Methyl tetrahydro-2-furancarboxylate

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 28 November 1995 to 6 January 1996

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study according to international guideline

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Report date:

1996

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: Magnusson, B. and Kligman, A.M. (1970) Allergic Contact Dermatitis in the Guinea-pig/ Idetification of contact allergens, Thomas, C.C., Springfield, Illinois, U.S.A.

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Test material

Test material information

Constituent 1

Reference substance name:

Methyl tetrahydro-2-furancarboxylate

EC Number:

420-670-1

EC Name:

Methyl tetrahydro-2-furancarboxylate

Cas Number:

37443-42-8

Molecular formula:

C6H10O3

IUPAC Name:

methyl oxolane-3-carboxylate

Test material form:

other: liquid

Details on test material:

Identity: Methfat
Chemical name: Methyl tetrahydro-2-furoate
Intended use: Pharmaceutical intermediate
Appearance: Clear colourless liquid
Storage conditions: room temperature
Batch number: 17-5C03 (GLFC Bx No. 0002)
Expiry: 7 November 1996
Purity: 99.40%
Date received: 17 November 1995

In vivo test system

Test animals

Species:

guinea pig

Strain:

Dunkin-Hartley

Details on test animals and environmental conditions:

The animals were in the weight range of 293 to 338g on arrival and approximately four to five weeks of age. All the guinea-pigs were acclimatised to the experimental environment for six days prior to the allocation to the main study.
An additional six animals, from the same supplier, were used for the preliminary investigations.

The guinea-pigs were housed in groups of five in suspended metal cages with wire mesh floors in Buildings R17 room 14.
A vitamin C enriched guinea-pig diet FD2 and drinking water were provided as libitum. Hay was given weekly.
The batch of diet used for the study was not analysed for nutrients, possible contaminants or micro-organisms.
Animal room temperature was maintained at approximately 21°C and relative humidity at 30-70%. These environmental parameters were recorded daily. Air exchange was maintained at approximately 15 air changes per hour and lighting was controlled by means of a time switch to give 12 hours of artificial light (0.700-1900 hours) in each 24 hours period.
Each animal was identified by ear tattoo number. This number was unique within the Huntingdon Life Sciences Industrial Toxicology Department throughout the duration of the study. Each cage was identified by a coloured label displaying the study schedule number, animal numbers and the initials of the Study Director and Home Office licensee.

Study design: in vivo (non-LLNA)

Induction

Route:

intradermal and epicutaneous

Vehicle:

other: Alembicol D

Challenge

Route:

epicutaneous, occlusive

Vehicle:

other: Alembicol D

No. of animals per dose:

Control animals: 5
Test animals: 10

Details on study design:

Induction intradermal injections - test animals
A 40 x 60 mm area of dorsal skin on the scapular region of the guinea-pig was clipped free of hair with electric clippers. Three pairs of intradermal injections were made into a 20 x 40 mm area within the clipped area.
Injectables for the test animals were prepared as follows:
1. Freund's complete adjuvant was diluted with an equal volume of water for irrigation
2. Methfat, 2.5% v/v in Alembicol D
3. Methfat, 2.5% v/v in a 50:50 mixture of Freund's complete adjuvant and Alembicol D.

Induction topical application - test animals
The preliminary investigations indicated that the maximum practical concentration of the test substance for topical application (as supplied) did not produce skin irritation. Therefore, six days after the injections, the same 40 x 60 mm interscapular area was clipped and shaved free of hair and the site was pre-treated by gentle rubbing with 0.5 ml per site of 10% w/w sodium lauryl sulphate in petrolatum. Twenty-four hours later a 20 x 40 mm patch of Whatman No. 3 paper was saturated with approximately 0.4 ml of Methfat, as supplied. The patch was placed on the skin of the test animals and covered by a length of impermeable plastic adhesive tape (50 mm width "Blenderm"). This in turn was firmly secured by elastic adhesive bandage (50 mm width "Elastoplast") wound round the torso of the animal and fixed with "Sleek" impervious plastic adhesive tape. The dressing was left in place for 48 hours.

Induction - control animals
During the induction phase, the control animals were treated similarly to the test animals with the exception that the test substance was omitted from the intradermal injections and topical application.

Challenge controls:

Challenge - control and test animals
The control and test animals were challenged topically two weeks after the topical induction application using Methfat, as supplied and 50 % v/v in Alembicol D.
Hair was removed by clipping and then shaving from an area on the left flank of each guinea-pig. A 20 x 20 mm patch of Whatman No. 3 paper was saturated with approximately 0.2 ml of methfat, 50 % v/v i, Alembicol D was applied in a similar manner to a posterior site. The patches were sealed to the flank for 24 hours under strips of "Blenderm" covered by "Elastoplast" wound round the trunk and secured with "Sleek".

Positive control substance(s):

yes

Remarks:

The sensitivity of the guinea-pig strain used is checked periodically at Huntingdon Life Sciences with hexyl cinnamic aldehyde, a known sensitiser.

Results and discussion

In vivo (non-LLNA)

Results

Results 1

Group:

other: Freund's treated controls

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

Intradermal injection: Necrosis or slight irritation / Topical application Moderate erythema

Remarks on result:

other: Group: other: Freund's treated controls. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: Intradermal injection: Necrosis or slight irritation / Topical application Moderate erythema.

Results 2

Group:

test chemical

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

Intradermal injection: Necrosis or slight irritation / Topical application: Moderate erythema

Remarks on result:

other: Group: test group. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: Intradermal injection: Necrosis or slight irritation / Topical application: Moderate erythema.

Any other information on results incl. tables

Clinical signs

No signs of ill health or toxicity were recorded.

Bodyweight

Bodyweight increases were recorded for all guinea-pigs over the period of the study.

Induction

- Intradermal injections

Necrosis was recorded at site receiving Freund's complete adjuvant in test and control animals

Slight irritation was seen in test animals at sites receiving Methfat, 2.5% v/v in Alembicol D and slight irritation was observed in control animals receiving Alembicol D.

- Topical application

Moderate erythema was observed in test animals following topical application with Methfat, as supplied.

Moderate erythema was seen in the control guinea-pigs.

Challenge

There were no dermal reactions seen in any of the test or control animals.

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

In this study, Methfat did not produce evidence of skin sensitisation (delayed contact hypersensitivity) in any of the ten test animals.