Octanal

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

no data

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: No indication of guideline or GLP compliance.

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

publication

Title:

An Examination of Octanol and Pentanol Metabolism to Octanoic Acid by Horse Liver Alcohol Dehydrogenase.

Author:

Hinson, J.A., Neal, R.A.

Year:

1975

Bibliographic source:

Biochimica et Biophysica. Acta, 384 (1973) 1-11

Report date:

1974

Materials and methods

Objective of study:

metabolism

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The rate of oxidation of octanal was determined either spectrophotometrically using a Gilford recording spectrophotometer or by gas chromatography. The enzyme activity was measured spectrophotometrically.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Octanal

EC Number:

204-683-8

EC Name:

Octanal

Cas Number:

124-13-0

Molecular formula:

C8H16O

IUPAC Name:

octanal

Test material form:

not specified

Details on test material:

- Name of test material (as cited in study report): Octanal

- Other: The Octanal was purified from contaminating octanoic acid and possible contamination with octanol by vacuum distillation

Radiolabelling:

not specified

Test animals

Species:

other: horse liver alcohol dehydrogenase

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

Not relevant

Administration / exposure

Route of administration:

other: spectrophotometric analysis

Vehicle:

not specified

Remarks:

see details on exposure section

Details on exposure:

The rate of oxidation of octanal was determined either spectrophotometrically using a Gilford recording spectrophotometer or by gas chromatography. The enzyme activity was measured spectrophotometrically by adding horse liver alcohol dehydrogenase to a 10-mm cuvette containing 200 µmol of sodium bicarbonate/C02 buffer, pH 7.4 and NAD+. This solution was temperature equilibrated for 5 min at 37°C. Following equilibration, substrate was quickly added and the initial rate of increase in optical density at 340 nm was measured and compared with the rate observed in a cuvette containing buffer, enzyme, and NAD+ but no substrate. The final volume of all incubations was 2.0 ml.
Solutions of NAD+ and NADH were prepared fresh daily and their concentrations were determined spectrophotometrically.
In the analysis of octanal by gas chromatography, octanal could not be completely extracted from the incubations. As a result of this, its concentration resulting from the enzymatic oxidation of octanol was estimated indirectly by subtracting two times the amount of octanoic acid formed in the incubation from the amount of NADH formed. The remainder was considered to be equal to the amount of octanal present in the incubation at the time of assay.

Duration and frequency of treatment / exposure:

No additional information provided.

Doses / concentrations

Remarks:

Doses / Concentrations:
No additional information provided.

No. of animals per sex per dose / concentration:

Not relevant

Control animals:

not specified

Positive control reference chemical:

No additional information provided.

Details on study design:

The rate of oxidation of octanal was determined either spectrophotometrically using a Gilford recording spectrophotometer or by gas chromatography. The enzyme activity was measured spectrophotometrically by adding horse liver alcohol dehydrogenase to a 10-mm cuvette containing 200 µmol of sodium bicarbonate/C02 buffer, pH 7.4 and NAD+. This solution was temperature equilibrated for 5 min at 37°C. Following equilibration, substrate was quickly added and the initial rate of increase in optical density at 340 nm was measured and compared with the rate observed in a cuvette containing buffer, enzyme, and NAD+ but no substrate. The final volume of all incubations was 2.0 ml.
Solutions of NAD+ and NADH were prepared fresh daily and their concentrations were determined spectrophotometrically.
In the analysis of octanal by gas chromatography, octanal could not be completely extracted from the incubations. As a result of this, its concentration resulting from the enzymatic oxidation of octanol was estimated indirectly by subtracting two times the amount of octanoic acid formed in the incubation from the amount of NADH formed. The remainder was considered to be equal to the amount of octanal present in the incubation at the time of assay.

Details on dosing and sampling:

No additional information provided.

Statistics:

Not documented

Results and discussion

Preliminary studies:

Not relevant

Main ADME results

Type:

metabolism

Results:

The rate of reduction of octanal is approximately 750 times greater than the rate of oxidation

Toxicokinetic / pharmacokinetic studies

Details on absorption:

No information provided.

Details on distribution in tissues:

No information provided.

Details on excretion:

No information provided.

Metabolite characterisation studies

Metabolites identified:

yes

Details on metabolites:

Octanal was metabolized into octanoic acid. The production of octanoic acid is approximately linear over the entire incubation period. Approximately 2 mol of NADH are formed per mol of acid formed. In the presence of 10mM semicarbazide, the rate of octanoic acid formation decreased. However, despite this decrease in the rate of formation, significant amounts are still produced

Any other information on results incl. tables

Octanal is one of the initial products of octanol oxidation by horse liver alcohol dehydrogenase. However, on continued incubation (>2 min) the computed octanal concentration progressively decreases to where only negligible quantities are present in the incubation after 10 min. NADH production appears to be biphasic. An initial phase is followed in about 2 minutes with a slower but linear rate of NADH production.

In the presence of semicarbazide (10mM), the rate of formation of octanal was increased.

Octanal free in the incubation media could then reassociate with the enzyme and, in the presence of NAD+ be oxidized to octanoic acid.

Once an enzyme-octanal-NADH complex has formed, the probability that it will react to form products before either the octanal or NADH dissociates is more likely than is the case with the enzyme· octanal-NAD+ complex. Therefore, high concentrations of NAD+ are required in the incubation to force the reaction in the direction of octanal oxidation. No similar competitive reaction occurs in the oxidation of octanol to octanal.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): bioaccumulation potential cannot be judged based on study results
The results of this study suggest that in the oxidation of octanol to octanoic acid a portion of the octanal formed from octanol is not released from the enzyme but, in the presence of NAD+ is oxidized to octanoic acid.

Executive summary:

In a study conducted by Hinson et al, (1975), the metabolism of the test substance, octanal, was examined. On incubation of octanol with horse liver dehydrogenase in the presence of NAD+, NADH as octanal and octanoic acid were seen as the initial products. However, on continued incubation, the octanal concentration progressively decreased to where only negligible quantities were present in the incubation after 10 min. An initial phase was followed in about 2 min with a slower but linear rate of NADH production. Since octanal is an intermediate in the oxidation of octanol to octanoic acid, the ability of semicarbazide to inhibit the metabolism of octanol to octanoic acid was examined. The results of this study indicate that in the oxidation of octanol to octanoic acid a portion of the octanal formed from octanol is not released from the enzyme but, in the presence of NAD+ is oxidized to octanoic acid.