Succinic acid

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

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

Adequacy of study:

key study

Study period:

unknown

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study published in a peer-reviewed journal, Read across.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1990

Report date:

1990

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

less animals, shorter observation period, no body weights reported

Principles of method if other than guideline:

Administration of 5 different to doses to groups of 4 male and 4 female rats each.
Observation period 10 days.
Recording of clinical signs and mortality.
Necropsy of survivors.

GLP compliance:

not specified

Test type:

other: standard procedure with variations

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Sodium hydrogen succinate

EC Number:

220-871-2

EC Name:

Sodium hydrogen succinate

Cas Number:

2922-54-5

IUPAC Name:

sodium hydrogen succinate

Constituent 2

Reference substance name:

Monosodium succinate

IUPAC Name:

Monosodium succinate

Details on test material:

- Name of test material (as cited in study report): Monosodium succinate
- Analytical purity: 100.2 % (99.7-100.7 %)
- Producer: Mitsubishi Kasei Food Co. (Tokyo, Japan)
- Provider: Japan Food Additives Association (Tokyo, Japan)
- Stability under test conditions: The stability of a 2 % aqueous solution of the test substance was ascertained for at least one week at room temperature.

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Japan, Inc. (Kanagawa, Japan)
- Status: SPF
- Age at study initiation: 6 weeks
- Weight at study initiation: between 100 and 200 g, not reported (only growth curves available)
- Fasting period before study: none reported
- Diet: basal diet (CRF-1), Oriental Yeast Inc., Tokyo, Japan)
- Water: tap water
- Acclimation period: one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): not reported
- Humidity (%): not reported
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): not reported

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

distilled water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: not reported
- Amount of vehicle (if gavage): not reported
- Justification for choice of vehicle: not reported

MAXIMUM DOSE VOLUME APPLIED: not reported

Doses:

0.5, 1, 2, 4, 8 g monosodium succinate per kg body weight

No. of animals per sex per dose:

4

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 10 days
- Frequency of observations and weighing: not reported
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, necropsy

Statistics:

None reported

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 8 000 other: mg Na-succinate / kg bw

Based on:

test mat.

Effect levels 2

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 6 740 other: mg succinic acid / kg bw

Based on:

other: LD50 for Na-succinate was transformed to succinic acid, taking into account the different molecular weights.

Remarks on result:

other: The transformation from Na-succinate to succinic acid seems justified, as both substances will be in the ionised form in dilute aqueous solution.

Mortality:

1/4 females (dose: 8 g/kg) at week 1

Clinical signs:

other: 4 or 8 g/kg: decrease in spontaneous activity, recovering in a few days

Gross pathology:

8 g/kg: haemorrhage of the lungs in some animals

Applicant's summary and conclusion

Interpretation of results:

study cannot be used for classification

Remarks:

Migrated information

Conclusions:

The LD50 in an acute toxicity study with rats was >8000 mg monosodium succinate per kg body weight.
No classification for monosodium succinate is derived from the results of this study and also no classification for succinic acid.
The corresponding LC50 of succinic acid is >6740 mg/kg bw. The transformation of the LD50 from monosodium succinate to succinic acid seems justified, as both substances will be in the ionised form in dilute aqueous solution and the relevant anion is then the same.

Executive summary:

Monosodium succinate was dissolved in distilled water and was administered orally via gavage to 5 groups of 4 male and 4 female rats each at doses of 0.5, 1, 2, 4 or 8 g per kg body weight. The survivors were necropsied after 10 days.

No other clinical signs were noted than a transient decrease in spontaneous activity of the animals at the highest dose. One high dosed female died in week 1. Necropsy showed haemorrhage of the lungs in some high dose group animals.

The LD50 was higher than 8000 mg monosodium succinate per mg body weight. Even if the different molecular weights of monosodium succinate and succinic acid are taken into account, the LD50 is far above 2000 mg per kg body weight and no classification is derived for succinic acid.