Registration Dossier

Toxicological information

Exposure related observations in humans: other data

Administrative data

Endpoint:
exposure-related observations in humans: other data
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study predates GLP, human experimental study. Limitations in design and/or reporting but otherwise adequate for assessment

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Acute and repetitive human exposure to isobutane
Author:
Stewart RD, Herrmann AA, Baretta ED, Forster HV, Sikora JJ, Newton PE and Soto RJ
Year:
1977
Bibliographic source:
Scand. J. work. environ. & health 3 234-243
Reference Type:
publication
Title:
Physiological response to aerosol propellants.
Author:
Stewart RD, Newton PE, Baretta ED, Hermann AA, Forster HV, and Soto RJ
Year:
1978
Bibliographic source:
Environ. Health Perspect. 26, 275-285.

Materials and methods

Type of study / information:
Experimental results following human volunteer study
Endpoint addressed:
acute toxicity: inhalation
repeated dose toxicity: inhalation
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Adult volunteers exposed to acute & repeat concentrations of isobutane in a controlled environment chamber.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): isobutane and propane- Physical state: gas- Supplied by: Phillips Petroleum CompanyIsobutane: boiling point -11.73°C, vapour pressure 3733 mm Hg, vapour density 2.068, SG 0.563Propane: boiling point -42.49°C, vapour pressure 6612 mm Hg, vapour density 1.549, SG 0.509

Method

Ethical approval:
confirmed and informed consent free of coercion received
Details on study design:
Adult volunteers exposed to isobutane in a controlled environment chamber. Acute exposure of 250-1000 ppm for 1 min, 2 min, 1 hour, 2 hours and 8 hours. Repeat exposure at 500 ppm 1, 2 or 8 hours/day, five days/week for 2 weeks. Acute exposures to mixtures of isobutane and propane for 1, 2 or 8 hours/day. During the investigations, all volunteers were kept under comprehensive medical surveillance including cardiac and pulmonary responses (by continuous ECG telemetry and serial computerised spirometric measurements).
Exposure assessment:
measured
Details on exposure:
TYPE OF EXPOSURE: inhalationTYPE OF EXPOSURE MEASUREMENT: Area air sampling EXPOSURE LEVELS: Acute exposure: 250, 500 and 1000 ppm isobutaneAcute exposure: isobutane/propane mix (82.5%/17.5%), propane/isobutane mix (89%/11% and 87.5%/12.5%)Repeated exposure: 500 ppm isobutaneEXPOSURE PERIOD: Acute exposure: 1 min, 2 min, 10 min, 1 hour, 2 hour, 8 hourAcute exposure: isobutane/propane mix 1 hour, 2 hours, 8 hoursRepeated exposure: 1, 2 and 8 hours

Results and discussion

Results:
Acute exposures to isobutane at 250, 500 and 1000 ppm for periods of 1 min to 8 hours did not produce any untoward physiological effect. Repetitive exposures to isobutane at 500 ppm for 1, 2 or 8 hours, 5 days/week for ten exposures were also without any measurable untoward physiological effect. Mixtures of isobutane and propane exerted no untoward physiological effects.

Any other information on results incl. tables

Analysis of exposure chamber atmospheres:Actual concentrations were within a few per cent of target for each exposure..

Acute exposures: There were no untoward responses to the acute exposures.

Repeat exposures to isobutane and isobutane/propane mixtures: There were no untoward subjective responses or abnormal physiological responses during or after these exposures. The following serial laboratory studies were unaltered: complete blood count, urinalysis, serum alkaline phosphatise, SGOT, LDH, serum bilirubin, blood sugar, serum calcium, serum phosphorus, BUN, spontaneous electroencephalogram, visual evoked response, a battery of cognitive tests and an ACTH stimulation test.

During the final week of exposure a reduction in the amplitudes of the 3,4 and 5 waves was observed in the visual evoked response.

Applicant's summary and conclusion

Conclusions:
Acute exposures to isobutane at 250, 500 and 1000 ppm for periods of 1 min to 8 hours did not produce any untoward physiological effect. Repetitive exposures to isobutane at 500 ppm for 1, 2 or 8 hours, 5 days/week for ten exposures were also without any measurable untoward physiological effect. Mixtures of isobutane and propane exerted no untoward physiological effects.
Executive summary:

Adult volunteers exposed to isobutane in a controlled environment chamber. Acute exposure of 250-1000 ppm (594 -2377 mg/m3 (MW 58.12) ) for 1 min, 2 min, 1 hour, 2 hours and 8 hours. Repeat exposure at 500 ppm 1, 2 or 8 hours/day, five days/week for 2 weeks. Acute exposures to mixtures of isobutane and propane for 1, 2 or 8 hours/day.

During the investigations, all volunteers were kept under comprehensive medical surveillance including cardiac and pulmonary responses (by continuous ECG telemetry and serial computerised spirometric measurements).

Acute exposures to isobutane at 250, 500 and 1000 ppm for periods of 1 min to 8 hours did not produce any untoward physiological effect. Repetitive exposures to isobutane at 500 ppm for 1, 2 or 8 hours, 5 days/week for ten exposures were also without any measurable untoward physiological effect. Mixtures of isobutane and propane exerted no untoward physiological effects.

Acute NOAEL > 1000 ppm (2377 mg/m3)

Repeat 2 week exposure NOAEL > 500 ppm (1189 mg/m3)