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EC number: 939-600-0 | CAS number: 1471316-27-4
- 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:
- 196 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):
- 4.5
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 882 mg/m³
- Explanation for the modification of the dose descriptor starting point:
- Route specific dose descriptor is not available.
- AF for dose response relationship:
- 1
- Justification:
- NOAEL is chosen as starting point.
- AF for differences in duration of exposure:
- 1.5
- Justification:
- Batke et al., 2011
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- AF not used for inhalation route.
- AF for other interspecies differences:
- 1
- Justification:
- ECETOC, Technical Report No. 110
- AF for intraspecies differences:
- 3
- Justification:
- ECETOC, Technical Report No. 110
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:
- 1 042 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):
- 24
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 25 000 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
- Route specific dose descriptor is not available.
- AF for dose response relationship:
- 1
- Justification:
- NOAEL is chosen as starting point.
- AF for differences in duration of exposure:
- 2
- Justification:
- ECETOC, Technical Report No. 110
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- Species: rat
- AF for other interspecies differences:
- 1
- Justification:
- ECETOC, Technical Report No. 110
- AF for intraspecies differences:
- 3
- Justification:
- ECETOC, Technical Report No. 110
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
Workers - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- no hazard identified
Additional information - workers
Conversion of oral NOAEL to inhalatory NAEC
Since there is no dose descriptor for every exposure route, dose descriptors were converted into a correct starting point by route-to-route extrapolation based on the ECHA guidance document "Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose [concentration]-response for human health", November 2012.
The conversion of an oral NOAEL (500 mg/kg bw/d; Hendy, 1982) into an inhalatory NAEC is performed using the following equation; for workers the resulting concentration needs to be additionally corrected for the difference between basal caloric demand and caloric demand under light activity:
Corrected inhalatory NAEC = oral NOAEL x 1/sRVratx ABSoral-rat/ ABSinh-humanx sRVhuman/wRV
= oral NOAEL mg/kg bw/d x 1/0.38m³/kg bw x 1 x 6.7 m³/10 m³
sRV: standard respiratory volume, ABS: absorption, wRV: worker respiratory volume
Thus, the corrected starting point for inhalation route was 500 x 6.7 / (10 x 0.38) = 882 mg/m3
DNEL derivation using the inhalatory NAEC
In the ECHA Guidance a factor of 2 is suggested for the extrapolation from oral to inhalation absorption. On the contrary, the Technical guidance document on risk assessment in support of Commission directive 93/67/EEC, 2003 appendix IV A and B gives a number of physico-chemical properties that normally determine oral, inhalation and dermal absorption. These parameters include molecular weight, log Kow, pKa values and for inhalation also particle size distribution, vapour pressure etc. Molecules with a molecular weight < 500 and a log Kow between 0 and 4 can be assumed to be well absorbed equivalently by the oral and inhalation route. Oral absorption may be reduced for acids and bases depending on their pKa value and their possibility of absorption in the GI tract. More lipophilic substances may be better absorbed in the GI tract due to the solubilisation with bile acids and thus oral absorption may be higher than inhalation absorption. Physico-chemical and toxicokinetic parameters should be considered before using default assumptions. It is assumed that the absorption rate of AEs after oral application is almost complete (>75%, see IUCLID section 7.1). Therefore, and unless valid data suggest that inhalation leads to higher absorption than oral ingestion, equal absorption will be assumed when extrapolating from oral to inhalation route. Thus, the factor of 2 is considered to be not relevant for AE. Due to their structural similarity this assumption can also be made for alcohols propoxylated.
To extrapolate from the sub-chronic to chronic situation an assessment factor of 1.5 was applied. This assessment factor is supported by a publication of the Fraunhofer Institute for Toxicology and Experimental Medicine in cooperation with Cognis GmbH (Batke et al., 2011). Within this publication large datasets of repeated dose toxicity studies were evaluated to derive a scientifically sound assessment factor for time extrapolation, based on NOEL/C or LOEL/C ratios (short term N(L)OEL/long term N(L)OEL) for oral or inhalation administration. It was shown that an extrapolation factor of 1.5 should be used to extrapolate from the sub-chronic to the chronic situation for both, the oral and the inhalation route. Based on this newly available scientific evaluation of repeated dose toxicity studies, a time extrapolation factor of 1.5 is used. For the dermal route a factor of 2 was used as recommended by ECETOC, Technical Report No. 110
Factors applied for interspecies differences (1) and intraspecies differences (3) were applied according to ECETOC Technical Report No.110. ECETOC Assessment factors were used as these AFs are based on a critical and extensive review of the literature and represent a current state of the scientific knowledge.
Thus, the inhalatory DNEL is calculated to be 196 mg/m3.
Conversion of oral NOAEL to dermal NAEL
To convert an oral NOAEL into a dermal NAEL, the differences in absorption between routes as well as differences in dermal absorption between rats and humans have to be accounted for.
The dermal penetration rate for alcohol ethoxylates was calculated on the basis of a dermal penetration study with 14C-labelled C12EO6 in two human volunteers (Drotman, 1980). This penetration rate is derived from measured data and assumes - conservatively - 2% absorption within the first 24 h following dermal application.
In the study, however, the maximum systemically available C12AE6 after 144 h exposure was determined to be 1.82%. It should be noted that the study was performed only on few test subjects and that reporting was limited. However, the study clearly demonstrated that AEs penetrate poorly through human skin and clearly less readily than through rat skin. The human study was therefore judged to represent reliably the systemic availability of AEs in humans following dermal exposures to AE containing cleaning products.
It should also be noted that studies in hairless mice have shown that cutaneous absorption decreases with increasing degree of ethoxylation (EO6 to EO10) (Nishiyama et al., 1983). Thus, calculating dermal exposures to the whole range of AEs on the basis of a dermal penetration rate derived from a low ethoxylated AE such as C12AE6 can be considered as a conservative scenario. The low dermal penetration rate is also assumed for alcohols propoxlytated due to their structural similarity.
Thus, an absorption rate of 2 % after dermal application was used to correct the dermal NAEL for the differences in the absorption rate.
Corrected dermal NAEL = oral NOAEL x ABSoral-rat/ABSdermal
= oral NOAEL mg/kg bw/d x 100% / 2%
ABS: absorption
Thus, the corrected starting point for dermal route was 500 x 100 / 2 = 25000 mg/kg bw/d.
DNEL derivation using the dermal NAEC
Factors applied for differences in exposure duration (2), allometric scaling (4), interspecies differences (1) and intraspecies differences (3) were applied according to ECETOC Technical Report No.110. ECETOC Assessment factors were used as these AFs are based on a critical and extensive review of the literature and represent a current state of the scientific knowledge.
Thus, the dermal DNEL is calculated to be 1042 mg/kg bw/d.
Since short-term exposure scenarios will not be assessed, only long-term DNELs for workers are derived. The oral route is not relevant for workers. In addition it is assumed that only workers will come in contact with the neat substances.
References:
Batke et al. 2011
M. Batke, S. Escher ,S. Hoffmann-Doerr, C. Melber ,H. Messinger, I. Mangelsdorf
Evaluation of time extrapolation factors based on the database RepDose. Toxicology Letters 205 (2011) 122– 129
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 58 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):
- 7.5
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 435 mg/m³
- Explanation for the modification of the dose descriptor starting point:
- Route specific dose descriptor is not available.
- AF for dose response relationship:
- 1
- Justification:
- NOAEL is chosen as starting point.
- AF for differences in duration of exposure:
- 1.5
- Justification:
- Batke et al., 2011
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- AF not used for inhalation route.
- AF for other interspecies differences:
- 1
- Justification:
- ECETOC, Technical Report No. 110
- AF for intraspecies differences:
- 5
- Justification:
- ECETOC, Technical Report No. 110
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:
- 625 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):
- 40
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 25 000 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
- Route specific dose descriptor is not available.
- AF for dose response relationship:
- 1
- Justification:
- NOAEL is chosen as starting point.
- AF for differences in duration of exposure:
- 2
- Justification:
- ECETOC, Technical Report No. 110
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- Species: rat
- AF for other interspecies differences:
- 1
- Justification:
- ECETOC, Technical Report No. 110
- AF for intraspecies differences:
- 5
- Justification:
- ECETOC, Technical Report No. 110
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
General Population - Hazard via oral route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 17 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):
- 30
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 500 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
- not applicable
- AF for dose response relationship:
- 1
- Justification:
- NOAEL is chosen as starting point.
- AF for differences in duration of exposure:
- 1.5
- Justification:
- Batke et al., 2011
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- Species: rat
- AF for other interspecies differences:
- 1
- Justification:
- ECETOC, Technical Report No. 110
- AF for intraspecies differences:
- 5
- Justification:
- ECETOC, Technical Report No. 110
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
Conversion of oral NOAEL to inhalatory NAEC
Since there is no dose descriptor for every exposure route, dose descriptors were converted into a correct starting point by route-to-route extrapolation based on the ECHA guidance document "Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose [concentration]-response for human health", November 2012.
The conversion of an oral NOAEL(500 mg/kg bw/d; Hendy, 1982) into an inhalatory NAEC is performed using the following equation:
Corrected inhalatory NAEC = oral NOAEL x 1/sRVrat x ABSoral-rat/ABSinh-human
= oral NOAELmg/kg bw/dx 1/1.15 m³/kg bw x 1
sRV: standard respiratory volume, ABS: absorption
Thus, the corrected starting point for inhalation route was 500 x 1 / 1.15 = 435 mg/m3
DNEL derivation using the inhalatory NAEC
In the ECHA Guidance a factor of 2 is suggested for the extrapolation from oral to inhalation absorption. On the contrary, the Technical guidance document on risk assessment in support of Commission directive 93/67/EEC, 2003 appendix IV A and B gives a number of physico-chemical properties that normally determine oral, inhalation and dermal absorption. These parameters include molecular weight, log Kow, pKa values and for inhalation also particle size distribution, vapour pressure etc. Molecules with a molecular weight < 500 and a log Kow between 0 and 4 can be assumed to be well absorbed equivalently by the oral and inhalation route. Oral absorption may be reduced for acids and bases depending on their pKa value and their possibility of absorption in the GI tract. More lipophilic substances may be better absorbed in the GI tract due to the solubilisation with bile acids and thus oral absorption may be higher than inhalation absorption. Physico-chemical and toxicokinetic parameters should be considered before using default assumptions. It is assumed that the absorption rate of AEs after oral application is almost complete (>75%, see IUCLID section 7.1). Therefore, and unless valid data suggest that inhalation leads to higher absorption than oral ingestion, equal absorption will be assumed when extrapolating from oral to inhalation route. Thus, the factor of 2 is considered to be not relevant for AEs. Due to their structural similarity this assumption can also be made for alcohols propoxylated.
To extrapolate from the sub-chronic to chronic toxicity an assessment factor of 1.5 was applied. This assessment factor is supported by a publication of the Fraunhofer Institute for Toxicology and Experimental Medicine in cooperation with Cognis GmbH (Batke et al., 2011). Within this publication large datasets of repeated dose toxicity studies were evaluated to derive a scientifically sound assessment factor for time extrapolation, based on NOEL/C or LOEL/C ratios (short term N(L)OEL/long term N(L)OEL) for oral or inhalation administration. It was shown that an extrapolation factor of 1.5 should be used to extrapolate from the sub-chronic to the chronic situation for both, the oral and the inhalation route. Based on this newly available scientific evaluation of repeated dose toxicity studies a time extrapolation factor of 1.5 is used. For the dermal route a factor of 2 was used as recommended by ECETOC, Technical Report No. 110
Factors applied for interspecies differences (1) and intraspecies differences (5) were applied according to ECETOC Technical Report No.110. ECETOC Assessment factors were used as these AFs are based on a critical and extensive review of the literature and represent a current state of the scientific knowledge.
Thus, the inhalatory DNEL is calculated to be 58 mg/m3.
Conversion of oral NOAEL to dermal NAEL
To convert an oral NOAEL into a dermal NAEL, the differences in absorption between routes as well as differences in dermal absorption between rats and humans have to be accounted for.
The dermal penetration rate for alcohol ethoxylates was calculated on the basis of a dermal penetration study with 14C-labelled C12EO6 in two human volunteers (Drotman, 1980). This penetration rate is derived from measured data and assumes - conservatively - 2% absorption within the first 24 h following dermal application.
In the study, however, the maximum systemically available C12AE6 after 144 h exposure was determined to be 1.82%. It should be noted that the study was performed only on few test subjects and that reporting was limited. However, the study clearly demonstrated that AEs penetrate poorly through human skin and clearly less readily than through rat skin. The human study was therefore judged to represent more reliably the systemic availability of AEs in humans following dermal exposures to AE containing cleaning products. It should also be noted that studies in hairless mice have shown that cutaneous absorption decreases with increasing degree of ethoxylation (EO6 to EO10) (Nishiyama et al., 1983). Thus, calculating dermal exposures to the whole range of AEs on the basis of a dermal penetration rate derived from a low ethoxylated AE such as C12AE6 can be considered as a conservative scenario. The low dermal penetration rate is also assumed for alcohols propoxylated due to their structural similarity.
Thus, an absorption rate of 2 % after dermal application was used to correct the dermal NAEL for the differences in the absorption rate.
Corrected dermal NAEL = oral NOAEL x ABSoral-rat/ABSdermal
= oral NOAELmg/kg bw/d x100% / 2%
ABS: absorption
Thus, the corrected starting point for dermal route was 500 x 100 / 2 = 25000 mg/kg bw/d.
DNEL derivation using the dermal NAEC
Factors applied for differences in exposure duration (2), allometric scaling (4), interspecies differences (1) and intraspecies differences (5) were applied according to ECETOC Technical Report No.110. ECETOC Assessment factors were used as these AFs are based on a critical and extensive review of the literature and represent a current state of the scientific knowledge.
Thus, the dermal DNEL is calculated to be 625 mg/kg bw/d.
Since short-term exposure scenarios will not be assessed, only long-term DNELs for general population are derived.
DNEL derivation for oral route
To extrapolate from the sub-chronic to chronic toxicity an assessment factor of 1.5 was applied. This assessment factor is supported by a publication of the Fraunhofer Institute for Toxicology and Experimental Medicine in cooperation with Cognis GmbH (Batke et al., 2011). Within this publication large datasets of repeated dose toxicity studies were evaluated to derive a scientifically sound assessment factor for time extrapolation, based on NOEL/C or LOEL/C ratios (short term N(L)OEL/long term N(L)OEL) for oral or inhalation administration. It was shown that an extrapolation factor of 1.5 should be used to extrapolate from the sub-chronic to the chronic situation for both, the oral and the inhalation route. Based on this newly available scientific evaluation of repeated dose toxicity studies a time extrapolation factor of 1.5 is used.
Factors applied for allometric scaling (4), interspecies differences (1) and intraspecies differences (5) were applied according to ECETOC Technical Report No.110. ECETOC Assessment factors were used as these AFs are based on a critical and extensive review of the literature and represent a current state of the scientific knowledge.
Thus, the oral DNEL is calculated to be 17 mg/kg bw/d.
References:
Batke et al. 2011
M. Batke, S. Escher ,S. Hoffmann-Doerr, C. Melber ,H. Messinger, I. Mangelsdorf
Evaluation of time extrapolation factors based on the database RepDose. Toxicology Letters 205 (2011) 122– 129
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