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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2002
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2002
Report date:
2002

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
1998
Deviations:
no
Remarks:
No deviations ocurred that impacted the integrity of the study.
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
This study was conducted prior to inception of the REACH registration program. Additionally, this study was conducted prior to the creation of the LLNA OECD Guideline.

Test material

Constituent 1
Chemical structure
Reference substance name:
1-BUTANESULFONAMIDE, 1,1,2,2,3,3,4,4,4-NONAFLUORO-N-METHYL-
EC Number:
614-396-3
Cas Number:
68298-12-4
Molecular formula:
C5H4F9NO2S
IUPAC Name:
1-BUTANESULFONAMIDE, 1,1,2,2,3,3,4,4,4-NONAFLUORO-N-METHYL-
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch number of test material:
3M Company, Lot 3
- Expiration date of the lot/batch:
06 August, 2002
- Purity test date:
30 January, 2002

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material:
At room temperature in the dark.
- Stability under storage conditions:
Stable
- Stability under test conditions:
Stable
- Solubility and stability of the test substance in the solvent/dispersant/vehicle/test medium:
The test article formed a stable suspension in polyproylene glycol.

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing:
The test article was suspended in polypropylene glycol.
- Final preparation of a solid:
The test article was suspended in polypropylene glycol.

FORM AS APPLIED IN THE TEST: The test article was suspended in polypropylene glycol.

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Kisselegg, Germany.
- Females (if applicable) nulliparous and non-pregnant: Yes
- Microbiological status of animals, when known: No data
- Age at study initiation: 6 weeks
- Weight at study initiation: 387-502 g
- Housing: Group housing of 5 animals per labelled metal cagewith wire-mesh floors.
- Diet (e.g. ad libitum): Free access to standard guinea pig diet, including ascorbic acid (1000 mg/kg); (Charles RiverBreeding and Maintenance Diet for Guinea Pigs, Altromin, Lage, Germany).
- Water (e.g. ad libitum): Tap water, ad libitum.
- Acclimation period: 5 days.
- Indication of any skin lesions: None

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-24
- Humidity (%): 30-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
- IN-LIFE DATES: From: 19 November, 2001 To: 01 February, 2002

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal
Vehicle:
propylene glycol
Concentration / amount:
20% test article in propylene glycol
Day(s)/duration:
Day 1
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Route:
intradermal
Vehicle:
propylene glycol
Concentration / amount:
40% test article in Freund's Complete Adjuvant
Day(s)/duration:
Day 1
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Route:
epicutaneous, occlusive
Vehicle:
propylene glycol
Concentration / amount:
50% test article
Day(s)/duration:
Day 8, dressing held in place for 48 hours.
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Challenge
No.:
#1
Route:
epicutaneous, semiocclusive
Vehicle:
propylene glycol
Concentration / amount:
10% test article.
Day(s)/duration:
Day 21, dressing in place for 24 hours.
Adequacy of challenge:
not specified
No. of animals per dose:
5 control animals and 10 experimental animals were utilized.
Details on study design:
RANGE FINDING TESTS:

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 simultaneous intradermal injections and one epidermal exposure a week later.
- Exposure period: Intradermal injections on Day 1, epidermal exposures on Day 8.
- Test groups: 1 experimental group of 10 females.
- Control group: One control group of 5 females.
- Site: Intradermal injections in the scapular region, epidermal exposure in the scapular region, between the injection sites.
- Frequency of applications: Intradermal injections on Day 1, epidermal exposures on Day 8, held in place for 48 hours.
- Duration: Intradermal injections on Day 1, epidermal exposures on Day 8, held in place for 48 hours.
- Concentrations: See study design table.

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: Day 21
- Exposure period: The dressing was held in place for 24 hours.
- Test groups: 1 group of 10 females.
- Control group: 1 group of 5 females.
- Site: Flank
- Concentrations: See study design table.
- Evaluation (hr after challenge): The treated sites were assessed for challenge reactions 24 and 48 hours after removal of the dressing

Challenge controls:
Every 6 months a test system reliability check is conducted with alpha-hexylcinnamicaldehyde (85%). The results of the most recent study were as expected.
Positive control substance(s):
yes
Remarks:
See "Challenge controls"

Results and discussion

Positive control results:
100% response at first challenge, 29-80% reponse upon second challenge.

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
10% challenge
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None reported.
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
10% challenge
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None reported.
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
None reported.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
None reported.
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
5%
No. with + reactions:
10
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
5%
No. with + reactions:
10
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The test article was not sensitizing (0% responding) in the Guinea Pig Maximization Test (GPMT)
Executive summary:

The dermal sensitization potential of the test article (off white solid, Lot 3) was evaluated in the Maximization Testusing female Dunkin Hartley albino guinea pigs. This study was performed in compliance with OECD GLP.The study designwas based on OECD 406 (1992), Commission Directive 96/54/EC An IV B.6 (1996), US EPA OPPTS 870.2600 (1998), and Magnusson and Kligman (1970).The test article was prepared in propylene glycol (vehicle) just prior to each dosing procedure.A pre-test rangefinder determined the appropriate doses for theintradermal and epidermal inductions and for the challenge phase.The test group (10 animals) received intradermal induction injections of 0.1 ml/site of a 1:1mixture of Freund's Complete Adjuvant (FCA):water for injection, 20% test article in vehicle, and 1:1 mixture of 40% test article and FCA.A control group (5animals) received the same induction treatment with the exclusion of test article.The epidermal induction of sensitization was conducted under occlusion with50% test article (test group) or vehicle only (control group) one week after the intradermal induction.Two weeks after epidermal induction the control and testanimals were challenged by epidermal application of 10% test article and vehicle under occlusive dressing.Skin reactions were evaluated at 24 and 48 hours afterremoval of the dressing. A positive control (alpha-hexylcinnamic aldehyde) is tested by this contract lab approximately every 6 months and the most recent testconfirmed the validity of the experimental technique. No erythema or edema was observed at any site in either the control or test article group (0%responders). The test article was not sensitizing (0% responding) in the Guinea Pig Maximization Test (GPMT).