Disodium 2-hydroxyethyliminodi(acetate)

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From Oct. 1985 to Nov. 1985

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Limitations in study performance and reporting

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1985

Report date:

1985

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

See below

Principles of method if other than guideline:

Deviations: One single dose was tested, however this dose was 2 mL/kg of a 40% slurry and not 2000 mg/kg bw; 3 animals (rabbits)/sex were used; 3 animals out of 6 animals were abraded while guideline suggests the use of intact animals

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Disodium 2-hydroxyethyliminodi(acetate)

EC Number:

205-187-4

EC Name:

Disodium 2-hydroxyethyliminodi(acetate)

Cas Number:

135-37-5

Molecular formula:

C6H9NO5.Na2

IUPAC Name:

disodium 2-hydroxyethyliminodi(acetate)

Constituent 2

Reference substance name:

N-(2-Disodium 2-hydroxyethyliminodi(acetate)

IUPAC Name:

N-(2-Disodium 2-hydroxyethyliminodi(acetate)

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material: Hydroxyethyliminodiacetic acid Na salt (HEIDA, Na2)
- TSIN: E2748.01
- Molecular formula: Not reported
- Molecular weight: Not reported
- Substance type: Pure active substance
- Physical state: White powder
- Stability under test conditions: Not reported
- Storage condition of test material: Room 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: Ranch Rabbits, Crawley
- Age at study initiation: 11 to 20 weeks
- Weight at study initiation: 2.74 to 3.22 kg
- Fasting period before study: Not reported
- Housing: Animals were individually housed
- Diet : SOC Rabbit Diet, Special Diets Services Ltd, Stepfield, ad libitum
- Water: Ad libitum. Water was supplied by an automatic system. The diet and drinking water were considered not to contain any contaminant at a level that might have affected the objectives or integrity of the study. Water bottles were cleaned at weekly intervals.
- Acclimation period: At least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature: 16 to 20 °C
- Humidity: Not reported
- Air changes (per hr): Not reported
- Photoperiod: A cycle of 14 hours fluorescent light (6.00-20.00 h) and 10 hours darkness

IN-LIFE DATES: Not reported

Administration / exposure

Type of coverage:

occlusive

Vehicle:

water

Remarks:

Distilled

Details on dermal exposure:

APPLICATION OF TEST MATERIAL:
- The day before treatment the back and flank of each animal were clipped free of hair using electric clippers.
- The skin of 3 animals (2 males, 1 female) were left intact and the skin of the other 3 animals (1 male, 2 females) was abraded with the clipper head so as to penetrate the horny layer of the epidermis but without causing bleeding.
- Type of wrap used: The test material was applied uniformly to the shaved area and a porous gauze dressing was placed over the treated area and the treatment area occluded with a strip of impermeable plaster wound around the trunk of the animal.
- Each animal was placed in a plastic collar for the treatment period to prevent removal of the wrappings.
- After a 24 hour contact period the wrappings were cut through using blunt ended scissors and removed.

TEST SITE
- Area of exposure: Back and flanks of animal
- % coverage: Not reported

REMOVAL OF TEST SUBSTANCE
- Washing: Yes. Treated skin and surrounding area were wiped with a moist disposable towel
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied: 2 mL/kg
- Constant volume or concentration used: Yes
- For solids, paste formed: Yes. The test material was formulated as 40% w/v slurry in distilled water. The pH was adjusted with sodium hydroxide to 10.5

Duration of exposure:

24 hours

Doses:

2 mL/kg

No. of animals per sex per dose:

3 animals per sex

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed daily for 14 days. Body weights were recorded on the day of treatment and on Day 14 of observation.
- Necropsy of survivors performed: Yes
- Other examinations performed: Clinical signs, body weight, skin reaction, and necropsy.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 mL/kg bw

Based on:

test mat.

Remarks on result:

other: The test material was administered as 40% w/v slurry.

Mortality:

Two animals with abraded skin died within 96 hours of treatment. These differences were too small to positively infer a difference between intact and abraded animals.

Clinical signs:

other: Immediately prior to death lethargy, prostration and rapid respiration were observed in one animal. Slight erythema was noted in all animals with intact skin up to 3 days after treatment and in the 2 animals with abraded skin. Slight to moderate atonia wa

Gross pathology:

All animals were necropsied. No abnormalities were detected in those animals killed at termination. Gelatinous fluid in the abdominal cavity was observed in animals that died during the study. Lung discolouration was also observed which may have been an agonal change.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The acute percutaneous toxicity (LD50) of Hydroxyethyliminodiacetic acid Na salt was >2 mL/kg bw when administered as a 40% w/v slurry to New Zealand White rabbits.

Executive summary:

The acute dermal toxicity of hydroxyethyliminodiacetic acid Na salt was performed by following methods similar to the OECD Guideline 402 (Acute Dermal Toxicity).

Six young adult New Zealand white rabbits (3 males and 3 females) weighing 2.74 to 3.22 kg obtained from Ranch Rabbits, Crawley were used in the study. The animals were individually housed in a single air-conditioned room routinely maintained at temperature 16-20 °C. The animals were allowed free access to water and food (SQC Rabbit Diet, Special Diets Services Ltd., Stepfield). Animals were acclimatized for at least 7 days prior to the initiation of study.

One day before treatment, the back and flank of each animal were clipped free of hair using electric clippers. The test material was formulated as 40% w/v slurry in distilled water and applied at a dose level of 2 mL/kg. The test material was applied uniformly to the shaved area and a porous gauze dressing was placed over the treated area. The treatment area was occluded with a strip of impermeable plaster wound around the trunk of the animal. Each animal was placed in a plastic collar for the treatment period to prevent removal of the wrappings.

After a 24 hour contact period, the wrappings were removed. The treated skin and surrounding areas were wiped with a moist disposable towel to remove any residual test material.

The test sites were examined for local skin reactions. Observations for mortality, local skin reactions and behavioral abnormality were continued for a total of 14 days following the skin applications. Individual body weights were recorded on the day of treatment and on Day 14 of observation. A necropsy examination was conducted in all animals.

2 of the 3 animals with abraded skin died within 96 hours of treatment. All surviving animals showed normal body weight gains at termination.

The conclusion that mortality was treatment related was considered equivocal in view of the absence of changes in the surviving animals. The possibility exist that the deaths were caused by an exacerbation of an underlying pathological condition. This suggestion was supported by the presence of gelatinous fluid at necropsy in the animals that died during the study, suggesting the possibility of an infection.

Based on above it was concluded that, the acute percutaneous toxicity (LD50) of Hydroxyethyliminodiacetic acid Na salt was > 2 mL/kg bw when administered as 40% w/v slurry to New Zealand White rabbits.