Pentasodium pentahydrogen [[(phosphonatomethyl)imino]bis[ethane-2,1-diylnitrilobis(methylene)]]tetrakisphosphonate

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:

other: 1a The study was conducted according to the appropriate OECD test guideline, and in compliance with GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1982

Report date:

1982

Materials and methods

Principles of method if other than guideline:

Method: other: Safepharm protocol (number GM 11/80/21A). Broadly compatible with the now deleted OECD 401.

GLP compliance:

yes

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

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

Details on test material:

- Name of test material (as cited in study report): Briquest 543-33S (heptasodium salt of Diethylenetriamine penta(methylene phosphonic acid)
- Lot/batch No.: PD 4000
- Stability under test conditions: Not determined
- Storage condition of test material: Ambient temperature
No further details available.

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): Ad libitum
- Water (e.g. ad libitum): 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.
- 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

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 10 mL/kg bw

Mortality:

No deaths occurred.

Clinical signs:

other: At 3.0 ml/kg bw: General signs of toxicity in all animals included in this study included pilo-erection, abnormal body carriage (hunched posture) and lethargy for the first day after dosing. From day 2 after dosing, no abnormal symptoms observed.  No deat

Gross pathology:

No abnormal findings.

Other findings:

None reported.

Applicant's summary and conclusion

Interpretation of results:

study cannot be used for classification

Remarks:

Migrated information

Conclusions:

In a well conducted acute oral toxicity study (reliability score 1) conducted using a protocol comparable to the now deleted OECD 401, and to GLP, the LD50 for the sodium salt of DTPMP was >10 ml/kg bw in rats (reviewer comment: presumed equivalent to >5838 mg active salt/kg).

Taking the results of this study together with SafePharm study 92/8208 (1982), an LD50 of 10 ml/kg < LD50 < 15 ml/kg is determined for the test substance in the rat (reviewer comment: presumed equivalent to 5838 mg < LD50 < 8757 mg active salt/kg bw).

Executive summary:

In a well conducted acute oral toxicity study (reliability score 1) conducted using a protocol comparable to the now deleted OECD 401, and to GLP, the LD₅₀ for the sodium salt of DTPMP was >10 ml/kg bw in rats (reviewer comment: presumed equivalent to >5838 mg active salt/kg).

Taking the results of this study together with SafePharm Laboratories study 92/8208 (1982b), an LD₅₀ of 10 ml/kg < LD₅₀ < 15 ml/kg

is determined for the test substance in the rat (reviewer comment: presumed equivalent to 5838 mg < LD₅₀ < 8757 mg

active salt/kg bw).