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EC number: 203-710-0 | CAS number: 109-83-1
- 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
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- 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
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- Endpoint summary
- Stability
- Biodegradation
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- 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:
- 0.275 mg/m³
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 75
- Dose descriptor starting point:
- LOAEC
- Value:
- 50 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 20.6 mg/m³
- Explanation for the modification of the dose descriptor starting point:
Dose descriptor: LOAEL= 50 mg/kg bw/day from the oral OECD 422 (BASF, 2010).
LOAEL corrected by an AF of 3 to obtain a NOAEL; and corrected for differences in respiratory volumes (1/0.38) and differences in Absorption (50/100) and respiratory volume by light activity (6.7/10) and for differences in exposure duration (7/5)
Corr. NOAEC = 20.6 mg/m³
- AF for dose response relationship:
- 1
- Justification:
- default as correction factor of 3 for using a LOAEL as starting point already regarded above during modification of soe descriptor starting point
- AF for differences in duration of exposure:
- 6
- Justification:
- default for sub-acute to chronic
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- already accounted for by correction for differences in respiratory volumes
- AF for other interspecies differences:
- 2.5
- Justification:
- default
- AF for intraspecies differences:
- 5
- Justification:
- default
- AF for the quality of the whole database:
- 1
- Justification:
- default
- AF for remaining uncertainties:
- 1
- Justification:
- there are no other remaining uncertainties
Acute/short term exposure
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
Acute/short term exposure
- Hazard assessment conclusion:
- medium 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:
- 0.08 mg/kg bw/day
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 300
- Dose descriptor starting point:
- LOAEL
- Value:
- 50 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 23.33 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
It is assumed, that the dermal absorption will not be higher than the oral absorption (ECHA's Guidance R.8, v2.1, Nov 2012). Therefore, the NOAEL obtained via the oral route is regarded as a worst-case starting point to determine the dermal DNEL. This LOAEL is corrected by an AF of 3 to obtain a NOAEL; and corrected for differences in exposure conditions (7/5)
Corr.NOAEC= 23.33 mg/kg bw/day
- AF for dose response relationship:
- 1
- Justification:
- default as correction factor of 3 for using a LOAEL as starting point already regarded above during modification of soe descriptor starting point
- AF for differences in duration of exposure:
- 6
- Justification:
- default for sub-acute to chronic
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- default for allometric scaling from rat to human
- AF for other interspecies differences:
- 2.5
- Justification:
- default for remaining interspecies differences
- AF for intraspecies differences:
- 5
- Justification:
- default for workers
- 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:
- medium hazard (no threshold derived)
DNEL related information
- Explanation for the modification of the dose descriptor starting point:
According to ECHA’s Guidance Part E (v3, May 2016)
Local effects
Long term exposure
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
Acute/short term exposure
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
Workers - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
Additional information - workers
For MMEA, DNELs are needed for acute and chronic exposures by the inhalation and dermal exposure routes.
The calculation of the DNELs is performed in accordance with the principles given in ECHA (2008) “Guidance of Information Requirements and Chemical Safety Assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health.”
Available dose descriptors:
From all available data for the different human health endpoints it is clear that MMEA exerts its effect by a threshold mode of action. Thus, DNELs can be calculated for the different threshold endpoints based on the most relevant dose descriptors per endpoint. DNELs are derived from the available toxicity data of MMEA, reflecting the routes, duration and frequency of exposure. DNELs are derived for workers and general population. The general population includes consumers and humans exposed via the environment. There are following annotations for the whole database:
- DNELs for acute toxicity (inhalation and dermal) should have been established because MMEA is classified for acute toxicity. However, no repated dose toxicity data is available for the exposure routs inhalation and dermal. Even though LD50values are available for oral and dermal routes of exposures, these results are not considered to be suitable starting points for DNEL derivation. As MMEA is considered to be of moderate acute toxicity and can represent an acute hazard in case if peaks of exposure are significantly higher the average daily exposure level, and adequate data is missing, no DNELs can be delineated. Instead a qualitative approach is followed and a "medium hazard" is assigned, according to EHCA's Guidance Part E (v3, May, 2016).
- furthermore, a qualitative approach for the DNEL derivation of eye and respiratory tract irritation/corrosion, skin sensitization, mutagenicity and carcinogenicity is used because no dose descriptors are available on these endpoints.
- A quantitative approach for the derivation of DNELs of skin irritation/corrosion is also used because MMEA is classified as a skin irritant. Moreover, it was possible to identify a NOAEL from a sensitization study.
- DNELs for long-term systemic effects are derived using data of the Combined Repeated Dose Toxicity with the Reproduction/Developmental Toxicity Screening Test (BASF, 2010) (OECD 422).
- For the non-threshold endpoints (mutagenicity and carcinogenicity) no DNELs can be derived because a No-Effect Level could not be established from the relevant studies. Hence the hazard characterization is based on a qualitative approach.
In order to address the differences between toxicological effect data obtained in animal studies and the real human situation, assessment factors are applied. First of all, available dose descriptors were converted into a correct starting point to take account of differences in routes of exposure between experimental animals and humans, differences in human and animal exposure conditions and possible differences in absorption between routes and between experimental animals and humans. Consecutively, the assessment factors have been applied to the correct starting point to obtain the endpoint specific DNELs. Assessment factors (AFs) correct uncertainties and variability within and between species in the effect data.
The assessment factors are applied in accordance with the default values given in ECHA (2012) “Guidance of Information Requirements and Chemical Safety Assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health”.
Modification of the relevant dose descriptors to the correct starting point:
Bioavailability
Bioavailability for experimental animals and humans for all exposure routes was assumed to be the same because of the absence of information.
Route-to-route extrapolation:
o No default factor (i.e. factor 1) is applied when oral-to-dermal extrapolation is performed in accordance with Section R.8.4.2 (p.25).
o A default factor of 2 (50 % for oral absorption and 100 % for inhalation) is applied when oral-to-inhalation extrapolation is performed.
Exposure conditions:
o Exposure times differed in the acute inhalation and repeated dose inhalation studies. The dose descriptors were corrected as described in the Appendix R.8-2.
o the LOAEL obtained via the oral route is regarded as a worst-case staring point to determine the dermal DNEL. This LOAEL is corrected by a factor of 3 for extrapolation from LOAEL to NOAEL and a factor of 1.4 to account for differences in exposure conditions (5 days/week for workers and 7 days for week for animals in the test).
Absorption:
o Differences in the respiratory volumes between experimental animals and humans were used when an oral LOAEL from a rat study was used to assess inhalation exposure in humans.
o 100 % dermal absorption is assumed, based on the criteria set out in Annex IV-B of the EU Technical Guidance Document on Risk Assessment (TGD; 2003, Part I).
Applying of assessment factors:
Interspecies differences:
o The species-specific default assessment factor for allometric scaling from Table R.8-3 is applied in case of repeated oral and dermal exposures.
o No species-specific default assessment factor for allometric scaling is applied in case of inhalation exposure routes in animals which were taken to assess human inhalatory exposure. Inhalatory dose descriptors are modified into a correct starting point taken into account only the differences of exposure conditions between experimental animals and humans as well as differences in the respiratory volumes between experimental animals and humans. No additional assessment factors are applied for inhalation route and for local effects to obtain a corrected starting point (Table R8-4, Appendix R.8-2, part 2, example A.2).
o an additional assessment factor if 2.5 is applied for remaining interspecies differences.
Intraspecies differences:
o Assessment factors of 5 and 10 are applied for workers and general population, respectively, for all endpoints and all exposure routes
Extrapolation of duration:
o The relevant default assessment factors from Table R.8.5 are applied.
Issues related to dose response:
o An assessment factor of 3 was applied if an identified LOAEL was used as a starting point.
Quality of whole data base:
o The assessment factor for uncertainties to the quality of the data base is regarded to be 1.
Long-term dermal exposure - systemic effects
For long-term effects, data from the OECD 422 Combined Repeated-Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test were used. A dermal DNEL is calculated using the oral rat LOAEL of 50 mg/kg bw, which did not need a correctionfor absorption (Appendix R.8-2, Example A.1 and Table R.8 -4), assuming that that dermal absorption will not be higher than oral absorption and there are no differences in oral and dermal absorption between rats and humans. However, this LOAEL is corrected by a factor of 3 (for extrapolation from LOAEL to NOAEL) and a factor of 1.4 to account for differences in exposure conditions (5 days/week for workers and 7 days for week for animals in the test).
Overall assessment factors are 4 x 2.5 x 5 x 6: Factor of 4 is used for inter-species differences. Factor of 2.5 is used for remaining inter-species differences. Factor of 5 is used to characterise intra-species differences between humans. Factor of 6 is used to cover differences in duration of exposure (sub-acute to chronic) (Table R. 8-5). MMEA was administered a 2-week pre-mating and mating period, approximately 1 week post-mating in males, and the entire gestation period as well as 4 days of lactation in females.
Calculation:
DNEL = 23.33/(4 x 2.5 x 5 x 6) = 0.08 mg/kg bw.
Long-term inhalation exposure - systemic effects
For the inhalation long-term systemic effects, DNEL was derived using the oral rat LOAEL of 50 mg/kg bw (OECD 422). The conversion of an oral rat LOEAL into a corrected inhalatory NOAEC was performed as described in Figure R.8 -3 of the ECHA guidance. In a first step the LOAEL is corrected by a factor of for extrapolation from LOAEL to NOAEL. Subsequently the followgin corrections are undertaken:
Corrected inhalatory NOAEC = oral NOAEL x (1/0.38) x (ABS oral-rat / ABs inh-human) x (6.7/10) =
corr. NOAEC = 16.67 mg/kg bw/d /0.38 m³/kg bw * (6.7 m³/d /10 m³/d) * 1/2 * 7d / 5 d = 20.6 mg/m³
Overall assessment factors are 2.5 x 5 x 6: Factor 5 is used for intraspecies differences between humans. Factor 6 is used to cover differences in duration of exposure from Table R. 8-5. No allometric scaling (factor 4) is applied because of oral- to-inhalation extrapolation.
Calculation:
DNEL = 20.6/(75) = 0.275 mg/m³
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.048 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):
- 150
- Dose descriptor starting point:
- LOAEL
- Value:
- 50 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 7.246 mg/m³
- Explanation for the modification of the dose descriptor starting point:
Dose descriptor: LOAEL= 50 mg/kg bw/day from the oral OECD 422 (BASF, 2010).
LOAEL corrected by an AF of 3 to obtain a NOAEL; and corrected for differences in respiratory volumes (1/1.15) and differences in Absorption (50/100)
corrected NOAEC = 16.67 mg/kg bw/d /1.15 m³/kg bw /2 = 7.246 mg/m³
- AF for dose response relationship:
- 1
- Justification:
- default as correction factor of 3 for using a LOAEL as starting point already regarded above during modification of soe descriptor starting point
- AF for differences in duration of exposure:
- 6
- Justification:
- default for subacute to chronic
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- already regarded by deriving a corrected NOAEC
- AF for other interspecies differences:
- 2.5
- Justification:
- default for remaining interspecies differences
- AF for intraspecies differences:
- 10
- Justification:
- default for general population
- 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:
- hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
- Hazard assessment conclusion:
- hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information
General Population - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
- Hazard assessment conclusion:
- hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
- Hazard assessment conclusion:
- hazard unknown but no further hazard information necessary as no exposure expected
General Population - Hazard via oral route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.028 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):
- 600
- Dose descriptor starting point:
- LOAEL
- Value:
- 50 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 16.7 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
LOAEL of 50 mg/kg bw (BASF, 2010. OECD 422) is the dose descriptor starting point. This LOAEL is corrected by an AF of 3 to obtain a NOAEL
Corr. NOAEC= 16.7 mg/m³
- AF for dose response relationship:
- 1
- Justification:
- default as correction factor of 3 for using a LOAEL as starting point already regarded above during modification of soe descriptor starting point
- AF for differences in duration of exposure:
- 6
- Justification:
- default for subacute to chronic
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- default for allometric scaling from rat to human
- AF for other interspecies differences:
- 2.5
- Justification:
- default for remaining interspecies differences
- AF for intraspecies differences:
- 10
- Justification:
- default for general population
- 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:
- hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information
General Population - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- hazard unknown but no further hazard information necessary as no exposure expected
Additional information - General Population
Calculation of Consumer DNELs is not relevant, since no uses for consumers are intended.
However, the DNEL for systemic long-term exposure via inhalation and via oral exposure are needed for the exposure assessment part "man via environment".
Please also refer to the detailes remarks under: " Additional information - workers".
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.
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