Methacrylonitrile

Direct observations: clinical cases, poisoning incidents and other

Administrative data

Endpoint:

direct observations: clinical cases, poisoning incidents and other

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:

Am. Ind. Hyg. Assoc. J. 29: 202-210

Materials and methods

Study type:

study with volunteers

Endpoint addressed:

acute toxicity: inhalation

Test guideline

Qualifier:

according to guideline

Guideline:

other: no data

Deviations:

not specified

Principles of method if other than guideline:

Groups of 8-9 humans were exposed to a series of concentrations of methacrylonitrile vapour

GLP compliance:

no

Remarks:

study predates GLP

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:

- Purity: > 99 wt.%
- Inhibitor: 35 - 45 ppm MEHQ

Method

Type of population:

not specified

Subjects:

22-57 years old

Ethical approval:

not specified

Route of exposure:

inhalation

Reason of exposure:

intentional

Exposure assessment:

not specified

Details on exposure:

In order to ascertain the responses of humans to methacrylonitrile vapour, volunteers inhaled a series of known concentrations for one minute periods. Inhalation took place in a glass lined 12.8 cubic meter room from which air was exhausted at 2.5 to 3.2 cubic meters per minute. The vapour concentrations were determined by gas chromatography. The volunteers were not screened for olfactory activity and did not know the concentration they were inhaling. The interrogator and technician who prepared the vapours ensured that vapour concentrations were introduced in the following sequence: 24, 14, zero, 7, 14, 24, 7, 2, zero and 2 ppm and the group inhaled the same series of concentrations twice. Intervals between each inhalation period were at least 45 minutes but were usually much longer. Volunteers faced the wall and answered questions in the affirmative by extending a finger. In the second part of the study nine subjects were exposed to a vapour at a concentration of 2 ppm for 10 minutes and additional seven subjects were exposed to a vapour at a concentration of 14 ppm also for 10 minutes.

Examinations:

No data

Medical treatment:

No data

Results and discussion

Clinical signs:

Olfactory fatigue was reported by most subjects at 14 and 7 ppm, and by two subjects at 24 ppm. Most subjects could detect an odour initially at 24 and 14 ppm, but only one half of the group could detect methacrylonitrile vapour at a concentration of 7 ppm. No individuals could differentiate between 2 and zero ppm. Among the subjects exposed to 24 ppm for 1 minute, 6-22 % experienced nose, throat, or eye irritation; no irritation was noted at the other concentrations. At exposure levels of 2 ppm or 14 ppm for 10 minutes, transitory irritating effects were seen (see tables below)

Results of examinations:

No data

Effectivity of medical treatment:

No data

Outcome of incidence:

No data

Any other information on results incl. tables

Human response to one minute inhalation exposures to methacrylonitrile vapour
Mean concentration (ppm)	24	14	7	2	Zero
Number of subject inhalations	18	17	17	18	18
Incidence of odour detection (%)	89	88	47	Zero	Zero
Incidence of throat irritation (%)	22	Zero	Zero	Zero	Zero
Incidence of eye irritation (%)	17	Zero	Zero	Zero	Zero
Incidence of nose irritation (%)	6	Zero	Zero	Zero	Zero

Responses of nine subjects to 2 ppm methacrylonitrile vapour for 10 minutes
Time (min)	1	2	3	4	5	6	7	8	9	10
Odour detection	4	4	3	0	0	0	0	0	0	0
Eye irritation	2	1	0	0	0	0	0	1	0	0
Tears	1	0	0	0	0	0	0	0	0	0
Nose irritation	0	0	0	0	0	0	2	1	0	0
Throat irritation	0	1	1	0	0	0	0	0	0	0

Responses of seven subjects to 14 ppm methacrylonitrile vapour for 10 minutes
Time (min)	1	2	3	4	5	6	7	8	9	10
Odour detection	7	6	1	0	0	0	0	0	0	0
Eye irritation	0	1	1	1	1	1	1	1	0	0
Tears	0	0	0	0	0	0	0	0	0	1
Nose irritation	0	0	0	0	0	0	1	1	1	0
Throat irritation	1	0	0	0	0	1	0	0	0	0

Applicant's summary and conclusion

Conclusions:

The human response to methacrylonitrile vapour indicates that the solvent has very poor warning properties. It is very likely that most people will not be able to deect the odour of dangerous concentrations of methacrylonitrile vapours after 2-3 minutes. From other sections of the same publication, the authors conclude that the rat appears to be considerably more resistant to repeated inhalation of methacrylonitrile vapour than the dog. The 'no ill-effect' level for the rat over 91 days lies between 52.6 and 19.3 ppm, whereas that for the dog lies between 8.8 and 3.2 ppm. Since the position of man is unknown relative to the rat and the dog, the authors conclude that it is safest to assume man is similar to the dog and suggest that workmen should not be allowed to inhale more than 3 ppm of methocrylonitrile vapour for extended periods of time (8 hours per day on 5 days per week)