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EC number: 267-500-0 | CAS number: 67874-72-0
- 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
Description of key information
Skin corrosion: Not corrosive based on absence of acidic or base groups and OECD testing
Skin irritation: Not irritating based on read across from Verdox which was tested in OECD TG 404
Eye irritation: Irritant based on OECD TG 405
Respiratory irritation: Not a respiratory irritant
Key value for chemical safety assessment
Skin irritation / corrosion
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not irritating)
Eye irritation
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (irritating)
Respiratory irritation
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not irritating)
Additional information
The information on skin irritation for Coniferan is retreived from the anologue Verdox, which summary will be presented first. Thereafter the eye irritation information from Coniferan will be presented. At the end the read across justification will be presented.
Skin corrosion: The substance is not considered corrosive in absence of skin irritation.
Skin irritation based on the analogue Verdox
In the skin irritation test with 7 New-Zealand rabbits, similar to OECD TG 404 but non-GLP, mean erythema and oedema scores over 24 + 48 + 72 hours were 1.7 and 1.05.In only one out of 7 animals mean erythema score over 24, 48 and 72 hours was 2.33.When applied to rabbit skin under semi-occlusive conditions for 4 hours, the test substance produced fairly distinct erythema and marginal to fairly distinct oedema, cracking and scaling. The skin effects were not fully reversible within 72 hours, after which the observation stopped. Considering their slight severity, the dermal changes are likely to be fully reversible within 14 days. Based on the average erythema and oedema scores, the substance is considered to be not irritating to skin.
Eye irritation using Coniferan
In a pre-GLP acute toxicity study similar to OECD 405, 0.1 mL neat test material was installed in the right eye of 3 albino rabbits. The left untreated eye served as control. The eyes were examined 24, 48, 72 hours and 7 days after instillation of the test substance and scored according to the Draize scale. No corneal opacity or iris congestion was observed. Redness and chemosis were observed in all animals, but the effects were reversible in all animals within 7 days. Mean 24, 48 and 72 hour redness was 1.33 in one animal and 2 in two animals. Therefore, the test substance was considered irritating to eyes.
Respiratory irritation
There are no occupational or consumer data indicating respiratory tract irritation. There are also no relevant experimental guidelines or results available that indicate respiratory irritation. The ECHA guidance presents (R7a: 7.2.12.1, 2017) that respiratory irritation maybe be indicated when the substance is a severe irritant. However, the substance is not a skin irritant, it is an eye irritant (Cat 2) not indicating severe irritation and therefore not a respiratory irritant.
Read across justification
The skin irritation of Coniferan (CAS #67874-72-0) using read across from Verdox (CAS #20298-69-5)
Introduction and hypothesis for the analogue approach
Coniferan is an acetate-ester attached to a cyclohexyl ring with a tert-pentyl- group attached at the ortho-position. For this substance no skin irritation data are available. In accordance with Article 13 of REACH, lacking information can be generated whenever possible, i.e. e. applying alternative methods such as in vitro tests, QSARs, grouping and read-across. For assessing the irritating potential of Coniferan the analogue approach is selected because for a closely related analogue, Verdox, skin irritation information is available which can be used for read across.
Hypothesis: Coniferan has similar irritating potential compared to Verdox as the additional methyl group attached to the tert-butyl -group in Coniferan is not expected to influence the irritation potential.
Available information: The target chemical Verdox is tested undiluted in vivo similar to an OECD TG 404 study. The test is well conducted but pre-GLP guidelines and therefore receives a reliability of 2.
Target chemical and source chemical(s)
Chemical structures of the target chemical and the source chemicals are shown in the data matrix, including physico-chemical properties and toxicological information, thought relevant for irritation, of both substances.
Purity / Impurities
It is not expected that the impurities of the source chemical affect the read-across justification. Coniferan is a multi-constituent containing two stereo isomers. The purity of Coniferan is close to 100% therefore impurities will not affect irritation. In view of Verdox being a multi-constituent also containing two stereo isomers and having a purity close to 100%, there will be no significant impurities relevant for read across.
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.
In accordance with ECHA guidance (2017, RAAF) Verdox was selected as an analogue because it has only one methyl group less being the closest analogue for which information is available.
Structural similarities and differences: Coniferan as well as the structural analogue Verdox have a cyclohexyl ring, the backbone, with an acetate ester and a tert-butyl-group in ortho position attached. Coniferan has one additional methyl group attached to this tert-butyl group. This difference between the target and source chemical is not expected to influence significantly the skin irritating potential of these chemicals.
Toxico-kinetic similarities and differences: Bioavailability: Most skin irritating substances need to be absorbed through the skin to a certain extent to present irritating properties. Coniferan and Verdox are both liquids, have similar molecular weight and physico-chemical properties indicating similar absorption characteristics: molecular weight (212.33 and 198.31 g/mol), log Kow (5.4 and 4.75), water solubility (7.6 and 10 mg/L), and vapour pressure (4.24 and 9.72 Pa at 25 °C), for Coniferan and Verdox, respectively). The log Kow being > 4 present that skin absorption is not in the favourable range of log Kow 1-4 and skin absorption cannot be excluded.
Reactivity: The reactive group in both Coniferan and Verdox is the ester group which may present irritation. In view of Verdox not showing classifiable skin irritating properties also Coniferan will not present a classifiable skin irritation.
Metabolism: Although metabolism is of lesser importance for local effects compared to systemic effects some local metabolism in the skin could occur. Small chain straight alkyl esters such as this Coniferan and Verdox are likely to be metabolized by carboxylesterases in the skin into the respective: 2-methylbutan-2-yl-cyclohexanol and acetic acid and 2-tertbutyl-cylohexyl-alchol and acetic acid, respectively (Belsito et al., 2008, Yamada et al., 2013). The similarity in metabolites presents similar skin irritating properties and this means that the skin irritation information on Verdox can be used for Coniferan.
Uncertainty of the prediction: There is no remaining uncertainty, in view of similarities in structure, toxico-kinetic profile (absorption and metabolism) and reactivity between the substances. If anything, Verdox is slightly more bioavailable via the skin based on a lower log Kow and therefore the read across can be considered conservative. According to ECHA guidance (2017, RAAF) the score 5 can be applied.
Data matrix
The relevant information on physico-chemical properties and toxicological characteristics are presented in the Data matrix below.
Conclusions per endpoint for Hazard assessment and C&L.
Verdox is not a skin irritant in a similar to OECD 404 pre-GLP study (reliability 2). Based on these results it can be concluded that Coniferan is not skin irritating either.
Final conclusion on hazard and C&L
Coniferan is not skin irritating. Classification and labelling is not needed for this endpoint according to CLP Regulation (EC) No. 1272/2008 and its updates.
Data matrix for the read across to Coniferan from Verdox
Common names | Coniferan | Verdox |
Chemical structures | ||
CAS no | 67874-72-0 | 20298-69-5 |
EC no | Registration in 2018 | 243-718-1 (registered) |
Empirical formula | C13H24O2 | C12H22O2 |
Physico-chemical data |
|
|
Molecular weight | 212.33 | 198.31 |
Physical state | Liquid | Liquid at 30°C |
Melting point, °C | -20 | 29.8 |
Boiling point, °C | 251.9 | 232 |
Vapour pressure, Pa | 4.24 at 24°C | 9.72 at 23°C |
Water solubility, mg/L | 7.6 at 24°C | 10 at 23°C |
Log Kow | 5.4 | 4.75 |
Human health endpoints |
|
|
Skin irritation | Read across from Verdox | Similar to OECD 404 not irritating |
Justification for classification or non-classification
The substance does not have to be classified for Skin irritation according to EU CLP (EC No. 1272/2008 and its amendments).
The substance has to be classified as Eye irritant and shall be labelled with H319: Causes serious eye irritation according to EU CLP (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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