Registration Dossier
Registration Dossier
Diss Factsheets
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EC number: 271-360-6 | CAS number: 68551-08-6
- 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:
- 36.7 mg/m³
- Most sensitive endpoint:
- developmental toxicity / teratogenicity
- Route of original study:
- Oral
DNEL related information
- Overall assessment factor (AF):
- 24
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 881.6 mg/m³
- Explanation for the modification of the dose descriptor starting point:
Per ECHA guidance (Pg21, Figure R.8-3, Chapter R.8:Characterisation of dose [concentration]-response for human health https://echa.europa.eu/documents/10162/13632/information_requirements_r8_en.pdf):
500mg/kg/d (oral NOAEL) was converted to an 8 hour worker inhalatory NOAEC using the following equation:
Inhalatory NOAEC = [oral NOAEL*(1/sRVrat)*(ABSoral-rat)/ABSinh-human)*(sRVhuman/wRV)]
Inhalatory NOAEC = [500mg/kg/d*(1/0.38m3/kg/d)*(100/100)*(6.7m3/10m3)]
Inhalatory NOAEC = 881.6mg/m3
- AF for dose response relationship:
- 1
- Justification:
- The point of departure is a NOAEL from an OECD guideline study.
- AF for differences in duration of exposure:
- 1
- Justification:
- The exposure window of the key study (per OECD 414 guideline) was approximately two weeks. However, the exposure duration encompassed the entire developmental window (GD6-20; from parturition to closing of the palate); as such, there is no applicable equivalent extrapolation for exposure duration to a chronic exposure, as the exposure duration in the study reflects the entire developmental window.
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- ECHA guidance states that “If no substance-specific data are available, the standard procedure for threshold effects would be, as a default, to correct for differences in metabolic rate (allometric scaling)…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 in different default allometric scaling factors for the different animal species when compared with humans.”
Thus, for the key study, the allometric factor is 4 (rat-human extrapolation). - AF for other interspecies differences:
- 1
- Justification:
- ECHA guidance states the following regarding interspecies differences:
“…the standard procedure for threshold effects would be, as a default, to correct for differences in metabolic rate (allometric scaling) and to apply an additional factor of 2.5 for other interspecies differences, i.e. toxicokinetic differences not related to metabolic rate (small part) and toxicodynamic differences (larger part). In case substance-specific information shows specific susceptibility differences between species, which are not related to differences in basal metabolic rate, the additional factor of 2.5 for ‘remaining differences’ should be modified accordingly.”
The Fraunhofer Institute for Toxicology and Experimental Medicine has published evidence that applying 2.5 as a standard ‘remaining’ interspecies differences is not necessarily applicable based on available evidence (Escher and Mangelsdorf, 2009; Batke et al, 2010; Bitsch et al, 2006). The RepDose database has been utilized to extract data on repeat dose toxicity studies, and probabilistic modeling exercises have examined time- and interspecies-extrapolations which included chemicals under comparable exposure and route of application to demonstrate the sufficiency of an allometric factor application to account for interspecies differences (Escher et al. 2013). At time of publication, the RepDose database contained 2500 repeat dose toxicity studies (rodent) with data on approximately 700 organic chemicals, and study authors utilized a subset of these studies to derive the geometric mean (GM) of fitted distributions and corrected for allometric scaling (GM = 0.91 median AF/1.03 all AF) to arrive at this conclusion (Escher et al. 2013). This conclusion aligns with previously reported GMs of 1 for interspecies differences (Schneider et al. 2005, Rennen et al. 2001).
See information panel attachment for references. - AF for intraspecies differences:
- 3
- Justification:
- While ECHA guidance suggests an AF of 5 to account for intraspecies variability within worker populations, this can be further refined with published analyses. An AF of 3 is applied for worker populations, based on assessments of variability in toxicokinetics and toxicodynamics in healthy, adult human populations. A small study (7 toxicokinetic and 8 toxicodynamic studies) concluded that an AF of 3-4 would address the uncertainty in 99% of the healthy adult population for 80% of the substances assessed (Renwick, 1991). A more extensive study analyzed a more robust dataset (toxicokinetic data on 60 substances and 49 substances with toxicodynamic data) to assess human variability and resulted in recommendation of an AF for 3.2 to cover 95% of the population; since most of the studies included health young adults only, this AF recommendation is more appropriate for workers than the general population (Renwick and Lazarus, 1998). Further research was conducted to refine our understanding of metabolism in healthy adult populations in which variability of key metabolic enzymes in healthy populations (ie polymorphisms do not impact susceptibility), and determined that an AF of 3.2 would cover ≥99% of healthy adults (Falk-Filipsson, 2007).
Falk-Filipsson A, Hanberg A, Victorin K, Warholm M, Wallen M. 2007. Assessment factors— Applications in health risk assessment of chemicals. Environ Res 104:108-127.
Renwick AG. 1991. Safety factors and establishment of acceptable daily intakes. Food Additives and Contaminants: Part A: Chemistry, Analysis, Control, Exposure and Risk Assessment, 1944-0057, 8(2):135-149.
Renwick AG, Lazarus NR. 1998. Human variability and noncancer risk assessment – an analysis of the default uncertainty factor. Regul Toxicol Pharmacol 27:3-20. - AF for the quality of the whole database:
- 1
- Justification:
- The test substance is part of a well-understood category of aliphatic alcohols, for which category documents are available (OECD SIDS, USEPA HPV), in addition to product registrations through EU REACH. The key study for the derivation of the DNELs in this dossier are from an OECD guideline developmental study done to GLP standards (Charles River Laboratories, Study ID 438046, 2020). Because this assessment factor is intended to adjust for missing data on sensitive endpoints (ie developmental exposures), the database on this substance is considered sufficiently robust.
- AF for remaining uncertainties:
- 2
- Justification:
- Route-to-route extrapolation uncertainty in characterizing an inhalation hazard using an oral exposure 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:
- 417 mg/kg bw/day
- Most sensitive endpoint:
- developmental toxicity / teratogenicity
- Route of original study:
- Oral
DNEL related information
- Overall assessment factor (AF):
- 12
- Dose descriptor starting point:
- NOAEL
- Value:
- 500 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 5 000 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
Based on Guidance on information requirements and chemical safety assessment, (Chapter R.7a) the following considerations for dermal absorptions were made:
1) The log Kow is 4.2; therefore the substance is not expected to migrate from the stratum corneum to the epidermidis (log Kow>4 is associated with high lipophilicity) (OECD, 2011)
2) The molecular weight is 172 g/mol, so it does not meet the threshold of dermal absorption (below 100: in favor of dermal absorption, above 500, not in favor of absorption)
3) The substance is not classified as a skin irritant, and dermal LD50 >3160mg/kg bw
Therefore, dermal absorption is set to 10%.
OECD (2011) Guidance Notes On Dermal Absorption. Environment, Health and Safety Publications, Series on Testing and Assessment No. 156 (ENV/JM/MONO(2011)36).
- AF for dose response relationship:
- 1
- Justification:
- The point of departure is a NOAEL from an OECD guideline study.
- AF for differences in duration of exposure:
- 1
- Justification:
- The exposure window of the key study (per OECD 414 guideline) was approximately two weeks. However, the exposure duration encompassed the entire developmental window (GD6-20; from parturition to closing of the palate); as such, there is no applicable equivalent extrapolation for exposure duration to a chronic exposure, as the exposure duration in the study reflects the entire developmental window.
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- ECHA guidance states that “If no substance-specific data are available, the standard procedure for threshold effects would be, as a default, to correct for differences in metabolic rate (allometric scaling)…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 in different default allometric scaling factors for the different animal species when compared with humans.”
Thus, for the key study, the allometric factor is 4 (rat-human extrapolation). - AF for other interspecies differences:
- 1
- Justification:
- ECHA guidance states the following regarding interspecies differences:
“…the standard procedure for threshold effects would be, as a default, to correct for differences in metabolic rate (allometric scaling) and to apply an additional factor of 2.5 for other interspecies differences, i.e. toxicokinetic differences not related to metabolic rate (small part) and toxicodynamic differences (larger part). In case substance-specific information shows specific susceptibility differences between species, which are not related to differences in basal metabolic rate, the additional factor of 2.5 for ‘remaining differences’ should be modified accordingly.”
The Fraunhofer Institute for Toxicology and Experimental Medicine has published evidence that applying 2.5 as a standard ‘remaining’ interspecies differences is not necessarily applicable based on available evidence (Escher and Mangelsdorf, 2009; Batke et al, 2010; Bitsch et al, 2006). The RepDose database has been utilized to extract data on repeat dose toxicity studies, and probabilistic modeling exercises have examined time- and interspecies-extrapolations which included chemicals under comparable exposure and route of application to demonstrate the sufficiency of an allometric factor application to account for interspecies differences (Escher et al. 2013). At time of publication, the RepDose database contained 2500 repeat dose toxicity studies (rodent) with data on approximately 700 organic chemicals, and study authors utilized a subset of these studies to derive the geometric mean (GM) of fitted distributions and corrected for allometric scaling (GM = 0.91 median AF/1.03 all AF) to arrive at this conclusion (Escher et al. 2013). This conclusion aligns with previously reported GMs of 1 for interspecies differences (Schneider et al. 2005, Rennen et al. 2001). - AF for intraspecies differences:
- 3
- Justification:
- While ECHA guidance suggests an AF of 5 to account for intraspecies variability within worker populations, this can be further refined with published analyses. An AF of 3 is applied for worker populations, based on assessments of variability in toxicokinetics and toxicodynamics in healthy, adult human populations. A small study (7 toxicokinetic and 8 toxicodynamic studies) concluded that an AF of 3-4 would address the uncertainty in 99% of the healthy adult population for 80% of the substances assessed (Renwick, 1991). A more extensive study analyzed a more robust dataset (toxicokinetic data on 60 substances and 49 substances with toxicodynamic data) to assess human variability and resulted in recommendation of an AF for 3.2 to cover 95% of the population; since most of the studies included health young adults only, this AF recommendation is more appropriate for workers than the general population (Renwick and Lazarus, 1998). Further research was conducted to refine our understanding of metabolism in healthy adult populations in which variability of key metabolic enzymes in healthy populations (ie polymorphisms do not impact susceptibility), and determined that an AF of 3.2 would cover ≥99% of healthy adults (Falk-Filipsson, 2007).
Falk-Filipsson A, Hanberg A, Victorin K, Warholm M, Wallen M. 2007. Assessment factors— Applications in health risk assessment of chemicals. Environ Res 104:108-127.
Renwick AG. 1991. Safety factors and establishment of acceptable daily intakes. Food Additives and Contaminants: Part A: Chemistry, Analysis, Control, Exposure and Risk Assessment, 1944-0057, 8(2):135-149.
Renwick AG, Lazarus NR. 1998. Human variability and noncancer risk assessment – an analysis of the default uncertainty factor. Regul Toxicol Pharmacol 27:3-20. - AF for the quality of the whole database:
- 1
- Justification:
- The test substance is part of a well-understood category of aliphatic alcohols, for which category documents are available (OECD SIDS, USEPA HPV), in addition to product registrations through EU REACH. The key study for the derivation of the DNELs in this dossier are from an OECD guideline developmental study done to GLP standards (Charles River Laboratories, Study ID 438046, 2020). Because this assessment factor is intended to adjust for missing data on sensitive endpoints (ie developmental exposures), the database on this substance is considered sufficiently robust.
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
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 10.87 mg/m³
- Most sensitive endpoint:
- developmental toxicity / teratogenicity
- Route of original study:
- Oral
DNEL related information
- Overall assessment factor (AF):
- 40
- Dose descriptor starting point:
- NOAEL
- Value:
- 500 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 434.78 mg/m³
- Explanation for the modification of the dose descriptor starting point:
Per ECHA guidance (Pg21, Figure R.8-3, Chapter R.8:Characterisationof dose [concentration]-response for human healthhttps://echa.europa.eu/documents/10162/13632/information_requirements_r8_en.pdf):
500mg/kg/d (oral NOAEL) was converted to a 24 hour general population inhalatory NOAEC using the following equation:
Inhalatory NOAEC = [oral NOAEL*(1/sRVrat)*(ABSoral-rat)/ABSinh-human)*(ABSinh-rat/ABSinh-human)]
Inhalatory NOAEC = [500mg/kg/d*(1/1.15m3/kg/d)*(100/100)*(100/100)]
Inhalatory NOAEC = 434.78mg/m3
- AF for dose response relationship:
- 1
- Justification:
- The point of departure is a NOAEL from an OECD guideline study.
- AF for differences in duration of exposure:
- 1
- Justification:
- The exposure window of the key study (per OECD 414 guideline) was approximately two weeks. However, the exposure duration encompassed the entire developmental window (GD6-20; from parturition to closing of the palate); as such, there is no applicable equivalent extrapolation for exposure duration to a chronic exposure, as the exposure duration in the study reflects the entire developmental window.
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- ECHA guidance states that “If no substance-specific data are available, the standard procedure for threshold effects would be, as a default, to correct for differences in metabolic rate (allometric scaling)…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 in different default allometric scaling factors for the different animal species when compared with humans.”
Thus, for the key study, the allometric factor is 4 (rat-human extrapolation). - AF for other interspecies differences:
- 1
- Justification:
- ECHA guidance states the following regarding interspecies differences:
“…the standard procedure for threshold effects would be, as a default, to correct for differences in metabolic rate (allometric scaling) and to apply an additional factor of 2.5 for other interspecies differences, i.e. toxicokinetic differences not related to metabolic rate (small part) and toxicodynamic differences (larger part). In case substance-specific information shows specific susceptibility differences between species, which are not related to differences in basal metabolic rate, the additional factor of 2.5 for ‘remaining differences’ should be modified accordingly.”
The Fraunhofer Institute for Toxicology and Experimental Medicine has published evidence that applying 2.5 as a standard ‘remaining’ interspecies differences is not necessarily applicable based on available evidence (Escher and Mangelsdorf, 2009; Batke et al, 2010; Bitsch et al, 2006). The RepDose database has been utilized to extract data on repeat dose toxicity studies, and probabilistic modeling exercises have examined time- and interspecies-extrapolations which included chemicals under comparable exposure and route of application to demonstrate the sufficiency of an allometric factor application to account for interspecies differences (Escher et al. 2013). At time of publication, the RepDose database contained 2500 repeat dose toxicity studies (rodent) with data on approximately 700 organic chemicals, and study authors utilized a subset of these studies to derive the geometric mean (GM) of fitted distributions and corrected for allometric scaling (GM = 0.91 median AF/1.03 all AF) to arrive at this conclusion (Escher et al. 2013). This conclusion aligns with previously reported GMs of 1 for interspecies differences (Schneider et al. 2005, Rennen et al. 2001).
See information panel attachment for references. - AF for intraspecies differences:
- 5
- Justification:
- General Population: While ECHA guidance suggests an AF of 10 to account for intraspecies variability across the general population, this can be further refined with published analyses of extensive databases. An AF of 5 is applied for the general population, based on analysis of a database of 447 data groups of toxicokinetic and toxicodynamic data and resulted in the 95th or the 90th percentile for the intraspecies AF of the general human population estimated as approximately 6 and 4, respectively (Hattis, 2002).
Additionally, there is little scientific basis for the need of an additional AF for children of 6-12 months due to the rapid maturation of liver and kidney function in young children (ie within a few months of age) (Renwick, 1998). Because animals show similar patterns of immaturity to those found in humans, an increased AF would not be required because the DNEL is derived from a high quality developmental study in rats.
Hattis D, Baird S, Goble R. 2002. Drug Chem Toxico 25:403-436.
Renwick AG. 1998. Food Additives and Contaminants: Part A: Chemistry, Analysis, Control, Exposure and Risk Assessment, 1944-0057, 15(1):17-35. - AF for the quality of the whole database:
- 1
- Justification:
- The test substance is part of a well-understood category of aliphatic alcohols, for which category documents are available (OECD SIDS, USEPA HPV), in addition to product registrations through EU REACH. The key study for the derivation of the DNELs in this dossier are from an OECD guideline developmental study done to GLP standards (Charles River Laboratories, Study ID 438046, 2020). Because this assessment factor is intended to adjust for missing data on sensitive endpoints (ie developmental exposures), the database on this substance is considered sufficiently robust.
- AF for remaining uncertainties:
- 2
- Justification:
- Route-to-route extrapolation uncertainty in characterizing an inhalation hazard using an oral exposure 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:
- 250 mg/kg bw/day
- Most sensitive endpoint:
- developmental toxicity / teratogenicity
- Route of original study:
- Oral
DNEL related information
- Overall assessment factor (AF):
- 20
- Dose descriptor starting point:
- NOAEL
- Value:
- 500 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 5 000 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
Based on Guidance on information requirements and chemical safety assessment, (Chapter R.7a) the following considerations for dermal absorptions were made:
1) The log Kow is 4.2; therefore the substance is not expected to migrate from the stratum corneum to the epidermidis (log Kow>4 is associated with high lipophilicity) (OECD, 2011)
2) The molecular weight is 172 g/mol, so it does not meet the threshold of dermal absorption (below 100: in favor of dermal absorption, above 500, not in favor of absorption)
3) The substance is not classified as a skin irritant, and dermal LD50 >3160mg/kg bw
Therefore, dermal absorption is set to 10%.
OECD (2011) Guidance Notes On Dermal Absorption. Environment, Health and Safety Publications, Series on Testing and Assessment No. 156 (ENV/JM/MONO(2011)36).
- AF for dose response relationship:
- 1
- Justification:
- The point of departure is a NOAEL from an OECD guideline study.
- AF for differences in duration of exposure:
- 1
- Justification:
- The exposure window of the key study (per OECD 414 guideline) was approximately two weeks. However, the exposure duration encompassed the entire developmental window (GD6-20; from parturition to closing of the palate); as such, there is no applicable equivalent extrapolation for exposure duration to a chronic exposure, as the exposure duration in the study reflects the entire developmental window.
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- ECHA guidance states that “If no substance-specific data are available, the standard procedure for threshold effects would be, as a default, to correct for differences in metabolic rate (allometric scaling)…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 in different default allometric scaling factors for the different animal species when compared with humans.”
Thus, for the key study, the allometric factor is 4 (rat-human extrapolation). - AF for other interspecies differences:
- 1
- Justification:
- ECHA guidance states the following regarding interspecies differences:
“…the standard procedure for threshold effects would be, as a default, to correct for differences in metabolic rate (allometric scaling) and to apply an additional factor of 2.5 for other interspecies differences, i.e. toxicokinetic differences not related to metabolic rate (small part) and toxicodynamic differences (larger part). In case substance-specific information shows specific susceptibility differences between species, which are not related to differences in basal metabolic rate, the additional factor of 2.5 for ‘remaining differences’ should be modified accordingly.”
The Fraunhofer Institute for Toxicology and Experimental Medicine has published evidence that applying 2.5 as a standard ‘remaining’ interspecies differences is not necessarily applicable based on available evidence (Escher and Mangelsdorf, 2009; Batke et al, 2010; Bitsch et al, 2006). The RepDose database has been utilized to extract data on repeat dose toxicity studies, and probabilistic modeling exercises have examined time- and interspecies-extrapolations which included chemicals under comparable exposure and route of application to demonstrate the sufficiency of an allometric factor application to account for interspecies differences (Escher et al. 2013). At time of publication, the RepDose database contained 2500 repeat dose toxicity studies (rodent) with data on approximately 700 organic chemicals, and study authors utilized a subset of these studies to derive the geometric mean (GM) of fitted distributions and corrected for allometric scaling (GM = 0.91 median AF/1.03 all AF) to arrive at this conclusion (Escher et al. 2013). This conclusion aligns with previously reported GMs of 1 for interspecies differences (Schneider et al. 2005, Rennen et al. 2001).
See information panel attachment for references. - AF for intraspecies differences:
- 5
- Justification:
- General Population: While ECHA guidance suggests an AF of 10 to account for intraspecies variability across the general population, this can be further refined with published analyses of extensive databases. An AF of 5 is applied for the general population, based on analysis of a database of 447 data groups of toxicokinetic and toxicodynamic data and resulted in the 95th or the 90th percentile for the intraspecies AF of the general human population estimated as approximately 6 and 4, respectively (Hattis, 2002).
Additionally, there is little scientific basis for the need of an additional AF for children of 6-12 months due to the rapid maturation of liver and kidney function in young children (ie within a few months of age) (Renwick, 1998). Because animals show similar patterns of immaturity to those found in humans, an increased AF would not be required because the DNEL is derived from a high quality developmental study in rats.
Hattis D, Baird S, Goble R. 2002. Drug Chem Toxico 25:403-436.
Renwick AG. 1998. Food Additives and Contaminants: Part A: Chemistry, Analysis, Control, Exposure and Risk Assessment, 1944-0057, 15(1):17-35. - AF for the quality of the whole database:
- 1
- Justification:
- The test substance is part of a well-understood category of aliphatic alcohols, for which category documents are available (OECD SIDS, USEPA HPV), in addition to product registrations through EU REACH. The key study for the derivation of the DNELs in this dossier are from an OECD guideline developmental study done to GLP standards (Charles River Laboratories, Study ID 438046, 2020). Because this assessment factor is intended to adjust for missing data on sensitive endpoints (ie developmental exposures), the database on this substance is considered sufficiently robust.
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:
- 25 mg/kg bw/day
- Most sensitive endpoint:
- developmental toxicity / teratogenicity
- Route of original study:
- Oral
DNEL related information
- Overall assessment factor (AF):
- 20
- Dose descriptor starting point:
- NOAEL
- Value:
- 500 mg/kg bw/day
- AF for dose response relationship:
- 1
- Justification:
- The point of departure is a NOAEL from an OECD guideline study.
- AF for differences in duration of exposure:
- 1
- Justification:
- The exposure window of the key study (per OECD 414 guideline) was approximately two weeks. However, the exposure duration encompassed the entire developmental window (GD6-20; from parturition to closing of the palate); as such, there is no applicable equivalent extrapolation for exposure duration to a chronic exposure, as the exposure duration in the study reflects the entire developmental window.
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- ECHA guidance states that “If no substance-specific data are available, the standard procedure for threshold effects would be, as a default, to correct for differences in metabolic rate (allometric scaling)…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 in different default allometric scaling factors for the different animal species when compared with humans.”
Thus, for the key study, the allometric factor is 4 (rat-human extrapolation). - AF for other interspecies differences:
- 1
- Justification:
- ECHA guidance states the following regarding interspecies differences:
“…the standard procedure for threshold effects would be, as a default, to correct for differences in metabolic rate (allometric scaling) and to apply an additional factor of 2.5 for other interspecies differences, i.e. toxicokinetic differences not related to metabolic rate (small part) and toxicodynamic differences (larger part). In case substance-specific information shows specific susceptibility differences between species, which are not related to differences in basal metabolic rate, the additional factor of 2.5 for ‘remaining differences’ should be modified accordingly.”
The Fraunhofer Institute for Toxicology and Experimental Medicine has published evidence that applying 2.5 as a standard ‘remaining’ interspecies differences is not necessarily applicable based on available evidence (Escher and Mangelsdorf, 2009; Batke et al, 2010; Bitsch et al, 2006). The RepDose database has been utilized to extract data on repeat dose toxicity studies, and probabilistic modeling exercises have examined time- and interspecies-extrapolations which included chemicals under comparable exposure and route of application to demonstrate the sufficiency of an allometric factor application to account for interspecies differences (Escher et al. 2013). At time of publication, the RepDose database contained 2500 repeat dose toxicity studies (rodent) with data on approximately 700 organic chemicals, and study authors utilized a subset of these studies to derive the geometric mean (GM) of fitted distributions and corrected for allometric scaling (GM = 0.91 median AF/1.03 all AF) to arrive at this conclusion (Escher et al. 2013). This conclusion aligns with previously reported GMs of 1 for interspecies differences (Schneider et al. 2005, Rennen et al. 2001).
See information panel attachment for references. - AF for intraspecies differences:
- 5
- Justification:
- General Population: While ECHA guidance suggests an AF of 10 to account for intraspecies variability across the general population, this can be further refined with published analyses of extensive databases. An AF of 5 is applied for the general population, based on analysis of a database of 447 data groups of toxicokinetic and toxicodynamic data and resulted in the 95th or the 90th percentile for the intraspecies AF of the general human population estimated as approximately 6 and 4, respectively (Hattis, 2002).
Additionally, there is little scientific basis for the need of an additional AF for children of 6-12 months due to the rapid maturation of liver and kidney function in young children (ie within a few months of age) (Renwick, 1998). Because animals show similar patterns of immaturity to those found in humans, an increased AF would not be required because the DNEL is derived from a high quality developmental study in rats.
Hattis D, Baird S, Goble R. 2002. Drug Chem Toxico 25:403-436.
Renwick AG. 1998. Food Additives and Contaminants: Part A: Chemistry, Analysis, Control, Exposure and Risk Assessment, 1944-0057, 15(1):17-35. - AF for the quality of the whole database:
- 1
- Justification:
- The test substance is part of a well-understood category of aliphatic alcohols, for which category documents are available (OECD SIDS, USEPA HPV), in addition to product registrations through EU REACH. The key study for the derivation of the DNELs in this dossier are from an OECD guideline developmental study done to GLP standards (Charles River Laboratories, Study ID 438046, 2020). Because this assessment factor is intended to adjust for missing data on sensitive endpoints (ie developmental exposures), the database on this substance is considered sufficiently robust.
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
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.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.

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