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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Not stated
Reliability:
1 (reliable without restriction)
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.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1977

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Principles of method if other than guideline:
Groups of 5 rats were administered a single dose of the test material by gavage to determine single oral dose toxicity.
GLP compliance:
no
Remarks:
Study conducted prior to establishment of GLP guidelines
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Reference substance name:
Fumaric acid
EC Number:
203-743-0
EC Name:
Fumaric acid
Cas Number:
110-17-8
IUPAC Name:
but-2-enedioic acid
Details on test material:
Only the common name provided in publication

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
Rats weighed between 200 and 300 g and were maintained on Purina Formulab Chow 5008.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
not specified
Details on oral exposure:
Groups of five rats were administered various concentrations of the test material via gastic intubation.
Doses:
The dosages were arranged in a logarithmic series differing by a factor of two.
No. of animals per sex per dose:
5 males and 5 females per dose
Control animals:
not specified
Details on study design:
Single dose oral toxicity was determined by the method of Smyth et al, 1962. Based upon mortalities during the 14-day observation period, the most probable LD50 value was estimated using a moving average interpolation method or probit where sufficient data existed. The 95% confidence limits were estimated by the moving average technique.
Statistics:
Moving average interpolation or probit analysis

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
10 700 mg/kg bw
95% CL:
7 200 - 15 800
Sex:
female
Dose descriptor:
LD50
Effect level:
9 300 mg/kg bw
95% CL:
6 300 - 13 800
Mortality:
No data
Clinical signs:
other: No data
Gross pathology:
No data
Other findings:
No data

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
This study supports the conclusion that fumaric acid is of very low acute oral toxicity and would not require classification for oral toxicity under EU, CLP or GHS systems.
Executive summary:

Single dose oral toxicity of fumaric acid using Sprague-Dawley rats was reported as 10700 mg/kg for males and 9300 mg/kg for females.

Read across to fumaric acid is considered valid and malic acid is concluded to have low toxicity and classification is not required

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 to membranes and increase transport.

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

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