[ethane-1,2-diylbis[nitrilobis(methylene)]]tetrakisphosphonic acid

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1980

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

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:

[ethane-1,2-diylbis[nitrilobis(methylene)]]tetrakisphosphonic acid

EC Number:

215-851-5

EC Name:

[ethane-1,2-diylbis[nitrilobis(methylene)]]tetrakisphosphonic acid

Cas Number:

1429-50-1

Molecular formula:

C6H20N2O12P4

IUPAC Name:

[ethane-1,2-diylbis[nitrilobis(methylene)]]tetrakisphosphonic acid

Test material form:

solid: particulate/powder

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: River Breeding Laboratories, Wilmington, Massachusetts

- Animal weight: 239-263g (males), 218-240g (females)

Administration / exposure

Route of administration:

inhalation: dust

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Wright Dust Feed cylinders using a carver hydraulic press
- Exposure chamber volume: 26.5 litre chamber
- Source and rate of air: 15 litres / minute
- System of generating particulates/aerosols: The test material was sieved through a #60 mesh sieve and packed into the Wright Dust cylinders using the Carver hydraulic press operating at 200 pounds per square inch. Dry air was passed through a modified Wright Dust Feed generator with a specially machined cutting blade to generate a dust laden atmosphere.


TEST ATMOSPHERE
- Brief description of analytical method used: The cylinders, cutting blade and nozzle were weighed before and after the exposure. The difference in weight represented the total amount of test material delievered into the test chamber; this divided by the total volume of air delivered yielded the nominal exposure concentration. Air samples were withdrawn each hour for gravimetric determination of the airborne concentration; these samples were withdrawn for determination of the particle size distribution using castella Cascade Impactor.
- Samples taken from breathing zone: yes

- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 2.7 microns / 2-2.7

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

4.60 mg/l (3.78-5.17 mg/l) i.e. approximately 30% of the nominal value which was 15.5 mg/l

No. of animals per sex per dose:

5M, 5F

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 abnormal signs before exposure, every 15 minutes for first hour, hourly thereafter, upon removal from the chamber hourly for four hours post-exposure and daily thereafter for 14 days. Individual body weights for all rats were recorded on day 0 (prior to exposure) and on days 1,2,4,7 and 14.

- Necropsy of survivors performed: yes

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 4.6 mg/L air (analytical)

Based on:

test mat.

Remarks on result:

other: dust

Mortality:

There were no mortalities.

Clinical signs:

other: Beginning ca. 15 minutes after initiation of exposure: hypoactivity, salivation, red nasal discharge, swollen eyelids, lacrimation, rapid or laboured respiration and soft stool were observed. Due to the density of the dust cloud visibility of the animals

Body weight:

Transient body weight losses were seen in most rats but in most cases these had recovered to the starting weights by day 4 or 7. Weight gains in the second week were within the range of normal expectation.

Gross pathology:

At necropsy lung discolouration was seen in all males and two females. These are common macropathological entities in this strain of rat but the incidence in males may reflect a slight response to treatment, especially if viewed in conjunction with the in vivo evidence of irritant effects on the ocular, buccal, nasal and respiratory mucosae on the day of exposure.

Other findings:

None reported.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

An LC50 value of 4.60 mg/l (3.78-5.17 mg/l) i.e. approximately 30% of the nominal value which was 15.5 mg/l is reported in a reliable study conducted according to a protocol equivalent to current guideline. The study was not compliant with GLP.