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Description of key information

An in vivo skin sensitization study - Local lymph node assay is available and was assigned as a key study. This LLNA study was performed according to OECD test guidline no.429 and OPPTS 870.260 and following GLP.

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:
2004
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP and appropriate guidelines
Reason / purpose for cross-reference:
reference to same study
Qualifier:
according to guideline
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Qualifier:
according to guideline
Guideline:
EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)
Qualifier:
according to guideline
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)
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
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
Positive control results:
see attached document on positive control
Key result
Parameter:
SI
Value:
1.1
Test group / Remarks:
1% test item, 5 females 10 weeks old, nulliparous and non-pregnanat
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.
Key result
Parameter:
SI
Value:
1.1
Test group / Remarks:
5% test item, 5 females 10 weeks old, nulliparous and non-pregnanat
Key result
Parameter:
SI
Value:
0.9
Test group / Remarks:
10% 1% test item, 5 females 10 weeks old, nulliparous and non-pregnanat

see attached document on results and tables

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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Following a contact hypersensitivity to FR-513 in the mouse (LLNA), the simulation index (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 SI ≥ 3.

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


Migrated from Short description of key information:
Assessment of contact hypersensitivity to FR-513 in the mouse (Local Lymph Node Assay)

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on the experimental results and according to the EEC criteria for classification and labelling requirements for dangerous substances and preparations (Guidelines in Commission Directive 93/21/EEC, 27th April 1993), FR-513 does not have to be classified and has no obligatory labelling requirement for skin sensitization.

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