Trisodium dihydrogen -N,N-[bis[2-[bis(carboxylatomethyl)amino]ethyl]]glycinate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

August 1984

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: No data on batch number and composition; basic data given, comparable to guidelines (max reliability score can be 2)

Justification for type of information:

The source substance (DTPA 5K) and the target substance (DTPA 3Na) are the pentapotassium and trisodium salts of the same organic acid and are therefore structurally very similar. The purity/impurity profile for the source material is not characterised in the acute oral toxicity robust summary, but since the target material is > 99.9% pure and contains no detectable impurities, the extrapolation of acute oral toxicological properties from the source material to the target material is considered valid as a ‘worst case' scenario. The source material acute oral toxicity study was conducted according to OECD test guideline 401 and is considered reliable with restrictions (Category 2).

Cross-reference

Reason / purpose for cross-reference:

read-across: supporting information

Reference

Endpoint:

acute toxicity: oral

Type of information:

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

Adequacy of study:

key study

Justification for type of information:

The source substance (DTPA 5K) and the target substance (DTPA 3Na) are the pentapotassium and trisodium salts of the same organic acid (Diethylenetriaminepentaacetic acid) and are therefore structurally very similar. The two substances have comparable high water solubility and would be rapidly and fully dissociated into a common anion and sodium and potassium cations in the gastro-intestinal tract. The absorption, distribution and metabolism of the two substances would therefore be expected to be essentially identical. The common organic acid moiety has a chelating mode of action and would be expected to exert long-term, secondary adverse effects by the sequestration of essential metal ions, rather than specific acute organ toxicity. Sodium and potassium are normal physiological components of the body and are considered not to have any significant impact on the robustness of the read-across hypothesis.

Reason / purpose for cross-reference:

read-across source

Specific details on test material used for the study:

> 99% pure

Species:

rat

Route of administration:

oral: gavage

Vehicle:

not specified

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

5 000 mg/kg bw

Based on:

test mat.

Conclusions:

The acute oral toxicty of DTPA trisodium salt is predicted to be in excess of 5,000 mg/Kg.bw.

Executive summary:

The acute oral toxicity of DTPA pentapotassium salt is low with an LD50 value in excess of 5,000 mg/kg (OECD 401 guideline). DTPA pentapotassium salt is structurally similar to DTPA trisodium salt and the analogue has a similar chelating mode of action to the target substance. Based on a read-across approach DTPA trisodium salt is predicted to have similar low acute oral toxicity, with an LD50 in excess of 5,000 mg/kg.bw.

 

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1984

Report date:

1984

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Principles of method if other than guideline:

Limit test was carried out at 5000 mg/kg bw instead of 2000 mg/kg bw.

GLP compliance:

yes

Remarks:

audited in-house

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Reference substance 001

EC Number:

615-726-9

Cas Number:

7216-95-7

Test material form:

liquid

Details on test material:

No details on batch number and composition/purity
Appearance: clear colorless liquid
Date of receipt: 9 July 1984
Stored at ambient temperature

Test animals

Species:

rat

Strain:

other: HC/CFY (Remote Sprague Dawley)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hacking and Churchill Ltd. Huntingdon, UK
- Age at study initiation: 4-6 weeks
- Weight at study initiation: 114-132 g
- Fasting period before study: overnight prior to exposure
- Housing: in groups by sex in metal cages with wire mesh floors
- Diet (e.g. ad libitum): ad lib
- Water (e.g. ad libitum): ad lib
- Acclimation period: for a minimum of 8 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 64 (mean)
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 3 To: 17 August 1984

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

Test material applied as received.
DOSE VOLUME APPLIED: 3.76 ml/kg

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

2/sex in preliminary study
5/sex in main study

Control animals:

no

Details on study design:

- Duration of observation period following administration: 5 days (preliminary study), 14 days (main study)
- Frequency of observations and weighing: frequently on day of dosing, at least twice on following days. Weekly weighing.
- Necropsy of survivors performed: yes (main study)

Statistics:

Not needed because of limit test

Results and discussion

Preliminary study:

No mortality (0/4)

Effect levels

Sex:

male/female

Dose descriptor:

LD0

Effect level:

> 5 000 mg/kg bw

Mortality:

No mortality (0/10)

Clinical signs:

other: All animals (10/10): piloerection, hunched posture, abnormal gait, lethargy, decreased respiration rate, pallor of extremities, increased salivation, diarrhoea. Recovery was complete on day 5.

Gross pathology:

Terminal autopsy findings were normal.

Other findings:

None.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test material is not toxic as the acute lethal dose was > 5000 mg/kg bw

Executive summary:

The study was performed to assess the acute toxicity of the test material following a single oral administration to the Sprague-Dawley strain rat. The procedure permitted identification of the highest dose which could be administered without causing compound related mortality) . The study was performed according to OECD guideline 401. Following a preliminary test, a group of ten animals (five male and five female) was given a single, oral dose of the test material at a dose level of 5000 mg/kg bodyweight. The animals were observed for 14 days after the day of dosing and were then killed for gross pathological examination. There were no deaths. Clinical signs of toxicity noted were piloerection, hunched posture, abnormal gait, lethargy, decreased respiratory rate, pallor of extremities, increased salivation, and diarrhoea; recovery was complete on day 5.

All animals showed expected gains in bodyweight over the study period. No abnormalities were noted at necropsy. The acute median lethal dose (LD50) of the test material was found to be greater than 5000 mg/kg bodyweight. The test material was considered not to have significant acute toxicity and does not require classification as harmful, toxic or very toxic according to the GHS scheme.