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EC number: 947-964-7 | CAS number: -
- 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)
- Endpoint:
- basic toxicokinetics, other
- Remarks:
- expert statement
- Type of information:
- other: Expert Statement
- Adequacy of study:
- key study
- Study period:
- 2019-05-03
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Expert statement, no other study available
- Principles of method if other than guideline:
- Expert Statement
- GLP compliance:
- no
- Details on absorption:
- Oral route
Generally, oral absorption is favoured for molecular weights below 500 g/mol. The low water solubility of ca. 1.67 mg/L will probably not allow ready dissolution of the test item in the gastrointestinal fluids. Thus, a direct uptake into the systemic circulation through aqueous pores or via carriage with the bulk passage of water is considered as less relevant. The logPow value of 4.44 is also already above the range of -1 to 4 which is usually considered to be favored for absorption by passive diffusion through biological membranes. With a logPow of greater than 4, the test item may be taken up by micellular solubilisation. Moreover, hydrolysis of the test item in the GIT is not expected based on QSAR calculation the hydrolytic half-life is greater than a year. Overall, physicochemical properties of the test item indicate that it might not be readily absorbed via the oral route. This is supported by oral acute as well as repeated dose toxicity data, where no or only minor signs of toxicity were observed after administration up to the limit dose (2000 mg/kg bw and 1000 mg/kg bw/d, respectively).
Inhalation route
Due to its low volatile properties availability of the test item via the inhalation route cannot be completely ruled out. Since the substance is a liquid at ambient temperature the generation of dust is excluded. However, in case of inhalation, absorption via the respiratory tract cannot completely be ruled out.
Dermal route
Dermal absorption is considered limited since the logPow value is above 4 and thus considered to limit transfer between stratum corneum and the epidermis. However, uptake into the stratum corneum will probably be high. Another parameter that affects transport of a substance from the stratum corneum into the epidermis is the water solubility of a substance. Below 1 mg/L dermal uptake is considered to be low.
However, based on in vitro test battery results the test item was shown to have a skin sensation potential. Thus, even small amounts of the substance becoming bioavailable through the dermal route could be important. Moreover, the substance is classified as skin irritant and thus absorption may be facilitated due to the damage of the upper skin layers. - Details on distribution in tissues:
- Physicochemical properties of the test item as well as toxicity data indicate a rather low systemic bioavailability following oral, inhalative and dermal uptake.
However, after being absorbed into the body, the test item is likely distributed into cells and intracellular concentrations may be higher than extracellular concentrations due to rather lipophilic properties (log Pow 4.44). This applies especially for fatty tissues.
However, the test item is unlikely to have a bio-accumulative potential, even though it might be considered as lipophilic (logPow is greater than 4). The subacute repeated dose toxicity study in rats did not reveal any signs of target organ toxicity or other indications for an accumulation in any organ or tissue, there is also no other evidence for an accumulative property of this compound. Moreover, its metabolic transformation to more hydrophilic compounds is anticipated as described below. - Details on excretion:
- As discussed below, the test item is probably substrate to phase I metabolizing enzymes and its hydrophilicity will likely be increased by this process. Taking into account its low molecular weight it can be assumed that the test item is rather excreted via the kidneys and the urine than via feces after it has been metabolised.
- Details on metabolites:
- It can be assumed that P450-enzymes are substantially involved in the metabolism of the test item, based on findings in the bacterial reverse mutation assay (Ames) as well as in the mammalian cell gene mutation assay (HPRT). In both assays cytotoxicity was observed in the absence of the metabolizing system (S9). In the presence of S9, however, the same substance concentration did not induce cytotoxicity anymore. Thus, a detoxification by metabolism of phase I enzymes could be anticipated. This metabolism usually aims to enhance hydrophilicity of the substance, for example by hydroxylation reactions, in order to facilitate excretion of the xenobiotic. This supports the assumption that the test item is not considered of concern in regards to bioaccumulation.
- Conclusions:
- Based on physicochemical characteristics, particularly molecular weight and octanol-water partition coefficient, absorption by the dermal, oral and inhalation route is expected to be low. This assumption is further supported by the results of the oral acute toxicity study as well as the subacute repeated dose study. There are no indications that the test item or its metabolites could have a bioaccumulating potential. Metabolic transformation by phase I enzymes is expected and excretion via urine can be anticipated.
Reference
Description of key information
Key value for chemical safety assessment
- Bioaccumulation potential:
- no bioaccumulation potential
Additional information
Toxicokinetic Assessment Dihydromyrcene
There are no experimental data available on toxicokinetic behavior of the test item. Therefore, the following considerations are based on physico chemical properties of the test item as well as on results of in vivo and in vitro toxicity studies available.
Phys-Chem
properties
The
test item is a colorless liquid at ambient conditions with a melting
point <-30 °C and a boiling point of 163 °C. The substance is an UVCB
consisting of different isomers with the same molecular formula.
Therefore, molecular weight of every constituent is always 138.25 g/mol.
Vapor pressure of the test item was determined to be quite high with 2.14 hPa at 20°C and the test item is considered to be volatile. The test item is only poorly soluble in water based on QSAR calculations (WS = ca. 1.67 mg/L) and there are no indications that it undergoes hydrolysis in contact with water. The octanol/water partition coefficient of the test item was calculated to be 4.44.
Summary of toxicological profile
Acute
toxicity:
An acute oral toxicity study was carried out using the class method
according to OECD guideline 423, applying 2000 mg/kg bw/d. No mortality
and no test item related adverse effects regarding body weight
development or clinical observations were revealed. Therefore, the test
item is not classified according to the GHS classification and the
median lethal dose derived was: LD50 cut off ≥ 5000 mg/kg bw according
to the guideline.
Irritation and sensitisation:
In vitro tests systems for skin and eye irritation revealed that the test item is irritating to the skin but not to the eye. Moreover, the test item is also considered to be a skin sensitizer based on in vitro test battery data.
Repeated dose toxicity:
The
test item was assessed for its repeated dose toxicity in combined
Repeated Dose Toxicity Study with the Reproduction/Developmental
Toxicity Screening Test (OECD 422). No adverse effects were observed up
to the highest dose tested i. e. 800 mg/kg bw/d. In male rats
hyaline-like droplets were observed by histopathological examination.
Further assessment confirmed alpha-u2-globulin positive. Thus, the
agglomerates are a sex and species related finding and are not
indicative for effects of human relevance.
Genotoxicity:
The test item was
shown to be not mutagenic or clastogenic in bacterial as well as in
mammalian cell systems.
Absorption
Oral
route
Generally, oral absorption is favoured for molecular weights below 500
g/mol. The low water solubility of ca. 1.67 mg/L will probably not allow
ready dissolution of the test item in the gastrointestinal fluids. Thus,
a direct uptake into the systemic circulation through aqueous pores or
via carriage with the bulk passage of water is considered as less
relevant. The logPow value of 4.44 is also already above the range of -1
to 4 which is usually considered to be favored for absorption by passive
diffusion through biological membranes. With a logPow of greater than 4,
the test item may be taken up by micellular solubilisation. Moreover,
hydrolysis of the test item in the GIT is not expected based on QSAR
calculation the hydrolytic half-life is greater than a year. Overall,
physicochemical properties of the test item indicate that it might not
be readily absorbed via the oral route. This is supported by oral acute
as well as repeated dose toxicity data, where no or only minor signs of
toxicity were observed after administration up to the limit dose (2000
mg/kg bw and 1000 mg/kg bw/d, respectively).
Inhalation
route
Due to its volatile
properties availability of the test item via the inhalation route cannot
be completely ruled out. Since the substance is a liquid at ambient
temperature the generation of dust is excluded. However, in case of
inhalation, absorption via the respiratory tract cannot be ruled out due
to the relatively high vapor pressure.
Dermal
route
Dermal
absorption is considered limited since the logPow value is above 4 and
thus considered to limit transfer between stratum corneum and the
epidermis. However, uptake into the stratum corneum will probably be
high. Another parameter that affects transport of a substance from the
stratum corneum into the epidermis is the water solubility of a
substance. Below 1 mg/L dermal uptake is considered to be low.
However, based on in vitro test battery results the test item was shown
to have a skin sensation potential. Moreover, the substance is
classified as skin irritant and thus absorption may be facilitated due
to the damage of the upper skin layers.
Distribution
Physicochemical properties of the test item as well as toxicity data indicate a rather low systemic bioavailability following oral, inhalative and dermal uptake.However, after being absorbed into the body, the test item is likely distributed into cells and intracellular concentrations may be higher than extracellular concentrations due to rather lipophilic properties (log Pow 4.44). This applies especially for fatty tissues. However, the test item is unlikely to have a bio-accumulative potential, even though it might be considered as lipophilic (logPow is greater than 4).The subacute repeated dose toxicity study in rats did not reveal any signs of target organ toxicity or other indications for an accumulation in any organ or tissue, there is also no other evidence for an accumulative property of this compound. Moreover, its metabolic transformation to more hydrophilic compounds is anticipated as described below.
Metabolism
It can be assumed that P450-enzymes are substantially involved in the metabolism of the test item, based on findings in the bacterial reverse mutation assay (Ames) as well as in the mammalian cell gene mutation assay (HPRT). In both assays cytotoxicity was observed in the absence of the metabolizing system (S9). In the presence of S9, however, the same substance concentration did not induce cytotoxicity anymore. Thus, a detoxification by metabolism of phase I enzymes could be anticipated. This metabolism usually aims to enhance hydrophilicity of the substance, for example by hydroxylation reactions, in order to facilitate excretion of the xenobiotic. This supports the assumption that the test item is not considered of concern in regards to bioaccumulation.
Excretion
As
discussed above, the test item is probably substrate to phase I
metabolizing enzymes and its hydrophilicity will likely be increased by
this process. Taking into account its low molecular weight it can be
assumed that the test item is rather excreted via the kidneys and the
urine than via feces after it has been metabolised.
Summary
Based on physicochemical characteristics, particularly molecular weight and octanol-water partition coefficient, absorption by the dermal, oral and inhalation route is expected to be low. This assumption is further supported by the results of the oral acute toxicity study as well as the subacute repeated dose study. There are no indications that the test item or its metabolites could have a bioaccumulating potential. Metabolic transformation by phase I enzymes is expected and excretion via urine can be anticipated.
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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