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EC number: 609-330-5 | CAS number: 370865-89-7
- 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:
- 6.64 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- other: ECHA REACH guidance and ECETOC guidance for intraspecies differences
- Overall assessment factor (AF):
- 45
- Dose descriptor starting point:
- NOAEL
- Value:
- 339 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 298.9 mg/m³
- Explanation for the modification of the dose descriptor starting point:
The starting point is a NOAEL (oral administration) of 339.0 mg/kg bw. A factor 2 is applied for route to route extrapolation, oral to inhalation. The resulting rat NOAEL was converted into inhalatory worker NOAEC by converting the oral dose to corresponding air concentration (8 hours exposure for workers) and correcting for respiratory rate based on activity (6.7 m³ for normal light activity versus 10 m³ for worker activity): 169.5 * (1/0.38) * (6.7/10) = 298.9 mg/m³
- AF for dose response relationship:
- 1
- Justification:
- In accordance with ECHA Guidance on information requirements and chemical safety assessment – R.8: Characterisation of dose [concentration]-response for human health (v2.1, 2012), for the dose-response relationship, consideration should be given to the uncertainties in the dose descriptor (NOAEL, benchmark dose…) as the surrogate for the true no-adverse-effect-level (NAEL). In this case the starting point for the DNEL calculation is a NOAEL, derived from a study which is of good quality and without uncertainties. Therefore, the default assessment factor, as a standard procedure, is 1.
- AF for differences in duration of exposure:
- 6
- Justification:
- In accordance with ECHA Guidance R.8 (v2.1, 2012), a factor allowing for differences in the experimental exposure duration and the duration of exposure for the worker and scenario under consideration needs to be considered taking into account that a) in general the experimental NOAEL will decrease with increasing exposure times and b) other and more serious adverse effects may appear with increasing exposure times. Consequently, to end up with the most conservative DNEL for repeated dose toxicity, chronic exposure is the ‘worst case’. So, as only a sub-acute toxicity study is available, default assessment factor of 6 is to be applied, as a standard procedure.
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- In accordance with ECHA Guidance R.8 (v2.1, 2012), as long as route-to-route extrapolation is not needed, allometric scaling should not be applied in cases where doses in experimental animal studies are expressed as concentrations (e.g. in mg/m3 air, ppm in diet, or mg/L in the drinking water) as these are assumed to be already scaled according to the allometric principle, since ventilation rate and food intake directly depend on the basal metabolic rate. In this case the NOAEC is expressed as concentration (mg/m³), therefore a factor for allometric scaling is not needed. In ECETOC Derivation of Assessment Factors for Human Health Risk Assessment – Technical Report No. 86 and ECETOC Guidance on Assessment Factors to Derive a DNEL – Technical Report No. 110, a similar approach is followed. The rationale here is that allometric scaling should not be applied because in humans inhalation rate is 4-fold lower compared to rat according to the slower metabolic rate and thereby the allometric species difference is already implicitly taken into account.
- AF for other interspecies differences:
- 2.5
- Justification:
- In accordance with ECHA Guidance R.8 (v2.1, 2012), as long as no substance-specific data are available, an additional factor of 2.5 for other interspecies differences, i.e. toxicokinetic differences not related to metabolic rate and toxicodynamic differences, is applied.
- AF for intraspecies differences:
- 3
- Justification:
- In accordance with ECETOC Derivation of Assessment Factors for Human Health Risk Assessment – Technical Report No. 86 (2003) and ECETOC Guidance on Assessment Factors to Derive a DNEL – Technical Report No. 110 (2010), a default assessment factor for the general population is based on the distributions of human data for various toxicokinetic and toxicodynamic parameters. The upper extreme of the variability in these data was estimated by calculating the 95th percentile of the distribution, which is considered sufficiently conservative to account for intraspecies variability in the general population (the data analysed included both sexes, a variety of disease states and ages). This results in recommended default assessment factor of 5 for the general population. As the worker population is more homogeneous (i.e. younger, healthier, protected from exposures), a default assessment factor of 3 is recommended. This proposal of ECETOC is based on an evaluation of the available scientific literature while the ECHA Guidance R.8 (v2.1, 2012) refers to standard default procedures. Until the scientific basis for using an alternative approach has been established, it is proposed to follow the ECETOC guideline.
- AF for the quality of the whole database:
- 1
- Justification:
- In accordance with ECHA Guidance R.8 (v2.1, 2012), the evaluation of the total toxicological database should include an assessment whether the available information as a whole meets the tonnage driven data requirements necessary to fulfil the REACH requirements, or whether there are data gaps (completeness of the database). Furthermore, the hazard data should be assessed for the reliability and consistency across different studies and endpoints and taking into account the quality of the testing method, size and power of the study design, biological plausibility, dose-response relationships and statistical association (adequacy of the database). When taking into account the standard information requirements and the completeness and consistency of the database the default assessment factor of 1, to be applied for good/standard quality of the database, is recommended.
- AF for remaining uncertainties:
- 1
- Justification:
- default (DNEL derivation based on a GLP and OECD TG study)
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:
- 1.88 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- other: ECHA REACH guidance and ECETOC guidance for intraspecies differences
- Overall assessment factor (AF):
- 180
- Dose descriptor starting point:
- NOAEL
- Value:
- 339 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 339 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
The starting point is a NOAEL (oral administration) of 339.0 mg/kg bw. In accordance with ECHA Guidance on information requirements and chemical safety assessment – R.8: Characterisation of dose [concentration]-response for human health (v2.1, 2012), in absence of data on absorption via the dermal route, a worst case assumption has to be made. As it is assumed that, in general, dermal absorption will not be higher than oral absorption, no default factor (i.e. factor 1) is introduced.
- AF for dose response relationship:
- 1
- Justification:
- In accordance with ECHA Guidance R.8 (v2.1, 2012), for the dose-response relationship, consideration should be given to the uncertainties in the dose descriptor (NOAEL, benchmark dose…) as the surrogate for the true no-adverse-effect-level (NAEL). In this case the starting point for the DNEL calculation is a NOAEL, derived from a study which is of good quality and without uncertainties. Therefore, the default assessment factor, as a standard procedure, is 1.
- AF for differences in duration of exposure:
- 6
- Justification:
- In accordance with ECHA Guidance R.8 (v2.1, 2012), a factor allowing for differences in the experimental exposure duration and the duration of exposure for the worker and scenario under consideration needs to be considered taking into account that a) in general the experimental NOAEL will decrease with increasing exposure times and b) other and more serious adverse effects may appear with increasing exposure times. Consequently, to end up with the most conservative DNEL for repeated dose toxicity, chronic exposure is the ‘worst case’. So, as only a sub-acute toxicity study is available, default assessment factor of 6 is to be applied, as a standard procedure.
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- In accordance with ECHA Guidance R.8 (v2.1, 2012), allometric scaling extrapolates doses according to an overall assumption that equitoxic doses (when expressed in mg/kg bw/day) scale with body weight to the power of 0.75. This results a default allometric scaling factor for the rat when compared with humans, namely 4. In ECETOC TR86 Derivation of Assessment Factors for Human Health Risk Assessment (2003) and ECETOC TR110 Guidance on Assessment Factors to Derive a DNEL (2010), a similar approach is followed. Toxicokinetic differences can be explained by basal metabolic rate which can be accounted for by allometric scaling. The underlying principle is that due to the faster metabolic rate of small animals, humans would less effectively detoxify and/or excrete xenobiotics than laboratory animals and thus are more vulnerable. The allometric scaling factor for the rat versus humans is 4.
- AF for other interspecies differences:
- 2.5
- Justification:
- In accordance with ECHA Guidance R.8 (v2.1, 2012), as long as no substance-specific data are available, an additional factor of 2.5 for other interspecies differences, i.e. toxicokinetic differences not related to metabolic rate and toxicodynamic differences, is applied.
- AF for intraspecies differences:
- 3
- Justification:
- In accordance with ECETOC TR86 (2003) and ECETOC TR110 (2010), a default assessment factor for the general population is based on the distributions of human data for various toxicokinetic and toxicodynamic parameters. The upper extreme of the variability in these data was estimated by calculating the 95th percentile of the distribution, which is considered sufficiently conservative to account for intraspecies variability in the general population (the data analysed included both sexes, a variety of disease states and ages). This results in recommended default assessment factor of 5 for the general population. As the worker population is more homogeneous (i.e. younger, healthier, protected from exposures), a default assessment factor of 3 is recommended. This proposal of ECETOC is based on an evaluation of the available scientific literature while the ECHA Guidance R.8 (v2.1, 2012) refers to standard default procedures. Until the scientific basis for using an alternative approach has been established, it is proposed to follow the ECETOC guideline.
- AF for the quality of the whole database:
- 1
- Justification:
- In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose [concentration]-response for human health, the evaluation of the total toxicological database should include an assessment whether the available information as a whole meets the tonnage driven data requirements necessary to fulfil the REACH requirements, or whether there are data gaps (completeness of the database). Furthermore, the hazard data should be assessed for the reliability and consistency across different studies and endpoints and taking into account the quality of the testing method, size and power of the study design, biological plausibility, dose-response relationships and statistical association (adequacy of the database). When taking into account the standard information requirements and the completeness and consistency of the database the default assessment factor of 1, to be applied for good/standard quality of the database, is recommended.
- AF for remaining uncertainties:
- 1
- Justification:
- default
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 2 166.7 µg/cm²
- Most sensitive endpoint:
- sensitisation (skin)
DNEL related information
- DNEL derivation method:
- other: ECHA REACH guidance and ECETOC guidance
- Overall assessment factor (AF):
- 3
- Dose descriptor:
- other: human NOEL
- Value:
- 65 000 mg/m³
- AF for dose response relationship:
- 1
- Justification:
- In accordance with ECHA Guidance on information requirements and chemical safety assessment – R.8: Characterisation of dose [concentration]-response for human health (v2.1, 2012), for the LLNA study an assessment factor of 1 is applicable, because 1) the NOAEL is used as a starting point; 2) the doses were well separated (10, 25 and 50%) and; 3) a dose response was observed (stimulation index was 2.27, 2.98 and 3.53% respectively).
- AF for differences in duration of exposure:
- 1
- Justification:
- In accordance with ECHA Guidance R.8 (v2.1, 2012), for the dose-response relationship, the LLNA is considered to be sufficiently sensitive for assessing skin sensitization; 1) considering presence and absence of skin sensitization and; 2) determining a quantitative value for risk characterization (see note 17 in R.8, Application of AFs to the correct starting point to obtain the induction-specific DNEL, page 125, 1st part). Therefore, an assessment factor of 1 is applicable.
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- An assessment factor for interspecies differences is not needed as the starting dose descriptor is the human NOEL for skin sensitisation, which is considered to match to the EC3 in the LLNA in mice; see also explanation for hazard conclusion.
- AF for other interspecies differences:
- 1
- Justification:
- An assessment factor for other interspecies differences is not needed as the starting dose descriptor is the human NOEL for skin sensitisation, which is considered to match to the EC3 in the LLNA in mice; see also explanation for hazard conclusion.
- AF for intraspecies differences:
- 3
- Justification:
- In accordance with ECETOC TR86 Derivation of Assessment Factors for Human Health Risk Assessment (2003) and ECETOC TR110 Guidance on Assessment Factors to Derive a DNEL (2010), a default assessment factor for the general population is based on the distributions of human data for various toxicokinetic and toxicodynamic parameters. The upper extreme of the variability in these data was estimated by calculating the 95th percentile of the distribution, which is considered sufficiently conservative to account for intraspecies variability in the general population (the data analysed included both sexes, a variety of disease states and ages). This results in recommended default assessment factor of 5 for the general population. As the worker population is more homogeneous (i.e. younger, healthier, protected from exposures), a default assessment factor of 3 is recommended. This proposal of ECETOC is based on an evaluation of the available scientific literature while the ECHA Guidance R.8 (v2.1, 2012) refers to standard default procedures. Until the scientific basis for using an alternative approach has been established, it is proposed to follow the ECETOC guideline.
- AF for the quality of the whole database:
- 1
- Justification:
- In accordance with ECHA Guidance R.8 (v2.1, 2012), the evaluation of the total toxicological database should include an assessment whether the available information as a whole meets the tonnage driven data requirements necessary to fulfil the REACH requirements, or whether there are data gaps (completeness of the database). Furthermore, the hazard data should be assessed for the reliability and consistency across different studies and endpoints and taking into account the quality of the testing method, size and power of the study design, biological plausibility, dose-response relationships and statistical association (adequacy of the database). When taking into account the standard information requirements and the completeness and consistency of the database the default assessment factor of 1, to be applied for good/standard quality of the database, is recommended.
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
Workers - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- no hazard identified
Additional information - workers
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 1.97 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- other: ECHA REACH guidance and ECETOC guidance for intraspecies differences
- Overall assessment factor (AF):
- 75
- Dose descriptor starting point:
- NOAEL
- Value:
- 339 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 147.39 mg/m³
- Explanation for the modification of the dose descriptor starting point:
The starting point is a NOAEL (oral administration) of 339.0 mg/kg bw. A factor 2 is applied for route to route extrapolation, oral to inhalation. The resulting rat NOAEL was converted into inhalatory consumer NOAEC by converting the oral dose to corresponding air concentration. NOAEC = NOAEL (oral, rat, OECD422) *abs oral/inhal *1/1.15 m3/kg/d = 339 mg/kg *50/100 *1/1.15m3/kg/d = 147.39 mg/m3
- AF for dose response relationship:
- 1
- Justification:
- In accordance with ECHA Guidance on information requirements and chemical safety assessment – R.8: Characterisation of dose [concentration]-response for human health (v2.1, 2012), for the dose-response relationship, consideration should be given to the uncertainties in the dose descriptor (NOAEL, benchmark dose…) as the surrogate for the true no-adverse-effect-level (NAEL). In this case the starting point for the DNEL calculation is a NOAEL, derived from a study which is of good quality and without uncertainties. Therefore, the default assessment factor, as a standard procedure, is 1.
- AF for differences in duration of exposure:
- 6
- Justification:
- In accordance with ECHA Guidance R.8 (v2.1, 2012), a factor allowing for differences in the experimental exposure duration and the duration of exposure for the worker and scenario under consideration needs to be considered taking into account that a) in general the experimental NOAEL will decrease with increasing exposure times and b) other and more serious adverse effects may appear with increasing exposure times. Consequently, to end up with the most conservative DNEL for repeated dose toxicity, chronic exposure is the ‘worst case’. So, as only a sub-acute toxicity study is available, default assessment factor of 6 is to be applied, as a standard procedure.
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- In accordance with ECHA Guidance R.8 (v2.1, 2012), as long as route-to-route extrapolation is not needed, allometric scaling should not be applied in cases where doses in experimental animal studies are expressed as concentrations (e.g. in mg/m3 air, ppm in diet, or mg/L in the drinking water) as these are assumed to be already scaled according to the allometric principle, since ventilation rate and food intake directly depend on the basal metabolic rate. In this case the NOAEC is expressed as concentration (mg/m³), therefore a factor for allometric scaling is not needed. In ECETOC Derivation of Assessment Factors for Human Health Risk Assessment – Technical Report No. 86 and ECETOC Guidance on Assessment Factors to Derive a DNEL – Technical Report No. 110, a similar approach is followed. The rationale here is that allometric scaling should not be applied because in humans inhalation rate is 4-fold lower compared to rat according to the slower metabolic rate and thereby the allometric species difference is already implicitly taken into account.
- AF for other interspecies differences:
- 2.5
- Justification:
- In accordance with ECHA Guidance R.8 (v2.1, 2012), as long as no substance-specific data are available, an additional factor of 2.5 for other interspecies differences, i.e. toxicokinetic differences not related to metabolic rate and toxicodynamic differences, is applied.
- AF for intraspecies differences:
- 5
- Justification:
- In accordance with ECETOC Derivation of Assessment Factors for Human Health Risk Assessment – Technical Report No. 86 (2003) and ECETOC Guidance on Assessment Factors to Derive a DNEL – Technical Report No. 110 (2010), a default assessment factor for the general population is based on the distributions of human data for various toxicokinetic and toxicodynamic parameters. The upper extreme of the variability in these data was estimated by calculating the 95th percentile of the distribution, which is considered sufficiently conservative to account for intraspecies variability in the general population (the data analysed included both sexes, a variety of disease states and ages). This results in recommended default assessment factor of 5 for the general population. As the worker population is more homogeneous (i.e. younger, healthier, protected from exposures), a default assessment factor of 3 is recommended. This proposal of ECETOC is based on an evaluation of the available scientific literature while the ECHA Guidance R.8 (v2.1, 2012) refers to standard default procedures. Until the scientific basis for using an alternative approach has been established, it is proposed to follow the ECETOC guideline.
- AF for the quality of the whole database:
- 1
- Justification:
- In accordance with ECHA Guidance R.8 (v2.1, 2012), the evaluation of the total toxicological database should include an assessment whether the available information as a whole meets the tonnage driven data requirements necessary to fulfil the REACH requirements, or whether there are data gaps (completeness of the database). Furthermore, the hazard data should be assessed for the reliability and consistency across different studies and endpoints and taking into account the quality of the testing method, size and power of the study design, biological plausibility, dose-response relationships and statistical association (adequacy of the database). When taking into account the standard information requirements and the completeness and consistency of the database the default assessment factor of 1, to be applied for good/standard quality of the database, is recommended.
- AF for remaining uncertainties:
- 1
- Justification:
- default (DNEL derivation based on a GLP and OECD TG study)
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:
- 1.13 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- other: ECHA REACH guidance and ECETOC guidance for intraspecies differences
- Overall assessment factor (AF):
- 300
- Dose descriptor starting point:
- NOAEL
- Value:
- 339 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
The starting point is a NOAEL (oral administration) of 339.0 mg/kg bw. In accordance with ECHA Guidance on information requirements and chemical safety assessment – R.8: Characterisation of dose [concentration]-response for human health (v2.1, 2012), in absence of data on absorption via the dermal route, a worst case assumption has to be made. As it is assumed that, in general, dermal absorption will not be higher than oral absorption, no default factor (i.e. factor 1) is introduced.
- AF for dose response relationship:
- 1
- Justification:
- In accordance with ECHA Guidance R.8 (v2.1, 2012), for the dose-response relationship, consideration should be given to the uncertainties in the dose descriptor (NOAEL, benchmark dose…) as the surrogate for the true no-adverse-effect-level (NAEL). In this case the starting point for the DNEL calculation is a NOAEL, derived from a study which is of good quality and without uncertainties. Therefore, the default assessment factor, as a standard procedure, is 1.
- AF for differences in duration of exposure:
- 6
- Justification:
- In accordance with ECHA Guidance R.8 (v2.1, 2012), a factor allowing for differences in the experimental exposure duration and the duration of exposure for the worker and scenario under consideration needs to be considered taking into account that a) in general the experimental NOAEL will decrease with increasing exposure times and b) other and more serious adverse effects may appear with increasing exposure times. Consequently, to end up with the most conservative DNEL for repeated dose toxicity, chronic exposure is the ‘worst case’. So, as only a sub-acute toxicity study is available, default assessment factor of 6 is to be applied, as a standard procedure.
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- In accordance with ECHA Guidance R.8 (v2.1, 2012), allometric scaling extrapolates doses according to an overall assumption that equitoxic doses (when expressed in mg/kg bw/day) scale with body weight to the power of 0.75. This results a default allometric scaling factor for the rat when compared with humans, namely 4. In ECETOC TR86 Derivation of Assessment Factors for Human Health Risk Assessment (2003) and ECETOC TR110 Guidance on Assessment Factors to Derive a DNEL (2010), a similar approach is followed. Toxicokinetic differences can be explained by basal metabolic rate which can be accounted for by allometric scaling. The underlying principle is that due to the faster metabolic rate of small animals, humans would less effectively detoxify and/or excrete xenobiotics than laboratory animals and thus are more vulnerable. The allometric scaling factor for the rat versus humans is 4.
- AF for other interspecies differences:
- 2.5
- Justification:
- In accordance with ECHA Guidance R.8 (v2.1, 2012), as long as no substance-specific data are available, an additional factor of 2.5 for other interspecies differences, i.e. toxicokinetic differences not related to metabolic rate and toxicodynamic differences, is applied.
- AF for intraspecies differences:
- 5
- Justification:
- n accordance with ECETOC TR86 (2003) and ECETOC TR110 (2010), a default assessment factor for the general population is based on the distributions of human data for various toxicokinetic and toxicodynamic parameters. The upper extreme of the variability in these data was estimated by calculating the 95th percentile of the distribution, which is considered sufficiently conservative to account for intraspecies variability in the general population (the data analysed included both sexes, a variety of disease states and ages). This results in recommended default assessment factor of 5 for the general population. As the worker population is more homogeneous (i.e. younger, healthier, protected from exposures), a default assessment factor of 3 is recommended. This proposal of ECETOC is based on an evaluation of the available scientific literature while the ECHA Guidance R.8 (v2.1, 2012) refers to standard default procedures. Until the scientific basis for using an alternative approach has been established, it is proposed to follow the ECETOC guideline.
- AF for the quality of the whole database:
- 1
- Justification:
- n accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose [concentration]-response for human health, the evaluation of the total toxicological database should include an assessment whether the available information as a whole meets the tonnage driven data requirements necessary to fulfil the REACH requirements, or whether there are data gaps (completeness of the database). Furthermore, the hazard data should be assessed for the reliability and consistency across different studies and endpoints and taking into account the quality of the testing method, size and power of the study design, biological plausibility, dose-response relationships and statistical association (adequacy of the database). When taking into account the standard information requirements and the completeness and consistency of the database the default assessment factor of 1, to be applied for good/standard quality of the database, is recommended.
- AF for remaining uncertainties:
- 1
- Justification:
- default (DNEL derivation based on a GLP and OECD TG study)
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 1 300 µg/cm²
- Most sensitive endpoint:
- sensitisation (skin)
DNEL related information
- DNEL derivation method:
- other: ECHA REACH guidance and ECETOC guidance
- Overall assessment factor (AF):
- 5
- Dose descriptor:
- other: human NOEL
- Value:
- 65 000 mg/m³
- AF for dose response relationship:
- 1
- Justification:
- In accordance with ECHA Guidance on information requirements and chemical safety assessment – R.8: Characterisation of dose [concentration]-response for human health (v2.1, 2012), for the LLNA study an assessment factor of 1 is applicable, because 1) the NOAEL is used as a starting point; 2) the doses were well separated (10, 25 and 50%) and; 3) a dose response was observed (stimulation index was 2.27, 2.98 and 3.53% respectively).
- AF for differences in duration of exposure:
- 1
- Justification:
- In accordance with ECHA Guidance R.8 (v2.1, 2012), for the dose-response relationship, the LLNA is considered to be sufficiently sensitive for assessing skin sensitization; 1) considering presence and absence of skin sensitization and; 2) determining a quantitative value for risk characterization (see note 17 in R.8, Application of AFs to the correct starting point to obtain the induction-specific DNEL, page 125, 1st part). Therefore, an assessment factor of 1 is applicable.
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- An assessment factor for interspecies differences is not needed as the starting dose descriptor is the human NOEL for skin sensitisation, which is considered to match to the EC3 in the LLNA in mice; see also explanation for hazard conclusion.
- AF for other interspecies differences:
- 1
- Justification:
- An assessment factor for other interspecies differences is not needed as the starting dose descriptor is the human NOEL for skin sensitisation, which is considered to match to the EC3 in the LLNA in mice; see also explanation for hazard conclusion.
- AF for intraspecies differences:
- 5
- Justification:
- In accordance with ECETOC TR86 Derivation of Assessment Factors for Human Health Risk Assessment (2003) and ECETOC TR110 Guidance on Assessment Factors to Derive a DNEL (2010), a default assessment factor for the general population is based on the distributions of human data for various toxicokinetic and toxicodynamic parameters. The upper extreme of the variability in these data was estimated by calculating the 95th percentile of the distribution, which is considered sufficiently conservative to account for intraspecies variability in the general population (the data analysed included both sexes, a variety of disease states and ages). This results in recommended default assessment factor of 5 for the general population. As the worker population is more homogeneous (i.e. younger, healthier, protected from exposures), a default assessment factor of 3 is recommended. This proposal of ECETOC is based on an evaluation of the available scientific literature while the ECHA Guidance R.8 (v2.1, 2012) refers to standard default procedures. Until the scientific basis for using an alternative approach has been established, it is proposed to follow the ECETOC guideline.
- AF for the quality of the whole database:
- 1
- Justification:
- In accordance with ECHA Guidance R.8 (v2.1, 2012), the evaluation of the total toxicological database should include an assessment whether the available information as a whole meets the tonnage driven data requirements necessary to fulfil the REACH requirements, or whether there are data gaps (completeness of the database). Furthermore, the hazard data should be assessed for the reliability and consistency across different studies and endpoints and taking into account the quality of the testing method, size and power of the study design, biological plausibility, dose-response relationships and statistical association (adequacy of the database). When taking into account the standard information requirements and the completeness and consistency of the database the default assessment factor of 1, to be applied for good/standard quality of the database, is recommended.
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
General Population - Hazard via oral route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 1.13 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- other: ECHA REACH guidance and ECETOC guidance for intraspecies differences
- Dose descriptor starting point:
- NOAEL
- Value:
- 339 mg/kg bw/day
- AF for dose response relationship:
- 1
- Justification:
- DNEL calculation is a NOAEL, derived from a study which is of good quality and without uncertainties. Therefore, the default assessment factor, as a standard procedure, is 1.
- AF for differences in duration of exposure:
- 6
- Justification:
- Consequently, to end up with the most conservative DNEL for repeated dose toxicity, chronic exposure is the ‘worst case’. So, as only a sub-acute toxicity study is available, default assessment factor of 6 is to be applied, as a standard procedure.
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- In accordance with ECHA Guidance R.8 (v2.1, 2012), as long as route-to-route extrapolation is not needed, allometric scaling should not be applied in cases where doses in experimental animal studies are expressed as concentrations (e.g. in mg/m3 air, ppm in diet, or mg/L in the drinking water) as these are assumed to be already scaled according to the allometric principle, since ventilation rate and food intake directly depend on the basal metabolic rate. In this case the NOAEC is expressed as concentration (mg/m³), therefore a factor for allometric scaling is not needed. In ECETOC Derivation of Assessment Factors for Human Health Risk Assessment – Technical Report No. 86 and ECETOC Guidance on Assessment Factors to Derive a DNEL – Technical Report No. 110, a similar approach is followed. The rationale here is that allometric scaling should not be applied because in humans inhalation rate is 4-fold lower compared to rat according to the slower metabolic rate and thereby the allometric species difference is already implicitly taken into account.
- AF for other interspecies differences:
- 2.5
- Justification:
- In accordance with ECHA Guidance R.8 (v2.1, 2012), as long as no substance-specific data are available, an additional factor of 2.5 for other interspecies differences, i.e. toxicokinetic differences not related to metabolic rate and toxicodynamic differences, is applied.
- AF for intraspecies differences:
- 5
- Justification:
- In accordance with ECETOC Derivation of Assessment Factors for Human Health Risk Assessment – Technical Report No. 86 (2003) and ECETOC Guidance on Assessment Factors to Derive a DNEL – Technical Report No. 110 (2010), a default assessment factor for the general population is based on the distributions of human data for various toxicokinetic and toxicodynamic parameters. The upper extreme of the variability in these data was estimated by calculating the 95th percentile of the distribution, which is considered sufficiently conservative to account for intraspecies variability in the general population (the data analysed included both sexes, a variety of disease states and ages). This results in recommended default assessment factor of 5 for the general population. As the worker population is more homogeneous (i.e. younger, healthier, protected from exposures), a default assessment factor of 3 is recommended. This proposal of ECETOC is based on an evaluation of the available scientific literature while the ECHA Guidance R.8 (v2.1, 2012) refers to standard default procedures. Until the scientific basis for using an alternative approach has been established, it is proposed to follow the ECETOC guideline.
- AF for the quality of the whole database:
- 1
- Justification:
- In accordance with ECHA Guidance R.8 (v2.1, 2012), the evaluation of the total toxicological database should include an assessment whether the available information as a whole meets the tonnage driven data requirements necessary to fulfil the REACH requirements, or whether there are data gaps (completeness of the database). Furthermore, the hazard data should be assessed for the reliability and consistency across different studies and endpoints and taking into account the quality of the testing method, size and power of the study design, biological plausibility, dose-response relationships and statistical association (adequacy of the database). When taking into account the standard information requirements and the completeness and consistency of the database the default assessment factor of 1, to be applied for good/standard quality of the database, is recommended.
- AF for remaining uncertainties:
- 1
- Justification:
- default (DNEL derivation based on a GLP and OECD TG study)
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
General Population - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- hazard unknown but no further hazard information necessary as no exposure expected
Additional information - General Population
There are no consumer uses known for EMIM DCA. However, for the assessment of the AC13, the DNELs for the general population were derived.
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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