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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:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Peer reviewed data

Data source

Reference
Reference Type:
review article or handbook
Title:
Metabolism of anethole I. Pathways of metabolism in the rat and mouse
Author:
S.A. Sangster, J. Caldwell and R.L. Smith
Year:
1984
Bibliographic source:
Fd Chem. Toxic. Vol. 22, No. 9, pp. 695-706, 1984

Materials and methods

Objective of study:
metabolism
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Anglia Laboratory Animals (Alconbury, Cambs.)
- Weight at study initiation: 200-250 g
- Housing: The animals were housed in all-glass metabolism cages equipped for the separate collection of urine, faeces and expired air (metabowls)
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: trioctanoin
Duration and frequency of treatment / exposure:
Urine, faeces and expired air were collected for 72hr after dosing.
Doses / concentrations
Remarks:
Doses / Concentrations:
50 mg/kg, 100 uCi/kg
No. of animals per sex per dose:
no data
Control animals:
not specified
Positive control:
no data
Details on study design:
no data
Details on dosing and sampling:
trans-[methoxy-14C]Anethole (50 mg/kg, uCi/ kg) was administered in trioctanoin by gavage to rats. Urine, faeces and expired air were collected for 72 hr after dosing. Urine and faeces were counted for 14C immediately after collection and were stored at -20"C without preservative until analysis. The trapping solutions were counted for 14C immediately after each change. At the end of the experiment, the animals were killed and residual 14C in the carcass was determined (Emudianughe, Caldwell, Dixon & Smith, 1978).
Statistics:
no data

Results and discussion

Preliminary studies:
no data
Main ADME results
Type:
metabolism
Results:
(E)-anethole was totally metabolized by rats

Toxicokinetic / pharmacokinetic studies

Details on absorption:
no data
Details on distribution in tissues:
no data
Details on excretion:
Excretion of 14C
In rats the principal route of elimination of 14C was via the expired air as 14CO2. This accounted in the rat for 42% of the dose. Less than 0.1% of the dose was trapped in the methanol 'cold finger', indicating that neither volatile radioactive metabolites nor trans-anethole were eliminated in the expired air. Rats excreted 41% of the dose in the urine. The faeces contained less than 2% of the dose of 14C. The carcasses contained <0.1% of the 14C dose 72hr after administration.

Metabolite characterisation studies

Metabolites identified:
yes
Details on metabolites:
Urinary metabolites of trans-[methoxy-14C]anethole in the rat
TLC of neat rat urine in system B revealed three radioactive bands (RF 0. 1, RFr 0.29 and RF 0.38). That at RF 0.1 was positive (blue) to naphthoresorcinol, indicating the presence of glucuronide(s), and that at RF 0.38 was positive (orange) to pDMAB spray, indicating the presence of glycine conjugate(s).
The analytical procedure described in Experimental revealed six radioactive metabolites in the pH 5.0 extract prior to B-glucuronidase treatment and, in addition, two further radioactive and one non- radioactive metabolite in the pH 5.0 extract after B-glucuronidase treatment. The metabolites are numbered 1-9 in increasing order of HPLC retention time. Inhibition of B-glucuronidase with saccharo-1,4-lactone or incubation with buffer alone prevented further extraction of radioactivity into ether at pH 5.0.
The radioactivity extracted at pH 1.0 was separated by TLC into two major (A and B) and four minor radioactive metabolites. The four minor metabolites were shown after further chromatographic and MS analysis to be metabolites 1, 2, 4 and 5 extracted in greater amounts of pH 5.0.

Bioaccessibility

Bioaccessibility testing results:
no data

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): no bioaccumulation potential based on study results
trans-(E)-anethole was totally metabolized by rodents