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EC number: 207-668-4 | CAS number: 488-10-8
- 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:
- 4.514 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- other: Guidance on Assessment Factors to Derive a DNEL (ECETOC, Technical Report No. 110)
- Overall assessment factor (AF):
- 18
- Dose descriptor starting point:
- NOAEL
- Value:
- 92.17 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 81.25 mg/m³
- Explanation for the modification of the dose descriptor starting point:
inhalation NOAEC = NOAELoral*(1/0.38 m³/kg bw/day)*(ABSoral-rat/ABSinh-human)*(6.7 m³ (8h)/10 m³ (8h)) = 92.17 mg/kg bw/day*(1/0.38 m³/kg bw/day)*(0.5/1)*0.67 = 81.25 mg/m³
ABSoral-rat=oral absorption rate in rats,
ABSinh-human=inhalation absorption rate in humans.
In a worst case approach the default oral absorption rate of 50% for the rat was used in the calculations (default 0.5/1 according to ECHA Guidance on Information Requirements and Chemical Safety Assessment - Chapter R.8: Characterisation of dose [concentration]-response for human health)
.
- AF for dose response relationship:
- 1
- Justification:
- NOAEC is chosen as starting point.
- AF for differences in duration of exposure:
- 6
- Justification:
- DNEL is based on an oral combined repeated dose toxicity study with the reproduction/developmental toxicity screening test (according to OECD TG 422).
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- AF for allometric scaling already included in starting point derivation method; no further factor required.
- AF for other interspecies differences:
- 1
- Justification:
- Based on ECETOC, Technical Report No. 110.
- AF for intraspecies differences:
- 3
- Justification:
- Based on ECETOC, Technical Report No. 110.
- AF for the quality of the whole database:
- 1
- AF for remaining uncertainties:
- 1
Acute/short term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
- Most sensitive endpoint:
- skin irritation/corrosion
- Route of original study:
- Dermal
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
- Most sensitive endpoint:
- skin irritation/corrosion
Acute/short term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
- Most sensitive endpoint:
- skin irritation/corrosion
DNEL related information
Workers - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 1.6 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- other: Guidance on Assessment Factors to Derive a DNEL (ECETOC, Technical Report No. 110)
- Overall assessment factor (AF):
- 72
- Dose descriptor starting point:
- NOAEL
- Value:
- 92.17 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 115.2 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
Dermal NOAEL=NOAELoral*(ABSoral-rat/ABSdermal-human) = 92.17 mg/kg bw/day*(1/0.8) = 115.2 mg/kg bw/day
ABSoral-rat = oral absorption rate in rats,
ABSdermal-human = dermal absorption rate in humans = 80% (as estimated using the Skin Absorption Model (SAM) developed by the Research Institute for Fragrance Material (RIFM))
- AF for dose response relationship:
- 1
- Justification:
- NOAEL is chosen as starting point.
- AF for differences in duration of exposure:
- 6
- Justification:
- DNEL is based on an oral combined repeated dose toxicity study with the reproduction/developmental toxicity screening test (according to OECD TG 422).
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- Based on ECETOC, Technical Report No. 110.
- AF for other interspecies differences:
- 1
- Justification:
- Based on ECETOC, Technical Report No. 110.
- AF for intraspecies differences:
- 3
- Justification:
- Based on ECETOC, Technical Report No. 110.
- AF for the quality of the whole database:
- 1
- AF for remaining uncertainties:
- 1
Acute/short term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
- Most sensitive endpoint:
- skin irritation/corrosion
- Route of original study:
- Dermal
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
- Most sensitive endpoint:
- skin irritation/corrosion
Acute/short term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
- Most sensitive endpoint:
- skin irritation/corrosion
Workers - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- low hazard (no threshold derived)
Additional information - workers
INHALATION
The long-term systemic inhalation DNEL has been derived from an oral NOAEL of 92.17 mg/kg bw/day obtained from an oral combined repeated dose toxicity study with the reproduction/developmental toxicity screening test (according to OECD TG 422) in rats. After route to route extrapolation by correction for the differences in the respiratory volumes of rats and humans over the relevant assessment period and correction for the differences in the respiratory volumes of humans in rest and during light activity a NOAECcorr of 81.25 mg/m³ has been used as dose descriptor starting point. In compliance with “ECHA Guidance on Information Requirements and Chemical Safety Assessment – Chapter R.8: Characterisation of dose [concentration]-response for human health” a value of 50% for oral absorption has been included in the calculation. Since respiratory rates depend directly on caloric demand no additional allometric scaling for metabolic differences between rats and humans is required anymore. Additional assessment factors of 6 for the transformation of subacute to subchronic data and of 3 to account for intraspecies differences among workers (based on ECETOC, Technical Report No. 110) were used. In conclusion, a DNEL of 4.514 mg/m³ has been determined.
No acute systemic inhalation DNEL has been derived. The substance is classified as irritating to the skin and eyes (Skin Irrit. 2; Eye Irrit. 2), which also comprise mucous membranes. According to “ECHA Guidance on Information Requirements and Chemical Safety Assessment – Part E: Risk Characterisation, TableE.3-1” the hazard via the inhalation route has to be considered low. No acute acute toxicity was observed after oral and dermal exposure. The acute toxicity after inhalation exposure is therefore also considered to be low and any short-term effects are expected to be caused by the irritating properties. The derivation of an acute DNEL is not recommended, and time scaling is not considered appropriate when the toxic effect is mainly driven by the exposure concentration, as is the case for irritation, according to "ECHA Guidance on Information Requirements and Chemical Safety Assessment - Chapter R.8: Characterisation of dose [concentration]-response for human health - Appendix R.8-8 Acute toxicity". In conclusion, according to "ECHA Guidance on Information Requirements and Chemical Safety Assessment - Part E: Risk Characterisation, Table E.3-1" the hazard for the inhalation route has to be considered as low. Due to the well-known irritating characteristics general Risk Management Measures and Operational Conditions (RMMs/OCs) are implemented, and the corresponding use of PPE (incl. appropriate respiratory protection) is mandatory, if inhalation exposure is possible. Therefore, the risk of peak exposures of workers by inhalation is considered to be sufficiently controlled.
Local DNELs for the inhalation route are not derived in compliance with “ECHA Guidance on Information Requirements and Chemical Safety Assessment – Chapter R.8: Characterisation of dose [concentration]-response for human health”. The neat substance is classified as irritating to the skin and eyes (Skin Irrit. 2; Eye Irrit. 2), which also comprise mucous membranes in form of the conjunctivae. Therefore, a comparable effect on the mucous membranes of the respiratory tract can be assumed. According to ECHA Guidance on Information Requirements and Chemical Safety Assessment – Part E: Risk Characterisation, Table E.3-1” the local hazard by respiratory irritation is considered as low. Due to the well-known irritating characteristics, general RMMs and OCs are implemented, and the corresponding use of PPE including appropriate respiratory protection is mandatory, if inhalation exposure is possible. In conclusion, the risk of local effects, both long-term and acute, on the respiratory tract of workers is considered to be sufficiently controlled.
DERMAL
The long-term systemic dermal DNEL has also been derived from the oral NOAEL of 92.17 mg/kg bw/day derived from an oral combined repeated dose toxicity study with the reproduction/developmental toxicity screening test (according to OECD TG 422) in rats. Route to route extrapolation has been done assuming a dermal absorption rate of 80% which was estimated using the Skin Absorption Model (SAM) developed by the Research Institute for Fragrance Material (RIFM). Hence, as dose descriptor starting point for DNEL derivation a NOAELcorr of 115.2 mg/kg bw/day has been used, followed by allometric scaling for interspecies differences between rats and humans, inclusion of an additional factor of 6 for transforming subacute into subchronic data and an assessment factor of 3 to account for intraspecies differences among the workers (based on ECETOC, Technical Report No. 110). In conclusion, a DNEL of 1.6 mg/kg bw/day has been derived.
No acute systemic dermal DNEL has been derived. According to “ECHA Guidance on Information Requirements and Chemical Safety Assessment – Chapter R.8: Characterisation of dose [concentration]-response for human health – Appendix R.8-8” a DNEL for acute toxicity should be derived if an acute toxicity hazard has been identified and if there is a potential for high peak exposures. High peak exposures are usually assessed for the inhalation route only. Although peak exposures in theory may also occur for the dermal route they are not normally assessed, so the establishment of acute toxicity DNELs for the dermal route appears superfluous. Short-term exposures should normally be assessed using the long-term DNELs. However, no data on the long-term toxicity via the dermal route is available, and DNELs cannot be derived from irritation studies; hence, there are no results to derive an acute DNEL. The neat substance and the concentration contained in the industrially marketed formulations are classified as irritating to the skin (Skin Irrit. 2). According to “ECHA Guidance on Information requirements and Chemical Safety Assessment – Part E: Risk Characterisation, Table E.3-1” the hazard via the dermal route has been considered as low. Due to the well-known irritant characteristics general RMMs and OCs are implemented, and the corresponding use of PPE including appropriate gloves is mandatory, if skin contact is possible. In conclusion, the risk of peak exposures of workers via the dermal route is considered to be sufficiently controlled although no DNELs can be derived from irritation studies.
Local DNELs for the dermal route are not derived in compliance with “ECHA Guidance on Information Requirements and Chemical Safety Assessment – Chapter R.8: Characterisation of dose [concentration]-response for human health”. According to this guidance DNELs covering local dermal effects can only be derived if route-specific data is available. However, no data on the long-term toxicity via the dermal route is available, and DNELs cannot be derived from irritation studies; hence, there are no results to derive a local DNEL. The neat substance and the concentration contained in the industrially marketed formulations are classified as irritating to the skin (Skin Irrit. 2), so the hazard for the dermal route has been considered as low according to “ECHA Guidance on Information Requirements and Chemical Safety Assessment – Part E: Risk Characterisation, Table E.3-1”. Due to the well-known irritating characteristics of the substance general RMMs and OCs are implemented, and the corresponding use of PPE including appropriate gloves, is mandatory, if skin contact is possible. In conclusion, the risk of local effects, both long-term and acute, on the skin of workers is considered to be sufficiently controlled, although no DNELs can be derived from irritation studies.
EYES
The neat substance is anticipated to be irritating to the eyes, resulting in the corresponding classification Eye Irrit. 1. According to "ECHA Guidance on Information Requirements and Chemical Safety Assessment - Part E: Risk Characterisation, Table E.3-1" the substance is considered to exert a low hazard for the eyes. Due to the well-known irritating characteristics of the substance general RMMs and OCs are implemented, and the corresponding use of PPE including appropriate eye protection in form of chemical goggles is mandatory. In conclusion, the risk for effects on the eyes of workers is considered to be sufficiently controlled.
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 1.336 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- other: Guidance on Assessment Factors to Derive a DNEL (ECETOC, Technical Report No. 110)
- Overall assessment factor (AF):
- 30
- Dose descriptor starting point:
- NOAEL
- Value:
- 92.17 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 40.07 mg/m³
- Explanation for the modification of the dose descriptor starting point:
NOAECcorr = NOAELoral*(1/1.15 m³/kg bw/day)*(ABSoral-rat/ABSinh-human) = 92.17 mg/kg bw/day*(1/1.15 m³/kg bw/day)*(0.5/1) = 40.07 mg/m³.
ABSoral-rat=oral absorption rate in rats
ABSinh-human=inhalation absorption rate in humans
In a worst case approach the default oral absorption rate of 50% for the rat was used in the calculations (default 0.5/1 according to ECHA Guidance on Information Requirements and Chemical Safety Assessment - Chapter R.8: Characterisation of dose [concentration]-response for human health).
- AF for dose response relationship:
- 1
- Justification:
- NOAEL is chosen as starting point.
- AF for differences in duration of exposure:
- 6
- Justification:
- DNEL is based on an oral combined repeated dose toxicity study with the reproduction/developmental toxicity screening test (according to OECD TG 422).
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- AF for allometric scaling already included in starting point derivation method; no further factor required.
- AF for other interspecies differences:
- 1
- Justification:
- Based on ECETOC, Technical Report No. 110.
- AF for intraspecies differences:
- 5
- Justification:
- Based on ECETOC, Technical Report No. 110.
- AF for the quality of the whole database:
- 1
- AF for remaining uncertainties:
- 1
Acute/short term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
- Most sensitive endpoint:
- skin irritation/corrosion
- Route of original study:
- Dermal
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
- Most sensitive endpoint:
- skin irritation/corrosion
Acute/short term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
- Most sensitive endpoint:
- skin irritation/corrosion
DNEL related information
General Population - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.96 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 120
- Dose descriptor starting point:
- NOAEL
- Value:
- 92.17 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 115.2 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
Dermal NOAEL=NOAELoral*(ABSoral-rat/ABSdermal-human) = 92.17 mg/kg bw/day*(1/0.8) = 115.2 mg/kg bw/day
ABSoral-rat = oral absorption rate in rats,
ABSdermal-human = dermal absorption rate in humans = 80% (as estimated using the Skin Absorption Model (SAM) developed by the Research Institute for Fragrance Material (RIFM))
- AF for dose response relationship:
- 1
- Justification:
- NOAEL is chosen as starting point.
- AF for differences in duration of exposure:
- 6
- Justification:
- DNEL is based on an oral combined repeated dose toxicity study with the reproduction/developmental toxicity screening test (according to OECD TG 422).
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- Based on ECETOC, Technical Report No. 110.
- AF for other interspecies differences:
- 1
- Justification:
- Based on ECETOC, Technical Report No. 110.
- AF for intraspecies differences:
- 5
- Justification:
- Based on ECETOC, Technical Report No. 110.
- AF for the quality of the whole database:
- 1
- AF for remaining uncertainties:
- 1
Acute/short term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
- Most sensitive endpoint:
- skin irritation/corrosion
- Route of original study:
- Dermal
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
- Most sensitive endpoint:
- skin irritation/corrosion
Acute/short term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
- Most sensitive endpoint:
- skin irritation/corrosion
General Population - Hazard via oral route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.768 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 120
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 92.17 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
No route-to-route extrapolation required, NOAEL derived from oral study. Equal oral absorption is anticipated for rats and humans.
- AF for dose response relationship:
- 1
- Justification:
- NOAEL is chosen as starting point.
- AF for differences in duration of exposure:
- 6
- Justification:
- DNEL is based on an oral combined repeated dose toxicity study with the reproduction/developmental toxicity screening test (according to OECD TG 422).
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- Based on ECETOC, Technical Report No. 110.
- AF for other interspecies differences:
- 1
- Justification:
- Based on ECETOC, Technical Report No. 110.
- AF for intraspecies differences:
- 5
- Justification:
- Based on ECETOC, Technical Report No. 110.
- AF for the quality of the whole database:
- 1
- AF for remaining uncertainties:
- 1
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
- Most sensitive endpoint:
- acute toxicity
- Route of original study:
- Oral
DNEL related information
General Population - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- low hazard (no threshold derived)
Additional information - General Population
INHALATION
The long-term systemic inhalation DNEL has been derived from an oral NOAEL of 92.17 mg/kg bw/day derived from an oral combined repeated dose toxicity study with the reproduction/developmental toxicity screening test (according to OECD TG 422) in rats. After route to route extrapolation by correction for the differences in the respiratory volumes of rats and humans over the relevant assessment period for the general public, a NOAECcorr of 40.07 mg/m³ has been used as dose descriptor starting point. In compliance with “ECHA Guidance on Information Requirements and Chemical Safety Assessment – Chapter R.8: Characterisation of dose [concentration]-response for human health” the default value of 50% for oral absorption has been included in the calculation in a worst case approach. Since respiratory rates depend directly on caloric demand no additional allometric scaling for metabolic differences between rats and humans is required anymore. An additional assessment factor of 5 has been included to account for intraspecies differences in the general population (based on ECETOC, Technical Report No. 110) and another one of 6 for transformation of subacute to chronic data. In conclusion, a DNEL of 1.336 mg/m³ has been determined.
No acute systemic inhalation DNEL has been derived. The substance is classified as irritating to the skin and eyes (Skin Irrit. 2; Eye Irrit. 2), which also comprise mucous membranes. According to “ECHA Guidance on Information Requirements and Chemical Safety Assessment – Part E: Risk Characterisation, TableE.3-1” the hazard via the inhalation route has to be considered low. No acute acute toxicity was observed after oral and dermal exposure. The acute toxicity after inhalation exposure is therefore also considered to be low and any short-term effects are expected to be caused by the irritating properties. The derivation of an acute DNEL is not recommended, and time scaling is not considered appropriate when the toxic effect is mainly driven by the exposure concentration, as is the case for irritation, according to "ECHA Guidance on Information Requirements and Chemical Safety Assessment - Chapter R.8: Characterisation of dose [concentration]-response for human health - Appendix R.8-8 Acute toxicity". In conclusion, according to "ECHA Guidance on Information Requirements and Chemical Safety Assessment - Part E: Risk Characterisation, Table E.3-1" the hazard for the inhalation route has to be considered low. The risk for workers in industrial and professional settings is controlled by the implementation of appropriate RMMs and OCs; however, since compliance with RMMs and OCs could not be controlled for the general population, and the use of PPE could not be assumed, the risk for the general population is controlled by limiting the concentration of the substance in consumer products to levels resulting in no hazard or low hazard via the respective routes according to “ECHA Guidance on Information Requirements and Chemical Safety Assessment – Part E: Risk Characterisation, Table E.3-1”, including appropriate labelling, and by establishing appropriate use profiles. In conclusion, the risk of peak exposures of consumers by inhalation is considered to be adequately controlled.
Local DNELs for the inhalation route are not derived in compliance with “ECHA Guidance on Information Requirements and Chemical Safety Assessment – Chapter R.8: Characterisation of dose [concentration]-response for human health”. The neat substance has to be regarded as irritating to the skin and eyes (Skin Irrit. 2; Eye Irrit. 2), which also comprise mucous membranes in form of the conjunctivae. Therefore, a comparable effect on the mucous membranes of the respiratory tract can be assumed. According to ECHA Guidance on Information Requirements and Chemical Safety Assessment – Part E: Risk Characterisation, Table E.3-1” the local hazard by respiratory irritation is considered as low. The risk for workers in industrial and professional settings is controlled by the implementation of appropriate RMMs and OCs; however, since compliance with RMMs and OCs could not be controlled for the general population, and the use of PPE could not be assumed, the risk for the general population is controlled by limiting the concentration of the substance in consumer products to levels resulting in no hazard or low hazard via the respective routes according to “ECHA Guidance on Information Requirements and Chemical Safety Assessment – Part E: Risk Characterisation, Table E.3-1”, including appropriate labelling, and by establishing appropriate use profiles. In conclusion, the risk of local effects, both long-term and acute, on the respiratory tract of consumers is considered to be adequately controlled.
DERMAL
The long-term systemic dermal DNEL has also been derived from the oral NOAEL of 92.17 mg/kg bw/day derived from an oral combined repeated dose toxicity study with the reproduction/developmental toxicity screening test (according to OECD TG 422) in rats. Route to route extrapolation has been done assuming a dermal absorption rate of 80% which was estimated using the Skin Absorption Model (SAM) developed by the Research Institute for Fragrance Material (RIFM). Hence, as dose descriptor starting point for DNEL derivation a NOAELcorr of 115.2 mg/kg bw/day has been used, followed by allometric scaling for interspecies differences between rats and humans, inclusion of an additional factor of 2.5 for other interspecies differences and an assessment factor of 5 to account for intraspecies differences in the general population (based on ECETOC, Technical Report No. 110) as well as an additional factor of 6 for transforming subacute into chronic data. In conclusion, a DNEL of 0.96 mg/kg bw/day has been derived.
No acute systemic dermal DNEL has been derived. According to “ECHA Guidance on Information Requirements and Chemical Safety Assessment – Chapter R.8: Characterisation of dose [concentration]-response for human health – Appendix R.8-8” a DNEL for acute toxicity should be derived if an acute toxicity hazard has been identified and if there is a potential for high peak exposures. High peak exposures are usually assessed for the inhalation route only. Although peak exposures in theory may also occur for the dermal route they are not normally assessed, so the establishment of acute toxicity DNELs for peak exposures via the dermal route appears superfluous. Short-term exposures should normally be assessed using the long-term DNELs. However, no data on long-term toxicity via the dermal route is available, and DNELs cannot be derived from irritation studies; hence, there are no results to derive an acute DNEL. The neat substance and the concentration contained in the industrially marketed formulations are classified as irritating to the skin (Skin Irrit. 2). According to “ECHA Guidance on Information requirements and Chemical Safety Assessment – Part E: Risk Characterisation, Table E.3-1” the hazard via the dermal route is considered as low. The risk for workers in industrial and professional settings is controlled by the implementation of appropriate RMMs and OCs; however, since compliance with RMMs and OCs could not be controlled for the general population, and the use of PPE could not be assumed, the risk for the general population is controlled by limiting the concentration of the substance in consumer products to levels resulting in no hazard or low hazard via the respective routes according to “ECHA Guidance on Information Requirements and Chemical Safety Assessment – Part E: Risk Characterisation, Table E.3-1”, including appropriate labelling, and by establishing appropriate use profiles. In conclusion, the risk of peak exposures of consumers via the dermal route is considered to be adequately controlled although no DNELs can be derived from irritation studies.
Local DNELs for the dermal route are not derived in compliance with “ECHA Guidance on Information Requirements and Chemical Safety Assessment – Chapter R.8: Characterisation of dose [concentration]-response for human health”. According to this guidance DNELs covering local dermal effects can only be derived if route-specific data is available. However, no data on long-term toxicity via the dermal route is available, and DNELs cannot be derived from irritation studies; hence, there are no results to derive a local DNEL. The neat substance and the concentration contained in the industrially marketed formulations are classified as irritating to the skin (Skin Irrit. 2), so the hazard for the dermal route is considered as low according to “ECHA Guidance on Information Requirements and Chemical Safety Assessment – Part E: Risk Characterisation, Table E.3-1”. The risk for workers in industrial and professional settings is controlled by the implementation of appropriate RMMs and OCs; however, since compliance with RMMs and OCs could not be controlled for the general population, and the use of PPE could not be assumed, the risk for the general population is controlled by limiting the concentration of the substance in consumer products to levels resulting in no hazard or low hazard via the respective routes according to “ECHA Guidance on Information Requirements and Chemical Safety Assessment – Part E: Risk Characterisation, Table E.3-1”, including appropriate labelling, and by establishing appropriate use profiles. In conclusion, the risk of local effects, both long-term and acute, on the skin of consumers is considered to be adequately controlled although no DNELs can be derived from irritation studies.
ORAL
The long-term systemic oral DNEL has also been derived from the oral NOAEL of 92.17 mg/kg bw/day derived from an oral combined repeated dose toxicity study with the reproduction/developmental toxicity screening test (according to OECD TG 422) in rats. Route to route extrapolation is not required, and in a worst case approach equal oral absorption for rats and humans (absorption of 100% is assumed for the rat) has been anticipated. Hence, as dose descriptor starting point for DNEL derivation a NOAELcorr of 92.17 mg/kg bw/day has been used, followed by allometric scaling for interspecies differences between rats and humans, inclusion of an assessment factor of 5 to account for intraspecies differences in the general population (based on ECETOC, Technical Report No. 110) as well as an additional factor of 6 for transforming subacute into chronic data. In conclusion, a DNEL of 0.7681 mg/kg bw/day has been derived.
No acute systemic oral DNEL has been derived. According to “ECHA Guidance on Information Requirements and Chemical Safety Assessment – Chapter R.8: Characterisation of dose [concentration]-response for human health – Appendix R.8-8” a DNEL for acute toxicity should be derived if an acute toxicity hazard has been identified and if there is a potential for high peak exposures. High peak exposures are usually assessed for the inhalation route only. Although peak exposures in theory may also occur for the oral route they are not normally assessed, so the establishment of acute toxicity DNELs for peak exposures via the oral route appears superfluous. Short-term exposures should normally be assessed using the long-term DNELs. However, there are data from acute toxicity studies via the oral route available; all data indicate a low acute toxicity and LD50 values determined (4300 and approx. 5000 mg/kg bw, for the two studies, respectively) and are well above the threshold for classification of 2000 mg/kg bw according to Regulation (EC) No. 1272/2008 (CLP). Hence, no hazard via the oral route has been identified, the substance is not classified for acute toxicity via the oral route, and the derivation of an acute DNEL is not required. In conclusion, the risk of peak exposures via the oral route is considered to be adequately controlled although no acute DNEL has been derived.
EYES
The neat substance is anticipated to be irritating to the eyes, resulting in the corresponding classification Eye Irrit. 2. According to “ECHA Guidance on Information Requirements and Chemical Safety Assessment – Part E: Risk Characterisation, Table E.3-1” the substance is considered to exert a low hazard for the eyes. The risk for workers in industrial and professional settings is controlled by the implementation of appropriate RMMs and OCs; however, since compliance with RMMs and OCs could not be controlled for the general population, and the use of PPE could not be assumed, the risk for the general population is controlled by limiting the concentration of the substance in consumer products to levels resulting in no hazard or low hazard via the respective routes according to “ECHA Guidance on Information Requirements and Chemical Safety Assessment – Part E: Risk Characterisation, Table E.3-1”, including appropriate labelling, and by establishing appropriate use profiles. In conclusion, the risk of effects on the eyes of consumers is considered to be adequately controlled.
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