Hydrocarbons, C6-C7, n-alkanes, isoalkanes, cyclics, <5% n-hexane

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.

Justification for type of information:

A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.

Cross-reference

Reason / purpose for cross-reference:

read-across: supporting information

Reference

Endpoint:

basic toxicokinetics in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

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.

Justification for type of information:

A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.

Reason / purpose for cross-reference:

read-across source

Preliminary studies:

Not performed

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.

Key result

Test no.:

#1

Transfer type:

blood/brain barrier

Observation:

distinct transfer

Details on excretion:

Not addressed.

Metabolites identified:

not measured

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.

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:

This data is being read across from the source study that tested heptane based on analogue read across.

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.

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

Test material information

Constituent 1

Reference substance name:

Heptane

EC Number:

205-563-8

EC Name:

Heptane

Cas Number:

142-82-5

Molecular formula:

C7H21

IUPAC Name:

heptane

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 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)

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:

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

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	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.