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EC number: 230-601-5 | CAS number: 7214-18-8
- 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
Description of key information
Acute oral toxicity (based on read across from Verdox after conversion for molecular weight difference ): LD50 = 3624 mg/kg bw
Key value for chemical safety assessment
Acute toxicity: via oral route
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- LD50
- Value:
- 3 624 mg/kg bw
- Quality of whole database:
- The acute oral toxicity result is of sufficient quality and adequate for this dossier.
Additional information
- Belsito, D., Bickers, D., Bruze, M., Calow, P., Greim, H., Hanifin, J.M., Rogers, A.E., Saurat, J.H., Sipes, I.G., Tagami, H., 2008, A toxicologic and dermatologic assessment of cyclic acetates when used as fragrance ingredients, Food and Chemical Toxicology 46, Suppl 12:S1-27.
- Wu, S., Blackburn, K., Amburgery, J., Jaworska, J., and Federle, T., 2010, A framework for using structural, reactivity, metabolic and physico-chemical similarity to evaluate the suitability of analogs for SAR-based toxicological assessments, Regul. Toxicol. Pharmacol., 56, 67-81.
- Yamada, T., Tanaka, Y., Hasegawa, R., Sakuratani, Y., Yamada, J., Kamata, E., Ono, A., Hirose., A., Yamazoe, Y., Mekenyan, O., Hayashi, M., 2013, A category approach to predicting the repeated-dose hepatotoxicity of allyl esters, Reg. Toxicol. Pharmacol, 65, 189-195.
First the experimental information from Verdox is presented being used for read-across to Verdol and thereafter the read across justification.
Verdox and its acute oral toxicity:
In this study with rats testing Verdox, similar to OECD TG 401 but without GLP, the LD50 was 4600 mg/kg bw. Groups of 10 animals (sex, strain and age unspecified) were dosed with 1.3, 3.2, 5.0 and 6.5 g/kg bw and observed for 14 days. The numbers of animals that died were 1 at 1.31 g/kg bw, 5 at 3.2 g/kg bw, 6 at 5.0 g/kg bw, and 4 at 6.5 g/kg bw. Clinical findings included ataxia, piloerection, lethargy, convulsions and ptosis. Necropsy findings included very dark lungs, very red stomach and small intestines, and blood around the nose and mouth.
The acute oral toxicity of Verdol (CAS no 7214-18-8) using read across from Verdox (Cas no 20298-69-5).
1. Introduction and hypothesis for the analogue approach
Verdol is cis-2-tert-Butylcyclohexan-1-ol. For this substance no acute oral/dermal toxicity data are available. In accordance with Article 13 of REACH, lacking information should be generated whenever possible by means other than vertebrate animal tests, i.e. applying alternative methods such as in vitro tests, QSARs, grouping and read-across. For assessing the acute oral toxicity of Verdol the analogue approach is selected because acute oral toxicity information on one closely related analogue is available.
Hypothesis: Verdol has a similar acute oral toxicity profile compared to Verdox resulting in a similar LD50. Verdox can be used for read across because the ester group in verdox will metabolise into its alcohol, which is Verdol and acetic acid.
Available experimental information: For Verdox acute oral toxicity in rats is available using the OECD TG 401 method (Kl 2), resulting in an LD50 of 4600 mg/kg bw. The LD50 for Acetic acid (Cas no 64-19-7) is > 2000 mg/kg bw as presented on the ECHA dissemination site (https://echa.europa.eu/registration-dossier/-/registered-dossier/15549/7/3/2 accessed 24-01-2023).
2. Target chemical and source chemical(s)
The physico-chemical properties and toxicological information, thought relevant for acute oral toxicity are presented in data-matrix.
3. Purity / Impurities
Both Verdol and Verdox are mono-constituent with >80% purity.
4. Analogue approach justification
According to Annex XI 1.5 read across can be used to replace testing when the similarity can be based on a common backbone and a common functional group. It can also be used when the analogues used will have the same or similar metabolites. When using read across the result derived should be applicable for C&L and/or risk assessment and it should be presented with adequate and reliable documentation.
Analogue selection: In view of Verdox being an ester, it will be cleaved by carboxylesterases in the gut (and liver) and result in Verdol. For Verdox acute oral toxicity data is available.
Structural similarities and differences: Verdol and Verdox have the same backbone: a cyclohexene ring to which 2-tert-butyl group at positions 2 are attached. The functional group of Verdox is an acetate group on position 1, while Verdol has an alcohol at this position.
Toxico-kinetics:
Absorption: Verdol and Verdox are expected to have similar absorption potential based on the similarity in chemical structure. Verdox is an ester and Verdol is an alcohol resulting in some expected differences in physico-chemical properties: the water solubility of Verdox is somewhat lower and the log Kow being somewhat higher than for Verdol. For both substances the physico-chemical values indicate readily absorption from the intestinal tract.
Metabolisation: Verdox will fully metabolise into Verdol and acetic acid due to activity of carboxylesterases in the gut and liver (Belsito et al., 2008, Yamada et al., 2013 and Wu et al., 2010). This is also presented in the OECD Toolbox rat liver simulator (version 3.3.5.17). Thereafter, Verdox and Verdol will follow a similar metabolic pathway. Acetic acid is a natural component in the body, which will be consumed in the Krebs cycle and will therefore not be considered further.
Uncertainty of the prediction: There or no remaining uncertainties other than those already addressed above. Verdox showed an LD50 value of 4600 mg/kg bw. The acute oral toxicity of Verdol will be 3624 mg/kg bw after conversion for molecular weight ((4600/198)*156).
5. Data matrix
The relevant information on physico-chemical properties and toxicological characteristics are presented in the Data matrix at the end of this document.
6. Conclusions per endpoint for C&L and/or risk assessment
When using read across the result derived should be applicable for C&L and/or risk assessment, cover an exposure period duration comparable to the corresponding method and be presented with adequate and reliable documentation.
The hydrolysis of esters in the gut to the respective alcohol is well known and referenced (see above) and therefore Verdox can be used for read across. The LD50 of Verdox is 4600 mg/kg bw and therefore the LD50 for Verdol will be 3624 mg/kg bw after conversion for molecular weight difference.
Final conclusion on hazard and C&L:
Verdol has an LD50 > 2000 mg/kg bw and does not need to be classified for acute oral toxicity.
References:
Data matrix for Verdol using read across from Verdox for assessment of acute oral toxicity properties.
Name of substance | Verdol cis-2-tert-butylcyclohexan-1-ol | Verdox cis 2-tert-Butylcyclohexyl acetate |
Chemical structure |
|
|
Empirical formula | C10H20O | C12H22O2 |
Cas no. | 7214-18-8 | 20298-69-5 |
EC no. | 230-601-5 | 243-718-1 |
Mol weight | 156.26 | 198 |
Phys-chem |
|
|
Appearance | Crystalline solid | Crystalline solid |
Melting point (°C) | 50.5 | 29.8 |
Vapour pressure (Pa) | 27 | 9.72 |
Water solubility (mg/L) | 613 | 10 |
Log Kow | 3.8 | 4.75 |
Human health |
|
|
Acute oral toxicity (mg/kg bw) | LD50 = 3624 (after conversion for molecular weight difference) | LD50 = 4600 |
Justification for classification or non-classification
Based on the available data, Verdol does not need to be classified for acute oral toxicity according to EU CLP Regulation (EC) No. 1272/2008 and its amendments.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
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