Registration Dossier

Administrative data

Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Guideline study conducted in compliance with GLP regulations. Read-across of data from a category member. Because these substances exhibit similarity in their physicochemical properties and toxicological properties in mammals, and because available data indicates that parent molecules are not reactive toward biological molecules and cannot undergo bioactivation by normal enzymatic processes, they can be considered to constitute a chemical category. Data gaps for partitioning properties, mammalian and ecological toxicity can therefore be addressed by read-across and/or trend analysis between category members.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2007
Report Date:
2007

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
Type of study:
mouse local lymphnode assay (LLNA)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): MTDID 7145
- Substance type: Clear colorless liquid
- Physical state: liquid
- Analytical purity: ~94.5%
- Lot/batch no.: Batch 142072:43
- Expiration date of the lot/batch: 30 December 2007
- Stability under test conditions: Stable (but test substance is volatile)
- Storage condition of test material: At room temperature in the dark
- Other: pH: 7.2. Specific gravity: 1.8

In vivo test system

Test animals

Species:
mouse
Strain:
other: CBA; inbred, SPH quality
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Frances, L'Arbresle Cedex, France
- Age at study initiation: 10-11 weeks
- Weight at study initiation: 19-26 g
- Housing: Individual housing in labeled Macrolon cages containing sterilized sawdust as bedding material
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.8-23.9 C
- Humidity (%): 38-77%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 hrs dark/ 12hrs light

Study design: in vivo (LLNA)

Vehicle:
unchanged (no vehicle)
Concentration:
0% (control) and 100%(undiluted)
No. of animals per dose:
5
Details on study design:
RANGE FINDING TESTS:
- Irritation:No irritation was observed in the one animal tested.
- Lymph node proliferation response: not evaluated
MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method:Local Lymph Node Assay (LLNA)
- Criteria used to consider a positive response: a simulation index greater than or equal to 3 relative to the naive control group
TREATMENT PREPARATION AND ADMINISTRATION: The test article was administered undiluted by pipette to the dorsal surface of both ears (25microliters/ear) or animals in the 100% treatment group at approximiately the same time each day for three consecutive days.
Positive control substance(s):
other:
Statistics:
None

Results and discussion

Positive control results:
A concurrent positive control was not evaluated in this study. A reliability check on the test system was last performed in March 2007 using the positive control substance alpha-hexyl cinnamaldehyde (HCA). In this test, stimulation indicates for the positive control stubstance at 5%, 10% and 25% concentrations were 1.3, 1.5 and 5.5, respectivley, relative to the vehicle control (acetone/olive oil 4:1 v/v). The EC3 was 15.6%. The EC3 was in the acceptable range of 2% to 20%. EC3 values for HCA for the previous 4 reliability checks ranged from 7.3% to 13.1%

In vivo (LLNA)

Resultsopen allclose all
Parameter:
SI
Remarks on result:
other: 100% Test Substance: 3.0 Control: 1.0 *In additionally treated animals: 100% Test Substance: 2.5 Control: 1.0
Parameter:
other: disintegrations per minute (DPM)
Remarks on result:
other: 100% Test Substance: 466 DPM Control: 154 DPM *In additionaly treated animals: 100% Test Substance: 312 DPM Control: 123 DPM

Any other information on results incl. tables

*In order to achieve more information regarding the SI=3 value, an additional group of animals was treated with 100% test substance concentration.

No irritation/skin reactions, mortality and systemic toxicity were observed in any of the animals examined. All nodes of all the animals were considered normal in size and body weights of the experimental animals remained in the same range.

FC-3284 is a member of the Perfluorinated Organic Chemicals, C5-C18, category. All of these chemicals stem from the same manufacturing process, have similar physicochemical properties including high vapor pressure and low water solubility relative to the hydrocarbon analogs (e.g., hexanes v. perfluorohexanes), and also lack any chemically reactive groups, which forms the technical basis for the category. Members of this category are fully fluorinated, meaning that fluorine, rather than hydrogen, is bonded to all carbon atoms in the molecule. Fluorine is the most electronegative of the elements (fluorine has an electronegativity of 3.98 on the Pauling scale, as compared to 2.55 for carbon or 2.20 for hydrogen). This electronegativity is expected to dominate over all other aspects of substance chemistry and is the underlying basis for similarity of substances in this category. Because these substances exhibit similarity in their physicochemical properties and toxicological properties in mammals, and because available data indicates that parent molecules are not reactive toward biological molecules and cannot undergo bioactivation by normal enzymatic processes, they can be considered to constitute a chemical category. Data gaps for partitioning properties, mammalian and ecological toxicity can therefore be addressed by read-across from FC-770.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Remarks:
Migrated information
Conclusions:
CAS 382-28-5 is not a dermal sensitizer at concentrations up to 100%.
Executive summary:

Skin sensitization results for FC-770 (PIPM, CAS# 1093615-61-2) are reported for read-across to FC-3284 (PMM, CAS# 382-28-5). The dermal sensitizing potential of the test article was evaluated in a local lymph node assay (LLNA) in female CBA/J mice following OECD Guideline 429 (effective April 2002). This concentration did not cause irritation in a preliminary irritation screen. In the definitive study, animals (5/group) were administered 25 µL of control (Milli-Q or Milli-U water) or 100% of the test article by topical application to the dorsum of each ear once daily for three consecutive days. Clinical observations were recorded daily. Body weights were recorded on days 1 and 6. Ear swelling measurements were recorded on days 1, 3 and 6. On day 6, the number of proliferating lymph node cells in the auricular lymph nodes were determined using a 3H-methyl thymidine method. The Stimulation Index (SI) was calculated and substances with a SI ? 3 are considered to be potential sensitizers. To achieve more information regarding the SI value, the study was repeated with two additional groups. No skin reactions were observed in any animals. The calculated median SI was 2.8 and there was no indication that the test substance could elicit an SI = 3 when tested up to 100%. The positive control (hexylcinnamaldehyde) is tested once every 6 months at NOTOX and the most recent test indicated that the test method was valid. Based on the results of this study, the test article is not a dermal sensitizer at concentrations up to 100%. By read-across, the tartget substance is also not sensitizing to the skin and has no labelling requirement under GHS/CLP.

Study conducted under GLP conditions. Because these substances exhibit similarity in their physicochemical properties and toxicological properties in mammals, and because available data indicates that parent molecules are not reactive toward biological molecules and cannot undergo bioactivation by normal enzymatic processes, they can be considered to constitute a chemical category. Data gaps for partitioning properties, mammalian and ecological toxicity can therefore be addressed by read across and/or trend analysis between category members. The readacross is considered reliable with restrictions and the result is suitable for use in Risk Assessment, Classification & Labelling, and PBT Analysis.