[cyclohexane-1,2-diylbis[nitrilobis(methylene)]]tetrakisphosphonic acid, sodium salt

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

11 August 1992-09 September 1992

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Ltd., Manston, Kent, UK
- Age at study initiation: 5 to 8 weeks
- Weight at study initiation: 138-160g (males), 144-158g (females)
- Fasting period before study: over night fast and ca. 2 hours after dosing
- Housing: in groups of 5 by sex in solid floor polypropylene cages with saw dust bedding.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: minimum of five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-22
- Humidity (%): 52-75
- Air changes (per hr): ca. 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

DOSE VOLUME APPLIED: 1.71 ml/kg

Doses:

2000 mg/kg at dose volume of 1.71 ml/kg (specific gravity 1.171)

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: Deaths and overt signs of toxicity were recorded 0.5, 1, 2 and 4 hours after dosing and subsequently once daily. Individual bodyweights were recorded prior to dosing on day 0 and days 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: All animals were subjected to gross pathological examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded.

Statistics:

Using the mortality data obtained, an estimate of the acute oral median lethal dose (LD50) of the test substance was made.

Results and discussion

Preliminary study:

A range finding study was performed to establish a dosing regime. 1000 and 2000 mg/kg bw were administered to one male and one female animal per dose. There were no deaths or clinical signs of toxicity. Based on this information a dose level of 2000 mg/kg was selected for main study.

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths.

Clinical signs:

No signs of systemic toxicity were noted during the study.

Body weight:

All animals showed expected gain in bodyweight during the study.

Gross pathology:

No abnormalities were noted at necropsy.

Other findings:

None reported.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The oral LD50 value of >2000 mg/kg was reported for [cyclohexane-1,2-diylbis[nitrilobis(methylene)]]tetrakisphosphonic acid, sodium salt in a reliable limit test conducted according to the now deleted OECD test guideline 401, and in compliance with GLP.