L-Leucine, 4-fluoro-N-[(1S)-2,2,2-trifluoro-1-[4'-(methylsulfonyl)[1,1'-biphenyl]-4-yl]ethyl]-, compd. with N-cyclohexylcyclohexanamine (1:1)

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

October 5th to October 8th, 2005

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study followed GLP and OECD method.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2005

Report date:

2005

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

N-cyclohexylcyclohexanaminium (2S)-4-fluoro-4-methyl-2-{[(1S)-2,2,2-trifluoro-1-{4'-methanesulfonyl-[1,1'-biphenyl]-4-yl}ethyl]amino}pentanoate

EC Number:

700-778-8

Cas Number:

1064076-86-3

Molecular formula:

C21H23F4NO4S.C12H23N

IUPAC Name:

N-cyclohexylcyclohexanaminium (2S)-4-fluoro-4-methyl-2-{[(1S)-2,2,2-trifluoro-1-{4'-methanesulfonyl-[1,1'-biphenyl]-4-yl}ethyl]amino}pentanoate

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source:Millbrook Breeding Labs, Amherst, MA
- Age at study initiation: 10 weeks
- Weight at study initiation:2.11 to 2.3 kg
- Housing: Single housing, suspended stainless steel cages with hardwood chip bedding
- Diet (e.g. ad libitum): TEK 8630 Rabbit Diet from Harlan Teklad, ad libitum
- Water (e.g. ad libitum):tap water as libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 68°± 5°
- Humidity (%): 30-70 %
- Air changes (per hr): 10 to 15
- Photoperiod (hrs dark / hrs light):12 hour light/dark cycle, full spectrum fluorescent lights

Test system

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

water

Controls:

yes

Amount / concentration applied:

0.5 mg test substance was wetted with 2.0 ml of sterile water for injection and applied directly to the skin of the rabbit.

Duration of treatment / exposure:

One animal was initially tested for 3 minutes, then 1 hour and then 4 hours. As no response was noted 2 additional animals were tested for the 4 hour period.

Observation period:

After the inital 4 hour exposure period and the patch was removed,the anaimals checked for signs of erythema or edema after 60 minutes, 24 hours, 48 hours and 72 hours.

Number of animals:

3 animals ( 1 male and 2 females)

Details on study design:

TEST SITE
- Area of exposure: 6cm squared
- % coverage: not less than 10% of the surface area was cleared.
- Type of wrap if used:gauze patch held in place with non-irritating skin
REMOVAL OF TEST SUBSTANCE
- Washing (if done):none noted
- Time after start of exposure: 4 hours

SCORING SYSTEM:draize

body weight was weighed at administration and at the 72 hour observation point

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 60 minutes, , 48 and 72 hours

Score:

0

Max. score:

0

Results 2

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 60 minutes, 24, 48 and 72 hours

Score:

0

Max. score:

0

Irritant / corrosive response data:

no signs of erythema and edema were observed in test animals or control animals

Other effects:

no impact on gain in body weights were noted; no signs of clinical toxicity were observed.

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

No signs of dermal irritation were observed and test substance is considered a non-irritant.