Aspartic acid

Endpoint summary

Description of key information

L-aspartic acid is a naturally occurring amino acid and is practically non-toxic in the acute toxicity studies available.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2002

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study with GLP.

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Strain: Crl:CD(SD)IGS BR.
Supplier: Charles River WIGA, Germany
Age: Ca. 8 weeks at the time of the administration.

Room temperature: Average of 22.1 °C.
Relative humidity: Average of 47.6 %.
Air exchange: 12 per hour.
Light: Artificial light from 6 a.m. to 6 p.m.
Cages: Single caging in Makrolon cages type III (39 cm x 23 cm bottom area, 18 cm height). Wire mesh lids.
Bedding material: Aspen wood chips, autoclaved.
Environmental enrichment: Nibbling wood bricks (10 cm x 2 cm x 2 cm) and nesting material.
Feed: Altromin 1324 forte, gamma irradiated with 25 kGy 60Co, ad libitum. Exception: The feed was withdrawn the evening before the administration of the test substance and was offered again about three hours afterwards.
Water: Tap water, ad libitum.
Acclimatisation: At least 5 days.

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Details on oral exposure:

The test substance was suspended in 0.1 % carboxymethyl cellulose, as an aqueous solution.

Doses:

200 and 2000 mg/kg bw.
Dose volume: 10 mL/kg bw.

No. of animals per sex per dose:

3 m + 3 f per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days.
- Frequency of observations and weighing: Observations were performed within the periods 0 - 0.5, 0.5 - 1, 1 - 2, 2 - 4 and 4 - 6 hours after administration (p.a.) of the test substance and then at least once a day. Body weights were determined before administration, 7 days p.a. and 14 days p.a.
- Necropsy of survivors performed: yes.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed.

Clinical signs:

other: No toxic effects were observed.

Gross pathology:

All animals were normal at the necropsy 14 d p.a.

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: OECD GHS

Conclusions:

No toxic effects of the test substance were noted by signs in life and post mortem. The oral LD50 of L-aspartic acid to rats was estimated to be higher than 2000 mg/kg body weight.

Executive summary:

Methods and investigations were performed in conformance with the OECD-Guideline 423, 1996 and the Directive 96/54/EC, method B.1.tris. L-Aspartic acid was administered once by stomach intubation to 6 male and 6 female rats as a suspension in 0.1 % aqueous carboxymethyl cellulose. The dosing was performed sequentially to groups of 3 animals per sex using a starting dose of 200 mg per kg body weight and 2000 mg per kg body weight as the second dose.

No toxic effects of the test substance were noted by signs in life and post mortem. According to the decision trees of the guidelines the LD50,oral of L-aspartic acid was estimated to be higher than 2000 mg/kg body weight in rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Guideline study with GLP.
The LD50 in the key study is not 2000 mg/kg bw but greater than 2000 mg/kg bw. This result can not be entered in the preceding field.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

other justification

Justification for data waiving:

other:

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: Citation in a peer reviewed journal.

Principles of method if other than guideline:

Tada 2008 cited in his publication a study on the acute dermal toxicity with rabbits and the result of the study.

Test type:

standard acute method

Species:

rabbit

Sex:

not specified

Dose descriptor:

LD50

Effect level:

5 000 mg/kg bw

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: OECD GHS

Conclusions:

The dermal LD50 of L-aspartic acid to rabbits is reported to be 5000 mg/kg bw.

Executive summary:

Tada 2008 cited in his publication a study on the acute dermal toxicity with rabbits and the result of the study.

The dermal LD50 of L-aspartic acid to rabbits is reported to be 5000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

The weight of evidence, including a acute dermal toxicity study and acute toxicity studies with other routes and no local effects, is considered to be sufficient to conclude a low toxicity and no classification of L-aspartic acid after acute dermal dosing.

Additional information

Justification for selection of acute toxicity – oral endpoint
The key study was chosen.
The result is supported by two further data: In the first cited study, the oral LD50 of L-aspartic acid to rats is 5 000 mg/kg bw.
In the second cited study, the oral LD50 of L-aspartic acid to rats is greater than 16 000 mg/kg bw.

Justification for selection of acute toxicity – inhalation endpoint
According to column 2 of Annex VIII of REACH, i.e. "Testing by the inhalation route is appropriate if exposure of humans via inhalation is likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size." The high mass median diameter of the substance is between 372 and 401 µm. The low vapour pressure is 0.000035 Pa at 25 °C. No relevant exposure of humans is therefore expected and no justification to perform an acute inhalation toxicity test is obtained.
In addition, L-aspartic acid is not classified as to local irritation and does not show toxic effect in the acute toxicity studies with oral, dermal and intraperitoneal routes of administration, even at high doses of 5000 mg/kg bw and above. Therefore and with respect to animal welfare an acute inhalation toxicity study is not justified.

Justification for selection of acute toxicity – dermal endpoint
The substance is not classified as to local irritation and does not show toxic effect in the acute toxicity studies with oral, dermal and intraperitoneal route of administration even at high doses of 5000 mg/kg bw and above. Therefore and with respect to animal welfare, the repetition of the acute dermal toxicity study, which is not described to present standards, is not justified.

Justification for classification or non-classification

There is no indication from the various studies with different routes of application that a classification might be required.