Fumaric acid

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

GLP compliance:

no

Remarks:

GLP was not yet legally implemented when the study was conducted.

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

Study report from 1989 available.

Test material

Test material information

Constituent 1

Reference substance name:

Fumaric acid

EC Number:

203-743-0

EC Name:

Fumaric acid

Cas Number:

110-17-8

Molecular formula:

C4H4O4

IUPAC Name:

but-2-enedioic acid

Details on test material:

- Physical state: Solid
- Analytical purity: >99.6%
- Lot/batch No.: Month average March 1989

In vivo test system

Test animals

Species:

guinea pig

Strain:

other: Bor: DHPW

Sex:

female

Details on test animals and environmental conditions:

One to five animals were kept in type IV Makrolon cages for an acclimation period of 5-8 days. Average weight of animals was 400 g. G4 general diet for guinea pigs and water were provided ad libitum. Room temperature was 20 °C with 60 % relative humidity. There were 15 air exchanges per hour with a 12 hr light-dark rhythm.

Study design: in vivo (non-LLNA)

Induction

Route:

intradermal and epicutaneous

Vehicle:

corn oil

Concentration / amount:

Induction, intradermal: 0.5%
Induction, epicutaneous: 25% test material

Day(s)/duration:

7

Adequacy of induction:

non-irritant substance, but skin pre-treated with 10% SDS

Challenge

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

corn oil

Concentration / amount:

Challenge: 25 %

Day(s)/duration:

2

Adequacy of challenge:

not specified

No. of animals per dose:

19 animals per dose

Details on study design:

A total of six intracutaneous injections were made in the right and left shoulder area of animals: a mixture of Freunds Complete Adjuvant and water, 0.5 % test material in corn oil, and 0.5 % test material in a mixture of FCA and corn oil. A patch test was carried out a week later. Twenty-four hours prior to the patch test, the shoulder region was shaved and 10 % SDS prepared in vaseline was massaged into the skin to provoke a mild skin irritation. Filter paper was coated with 25 % test material in corn oil, applied to the injection region and covered with an adhesive bandage. The patch was secured for 48 hrs with an elastic bandage.
Two weeks later, a filter paper patch coated with 25% test substance in corn oil was applied to the left flank of animals and covered with an adhesive bandage. An elastic bandage was used to secure the patch for 24 hours. A patch containing only corn oil was applied to the right flank of animals.

Challenge controls:

A total of six intracutaneous injections were made in the right and left shoulder area of animals: A mixture of Freunds Complete Adjuvant and water, corn oil, and a mixture of FCA and corn oil. A patch test was carried out a week later. Filter paper was coated with corn oil, applied to the injection region and covered with an adhesive bandage. The patch was secured for 48 h with an elastic bandage. Two weeks later, a filter paper patch coated with 25 % test substance in corn oil was applied to the left flank of animals and covered with an adhesive bandage. An elastic bandage was used to secure the patch for 24 hours. A patch containing only corn oil was applied to the right flank of animals.

Positive control substance(s):

not required

Results and discussion

Positive control results:

None - not necessary according to guideline.

In vivo (non-LLNA)

Results

Results 1

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

25 %

No. with + reactions:

0

Total no. in group:

19

Remarks on result:

no indication of skin sensitisation

Results 2

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

25 %

No. with + reactions:

0

Total no. in group:

19

Remarks on result:

no indication of skin sensitisation

Results 3

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

no indication of skin sensitisation

Results 4

Reading:

2nd reading

Hours after challenge:

45

Group:

negative control

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

no indication of skin sensitisation

Results 5

Group:

positive control

Remarks on result:

not measured/tested

Any other information on results incl. tables

Local reactions during experiment

After intracutaneous injection: All injection sites treated with FCA showed intense redness and swelling, as well as necrosis, in both control and treated animals. Mild redness and swelling was also seen in control animals treated with corn oil. Twenty-four hours after patch removal, all injection sites treated with FCA were crusted and scabby.

After patch test of 48 h duration: Intense inflammation, at times bloody, was seen in control and test animals treated with FCA and demineralised water. 24 hours after patch removal: all injections sites treated with FCA were crusted and scabby.

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Conclusions:

This study supports the conclusion that fumaric acid is not a skin sensitiser.

Executive summary:

Fumaric acid shows no sensitisation effect on the skin of female guinea pigs according to the Magnusson-Kligman maximization test.