Diphosphoric acid, compd. with piperazine (1:1)

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

11 March to 25 March 2003

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2003

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

457-330-7

EC Name:

-

Cas Number:

66034-17-1

Molecular formula:

Hill formula: C4H10N2:H4O7P2 CAS formula: C4H10N2:H4O7P2

IUPAC Name:

(phosphonooxy)phosphonic acid; piperazine

Test material form:

solid: particulate/powder

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

Species: Wistar outbred rat; Crl:(WI) WU BR
Supplier: Charles River, Germany
Sex and age: females, ca 7-8 weeks old upon arrival
Date of arrival: 26 February 2003
Quarantine/acclimatization: 13 days
Caging: a maximum of six animals per macrolon cage
Lighting: 12 hours light/12 hours dark cycle
Temperature during testing: 22± 3°C.
Relative humidity during testing: 30-70%. Upper limit incidentally up to 100%, because of meteorological circumstances and/or wet cleaning of the animal room.
Ventilation: ca 10 air changes/hour
Diet/water: standard laboratory diet ad libitum. Each batch of this diet is analysed by the supplier (SDS Special Diets services, Whitham, England) for the nutrients and contaminants and the results are kept available in the archives. Tap water (N.V. Hydron MiddenNederland) ad libitum. Results of routine physical, chemical and microbiological examination of drinking water as conducted by the supplier are kept available in the archives. The results of diet and water analyses were considered acceptable for this study.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

The animals were dosed with a 10 ml/kg body weight of a 200 mg/ml aqueous suspension of the test substance in order to obtain the 2000 mg/kg dose level.

Doses:

2000 mg/kg

No. of animals per sex per dose:

6 animals

Control animals:

no

Details on study design:

The study was started with treatment of three females with a dose level of 2000 mg/kg body weight. Since none of the animals died during the following hours, the test was continued with the same dosing of another three females. The animals were dosed with a 10 ml/kg body weight of a 200 mg/ml aqueous suspension of the test substance in order to obtain the 2000 mg/kg dose level. The exact amount of the test substance to be dosed was calculated for each animal individually and administered by means of a syringe, equipped with an oral gavage. Prior to dosing, the animals had fasted overnight.
Approximately 4 hours after dosing, they had access to food again. The animals were observed for mortality up to 14 days after treatment.

Observation and measurements
Clinical signs: All visible reactions to treatment were recorded, including type, severity, onset and duration. Observations were made within 1 hour and within 4 hours after dosing, and subsequently in surviving animals at least once daily throughout an observation period of 14 days.
Body weights: The body weight of each animal was recorded immediately before dosing on day 0, and of the surviving animals on days 3, 7 and 14 of the study.
Termination of the study: At the end of the observation period, on day 14 of the study, all surviving animals were killed with carbon dioxide and examined for external changes. Next, the abdomen and the thorax of each animal was opened and examined for gross pathological changes.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed during the 14-day study period.

Clinical signs:

other: No clinical signs was observed during the 14-day study period.

Gross pathology:

Examination at necropsy of the animals did not reveal distinct treatment-related gross alterations.

Other findings:

No further findings investigated in this study.

Any other information on results incl. tables

Table 1

Acute oral toxicity of T-1063FM in rats; individual and mean bodyweights, dose amounts applied and mortality

 

Animal no.	Dose (ml) applied^1	Bodyweights (g) recorded on day:				Mortality^2
		0	3	7	14
2000 mg/kg (first group)
35	1.7	173	183	187	202	-
37	1.7	175	191	197	210	-
39	1.8	176	191	198	214	-
Mean bodyweight		175	188	194	209	0/3
(second group)
101	1.7	167	181	189	204	-
103	1.7	172	190	198	212	-
105	1.8	180	195	205	212	-
Mean bodyweight		173	189	197	209	0/3

¹2000 mg/kg; dose of 10 ml/kg bodyweight of a 200 mg/ml aqueous suspension of the test substance

²- = animal survived; + = animal died

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

Since all animals survived the 2000 mg/kg dose level, the oral LD50 of T-1063FM is considered to be higher than 2000 mg/kg body weight.