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EC number: 202-473-0 | CAS number: 96-05-9
- 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:
- 1.47 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- other: ECHA Guidance (ECHA R.8, 2012) and ECETOC Technical Report No. 110
- Overall assessment factor (AF):
- 10.2
- Dose descriptor starting point:
- NOAEL
- Value:
- 15 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 26.44 mg/m³
- Explanation for the modification of the dose descriptor starting point:
- There are no relevant experimental data on repeated exposure by inhalation. The recommended approach using oral data and assuming the same absorption for inhalation and oral route is used which is also justified by DNEL comparison with the toxicological relvant metabolite. For details, please refer to the discussion.
- AF for dose response relationship:
- 1
- Justification:
- The NOAEL is reliable. No adjustment is required.
- AF for differences in duration of exposure:
- 6
- Justification:
- default AF 6 for extrapolation from sub-acute to chronic according to ECHA R.8 ( 2012).
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- No allometric scaling rat to humans as intraspecies adjustment is accounted for in relative breathing volumes (ECHA R.8, 2012)
- AF for other interspecies differences:
- 1
- Justification:
- There is no evidence for species differences in the general mode of actions or kinetics.
- AF for intraspecies differences:
- 3
- Justification:
- Known mode of action involving ubiquitous and non-specific enzyme systems (carboxylesterases, tricarboxylic acid cycle) and well investigated metabolites makes a lower variability likely, hence the AF of 3 is sufficiently conservative. (ECETOC, 2010)
- AF for the quality of the whole database:
- 1
- Justification:
- The key study is of high quality, being rated K1. No adjustment is required.
- AF for remaining uncertainties:
- 1
- Justification:
- No remaining uncertainties.
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 7.35 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 0.2
- DNEL extrapolated from long term DNEL
- Modified dose descriptor starting point:
- other: DNEL long-term, inhal.
- Value:
- 1.47 mg/m³
- Explanation for the modification of the dose descriptor starting point:
- According to the ECHA document "Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health", a DNEL for acute systemic toxicity should be derived if an acute systemic toxicity hazard leading to classification is identified.
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
- Most sensitive endpoint:
- repeated dose toxicity
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
- Most sensitive endpoint:
- acute toxicity
DNEL related information
Workers - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.58 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Dermal
DNEL related information
- DNEL derivation method:
- other: ECHA Guidance and ECETOC Technical Report No. 110
- Overall assessment factor (AF):
- 43.2
- Dose descriptor starting point:
- NOAEL
- Value:
- 25 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 25 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
- No route to route extrapolation is necessary as a subacute dermal toxicity study is available.
- AF for dose response relationship:
- 1
- Justification:
- The NOAEL is reliable. No adjustment is required.
- AF for differences in duration of exposure:
- 6
- Justification:
- default AF 6 for extrapolation from sub-acute to chronic according to ECHA R.8 ( 2012).
- AF for interspecies differences (allometric scaling):
- 2.4
- Justification:
- Allometric scaling rabbit to humans (ECHA R.8, Table R.8-3; 2012)
- AF for other interspecies differences:
- 1
- Justification:
- There is no evidence for species differences in the general mode of actions or kinetics.
- AF for intraspecies differences:
- 3
- Justification:
- Known mode of action involving ubiquitous and non-specific enzyme systems (carboxylesterases, tricarboxylic acid cycle) and well investigated metabolites makes a lower variability likely, hence the AF of 3 is sufficiently conservative. (ECETOC, 2010)
- AF for the quality of the whole database:
- 1
- Justification:
- The key study is of high quality, being rated K2. No adjustment is required.
- AF for remaining uncertainties:
- 1
- Justification:
- No remaining uncertainties
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 2.9 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Dermal
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 0.2
- DNEL extrapolated from long term DNEL
- Modified dose descriptor starting point:
- other: DNEL, long-term, dermal
- Value:
- 0.58 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
According to the ECHA document "Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health", a DNEL for acute systemic toxicity should be derived if an acute systemic toxicity hazard leading to classification is identified.
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
- Most sensitive endpoint:
- repeated dose toxicity
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
- Most sensitive endpoint:
- skin irritation/corrosion
Workers - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- no hazard identified
Additional information - workers
DNEL inhal worker long-term
Description |
Value/ factor |
Remark |
|
Step 1) Relevant dose-descriptor |
NOAEL:15 mg/kg bw/d |
NOAEL for liver effectsin rats given AMA by oral gavage in a OECD 422 protocol |
|
Step 2) Modification of starting point |
0.38 m³/kg
6.7 m3/10 m3 |
Correction for rat standard breathing volume, 8 hrs (ECHA R.8, 2012) -Correction for activity driven differences of respiratory volumes in workers compared to workers in rest (10 m3/6.7 m3;ECHA R.8, 2012)
|
|
Route-to-Route extrapolation |
1 |
A default oral to inhalation extrapolation factor of 2 (ECHA R.8, 2012) isnot justified when comparing the DNEL with the currently applied factors vs. the DNEL of allyl alcohol as toxicological relevant metabolite (see below) |
|
NAEC worker |
26.44 mg/m3 |
|
|
Step 3) Assessment factors |
|
|
|
Interspecies |
1 |
No allometric scaling rat to humans as intraspecies adjustment is accounted for in relative breathing volumes (ECHA R.8, 2012) |
|
Intraspecies |
3 |
Known mode of action involving ubiquitous and non-specific enzyme systems (carboxylesterases, tricarboxylic acid cycle) and well investigated metabolites makes a lower variability likely, hence the AF of 3 is sufficiently conservative. (ECETOC, 2010) |
|
Exposure duration |
6 |
The NOAEL is based on an subacute study: default AF 6 for extrapolation from sub-acute to chronic according to ECHA R.8 ( 2012). |
|
Dose response |
1 |
The NOAEL is reliable. No adjustment is required. |
|
Quality of database |
1 |
The key study is of high quality, being rated K1. No adjustment is required. |
|
Remaining uncertainties |
1 |
No remaining uncertainties. |
|
DNELlong-term |
|
||
Based upon a NOAEL of 15 mg/kg bw/d for male rats, for approx. 50 d by the oral route. |
1,47 mg/m3 |
Using a total factor (POD modifier and AF) of 10.2 (/ 0.38 x 10/6.7 m³ x 1 x 1 x 3 x 6 x 1 x 1 x 1) a DNELlong-term, inhal, workerof 1,468 mg/m³ is derived. |
|
DNELshort-term |
|
||
Long-term to short term extrapolation |
5 |
Upper end of value range 1 to 5 according to ECHA R.8 (2012) |
|
Based upon a NOAEL of 15 mg/kg bw/d for rats by the oral route. |
7.35 mg/m3 |
Using a total factor (POD modifier and AF) of 2.0 (/ 0.38 x 10/6.7 m³ x 1 x 1 x 3 x 6 x 1 x 1 x 1 / 5) a DNELshort-term, inhal, workerof 7.35 mg/m³ is derived. |
|
DNEL dermal worker long-term
Description |
Value/ factor |
Remark |
|
Step 1) Relevant dose-descriptor |
NOAEL:25 mg/kg bw/d |
NOAEL for mortality and body weighteffectsin rabbits in a subacute treatment, Val 2 (Siddiqui 1982) |
|
Step 2) Modification of starting point |
1 |
No route-to-route extrapolation required. |
|
NAEL worker |
25 mg/kg bw/d |
|
|
Step 3) Assessment factors |
|
|
|
Interspecies |
2.4 |
Allometric scaling rabbit to humans (ECHA R.8, Table R.8-3; 2012) |
|
Intraspecies |
3 |
Known mode of action involving ubiquitous and non-specific enzyme systems (carboxylesterases, tricarboxylic acid cycle) and well investigated metabolites makes a lower variability likely, hence the AF of 3 is sufficiently conservative. (ECETOC, 2010) |
|
Exposure duration |
6 |
The NOAEL is based on an subacute study: default AF 6 for extrapolation from sub-acute to chronic according to ECHA R.8 ( 2012). |
|
Dose response |
1 |
The NOAEL is reliable. No adjustment is required. |
|
Quality of database |
1 |
The key study is of high quality, being rated K2. No adjustment is required. |
|
Remaining uncertainties |
1 |
No remaining uncertainties |
|
DNEL long-term |
|
||
Based upon a NOAEL of 25 mg/kg bw/d for rabbits, for subacute treatment by the dermal route. |
0.58 mg/kg bw/d |
Using a total factor (POD modifier and AF) of 43,2 (1 x 2.4 x 3 x 6 x 1 x 1) a DNELlong-term, dermal, workerof 0.58 mg/kg bw/d is derived. |
|
DNELshort-term |
|
||
Long-term to short term extrapolation |
5 |
Upper range of value range 1 to 5 according to ECHA R.8 (2012) |
|
Based upon a NOAEL of 25 mg/kg bw/d for rabbits, for subacute treatment by the dermal route. |
2.9 mg/m3 |
Using a total factor (POD modifier and AF) of 8.6 (1 x 2.4 x 3 x 6 x 1 x 1 / 5) a DNELshort-term, dermal, workerof 2.9 mg/kg bw/d is derived. |
|
Discussion/ further considerations
Comparison of DNELlong-term, systemicvalues of AMA and its metabolites on molar base (mmol/m3or mg/kg bw/d)
|
Worker |
General Population |
Source |
|||
|
Inhal |
Dermal |
Inhal |
dermal |
oral |
|
Substance |
||||||
AMA, MW 126.1g/mol |
0.012 |
0.005 |
0.003 |
0.003 |
0.001 |
this CSR |
Metabolites |
||||||
Allyl alcohol, MW 58.1g/mol |
0.080 |
0.002 |
no data |
no data |
0.001 |
ECHA 2018, CAS 107-18-6 |
Methyl Methacrylate, MW 100.1g/mol |
2.1 |
0.017 |
0.74 |
0.08 |
no data |
ECHA 2018, CAS 80-62-6 |
Given a rapid hydrolysis of AMA to its primary metabolites, a comparison of the DNELs of the (parent) substance and the primary metabolites on molar basis show that
- Allyl alcohol is the toxicological relevant metabolite (as indicated by lower DNEL levels)
- The hazard levels of AMA is calculated with a suitable margin of safety (as indicated by lower or equal DNEL levels of AMA vs. those of the metabolites, where available)
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.43 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- other: ECETOC Technical Report No. 110 and ECHA R.8, 2012
- Overall assessment factor (AF):
- 34.55
- Dose descriptor starting point:
- NOAEL
- Value:
- 15 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 13.04 mg/m³
- Explanation for the modification of the dose descriptor starting point:
- There are no relevant experimental data on repeated exposure by inhalation. The recommended approach using oral data and assuming the same absorption for inhalation and oral route is used. For details, please refer to the discussion.
- AF for dose response relationship:
- 1
- Justification:
- The NOAEL is reliable. No adjustment is required.
- AF for differences in duration of exposure:
- 6
- Justification:
- The NOAEL is based on an subacute study: default AF 6 for extrapolation from sub-acute to chronic according to ECHA R.8 ( 2012).
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- No allometric scaling rat to humans as intraspecies adjustment is accounted for in relative breathing volumes (ECHA R.8, 2012)
- AF for other interspecies differences:
- 1
- Justification:
- There is no evidence for species differences in the general mode of actions or kinetics.
- AF for intraspecies differences:
- 5
- Justification:
- Known mode of action involving ubiquitous and non-specific enzyme systems (carboxylesterases, tricarboxylic acid cycle) and well investigated metabolites makes a lower variability likely, hence the AF of 5 is sufficiently conservative. (ECETOC, 2010)
- AF for the quality of the whole database:
- 1
- Justification:
- The key study is of high quality, being rated K1. No adjustment is required.
- AF for remaining uncertainties:
- 1
- Justification:
- No remaining uncertainties
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 2.15 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 0.2
- DNEL extrapolated from long term DNEL
- Modified dose descriptor starting point:
- other: DNEL,long-term, inhalation
- Value:
- 0.43
- Explanation for the modification of the dose descriptor starting point:
- According to the ECHA document "Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health", a DNEL for acute systemic toxicity should be derived if an acute systemic toxicity hazard leading to classification is identified.
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
- Most sensitive endpoint:
- repeated dose toxicity
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
- Most sensitive endpoint:
- acute toxicity
DNEL related information
General Population - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.35 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Dermal
DNEL related information
- DNEL derivation method:
- other: ECETOC Technical Report No. 110 and ECHA R.8 (2012)
- Overall assessment factor (AF):
- 72
- Dose descriptor starting point:
- NOAEL
- Value:
- 25 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 25 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
- No route to route extrapolation is necessary as a subacute dermal toxicity study is available.
- AF for dose response relationship:
- 1
- Justification:
- The NOAEL is reliable. No adjustment is required.
- AF for differences in duration of exposure:
- 6
- Justification:
- The NOAEL is based on an subacute study: default AF 6 for extrapolation from sub-acute to chronic according to ECHA R.8 ( 2012).
- AF for interspecies differences (allometric scaling):
- 2.4
- Justification:
- Allometric scaling rabbit to humans (ECHA R.8, Table R.8-3; 2012)
- AF for other interspecies differences:
- 1
- Justification:
- There is no evidence for species differences in the general mode of actions or kinetics.
- AF for intraspecies differences:
- 5
- Justification:
- Known mode of action involving ubiquitous and non-specific enzyme systems (carboxylesterases, tricarboxylic acid cycle) and well investigated metabolites makes a lower variability likely, hence the AF of 5 is sufficiently conservative. (ECETOC, 2010)
- AF for the quality of the whole database:
- 1
- Justification:
- The key study is of high quality, being rated K2. No adjustment is required.
- AF for remaining uncertainties:
- 1
- Justification:
- No remaining uncertainties
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 1.75 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Dermal
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 0.2
- DNEL extrapolated from long term DNEL
- Modified dose descriptor starting point:
- other: DNEL, long-term, dermal
- Value:
- 0.35 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
According to the ECHA document "Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health", a DNEL for acute systemic toxicity should be derived if an acute systemic toxicity hazard leading to classification is identified.
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
- Most sensitive endpoint:
- repeated dose toxicity
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
- Most sensitive endpoint:
- skin irritation/corrosion
General Population - Hazard via oral route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.13 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- other:
- Overall assessment factor (AF):
- 120
- Dose descriptor starting point:
- NOAEL
- Value:
- 15 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 15 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
- No route to route extrapolation is necessary as a subacute oral toxicity study is available.
- AF for dose response relationship:
- 1
- Justification:
- The NOAEL is reliable. No adjustment is required.
- AF for differences in duration of exposure:
- 6
- Justification:
- The NOAEL is based on an subacute study: default AF 6 for extrapolation from sub-acute to chronic according to ECHA R.8 ( 2012).
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- Allometric scaling rat to humans (ECHA R.8, Table R.8-3; 2012)
- AF for other interspecies differences:
- 1
- Justification:
- There is no evidence for species differences in the general mode of actions or kinetics.
- AF for intraspecies differences:
- 5
- Justification:
- Known mode of action involving ubiquitous and non-specific enzyme systems (carboxylesterases, tricarboxylic acid cycle) and well investigated metabolites makes a lower variability likely, hence the AF of 5 is sufficiently conservative. (ECETOC, 2010)
- AF for the quality of the whole database:
- 1
- Justification:
- The key study is of high quality, being rated K1. No adjustment is required.
- AF for remaining uncertainties:
- 1
- Justification:
- No remaining uncertainties
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.65 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 0.2
- Modified dose descriptor starting point:
- other: DNEL, long-term, oral
- Value:
- 0.13 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
According to the ECHA document "Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health", a DNEL for acute systemic toxicity should be derived if an acute systemic toxicity hazard leading to classification is identified.
General Population - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- no hazard identified
Additional information - General Population
DNEL inhal gen pop long-term
Description |
Value/ factor |
Remark |
|
Step 1) Relevant dose-descriptor |
NOAEL:15 mg/kg bw/d |
NOAEL for liver effectsin rats given AMA by oral gavage in a OECD 422 protocol |
|
Step 2) Modification of starting point |
1.15 m³/kg |
Correction for rat standard breathing volume, 24 hrs (ECHA R.8, 2012) |
|
Route-to-Route extrapolation |
1 |
A default oral to inhalation extrapolation factor of 2 (ECHA R.8, 2012) is not justified when comparing the DNEL with the currently applied factors vs. the DNEL of allyl alcohol as toxicological relevant metabolite (see below) |
|
NAEC general population |
13.04 mg/m3 |
|
|
Step 3) Assessment factors |
|
|
|
Step 3) Assessment factors |
|
|
|
Interspecies |
1 |
No allometric scaling rat to humans as intraspecies adjustment is accounted for in relative breathing volumes (ECHA R.8, 2012) |
|
Intraspecies |
5 |
Known mode of action involving ubiquitous and non-specific enzyme systems (carboxylesterases, tricarboxylic acid cycle) and well investigated metabolites makes a lower variability likely, hence the AF of 5 is sufficiently conservative. (ECETOC, 2010) |
|
Exposure duration |
6 |
The NOAEL is based on an subacute study: default AF 6 for extrapolation from sub-acute to chronic according to ECHA R.8 ( 2012). |
|
Dose response |
1 |
The NOAEL is reliable. No adjustment is required. |
|
Quality of database |
1 |
The key study is of high quality, being rated K1. No adjustment is required. |
|
Remaining uncertainties |
1 |
No remaining uncertainties |
|
DNEL long-term |
|
||
Based upon a NOAEL of 15 mg/kg bw/d for rats by the oral route. |
0,43 mg/m3 |
Using a total factor (POD modifier and AF) of 34.55 (/ 1.15 m³ x 1 x 1 x 5 x 6 x 1 x 1 x 1) a DNELlong-term, inhal, gen-popof 0.435 mg/m³ is derived. |
|
DNELshort-term |
|
|
|
Long-term to short term extrapolation |
5 |
Upper range of value range 1 to 5 according to ECHA R.8 (2012) |
|
Based upon a NOAEL of 15 mg/kg bw/d for rats by the oral route. |
2.15 mg/m3 |
Using a total factor (POD modifier and AF) of 11.5 (/ 1.15 m³ x 1 x 1 x 5 x 6 x 1 x 1 x 1 /5) a DNELshort-term, inhal, gen-popof 2.15 mg/m³ is derived. |
|
DNEL dermal general population long-term
Description |
Value/ factor |
Remark |
|
Step 1) Relevant dose-descriptor |
NOAEL:25 mg/kg bw/d |
NOAEL for mortality and body weighteffectsin rabbits in a subacute treatment, Val 2 (Siddiqui 1982) |
|
Step 2) Modification of starting point |
1 |
No route-to-route extrapolation required. |
|
NAEL worker |
25 mg/kg bw/d |
|
|
Step 3) Assessment factors |
|
|
|
Interspecies |
2.4 |
Allometric scaling rabbit to humans (ECHA R.8, Table R.8-3; 2012) |
|
Intraspecies |
5 |
Known mode of action involving ubiquitous and non-specific enzyme systems (carboxylesterases, tricarboxylic acid cycle) and well investigated metabolites makes a lower variability likely, hence the AF of 5 is sufficiently conservative. (ECETOC, 2010) |
|
Exposure duration |
6 |
The NOAEL is based on an subacute study: default AF 6 for extrapolation from sub-acute to chronic according to ECHA R.8 ( 2012). |
|
Dose response |
1 |
The NOAEL is reliable. No adjustment is required. |
|
Quality of database |
1 |
The key study is of high quality, being rated K2. No adjustment is required. |
|
Remaining uncertainties |
1 |
No remaining uncertainties |
|
DNEL |
|
||
Based upon a NOAEL of 25 mg/kg bw/d for rabbits, for subacute treatment by the dermal route. |
0.35 mg/kg bw/d |
Using a total factor (POD modifier and AF) of 72 (1 x 2.4 x 5 x 6 x 1 x 1) a DNELlong-term, dermal, gen-popof 0.35 mg/kg bw/d is derived. |
|
DNELshort-term |
|
|
|
Long-term to short term extrapolation |
5 |
Upper range of value range 1 to 5 according to ECHA R.8 (2012) |
|
Based upon a NOAEL of 25 mg/kg bw/d for rabbits, for subacute treatment by the dermal route. |
1.75 mg/m3 |
Using a total factor (POD modifier and AF) of 14.4 (1 x 2.4 x 5 x 6 x 1 x 1 / 5) a DNELlong-term, dermal, gen-popof 1.75 mg/kg bw/d is derived. |
|
DNEL oral general population long-term
Description |
Value/ factor |
Remark |
|
Step 1) Relevant dose-descriptor |
NOAEL:15 mg/kg bw/d |
NOAEL for liver effectsin rats given AMA by oral gavage in a OECD 422 protocol |
|
Step 2) Modification of starting point |
1 |
No route-to-route extrapolation required. |
|
NAEL general population |
15 mg/kg bw/d |
|
|
Step 3) Assessment factors |
|
|
|
Interspecies |
4 |
Allometric scaling rat to humans (ECHA R.8, Table R.8-3; 2012) |
|
Intraspecies |
5 |
Known mode of action involving ubiquitous and non-specific enzyme systems (carboxylesterases, tricarboxylic acid cycle) and well investigated metabolites makes a lower variability likely, hence the AF of 5 is sufficiently conservative. (ECETOC, 2010) |
|
Exposure duration |
6 |
The NOAEL is based on an subacute study: default AF 6 for extrapolation from sub-acute to chronic according to ECHA R.8 ( 2012). |
|
Dose response |
1 |
The NOAEL is reliable. No adjustment is required. |
|
Quality of database |
1 |
The key study is of high quality, being rated K1. No adjustment is required. |
|
Remaining uncertainties |
1 |
No remaining uncertainties |
|
DNEL |
|
||
Based upon a NOAEL of 50 mg/kg bw/d for rats by the oral route. |
0,13 mg/kg bw/d |
Using a total factor (POD modifier and AF) of 120 (1 x 4 x 5 x 6 x 1 x 1) a DNELlong-term,oral, gen.pop.of 0.125 mg/kg bw/d is derived. |
|
DNELshort-term |
|
|
|
Long-term to short term extrapolation |
5 |
Upper range of value range 1 to 5 according to ECHA R.8 (2012) |
|
Based upon a NOAEL of 15 mg/kg bw/d for rats by the oral route. |
0,65 mg/m3 |
Using a total factor (POD modifier and AF) 24 (1 x 4 x 5 x 6 x 1 x 1 / 5) a DNELshort-term,oral, gen.pop.of 0.65 mg/kg bw/d is derived. |
Discussion/ further considerations
Comparison of DNELlong-term, systemicvalues of AMA and its metabolites on molar base (mmol/m3or mg/kg bw/d)
|
Worker |
General Population |
Source |
|||
|
Inhal |
Dermal |
Inhal |
dermal |
oral |
|
Substance |
||||||
AMA, MW 126.1g/mol |
0.012 |
0.005 |
0.003 |
0.003 |
0.001 |
this CSR |
Metabolites |
||||||
Allyl alcohol, MW 58.1g/mol |
0.080 |
0.002 |
no data |
no data |
0.001 |
ECHA 2018, CAS 107-18-6 |
Methyl Methacrylate, MW 100.1g/mol |
2.1 |
0.017 |
0.74 |
0.08 |
no data |
ECHA 2018, CAS 80-62-6 |
Given a rapid hydrolysis of AMA to its primary metabolites, a comparison of the DNELs of the (parent) substance and the primary metabolites on molar basis show that
- Allyl alcohol is the toxicological relevant metabolite (as indicated by lower DNEL levels)
- The hazard levels of AMA is calculated with a suitable margin of safety (as indicated by lower or equal DNEL levels of AMA vs. those of the metabolites, where available)
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