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EC number: 289-904-6 | CAS number: 90045-43-5 Extractives and their physically modified derivatives such as tinctures, concretes, absolutes, essential oils, oleoresins, terpenes, terpene-free fractions, distillates, residues, etc., obtained from Citrus paradisi M., Rutaceae.
- 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
Toxicological Summary
- Administrative data
- Workers - Hazard via inhalation route
- Workers - Hazard via dermal route
- Workers - Hazard for the eyes
- Additional information - workers
- General Population - Hazard via inhalation route
- General Population - Hazard via dermal route
- General Population - Hazard via oral route
- General Population - Hazard for the eyes
- Additional information - General Population
Administrative data
Workers - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 31.1 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- Overall assessment factor (AF):
- 112.5
- Modified dose descriptor starting point:
- LOAEC
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Workers - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 8.89 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- Overall assessment factor (AF):
- 112.5
- Modified dose descriptor starting point:
- LOAEL
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
- Most sensitive endpoint:
- sensitisation (skin)
Workers - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- no hazard identified
Additional information - workers
- interspecies effects – remaining differences 2.5
- intraspecies effects – worker 5
- duration – subchronic to chronic 2
- dose response – use of LOAEL 3
- quality of the database – 1.5, based on limitations of report (publications) or limitations in experimental set-up (NTP-studies)
There is no information on repeated dose toxicity for grapefruit oil, however, several sub-chronic repeated dose toxicity studies are available for its major constituent limonene, in different species (mouse, rat and dog). Although the most sensitive NOAEL is from the dog study, it may not be the most appropriate NOAEL to base the DNEL on, because the study design is such that the difference in concentration between the NOAEL and LOAEL is quite high (100 mg/kg bw/day and 1000 mg/kg bw/day, respectively). When the studies in other species are taken into account, the same LOAEL is observed, but, due to another study design, a higher NOAEL. In the 90-d mouse study (NTP, 1990), the LOAEL is also 1000 mg/kg bw/day, but a NOAEL of 500 mg/kg bw/day was observed. However, as the studies are performed in different species, the choice for the mouse NOAEL of 500 mg/kg bw/day is arbitrary. Furthermore, an additional dog study is available in which a LOAEL of 1000 mg/kg bw/day was observed (NOAEL 340 mg/kg bw/day), and a 90-day rat study which resulted in a LOAEL of 1200 mg/kg bw/day. Therefore, the shared LOAEL of 1000 mg/kg bw/day can be used as a starting point for the derivation of the DNEL.
As three different species support the LOAEL, interspecies differences due to allometric scaling do not have to be taken into account. Consequently, route-to route extrapolation from oral to inhalation was performed by correcting for bodyweight and respiratory volume of humans only. In accordance with the Guidance Document on Information Requirements, Chapter R8., absorption of 100% was assumed via the inhalation route, with regard to an oral absorption of 50%. Additionally, the following assessment factors were applied:
The DNELs were derived in accordance with the Guidance on Information Requirements and Chemical Safety Assessment Chapter R8.
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 7.78 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- Overall assessment factor (AF):
- 225
- Modified dose descriptor starting point:
- LOAEC
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
General Population - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 4.44 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- Overall assessment factor (AF):
- 225
- Modified dose descriptor starting point:
- LOAEL
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
- Most sensitive endpoint:
- sensitisation (skin)
General Population - Hazard via oral route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 4.44 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- Overall assessment factor (AF):
- 225
- Modified dose descriptor starting point:
- LOAEL
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
General Population - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- no hazard identified
Additional information - General Population
- interspecies effects – remaining differences 2.5
- intraspecies effects – general population 10
- duration – subchronic to chronic 2
- dose response – use of LOAEL 3
- quality of the database – 1.5, based on limitations of report (publications) or limitations in experimental set-up (NTP-studies)
There is no information on repeated dose toxicity for grapefruit oil, however, several sub-chronic repeated dose toxicity studies are available for its major constituent limonene, in different species (mouse, rat and dog). Although the most sensitive NOAEL is from the dog study, it may not be the most appropriate NOAEL to base the DNEL on, because the study design is such that the difference in concentration between the NOAEL and LOAEL is quite high (100 mg/kg bw/day and 1000 mg/kg bw/day, respectively). When the studies in other species are taken into account, the same LOAEL is observed, but, due to another study design, a higher NOAEL. In the 90-d mouse study (NTP, 1990), the LOAEL is also 1000 mg/kg bw/day, but a NOAEL of 500 mg/kg bw/day was observed. However, as the studies are performed in different species, the choice for the mouse NOAEL of 500 mg/kg bw/day is arbitrary. Furthermore, an additional dog study is available in which a LOAEL of 1000 mg/kg bw/day was observed (NOAEL 340 mg/kg bw/day), and a 90-day rat study which resulted in a LOAEL of 1200 mg/kg bw/day. Therefore, the shared LOAEL of 1000 mg/kg bw/day can be used as a starting point for the derivation of the DNEL.
As three different species support the LOAEL, interspecies differences due to allometric scaling do not have to be taken into account. Consequently, route-to route extrapolation from oral to inhalation was performed by correcting for bodyweight and respiratory volume of humans only. In accordance with the Guidance Document on Information Requirements, Chapter R8., absorption of 100% was assumed via the inhalation route, with regard to an oral absorption of 50%. Additionally, the following assessment factors were applied:
The DNELs were derived in accordance with the Guidance on Information Requirements and Chemical Safety Assessment Chapter R8.
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