L-Aspartic acid, N,N'-1,2-ethanediylbis-, sodium salt (1:3)

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

26 April to 10 May 1989

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

416-530-4

EC Name:

-

Cas Number:

178949-82-1

Molecular formula:

C10H13N2Na3O8

IUPAC Name:

trisodium 2-({2-[(1-carboxy-2-carboxylatoethyl)amino]ethyl}amino)butanedioate

Details on test material:

- Name of test material (as cited in study report): trisodium EDDS (under code)
- Substance type: technical product
- Physical state: white, granular powder
- Purity test date: no data
- Lot/batch No.: no data
- Expiration date of the lot/batch: March 1990
- Stability under test conditions: no data
- Storage condition of test material: ambient temperature

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Froxfield Rabbits, Petersfield, Hampshire, UK
- Age at study initiation: 6-8 weeks
- Weight at study initiation: 2.3-2.7 kg (although report states 2.3-2.7 g)
- Fasting period before study: no
- Housing: individually in metal cages with perforated floors
- Diet (e.g. ad libitum): conventional, ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: minimum 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.6-21.0
- Humidity (%): mean 52
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

water

Remarks:

used to moisten the test substance and aid adhesion to the skin

Details on dermal exposure:

TEST SITE
- Area of exposure: dorso-lumbar region
- % coverage: 10
- Type of wrap if used: gauze held in place with a "non-occlusive" dressing encirclating the trunk

REMOVAL OF TEST SUBSTANCE
- Washing (if done): warm water (30-40oC) and blotted dry
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.64 mL/kg bw
- For solids, paste formed: no (moistened with water after application)

VEHICLE
- Amount(s) applied (volume or weight with unit): 2.64 mL/kg bw

Duration of exposure:

24 h

Doses:

2640 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observed at "frequent intervals" on day of dosing, then at least twice daily until study termination. Weighed before dosing, then weekly
- Necropsy of survivors performed: yes
- Other examinations performed: macroscopic examination of abdominal and thoracic cavities
other: erythema, eschar formation, oedema of the test site scored daily

Statistics:

not applicable

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 640 mg/kg bw

Based on:

test mat.

Remarks on result:

no indication of skin irritation up to the relevant limit dose level

Mortality:

No deaths occurred during the study

Clinical signs:

other: Diarrhoea was observed in 3 males and 3 females lasting about 2 days for each animal, but this was not considered to be treatment-related

Gross pathology:

No abnormalities were observed following macroscopic examination of the thoracic and abdominal organs and tissues

Other findings:

No irritation reactions were detected

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

In a GLP study conducted according to OECD Guideline 402 (available at the time), an acute dermal 24-h LD50 value of >2640 mg/kg bw was determined for trisodium EDDS in male and female rabbits following semi-occlusive application.

Executive summary:

In a GLP study conducted according to OECD Guideline 402 (available at the time), the acute dermal toxicity of trisodium EDDS was assessed in male and female New Zealand White rabbits.

The test powder (2.64 g/kg bw) was applied to the clipped backs of five rabbits of each sex, moistened with water to aid adhesion to the skin and covered with a semi-occlusive dressing for 24 h. The test substance was subsequently removed by washing in warm water and blotting dry. The animals were observed for 14 days for mortality, clinical signs of systemic toxicity, irritation of the application area and body weight changes, after which they were killed and the organs of the thoracic and abdominal cavities were examined macroscopically.

No clinical signs of toxicity were seen in any of the animals and no deaths occurred during the 14-d observation period. Diarrhoea, lasting about 2 days in three animals of each sex was not considered to be treatment-related. At necropsy, no gross changes in organs or tissues were detected.

An acute dermal 24-h LD50 value of >2640 mg/kg bw was determined for trisodium EDDS in male and female rabbits. According to EU CLP regulation, trisodium EDDS would not be classified as acutely toxic by the dermal route under the conditions of this test.