Renewable hydrocarbons (diesel type fraction)

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Non-GLP, non-guideline experimental investigation

Data source

Reference

Reference Type:

publication

Title:

Prediction of in vivo metabolic clearance of 25 different petroleum hydrocarbons by a rat liver head-space technique

Author:

Mortensen, B, Eide, I, Zahlsen, K and Nilsen, OG

Year:

2000

Bibliographic source:

Archives of Toxicology, 74, 308-312

Materials and methods

Principles of method if other than guideline:

Michaelis-Menten constants were quantified (GC-FID) for the metabolism of six normal- and six iso- alkanes (C6-C10) by rat liver slices in vitro.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

2-methylpentane

EC Number:

203-523-4

EC Name:

2-methylpentane

Cas Number:

107-83-5

Molecular formula:

C6H14

IUPAC Name:

2-methylpentane

Constituent 2

Reference substance name:

2-methylhexane

EC Number:

209-730-6

EC Name:

2-methylhexane

Cas Number:

591-76-4

Molecular formula:

C7H16

IUPAC Name:

2-methylhexane

Constituent 3

Reference substance name:

2-methylheptane

EC Number:

209-747-9

EC Name:

2-methylheptane

Cas Number:

592-27-8

Molecular formula:

C8H18

IUPAC Name:

2-methylheptane

Constituent 4

Reference substance name:

2-methyloctane

EC Number:

221-748-6

EC Name:

2-methyloctane

Cas Number:

3221-61-2

Molecular formula:

C9H20

IUPAC Name:

2-methyloctane

Constituent 5

Reference substance name:

2-methylnonane

EC Number:

212-814-5

EC Name:

2-methylnonane

Cas Number:

871-83-0

Molecular formula:

C10H22

IUPAC Name:

2-methylnonane

Constituent 6

Reference substance name:

N-hexane

EC Number:

203-777-6

EC Name:

N-hexane

Cas Number:

110-54-3

Molecular formula:

C6H14

IUPAC Name:

n-hexane

Constituent 7

Reference substance name:

n-heptane

IUPAC Name:

n-heptane

Constituent 8

Reference substance name:

n-octane

IUPAC Name:

n-octane

Constituent 9

Reference substance name:

n-nonane

IUPAC Name:

n-nonane

Constituent 10

Reference substance name:

n-decane

IUPAC Name:

n-decane

Details on test material:

i-alkanes:2-methylpentane (CAS No 107-83-5), 2-methylhexane (CAS No 591-76-4), 2-methylheptane (CAS No 592-27-8), 2-methyloctane (CAS No 3221-61-2), 2-methylnonane (CAS No 871-83-0)

n-alkanes: n-hexane (CAS No 110-54-3), n-heptane (CAS No 142-82-5), n-octane (CAS No 111-65-9), n-nonane (CAS No 111-84-2), n-decane (CAS No 124-18-5)

Supplied by Fluka Chemie (Buchs, Switzerland), Merck (Darmstadt, Germany), Aldrich-Chemie (Steinheim, Germany) or Sigma Chemical Co. (St Louis, Mo, USA) with a quoted purity of 97% or higher.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Mollegaard A/S, Skensved, Denmark
- Weight at study initiation: 175-200 g
- Diet: pelleted diet ad libitum (Ewos, Sweden)
- Water: ad libitum (tap water)

ENVIRONMENTAL CONDITIONS
- Relative humidity: 55%
- 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:

Michaelis-Menten constants (apparent Km, apparent Vmax) were both generally greater for n-alkanes relative to the corresponding i-alkanes
e.g.
i-C10: Km = 0.95 mg/l, Vmax = 0.30 mg/hr
n-C10: Km = 1.50 mg/l, Vmax = 0.40 mg/hr

Metabolism of iso-C6-C10 alkanes may be slower than metabolism of equivalent n-alkanes.

Any other information on results incl. tables

Michaelis-Menten constants for metabolism of C6 -C10 iso and normal alkanes by rat liver slices were as follows:

i-alkanes:
C6 Km = 1.02, Vmax = 0.10
C7 Km = 1.68, Vmax = 0.17
C8 Km = 1.90, Vmax = 0.32
C9 Km = 0.70, Vmax = 0.18
C10 Km = 0.95, Vmax = 0.30

n-alkanes:
C6 Km = 3.65, Vmax = 0.45
C7 Km = 2.36, Vmax = 0.44
C8 Km = 1.19, Vmax = 0.25
C9 Km = 0.89, Vmax = 0.21
C10 Km = 1.50, Vmax = 0.40

Km (substrate concentration giving half Vmax) = mg/l

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

Applicant's summary and conclusion

Executive summary:

Michaelis-Menten constants (Km, Vmax) were derived for the metabolism of a series of C6-C10 iso- and normal alkanes in vitro using a rat liver slice head-space technique with analysis by GC-FID using substrate concentrations of 50, 100, 200 and 400 ppm. For a given carbon number, apparent Vmax (mg/hr) and apparent Km (mg/l) were both generally greater for n-alkanes relative to the corresponding i-alkanes. The results demonstrate metabolism of C6-C10 iso- and normal alkanes by rat liver enzymes but suggest that hepatic metabolism of i-alkanes may be slower relative to that of equivalent n-alkanes.