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Toxicological information

Basic toxicokinetics

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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:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1993

Materials and methods

Objective of study:
distribution
excretion
toxicokinetics
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
- Short description of test conditions:
n-Hexanal was dissolved in physiological saline containing 1 % bovine serum albumin and administered to mice at a dose of 6.8 µmol/10g body weight by i.v. injection into the tail vein. Mice administered the aldehyde were dissected under ether anesthesia at 0, 5, 10, 30, 60, and 120 min after the treatments. Blood was drawn from the heart and the plasma was prepared by centrifugation.

- Parameters analysed / observed: The content of n-hexanal in the plasma and liver and lung homogenates was determined.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:
purchased from Wako Pure Chemicals
Radiolabelling:
no

Test animals

Species:
mouse
Strain:
other: ddY
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Clea Japan Inc.
- Age at study initiation: 6 weeks
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum

Administration / exposure

Route of administration:
intravenous
Vehicle:
physiological saline
Remarks:
containing 1 % bovine serum albumin
Details on exposure:
n-Hexanal was dissolved in physiological saline containing 1 % bovine serum albumin and administered to mice at a dose of 6.8 µmol/10g body weight by i.v. injection into the tail vein.
Duration and frequency of treatment / exposure:
once
Doses / concentrations
Dose / conc.:
6.8 other: µmol/10 g bw
No. of animals per sex per dose:
not specified
Control animals:
yes
Positive control:
no
Details on study design:
no details given
Details on dosing and sampling:
TOXICOKINETIC / PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled (delete / add / specify): blood, plasma, liver, lung
- Time and frequency of sampling: 0, 5, 10, 30, 60 and 120 min after treatment

Results and discussion

Main ADME resultsopen allclose all
Type:
distribution
Results:
After injection n-hexanal is transported to the lung and the liver.
Type:
excretion
Results:
It is thought that n-hexanal could be either metabolized by the enzymes and/or transferred into the lung as such and excreted into expired gas easily.

Toxicokinetic / pharmacokinetic studies

Details on absorption:
not examined
Details on distribution in tissues:
After the injection of n-hexanal, the plasma content reached to ca. 500 nmol/ml at 5 min and decreased to less than half at 10 min. In the lung, the content of n-hexanal increased immediately and reached ca. 150 nmol/g in 30 min. From the mean of lung weight being ca. 0.17 g, the amount of n-hexanal in whole lung was ca. 26 nmol. This value corresponded to ca. 0.080 % of the whole injected aldehyde. After 30 min, the content of n-hexanal decreased significantly. The amount of n-hexanal at 120 min was ca. 20 % of that seen at 30 min. In the liver, the content of n-hexanal increased slightly 10 min after the injection. The content at 30 min decreased to the level of the untreated group.
Details on excretion:
It is thought that n-hexanal could be either metabolized by the enzymes and/or transferred into the lung as such and excreted into expired gas easily.

Metabolite characterisation studies

Metabolites identified:
not measured

Any other information on results incl. tables

no effect on the activities of GSH-Px and GSSGR and the content of GSH was observed

Applicant's summary and conclusion

Conclusions:
After the injection of n-hexanal, the plasma content reached to ca. 500 nmol/ml at 5 min and decreased to less than half at 10 min. In the lung, the content of n-hexanal increased immediately and reached ca. 150 nmol/g in 30 min. From the mean of lung weight being ca. 0.17 g, the amount of n-hexanal in whole lung was ca. 26 nmol. This value corresponded to ca. 0.080 % of the whole injected aldehyde. After 30 min, the content of n-hexanal decreased significantly. The amount of n-hexanal at 120 min was ca. 20 % of that seen at 30 min. In the liver, the content of n-hexanal increased slightly 10 min after the injection. The content at 30 min decreased to the level of the untreated group. It is thought that n-hexanal could be either metabolized by the enzymes and/or transferred into the lung as such and excreted into expired gas easily.
Executive summary:

n-Hexanal was dissolved in physiological saline containing 1 % bovine serum albumin and administered to mice at a dose of 6.8 µmol/10g body weight by i.v. injection into the tail vein. Mice administered the aldehyde were dissected under ether anesthesia at 0, 5, 10, 30, 60, and 120 min after the treatments. Blood was drawn from the heart and the plasma was prepared by centrifugation. The content of n-hexanal in the plasma and liver and lung homogenates was determined. After the injection of n-hexanal, the plasma content reached to ca. 500 nmol/ml at 5 min and decreased to less than half at 10 min. In the lung, the content of n-hexanal increased immediately and reached ca. 150 nmol/g in 30 min. From the mean of lung weight being ca. 0.17 g, the amount of n-hexanal in whole lung was ca. 26 nmol. This value corresponded to ca. 0.080 % of the whole injected aldehyde. After 30 min, the content of n-hexanal decreased significantly. The amount of n-hexanal at 120 min was ca. 20 % of that seen at 30 min. In the liver, the content of n-hexanal increased slightly 10 min after the injection. The content at 30 min decreased to the level of the untreated group. It is thought that n-hexanal could be either metabolized by the enzymes and/or transferred into the lung as such and excreted into expired gas easily.