2-{2-[(2R,4R,6R)-4,6-dihydroxytetrahydro-2H-pyran-2-yl]ethyl}-1H-isoindole-1,3(2H)-dione

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

29 January 2008 - 01 February 2008

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study performed to OECD, European and other guidelines and statement of GLP compliance is included in report.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000, including the most recent partial revisions.

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2-{2-[(2R,4R,6R)-4,6-dihydroxyoxan-2-yl]ethyl}-2,3-dihydro-1H-isoindole-1,3-dione

EC Number:

700-188-0

Cas Number:

1333481-90-5

Molecular formula:

C15H17NO5

IUPAC Name:

2-{2-[(2R,4R,6R)-4,6-dihydroxyoxan-2-yl]ethyl}-2,3-dihydro-1H-isoindole-1,3-dione

Constituent 2

Reference substance name:

Lactol

IUPAC Name:

Lactol

Details on test material:

- Name of test material (as cited in study report): Lactol
- Physical state: Solid (white powder)
- Analytical purity: Not indicated by the sponsor; treated as 100% pure.
- Impurities (identity and concentrations): Not indicated.
- Purity test date: Not indicated.
- Lot/batch No.: PDC-010-194
- Expiration date of the lot/batch: 13 December 2008 (allocated by NOTOX, 1 year after receipt of the test substance).
- Stability under test conditions: Stable
- Storage condition of test material: Room temperature in the dark.

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan, Horst, The Netherlands
- Age at study initiation: One animal used within the study was 9 to 11 weeks old and the two other animals were at least 11 weeks old.
- Weight at study initiation: At least 2.0 kg.
- Housing: Individually in labelled cages with perforated floors (Scanbur, Denmark, dimensions 56x44x37.5 cm).
- Diet (e.g. ad libitum): Pelleted diet for rabbits (K-H from SSNIFF® Spezialdiaten GmbH, Soest, Germany) approximately 100 grams per day. Hay
(TecniLab-BMI BV, Someren, The Netherlands) 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 ± 3.0°C (actual range: 18.3 - 21.4°C)
- Humidity (%): relative humidity of 30 - 70% (actual range: 38 - 56%)
- 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: 29 January 2008 To: 01 February 2008

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

other: Test substance moistened with water immediately before application.

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g

VEHICLE
Water (Elix, Millipore S.A.S., Molsheim, France)
- Amount(s) applied (volume or weight with unit): 0.7 mL.

Duration of treatment / exposure:

Test item was applied, them removed (washed off) after fours hours.

Observation period:

Skin reactions were assessed at approximately 1, 24, 48 and 72 hours after the removal of the dressings and test substance.

Number of animals:

3 males.

Details on study design:

TEST SITE
- Area of exposure: 2 x 3 cm (6 cm²)
- % coverage: Not specified.
- Type of wrap if used: Metalline patch (Lohmann GmbH, Neuwied, Germany) mounted on Micropore tape which was wrapped around the abdomen and secured with Coban elastic bandage (Micropore and Coban - 3M, St. Paul, Minnesota, USA).


REMOVAL OF TEST SUBSTANCE
Four hours after the application, the dressing was removed and the skin cleaned of residual test substance using tap water.

SCORING SYSTEM:

Erythema and eschar formation:
No erythema 0
Very slight erythema (barely perceptible) 1
Well-defined erythema 2
Moderate to severe erythema 3
Severe erythema (beet redness) 4
* Where signs of necrosis or corrosion (injuries in depth) prevent erythema scoring, the maximum grade for erythema (= 4) is given.

Oedema formation:
No oedema 0
Very slight oedema (barely perceptible) 1
Slight oedema (edges of area well-defined by definite raising) 2
Moderate oedema (raised approximately 1 millimeter) 3
Severe oedema (raised more than 1 millimeter and extending beyond the area of exposure) 4

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal: All animals

Time point:

other: 1, 24, 48 and 72 hours

Score:

0

Max. score:

0

Results 2

Irritation parameter:

other: Oedema

Basis:

animal: All animals

Time point:

other: 1, 24, 48 and 72 hours

Score:

0

Max. score:

0

Irritant / corrosive response data:

No skin irritation was caused by 4 hours exposure to LACTOL. There was no evidence of a corrosive effect on the skin.

Other effects:

Colouration / Remnants
No staining of the treated skin by the test substance was observed and no test substance remnants were seen.
Toxicity / Mortality
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

Table 1: Individual skin irritation scores

Animal	684^1			711			713
Time after exposure	Erythema	Oedema	Comments	Erythema	Oedema	Comments	Erythema	Oedema	Comments
1 hour	0	0		0	0		0	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

¹Sentinel

Refer also to figure 1, attached.

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: other: EU and GHS

Conclusions:

Treatment with LACTOL caused no skin irritation in three (3/3) rabbits.

Executive summary:

A Skin Irritation study was performed by NOTOX B.V. on behalf of Pfizer Ireland Pharmaceuticals, Ltd to assess the potential for skin irritation or corrosion of the test substance LACTOL. The study was performed to GLP and according to OECD guideline 404, EC guideline B4, and aditional US and Japanese guidelines.

Test substance (0.5 g) was applied to the skin of three rabbits for four hours then washed off. Skin reactions were assessed 1, 24, 48 and 72 hours after removal of the test substance.

No skin irritation was caused by 4 hours exposure to LACTOL in three (3/3) rabbits. The substance can be considered non irritant.