Phosphine

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian germ cell study: cytogenicity / chromosome aberration

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Protocols for the care, treatment and killing of the mice were approved by the Animal Care Committees of the Health Effects Research Laboratory of the US EPA and the NIEHS and meet all guidelines set by the National Institutes of Health.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

publication

Title:

Cytogenetic and germ cell effects of phosphine inhalation by rodents: II. Subacute exposures to rats and mice.

Author:

Kligerman A.D., Bishop J.B., Erexson G.L., Price H.C., O'Connor R.W. and Morgan D.L.

Year:

1994

Bibliographic source:

Environ Mol Mutagen 24(4):301-306

Materials and methods

Principles of method if other than guideline:

Rodents are exposed to target concentrations of phosphine by inhalation for an appropriate period and are sacrificed at appropriate times after treatment. Specific cells are collected (blood lymphocytes) and treated to study specific endpoints chromosome aberrations

GLP compliance:

not specified

Type of assay:

chromosome aberration assay

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:

gas was procured in cylinders containing 2,500 ppm PH3 in nitrogen (AGA specialty Gas, Inc, Maumee, OH).

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male

Details on test animals or test system and environmental conditions:

After exposition, male rat (approximately 8 weeks of age) were returned to the holding cages with food and tap water ad libitum. Animals wera maintened on a 12 hours light/dark cycle with controlled temperature and humidity.

Administration / exposure

Route of administration:

inhalation: gas

Vehicle:

The desired exposure concentration were obtained by introducing metered quantites of PH3 directly into the process air stream just prior to a set of static mixing element.

Details on exposure:

Male rats were placed in the inhalation chambers without food or water and exposed to target concentration.

Duration of treatment / exposure:

9 days over 11 day period (5 days exposed, 2 days off, 4 days exposed)

Frequency of treatment:

6 hours per day.

Post exposure period:

18 to 20 hours.

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
1.25 ppm
Basis:
nominal conc.

Doses / concentrations 2

Remarks:

Doses / Concentrations:
2.5 ppm
Basis:
nominal conc.

Doses / concentrations 3

Remarks:

Doses / Concentrations:
5 ppm
Basis:
nominal conc.

No. of animals per sex per dose:

5 animals per dose

Control animals:

yes

Positive control(s):

No data

Examinations

Tissues and cell types examined:

blood lymphocytes

Details of tissue and slide preparation:

Blood was removed from the rats by cardiac puncture.
2 ml cultures were established containing 5*10E5 mononuclear leukocytes, RPMI-1640, 10% heat-inactivated fetal bovine serum, an additionnal 1% L-Glutamine, 1% penicillin-streptomycin and 10 µg/ml concanavalin A.BrdUrd (5µM) was added at 21 hours for analyses of sisterchromatid exchange and cell cycle kinetics and the culture was harvested by cytocentrifugation at 54 hours of culture following a 3 hours demecocline treatment.
Cells were treated with a hypotonic 0.075M KCl solution and fixed in 3:1 methanol:acetic acid. Slides were made, mounted ans stained according to Erexson and Kligerman (1987).

Evaluation criteria:

For each animal, 100 first division metaphases were scored for chromosome aberrations. The replicative index was calculated from 100 consecutive metaphases.

Statistics:

For chromosome aberration and percentage polychromatic erythrocytes date, the trend test was performed.
The level of significance chosen was 0.05.

Results and discussion

Test results

Sex:

male

Genotoxicity:

negative

Remarks:

Peripheral blood lymphocyte

Toxicity:

no effects

Vehicle controls validity:

valid

Negative controls validity:

not specified

Positive controls validity:

not specified

Additional information on results:

PH3 inhalation caused no statistically significant increases in Chromsome aberrations in peripheral blood lymphocytes

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative Peripheral blood lymphocyte
No increase in cytogenetic end points (chromosome aberration) was observed over controls in cultured lymphocytes.
The concentrations of PH3 up to 5 ppm (7.1 mg/m3) are not genotoxic to rodents when administrated by inhalation for 9 days during an 11 day period.

Executive summary:

Male F344/N rats were exposed to 0 ; 1.25 ; 2.5 or 5 ppm of phosphine to 6 hours per day for 9 days over an 11 days period. Approximately 20 hours after the termination of exposure, blood was removed from the rats and the lymphocytes cultured for analyses chromosome aberration. No significant increase in chromosome aberration was observed over controls in cultured lymphocytes.