t-Butyl (2S,2aS,5aR)-1-azabicyclo[3.3.0] oct-2-carboxylate monooxalate salt

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2006-11-09 to 2007-4-11

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study performed according to OECD Guideline 404 (Acute Dermal Irritation/Corrosion) and EU Method B.4 (Acute Toxicity: Dermal Irriation/Corrosion) without deviations.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2007

Report date:

2007

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Remarks:

The testing facility indicated that the protocol was followed without deviations.

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Remarks:

The testing facility indicated that the protocol was followed without deviations.

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Remarks:

Certificate from the Department of Health of the Government of the United Kingdom

Test material

Reference

Name:

Unnamed

Type:

Constituent

Details on test material:

- Name of test material (as cited in study report): VRT-126028
- Molecular formula (if other than submission substance): C14H23NO6
- Substance type: pure active substance
- Physical state: solid, white powder
- Analytical purity: 99.3% area by GC
- Purity test date: 2006-05-22
- Lot/batch No.: lot# WYJ11410404533/ batch 25414
- Expiration date of the lot/batch: 2008-05-01
- Storage condition of test material: room temperature

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Highgate Farm, Market Rasen, Lincolnshire, England
- Age at study initiation: 33-39 weeks
- Weight at study initiation: 4.59 – 4.68 kg
- Housing: housed individually in plastic cages with perforated floors
- Diet (e.g. ad libitum): Each rabbit was offered 125 g of a standard laboratory rabbit diet (Rabbit Diet Pellets (GD) supplied by Highgate Farm) per day in addition to a dietary supplement of hay.
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 weeks


ENVIRONMENTAL CONDITIONS
- Temperature (deg C): 16 to 20 deg C
- Humidity (%): 40 to 70%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 hours dark/12 hours artificial light in each 24-hour period


IN-LIFE DATES: From: no data To: no data

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

other: An additional site on each treatment animal was similarly treated with the exception of test substance and acted as a control.

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g of test substance
- Concentration (if solution): no data


VEHICLE
- Amount(s) applied (volume or weight with unit): not applicable
- Concentration (if solution): not applicable
- Lot/batch no. (if required): not applicable
- Purity: not applicable

Duration of treatment / exposure:

Single 4 hour treatment

Observation period:

72 hours (observations made at 24, 48, and 72 hours for skin reaction)

Number of animals:

three

Details on study design:

TEST SITE
- Area of exposure: dorso-lumbar region
- % coverage: no data
- Type of wrap if used: The test substance was applied under a 2-ply 25 mm x 25 mm porous gauze pad secured with ‘blenderm’ surgical tape to intact skin sites, covered with cotton wool and "Tubigrip" elasticated bandage dressing for the duration of the exposure period.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): washed with lukewarm water (30-40 deg C) to remove any residual test substance and blotted dry with absorbent paper
- Time after start of exposure: 3 minutes, 1 hour, or 4 hours


SCORING SYSTEM:
A primary irritation index (PII) was calculated from the erythema and oedema scores according to the following formula as described in Technical Report No. 66 “Skin irritation and Corrosion: Reference chemicals data bank” (March 1995) ECETOC, Brussels. The maximum possible score was 8.0.
PII= (Σ Erythema at 24/48/72 hours + Σ Oedema at 24/48/72 hours)/(3 x number of animals)

Results and discussion

In vivo

Results

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: Mean of scores at approximately 24, 48, and 72 hours

Score:

0

Max. score:

8

Reversibility:

other: Not applicable

Irritant / corrosive response data:

No dermal irritation was apparent at any treatment site at any time during the study period.

Other effects:

There was no sign of toxicity or ill health in any rabbit during the observation period.

Any other information on results incl. tables

Not applicable

Applicant's summary and conclusion

Conclusions:

The Primary Irritation Index was calculated to be 0.0; the test substance was classified as ‘non-irritant’ according to the criteria of the ECETOC and did not require labelling with the risk phrase R38, “Irritating to skin”, in accordance with Commission Directive 2001/59/EC.

Executive summary:

Not applicable