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Diss Factsheets

Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Cross-reference
Reason / purpose for cross-reference:
reference to same study

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Comparative toxicokinetics of methanol in the female mouse and rat.
Author:
Ward, K.W. et al.
Year:
1995
Bibliographic source:
Fundamental and Applied Toxicology 26: 258-264
Reference Type:
publication
Title:
Unnamed
Year:
1996

Materials and methods

Objective of study:
toxicokinetics
Principles of method if other than guideline:
The study was performed to examine the absorption of methanol after oral administration and the rate and the extent of methanol absorption during inhalation exposure in rats and mice.
GLP compliance:
not specified

Test material

Constituent 1
Chemical structure
Reference substance name:
Methanol
EC Number:
200-659-6
EC Name:
Methanol
Cas Number:
67-56-1
Molecular formula:
CH4O
IUPAC Name:
methanol
Radiolabelling:
no

Test animals

Species:
other: rats and mice
Strain:
other: Sprague-Dawley and CD-1
Sex:
female

Administration / exposure

Route of administration:
other: oral:gavage and inhalation: vapour
Vehicle:
other: water and unchanged

Results and discussion

Metabolite characterisation studies

Details on metabolites:
After oral administration of 100 and 2500 mg methanol/kg to female rats, gastrointestinal absorption was 100% within minutes (abs. half-life 1.5 min and 7.6 min, respectively).
The maximum elimination rate is about twice as high in mice as in rat: 117.0 ± 3 and 60.7 ± 1.4 mg/hour/kg.
After inhalation at exposure concentrations from 1.3 to 6.7 mg/L (corresponding to 1000 to 5000 ppm), the mean fractional respiratory absorption of methanol in rats and mice was found to about 85%. At exposure concentrations from 13.3 to 26.6 mg/L (corresponding to 10000 - 20000 ppm), the mean fractional respiratory absorption of methanol tended to be lower (approximately 70%) in rats, but not in mice.
Blood levels in rats were about 1000 mg/L (observed: 1047 ± 298 mg/L; predicted: 1018 mg/L) at 6.7 mg/L methanol (corresponding to 5000 ppm; 8 hour exposure). Blood levels in mice were about 3500 mg/L (observed: 3580 ± 599 mg/L; predicted: 4188 mg/L) at 6.7 mg/L methanol (corresponding to 5000 ppm; 8 hour exposure).

Applicant's summary and conclusion