Registration Dossier

Toxicological information

Basic toxicokinetics

Currently viewing:

Administrative data

Endpoint:
basic toxicokinetics in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1982
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Limited methodological detail.

Data source

Reference
Reference Type:
publication
Title:
The Inhibition of Rat Nasal Cytochrome P-450-dependent mono-oxygenase by the Essence Heliotropin (Piperonal)
Author:
Dahl AR
Year:
1982
Bibliographic source:
Drug Metabolism and Disposition. 1982;10(5):553-554

Materials and methods

Objective of study:
other: Test for the ability of heliotropin to inhibit cytochrome P450-mediated oxidation reactions.
Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
The effects of heliotropin on cytochrome P450-mediated oxidative reactions were evaluated in vitro in rat nasal and liver microsomes.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
not specified
Details on test material:
- Name of test material (as cited in study report): Heliotropin
- Analytical purity: 99%
Radiolabelling:
no

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Lovelace Inhalation Toxicology Research Institute
- Age at study initiation: 12 to 16 weeks

Further details were not reported.

Administration / exposure

Route of administration:
other: in vitro
Vehicle:
other: A vehicle was used but its identity was not reported.
Details on exposure:
Heliotropin (3 mM) was incubated with nasal and liver microsomes for 30 minutes at 37°C to evaluate its possible effect on oxidative metabolism of methyl N-methylanthranilate (DMA). Further details were not reported.
Duration and frequency of treatment / exposure:
30 minute incubation period.
Doses / concentrations
Remarks:
Doses / Concentrations:
3 mM
No. of animals per sex per dose / concentration:
Not applicable
Control animals:
other: Not applicable
Positive control reference chemical:
Not applicable
Details on study design:
Heliotropin (3 mM) was incubated with nasal and liver microsomes for 30 minutes at 37°C to evaluate its possible effect on oxidative metabolism of methyl N-methylanthranilate (DMA). Further details were not reported.
Details on dosing and sampling:
No details provided.
Statistics:
Not required.

Results and discussion

Main ADME results
Type:
other: Inhibition
Results:
Heliotropin inhibited CYP450 activity in nasal, but not liver, microsomes.

Any other information on results incl. tables

Table 1: Percentage of DMA Metabolism in the Presence of Heliotropin Comapred to Control

Microsomes

Heliotropin

Nasal

23.1 ± 0*

Liver

83.6 ± 2.6

* Probability that rates are the same as control < 0.05 (N=2)

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): other: Heliotropin inhibited CYP450 activity in nasal but not liver microsomes.
Heliotropin inhibited CYP450 activity in nasal but not liver microsomes.
Executive summary:

This study demonstrated that incubation with heliotropin (3 mM) inhibited CYP450-mediated oxidative metabolism of methyl N-methylanthranilate by rat nasal microsomes. No such inhibition was observed in rat liver microsomes. These data suggest that heliotropin may exert an inhibitory effect on nasal, but not liver, CYP450-mediated oxidation reactions.