Phosphine

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Well described study with a consistant and relevant material & methods.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

publication

Title:

Acute and subacute inhalation toxicty of highly purified phosphine (PH3) in male ICR mice

Author:

Omae K., Ishizuka C. and Nakashima H

Year:

1996

Bibliographic source:

J Occup Health ; 38 : 36-42

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

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

Details on test material:

The 99.995% pure PH3 used in semiconductor manufacturing (Nippon Sanso, Co).

Test animals

Species:

mouse

Strain:

ICR

Sex:

male

Details on test animals or test system and environmental conditions:

Four week old male ICR mice were purchased from Charles River. After one week of acclimatation, they were used in the inhalation experiments. Five mice each were housed in plastic cages in a filtrated air-ventilated rack for small animal breeding. The cages were maintained at approximately 22°C, 60% relative humidity, and a 12 hour light, 12 hour dark cycle and fed pelleted rodent chow and water ad libitum throughout both the acclimation and observation period.

Administration / exposure

Route of administration:

inhalation: gas

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

The source gas was diluted with purified nitrogen. It was supplied at a constant rate, mixed with filtered room air, and introduced into the whole-body 550-L exposure chamber.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

Phosphine concentrations were measured via gas chromatography every 12 min during exposure. The oxygen concentration in the chamber was measured simultaneously with a digital oximeter.

Duration of exposure:

>= 1 - <= 8 h

Remarks on duration:

All exposures were followed by a 2-week observation period

Concentrations:

Experiment to determine LC50
First experiment: 17.2 ppm (+/- 1.3) ; 25.1 ppm (+/- 0.9) ; 31.7 ppm (+/- 1.4) ; 41.6 ppm (+/- 1.4) ; 59.2 ppm (+/- 2.0) for 1 hour
Second experiment: 22.5 ppm (+/- 3.8) ; 26.5 ppm (+/- 2.4) ; 33.4 ppm (+/- 2.6) ; 45.5 ppm (+/- 4.0) ; 66.9 (+/- 5.0) for 4 hours

Acute exposure experiment
Third experiment: 24.5 ppm (+/- 2.0) for 1 hour ; 23.9 ppm (+/- 1.6) for 2 hours ; 24.5 ppm (+/- 1.0) for 4 hours ; 24.9 ppm(+/- 1.2) for 8 hours

No. of animals per sex per dose:

10 mice per group

Control animals:

yes

Details on study design:

The mice were weighted, their behavior and external appearance were observed.
The observation period for the experiment to determine the LC50 was set at two weeks.
The blood was collected, three days after the exposure, from the axillary vessels under diethyl ether anesthesia and the liver, kidneys, spleen, lung, pancreas, brain and testes were promptly removed and then weighed.
The sciatic nerve, the skull for nasal cavity examination, and the femoral bone for bone marrow analysis were also removed.
Serum biochemical and hematological items examined were enzymic activites of AST, ALT, ALP, Ch-E, concentrations of Blood urea nitrogen and total counts of red blodd cells and white blood cells and the differential count.

Statistics:

Student's t-test of Welch's t-test was used for statistical testing of the difference in the mean of the effect variable for exposed and control mice.

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LC50

Effect level:

> 59.2 ppm

Based on:

test mat.

Exp. duration:

1 h

Effect levels 2

Sex:

male

Dose descriptor:

LC50

Effect level:

> 26.5 - < 33.4 ppm

Based on:

test mat.

Exp. duration:

4 h

Mortality:

Experiment to determine LC50
Table in the "other information" part shows the number of deaths and exposure concentrations.

Acute exposure experiment
All of the animals in the one, two and four hour exposure group survived, and all of the animals in the eight hour exposure group died (four immediately before the completion of exposure and six by day three).

Clinical signs:

other: In all of the 1-h exposed animals, the mice exhibited face-washing movements and were very active in the initial exposure period. No adverse signs were noted during the 3-day observation period after exposure. In the 4-h exposed mice, the initial observat

Body weight:

Body weight significantly decreased in the two and four-hour exposure groups when compared with the control group and the survival animals in the eight-hour exposure group also showed obvious weight loss.

Gross pathology:

Organ weights revealed significant differences from the control group in kidney weight in the one-hour exposure group, the heart in the two-hour exposure group, and the kidney, testes and heart in the four-hour exposure group but there was no clear trand in relation to the duration of exposure.

Other findings:

Experiment to determine LC50
In all groups, the mice appeared to do face washing mouvments and were extremely active in the initial period after the start of exposure.
In the 33.4 ppm and above exposure groups: the reactions of the mice to the noise made by tapping the wall of the exposure chamber became slower, and a supine posture was observed.

Acute exposure experiment
In the two, four and eight hour exposure groups, in the initial period after the stard of exposure, the animals were extremely active.
In the eight hour exposure group, spontaneous motor activity began to decrease approximately one hour after the start of exposure and at approximately three hours, the animal's reactions to the noise made by tapping the wall of the exposure chamber became slower and supine position was observed.

Any other information on results incl. tables

Experiment to determine LC50

The table 1 shows the number of deaths and exposure concentrations.

	Exposure concentration (ppm)	Mortality
One hour exposure	17.2 (+/ - 1.3)	0/10
	25.1 (+/- 0.9)	0/10
	31.7 (+/- 1.4)	0/10
	41.6 (+/- 1.4)	0/10
	59.2 (+/- 2.0)	0/10
Four hours exposure	22.5 (+/- 3.8)	0/10
	26.5 (+/- 2.4)	0/10
	33.4 (+/- 2.6)	10/10
	45.5 (+/- 4.0)	10/10
	66.9 (+/- 5.0)	10/10

Applicant's summary and conclusion

Interpretation of results:

very toxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute inhalation toxicity of PH3 in male ICR mice was investigated. LC50 for one hour exposure was greater then 59.2 ppm and that for four-hour expsure was between 26.5 ppm ande 33.4 ppm.
On the basis of LC50 for four hours, the phosphine is classified as T+, R26 and Acute Tox. Categorie I, H330.

Executive summary:

The acute inhalation toxicity of PH3 in male ICR mice was investigated. LC50 for one hour exposure was greater then 59.2 ppm and that for four-hour expsure was between 26.5 ppm ande 33.4 ppm. Experiment involving acute exposure to 25 ppm PH3 for one, two, four of eight hours were conducted. All mice subjected to acute eight-hour exposure died but a histopathological examination failed to reveal the actual causes of death. In the nasal cavity, exposure-time related inflammatory changes were observed in the acute two-, four- and eight hour exposure groups. Other histopathological, hematological, and serum biochemical examination dit not reveal PH3 related changes.