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EC number: 203-561-1 | CAS number: 108-21-4
- 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:
- 275 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- By inhalation
DNEL related information
- DNEL derivation method:
- other: ECETOC
- Overall assessment factor (AF):
- 6
- Dose descriptor starting point:
- NOAEC
- Value:
- 1 650 mg/m³
- AF for dose response relationship:
- 1
- Justification:
- Default
- AF for differences in duration of exposure:
- 2
- Justification:
- Default for extrapolation from sub-chronic to chronic data
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- No factor applicable for inhalation route of exposure
- AF for other interspecies differences:
- 1
- Justification:
- According to the ECETOC guidance document (ECETOC, 2010) , it is not appropriate in the majority of cases to apply an interspecies factor for ‘residual differences’ and that such a factor should only be supplied should the hazard data indicated a greater or lesser sensitivity of animals compared to man, eg significant differences in the mode of action. If such a factor was required, there would be evidence for it in a comparison of data between different animal species, as opposed to animals and humans. In a comparison of the repeat dose data between rats and mice, the ERASM project (see ECETOC reference) did not find evidence to support use of such a factor on a routine basis and any differences could be accounted for by allometric scaling factors alone. The data presented by ECETOC also support the conclusion that any ‘residual’ interspecies variability following allometric scaling is largely accounted for in the intraspecies factor, reflecting the interdependency of the individual assessment factors and avoiding ‘double counting’ of statistical variability. There is no scientific rationale provided in the ECHA document for the use of such a factor.
- AF for intraspecies differences:
- 3
- Justification:
- According to the ECHA guidance document, deviation from the default ECHA assessment factors is possible where scientific justification exists. As summarized in the ECETOC technical report No. 86, the distribution of human data for various toxicokinetic and toxicodynamic parameters were examined by various groups (Hattis et al., 1987 and 1999; Hattis and Silver, 1994; Renwick and Lazarus, 1998). These evaluations included data from healthy adults of both sexes, as well as limited data from young and elderly, mixed races and patients with various medical conditions such as cancer and hypertension. The authors came to the conclusion that a factor of 3 for workers (as a more homogenous group) or 5 for the general population is sufficiently conservative to account for intraspecies variability. This holds especially true for substances of low systemic toxicity, e.g. isopropyl acetate (isopropanol), for which transient behavioral clinical observations and transient body weight gain effects and other adaptive effects noted. As such it is considered that the lower assessment factors proposed and justified by ECETOC in the general case apply to isopropyl acetate (isopropanol). Thus, the factors proposed by ECETOC adequately address the intraspecies variability within the risk assessment.
- AF for the quality of the whole database:
- 1
- Justification:
- Default
- AF for remaining uncertainties:
- 1
- Justification:
- Default
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 558 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 227 mg/m³
- Most sensitive endpoint:
- irritation (respiratory tract)
DNEL related information
- DNEL derivation method:
- other: Bespoke for substance
- Overall assessment factor (AF):
- 1.2
- Dose descriptor:
- BMCL10
- Value:
- 272 mg/m³
- AF for dose response relationship:
- 1
- Justification:
- Default
- AF for differences in duration of exposure:
- 2
- Justification:
- Default for sub-chronic to chronic
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- No factor applicable for local effects
- AF for other interspecies differences:
- 0.2
- Justification:
- The PBPK model shows that for the end point that give the most conservative (lowest) value for the point of departure, the difference between the inhaled concentrations required to deliver the same concentrations of acetic acid in rats versus humans is a factor of 5.8. This is rounded down to 5 to give an AF for interspecies difference other than allometry of 0.2
- AF for intraspecies differences:
- 3
- Justification:
- Intraspecies variations are built into the PBPK model of Teeguarden and are taken into account by using the bottom end of the range of predicted human equivalent concentrations. The range spans a factor of 2. However, as a conservative approach an additional factor of 3 is applied based on the ECETOC factor for intraspecies differences. (See justification for inhalation, systemic effects, long term exposure.)
- AF for the quality of the whole database:
- 1
- Justification:
- Default
- AF for remaining uncertainties:
- 1
- Justification:
- Default
Acute/short term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
DNEL related information
Workers - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 27 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- By inhalation
DNEL related information
- DNEL derivation method:
- other: Route to route extrapolation
- Overall assessment factor (AF):
- 24
- Dose descriptor starting point:
- NOAEC
- Value:
- 1 675 mg/m³
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 637 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
The inhalation NOAEC is multiplied by the factor of 0.38m3/kgbw.day as recommended in the guidance for route to route extrapolation.
- AF for dose response relationship:
- 1
- Justification:
- Default
- AF for differences in duration of exposure:
- 2
- Justification:
- Standard assessment factor for sub-chronic to chronic extrapolation
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- Standard assessment factor for allometric scaling from rat to human
- AF for other interspecies differences:
- 1
- Justification:
- According to the ECETOC guidance document (ECETOC, 2010) , it is not appropriate in the majority of cases to apply an interspecies factor for ‘residual differences’ and that such a factor should only be supplied should the hazard data indicated a greater or lesser sensitivity of animals compared to man, eg significant differences in the mode of action. If such a factor was required, there would be evidence for it in a comparison of data between different animal species, as opposed to animals and humans. In a comparison of the repeat dose data between rats and mice, the ERASM project (see ECETOC reference) did not find evidence to support use of such a factor on a routine basis and any differences could be accounted for by allometric scaling factors alone. The data presented by ECETOC also support the conclusion that any ‘residual’ interspecies variability following allometric scaling is largely accounted for in the intraspecies factor, reflecting the interdependency of the individual assessment factors and avoiding ‘double counting’ of statistical variability. There is no scientific rationale provided in the ECHA document for the use of such a factor.
- AF for intraspecies differences:
- 3
- Justification:
- According to the ECHA guidance document, deviation from the default ECHA assessment factors is possible where scientific justification exists. As summarized in the ECETOC technical report No. 86, the distribution of human data for various toxicokinetic and toxicodynamic parameters were examined by various groups (Hattis et al., 1987 and 1999; Hattis and Silver, 1994; Renwick and Lazarus, 1998). These evaluations included data from healthy adults of both sexes, as well as limited data from young and elderly, mixed races and patients with various medical conditions such as cancer and hypertension. The authors came to the conclusion that a factor of 3 for workers (as a more homogenous group) or 5 for the general population is sufficiently conservative to account for intraspecies variability. This holds especially true for substances of low systemic toxicity, e.g. isopropyl acetate (isopropanol), for which transient behavioral clinical observations and transient body weight gain effects and other adaptive effects noted. As such it is considered that the lower assessment factors proposed and justified by ECETOC in the general case apply to isopropyl acetate (isopropanol). Thus, the factors proposed by ECETOC adequately address the intraspecies variability within the risk assessment.
- AF for the quality of the whole database:
- 1
- Justification:
- Default
- 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:
- low hazard (no threshold derived)
Acute/short term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
Workers - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- no hazard identified
Additional information - workers
There is no data available on the substance itself. According to the Guidance on Information Requirements and Chemical Safety Assessment Appendix R8-13), in cases where toxicological information and evaluations of health effects are used for setting a national OEL and are documented and available these may be used and taken into account in deriving the DNEL. A German MAK value of 100ppm (420mg/m3) 8hr TWA is available along with the criteria document. The value is based on irritation data in human volunteers (Silverman et al 1946 - see chapter 7.10.5 of this dossier). According to the MAK documentation the Silverman study reported irritation after 15 min exposure to 200 ppm of isopropyl acetate. However, the study concluded that 100 ppm would be an acceptable workplace concentration for 8 hour exposures. As the available studies with n- and iso-propyl acetate in humans are rather old, the MAK document also refers to more recent supporting data from the similar substances ethyl acetate and n-butyl acetate. The MAK values for ethyl- and butyl- acetate are 400 ppm and 100 ppm, respectively. As the data suggests that the irritation potential increases with increasing chain length of the molecule, the MAK documents concludes that the OEL for isopropyl acetate should be closer to the butyl-acetate value. It is not possible to derive a DNEL by a 'conventional' approach as there is not sufficient data on isopropyl acetate itself. It should be noted that there is an IOEL for ethyl acetate of 200ppm. The derived DNELS using the method more in line with the ECHA guidance, even with refined assessment factors, provide more conservative values than those derived by other authorities.
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 168 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- By inhalation
DNEL related information
- DNEL derivation method:
- other: ECETOC factors
- Overall assessment factor (AF):
- 10
- Dose descriptor starting point:
- NOAEC
- Value:
- 1 675 mg/m³
- AF for dose response relationship:
- 1
- Justification:
- Default
- AF for differences in duration of exposure:
- 2
- Justification:
- Default for sub-chronic to chronic extrapolation
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- Not applicable for inhalation route
- AF for other interspecies differences:
- 1
- Justification:
- According to the ECETOC guidance document (ECETOC, 2010) , it is not appropriate in the majority of cases to apply an interspecies factor for ‘residual differences’ and that such a factor should only be supplied should the hazard data indicated a greater or lesser sensitivity of animals compared to man, eg significant differences in the mode of action. If such a factor was required, there would be evidence for it in a comparison of data between different animal species, as opposed to animals and humans. In a comparison of the repeat dose data between rats and mice, the ERASM project (see ECETOC reference) did not find evidence to support use of such a factor on a routine basis and any differences could be accounted for by allometric scaling factors alone. The data presented by ECETOC also support the conclusion that any ‘residual’ interspecies variability following allometric scaling is largely accounted for in the intraspecies factor, reflecting the interdependency of the individual assessment factors and avoiding ‘double counting’ of statistical variability. There is no scientific rationale provided in the ECHA document for the use of such a factor.
- AF for intraspecies differences:
- 5
- Justification:
- According to the ECHA guidance document, deviation from the default ECHA assessment factors is possible where scientific justification exists. As summarized in the ECETOC technical report No. 86, the distribution of human data for various toxicokinetic and toxicodynamic parameters were examined by various groups (Hattis et al., 1987 and 1999; Hattis and Silver, 1994; Renwick and Lazarus, 1998). These evaluations included data from healthy adults of both sexes, as well as limited data from young and elderly, mixed races and patients with various medical conditions such as cancer and hypertension. The authors came to the conclusion that a factor of 3 for workers (as a more homogenous group) or 5 for the general population is sufficiently conservative to account for intraspecies variability. This holds especially true for substances of low systemic toxicity, e.g. isopropyl acetate (isopropanol), for which transient behavioral clinical observations and transient body weight gain effects and other adaptive effects noted. As such it is considered that the lower assessment factors proposed and justified by ECETOC in the general case apply to isopropyl acetate (isopropanol). Thus, the factors proposed by ECETOC adequately address the intraspecies variability within the risk assessment.
- AF for the quality of the whole database:
- 1
- Justification:
- Default
- AF for remaining uncertainties:
- 1
- Justification:
- Default
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 335 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 136 mg/m³
- Most sensitive endpoint:
- irritation (respiratory tract)
DNEL related information
- DNEL derivation method:
- other: bespoke for substance
- Overall assessment factor (AF):
- 2
- Dose descriptor:
- BMCL10
- Value:
- 272 mg/m³
- AF for dose response relationship:
- 1
- Justification:
- Default
- AF for differences in duration of exposure:
- 2
- Justification:
- Factor for sub-chronic to chronic
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- No factor required for local effects
- AF for other interspecies differences:
- 0.2
- Justification:
- The PBPK model shows that for the end point that give the most conservative (lowest) value for the point of departure, the difference between the inhaled concentrations required to deliver the same concentrations of acetic acid in rats versus humans is a factor of 5.8. This is rounded down to 5 to give an AF for interspecies difference other than allometry of 0.2
- AF for intraspecies differences:
- 5
- Justification:
- Intraspecies variations are built into the PBPK model of Teeguarden and are taken into account by using the bottom end of the range of predicted human equivalent concentrations. The range spans a factor of 2. However, as a conservative approach an additional factor of 5 is applied based on the ECETOC factor for intraspecies differences for the general population. (See justification for inhalation, systemic effects, long term exposure.)
- AF for the quality of the whole database:
- 1
- Justification:
- Default
- AF for remaining uncertainties:
- 1
- Justification:
- Default
Acute/short term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
DNEL related information
General Population - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 16 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- By inhalation
DNEL related information
- DNEL derivation method:
- other: Route to route extrapolation
- Overall assessment factor (AF):
- 40
- Dose descriptor starting point:
- NOAEC
- Value:
- 1 675 mg/m³
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 637 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
The inhalation NOAEC is multiplied by the factor of 0.38m3/kgbw.day as recommended in the guidance for route to route extrapolation.
- AF for dose response relationship:
- 1
- Justification:
- Default
- AF for differences in duration of exposure:
- 2
- Justification:
- Default for sub-chronic to chronic
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- Default for rat to human
- AF for other interspecies differences:
- 1
- Justification:
- According to the ECETOC guidance document (ECETOC, 2010) , it is not appropriate in the majority of cases to apply an interspecies factor for ‘residual differences’ and that such a factor should only be supplied should the hazard data indicated a greater or lesser sensitivity of animals compared to man, eg significant differences in the mode of action. If such a factor was required, there would be evidence for it in a comparison of data between different animal species, as opposed to animals and humans. In a comparison of the repeat dose data between rats and mice, the ERASM project (see ECETOC reference) did not find evidence to support use of such a factor on a routine basis and any differences could be accounted for by allometric scaling factors alone. The data presented by ECETOC also support the conclusion that any ‘residual’ interspecies variability following allometric scaling is largely accounted for in the intraspecies factor, reflecting the interdependency of the individual assessment factors and avoiding ‘double counting’ of statistical variability. There is no scientific rationale provided in the ECHA document for the use of such a factor.
- AF for intraspecies differences:
- 5
- Justification:
- According to the ECHA guidance document, deviation from the default ECHA assessment factors is possible where scientific justification exists. As summarized in the ECETOC technical report No. 86, the distribution of human data for various toxicokinetic and toxicodynamic parameters were examined by various groups (Hattis et al., 1987 and 1999; Hattis and Silver, 1994; Renwick and Lazarus, 1998). These evaluations included data from healthy adults of both sexes, as well as limited data from young and elderly, mixed races and patients with various medical conditions such as cancer and hypertension. The authors came to the conclusion that a factor of 3 for workers (as a more homogenous group) or 5 for the general population is sufficiently conservative to account for intraspecies variability. This holds especially true for substances of low systemic toxicity, e.g. isopropyl acetate (isopropanol), for which transient behavioral clinical observations and transient body weight gain effects and other adaptive effects noted. As such it is considered that the lower assessment factors proposed and justified by ECETOC in the general case apply to isopropyl acetate (isopropanol). Thus, the factors proposed by ECETOC adequately address the intraspecies variability within the risk assessment.
- AF for the quality of the whole database:
- 1
- Justification:
- Default
- AF for remaining uncertainties:
- 1
- Justification:
- Default
Acute/short term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
Acute/short term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
General Population - Hazard via oral route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 16 mg/kg bw/day
- Most sensitive endpoint:
- irritation (respiratory tract)
- Route of original study:
- By inhalation
DNEL related information
- DNEL derivation method:
- other: Route to route extrapolation
- Overall assessment factor (AF):
- 40
- Dose descriptor starting point:
- NOAEC
- Value:
- 1 675 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 637 mg/kg bw/day
- AF for dose response relationship:
- 1
- Justification:
- Default
- AF for differences in duration of exposure:
- 2
- Justification:
- Default for sub-chronic to chronic
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- Default for rat to human
- AF for other interspecies differences:
- 1
- Justification:
- According to the ECETOC guidance document (ECETOC, 2010) , it is not appropriate in the majority of cases to apply an interspecies factor for ‘residual differences’ and that such a factor should only be supplied should the hazard data indicated a greater or lesser sensitivity of animals compared to man, eg significant differences in the mode of action. If such a factor was required, there would be evidence for it in a comparison of data between different animal species, as opposed to animals and humans. In a comparison of the repeat dose data between rats and mice, the ERASM project (see ECETOC reference) did not find evidence to support use of such a factor on a routine basis and any differences could be accounted for by allometric scaling factors alone. The data presented by ECETOC also support the conclusion that any ‘residual’ interspecies variability following allometric scaling is largely accounted for in the intraspecies factor, reflecting the interdependency of the individual assessment factors and avoiding ‘double counting’ of statistical variability. There is no scientific rationale provided in the ECHA document for the use of such a factor.
- AF for intraspecies differences:
- 5
- Justification:
- According to the ECHA guidance document, deviation from the default ECHA assessment factors is possible where scientific justification exists. As summarized in the ECETOC technical report No. 86, the distribution of human data for various toxicokinetic and toxicodynamic parameters were examined by various groups (Hattis et al., 1987 and 1999; Hattis and Silver, 1994; Renwick and Lazarus, 1998). These evaluations included data from healthy adults of both sexes, as well as limited data from young and elderly, mixed races and patients with various medical conditions such as cancer and hypertension. The authors came to the conclusion that a factor of 3 for workers (as a more homogenous group) or 5 for the general population is sufficiently conservative to account for intraspecies variability. This holds especially true for substances of low systemic toxicity, e.g. isopropyl acetate (isopropanol), for which transient behavioral clinical observations and transient body weight gain effects and other adaptive effects noted. As such it is considered that the lower assessment factors proposed and justified by ECETOC in the general case apply to isopropyl acetate (isopropanol). Thus, the factors proposed by ECETOC adequately address the intraspecies variability within the risk assessment.
- AF for the quality of the whole database:
- 1
- Justification:
- Default
- AF for remaining uncertainties:
- 1
- Justification:
- Default
Acute/short term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
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.