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EC number: 500-036-1 | CAS number: 25214-70-4
- 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
Ecotoxicological Summary
Administrative data
Hazard for aquatic organisms
Freshwater
- Hazard assessment conclusion:
- PNEC aqua (freshwater)
- PNEC value:
- 0 mg/L
- Assessment factor:
- 50
- Extrapolation method:
- assessment factor
- PNEC freshwater (intermittent releases):
- 0.001 mg/L
Marine water
- Hazard assessment conclusion:
- PNEC aqua (marine water)
- PNEC value:
- 0 mg/L
- Assessment factor:
- 500
- Extrapolation method:
- assessment factor
STP
- Hazard assessment conclusion:
- PNEC STP
- PNEC value:
- 10 mg/L
- Assessment factor:
- 10
- Extrapolation method:
- assessment factor
Sediment (freshwater)
- Hazard assessment conclusion:
- PNEC sediment (freshwater)
- PNEC value:
- 0.074 mg/kg sediment dw
- Extrapolation method:
- equilibrium partitioning method
Sediment (marine water)
- Hazard assessment conclusion:
- PNEC sediment (marine water)
- PNEC value:
- 0.007 mg/kg sediment dw
- Extrapolation method:
- equilibrium partitioning method
Hazard for air
Air
- Hazard assessment conclusion:
- no hazard identified
Hazard for terrestrial organisms
Soil
- Hazard assessment conclusion:
- PNEC soil
- PNEC value:
- 0.128 mg/kg soil dw
- Assessment factor:
- 1 000
- Extrapolation method:
- assessment factor
Hazard for predators
Secondary poisoning
- Hazard assessment conclusion:
- PNEC oral
- PNEC value:
- 0.3 mg/kg food
- Assessment factor:
- 270
Additional information
Justification on read-across of data for the 4,4´-isomer of MDA for oligomeric MDA in the scope of REACH.
Oligomeric MDA (oMDA) is produced by a condensation reaction between aniline and formaldehyde. The main component of the crude product is 4,4’-MDA, which makes up 46 to 65%. Further, the crude product contains minor amounts of methylene-2,4’-dianiline and traces of methylene-2,2’-dianiline. The other main component is a mixture of higher oligomers.
The general molecular formula is:
H2N-C6H4-[H2N-C6H4]m-C6H4-NH2
The higher oligomers include mainly 3-ring (m=1; product of 3 aniline + 2 formaldehyde) together with other higher number ring types (m=4-7; 4 to 7 aniline with 3-6 formaldehyde) as shown in the table below.
Following nomenclature for the isoformes are defined:
1) CAS name: Benzenamine, 4,4'-methylenebis- (mono constituent substance), CAS number: 101-77-9. EC name: 4,4'-methylenedianiline, EC number:202-974-4
2) CAS name: Formaldehyde, polymer with benzenamine (UVCB), CAS number 25214-70-4. EC name: Formaldehyde, oligomeric reaction products with aniline, EC number: 500-036-1.
Concentration ranges of MDA-isoforms [%]:
CONTENT |
4,4’-MDA |
Oligomeric MDA |
4,4’-MDA |
75-100 |
46-65 |
2,4’-MDA |
0-20 |
0.8-1.4 |
2,2’-MDA |
0-5 |
<0.1 |
Formaldehyde, oligomeric reaction products with aniline |
0-15 |
3- to 7-ring isomers concentrations shown below |
3-ring isomers |
No data |
22-28 |
4-ring isomers |
No data |
12-14 |
5-ring isomers |
No data |
6-8 |
6-ring isomers |
No data |
3-5 |
7-ring isomers |
No data |
1-3 |
2,4'-methylenedianiline: CAS number 1208-52-2, EC number 214-900-8
2,2'-methylenedianiline: CAS number 6582-52-1, EC number 229-512-4
Comparison of physico-chemical properties of MDA-isoforms:
Property |
4,4’-MDA |
oligomeric MDA |
Melting range |
83 - 92°C |
30 - 70°C |
MW [g/mol] |
198.26 |
233 (average) |
water solubility [g/l] |
1.01 (at 25°C) |
0.36-1.22 (at 20°C) |
logPow(at 25°C) |
1.55 |
1.3 - 2.5 |
Vapor pressure [hPa] |
0.00025 Pa at 25°C |
<0.000001hPa at 20°C |
The higher oligomers are substantially less soluble than the diamine (4,4’-MDA: 1.25 g/l; 3-core-MDA: 42.5 mg/l) (EU RAR, 2001) and are emitted into the environment in much lower amounts than the diamines. If waste water is monitored, only the 4,4’-MDA is detected. It is unlikely the higher ring oligomers will significantly raise the total emissions and are therefore of less importance in any exposure assessment. Therefore as 4,4’-MDA is the main constituent of both isoforms, ecotoxicological properties of the incompletely tested oMDA can be extrapolated from this isomer in the absence of further data on oligomeric MDA.
Effects on Aquatic Organisms
Micro-organisms
An inhibition of respiration using activated sludge study was performed (Caspers et al) where a 3 hour EC50value of >100 mg/l and an NOEC = 100 mg/l was calculated. These values may be used to determine aPNECwwtpvalue of 10 mg/l, using an assessment factor of 10 for 4,4'-MDA according to table R.10 -6 of the Guidance document.
Method |
Results |
Reference |
activated sludge OECD Guideline 209 (Activated Sludge, Respiration Inhibition Test) |
EC50(3 h): > 100 mg/L |
Caspers N, Hamburger B, Kanne R & Klebert W (1986b) |
Water compartment
The current strategy for deriving a protective PNECwater, outlined in the REACH Guidance R10, indicates that the appropriate assessment factor should be applied to the lowest acute L(E)C50value obtained from toxicity testing in fish, aquatic invertebrate and algal species. In the event that chronic toxicity data are available from three separate trophic levels, the lowest NOEC value is used with an assessment factor of 10 applied for fresh water and 100 applied for marine water.
Detailed below is an assessment of the available ecotoxicological data together with recommendations for the endpoints which should be used to determine the Predicted No Effect Concentration for oligomeric MDA in the fresh water environment (PNECfresh water) and marine environment (PNECmarine water):-
Fish
A study was conducted exposingOryzias latipes(Mitsubishi (2002a)) to4,4'-MDAover 96 h. ALC50(96 h) of 20.6 mg/l was determined.
There were no long-term fish studies.
Method |
Results |
Comment |
Reference |
Oryzias latipes freshwater semi-static OECD Guideline 203 (Fish, Acute Toxicity Test) |
LC50(96 h): 20.6 mg/L test mat. (nominal) |
4,4'-MDA |
Mitsubishi (2002a) |
Invertebrates
Method |
Results |
Comment |
Reference |
Daphnia magna freshwater static Screening test |
EC50(48 h): > 0.1 — < 1 mg/L test mat. (nominal) based on: mobility |
oligomericMDA |
BASF SE (2010b) |
Daphnia magna freshwater semi-static OECD Guideline 202 (Daphnia sp. Acute Immobilisation Test) |
EC50(48 h): 2.47 mg/L test mat. (nominal) based on: mobility EC50(24 h): 8.08 mg/L test mat. (nominal) based on: mobility |
4,4'-MDA |
Mitsubishi (2002b) |
Daphnia magna freshwater semi-static OECD Guideline 211 (Daphnia magna Reproduction Test) |
NOEC (21 d): 0.00525 mg/L test mat. (meas. (TWA)) based on: reproduction LOEC (21 d): 0.0182 mg/L test mat. (meas. (TWA)) based on: reproduction |
4,4'-MDA |
Mitsubishi (2002c) |
Two studies were conducted usingDaphnia Magna; one study tested the active ingredient 4,4’-MDA and one screening study investigated oligomeric MDA.
The EC50(48 h) was found to be 2.47 mg/l (Mitsubishi (2002b))indicating that MDA is toxic to invertebrates. A screening study performed using oligomeric MDA produced an EC50(48 h) of >0.1 - <1 mg/L(BASF SE (2010b)). The result from this study indicates that oligomeric MDA may be more toxic than 4,4’-MDA. Further work is proposed to investigate this effect.
A long-term test was also conducted onDaphnia magnawith 4,4’-MDA which resulted in a NOEC of 0.00525 mg/L.
Aquatic Plants
Method |
Results |
Comment |
Reference |
Scenedesmus subspicatus (new name: Desmodesmus subspicatus)(algae) freshwater static National industrial standard test guideline DIN 38 412 part 9 |
EC50(72 h): 11 mg/L test mat. (nominal) based on: growth rate EC50(72 h): 9.8 mg/L test mat. (nominal) based on: biomass EC10(72 h): 0.3 mg/L test mat. (nominal) based on: growth rate EC10(72 h): 2.4 mg/L test mat. (nominal) based on: biomass |
Phenylbase MDA |
Bayer AG (1992) |
One study was conducted to investigate toxicity to aquatic plants. In this study, usingDesmodesmus subspicatusand a phenylbase MDA (Bayer AG (1992)), an EC50of 11 mg/L was determined.
There were no long-term aquatic plant studies.
Summary Water Compartment
The most sensitive species of the three trophic levels of the base-set (fish, daphnia and algae) was determined to be invertebrates. Oligomeric MDA, based on the results from a screening study, appears to be more toxic than 4,4’-MDA. In order to produce a PNECaquaticthat is protective to the aquatic environment the result of 0.1 mg/L will be used for the invertebrate acute toxicity test. The invertebrate long-term study provides the most sensitive endpoint overall and will be used for the PNECaquaticderivation.
As there are results from 3 short-term tests (fish, invertebrates and algae) and 2 long-term tests (invertebrates and algae) an assessment factor of 50 will be used to calculate the PNECfreshwater. Accordingly thePNECfreshwateris 1.05E-04 mg/L.
The proposedPNECmarine water1.05E-05 mg a.i./Lis based on the application of an additional assessment factor of 10 to the assessment factor of 50 applied to the EC50value obtained in the invertebrate toxicity study.
Sediment
A PNECsediment,freshwaterhas been determined using the equilibrium partitioning method based on the PNECfreshwaterderived above, in accordance with the TGD (equation 70).
Where:-
RHOsusp= 1150 kg/m3
PNECfreshwater= 1.05E-04 mg/l
Ksusp-water= 177 m3/m3(calculated using TGD equation 24)
PNECsediment,freshwater= 0.0162 mg/kgwwt(0.0743 mg/kg dwt)
A PNECsediment,marinehas been determined using the equilibrium partitioning method based on the PNECmarinewaterderived above, in accordance with the TGD (equation 70).
Where:-
RHOsusp= 1150 kg/m3
PNECmarinewater=1.05E-05mg/l
Ksusp-water= 177 m3/m3(calculated using TGD equation 24)
PNECsediment,marine= 1.62E-03 mg/kgwwt(7.43E-03 mg/kg dwt)
Terrestrial Compartment
A study was conducted to assess the effect on earthworms from 4,4’-MDA. The LC50value was determined to be 444 mg/kg dwt.
Method |
Results |
Remarks |
Reference |
Eisenia fetida(annelids) short-term toxicity (laboratory study) Substrate: artificial soil OECD Guideline 207 (Earthworm, Acute Toxicity Tests) |
NOEC (14 d): 180 mg/kg soil dw based on: mortality NOEC (14 d): 32 mg/kg soil dw based on: weight LC50 (14 d): 444 mg/kg soil dw based on: mortality |
4,4'-MDA |
van der Hoeven N, Roza P & Henzen L (1992a) |
Two studies were conducted to assess the effects on plants. The lowest EC50was determined to be 128 mg/kg dwt.
Method |
Results |
Remarks |
Reference |
Lactuca sativa(Dicotyledonae (dicots)) short-term toxicity (laboratory study) 1. seedling emergence toxicity test 2. early seedling growth toxicity test 3. survival Substrate: artificial soil OECD Guideline 208 (Terrestrial Plants Test: Seedling Emergence and Seedling Growth Test) |
Lactuca sativa: NOEC (17 d): 100 mg/kg soil dw based on: seedling emergence Lactuca sativa: EC50 (14 d): 128 mg/kg soil dw based on: growth Lactuca sativa: NOEC (14 d): 10 mg/kg soil dw based on: growth Lactuca sativa: NOEC (14 d): >= 1000 mg/kg soil dw based on: survival |
4,4'-MDA |
van der Hoeven N, Roza P & Henzen L (1992b) |
Avena sativa(Monocotyledonae (monocots)) short-term toxicity (laboratory study) 1. seedling emergence toxicity test 2. survival Substrate: artificial soil OECD Guideline 208 (Terrestrial Plants Test: Seedling Emergence and Seedling Growth Test) |
Avena sativa: NOEC (17 d): 320 mg/kg soil dw based on: seedling emergence Avena sativa: EC50 (14 d): 353 mg/kg soil dw based on: growth Avena sativa: NOEC (14 d): 100 mg/kg soil dw based on: growth Avena sativa: NOEC (14 d): >= 1000 mg/kg soil dw based on: survival |
4,4'-MDA |
van der Hoeven N, Roza P & Henzen L (1992b) |
Summary Terrestrial Compartment
Based upon the results of the 3 terrestrial studies, the lowest result was found to be the EC50from the plant study (128 mg/kg dwt). Applying an assessment factor of 1000 to the EC50value, the PNECsoilcan be determined to be 0.128 mg/kg dwt (0.113 mg/kg wwt).
PNECoral
The PNECoral(0.30 mg/kg food) was based on the LOAEL of 80 ppm from the subchronic drinking water study with rats (Ciba Geigy 1982). A factor of 3 was used to derive a NOAEL, and a factor of 90 to extrapolate from the subchronic study (Guidance chapter R.10.8).
It is not expected that MDA will enter the foodchain therefore the dervivation of the PNEC oral was a theoretical exercise.
Conclusion on classification
According to regulation 1272/208/EC, oligomeric MDA is classified as:
H410: very toxic to aquatic life with long lasting effects.
According to 67/548/EC, oligomeric MDA is classified as:
R50/53: very toxic to aquatic organisms, may cause long-term adverse effects in the aquatic environment.
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