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Acute Toxicity: inhalation

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acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
This study was conducted under GLP. However, as this was in the early days of GLP, the study report is lacking in detail. We have confirmed with the manager of the testing laboratory that during this time period, all work was conducted to the GLP standards of the day, even though the study reports do not specifically call it out.

Data source

Reference Type:
study report

Materials and methods

Test guideline
equivalent or similar to guideline
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
Test type:
Limit test:

Test material

Constituent 1
Chemical structure
Reference substance name:
EC Number:
EC Name:
Cas Number:
Molecular formula:
Details on test material:
Chemical name: n-Butyronitrile
CAS. No. 109-74-0
SRID or Lot No.: 36 T 200
ACC. No.: 900741
HAEL No.: 85-0055
Experiment No.: 850055I2 & I3
Molecular formula: C4H7N
Molecular weight: 69.1
Boiling point (°C): 116
Specific gravit.y (water = 1): 0.7919 at 20°/20°C
Vapor pressure (torr at 23°C): 24.3 (calculated using a linear equation from paired table
supplied by the Chemical Quality Services Division (Report No.
215515L TX-85-97)
Vapor density (Air=1) 2.4

Test animals

Details on test animals or test system and environmental conditions:
Male and female rats (CRL:CD8(SD)BR) were obtained from Charles River Laboratories, Inc., Wilmington, MA. Rats were chosen for this study
because they are a common representative species for toxicity studies. Animals were received on September 10, 1986, and were isolated for five days. On September 15, 1986 the animals were released in good health from isolation. Twenty males and twenty females approximately seven and eight weeks old respectively, were divided into four equal groups of five male and five females each, weighing 182 to 217g (males) and 171 to 194g (females) at the start of the study (Day 0). Housing Temperature and relative humidity were 70-77°F and 47-58%, respectively, during the isolation period. 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 (RKH 3000, pellets)] was available ad libitium during non-exposure periods. Water (Monroe County Water Authority) was available ad libitium 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.

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Details on inhalation exposure:
Exposures were to target concentrations of 2000, 4000, 6000, or 8000 ppm and were conducted in a 420 L stainless steel and glass inhalation chamber. 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 on the same day, except for the 2000 ppm group which was added to the experiment on the third day in order to better define the LC10 level. The chamber was maintained under negative pressure (0.5" water) and at 12 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 from the Kodak Park Utilities.. Chamber vapor concentrations were determined four or five times per hour by a HIIA infrared analyzer equipped for automated sampling and analysis. In addition, temperature and humidity were determined twice per hour and nominal vapor concentration for the exposure was calculated. Once during exposure, concentration of background nongaseous material was measured in the 6000 ppm 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 by measurement from ten positions throughout the chamber and was compared to a fixed reference position. Subsequently, determination of chamber vapor concentration as done remotely from the fixed reference position.

Analytical verification of test atmosphere concentrations:
Duration of exposure:
1 h
2000, 4000, 6000 or 8000 ppm
No. of animals per sex per dose:
5 per sex per dose
Control animals:
Details on study design:
Rats were exposed to the test article via whole body inhalation for 1 hour, followed by a 14-day observation period.
Mortality data were 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 levelsopen allclose all
Dose descriptor:
other: LC10
Effect level:
> 2 000 - < 4 000 ppm
Exp. duration:
1 h
Dose descriptor:
other: LC10
Effect level:
> 4 000 - < 6 000 ppm
Exp. duration:
1 h
1/5 males and 0/5 females at 2000 ppm
5/5 males and 2/5 females at 4000 ppm
5/5 males and 4/5 females and 6000 and 8000 ppm
Clinical signs:
other: .All males and females exposed to 4000, 6000, and 8000 ppm exhibited minor to severe central nervous system depression in a concentration-dependent manner during the exposure, while the 2000 ppm groups had no clinical signs of toxicity during the exposure
Body weight:
All males exposed to 4000, 6000, and 8000 ppm died within 24 hours of exposure. The four males in
the 2000 ppm group which survived the exposure exhibited sustained weight gain. Four females
exposed to 8000 ppm, four females exposed to 6000 ppm, and two females exposed to 4000 ppm died
within 24 hours after exposure. No mortality was seen in females exposed to 2000 ppm. All survivors
exhibited comparable weight female gains.
Gross pathology:
No treatment-related changes were observed on gross examination. No tissue was collected for microscopy. No cause of death was determined.

Applicant's summary and conclusion

Interpretation of results:
Migrated information Criteria used for interpretation of results: US CPSC / US OSHA
The LC10 value for males and females combined was 1848 ppm with a 95% confidence interval of 695 to 2656 ppm.
Executive summary:

Exposure of rats to vapor concentrations of 2000, 4000, 6000, or 8000 ppm of NBN for one hour resulted in acute central nervous system (CBS) depression and death. The severity of the CNS depression and the incidence of mortality were concentration-dependent. Mortality was greater among males than females. Survivors exhibited minimal signs of toxicity which resolved within 24 hours of exposure. No treatment-related changes were observed upon gross examination of animals found dead, or of those examined at the end of the study. No cause of death was identified in animals found dead. A no-observed-effect-level was not determined. The LC10 value for males and females combined was 1848 ppm with a 95% confidence interval of 695 to 2656 ppm.

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