Safety Evaluation of Cornmint Oil, Mentha arvensisa
Steps 2 and 3: Constituent Identification/Congeneric Grouping/Structural Class Assignment
Step 4: Oil Composition by Congeneric Group, Resulting Intake
3044 saturated and unsaturated alcohol/ketone/ ketal/ester (e.g., menthol, menthone, isomenthone, menthyl acetate)
High % From Structural Multiple
Congeneric Group Class (TTC) Commercial Assignment (pg/Person/d) Samples
Secondary alicyclic II (540) 95
Aliphatic terpene 1(1800) 8 256
hydrocarbon (e.g., limonene, pinene)
Steps 5,6,7,8: Metabolism/Toxicology Data/Evaluation
I. Glucuronic acid conjugation of the alcohol followed by excretion in the urine
Intake of Congeneric Group or Total of Unidentified Constituents Group < TTC for Class?
No, 3044 ng/person/d >540 ng/ person/d
Relevant Toxicity Data if Intake of Group >TTC
NOEL of 600,000 ng/ kg bw/d for menthol (103-week dietary study in mice) (NCI, 1979)
Among Congeneric Groups?
I. co-Oxidation of the side chain substituents to yield various polyols and hydroxy acids and excreted as glucuronic acid conjugates
I. co-Oxidation to yield polar hydroxy and carboxy metabolites excreted as glucuronic acid conjugates
NOEL of 400,000 ng/kg bw/d for menthone (28-day gavage study in rats) (Madsen et al., 1986) Not required
2-Isopropylidene cyclohexanone and metabolites (e.g., pulegone)
64 1. Reduction to yield menthone or isomenthone, followed by hydroxylation of ring or side chain positions and then conjugation with glucuronic acid
2. Conjugation with glutathione in a Michael-type addition leading to mercapturic acid conjugates that are excreted or further hydroxylated and excreted
3. Hydroxylation catalyzed by cytochrome P-450 to yield a series of ring- and side chain-hydroxylated pulegone metabolites, one of which is a reactive 2-ene-l,4-dicarbonyl derivative. This intermediate is known to form protein adducts leading to enhanced toxicity (Austin et al., 1988)
Note: In Steps 2 and 3, individual constituents and their assignment to structural classes are not shown. a Based on daily PCI of 3204 ng/person/d for cornmint oil, as determined in Step 1.
Not required. But NOAEL of 9375 ng/kg bw/d for pulegone (90-day gavage study in rats) (NTP, 2002)
Hydrolysis r-^^ Reduction r Isomerization
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