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Link to relevant study record(s)

Reference
Endpoint:
basic toxicokinetics in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Data is available online
Qualifier:
according to guideline
Guideline:
other:
Principles of method if other than guideline:
Details of guidelines not mentioned in the publication
GLP compliance:
not specified
Radiolabelling:
no
Species:
other: Guinea pigs (Liver microsomes & cytosol)
Strain:
Hartley
Sex:
male
Route of administration:
other: in-vitro hence not applicable
Vehicle:
other: in-vitro hence not applicable
Details on exposure:
MNMA was incubated with guinea pigs liver microsomes (5 µg protein) or cytosol (50 µg protein) in sodium-potassium phosphate buffer 38 mM (pH 7.4) in a final volume of 260 µl. The mixture was incubated at 37oC for 10 mins, and the reaction was terminated by the addition of acetonitrile 200 µl containing methyl p-methoxybenzoate (0.20 µg) as an internal standard. After the removal of protein by centrifugation, 50 µl of the supertanant was injected onto a High Performance Liquid Chromatography (HPLC) system.
Duration and frequency of treatment / exposure:
10 mins
Remarks:
Doses / Concentrations:
1000 µM
No. of animals per sex per dose / concentration:
Not applicable
Control animals:
no
Type:
metabolism
Results:
MNMA was hydrolyzed by guinea pigs liver microsomes to produce N-Methyl Anthranilic acid. MNMA was also N-Demthylated by Guinea pigs liver microsomes & cytosol to form anthranilic acid (AA).
Details on absorption:
Not Applicable
Details on distribution in tissues:
Not Applicable
Details on excretion:
Not Applicable
Metabolites identified:
yes
Details on metabolites:
N-Methyl Anthranilic acid &
Anthranilic acid (AA)

MNMA was hydrolyzed byguinea pigs liver microsomes to produceN-Methyl Anthranilic acid.MNMA was also N-Demthylated byGuinea pigs liver microsomes & cytosol to form anthranilic acid (AA).

Kinetic analysis indicated that Vmax/Km values were 7.4 fold higher in microsomes than in cytosol
Conclusions:
Interpretation of results (migrated information): low bioaccumulation potential based on study results
In vitro study of hepatic metabolism of Methyl N Methylanthranilate in guinea pigs liver microsomes was conducted wherein the kinetic analysis indicated that Vmax/Km values were 7.4 fold higher in microsomes than in cytosol. Vmax/Km values reflect the intrinsic clearance potential after hydrolysis and thus the bio-accumulation potential of Methyl N Methylanthranilate (MNMA) is expected to be low.
Executive summary:

In vitro study of hepatic metabolism of Methyl N Methylanthranilate in guinea pigs liver microsomes was conducted wherein the kinetic analysis indicated that Vmax/Km values were 7.4 fold higher in microsomes than in cytosol. Vmax/Km values reflect the intrinsic clearance potential after hydrolysis and thus the bio-accumulation potential ofMethyl N Methylanthranilate (MNMA)is expected to be low.

Description of key information

In vitro study of hepatic metabolism of Methyl N Methylanthranilate in guinea pigs liver microsomes was conducted wherein the kinetic analysis indicated that Vmax/Km values were 7.4 fold higher in microsomes than in cytosol. Vmax/Km values reflect the intrinsic clearance potential after hydrolysis and thus the bio-accumulation potential of Methyl N Methylanthranilate (MNMA) is expected to be low.

Key value for chemical safety assessment

Bioaccumulation potential:
low bioaccumulation potential

Additional information

In rats and humans, the main reaction of methyl N-methylanthranilate is hydrolysis to Nmethylanthranilic acid, with little N-demethylation, to yield anthranilic acid (ratio of Nmethylanthranilic acid:Anthranilic acid, approximately 20:1); the metabolites are rapidly eliminated in the urine (Morgareidge, 1963; JECFA, 2005).In vitro study of hepatic metabolism of Methyl N Methylanthranilate in guinea pigs liver microsomes alsoreflect high intrinsic clearance potential after hydrolysis. Metabolites are expected to be eliminated out of the living system via urine (as per the reports on rats and humans) suggesting low bio-accumulative potential.