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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non-GLP, non-guideline, data modelling study, published in peer reviewed literature, fully adequate for assessment.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
2001

Materials and methods

Objective of study:
toxicokinetics
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
A physiological toxicokinetic model was developed on the basis of previously reported models.
GLP compliance:
not specified

Test material

Constituent 1
Chemical structure
Reference substance name:
Isoprene
EC Number:
201-143-3
EC Name:
Isoprene
Cas Number:
78-79-5
Molecular formula:
C5H8
IUPAC Name:
isoprene
Constituent 2
Reference substance name:
2-methyl-1,3-butadiene
IUPAC Name:
2-methyl-1,3-butadiene

Test animals

Species:
other: human, rat, mouse

Administration / exposure

Route of administration:
inhalation
Vehicle:
not specified

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:
Atmospheric concentration-time curves fitted to data from rats and mice exposed by inhalation to isoprene demonstrated that metabolism is saturable.
Details on excretion:
The model predicts that in rats exposed by inhalation to 8 ppm isoprene, approximately 21% of inhaled isoprene is metabolised.
Toxicokinetic parametersopen allclose all
Toxicokinetic parameters:
other: the rate of endogenous production of isoprene in a 70 kg man was estimated to be 23.8 µmol/h (0.34 µmol/h/kg); approximately 90% is metabolised, the remaining 10% is exhaled unchanged
Toxicokinetic parameters:
other: the model predicts that endogenous production of isoprene will result in blood concentrations of 9.5 nmol/L in humans
Toxicokinetic parameters:
other: rats: Km=180ppm
Toxicokinetic parameters:
other: mice: Km=360ppm

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): other: For man, the estimated area under the blood concentration versus time curve (AUC) following exposure by inhalation to 10 ppm isoprene for 8h is 4-fold higher than the 24 h AUC resulting from exposure to endogenous isoprene.