Methacrylonitrile

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

no data

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Peer reviewed literature data

Data source

Reference

Reference Type:

publication

Title:

The Mammalian Toxicity of Methacrylonitrile

Author:

Pozzani UC, Kinkead ER & King JM

Year:

1968

Bibliographic source:

American Industrial Hygiene Association Journal 29:202-210

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: no data

Deviations:

not specified

Principles of method if other than guideline:

Groups of Harlan-Wistar rats were exposed to various concentrations of methacrylonitrile vapor for single four-hour periods.

GLP compliance:

not specified

Remarks:

study predates GLP

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Methacrylonitrile

EC Number:

204-817-5

EC Name:

Methacrylonitrile

Cas Number:

126-98-7

Molecular formula:

C4H5N

IUPAC Name:

2-methylprop-2-enenitrile

Details on test material:

- Name of test material (as cited in study report): Methacrylonitrile
- Source: Vistron Corporation, Midland Building, Cleveland, Ohio
- Molecular weight: 67.09
- Substance type: organic, monoconstituent
- Physical state: clear, colourless liquid
- Analytical purity: minimum of 99.0 wt %
- Boiling point: 90.3 degrees Centigrade at 760 mm
- Specific gravity: d 30°/4°, 0.7896
- Solubility in water: 2.54 wt % at 30 degrees Centigrade
- Flash point (Tag open cup): 55 degrees Fahrenheit
- Vapor pressure: 65 mm at 25 degrees Centigrade
- Inhibitor (MEHQ): 35-45 ppm
- Other: Air saturated with methacrylonitrile at 25 degrees Centigrade at 760 mm contains 85,526 ppm vapour, which has a relative vapour density of 1.11 (dry air=1)

Test animals

Species:

rat

Strain:

other: Harlan-Wister

Sex:

male/female

Details on test animals or test system and environmental conditions:

No data

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

not specified

Vehicle:

other: no data

Details on inhalation exposure:

No data

Analytical verification of test atmosphere concentrations:

yes

Remarks:

Gas chromatogram

Duration of exposure:

4 h

Concentrations:

Varied by a factor of 2

No. of animals per sex per dose:

Six

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

No data

Results and discussion

Preliminary study:

Six female Harlan-Wister rats were exposed to essentially saturated vapour (85,500 ppm) of methacrylonitrile for 14, 7.5, 3.75, 1.88, 0.93 and 0.47 minutes resulting in the respective mortality ratios 6/6, 6/6, 6/6, 1/6, 0/6 and 0/6. All victims died during the 14 minute exposure, with 1.5 hours after the 7.5 minutes exposure, and within 24 hours following the 3.75 and 1.88 minute exposures. Prostration and loss of consciousness always preceded death, but these symptoms also appeared in most of the survivors exposed for as short a period as 1.88 minutes. The rats exposed for 0.47 minutes appeared normal during and after the inhalation period. Most of the survivors of all the saturated vapour studies gained weight normally during the subsequent 14-day observation period. Convulsions were never observed in these experiments.

Effect levels

Effect levels 1

Sex:

female

Dose descriptor:

LC50

Effect level:

496 ppm

Based on:

test mat.

95% CL:

250 - 933

Exp. duration:

4 h

Remarks on result:

other: Weight range 95-172 g

Effect levels 2

Sex:

female

Dose descriptor:

LC50

Effect level:

700 ppm

Based on:

test mat.

95% CL:

213 - 2 327

Exp. duration:

4 h

Remarks on result:

other: Weight range 213-317 g

Effect levels 3

Sex:

male

Dose descriptor:

LC50

Effect level:

328 ppm

Based on:

test mat.

95% CL:

208 - 516

Exp. duration:

4 h

Remarks on result:

other: Weight range 344-510 g

Effect levels 4

Sex:

male

Dose descriptor:

LC50

Effect level:

328 ppm

Based on:

test mat.

95% CL:

231 - 494

Exp. duration:

4 h

Remarks on result:

other: Weight range 123-207 g

Mortality:

One male death (1/6) occurred at 180 minutes at a concentration of 176 ppm

Clinical signs:

other: Loss of consciousness and convulsions

Body weight:

Most animals gained weight normally during the subsequent 14-day observation period

Gross pathology:

No gross lesions attributable to exposure were found

Other findings:

No data

Any other information on results incl. tables

Table I - Summary Responses of Various Animal Species to Single Exposure Periods of Methacrylonitrile Vapour

Species	Sex	Wt. Range (g)	No. of Animals per Exposure Level	Length of Exposure Period (hr)	LC50and range (ppm)	Remarks*
Rats	(F)	213-317	6	4	700 (213-2,327)	176 ppm caused loss of consciousness within 180 min., but no deaths.
Rats	(F)	95-172	6	4	496 (250-993)	Same as above.
Rats	(M)	344-510	6	4	328 (208-516)	176 ppm caused loss of consciousness within 180 min., and one death preceded by convulsions.
Rats	(M)	123-207	6	4	328 (231-494)	176 ppm caused loss of consciousness within 180 min., but no deaths.
Guinea Pigs	(M)	585-1035	6	4	88 (62-124)	52.5 ppm caused no symptoms.
Rabbits	(M)	2356 - 4290	4	4	37 (23-57)	19.7 ppm caused no symptoms.
Mice	(M)	23-33	6	4	36 (25-43)	19.7 ppm caused no symptoms.
Mongrel Dog	(F)	9540	1	3		106.1 ppm caused convulsions, followed by death in 3 hours.
Mongrel Dog	(F)	6800	1	7		106.1 ppm caused vomiting, diarrhea, convulsions and death within 7 hours.
Cocker Spaniel Dog	(F)	8100	1	7		52.5 ppm caused vomiting, convulsions, and loss of consciousness within 7 hours. Dog died overnight.

* With exception of the dogs, the concentrations stated in this column were the lowest used in determining the LC₅₀value for the respective species.

The responses were consitently dose related and follwed a general pattern of loss of consciousness, tonic-clonic convulsions and death. Some survivors were unconscious, but none progressed to the convulsive stage.

Applicant's summary and conclusion

Conclusions:

The LC50 for the female rat is 496 ppm and 328 ppm for the male rat.