[ethylenebis[nitrilobis(methylene)]]tetrakisphosphonic acid, calcium sodium salt

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1980

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study was carried out according to a protocol similar to current guideline, but not in compliance with GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1980

Report date:

1980

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

no

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

EDTMP-xCaxNa

IUPAC Name:

EDTMP-xCaxNa

Constituent 2

Reference substance name:

[ethylenebis[nitrilobis(methylene)]]tetrakisphosphonic acid, calcium sodium salt

EC Number:

287-370-9

EC Name:

[ethylenebis[nitrilobis(methylene)]]tetrakisphosphonic acid, calcium sodium salt

Cas Number:

85480-89-3

Molecular formula:

C6H20-2x-yN2O12P4.xCa.yNa

IUPAC Name:

x calcium y sodium {ethane-1,2-diylbis[nitrilobis(methylene)]}tetrakis(phosphonate)

Details on test material:

- Name of test material (as cited in study report): Dequest 2047 (Mixed sodium-calcium salt of ethylene diamine tetra (methylene phosphonic acid)
- Physical state: white fine powder
- Storage condition of test material: in a dark cupboard under ambient conditions on arrival in the company dispensary.

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 Limited, Margate, Kent
- Age at study initiation: ca. 8 weeks
- Weight at study initiation: 150-160g
- Housing: stainless steel cages with detachable wire tops, 5 per cage of one sex
- Diet: ad libitum
- Water: ad libitum
- Acclimation period:

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +/- 2
- Humidity (%): ca. 50
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

inhalation: dust

Type of inhalation exposure:

nose only

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Wright Dust Feeder mechanism
- Exposure chamber volume: 14.7 l
- Method of holding animals in test chamber: each rat was held in an individual, tapered, polycarbonate restraint tube. Each tube was fitted onto the exposure chamber and sealed by means of a push fit through a rubber 'o' ring.
- Source and rate of air: The compressed air supply was maintained at between 8 and 12 l/min through the generator with additional diluent air being monitored into the chamber at flow rates up to 10 l/min.
- System of generating particulates/aerosols: a scraper blade removed powder at a steady rate from a pre-packed canister by a stream of clean, dry compressed air. After passing through a baffle plate positioned so as to break up any aggregates, the air containing the finely dispersed powder passed directly into the exposure chamber,
- Method of particle size determination: Andersen Mini Sampler, at a rate of 1.4 l/min
- Treatment of exhaust air: an extract duct in the base which was connected by way of high efficiency filter to a metered vacuum system.


TEST ATMOSPHERE
- Brief description of analytical method used: The chamber concentration was estimated gravimetrically during the exposure periods at approximately hourly intervals. The gravimetric method used employed pressed glass fibre filters placed in a filter holder. The conical input side of the holder was positioned and temporarily sealed in a port in the exposure chamber in the animals breathign zone. Chamber air was drawn through thte filter at a rate of 2.5 l/min using a vacuum pump. Each filter was weighed before and after sampling in order to calculate by difference the weight of collected material. By further calculation using the sample volume the chamber concentration was estimated.
- Samples taken from breathing zone: yes


TEST ATMOSPHERE (if not tabulated)
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): Group 2: 3.8 / 2.4 μm, Group 3: 2: 3 / 3.2 μm Group4: 2: 3.2 / 2.8 μm

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

0.87 mg/l, 2.7 mg/l, 4.17 mg/l (analytical). Percentage of respirable particles (<4.7μm) respectively 66.7%, 70.4%, 71%

No. of animals per sex per dose:

5M, 5F

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: All the rats were observed for clinical signs at frequent intervals throughout the exposure periods and for the first 4 h post dosing. All surviving animals were observed at least twice daily during the subsequent 14 days post exposure. All the rats were weighed immediately before dosing and on days 2,3,4,7,10 and 14 post exposure.

- Necropsy of survivors performed: yes

- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: All the animals were subjected to macroscopic examination. This included the opening of the abdominal and thoracic cavities. The respiratory tract of all animals was subjected to detailed macroscopic examination. The lungs were dissected out and weighed in order to calculate the lung to body weight ratio for each animal.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 4.17 mg/L air (analytical)

Remarks on result:

other: The technical maximum concentration achievable.

Mortality:

There were no mortalities.

Clinical signs:

other: All animals showed initial struggling with increased urination and defaecation during exposure. Control animals quickly became settled and the test animals showed regular breathing throughout the exposure periods.

Body weight:

There were no treatment related effects on body weights compared with controls.

Gross pathology:

Occasional foci of lung congestion in treated animals was seen but no indication of irritancy or general toxicity. Lung body weight ratios were comparable in control and treated animals, there being no dose related effects.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information

Conclusions:

An LD50 of >4.17 mg/l (dust) was reported; this was the maximum achievable concentration. The study was reliable and carried out according to a protocol similar to guideline, but not compliant with GLP.