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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vitro / ex vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Read across from a modern non-GLP, non-guideline experimental investigation on structural analogues.

Data source

Reference
Reference Type:
publication
Title:
In vitro rat hepatic metabolic of n-alkanes: nonane, decane and tetradecane
Author:
Anand SS, Campbell JL and Fisher JW
Year:
2007
Bibliographic source:
International Journal of Biochemistry 26, 325-329

Materials and methods

Principles of method if other than guideline:
Michaelis-Menten constants were quantified (GC-FID) for the metabolism of three normal alkanes (C9, C10, C14) using rat liver microsomes in vitro.
GLP compliance:
not specified

Test material

Constituent 1
Reference substance name:
n-nonane
IUPAC Name:
n-nonane
Constituent 2
Reference substance name:
n-decane
IUPAC Name:
n-decane
Constituent 3
Chemical structure
Reference substance name:
Tetradecane
EC Number:
211-096-0
EC Name:
Tetradecane
Cas Number:
629-59-4
Molecular formula:
C14H30
IUPAC Name:
tetradecane
Details on test material:
n-alkanes: n-nonane (CAS No 111-84-2), n-decane (CAS No 124-18-5), n-tetradecane (CAS No 629-59-4)

Supplied by Sigma Chemical Co. (St Louis, Mo, USA), purity greater than 99%.

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River, Raleigh, NC, USA
- Age at study initiation: approx. 90 days
- Diet: ad libitum, 5001 Rodent Diet (PMI Nutrition International, MO, USA)
- Water: ad libitum (tap water)

ENVIRONMENTAL CONDITIONS
- Relative humidity: 40-60%
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Statistics:
Data were analysed using Student's t-test.

Results and discussion

Metabolite characterisation studies

Details on metabolites:
Vmax for removal of n-nonane, n-decane, n-tetradecane by rat liver microsomes was inversely related to carbon number as follows:
C9>C10>>>C14 (no detectable removal of n-tetradecane)

Any other information on results incl. tables

Michaelis-Menten constants for metabolism of n-nonane, n-decane and n-tetradecane by rat hepatic microsomes were as follows:

n-nonane (C9) Km = 295, Vmax = 7.26
n-decane (C10) Km = 398, Vmax = 2.81

n-tetradecane (C14) Km = nd, Vmax = nd

Km (substrate concentration giving half Vmax) = uM

Vmax (maximum rate at infinite substrate concentration) = nmol/mg microsomal protein/hr

nd = no metabolic removal of n-tetradecane over the range 13 -1300 uM

Applicant's summary and conclusion

Executive summary:

Michaelis-Menten constants for the metabolism of three normal alkanes (n-nonane, 20-4000 µM; n-decane, 10-3500 µM; n-tetradecane, 13-1300 µM) by rat liver microsomes in vitro were derived in this study. Incubations were performed in sealed tubes in the presence and absence of NADPH using the microsomal fraction from four individual rats (one experiment per rat), and included control incubations containing heat-inactivated microsomes to account for non-metabolic removal of parent substance. Analyses were conducted using GC-FID, with the kinetic constants Vmax (nmol alkane removed/min/mg microsomal protein) and Km (µM) calculated using non-linear regression. The results indicated that metabolic clearance (as predicted by Vmax) was inversely related to carbon number as follows: C9>C10>>>C14 (no detectable removal of n-tetradecane under the conditions of the study).

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