Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 238-620-0 | CAS number: 14576-08-0
- 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
No experimental toxico-kinetic data are available for assessing adsorption, distribution, metabolisation and excretion of the substance. Based on effects seen in the human health toxicity studies and physico-chemical parameters the substance is expected to be readily absorbed via the oral and inhalation route and somewhat lower via the dermal route. Using the precautionary principle for route to route extrapolation the final absorption percentages derived are: 50% oral absorption, 50% dermal absorption and 100% inhalation absorption. In view of the conservative nature of the measured log Kow and the anticipated metabolism of the substance into Terpineol (multi), there is no bioaccumulation potential.
Key value for chemical safety assessment
- Bioaccumulation potential:
- no bioaccumulation potential
- Absorption rate - oral (%):
- 50
- Absorption rate - dermal (%):
- 50
- Absorption rate - inhalation (%):
- 100
Additional information
Orange Flower Ether (14576-08-0) and the assessment of its toxico-kinetic behaviour
Introduction
The test material Orange Flower Ether (14576-08-0) is an ether attached to a cyclohexyl ring with one double bond with a methyl-group attached at the para-position (see section 1 on identity). Orange Flower Ether is liquid with a melting point <-20°C and a boiling point of 222.2°C. The molecular weight of 168.28 g/mol does not preclude absorption. The substance is readily biodegradable. The log Kow is 4.5 at 25°C (but considered to be conservative, EpiSuite and Sparc predict 4.0 and 3.4, respectively), the solubility in water is 85 mg/L at 23°C and the vapour pressure is 9.91 Pa at 23°C.
Absorption
Oral: The relatively low molecular weight and the moderate octanol/water partition coefficient (measured Log Kow 4.5) and water solubility (85 mg/L) would favour absorption through the gut. According to Martinez and Amidon (2002) the optimal log Kow for oral absorption falls within a range of 2-7. This shows that Orange Flower Ether is likely to be absorbed by the GI-tract and the oral absorption is therefore expected to be >50%.
Skin: Based on the physical-chemical characteristics of the substance, being a liquid with a molecular weight of 168.28 g/mol, a log Kow of 4.5 and water solubility of 85 mg/L the absorption is expected to be low to moderate. The optimal MW and log Kow for dermal absorption is <100 g/mol and in the range of 1-4, respectively (ECHA guidance, 7.12, Table R.7.12-3). Orange Flower Ether is just outside the optimal range and therefore the skin absorption is not expected to exceed 50%.
Lungs: Absorption via the lungs is also based on these physico-chemical properties. Though the inhalation exposure route is to be minor, because of its low volatility (9.91 Pa), the octanol/water partition coefficient (4.5), indicates that inhalation absorption is possible. The blood/air (B/A) partition coefficient is another partition coefficient indicating lung absorption. Buist et al. 2012 have developed B/A portioning model for humans using the most important and readily available parameters:
Log P(BA) = 6.96 – 1.04 Log (VP) – 0.533 (Log) Kow – 0.00495 MW.
For Orange Flower Ether the B/A partition coefficient would result in:
Log P(BA) = 6.96 – 1.04 x 0.996 – 0.533 x 4.5 – 0.00495 x 168.28 = 2.69
This means that Orange Flower Ether has a slight tendency to go from air into the blood. It should, however, be noted that this regression line is only valid for substances which have a vapour pressure > 100 Pa. Despite Orange Flower Ether being somewhat out of the applicability domain and the exact B/A portioning may not be fully correct, it can be seen that the substance will be readily absorbed via the inhalation route.
Distribution
The moderate water solubility of the test substance would limit distribution in the body via the water channels. The log Kow would suggest that the substance would pass through the biological cell membrane. The substance is not expected to accumulate in the body fat, despite its log Kow of 4.5 because the log Kow is conservative and the substance is anticipated to be readily metabolized.
Metabolism
Orange Flower Ether metabolises into Terpineol (multi) by demethylation of the ether CH3 group, resulting in Terpineol-alpha (Toxicological handbooks). See Figure below.
.
Excretion
As Orange Flower Ether has a low molecular weight urinary excretion is favourable. Any unabsorbed substance will be excreted via the faeces
Discussion
Orange Flower Ether is expected to be readily absorbed, orally and via inhalation, based on the human toxicological information and physico-chemical parameters. The substance also is expected to be absorbed dermally based on the physico-chemical properties. The MW and the log Kow are higher than the favourable range for dermal absorption but significant absorption is likely. The IGHRC (2006) document of the HSE and mentioned in the ECHA guidance Chapter 8 will be followed to derive the final absorption values for the risk characterisation.
Conclusion
Orange Flower Ether is expected to be readily absorbed via the oral and inhalation route and somewhat lower via the dermal route based on toxicity and physico-chemical data. Using the precautionary principle for route to route extrapolation the final absorption percentages derived are: 50% oral absorption, 50% dermal absorption and 100% inhalation absorption.
References
Buist, H.E., Wit-Bos de, L., Bouwman, T., Vaes, W.H.J., 2012, Predicting blood:air partition coefficient using basic physico-chemical properties, Regul. Toxicol. Pharmacol., 62, 23-28.
Martinez, M.N., And Amidon, G.L., 2002, Mechanistic approach to understanding the factors affecting drug absorption: a review of fundament, J. Clinical Pharmacol., 42, 620-643.
IGHRC, 2006, Guidelines on route to route extrapolation of toxicity data when assessing health risks of chemicals
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.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.