Propiononitrile

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1981

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Data source

Reference

Reference Type:

publication

Title:

Inhalation Toxicology of Acute Exposure to Aliphatic Nitriles

Author:

CALVIN C. WILLHITE

Year:

1981

Bibliographic source:

Willhite, C.C., 1981. Inhalation Toxicology of Acute Exposure to Aliphatic Nitriles. CLINICAL TOXICOLOGY, 18, pp.991–1003.

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The toxicity of propionitrile inhaled by mice was determined

GLP compliance:

not specified

Test type:

other:

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Propiononitrile

EC Number:

203-464-4

EC Name:

Propiononitrile

Cas Number:

107-12-0

Molecular formula:

C3H5N

IUPAC Name:

propanenitrile

Specific details on test material used for the study:

propionitrile (99%, Aldrich)

Test animals

Species:

mouse

Strain:

CD-1

Sex:

male

Details on test animals or test system and environmental conditions:

Male CD- 1 mice (30-40 g) were purchased from Charles River Laboratories, North Wilmington, Massachusetts. The animals were maintained on tap water and laboratory chow ad libitum and pine shav- ings were utilized for bedding.

Administration / exposure

Route of administration:

inhalation: mixture of gas, vapour and aerosol

Type of inhalation exposure:

whole body

Vehicle:

air

Remarks:

dehumified

Details on inhalation exposure:

propionitrile (99%, Aldrich) was mixed with a stream of dehumidified air (10 L/min) and delivered to a single pass 45 L glass inhalation chamber. Fresh solutions of each of the nitriles were made up in chromatographic grade toluene (Fisher) and the concentrations of the nitriles both in toluene and in chamber air samples were determined by gas chromatography. One milli- liter samples of the chamber atmosphere were collected every 5 min utilizing gas-tight syringes (Precision Sampling Corp., Baton Rouge, Louisiana). The samples were chromatographed in a Hewlett Packard Model 5710A gas chromatograph (6'X 1/4" glass column packed with 50/80 mesh Porapak Type Q, Waters Associates, Milford, Massachusetts) equipped with a flame-ionization detector. Typical operating conditions for the gas chromatograph in acetonitrile analyses were:
30 mL/min (30 psig) He carrier gas flow, 40 mL/min (22 psig) Hz gas flow to detector, 240 mL/min (24 psig) airflow to detecto;, 250°C in- jection port temperature, 250" detector temperature, 180 column temperature. The column temperature was maintained at 200 and 220" for propionitrile and n-butyronitrile analyses, respectively. Correc- tions for nitrile gas phase volume expansion were made after values compiled by the United States Bureau of Mines.
The nitrile con- centration was maintained by metering the liquid nitrile (Harvard Ap- paratus, Millis, Massachusetts) into a 200-cm long system of glass tubing ( 1 cm internal diameter) carrying a stream of dehumidified air so that the volatile nitrile evaporated and mixed thoroughly with the air. Quantitation of nitrile concentrations was by peak height. The temperature within the chamber was 24".

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

60 min

Concentrations:

70-400 ppm

No. of animals per sex per dose:

10

Control animals:

yes

Details on study design:

Groups of 10 mice each were exposed for 60 min to one of six concentrations of propionitrile.
The mice were subjected to gross autopsy shortly after death and lung tissues were preserved in 10%buffered formalin. The tissues were routinely processed and
the sections were stained with hematoxylin and eosin.

Results and discussion

Effect levels

Sex:

male

Dose descriptor:

LC50

Effect level:

163 ppm

Based on:

test mat.

95% CL:

>= 116 - <= 211

Exp. duration:

60 min

Mortality:

When mice were exposed to 400 ppm propionitrile for 60 min, all of the ani- mals died within 180 min of initial contact with the nitrile.

Clinical signs:

other: Mice exposed to acetonitrile, propionitrile, or n-butyronitrile vapors exhibited the same syndrome regardless of the nitrile to which they were exposed; the signs were indistinguishable from those follow- ing intraperitoneal injection of lethal doses of t

Gross pathology:

The livers of dead mice that had been ex- posed to the higher concentrations of acetonitrile, propionitrile, or n- butyronitrile often appeared bright red when compared to those of mice exposed only to chamber air for 60 min and sacrificed by de- capitation. Gross autopsy of the mice that died following exposure to the nitriles was otherwise unremarkable.

Other findings:

Histopathological examina- tion of pulmonary tissues recovered from mice exposed to the nitriles failed to reveal marked differences when those tissues were compared with those recovered from mice exposed to dehumidified air.

Applicant's summary and conclusion

Interpretation of results:

study cannot be used for classification

Conclusions:

Mice were exposed to a mix of air and proprionitrile. The LC50 was determined at 163 ppm. This would lead to a classification of Acute Tox 2 according to CLP guidelines for gases. Propionitrile, however, is not a gas but a liquid, and is therefore administered as dust/mist.
In order to use the data point for classification, the LD50 should have been expressed as mg/L, and not as ppm.