[[(phosphonomethyl)imino]bis[ethylenenitrilobis(methylene)]]tetrakisphosphonic acid, ammonium salt

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

During November 1979

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1979

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

Conducted prior to adoption of OECD 401.

Deviations:

yes

Remarks:

Short acclimatisation period, wide variation in starting body weights, only 5 animals/sex.

Principles of method if other than guideline:

Method: other: Hazleton protocol (number P631/22/4/-/553/d/rev.1). The first four doses were in effect a dose-range finding study (only deaths recorded for 48 hours) and the highest dose a limit test.

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

[[(phosphonomethyl)imino]bis[(ethylenenitrilo)bis(methylene)]]tetrakisphosphonic acid, sodium salt

EC Number:

244-751-4

EC Name:

[[(phosphonomethyl)imino]bis[(ethylenenitrilo)bis(methylene)]]tetrakisphosphonic acid, sodium salt

Cas Number:

22042-96-2

Molecular formula:

C9H28N3O15P5.xNa

IUPAC Name:

sodium hydrogen [10,10-dihydroxy-10-oxido-2,5,8-tris(phosphonomethyl)-2,5,8-triaza-10-phosphadec-1-yl]phosphonate

Constituent 2

Reference substance name:

[[(phosphonomethyl)imino]bis[(ethylenenitrilo)bis(methylene)]]tetrakisphos phonic acid, sodium salt

IUPAC Name:

[[(phosphonomethyl)imino]bis[(ethylenenitrilo)bis(methylene)]]tetrakisphos phonic acid, sodium salt

Test material form:

liquid

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Bantin and Kingman Ltd
- Age at study initiation: No data
- Weight at study initiation: 150 to 250 g
- Fasting period before study: Overnight (18-20 hours)
- Housing: Groups of 2 or 5 in solid-bottomed plastic cages.
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: At least three days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 40-60
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): Natural light supplemented with fluorescent lighting during working hours (08.45-17.00)


IN-LIFE DATES: No data

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 25, 50, 100, 200, 500 mg/ml
- Justification for choice of vehicle: None given


MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg

Doses:

250, 500, 1000, 2000 and 5000 mg/kg bw. Doses presumed to be given in terms of DTPMP-xNa (not diluted solution), but not to have been corrected for purity, therefore presumed equivalent to 82.5, 165, 330, 660, and 1650 mg active salt/kg bw respectively.

No. of animals per sex per dose:

Two (except five at 500 mg/kg bw)

Control animals:

no

Details on study design:

- Duration of observation period following administration: High dose group only: 14 days
- Frequency of observations and weighing: High dose group only: All animals were observed for overt signs of toxicity or behavioural change at 15 minutes, 1, 2, and 4 hours after treatment and subsequently once daily for 14 days. Individual body weights were recorded on the day before treatment, on the day of treatment and 14 days after treatment.
- Necropsy of survivors performed: yes, in high dose group only.
- Other examinations performed: gross pathology.

Statistics:

None

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

>= 5 000 mg/kg bw

Effect levels 2

Sex:

male/female

Dose descriptor:

LD50

Effect level:

>= 1 650 mg/kg bw

Based on:

act. ingr.

Remarks:

active salt

Remarks on result:

other: equivalent to 1303 mg active acid/kg bw

Mortality:

No animals died during the observation period.

Clinical signs:

other: No clinical signs.

Gross pathology:

No animals died so no necropsies were performed.

Other findings:

None reported.

Any other information on results incl. tables

Calculation of equivalent dose: Based on DTPMP-xNa composed of 33% active salt including minor components, remainder water (MSDS).

For purposes of comparison with other Group 3 results, ≥1650 mg active salt/kg bw is equivalent to ≥1303 mg parent acid (DTPMP, CAS 15827-60-8)/kg bw.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Remarks:

No mortality or clinical signs of toxicity occurred in any of the test animals.

Conclusions:

In an acute oral toxicity study, conducted prior to the adoption of OECD Test Guidelines and GLP, the LD50 for DTPMP-xNa was ≥5000 mg/kg bw (equivalent to ≥1650 mg active salt/kg bw and ≥1303 mg active acid/kg bw) in the rat.