Renewable hydrocarbons (diesel type fraction)

Basic toxicokinetics

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:

other: Modern non-GLP, non-guideline experimental investigation

Data source

Reference

Reference Type:

publication

Title:

Inhalation kinetics of C8 to C10 1-alkenes and iso-alkanes in the rat after repeated exposures

Author:

Zahlsen, K, Eide, I, Nilsen, AM and Nilsen, OG

Year:

1993

Bibliographic source:

Pharmacology and Toxicology 73, 163-168

Materials and methods

Objective of study:

toxicokinetics

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The toxicokinetics of C8, C9 and C10 iso-alkanes in blood and selected body tissues was investigated in groups of male rats exposed to 100 ppm vapour (12 hr/d for 3 d)

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

2-methyl heptane

IUPAC Name:

2-methyl heptane

Constituent 2

Reference substance name:

2-methyl octane

IUPAC Name:

2-methyl octane

Constituent 3

Reference substance name:

2-methyl nonane

IUPAC Name:

2-methyl nonane

Details on test material:

2-methyl heptane, CAS No. 592-27-8, C8H18 (>97%)
2-methyl octane, CAS No. 3221-61-2, C9H20 (>99%)
2-methyl nonane, CAS No. 871-83-0, C10H22 (>99%)
All supplied by Fluka AG, Buchs, Switzerland

Radiolabelling:

no

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: 150-200 g
- Housing: 4/cage
- Individual metabolism cages: no (4/cage)
- Diet : ad libitum (no further details)
- Water : ad libitum (tap water)
- Acclimation period: 4-6 d

ENVIRONMENTAL CONDITIONS
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

inhalation: vapour

Vehicle:

other: air

Details on exposure:

Animals were exposed whole body to a target concentration of 100 ppm test substance (5 m3/hr) while housed in conical 0.7 m3 steel chambers with glass door and walls. A total of 16 animals (housed in 4 cages) were exposed on each occasion. Temperature and relative humidity were maintained at 22-24 degrees C and 50-90%, respectively, during exposure.

Duration and frequency of treatment / exposure:

12 hr/d for 3 d

Doses / concentrations

Remarks:

Doses / Concentrations:
100 ppm vapour

No. of animals per sex per dose / concentration:

4 males per substance per time point

Control animals:

no

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:

Tissue concentrations increased with increasing number of carbon atoms (C10 > C9 > C8)

Details on distribution in tissues:

Tissue concentrations were greatest in fat and lowest in blood (fat >> kidney, brain, liver >> blood).

Details on excretion:

Mean concentrations in fat immediately post-exposure was approx. 175-900 umol/kg decreasing to approx. 100-450 umol/kg 12 hr post-exposure. Mean concentrations in blood immediately following exposure were approx. 3-7 umol/kg and undetectable 12 hr post-exposure.

Any other information on results incl. tables

The tissue concentration of various iso-alkanes tested increased with increasing number of carbon atoms:
C10 > C9 > C8

The tissue concentration of iso-alkane was greatest in fat and lowest in blood:
fat >> kidney, brain, liver >> blood

Mean concentrations in fat immediately following exposure were in an approx. range 175-900 umol/kg,  with approx. 100-450 umol/kg detectable 12 hr post-exposure.

Mean concentrations in kidney, liver and brain immediately following exposure were in an approx. range 10-70 umol/kg and generally undetectable at 12 hr post-exposure.

Mean concentrations in blood immediately following exposure were in an approx. range 3-7 umol/kg,  and undetectable at 12 hr post-exposure.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): other: Uptake and distribution of inhaled C8-C10 isoalkanes in body tissues, with rapid elimination from blood, brain, liver and kidney but slower from fat.
The concentration of iso-alkane in blood, brain, liver and fat increased with increasing number of carbon atoms. Detectable levels remained only in fat 12 hr post-exposure.

Executive summary:

The toxicokinetic properties of C8, C9 and C10 iso-alkanes were investigated in groups of male SD rats exposed by inhalation (100 ppm, 12 hr/d for 3 d), with the concentration of each in blood, brain, liver, kidney and perirenal fat determined using headspace GC immediately following each daily exposure and also 12 hr after the final exposure. The tissue concentration of the various iso-alkanes increased with increasing number of carbon atoms (C10 > C9 > C8), with analysed tissue concentrations being greatest in fat and lowest in blood (fat >> kidney, brain, liver >> blood). Detectable levels remained only in fat 12 hr post-exposure. The results indicate uptake and distribution of inhaled C8-C10 isoalkanes in body tissues, with rapid elimination from blood, brain, liver and kidney but slower removal from fat.