ethynyl cyclopropane

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

The experimental phase of the study was undertaken between 3 and 17 March 1997.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP Guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1997

Report date:

1997

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Principles of method if other than guideline:

The method followed was based on that described in the EEC Methods for the determination of toxicity, Annex to Directive 92/69/EEC (OJ No. L383A, 29.12.92), Part B, Method B.3. Acute toxicity (dermal).

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

425-430-1

EC Name:

-

Cas Number:

6746-94-7

Molecular formula:

C5 H6

IUPAC Name:

ethynylcyclopropane

Details on test material:

- Name of test material (as cited in study report): EthynyI cyclopropane (SD 957)
- Physical state: Colourless liquid
- Analytical purity: 97-100 %
- Lot/batch No.: 3590-129-D4
- Expiration date of the lot/batch: January 1999
- Storage condition of test material: -20°C, under nitrogen and in the dark
- Intended use: Pharmaceutical intermediate

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan UK Ltd, Bicester, Oxon, England
- Age at study initiation: 7 to 10 weeks
- Weight at study initiation: 239 to 296 g
- Fasting period before study: no data
- Diet: standard laboratory rodent diet (RM 1(E) SQC) ad libitum
- Water: drinking water ad libitum
- Acclimation period: for a minimum period of five days prior to the start of the study


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 55 ± 15
- Air changes (per hr): 10 to 15
- Photoperiod (hrs dark / hrs light): 12/12

The batch(s) of diet used for the study was analysed for certain nutrients, possible contaminants and microorganisms.

Administration / exposure

Type of coverage:

occlusive

Details on dermal exposure:

ADMINISTRATION OF TEST SUBSTANCE
One day prior to treatment, hair was removed from the dorso-lumbar region of each rat with electric clippers taking care to avoid damaging the skin, exposing an area equivalent to approximately 10% of the total body surface area.
The test substance was applied by spreading it evenly over the prepared skin. The treatment area (approximately 50 mm x 50 mm) was covered with porous gauze. To reduce the likelihood of evaporation of test material from the treatment site the gauze was kept in place and protected by a sheet of aluminium foil. These were held in place with a non irritating dressing, and further covered by a waterproof dressing encircled firmly around the trunk of the animal.
Treatment in this manner was performed on Day 1(day of dosing) of the study only. At the end of the 24 hours exposure period the dressings were carefully removed and the treated area of skin was washed with warm water (30° to 40°C) to remove any residual test substance. The treated area was blotted dry with absorbent paper.

TEST SUBSTANCE PREPARATION
SD 957 was administered, as supplied by the Sponsor, at a volume of 2.56 ml/kg bodyweight (specific gravity 0.7825) to achieve a dose concentration of 2000 mg/kg. A sub-sample of SD 957 was transported just prior to, dosing in a closed container at ambient temperature from the Department of formulation to the animal holding area. In the main phase of the study, the test substance was retained in a fume cupboard housed in a walk-in ventilated cabinet which was separated from the cabinets in the main room in which the animals were housed.
The absorption of the test substance was not determined.
Characterisation of the homogeneity, stability and purity of the test substance was not undertaken in this study and remains the responsibility of the sponsor.

Duration of exposure:

24 hours

Doses:

2000 mg/kg bodyweight (the EU limit dose) .

No. of animals per sex per dose:

5 males and 5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: twice daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

OBSERVATIONS
Mortality
Cages of rats were checked at least twice daily for any mortalities.

Clinical signs
Animals were observed soon after dosing and at approximately hourly intervals for the remainder of Day 1. On subsequent days animals were observed once in the morning and again at the end of the experimental day (with the exception of Day 15 - morning only). The nature and severity of the clinical
signs and time were recorded at each observation.

Dermal responses
Local dermal irritation at the treatment site was assessed daily using the following numerical scoring system:
Erythema and eschar formation:
0 No erythema
1 Slight erythema
2 Well defined erythema
3 Moderate erythema
4 Severe erythema (beet redness) to slight eschar formation (injuries in depth)

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

Bodyweight
The bodyweight of each rat was recorded on Days 1(prior to dosing), 8 and 15. Individual weekly bodyweight changes and group mean bodyweights were calculated.

TERMINAL STUDIES
Termination
All animals were killed on Day 15 by cervical dislocation.

Macroscopic pathology
All animals were subjected to a macroscopic examination which consisted of opening the thoracic and abdominal cavities. The cranial cavity was not examined as observations did not indicate neurotoxic activity. The macroscopic appearance of all examined organs, was recorded and macroscopic
abnormalities (in this instance the treatment site) were preserved.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

There were no deaths in a group of ten rats (five males and five females) following a single dermal application of SD 957 at a dose level of 2000 mg/kg bodyweight.

Clinical signs:

other: There were no signs of systemic reaction to treatment.

Gross pathology:

No abnormalities were observed at the study termination necropsy .

Any other information on results incl. tables

The acute lethal dermal dose to rats of SD 957 was demonstrated to be greater than 2000 mg/kg bodyweight .