Registration Dossier

Administrative data

Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2004
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP and appropriate guidelines
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2004
Report Date:
2004

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Qualifier:
according to
Guideline:
EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)
Qualifier:
according to
Guideline:
EPA OPPTS 870.2600 (Skin Sensitisation)
Principles of method if other than guideline:
not relevant
GLP compliance:
yes
Type of study:
mouse local lymph node assay (LLNA)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Identification: FR-513
Mol. formula: C5H9Br3O
Mol. Weight: 324.92
CAS #: 36483-57-5
Description: White flakes
Batch: 039084 (taken from label)
Composition: Tribromoneopentyl alchohol 97%, Dibromoneopentyl glycol < 0.1%
Storage: At room temperature in the dark
Stability under storage conditions: Stable

In vivo test system

Test animals

Species:
mouse
Strain:
CBA
Sex:
female
Details on test animals and environmental conditions:
Mouse , CBA strain (SPF-Quality)
Source: Charles River France, L'Arbresle Cedex, France
Number of animals: 20 females (four groups of five females each group) (nulliparous and non-pregnant).
Age and body weight: Young adult animals (approx. 10 weeks old)were selected. Body weight variation was within +/- 20% of the sex mean.
Identification: tailmark
Housing: Individually in labelled Macrolon cages.
Acclimatisation: at least 5 days before start of treatment under laboratory conditions.
Diet: Standard laboratory diet
Water: Free access to tap water
Temperature (°C): 21.0 ± 3.0 °C (actual range:20.1-21.7°C)
Humidity (%): 30-70% (actual range 29-77%)
Air changes (per hr): 15
Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (LLNA)

Vehicle:
acetone/olive oil (4:1 v/v)
Concentration:
Preliminary irritation study: 100%, 50%, 25%, 10%, 5%, 2.5%, 1% and if needed further lower concentrations.
Main study: 1%, 5%, and 10%.
No. of animals per dose:
Preliminary irritation study: Two young adult animals were selected (5-14 weeks old). Each animal was treated with one concentration.
Main study: Three groups of five animals were treated with three test substance concentrations respectively. One group of five animals was treated
with vehicle.
Details on study design:
See attached document on study design
Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)
Statistics:
no

Results and discussion

Positive control results:
see attached document on positive control

In vivo (LLNA)

Resultsopen allclose all
Parameter:
SI
Remarks on result:
other: see Remark
Remarks:
The SI values for the positve control substance were 1.0 ± 0.4, 3.2 ± 0.4 and 7.1 ± 0.4 for the concentrations of 5%, 10% and 25% in Acetone: Olive oil (4:1) respectively. The SI values calculated for the test substance concentrations 1, 5 and 10% were 1.1, 1.1 and 0.9 respectively.
Parameter:
other: disintegrations per minute (DPM)
Remarks on result:
other: Mean DPM/animals values for the experimental groups treated with test substance concentrations 1, 5 and 10% were 358, 376 and 288 respectively. The mean DPM/amimal value for the vehicle control group was 328.

Any other information on results incl. tables

see attached document on results and tables

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
The SI values calculated for the test substance concentrations 1, 5 and 10% were 1.1, 1.1 and 0.9 respectively.
There was no indication that the test substance could elicit an SI ≥ 3.
Based on these results and according to the recommendations made in the test guidelines (OECD 429, OPPTS 870.2600) , FR-513 is not a skin
sensitiser.
Executive summary:

LLNA study has been conducted on mice using FR-513. The study was conducted using appropriate guidelines such as OECD 429 and OPPTS 870.2600. Test concentrations selected were based on preliminary study.

In the main test three groups of five animals were epidermally exposed to 1%, 5% and 10% concentration on three consecutive days. Five vehicle control animals were similarly treated with vehicle alone.

three days after the last exposure all animals were injected with 3H-methyl thymidine and after five hours the draining (auricular) lymph nodes were excised. After precipitating the DNA of the lymph nodes cells, radioactivity measurements were done. The SI values calculated for the test substance concentrations 1, 5 and 10% were 1.1, 1.1 and 0.9 respectively.

There was no indication that the test substance could elicit an SI ≥ 3.

Based on these results and according to the recommendations made in the test guidelines (OECD 429, OPPTS 870.2600) , FR-513 is not a skin sensitiser.