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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:
13 August 2014 to 08 September 2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted in GLP compliant laboratory according to latest test Guidelines

Data source

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

Materials and methods

Test guidelineopen allclose all
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
Qualifier:
according to
Guideline:
EPA OPPTS 870.2600 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of study:
mouse local lymph node assay (LLNA)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report): adca
- Molecular formula (if other than submission substance): C2H4N4O2
- Molecular weight (if other than submission substance): 116.08
- Physical state: Yellow powder
- Analytical purity: min 99%
- Lot/batch No.: 3L48J
- Expiration date of the lot/batch: 31 December 2014
- Storage condition of test material: Room temperature in the dark
- Other:

In vivo test system

Test animals

Species:
mouse
Strain:
CBA
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Reputable commercial supplier
- Age at study initiation: ca 11 weeks
- Weight at study initiation:
- Housing: Animals were group housed in labeled Makrolon cages (MIII type; height 18 cm) containing sterilised sawdust as bedding material. Paper and shelters were supplied as cage-enrichment.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period:

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 24°C
- Humidity (%): 40-70%
- Air changes (per hr): 10 air changes per hour
- Photoperiod (hrs dark / hrs light): a 12-hour light/12-hour dark cycle

IN-LIFE DATES: From: 13 August 2014 To: 08 September 2014

Study design: in vivo (non-LLNA)

No. of animals per dose:
5
Details on study design:
RANGE FINDING TESTS: Yes performed to select the highest test concentration to be used in the main study

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: days 1,2 3
- Test groups: 3 test groups
- Control group: yes vehicle alone tested
- Site: dorsal surface of both ears
- Frequency of applications: once a day at ca the same time each day
- Duration:
- Concentrations: 0 (control), 10, 25 and 50 % w/w


RANGE FINDING TESTS:

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures:
- Exposure period:
- Test groups:
- Control group:
- Site:
- Frequency of applications:
- Duration:
- Concentrations:

B. CHALLENGE EXPOSURE
- No. of exposures:
- Day(s) of challenge:
- Exposure period:
- Test groups:
- Control group:
- Site:
- Concentrations:
- Evaluation (hr after challenge):

OTHER:

Study design: in vivo (LLNA)

Vehicle:
propylene glycol
Concentration:
0 (control), 10, 25 and 50% w/w
No. of animals per dose:
5
Details on study design:
RANGE FINDING TESTS:
- Compound solubility:The vehicle was selected on the basis of maximizing the solubility using the test substance data provided by the sponsor and trial formulation results performed at WIL Research Europe
- Irritation: Measured but no irritation occured
- Lymph node proliferation response: Not performed

MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: Lymph node proliferation
- Criteria used to consider a positive response: Stimulation Index (SI)

TREATMENT PREPARATION AND ADMINISTRATION:

The test substance formulations (w/w) were prepared within 4 hours prior to each dosing. No adjustment was made for specific gravity of the vehicle. Homogeneity was obtained to visually acceptable levels.
The dorsal surface of both ears was topically treated (25 μL/ear) with the test substance concentration, at approximately the same time on each day. The concentrations were stirred with a magnetic stirrer immediately prior to dosing.
The control animals were treated in the same way as the experimental animals, except that the vehicle was administered instead of the test substance.
Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)
Statistics:
Mean values for each group calculated and SI values calculated. No statistical analysis performed.

Results and discussion

Positive control results:
The six-month reliability check with Alpha-hexylcinnamaldehyde indicates that the Local Lymph Node Assay as performed at this laboratory is an appropriate model for testing for contact hypersensitivity

In vivo (LLNA)

Resultsopen allclose all
Parameter:
SI
Remarks on result:
other: The SI values calculated for the substance concentrations 10, 25 and 50% were 1.2, 1.2 and 1.1, respectively
Parameter:
other: disintegrations per minute (DPM)
Remarks on result:
other: Mean DPM/animal values for the experimental groups treated with test substance concentrations 10, 25 and 50% were 1101, 1119 and 1012 DPM, respectively. The mean DPM/animal value for the vehicle control group was 907 DPM.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Remarks:
Migrated information
Conclusions:
Since there was no indication that the test substance elicited a SI ≥ 3 when tested up to 50%, ADCA was not considered to be a skin sensitizer.
Executive summary:

ADCA was not considered to be a skin sensitizer.