Sodium salts of [[(phosphonomethyl)imino]bis[ethane-2,1-diylnitrilobis(methylene)]]tetrakisphosphonic acid (5-7 Na:1)

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

19.08.1982 to 02.09.1982

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 401 (Acute Oral Toxicity)

Principles of method if other than guideline:

Method: SafePharm protocol (number GM 11/80/21A). Broadly compatible with the now-deleted OECD Test Guideline 401.

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

octadecasodium ({[2-({2-[bis(hydrogen phosphonatomethyl)amino]ethyl}(hydrogen phosphonatomethyl)amino)ethyl](hydrogen phosphonatomethyl)amino}methyl)phosphonate {[(hydrogen phosphonatomethyl)({2-[(hydrogen phosphonatomethyl)({2-[(hydrogen phosphonatomethyl)(phosphonatomethyl)amino]ethyl})amino]ethyl})amino]methyl}phosphonate {[(hydrogen phosphonatomethyl)({2-[(hydrogen phosphonatomethyl)({2-[(hydrogen phosphonatomethyl)(phosphonomethyl)amino]ethyl})amino]ethyl})amino]methyl}phosphonate

EC Number:

701-216-4

Molecular formula:

DTPMP-5Na C9H23N3Na5O15P5 DTPMP-6Na C9H22N3Na6O15P5 DTPMP-7Na C9H21N3Na7O15P5

IUPAC Name:

octadecasodium ({[2-({2-[bis(hydrogen phosphonatomethyl)amino]ethyl}(hydrogen phosphonatomethyl)amino)ethyl](hydrogen phosphonatomethyl)amino}methyl)phosphonate {[(hydrogen phosphonatomethyl)({2-[(hydrogen phosphonatomethyl)({2-[(hydrogen phosphonatomethyl)(phosphonatomethyl)amino]ethyl})amino]ethyl})amino]methyl}phosphonate {[(hydrogen phosphonatomethyl)({2-[(hydrogen phosphonatomethyl)({2-[(hydrogen phosphonatomethyl)(phosphonomethyl)amino]ethyl})amino]ethyl})amino]methyl}phosphonate

Test material form:

solid - liquid: 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 and Sons Ltd., Battlesbridge, Essex, UK.
- Age at study initiation: 4-6 weeks
- Weight at study initiation: Males: 98-120 g; Females: 90-115 g
- Fasting period before study: Overnight prior to dosing
- Housing: Groups of five in polypropylene cages
- Diet (e.g. ad libitum): "Standard laboratory rodent diet", ad libitum
- Water (e.g. ad libitum): Mains tap water, ad libitum
- Acclimation period: Minimum of five days


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


IN-LIFE DATES: From: 19.08.1982 to 02.09.1982

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg bw

Doses:

3 and 10 ml/kg bw

No. of animals per sex per dose:

Five

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Daily observations and weighing on days 0, 7 and 14.
-Further observations were made 0.5, 1, 2, 3, 4, and 5 hours following dosing for mortalities and signs of overt toxicity.
-All surviving animals were killed on day 14.
- Necropsy of survivors performed: yes
- Other examinations performed: macroscopic examination of abnormal organs.

Statistics:

Not required as no deaths occurred.

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

>= 10 mL/kg bw

Based on:

test mat.

Effect levels 2

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

>= 5 838 mg/kg bw

Based on:

act. ingr.

Remarks:

active salt

Remarks on result:

other: equivalent to 4612 mg active acid/kg bw/day

Mortality:

No deaths occurred.

Clinical signs:

irregular respiration

lethargy (hypoactivity)

other:

Body weight:

other body weight observations

Remarks:

Bodyweight gains of all rats were considered to be within normal limits, apart from one male dosed at 3.0 ml/kg. This decrease in weight gains was not seen in the higher dosage group, and therefore cannot be considered to be test substance related.

Gross pathology:

No abnormal findings.

Other findings:

None reported.

Any other information on results incl. tables

Calculation of equivalent dose:

1) average specific gravity of DTPMP (5-7Na) = 1.39 (email, I. Bartlett to R. Wildey, 09.04.2003), 

2) DTPMP (5-7Na) composed of 42% active salt including minor components, remainder presumed to be water (derived from online data sheet).

For purposes of comparison with other Group 3 results, >5838 mg active salt/kg bw is equivalent to >4612 mg parent acid (DTPMP, CAS 15827-60-8)/kg bw.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

In the acute oral toxicity study, conducted using a protocol comparable to the now-deleted OECD Test Guideline 401 and in compliance with GLP, the LD50 for DTPMP (5-7Na) was ≥10 ml/kg bw in rats (equivalent to ≥5838 mg active salt/kg bw and ≥4612 mg active acid/kg bw based on an aqueous solution containing 33% active acid).