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EC number: 908-114-0 | 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)
Description of key information
Based on physico-chemical parameters, Citronellyl Acetate Multi is expected to be readily absorbed via the oral and inhalation route and via the dermal route. For route to route extrapolation the final absorption percentages derived are: 50% oral absorption, 50% dermal absorption and 100% inhalation absorption.
Key value for chemical safety assessment
- Bioaccumulation potential:
- low bioaccumulation potential
- Absorption rate - oral (%):
- 50
- Absorption rate - dermal (%):
- 50
- Absorption rate - inhalation (%):
- 100
Additional information
The toxico-kinetic behaviour of Citronellyl Acetate Multi
Introduction
Citronellyl Acetate Multi is a multi-constituent. The main constituent of Citronellyl Acetate Multi isCitronellyl Acetate mono. The minor constituent is Dihydro-Citronellyl Acetate, which is very similar but its hydrocarbon backbone is saturated (and does not contain the double bond in the alkyl chain).
Citronellyl Acetate is a liquid with a molecular weight of 198.3, water solubility of 12.1 mg/L and a log Kow of 4.6 that does not preclude absorption. The test material has a hydrolysable acetate (ester) group. The substance has a vapour pressure of 2.58 Pa.
Absorption
Oral:For the endpoint oral repeated dose toxicity, data from the read-across substances Geranyl acetate and Geraniol 60 are considered, and for the endpoint reproduction and developmental toxicity data from the read-across substance Geraniol 60 are considered. From these data it can be concluded that the substance is being absorbed by the gastro-intestinal tract following oral administration, because effects were seen on mortality, body weight gain and developmental toxicity parameters. The relatively low molecular weight and the moderate octanol/water partition coefficient (Log Kow 4.6) 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 Citronellyl Acetate Multi is likely to be fully absorbed orally and therefore the oral absorption is expected to be > 50%.
Skin:Based on the physico-chemical characteristics of the substance, being a liquid, its molecular weight (198.3), log Kow (4.6) and water solubility (12.1 mg/L), dermal absorption is likely to occur. The optimal molecular weight and log Kow for dermal absorption is < 100 and in the range of -1 to +4, respectively (ECHA guidance, 7.12, Table R.7.12-3). In view of these characteristics being out of the optimum range, it is anticipated that dermal absorption will not exceed the oral absorption.
Lungs:Absorption via the lungs is also indicated based on these physico-chemical properties. Though the inhalation exposure route is thought minor, because of its low volatility (2.58 Pa), the octanol/water partition coefficient (4.6), indicates that inhalation absorption is possible.
The blood/air (B/A) partition coefficient (log (PBA)) is another coefficient indicating lung absorption. Buist et al. (2012) have developed a B/A portioning model for humans using the most important and readily available parameters:
Log (PBA) = 6.96 – 1.04 Log (VP) – 0.533 Log (Kow) – 0.00495 MW.
For Citronellyl Acetate multi the B/A partition coefficient would result in:
Log (PBA) = 6.96 – (1.04 x 0.41) – (0.533 x 4.6) – (0.00495 x 198) = 3.1
This means that the substance has a tendency to go from air into the blood. It should, however, be noted, that this regression is only valid for substances which have a vapour pressure > 100 Pa. Despite the fact that substance is out of the applicability domain and the exact B/A may consequently not be fully correct, it is suggested that the substance will be readily absorbed via the inhalation route and will be close to 100%.
Distribution
The low 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. Due to the expected metabolism the substance as such would not accumulate significantly in the body fat.
Metabolism
There are no actual data on the metabolism of Citronellyl Acetate Multi.
Ester metabolism: The stability and degradation of an acetate ester similar to Citronellyl Acetate Multi, Geranyl acetate Extra (pure trans-3,7-dimethyl-2,6-octadiene-1-yl-acetate) with two double bonds was studied in vitro in plasma, liver S9 fraction of rats, gastric juice simulant and intestinal-fluid simulant including pancreas lipase (Fabian, 2013, see study record). Geranyl acetate Extra was hydrolysed within 0.5 hour almost completely in rat plasma, liver S9 fraction of rats and intestinal fluid simulant, as demonstrated by the decrease of Geranyl acetate Extra and formation of the hydrolysis product Geraniol Extra (pure trans). In gastric fluid simulant the degradation was about 50% after 2 hours. The ester bond present in the acetate ester of Citronellyl Acetate Multi is expected to be hydrolysed at a comparable rate into the respective alcohol and acetic acid due to activity of enzymes in the gut and liver (Saghir et al., 1997, Chadha and Mayastha, 1984 and Wu et al., 2010).
Hydrocarbon-Terpene backbone: Beside the cleavage of the acetate ester also the hydrocarbon backbone is likely to be hydrolysed at the double bonds and/or further oxidised as presented in the OECD Toolbox rat S9 simulator. Based on metabolisation data of Geraniol (Chadha and Madyhasta, 1984,https://www.ncbi.nlm.nih.gov/pubmed/6475100), who determined the Geraniol metabolites in urine. They found Geranic acid, hydroxyl-citronellic acid, hydroxyl geraniol, 8-carboxy geraniol and Hildebrandt acid. Geraniol has one additional double bond in the backbone compared to Citronellol
Dihydro-Citronellyl Acetate will also be metabolised into a primary alcohol which can be further oxidised into and acid and one of the methyl group can be hydrolysed.
The alcohols are expected to be conjugated to further increase excretion via urine
Fig. 1 Metabolic scheme of Citronellyl Acetate mono based on information on Geranyl acetate and Geraniol metabolites in urine.
Excretion
Because of the relatively low molecular weight, the anticipated metabolism, Citronellyl Acetate Multi and its metabolites are expected to be excreted mainly via urine, and less so via the bile. Any unabsorbed substance will be excreted via the faeces.
Discussion
Citronellyl Acetate Multi 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 is below the limit value and the log Kow is in the favourable range for dermal absorption and therefore significant absorption is likely.
Oral to dermal extrapolation
There are adequate data via the oral route and the critical toxic effect is related to systemic effects and therefore route to route extrapolation is applicable. The toxicity of the substance will be due to the parent compound but also to its metabolites. The overriding principle will be to avoid situations where the extrapolation of data would underestimate toxicity resulting from human exposure to a chemical by the route to route extrapolation. Therefore for the oral route and dermal route 50% oral absorption will be used.
Oral to inhalation extrapolation
Though Citronellyl Acetate Multi is not a volatile liquid, inhalation exposure will be considered. Citronellyl Acetate Multi is not a corrosive for skin and eye and the systemic effect will overrule the effects at the site of contact. For inhalation absorption 100% will be used for route to route extrapolation.
Conclusion
Citronellyl Acetate Multi is expected to be readily absorbed. The IGHRC guidelines will be followed and for the oral and dermal absorption 50% and for inhalation 100% absorption will be used.
References
Buist, H.E., Wit-Bos de, L., Bouwman, T., Vaes, W.H.J., 2012, Predicting blood:air partion coefficient using basis physico-chemical properties, Regul. Toxicol. Pharmacol., 62, 23-28.
Chadha, A and Madyastha, 1984, Metabolism of geraniol and linolool in the rat and effects on liver and lung microsomal enzymes, Xenobiotica, 14, 365-74 (abstract):https://www.ncbi.nlm.nih.gov/pubmed/6475100
Fabian, E., Becker, M., Landsiedel, R., 2013, Geranylacetat Extra - Study on the hydrolysis-stability in rat plasma, rat liver S9 fraction, gastric-juice simulant and by pancreas lipase in intestinal-fluid simulant, BASF study report 09B0294/09B019.
IGHRC, 2006, Guidelines on route to route extrapolation of toxicity data when assessing health risks of chemicals,http://ieh.cranfield.ac.uk/ighrc/cr12[1].pdf
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.
Saghir. M., Werner, J., Laposta, M., 1997, Rapid in vivo hydrolysis of fatty acid ethyl esters, toxic nonoxidative ethanol metabolites, Am. J. Physiol., 273, G184-G190.
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