clinical signs were observed during the observation period.Body weights were unaffected by the test item treatment. No local reactions on the ears were observed in any animals. In all test item-treated groups, the increase in ear thickness was below 10%. The test item was therefore considered as non irritant. As the acceptance limit of 25% was not reached at any concentrations, no bias in the results of proliferation measurements linked to an excessive irritant potential was considered.

The stimulation index (SI) of the positive control was > 3; this experiment was therefore considered valid. A significant lymphoproliferation (SI > 3) was noted at the concentrations = 50% of the test item. In the absence of local irritation, the significant lymphoproliferative response observed was attributed to delayed contact hypersensitivity. The EC3 value was equal to 47%.

In conclusion, the test item gave a positive result in the murine Local Lymph Node Assay, indicative of skin sensitization properties.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:

Skin sensitisation (Duclos 2015):

The objective of this study was to evaluate the potential of the test item to induce contact hypersensitivity, using the murine Local Lymph Node Assay (LLNA).This study was conducted in compliance with the principles of Good Laboratory Practice.

A solution was obtained at the highest concentration of 50% in Acetone/Olive Oil(4/1; v/v).

In the main test, no unscheduled deaths and no clinical signs were observed during the observation period.Body weights were unaffected by the test item treatment.No local reactions on the ears were observed in any animals.In all test item-treated groups, the increase in ear thickness was below 10%. The test item was therefore considered as non irritant. As the acceptance limit of 25% was not reached at any concentrations, no bias in the results of proliferation measurements linked to an excessive irritant potential was considered.

The stimulation index (SI) of the positive control was > 3; this experiment was therefore considered valid.A significant lymphoproliferation (SI > 3) was noted at the concentrations = 50% of the test item. In the absence of local irritation, the significant lymphoproliferative response observed was attributed to delayed contact hypersensitivity.The EC3 value was equal to 47%.

In conclusion, the test item gave a positive result in the murine Local Lymph Node Assay, indicative of skin sensitization properties.

Justification for classification or non-classification

Based on the available data, Tricyclodecane dimethanol dimethacrylate is considered as a skin sensitizer.

According to the Regulation EC no.1272/2008, the test substance should be classified as skin sensitizer / category 1B, based on the EC3 value of 47%.