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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
migrated information: read-across based on grouping of substances (category approach)
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 naphthenic 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

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): n-Heptane
- Analytical purity: >99%
Radiolabelling:
no

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals 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:
4 per exposure duration
Control animals:
no
Positive control:
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:
Normal-Heptane demonstrated moderate concentrations in kidneys. In perirenal fat, concentration are highest, however decreasing with lasting exposure. This is in contrast to other n-alkanes, which showed increasing concentrations.
Transfer into organs
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

2.4 ± 0.8

2.9 ± 0.9

2.1 ± 0.2

Brain

5.2 ± 0.8

6.9 ± 0.6

6.2 ± 1.0

liver

1.6 ± 0.6

2.3 ± 0.1

1.5 ± 0.1

kidney

15.7 ± 4.2

15.2 ± 2.6

17.1 ± 3.0

fat

140 ± 14

127 ± 28

121 ± 10

Conclusion:

n-Heptane was found in moderate concentrations in the kidneys and only in marginal concentrations in blood, brain and liver. In perirenal fat, concentrations were the highest, however, decreasing with lasting exposure.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): other: see conclusions below
Normal-Heptane was found in moderate concentrations in the kidneys and only in marginal concentrations in blood, brain and liver. In perirenal fat, concentrations were the highest, however, decreasing with lasting exposure.
Executive summary:

Normal-Heptane was found in moderate concentrations in the kidneys and only in marginal concentrations in blood, brain and liver. In perirenal fat, concentrations were the highest, however, decreasing with lasting exposure.