Registration Dossier

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
2004-11-02 to 2005-02-04
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: OECD guideline compliant GLP compliant

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2005
Report Date:
2005

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
as at 2002
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Version / remarks:
as at 2004
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Version / remarks:
as at 1998
Deviations:
no
Qualifier:
according to
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000, including the most recent partial revisions (as at 2005).
Deviations:
no
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): dl-Lactone
- Physical state: white crystalline mass
- Analytical purity: 99.6
- Lot/batch No.: 451
- Expiration date of the lot/batch: 30 September 2005
- Stability under test conditions: Stable under storage conditions, Stability in vehicle (water) at least for 4 h
- Storage condition of test material: In refrigerator in the dark

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Kisslegg, Germany
- Age at study initiation: least 6 weeks old
- Weight at study initiation: at least 1.0 kg.
- Housing: Individually in labelled cages with perforated floors (Scanbur, Denmark, dimensions 56x44x37.5 cm).
- Diet (e.g. ad libitum): Standard laboratory rabbit diet (Charles River Breeding and Maintenance Diet for Rabbits, Altromin, Lage, Germany) approx. 100 g. per day + hay (BMI, Helmond, the Netherlands) provided at least three times a week.
- Water (e.g. ad libitum): ad libitum, tap-water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.0 ± 3.0 (actual range: 19.4 - 21.1),
- Humidity (%): 30-70 (actual range: 44 - 59)
- Air changes (per hr): ca. 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: Start: 02 November 2004, Completion: 26 November 2004

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 g, moistened with 0.1 mL vehicle (water)


Duration of treatment / exposure:
4 h
Observation period:
3 weeks for the first animal (sentinel, no. 317), not clearly described for the other two animals (probably 3 days)
Number of animals:
3, one as sentinel, two additional animals for validation
Details on study design:
Since no severe harm for the animals was to be expected, this in-vivo skin irritation study was performed and was started by treatment of a single rabbit (sentinel). The two other animals were treated in a similar manner three weeks later, after considering the degree of skin irritation observed in the
first animal.

TEST SITE
- Area of exposure: flank
- % coverage: 2 x 3 cm²
- Type of wrap if used: Metalline patch (Lohmann GmbH, Neuwied, Germany), mounted on Micropore tape (3M, St. Paul, Minnesota, U.S.A. (Micropore and Coban), which was wrapped around the abdomen and secured with Coban elastic bandage (3M, St. Paul, Minnesota, U.S.A. (Micropore and Coban).

REMOVAL OF TEST SUBSTANCE
- Washing: with water
- Time after start of exposure: 4 h

SCORING SYSTEM:
Draize score 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
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 24, 48 and 72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
No skin irritation was caused by 4 hours exposure to dl-Lactone.
There was no evidence of a corrosive effect on the skin.
No staining of the treated skin by the test substance was observed and no test substance
remnants were seen.
Other effects:
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 #

317 (sentinel)

369

372

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

-

- Table 2: Mean Value Irritation Scores

Animal #

Mean 24 — 72 hrs

 

Erythema

Oedema

317

0

0

369

0

0

372

0

0

Table 3: Animal specifications

Animal no

Sex

Age at start

(weeks)

Body weights (g)

prior to application

at termination

317

male

7-9

1551

1702

369

male

7-9

1521

1646

372

male

7-9

1635

1811

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
RS-Pantolactone was tested for its skin irritation potential according to OECD 404. The test item did not show any irritation potential on rabbit skin.
Executive summary:

Primary skin irritation/corrosion study with RS-Pantolactone (named dl-Lactone in the report) 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 Commission Directive 2004/73/EC, B.4, "Acute Toxicity - Skin irritation" (2004); US EPA, OPPTS 870.2500, Acute Dermal Irritation (1998) and JMAFF, Japanese Test Guidelines (2000) including the most recent partial revisions.

Three rabbits were exposed to 0.5 grams of RS-Pantolactone, applied onto clipped skin for 4 hours using a semi-occlusive dressing. Observations were made 1, 24, 48 and 72 hours after exposure.

No skin irritation was caused by 4 hours exposure to RS-Pantolactone.

By expert judgment it is concluded that L-Pantolactone will get the same results.

L-Pantolactone: no skin irritation, 4 hours.