PF-05201372

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

26th October 2011 to 26th January 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

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)

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nohsan, Notification No. 8147, April 2011; including the most recent partial revisions.

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

(2E)-N-(5-Cyano-4-{(E)-[(dimethylamino)methylene]amino}-2-methoxyphenyl)-4-(piperidin-1-yl)but-2-enamide

Molecular formula:

C20 H27 N5 O2

IUPAC Name:

(2E)-N-(5-Cyano-4-{(E)-[(dimethylamino)methylene]amino}-2-methoxyphenyl)-4-(piperidin-1-yl)but-2-enamide

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: between 10-20 weeks old
- Weight at study initiation: between 2-4 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: at least 5 days before start of treatment under laboratory conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.8 – 20.1ºC
- Humidity (%): 42 - 64%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light and 12 hours darkness per day.

IN-LIFE DATES: From: 10 November 2011 To: 18 November 2011

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

water

Controls:

yes, concurrent no treatment

Amount / concentration applied:

Each animal was treated by dermal application of 0.5 grams of the test substance moistened with 1 mL of the vehicle.

Duration of treatment / exposure:

Four hours

Observation period:

1, 24, 48 and 72 hours

Number of animals:

Three

Details on study design:

Observations
Mortality/Viability: Twice daily.
Toxicity: At least once daily.
Body Weight: Day of treatment (prior to application) and after 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 substance. 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.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

erythema 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:

Based on these results PF-05201372 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),
- Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures.

Executive summary:

Primary skin irritation/corrosion study with PF-05201372 in the rabbit (4-hour semi-occlusive application).
The study was carried out based on the guidelines described in:
OECD No.404, "Acute Dermal Irritation/Corrosion" (2002) EC, No 440/2008; B4: "Acute Toxicity: Dermal Irritation/Corrosion"
US EPA, OPPTS 870.2500 (1998), Acute Dermal Irritation 
JMAFF Guidelines (2011) including the most recent partial revisions.
Three rabbits were exposed to 0.5 grams of PF-05201372, moistened with water, 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.
No skin irritation was caused by 4 hours exposure to PF-05201372.
Based on these results PF-05201372 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),
- Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures.