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Toxicological information

Direct observations: clinical cases, poisoning incidents and other

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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

Constituent 1
Chemical structure
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)