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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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Basic data given which meets accepted scientific principles

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1959

Materials and methods

Study type:
study with volunteers
Endpoint addressed:
acute toxicity: inhalation
Test guideline
Guideline:
other: not specified
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Acetontitrile
- Source: Union Carbide Chemicals Company

Method

Type of population:
other: volunteers.
Subjects:
- Number of subjects exposed: 3
- Sex: Men
- Age: between 31 - 47 years of age.
Ethical approval:
not specified
Route of exposure:
inhalation
Reason of exposure:
intentional
Exposure assessment:
estimated
Details on exposure:
The men (designated as PEP, UCP and CPC - and apparently coauthors of the paper) inhaled 40ppm acetonitrile vapor for four hours in a 7,900 liter chamber. Air was exhausted from the chamber at 1,400 liters per minute, and the chamber air temperature was kept below a maximum of 76°F. One week later UCP and CPC were exposed to 80ppm for four hours. Nine days later these two subjects inhaled a metered concentration of 160ppm acetonitrile vapor for four hours.
Examinations:
- Urinary Thiocyanate:
40ppm exposure - thiocyanate content of 24-hour urine samples was determined 19, 18, and 1 day prior to the inhalation period and immediately after the inhalation period. Each sample consisted of two fractions: one taken between 8:00 a.m. and 4:00 p.m. and the other taken from 4:00 p.m to 8:00 a.m. the following morning.
80ppm and 160ppm exposures - Urinary thiocyanate was determined one day before, and one and two days after inhalation.

- Blood Cyanide:
40ppm exposure - cyanide content of the blood of each subject was determined 19 days and 1 day prior to, and immediately after, inhalation.
80ppm and 160ppm exposures - Blood cyanide levels were followed immediately before, and 1 hour, 3 hours, and 24 hours after the inhalation period.

Medical treatment:
The services of a physician were available during the inhalation period.

Results and discussion

Clinical signs:
40 ppm exposure - The two older subjects, CPC and UCP, reported no adverse subjective response during and after the four-hour inhalation period. The youngest subject, PEP, reported no adverse subjective response during the inhalation period, but he did experience a slight tightness in the chest that evening. The following morning he also reported a cooling sensation in the lung similar to that experienced when menthol is inhaled. This sensation persisted for approximately 24 hours. All three subjects detected the odor of acetonitrile for the first two or three hours, after which they experienced some olfactory fatigue. A hearty lunch was enjoyed by all immediately after the four-hour inhalation period.

80 ppm exposure - The subjective response of both subjects was again negative.

160ppm exposure - The only adverse subjective responses were reported by CPC, who experienced a slight transitory flushing of the face two hours after inhalation, and a slight feeling of bronchial tightness about five hours later. The latter symptom did not persist overnight. This subject had reported a slight nasal drip prior to the inhalation. Both subjects stated they would have no hesitation about inhaling 160ppm acetonitrile vapor again for a four-hour period.
Results of examinations:
- Urinary Thiocyanate:
40ppm - Two subjects had no appreciable increase in urinary thiocyanate; the third subject had a slight increase.
80ppm - The urinary thiocyanate picture was confused, for UCP had a higher urinary thiocyanate value immediately before inhalation than he did afterward. On the other hand, CPC values were relatively constant.
160ppm - The urinary thiocyanate levels of both subjects did not change significantly from pre-inhalation values.

- Blood Cyanide:
40ppm exposure - No detectable blood cyanide.
80ppm exposure - No blood cyanide was detected in any of the samples taken after the inhalation period.
160ppm exposure - The blood cyanide levels of both subjects did not change significantly from pre-inhalation values.
Outcome of incidence:
One subject reported slight tightness in the chest and a cooling sensation in the lungs following exposure to 40ppm acetonitrile vapor for 4 hours. Two of the three subjects reported no subjective symptoms from exposure up to 160 ppm for four hours and stated they would have no hesitation about inhaling 160ppm acetonitrile vapor again for a four-hour period. There was no correlation between thiocyanate excretion and acetonitrile concentration. No blood cyanide was found.

Applicant's summary and conclusion

Conclusions:
There was no correlation between thiocyanate excretion and acetonitrile concentration. No blood cyanide was found. The variability of subjective responses of humans to 40, 80, and 160ppm acetonitrile vapor suggests that, even if a concentration of the solvent vapor were selected that would not endanger the health of the majority of workers, it might cause discomfort to some. These considerations and others caused the authors to conclude that it was reasonable to suggest an initial hygienic standard for acetonitrile vapor of no more than 40ppm.
Executive summary:

Pozzani et al (1959) reported results of exposing human volunteers to acetonitrile vapor concentrations of 40ppm, 80ppm or 160ppm for four hours. One subject reported slight tightness in the chest and a cooling sensation in the lungs following exposure to 40ppm acetonitrile vapor for 4 hours. Two of the three subjects reported no subjective symptoms from exposure up to 160ppm for four hours and stated they would have no hesitation about inhaling 160ppm acetonitrile vapor again for a four-hour period. There was no correlation between thiocyanate excretion and acetonitrile concentration. No blood cyanide was found. These considerations and others caused the authors to conclude that it was reasonable to suggest an initial hygienic standard for acetonitrile vapor of no more than 40ppm.