.beta.-D-Galactopyranoside, ethyl 3-O-[(1S)-1-(cyclohexylmethyl)-2-oxo-2-(phenylmethoxy)ethyl]-1-thio-, 2,4,6-tribenzoate

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

22 September - 02 October 2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

(2S,3R,4S,5S,6R)-5-(benzoyloxy)-6-[(benzoyloxy)methyl]-4-{[(2S)-1-(benzyloxy)-3-cyclohexyl-1-oxopropan-2-yl]oxy}-2-(ethylsulfanyl)oxan-3-yl benzoate

EC Number:

805-702-8

Cas Number:

322761-81-9

Molecular formula:

C45H48O10S

IUPAC Name:

(2S,3R,4S,5S,6R)-5-(benzoyloxy)-6-[(benzoyloxy)methyl]-4-{[(2S)-1-(benzyloxy)-3-cyclohexyl-1-oxopropan-2-yl]oxy}-2-(ethylsulfanyl)oxan-3-yl benzoate

Test material form:

solid: particulate/powder

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River France, L’Arbresle Cedex, France
- Age at study initiation: 3 Males. At start of dosing, the animals were between 12 and 24 weeks old.
- Weight at study initiation: body weights were at least 1.5 kg.
- Housing: Animals were individually housed in labeled cages with perforated floors (Ebeco, Germany, dimensions 67 x 62 x 55 cm) and shelters (Ebeco, Germany, dimensions 40 x 32 x 23 cm).
- Diet: Pelleted diet for rabbits (Global Diet 2030 from Harlan Teklad®, Mucedola, Milanese, Italy) approximately 100 grams per day. Hay (TecniLab-BMI BV, Someren, The Netherlands) and wooden sticks (Swedish aspen wood, Bioservices, Uden, The Netherlands) were available during the study period.
- Water: Free access to tap water.
- Acclimation period: Acclimatization period was at least 5 days before start of treatment under laboratory conditions.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 24°C
- Humidity (%): A relative humidity of 40 to 70%.
- Air changes (per hr): At least 10 air changes/hour.
- Photoperiod (hrs dark / hrs light): A 12-hour light/12-hour dark cycle.

IN-LIFE DATES: From: 22 September 2015 To: 02 October 2015

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

water

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
Each animal was treated by dermal application of 0.5 grams of the test item.

VEHICLE
The test item was
moistened with 0.7 mL of the vehicle and applied to the skin of one flank, using a metalline patch# of 2x3 cm.

Duration of treatment / exposure:

4-hour semi-occlusive application.
Approximately 24 hours before treatment, the dorsal fur was clipped with electric clippers, exposing an area of approximately 150 square centimeters (10x15 cm). To facilitate scoring, treated skin areas were re-clipped at least 3 hours before the observations.
Each animal was treated by dermal application of 0.5 grams of the test item. The test item was moistened with 0.7 mL of the vehicle and applied to the skin of one flank, using a metalline patch of
2x3 cm. The patch was mounted on Micropore tape, which was wrapped around the abdomen and secured with Coban elastic bandage.
Four hours after the application, the dressing was removed and the skin cleaned of residual test item using tap water.
After the final observation, two animals were sacrificed by intra-venous injection of Euthasol® 20%. The other animal was removed from the study alive.

Observation period:

Mortality/Viability: Twice daily.
Toxicity: At least once daily.
Body Weight: Day of treatment (prior to application) and on the day of the final observation.
Irritation: The skin reactions were assessed at approximately 1, 24, 48 and 72 hours after the removal of the dressings and test item. The irritation scores and a description of all other (local) effects were recorded. Adjacent areas of the untreated skin of each animal served as controls.

Number of animals:

3 males.

Details on study design:

Three rabbits were exposed to 0.5 grams of PF-06460246, moistened with 50% watery ethanol by application onto clipped skin for 4 hours using a semi-occlusive dressing. Skin reactions were assessed 1, 24, 48 and 72 hours after exposure.
The study was performed in a stepwise manner and was started by treatment of a single rabbit (sentinel). The two other animals were treated in a similar manner one week later, after considering the degree of skin irritation observed in the first animal.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

No skin irritation was caused by 4 hours exposure to PF-06460246.
Based on these results PF-06460246 does not have to be classified and has no obligatory labelling requirement for skin irritation according to the:
- Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United
Nations (2011) (including all amendments),
- Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures
(including all amendments).