[nitrilotris(methylene)]trisphosphonic acid, sodium salt

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

20.08.1982 to 03.09.1982

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1982

Report date:

1982

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Principles of method if other than guideline:

Method: SafePharm protocol (number GM 11/80/21A), broadly comparable with now-deleted OECD 401 at limit dose.

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

[nitrilotris(methylene)]trisphosphonic acid, sodium salt

EC Number:

243-900-0

EC Name:

[nitrilotris(methylene)]trisphosphonic acid, sodium salt

Cas Number:

20592-85-2

Molecular formula:

General formula C3H12NO9P3.xNa where x=3-5 ATMP-3Na C3H9NNa3O9P3 ATMP-4Na C3H8NNa4O9P3 ATMP-5Na C3H7NNa5O9P3

IUPAC Name:

Sodium salt of [nitrilotris(methylene)]trisphosphonic acid (3-5Na:1)

Test material form:

solid - liquid: aqueous solution

Remarks:

aqueous solution

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: A. Tuck & Sons Limited, Battlesbridge, Essex.
- Age at study initiation: 4-6 weeks
- Weight at study initiation: Males: 92-110 g; Females: 103-115 g
- Fasting period before study: Yes, overnight
- Housing: Groups of five in polypropylene cages
- Diet: Ad libitum
- Water: Ad libitum
- Acclimation period: Minimum five days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2 °C
- Humidity (%): 65-72 %
- Air changes (per hr): approximately 15 per hour
- Photoperiod (hrs dark / hrs light): 12 hours dark / 12 hours light


IN-LIFE DATES: From: 20.08.1982 to 03.09.1982

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

Doses:

10 mL/kg

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: Animals were observed 0.5, 1, 2, 3, 4 and 5 hours following dosing. On subsequent days the animals were observed at least once. Body weights were recorded on days 0, 7 and 14.
- Necropsy of survivors performed: Yes
- Other examinations performed: None

Statistics:

None required

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

>= 10 mL/kg bw

Based on:

test mat.

Remarks on result:

other: equivalent to 5740 mg active salt/kg bw and 4437 mg active acid/kg bw

Mortality:

Two females died within 3-4 hours of dosing. No other deaths occurred.

Clinical signs:

other: Pilo-erection, abnormal body carriage (hunched posture), lethargy and decreased respiratory rate. These signs were accompanied by ptosis in two males and one female and pallor of the extremities in one female. Recovery of survivors occurred by Day 2.

Gross pathology:

Congestion of the lungs in both animals that died and haemorrhage of the small intestine in one. There were no abnormal findings in surviving animals.

Other findings:

None

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

In the acute oral limit study, conducted according to the now-deleted OECD Test Guideline 401 and in compliance with GLP (Reliability 1), the LD50 for ATMP-xNa (aqueous solution containing 41% w/w active salt) was concluded to be ≥10 mL/kg (equivalent to 5740 mg active salt/kg bw and 4437 mg active acid/kg bw) in rats.