Phosphine

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP but not a guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1991

Materials and methods

Principles of method if other than guideline:

Sinlge 6 hour exposure but with 24 hours observation (not 14 days). Additional haematology examinations at sacrifice.

GLP compliance:

yes

Test type:

other: acute investigative

Test material

Test material information

Constituent 1

Reference substance name:

Phosphine

EC Number:

232-260-8

EC Name:

Phosphine

Cas Number:

7803-51-2

Molecular formula:

H3P

IUPAC Name:

phosphane

Test material form:

other: gas

Details on test material:

1% phosphine in nitrogen

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Administration / exposure

Route of administration:

inhalation: gas

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

Animals were individually housed in wire-mesh, stainless steel cages within a 1000 litre glass and stainless steel exposure chamber. The chamber was operated dynamically at a calibrated air-flow rate of 200 litres per minute (1pm); this provided a complete air change every 5 minutes and a 99% equilibrium time of 23 minutes. The test gas was delivered to the chamber via stainless steel tubing and additional air for dilution was drawn in via a HEPA filter. Air temperature, relative humidity and air-flow rate were recorded every 30 minutes.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

ca. 6 h

No. of animals per sex per dose:

5 males + 5 females at 0, 1.3, 6.0 and 28 ppm
10 males at 0, 3.1, 10 and 18 ppm

Control animals:

yes

Details on study design:

Animals were given a single 6 hour whole body exposure; blood samples were taken prior to sacrifice on Day 2 for cytogenetic analysis. Haematology samples were taken from groups 0, 3 and 18 ppm. Blood sample analysis was done by a different laboratory and reported separately.

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

other: mortalities

Effect level:

ca. 28 ppm

Based on:

test mat.

Exp. duration:

6 h

Effect levels 2

Sex:

male/female

Dose descriptor:

other: LOEL

Effect level:

ca. 10 ppm

Based on:

test mat.

Exp. duration:

6 h

Effect levels 3

Sex:

male

Dose descriptor:

other: NOEL

Effect level:

ca. 3 ppm

Based on:

test mat.

Exp. duration:

6 h

Mortality:

3/5 males and 2/5 females given 28 ppm died.

Clinical signs:

other: Animals given 28 ppm appeared hunched, displayed tremors and decreased activity and were cold to touch; surviving animals in this group were unremarkable on Day 2. All other animals were unremarkable.

Body weight:

There was a decrease in bodyweight on Day 2 in animals exposed to 10, 18 or 28 ppm.

Other findings:

Mean haematology in the 0, 3, 10 and 18 ppm groups showed an increase in haemaglobin, haematocrit and erythrocyes at 10 and 18 ppm. There were no detectable Heinz bodies.

Any other information on results incl. tables

mean and nominal exposures were as follows: mean 0, 1.3, 6.0, 28, 0, 3.1, 10 and 18 ppm. nominal 0, 1.0, 5.4, 26, 0, 3.0, 12 and 18 ppm. Particle size distribution gave the mean mass median aerodynmaic diameter as 0.76 to 6.1 microns and particulate exposure was less than 7 ug/m3.

Applicant's summary and conclusion

Interpretation of results:

highly toxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Executive summary:

Following 6 hours inhalation exposure to phosphine, 5/10 rats given 28 ppm died; transient observations of tremors, decreased activity, hunched appearance and cold to touch were also noted in this group. There were no deaths at 10 ppm. There was a transient decrease in bodyweight the day after exposure at 10, 18 and 28 ppm and changes in haematology.