(1S,3S,5S)-2-azabicyclo[3.1.0]hexane-3-carboxamide

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

02 October 2003 to 25 October 2002

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2003

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)

Version / remarks:

92/69/EEC (Official Journal No. L383A, 29.12.92

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

(1S,3S,5S)-2-azabicyclo[3.1.0]hexane-3-carboxamide

EC Number:

615-206-1

Cas Number:

709031-45-8

Molecular formula:

C6H10N2O.CH4O3S

IUPAC Name:

(1S,3S,5S)-2-azabicyclo[3.1.0]hexane-3-carboxamide

Test material form:

solid: particulate/powder

Details on test material:

Batch no: AAQ0195UN

Specific details on test material used for the study:

Idenitity: BMS 482204-03
Appearance: Powder
Storage conditions: Room temperature in the dark
Batch Number PRF02-19-3
BMS ATM reference number: PGEHS-16
Purity:95%
Expiry: 15 August 2002

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Animals for this study were selected from a stock supply of healthy adult rabbits of the New Zealand White strain, obtained from Highgate Farm, Market Rasen, Lincolnshire, England.
They were in the weight range of 2.81 to 2.89 kg and at least twelve weeks of age, prior to treatment (Day I). All rabbits were acclimatised to the experimental environment for a period of at least 19 days prior to the start of the study.
All rabbits were housed individually in stainless steel cages with perforated floors at the Eye Research Centre, Eye, Suffolk, IP23 7PX.
Each rabbit was offered 125 g of a standard laboratory rabbit diet (Special Diet Services STANRAB (P) SQC pellet) per day, drinking water was provided ad libitum. The batch of diet used for the study was analysed by the supplier for nutrients, possible contaminants and micro-organisms likely to be present in the diet and which, if in excess of specified amounts, might have an undesirable effect on the test system. The animals were given a dietary supplement of hay.

During the acclimatisation and study period the animals were given small soft white untreated wood blocks for environmental enrichment. Results of routine physical and chemical examination of drinking water, as conducted by the supplier are made available to Huntingdon Life Sciences Limited.

Animal room environmental controls were set to maintain temperature within the range 1 5 to 23 °C, and relative humidity within 40 to 70%. These environmental parameters were recorded and the permanent record archived with other departmental raw data. Lighting was controlled by means of a time switch to give 1 2 hours of artificial light (06:00 to 18:00 GMT) in each 24 hour period.

Each animal was identified by a numbered tag placed through the edge of one ear. This identification was unique within the Department throughout the duration of the study. Each cage was identified by a coloured label displaying the study number, animal number, phase of study and initials of the Study Director and Home Office licensee

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Amount / concentration applied:

0.5 g of the test substance

Duration of treatment / exposure:

three minutes, one or four hours duration in a step-wise manner and acted as a preliminary screen. In the absence of a severe effect on removal of the dressings the next exposure was initiated.

Observation period:

Examination of the treated skin was made on removal of the dressings (for 3 minute or one hour exposures) and approximately 24, 48 and 72 hours later.

Number of animals:

3

Details on study design:

On the day before application of the test substance, hair was removed with clippers from the dorso­ lumbar region of each rabbit exposing an appropriate sized area of skin.
The treatment site was 'wetted' with 0.5ml of reverse osmosis water and approximately 0.5 g of the test substance was applied under a 2-ply 25 mm x 25 mm porous gauze pad to intact skin sites on three animals. An additional site was similarly treated with the exception of test substance and acted as a control.
A single animal (number 4556) received three exposures (of three minutes, one or four hours duration) in a step-wise manner and acted as a preliminary screen. In the absence of a severe effect on removal of the dressings the next exposure was initiated.
For exposures of one hour or more each treatment site was covered with cotton wool and "Tubigrip" elasticated bandage dressing for the duration of the exposure period. The animals were returned to their cages immediately after treatment.
At the end of the exposure period the semi-occlusive dressing and gauze pad were removed and the treatment site was washed with lukewarm water (30-40°C) to remove any residual test substance. The treated area was blotted dry with absorbent paper.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

Very-slight erythema was seen in one animal one hour after bandage removal; no dermal reaction was observed at any other time or in any other animal throughout the duration of the study

Other effects:

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

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

BMS 482204-03 is not irriting to the skin

Executive summary:

A study was performed to assess the skin irritation potential of BMS 482204-03 (MSA SALT) to the rabbit. The method followed was that described in: EEC Methods for the determination of toxicity, Annex to Directive 92/69/EEC (Official Journal No. L383A, 29.12.92), Part B, Method B.4. Acute toxicity (Skin Irritation). OECD  Guideline  for  Testing  of Chemicals  No. 404  "Acute  Dermal   Irritation/Corrosion". Adopted 17 July 1992.

Three rabbits received a single four hour, semi-occlusive, dermal administration of approximately 0.5 g of the test substance as supplied and were observed for four days.

Very-slight erythema was seen in one animal one hour after bandage removal; no dermal reaction was observed at any other time or in any other animal throughout the duration of the study.The means of scores for these reactions at approximately 24, 48 and 72 hours after administration, calculated separately for each animal. Mean Erthema and Oedema was 0. Classification is triggered if means of scores for either effect are :2: 2 for two or three animals (or if effects persist to Day 14 in at least two animals). BMS was not considered to be irriting in this study

 

BMS 482204-03 (MSA SALT) did not require labelling with the risk phrase R38, "Irritating to skin", in accordance with Commission Directive 2001/59/EC.