TETRASODIUM ETHYLENE 1,1-DIPHOSPHONATE

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2002-05-20 - 2002-06-24

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2002

Report date:

2002

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

GLP compliance:

yes (incl. QA statement)

Remarks:

2000-04-26

Test type:

acute toxic class method

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

443-520-7

EC Name:

-

Cas Number:

33016-77-2

Molecular formula:

C2H4Na4O6P2

IUPAC Name:

tetrasodium (1-phosphonatoethenyl)phosphonate

Test material form:

solid

Specific details on test material used for the study:

- Synonyms: ITC 908, vinylidenephosphonic acid tetrasodium salt (VDPA tetrasodium salt)
- Lot/batch No.of test material: 562CH/646
- Purity: 87.33%
- Storage condition of test material: Room temperature, in the dark

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Ltd, Margate, Kent, UK
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8-12 weeks old
- Fasting period before study: Overnight fast immediately before dosing
- Housing: Animals were housed in groups of three in suspended solid-floor polypropylene cages furnished with woodflakes.
- Diet: Certified Rat and Mouse Diete supplied by PMI Nutrition International, Nottingham UK, ad libitum
- Water: ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 30-70
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 30 and 200 mg/ml
- Amount of vehicle: 10 ml/kg

CLASS METHOD
- Rationale for the selection of the starting dose: In the absence of data suggesting the test material was toxic, 300 mg/kg was chosen as the starting dose.

All animals were dosed once only by gavage, using a metal cannula attached to a graduated syringe. Sufficient time was allowed between each group and each dose level to confirm the survival of the previously dosed animals.

Doses:

300, 2000 mg/kg

No. of animals per sex per dose:

6 (300 mg/kg)
3 (2000 mg/kg)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed for deaths or overt signs of toxicity 30min, 1, 2 and 4h after dosing and subsequently once daily; Individual bodyweights were recorded prior to dosing and seven and fourteen days after treatment or at death.
- Necropsy of survivors performed: yes

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths at 300 mg/kg
2/3 animals dead at 2000 mg/kg (within two or four hours after dosing)

Clinical signs:

other: Signs of systemic toxicity noted in animals treated with 2000 mg/kg were hunched posture, lethargy, decreased respiratory rate, ptosis, ataxia, clonic convulsions, splayed gait and diuresis. The surviving animal treated with 2000 mg/kg appeared normal fou

Gross pathology:

Abnormalities noted at necropsy of animals that died during the study were dark liver, sloughing of the gastric mucosa and non-glandular epithelium of the stomach and gaseous distension of the small intestine. No abnormalities were noted at necropsy of animals that were killed at the end of the study.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The acute oral median lethal dose (LD50) of the test material in female rats falls in the range 300-2000 mg/kg.

Executive summary:

The acute oral median lethal dose (LD50) of the test material in female rats was investigated according to OECD TG 423 and under GLP conditions. The LD50 falls in the range 300-2000 mg/kg, warranting a classification as Acute toxicity 4 H302.