Malic acid

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Guideline-similar study published in a peer-reviewed journal. The publication details and summarises results for circa 110 organic and inorganic materials for whch acute tests were completed prior to introduction of formal test guidelines. The conducting institute - Mellon Institute for Industrial Research or Carnegie-Mellon Institute of Research is a recognised unit publishing peer-reviewed data of reliable quality. For read-across justification see Section 13.

Data source

Reference

Reference Type:

publication

Title:

Acute Toxicity and Skin Corrosion Data for Some Organic and Inorganic Compounds and Aqueous Solutions

Author:

Vernot EH, MacEwen JD, Haun CC and Kinhead ER

Year:

1977

Bibliographic source:

Tox Appl Pharmacol 42: 417-423, 1977

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Mortality following single exposure assessed in groups of 3 female animals

GLP compliance:

no

Remarks:

Study conducted prior to establishment of GLP guidelines

Test type:

other:

Limit test:

no

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:

(2E)-but-2-enedioic acid

Constituent 2

Reference substance name:

2-Butenedioic acid

IUPAC Name:

2-Butenedioic acid

Details on test material:

- Name of test material (as cited in study report): Fumaric acid
- Molecular formula (if other than submission substance): C4 H4 O4
- Molecular weight (if other than submission substance): 116.07
- Smiles notation (if other than submission substance): O=C(O)C=CC(=O)O
- InChl (if other than submission substance): 1S/C4H4O4/c5-3(6)1-2-4(7)8/h1-2H,(H,5,6)(H,7,8)/b2-1+
- Structural formula attached as image file (if other than submission substance): see Fig. Fumaric acid structure.jpg

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

No data
TEST ANIMALS
- Weight at study initiation: 3-4 kg
- Diet (e.g. ad libitum): Purina rabbit chow, ad libitum

Administration / exposure

Type of coverage:

occlusive

Vehicle:

not specified

Duration of exposure:

24 hours

No. of animals per sex per dose:

3 females / group

Control animals:

not required

Details on study design:

No data

Statistics:

No data

Results and discussion

Effect levels

Sex:

not specified

Dose descriptor:

LD50

Effect level:

> 20 000 mg/kg bw

Based on:

not specified

Mortality:

No mortality occurred

Clinical signs:

other: No data

Gross pathology:

No data

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

This study supports the conclusion that fumaric acid is of very low acute dermal toxicity and would not require classification for oral toxicity under EU, CLP or GHS systems.

Executive summary:

Single dose dermal toxicity of fumaric acid using female rabbits was reported as being in excess of 20000 mg/kg.

Read across to fumaric acid is considered valid and malic acid is considered to exhibit similar low toxicity. The rational for read across is that fumaric acid will metabolise in biological systems to malic acid. Fumaric acid is also slightly more fat soluble and is considered more likely to absorb via membranes and increase transport.

It is not considered valid to perform further animal tests on malic acid.