2H-1-Benzopyran-2-methanol, alpha,alpha'-[[(phenylmethyl)imino]bis(methylene)]bis[6-fluoro-3,4-dihydro-, (alphaR,alpha'R,2R,2'S)-rel-

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2005-06-16 to 2005-06-17

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline non-GLP study. There were no deviations from the guideline that affected the study results.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2005

Report date:

2005

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Draft OECD Guideline 430 (In Vitro Skin Corrosion: Transcutaneous Electrical Resistance Test (TER))

Deviations:

yes

Remarks:

1) The sex of the rats was not specified in the study.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

2H-1-Benzopyran-2-methanol, alpha,alpha'-[[(phenylmethyl)imino]bis(methylene)]bis[6-fluoro-3,4-dihydro-, (alphaR,alpha'R,2R,2'S)-rel-

EC Number:

618-043-4

Cas Number:

876666-07-8

Molecular formula:

C29H31F2NO4

IUPAC Name:

2H-1-Benzopyran-2-methanol, alpha,alpha'-[[(phenylmethyl)imino]bis(methylene)]bis[6-fluoro-3,4-dihydro-, (alphaR,alpha'R,2R,2'S)-rel-

Test material form:

solid: particulate/powder

Details on test material:

- Name of test material (as cited in study report): JNJ-17303806-AAA (T001586)
- Physical state: solid, powder
- Appearance: white, beige

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: RT001586G1B121
- Expiration date of the lot/batch: 31-12-2005
- Purity test date: no data (purity = 100%)

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: at room temperature, light protected
- Stability under test conditions: no data
- Solubility and stability of the test substance in the solvent/vehicle:
solubility in water: 0.01 g/L
solubility in ethanol: 6.9 g/L
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: no data

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: The solid test item was ground to produce a granular material immediately prior to testing

In vitro test system

Test system:

isolated skin discs

Source species:

rat

Cell type:

non-transformed keratinocytes

Cell source:

other: dorsal skin of rats stripped of excess fat by carefully peeling it away from the skin

Source strain:

Wistar

Details on animal used as source of test system:

SOURCE ANIMAL
- Source: Harlan Winkelmann GmbH
- Sex: no data
- Age at study initiation (in days): 29 days old
- Weight at study initiation: no data
- Housing: single housing in Makrolon Type II, with wire mesh top, granulated soft wood bedding
- Diet (e.g. ad libitum): pelleted standard diet, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: 6 days

Justification for test system used:

The rat is required by the guidelines on which this assay system is based.

Vehicle:

other: deionised water

Details on test system:

SKIN DISC PREPARATION
- Procedure used: Animals were anaesthetised with CO2 and subsequently decapitated. The dorsal skin of each animal was removed and stripped of excess fat by carefully peeling it away from the skin. The skin was placed over the end of a PTFE (polytetrafluoroethylene) tube, ensuring that the epidermal surface was in contact with the tube. A rubber 'O' ring was press-fitted over the end of the tube to hold the skin in place and excess tissue was trimmed away. The tube was supported by a spring clip inside a receptor chamber containing magnesium sulphate solution (154 mM).
- Quality control for skin discs: no data
TEMPERATURE USED FOR TEST SYSTEM
no data
REMOVAL OF TEST MATERIAL AND CONTROLS
Washing with a jet of tap water at up to 30°C until no further material could be removed.
DYE BINDING METHOD
Sulforhodamine B
NUMBER OF INDEPENDENT TESTING RUNS / EXPERIMENTS TO DERIVE FINAL PREDICTION: Three skin discs were used for each test group - 1 independent run per skin disc
PREDICTION MODEL / DECISION CRITERIA (choose relevant statement)
If the mean TER value obtained for the test item is greater than 5 kOhm, then it is non-corrosive

Control samples:

yes, concurrent negative control

yes, concurrent positive control

Amount/concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1000 g, 0.0933 g, and 0.1065 g
- Concentration (if solution): not applicable


VEHICLE
- Amount(s) applied (volume or weight with unit): 150 µL of deionized water was added on top of the test material.
- Concentration (if solution): no data
- Lot/batch no. (if required): no data
- Purity: no data

NEGATIVE CONTROL
- Concentration (if solution): no data

POSITIVE CONTROL
- Amount(s) applied (volume or weight):
- Concentration (if solution): 10 M hydrochloric acid (36%)

Duration of treatment / exposure:

24 hours

Number of replicates:

Three skin discs for each test group

Results and discussion

In vitro

Results

Irritation / corrosion parameter:

transcutaneous electrical resistance (in kΩ)

Run / experiment:

1

Value:

165

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: not corrosive

Remarks:

result is presented as a mean value; standard deviation: 82.82 kOhm

Other effects / acceptance of results:

- OTHER EFFECTS:
The skin discs appeared macroscopically intact after treatment

ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: The mean TER-value of the negative control of the experiment remained well within the historical control range
- Acceptance criteria met for positive control: An appropriate reference substance was used as positive control and showed a distinct increase in conductivity indicating that the test was sensitive and valid. The actual impedance values remained in the range given by the guideline and were far below the general threshold of 5 kOhm indicating a substantial corrosive potential of the positive control substance.
- Acceptance criteria met for variability between replicate measurements: no data
- Range of historical values:
Negative control:
range: 6.0-21.4 kOhm
mean value: 12.6 kOhm
standard deviation: 5.70 kOhm

Positive control:
range: 0.8-3.9 kOhm
mean value: 1.11 kOhm
standard deviation: 1.58 kOhm

Individual results of the test substance:
replicate 1: 108.0 kOhm
replicate 2: 260.0 kOhm
replicate 3: 127.0 kOhm

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study, the test substance did not corrode rat skin in a rat TER study.