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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 24 Aug to 02 Sep 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report Date:
2010

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Specific details on test material used for the study:
- Purity: 100.0 % area (HPLC)
- Batch No.: E010010678 (PFI-09-01-097)

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals 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: 2-4 kg
- Housing: housed in labeled cages with perforated floors and shelters
- Diet (e.g. ad libitum): Pelleted diet approximately 100 grams per day, Hay was provided at least three times a week.
- Water (e.g. ad libitum): Free access to tap water
- Acclimation period: At least 5 days before start of treatment under laboratory conditions.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.0 ± 3.0ºC (actual range: 19.0-19.9ºC)
- Humidity (%): 40-70% (actual range: 49 - 87%)
- Air changes (per hr): approximately 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light and 12 hours darkness per day

IN-LIFE DATES: From: 2010-08-24 To: 2010-09-02

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
water
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 grams
- Concentration (if solution):

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration (if solution):
- Lot/batch no. (if required):
- Purity:
Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
3 males
Details on study design:
TEST SITE
- Area of exposure: approximately 150 square centimeters (10x15 cm)
- % coverage:
- Type of wrap if used: Micropore tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): tap water
- Time after start of exposure: 4 hours

SCORING SYSTEM: numerical scoring system

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal: 475
Time point:
24/48/72 h
Score:
0
Max. score:
1
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: The exposure period is 4 hours.
Irritation parameter:
erythema score
Basis:
animal: 486
Time point:
24/48/72 h
Score:
0
Max. score:
1
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: The exposure period is 4 hours.
Irritation parameter:
erythema score
Basis:
animal: 489
Time point:
24/48/72 h
Score:
0
Max. score:
1
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: The exposure period is 4 hours.
Irritation parameter:
edema score
Basis:
animal: 475
Time point:
24/48/72 h
Score:
0
Max. score:
1
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: The exposure period is 4 hours.
Irritation parameter:
edema score
Basis:
animal: 489
Time point:
24/48/72 h
Score:
0
Max. score:
1
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: The exposure period is 4 hours.
Irritation parameter:
edema score
Basis:
animal: 486
Time point:
24/48/72 h
Score:
0
Max. score:
1
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: The exposure period is 4 hours.
Irritant / corrosive response data:
Four hours exposure to 0.5 g of test substance resulted in very slight erythema in the treated skin areas of the three rabbits. The skin irritation resolved within 24 hours after exposure in all animals.
There was no evidence of a corrosive effect on the skin.
Other effects:
No staining of the treated skin by the test substance was observed and no test substance remnants were seen.
No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Any other information on results incl. tables

Individual skin irritation scores

Animal

475

489

486

Time after exposure

Erythema

(0-4)

Oedema

(0-4)

Erythema

(0-4)

Oedema

(0-4)

Erythema

(0-4)

Oedema

(0-4)

1 hour

1

0

1

0

1

0

24 hours

0

0

0

0

0

0

48 hours

0

0

0

0

0

0

72 hours

0

0

0

0

0

0

Applicant's summary and conclusion

Interpretation of results:
not irritating
Conclusions:
No skin irritation was caused by 4 hours exposure to the test substance.
Executive summary:

Primary skin irritation/corrosion study with PF-00968603 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 (2000) including the most recent partial revisions.

Three rabbits were exposed to 0.5 grams of PF-00968603, 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.

Exposure to PF-00968603 resulted in very slight erythema in the treated skin areas of the three rabbits. The skin irritation resolved within 24 hours after exposure in all animals.

No staining of the treated skin by the test substance was observed and no test substance remnants were seen.

Based on these results PF-00968603 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 (2007), - Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures.