Isobutyronitrile

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: Study was conducted in the early days of GLP, so detail is lacking in the report. However, we have confirmed with the laboratory that at the time the study was conducted, GLP was implemented at the facility.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1986

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

iso-Butyronitrile

IUPAC Name:

iso-Butyronitrile

Constituent 2

Reference substance name:

Isobutyronitrile

EC Number:

201-147-5

EC Name:

Isobutyronitrile

Cas Number:

78-82-0

Molecular formula:

C4H7N

IUPAC Name:

2-methylpropanenitrile

Details on test material:

Chemical Name: Isobutyronitrile
CAS. No. 78-82-0
SRID or Lot No.: TK 24
Acc. No.: 907253
HAEL No.: 85-0054
Experiment No.: 850054I2
Molecular formula: C4H7N
Molecular weight: 69.1
Boiling point (De): 102-104
Specific gravity (water= 1): 0.773 at 20"C
Vapor pressure (mm Hg at 23"C): 47.0 (determined by Chemical Quality Services Division, KodaK Park; Report No. 215514K TX-85-96

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Test Animals

Male and female rats (CRL:Co®(SD)BR)were obtained from Charles River Laboratories, Inc., Wilmington, HA. Animals were received on January 22,
1986, and were isolated in vivarium Room 1034 for five days. On January 27, 1986, the animals were released in good health from isolation
and transferred to vivarium Room 1056. Fifteen males and 15 females approximately eight weeks old were divided into three equal groups of five males and five females each, weighing 232 to 263 g (males)and 210 to 237 g (females)at the start of the study.

Housing

Temperature and relative humidity were 69-70F and 38-40%, respectively, during the isolation period and 68-72F and 53-58% , respectively. Animals were group housed in stainless steel suspended cages during the isolation period, but subsequently singly housed in multicompartmented stainless steel mesh cages designed for inhalation studies. Males and females in each group were housed on the same rack. A 12 hour (6 a.m. to 6 p.m.) light/dark cycle was maintained. Cages and racks were washed once per week. Absorbent paper under the cages was changed three times per week.
Feed and Water Certified feed [Agway Prolab Animal Diet (RHH 3000, pellets)] was available ad lib. during nonexposure periods. Water (Monroe County Water Authority)was available ad l ib. during nonexposure periods through an automatic watering system. No known contaminants in feed or water were expected to be present which would interfere with the outcome of this study.

Identification
All rats were identified by a unique metal ear tag.

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

exposures were to target concentrations of 2700, 1800, or 1200 ppm and were conducted in 420 L stainless steel and glass inhalation chambers.
Animals were exposed for one hour and then observed for 14 days. For each exposure concentration, males and females were exposed in the same
inhalation chamber. The exposures were run sequentially in the same chamber. All three exposure levels were completed in the same day. The
chamber was maintained under negative pressure (0.5" water)and at 13 air changes per hour. Vapors were generated by metering the test material
dropwise into a heated glass bead-packed column supplied with metered dried oil-free compressed air. Chamber concentrations were determined four times per hour by a Mirane IA infrared analyzer equipped for automated sampling and analysis. In addition, temperature and humidity was determined twice per hour and nominal chamber concentration for the exposure was calculated. Twice during each exposure, concentration of background nongaseous material was measured in each chamber relative to that of a chamber containing air in order to insure that exposures were
to vapor and not aerosol. Distribution of test material was determined initially by measurement from numerous positions throughout the chamber and was compared to a fixed reference position. Subsequently, determination of chamber concentration was done remotely from the fixed reference
position.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

1 h

Concentrations:

2700, 1800 or 1200 ppm

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

Animals were exposed to the test article for 1 hour followed by a 14 day observation period.

Statistics:

Mortality data was evaluated by probit analysis. The LC10 value and its 95% confidence limits were
estimated by probit analysis using a computer generated statistical analysis software package
(Version 5, 1985, SAS Institute Inc., Cary, NC).

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

other: LC10

Effect level:

1 173 ppm

95% CL:

474 - 1 173

Exp. duration:

1 h

Mortality:

2700 PPM: 5/5 males and 3/5 females died
1800 PPM: 4/5 males and 1/5 females died
1200 PPM: 1/5 males and 0/5 females died

Clinical signs:

other: All males and females exposed to 1800 and 2700 ppm IBN exhibited lethargy during exposure. The severity of the response was minor in males and females exposed to 1800 ppm, while animals exposed to 2700 ppm developed a gait disturbance and finally narcosis

Body weight:

Females which survived exposure to 2700 ppm and males and females which survived exposure to 1800 or 1200 ppm IBN showed
continued weight gains throughout the 14-day observation period. Weight gain of the surviving male exposed to 1800 ppm was less than that of
those exposed to 1200 ppm. Weight gain of females surviving exposure to 2700 ppm was greater than that of the 1800 ppm group which in turn was
greater than that of females exposed to 1200 ppm.

Applicant's summary and conclusion

Interpretation of results:

highly toxic

Remarks:

Migrated information Criteria used for interpretation of results: US CPSC / US OSHA

Conclusions:

The one-hour LC10 was 1143 ppm and 1630 ppm for males and females, respectively. The one-hour LC10 for males and females combined is 1173 ppm with a 95% confidence interval of 474 to 1488 ppm.

Executive summary:

Groups of five male and five female rats were exposed to target vapor concentrations of 2700, 1800, or 1200 ppm isobutyronitrile (IBN) for one hour and then held for 14 days of observation. IBN caused lethargy in animals during exposure to 1200 and 1800 ppm, and a gait disturbance, lethargy, and narcosis in animals during exposure to 2700 ppm. There were no deaths during the one-hour exposure. Mortality was 20, 80, and 100% males and 0, 20, and 60% females in the 1200, 1800, and 2700 ppm groups, respectively. All deaths occurred in the first 48 hours after exposure. Clinical signs of toxicity were central nervous system depression. Body weight gain appeared normal in survivors. No significant signs of toxicity were exhibited in survivors. No compound-related gross pathology was observed in animals dying spontaneously or in those examined at the termination of the study. No organ damage sufficient to cause death was found in rats dying spontaneously. The one-hour LC10 was 1143 ppm and 1630 ppm for males and females, respectively. The one-hour LC10 for males and females combined is 1173 ppm with a 95% confidence interval of 474 to 1488 ppm.