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Administrative data

Endpoint:
direct observations: clinical cases, poisoning incidents and other
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: Non-guideline, non-GLP, human experimental study, published in peer-reviewed literature. Well-documented with respect to end-point.

Data source

Reference
Reference Type:
publication
Title:
Acute exposure to 50 ppm toluene does not increase sleepiness
Author:
Muttray A, Spelmeyer U, Hommel G, Oesch F, Jung D, Rose D, Mayer-Popken O, Rossbach B and Letzel S
Year:
2005
Bibliographic source:
Environ. Toxicol. Pharmacol. 19, 665-669

Materials and methods

Study type:
study with volunteers
Endpoint addressed:
acute toxicity: inhalation
Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
Volunteers were exposed in an exposure chamber, once to 50 ppm toluene and once to air for a period of 4.5 hours. Sleepiness was assessed by the Pupillographic Sleepiness Test (PST) before and after exposure.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Toluene high purity solvent, supplied by Fluka AG, Buchs, Switzerland

Method

Type of population:
other: Healthy non-smoking male volunteers
Subjects:
- Number of subjects exposed: 20
- Sex: male
- Age: 30.5 (± 5.2) years
- Volunteers were exposed in an exposure chamber, once to 50 ppm toluene and once to air for a period of 4.5 hours. Sleepiness was assessed by the Pupillographic Sleepiness Test (PST) before and after exposure. Acute neurobehavioural symptoms were assessed by a questionnaire based on the Swedish Performance Evaluation System (SPES) self-assessment questionnaire completed, once before and during exposure (2, 60 and 265 minutes).
Ethical approval:
confirmed and informed consent free of coercion received
Route of exposure:
inhalation
Reason of exposure:
intentional
Exposure assessment:
measured
Details on exposure:
Exposure carried out in a 18 m3 chamber. 270 minute exposure period. Mean toluene concentration 51.5 ppm (+1.02 S.D.) by infrared-spectroscopy. Mean temperature: 21.0 °C (+0.4 S.D.), maen humidity: 52.0% (+0.65 S.D.). Air exchange: 6/hour.

Biological monitoring: 50 ppm toluene for 270 min resulted in a mean toluene blood concentration of 0.5 mg/L (±0.12 S.D.). After exposure to air mean toluene blood concentration was 0.01 mg/L (±0.005 S.D.).
Examinations:
Pupillographic sleepiness test (PST): Once before and once after exposure. Spontaneous pupillary movements were recorded for 11 min. The Pupillary-Unrest-Index (PUI in mm/min) was calculated automatically by the PST-machine. PUI is based on cumulative changes in pupil diameter.
Assessment of acute symptoms: A questionnaire based on the Swedish Performance Evaluation System (SPES) self-assessment questionnaire was completed, once before and during exposure (2, 60 and 265 minutes).
Blood analyses: Just before exposure began and immediately after exposure.
Urine analyses: Just before exposure began.

Results and discussion

Clinical signs:
"Sensation of bad smell" and "irritation to the throat" were recorded during exposure but no residual or period effects were seen. No other statistically significant differences in clinical signs were recorded.


Subjective symptoms: "sensation of bad smell" and "irritation to the throat" were recorded during exposure but no residual or period effects were seen. The score for "irritation to the throat" was statistically significant raised at 265 min. The solvent odour was identified correctly, instantly and sustained by the subjects. No other effects were statistically different.
PST: The statistical analysis performed on the logarithmic PUI values gave no evidence for any residual, period or treatment effects.
Results of examinations:
There was no effect of toluene exposure on Pupillographic Sleepiness Test (PST) or other acute symptoms (headache, dizziness, nausea, tiredness, pain or pressure on the chest, coughing spells, shortness of breath, irritation to the eyes, watering eyes, blurred vision, irritation to the nose, running nose, sensation of unpleasant taste, irritation to the skin, feeling of fainting or vertigo) in human volunteers exposed at 50 ppm (188 mg/m3) for 4.5 hours.

Any other information on results incl. tables

Parametric cross-over analysis of logarithmic Pupillary Unrest Index (PUI) values did not show an effect of toluene exposure. In a nonparametric cross-over analysis of SPES-scores a significant increase of the scores of unpleasant smell and irritation to the throat, but not of tiredness was found. In conclusion, acute exposure to 50 ppm toluene did not increase sleepiness.

Applicant's summary and conclusion

Conclusions:
The NOAEC for acute neurobehavioural effects in man was 50 ppm (188 mg/m3) toluene.
Executive summary:

Twenty healthy men were exposed to a constant level of 50 ppm toluene. The Pupillographic Sleepiness Test (PST) was performed before and after 4.5 h of exposure. Acute symptoms were assessed with the Swedish Performance Evaluation System (SPES) self-assessment questionnaire, once before and 3 times during exposure. There was no effect of toluene exposure on PST or tiredness but scores for unpleasant smell and irritation to the throat were increased.

In conclusion, a NOAEC of 50 ppm (188mg/m3) can be determined for acute neurobehavioural effects.