[nitrilotris(methylene)]trisphosphonic acid, ammonium salt

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

03.08.1982 to 17.08.1982

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

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 402 (Acute Dermal Toxicity)

Principles of method if other than guideline:

Method: SafePharm protocol (number GM 08/82/53A)

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, Essex, UK.
- Age at study initiation: 6-8 weeks
- Weight at study initiation: Males: 219-242 g: Females: 210-232 g.
- Fasting period before study: None
- Housing: Five per polypropylene cage
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: Minimum five days.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22± 3
- Humidity (%): 65-75
- Air changes (per hr): approximately 15
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 03.08.1982 to 17.08.1982

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: Dorsal, lateral and ventral.
- % coverage: No data
- Type of wrap if used: The trunks of the rats were encircled with a strip of elastic adhesive bandage, backed with aluminium foil. The bandage was tightened sufficiently to prevent the animal from wriggling free and wrapped round to form a double layer.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: 24 hours


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 10 ml/kg
- Constant volume or concentration used: yes

Duration of exposure:

24 hours

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:

No animals died.

Clinical signs:

other: Lethargy and increased red coloured lacrimation in one rat on the day of dosing.

Gross pathology:

No abnormal findings.

Other findings:

None

Any other information on results incl. tables

The dermal LD50 in the rat was determined to be >10 ml/kg bw (reviewer comment: presumed equivalent to >5740 mg active
salt/kg bw).

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

In the acute dermal toxicity study, conducted according to a protocol similar to OECD Test Guideline 402 and in compliance with GLP, 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.