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EC number: 227-231-1 | CAS number: 5726-19-2
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Endpoint summary
Administrative data
Link to relevant study record(s)
Description of key information
Key value for chemical safety assessment
Additional information
The common characteristic structural element of cyclic acetates is the acetate unit bound to a mono-, bi- or tri- cyclic alcohol, and the only substituents at the alcohol moiety are alkyl groups. It is assumed that unsubstituted monocyclic esters (e.g. cyclohexyl acetate) are rapidly hydrolysed to cyclohexanol and the component aliphatic carboxylic acids by classes of enzymes recognised as carboxylesterases [1] [2] [3], the most important of which are the beta-esterases. In mammals, these enzymes occur in most tissues [4] [3] but predominate in the hepatocytes [3].
Several studies have been performed on 2-methylcyclohexyl acetate’s analogues confirming the fast hydrolysis of cyclohexyl analogues. In a study conducted by Salzer [5],cis-andtrans-1-methylene-4-isopropenylcyclohexan-2-yl acetate were shown to be rapidly hydrolysed in vitro in the presence of rat liver homogenate. In accordance with Emberger [6], the structurally related ethylene glycol and propylene glycol carbonate esters of (-)-2isopropyl-5-methylcyclohexanol were completely hydrolysed after incubation for 1 hour with rat liver homogenate and according to White et al. [1], it was observed that esters of cyclohexanol were also readily hydrolysed in rat liver homogenate.
As indicated above, 2-methylcyclohexyl acetate is subjected to action of carboxylesterase and will undergo hydrolysis to yield 2-methylcyclohexanol. The major metabolic pathway involves conjugation of 2-methylcyclohexanol excreted primarily as the glucuronic acid conjugates [7] [8] [9] [10] [11]. This metabolic pathway can be derived from studies with t-butylcyclohexane and various cyclohexanol derivatives. Also it is shown that to a very minor extent, alicyclic ketones and secondary alcohols containing an alkyl side-chain undergo oxidation of the side-chain to form polar poly-oxygenated metabolites that are also excreted as the glucuronide or sulfate conjugates mainly in the urine.
Although it has been suggested that lipophilic alcohols or ketones with sterically hindered functional groups would undergo more extensive oxidation of alkyl ring substituents [12], studies on 2-, 3-, or 4-methylcyclohexanol, 2-isopropyl-5methylcyclohexanol, 3,5,5-trimethylcyclohexanol, and even 2-, 3-, or 4-tert-butylsubstituted cyclohexanol or cyclohexanones revealed that conjugation of the cyclohexanol moiety by glucuronic acid is the predominant excretion pathway regardless of the size or position of the ring substituent. In the studies conducted by Lington and Bevan and Topping, it was shown that the metabolic fate of alkyl-substituted cyclohexanol and cyclohexanone derivatives is similar to that of the un-substituted homologues [7] [8].
According to the scientific studies conducted with several analogue substances (see details on Rationale for read-across approach, attached to Section 13), the metabolic fate of the target substance 2-methylcyclohexyl acetate is subjected to the action of carboxylesterase and will undergo hydrolysis to yield 2-methylcyclohexanol. In the next metabolic step 2-methylcyclohexanol, in the same way as the analogue substance 2-isopropyl-5-methylcyclohexanol (menthol), is conjugated with glucuronic acid to yield the corresponding glucuronide that is excreted mainly in the urine. The analogue cyclic acetates are also assumed to be rapidly hydrolysed to the alcohol and the carboxylic acid.
References:
[1] White D. A., Heffron A., Miciak B., Middleton B., Knights S. and Knights D. (1990) Chemical synthesis of dual radiolabelled cyclandelate and its metabolism in rat hepatocytes and mouse J774 cells. Xenobiotica 20, 71.
[2] Ford D.M. and Moran E.J. (1978) Preliminary indications of in vitro hydrolysis of two flavor chemical esters. Private communication to FEMA. Submitted to WHO by the Flavor and Extract Manufacturers Association of the United States, Washington, DC, U.S.A.
[3] Heymann E. (1980) Carboxylesterases and amidases. In Enzymatic Basis of Detoxication. Edited by W. B. Jakoby. 2nd ed. pp. 291-323. Academic Press, New York.
[4] Anders M.W. (1989) Biotransformation and bioactivation of xenobiotics by the kidney. In Intermediary Xenobiotic Metabolism in Animals. Edited by D. H. Hutson, J. Caldwell, and G. D. Paulson. pp. 81-97. Taylor and Francis, New York.
[5] Salzer D. (1998) In Vitro Hydrolysis test cis and trans-p-1(7),8-menthadien-2-yl acetate. Private communication to FEMA. Submitted to WHO by the Flavor and Extract Manufacturers Association of the United States, Washington, DC, U.S.A.
[6] Emberger D. (1994) In vitro hydrolysis test on menthyl propyleneglycol carbonate. Private communication to FEMA. Submitted to WHO by the Flavor and Extract Manufacturers Association of the United States, Washington, DC, U.S.A.
[7] Lington A.W. and Bevan C. (1994) Alcohols in Patty’s Industrial Hygiene and Toxicology, 4th ed. Edited by Clayton and Clayton, Volume IID pp.2585-2760. John Wiley & Sons, Inc., New York.
[8] Topping D.C, Morgott, D.A., David R.M. and O’Donoghue J.L. (1994) Ketones in Patty’s Industrial Hygiene and Toxicology, 4th ed. Edited by Clayton and Clayton, Volume IIC pp.1739-1878. John Wiley & Sons, Inc., New York.
[9] Cheo K.L., Elliott T. H. and Tao R. C. C. (1967) The metabolism of the isomeric tertbutylcyclohexanones. Biochem. J. 104, 198-204.
[10] Elliott T.H., Tao R. C. C. and Williams R.T. (1965) Studies in detoxication. The metabolism of isomeric methylcyclohexanones. Biochemistry Journal 95, 59-65.
[11] Yamaguchi T., Caldwell J. and Farmer P.B. (1994) Metabolic fate of [3H]-l-menthol in the rat. Drug Metabolism and Disposition 22, 616-624.
[12] Nelson S. D., McClanahan R. H., Thomassen D., Gordon W. P. and Knebel N. (1992) Investigations of mechanisms of reactive metabolite formation from (R)-(+)pulegone. Xenobiotica 22, 1157-1164.
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