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 from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non-GLP, non-guideline, animal and human experimental study, predates implementation of GLP and/or development of study guidelines but otherwise acceptable for assessment
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
publication
Title:
Studies on the inhalation of 1,3-butadiene; with a comparison of its narcotic effect with benzol, toluol and styrene, and a note on the elimination of styrene by the human
Author:
Carpenter CP, Shaffer CB, Weir CS, Smyth HF
Year:
1944
Bibliographic source:
J Ind Hyg Toxicol 26; 69-78

Materials and methods

Type of study / information:
Evaluation of the effect on the psycho-motor response.
Endpoint addressed:
acute toxicity: inhalation
Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
Two male subjects inhaled 2000, 4000 or 8000 ppm 1,3-butadiene and their pulse rate, blood pressure and subjective symptoms were recorded. To evaluate the effect on the psycho-motor response, tapping rate and steadiness tests were performed before and during exposures.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Supplied by: Carbide and Carbon Chemicals Corporation

Method

Ethical approval:
not specified
Details on study design:
Two male subjects inhaled 1,3-butadiene at concentrations of 2000 ppm for 7 hours, 4000 ppm for 6 hours and 8000 ppm for 8 hours. During exposure Pulse rate and blood pressure and subjective symptoms were recorded. Before and during exposures tapping rate and steadiness tests were performed to evaluate the effect on the psycho-motor response
Exposure assessment:
estimated
Details on exposure:
The subjects were exposed to 3 concentrations of 1,3-butadiene: 2000 ppm for 7 hours, 4000 ppm for 6 hours and 8000 ppm for 8 hours. The exposures were performed in a 4000 cu. ft. Room. Rapid and thorough mixing of the air was achieved by fans. Butadiene was bled directly from a cylinder. The vapour concentrations were estimated using an interferometer (concentration of butadiene calculated using the iodine pentoxide method) and controlled manually.

Results and discussion

Results:
SUBJECTIVE SYMPTOMS: At 2000 (4425 mg/m3) and 4000 ppm (8851 mgm3) 1,3-butadiene resulted in slight smarting of the eyes and difficulty in focusing on instrument scales. The odour was described as objectionable.
At 8000 ppm (17702 mg/m3) butadiene there were no subjective symptoms reported. It was proposed that this was due to slight anxiety/preoccupation with the control of this concentration (explosion risk). Following the first single exposure to butadiene, the subjects became much less aware of subjective symptoms when exposed subsequently to the same or a higher concentration.
STEADINESS TEST: Although unsteadiness was seen in both subjects at 4000 ppm, there was little or no effect noted at 8000 ppm or 2000 ppm.
The maximum time in contact (as % of day’s normal) was 266 and 136 for 4000 and 8000 ppm. At 2000 ppm the test was considered too brief to be reliable.

Any other information on results incl. tables

OTHER RESULTS:

BLOOD PRESSURE / PULSE RATE: Results were too variable to be of any significance.

TAPPING TEST: Minimum tapping rate in any 6 seconds (as % of day’s normal) was 100 at 8000 ppm with a maximum co-efficient of variation of 0.087. At 2000 and 4000 ppm the tests were too brief to be reliable and therefore the results were inconclusive.

Applicant's summary and conclusion

Conclusions:
Two human volunteers inhaled 1,3-butadiene at concentrations up to 8000 ppm (17701 mg/m3). No immediate adverse effects were apparent at concentrations of 2000 and 4000 ppm (4425 and 8851 mg/m3) although the subjects stated that the odour was objectionable and smarting of the eyes was recorded.
Executive summary:

1,3-butadiene was judged to be innocuous at the concentrations inhaled. At concentrations of 2000 and 4000 ppm (4425 and 8851 mg/m3) odour was considered to be objectionable. The authors stated that provided that the lower explosive limit is not exceeded, it is unlikely that the health of anyone inhaling its vapours will be impaired.