Octane

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study meets generally accepted scientific principles, acceptable for assessment.

Data source

Reference

Reference Type:

publication

Title:

Inhalation kinetics of C6 to C10 aliphatic, aromatic and naphtenic hydrocarbons in rat after repeated exposures

Author:

Zahlsen, K. et al.

Year:

1992

Bibliographic source:

Pharmacology & Toxicology 71: 144-149

Materials and methods

Objective of study:

distribution

toxicokinetics

Principles of method if other than guideline:

3 day toxicokinetic study in rats.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Octane

EC Number:

203-892-1

EC Name:

Octane

Cas Number:

111-65-9

Molecular formula:

C8H18

IUPAC Name:

octane

Details on test material:

- Name of test material (as cited in study report): n-Octane
- Analytical purity: >99%

Radiolabelling:

no

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Møllegaard A/S, L1, Skensved, Denmark
- Age at study initiation: 40-50 days
- Weight at study initiation: 150 - 200 g
- Individual metabolism cages: no
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 4-6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23±1 during exposure
- Humidity (%): 70 ± 20 during exposure
- Photoperiod (hrs dark / hrs light): 10/14

Administration / exposure

Route of administration:

inhalation: vapour

Vehicle:

unchanged (no vehicle)

Details on exposure:

TYPE OF INHALATION EXPOSURE: whole body

GENERATION OF TEST ATMOSPHERE / CHAMPER DESCRIPTION
- Exposure apparatus: conical 0.7 m³ inhalation chambers with a glass front door and walls, accommodating 4 cages each containing 4 rats each.
TYPE OF INHALATION EXPOSURE: whole body

Dynamic exposure of anomals was performed in conically shaped 0.7 m3 steel chambers with glass front door and walls as described elsewhere (Walseth & Nilsen 1984). The concentration of hydrocarbons in the inhalation chambers was monitored automatically by on-line gas chromatography, Concentrations were measured in 15 min intervals. Altogehter 44 measurements at steady state each day.

Duration and frequency of treatment / exposure:

1, 2, and 3 days, 12 hours/day

Doses / concentrations

Remarks:

Doses / Concentrations:
0.52 mg/L (corresponding to 100 ppm)

No. of animals per sex per dose / concentration:

4 per exposure duration

Control animals:

no

Positive control reference chemical:

not applicable

Details on study design:

The aimed concentration was 1000 ppm. All exposures were performed at daytime for 12 hr (8 a.m. - 8 p.m.). Measurements were done on days 1, 2, and 3 after 12 hr exposure. Animals were one by one removed, killed, and blood and organs obtained within 3 min after removal from exposure chamber.

Details on dosing and sampling:

PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled: blood, brain, liver, kidneys, perirenal fat
- Time and frequency of sampling: day 1, 2, and 3 within 3 min of removal from inhalation chamber

Results and discussion

Preliminary studies:

Not performed

Toxicokinetic / pharmacokinetic studies

Details on absorption:

Not addressed.

Details on distribution in tissues:

n-Octane demonstrated the highest concentration in kidney and brain tissue with lowest levels on day 3. In perirenal fat, a different pattern was seen with concentrations increasing from day 1 to day 3.

Transfer into organs

Key result

Test no.:

#1

Transfer type:

blood/brain barrier

Observation:

distinct transfer

Details on excretion:

Not addressed.

Metabolite characterisation studies

Metabolites identified:

not measured

Any other information on results incl. tables

Blood and tissue values in µmol/kg (with SD):

day	1	2	3
blood	3.9 ± 0.9	4.2 ± 0.0	3.6 ± 0.5
Brain	37.8 ± 8.1	37.2 ± 7.4	25.2 ± 2.1
liver	10.2 ± 1.0	10.6 ± 1.7	8.4 ± 2.8
kidney	64.9 ± 21.1	66.2 ± 4.3	41.9 ± 9.3
fat	362 ± 63	548 ± 46	697 ± 71

Conclusion:

n-Octane was found in higher concentrations in kidneys and in lower concentrations in blood and liver. The lowest tissue levels were determined on day 3. In perirenal fat, concentrations were the highest with concentrations increasing from day 1 to day 3.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): other: see conclusions below
n-Octane was found in higher concentrations in kidneys and in lower concentrations in blood and liver. The lowest tissue levels were determined on day 3. In perirenal fat, concentrations were the highest with concentrations increasing from day 1 to day 3.

Executive summary:

n-Octane was found in higher concentrations in kidneys and in lower concentrations in blood and liver. The lowest tissue levels were determined on day 3. In perirenal fat, concentrations were the highest with concentrations increasing from day 1 to day 3.