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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
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EC number: 218-218-1 | CAS number: 2082-81-7
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
![](https://echa.europa.eu./o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
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:
- 14.5 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- other: ECHA REACH Guidance and ECETOC
- Overall assessment factor (AF):
- 18
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 261.72 mg/m³
- Explanation for the modification of the dose descriptor starting point:
- no repeated dose toxicity study via inhalation route 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 a 33-40 day study. AF for extrapolation from sub-acute to chronic (ECHA 2008).
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- No allometric scaling rat to humans as inhalation; differences in respiratory volume already included in route-to-route extrapolation (ECHA 2008).
- AF for other interspecies differences:
- 1
- Justification:
- The substances are metabolised via general metabolic pathways that are common and very similar to rodents and humans and the absence of any specific target organs indicating a specific MOA at high concentrations there is no reason to believe that an additional AF of 2.5 for remaining differences is justified.
- AF for intraspecies differences:
- 3
- Justification:
- Known mode of action involving ubiquitous and non-specific enzyme systems (carboxylesterases, tricaboxylic acid cycle) makes a lower variability likely, hence the AF of 3 by ECETOC (2010) is sufficiently conservative for workers.
- AF for the quality of the whole database:
- 1
- Justification:
- The key study was conducted according to modern regulatory standards and was adequately reported. On this basis the quality of the database is not considered to contribute uncertainty and it is therefore not necessary to apply an additional factor.
- AF for remaining uncertainties:
- 1
- Justification:
- No remaining uncertainties.
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:
- 4.2 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- other: ECHA REACH Guidance and ECETOC
- Overall assessment factor (AF):
- 72
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 300 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
- no dermal repeated dose 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 a 33-40 day study. AF for extrapolation from sub-acute to chronic (ECHA 2008).
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- Allometric scaling rat to humans AF 4 (ECHA 2008).
- AF for other interspecies differences:
- 1
- Justification:
- The substances are metabolised via general metabolic pathways that are common and very similar to rodents and humans and the absence of any specific target organs indicating a specific MOA at high concentrations there is no reason to believe that an additional AF of 2.5 for remaining differences is justified.
- AF for intraspecies differences:
- 3
- Justification:
- Known mode of action involving ubiquitous and non-specific enzyme systems (carboxylesterases, tricaboxylic acid cycle) makes a lower variability likely, hence the AF of 3 by ECETOC (2010) is sufficiently conservative for workers.
- AF for the quality of the whole database:
- 1
- Justification:
- The key study was conducted according to modern regulatory standards and was adequately reported. On this basis the quality of the database is not considered to contribute uncertainty and it is therefore not necessary to apply an additional factor.
- AF for remaining uncertainties:
- 1
- Justification:
- No remaining uncertainties.
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
- Most sensitive endpoint:
- sensitisation (skin)
Acute/short term exposure
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
- Most sensitive endpoint:
- sensitisation (skin)
Workers - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- no hazard identified
Additional information - workers
Route-to-route extrapolation:
Oral to inhalatory
Only oral studies are available.
Extrapolation oral to inhalation: AF 2
Oral to dermal
Only oral studies are available. In the absence of data on dermal uptake, 100% dermal absorption is assumed.
Extrapolation oral to dermal: AF 1
DNEL derivation is based on an OECD 422 guideline study (dose levels: 100, 300 and 1000 mg/kg bw/d).
6/10 females of the high dose group were not pregnant. Reduced litter and mean pup weights were found in the high dose group
Body weight/body weight gain and food consumption were low in the high dose group. A dose-dependent increase in bile acids was noted in males.
Upon microscopic examination in the high dose group the following was noted:
- non-glandular stomach: mild diffused hyperplasia of the squamous epithelium, associated with mild hyperkeratosis (however, no indication of inflammation and/or ulceration)
- liver: minimal degree of multifocal perilobular hepatocytic vacuolation (no inflammation and/or necrosis)
-> NOAEL (repeated dose, reproduction) = 300 mg/kg bw/d
DNEL worker, chronic dermal systemic: 4.2 mg/kg bw/d
Start value: 300 mg/kg bw/d
Route of original study: oral
Dose descriptor starting point after route-to-route extrapolation: 300 mg/kg bw/d
Overall AF: 4*1*3*6*1*1 = 72
DNEL worker, chronic inhalative systemic: 14.5 mg/m³
Start value: 300 mg/kg bw/d
Route of original study: oral
Dose descriptor starting point after route-to-route extrapolation: 261.72 mg/m³
inhalatory NOEC (8 h) = oral NOAEL x 1/sRVratx ABSoral-rat/ ABSinh-humanx sRVhuman/ wRV
= 300 x 1/0.384 x 50/100 x 6.7/10
Overall AF: 1*1*3*6*1*1 = 18
Relevance and robustness of the dataset:
The slight effects observed in the study of subacute duration at a limit dose of 1000 mg/kg bw/d suggest a relatively high inherent robustness of the NOAEL used in the assessment. Furthermore, in terms of repeated dose systemic toxicity the members of the category of multifunctional methacrylates demonstrate non-specific toxicity, i.e. effects on body weight gain, organ weight changes and slight histopathological changes thus supporting the findings for 1,4-BDDMA. Also, the current DNELs for the primary metabolites (methacrylic acid and 1,4-butanediol) have been derived from subchronic studies of longer duration and in the case of both metabolites they are in the same order of magnitude or up to several fold higher, indicating that the standard assessment factor is sufficient to compensate for effects of study duration.
The dataset is considered to be robust and reliable and further studies are not required.
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 4.3 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- other: ECHA REACH Guidance and ECETOC
- Overall assessment factor (AF):
- 30
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 130.21 mg/m³
- Explanation for the modification of the dose descriptor starting point:
- no repeated dose toxicity study via inhalation route 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 a 33-40 day study. AF for extrapolation from sub-acute to chronic (ECHA 2008).
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- No allometric scaling rat to humans as inhalation; differences in respiratory volume already included in route-to-route extrapolation (ECHA 2008).
- AF for other interspecies differences:
- 1
- Justification:
- The substances are metabolised via general metabolic pathways that are common and very similar to rodents and humans and the absence of any specific target organs indicating a specific MOA at high concentrations there is no reason to believe that an additional AF of 2.5 for remaining differences is justified.
- AF for intraspecies differences:
- 5
- Justification:
- Known mode of action involving ubiquitous and non-specific enzyme systems (carboxylesterases, tricarboxylic acid cycle) makes a lower variability likely, hence the AF of 5 by ECETOC (2010) is sufficiently conservative for the general population.
- AF for the quality of the whole database:
- 1
- Justification:
- The key study was conducted according to modern regulatory standards and was adequately reported. On this basis the quality of the database is not considered to contribute uncertainty and it is therefore not necessary to apply an additional factor.
- AF for remaining uncertainties:
- 1
- Justification:
- No remaining uncertainties.
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:
- 2.5 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- other: ECHA REACH Guidance and ECETOC
- Overall assessment factor (AF):
- 120
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 300 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
- no dermal repeated dose 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 a 33-40 day study. AF for extrapolation from sub-acute to chronic (ECHA 2008).
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- Allometric scaling rat to humans AF 4 (ECHA 2008).
- AF for other interspecies differences:
- 1
- Justification:
- The substances are metabolised via general metabolic pathways that are common and very similar to rodents and humans and the absence of any specific target organs indicating a specific MOA at high concentrations there is no reason to believe that an additional AF of 2.5 for remaining differences is justified.
- AF for intraspecies differences:
- 5
- Justification:
- Known mode of action involving ubiquitous and non-specific enzyme systems (carboxylesterases, tricarboxylic acid cycle) makes a lower variability likely, hence the AF of 5 by ECETOC (2010) is sufficiently conservative for the general population.
- AF for the quality of the whole database:
- 1
- Justification:
- The key study was conducted according to modern regulatory standards and was adequately reported. On this basis the quality of the database is not considered to contribute uncertainty and it is therefore not necessary to apply an additional factor.
- AF for remaining uncertainties:
- 1
- Justification:
- No remaining uncertainties.
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
- Most sensitive endpoint:
- sensitisation (skin)
Acute/short term exposure
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
- Most sensitive endpoint:
- sensitisation (skin)
General Population - Hazard via oral route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 2.5 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- other: ECHA REACH Guidance and ECETOC
- Overall assessment factor (AF):
- 120
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 300 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
- no route-to-route extrapolation required
- 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 a 33-40 day study. AF for extrapolation from sub-acute to chronic (ECHA 2008).
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- Allometric scaling rat to humans AF 4 (ECHA 2008).
- AF for other interspecies differences:
- 1
- Justification:
- The substances are metabolised via general metabolic pathways that are common and very similar to rodents and humans and the absence of any specific target organs indicating a specific MOA at high concentrations there is no reason to believe that an additional AF of 2.5 for remaining differences is justified.
- AF for intraspecies differences:
- 5
- Justification:
- Known mode of action involving ubiquitous and non-specific enzyme systems (carboxylesterases, tricarboxylic acid cycle) makes a lower variability likely, hence the AF of 5 by ECETOC (2010) is sufficiently conservative for the general population.
- AF for the quality of the whole database:
- 1
- Justification:
- The key study was conducted according to modern regulatory standards and was adequately reported. On this basis the quality of the database is not considered to contribute uncertainty and it is therefore not necessary to apply an additional factor.
- AF for remaining uncertainties:
- 1
- Justification:
- No remaining uncertainties.
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
Route-to-route extrapolation:
Oral to inhalatory
Only oral studies are available.
Extrapolation oral to inhalation: AF 2
Oral to dermal
Only oral studies are available. In the absence of data on dermal uptake, 100% dermal absorption is assumed.
Extrapolation oral to dermal: AF 1
DNEL derivation is based on an OECD 422 guideline study (dose levels: 100, 300 and 1000 mg/kg bw/d).
6/10 females of the high dose group were not pregnant.Reduced litter and mean pup weights were found in the high dose group
Body weight/body weight gain and food consumption were low in the high dose group. A dose-dependent increase in bile acids was noted in males.
Upon microscopic examination in the high dose group the following was noted:
- non-glandural stomach: mild diffused hyperplasia of the squamous epithelium, associated with mild hyperkerathosis (however, no indication of inflammation and/or ulceration)
- liver: minimal degree of multifocal perilobular hepatocytic vacuolation (no inflammation and/or necrosis)
-> NOAEL (repeated dose, reproduction) = 300 mg/kg bw/d
DNEL general population, chronic dermal systemic: 2.5 mg/kg bw/d
Start value: 300 mg/kg bw/d
Route of original study: oral
Dose descriptor starting point after route-to-route extrapolation: 300 mg/kg bw/d
Overall AF: 4*1*5*6*1*1 = 120
DNEL general population, chronic inhalative systemic: 4.3 mg/m³
Start value: 300 mg/kg bw/d
Route of original study: oral
Dose descriptor starting point after route-to-route extrapolation: 130.21 mg/m³
inhalatory NOEC (24 h) = oral NOAEL x 1/sRVratx ABSoral-rat/ ABSinh-human
= 300 x 1/1.152 x 50/100
Overall AF: 1*1*5*6*1*1 = 30
DNEL general population, chronic oral systemic: 2.5 mg/kg bw/d
Start value: 300 mg/kg bw/d
Route of original study: oral
Dose descriptor starting point: 300 mg/kg bw/d
Overall AF: 4*1*5*6*1*1 = 120
Relevance and robustness of the dataset:
The slight effects observed in the study of subacute duration at a limit dose of 1000 mg/kg bw/d suggest a relatively high inherent robustness of the NOAEL used in the assessment. Furthermore, in terms of repeated dose systemic toxicity the members of the category of multifunctional methacrylates demonstrate non-specific toxicity, i.e. effects on body weight gain, organ weight changes and slight histopathological changes thus supporting the findings for 1,4-BDDMA. Also, the current DNELs for the primary metabolites (methacrylic acid and 1,4-butanediol) have been derived from subchronic studies of longer duration and in the case of both metabolites they are in the same order of magnitude or up to several fold higher, indicating that the standard assessment factor is sufficient to compensate for effects of study duration.
The dataset is considered to be robust and reliable and further studies are not required.
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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