Registration Dossier

Administrative data

Endpoint:
repeated dose toxicity: other route
Remarks:
other: effect of menthol on cytochrome P-450 levels in rat liver
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: special study

Data source

Reference
Reference Type:
publication
Title:
The effect of terpenoid compounds on cytochrome P-450 levels in rat liver
Author:
Austin CA, Shephard EA, Pike SF, Rabin BR, Phillips IR
Year:
1988
Bibliographic source:
Biochemical Pharmacology 37, 2223-2229|(1988)

Materials and methods

Principles of method if other than guideline:
The rats were given three consecutive daily intraperitoneal injections of menthol dissolved in 10% ethanol, 90% corn oil at a dose of 40 mg/kg body weight. The rats were starved overnight and killed by cervical dislocation 18 hr after receiving the third injection. Cytochrome P-450 was assayed by CO-reduced difference spectroscopy, cytochrome b5 was determined spectrophotometrically.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
other: 10% ethanol, 90% corn oil
Duration of treatment / exposure:
3 d
Frequency of treatment:
daily
Doses / concentrations
Remarks:
Doses / Concentrations:
40 mg/kg bw/d
No. of animals per sex per dose:
no data
Control animals:
other: vehicle (10 % ethanol, 90 % corn oil) alone
Details on study design:
Post-exposure period: no

Results and discussion

Effect levels

Dose descriptor:
NOAEL
Remarks on result:
not determinable
Remarks:
no NOAEL identified

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

no significant change in the total cytochrome P-450 content of liver microsomal membranes, no visible change in the
pattern of liver microsomal membrane proteins, no effect on
the amount of hepatic cytochrome b5, small but significant
inductions of PB P- 450 in liver microsomal membrane
vesicles

Applicant's summary and conclusion

Executive summary:

The rats were given three consecutive daily intraperitoneal injections of menthol dissolved in 10% ethanol, 90% corn oil at a dose of 40 mg/kg body weight. The rats were starved overnight and killed by cervical dislocation 18 hr after receiving the third injection. Cytochrome P-450 was assayed by CO-reduced difference spectroscopy, cytochrome b5 was determined spectrophotometrically.

No significant change in the total cytochrome P-450 content of liver microsomal membranes, no visible change in the pattern of liver microsomal membrane proteins, no effect on the amount of hepatic cytochrome b5, small but significant inductions of PB P-450 in liver
vesicles was found.