Registration Dossier

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: Non-GLP, non-guideline animal and human experimental studies, reported in peer reviewed literature, minor restrictions in design but otherwise adequate for assessment
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
2008

Materials and methods

Study type:
study with volunteers
Endpoint addressed:
basic toxicokinetics
Principles of method if other than guideline:
Concentrations of propene & propene oxide measured in exhaled air of human volunteers
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Propene, purity ≥99.95%, ex Messer Griesheim (Krefeld, Germany)

Method

Type of population:
general
Subjects:
4 adult males healthy non-smokers aged 33-55 years and weighing 58 - 94 kg
Ethical approval:
confirmed, but no further information available
Route of exposure:
inhalation
Reason of exposure:
intentional
Exposure assessment:
measured
Details on exposure:
Exposed via 2-way mask, exposures of 3h at concentrations of approximately 10 and 23ppm propene
Examinations:
Propene was measured in inhaled and exhaled air by GC/FID. Propene oxide was quantified by GC/MSD from exhaled breath collected in gasbags. Blood concentrations of propene oxide were calculated based on the measured concentrations in air using the blood-to-air partition coefficient of 66.
Respiratory parameters of each volunteer were established immediately after each exposure by determining average breathing frequency, tidal volume and pulmonary ventilation, over a time span of 10 min, using a spirometer.

Results and discussion

Results of examinations:
The mean concentrations of propene were lower in the exhaled than in the inhaled air; this difference resulted predominantly from the metabolism of propene. At an exposure concentration of 25 ppm (43 mg/m3) propene, the mean rate of metabolism was 30 µmol/h; the majority of inhaled propene being exhaled unchanged. Mean blood concentrations of propene oxide calculated assuming a blood:air partition coefficient of 66 were 0.44 and 0.92 nmol/L at mean propene exposure concentrations of 9.82 and 23.4 ppm (17 and 40 mg/m3), respectively.

Applicant's summary and conclusion

Conclusions:
Propene oxide is produced in human volunteers following exposure by inhalation to propene.
The majority of inhaled propene is exhaled unchanged, steady state blood concentrations are similar to those in rats exposed to a similar concentration.
In human volunteers, propene oxide concentrations in blood were estimated to be 0.92nmol/L (38ppb) after exposure to 23.4ppm propene, this is 58x lower than in rats exposed to 20.1ppm propene.