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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
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
Acute/short term exposure
DNEL related information
Local effects
Acute/short term exposure
DNEL related information
Workers - Hazard via dermal route
Systemic effects
Acute/short term exposure
DNEL related information
Workers - Hazard for the eyes
Additional information - workers
- acute i.p. toxicity in mice was lower for oMDA (LD500,5 g/kg bw, BASF AG 1973) than for 4,4’-MDA (LD500.147 g/kg bw, BASF AG 1965).
- acute oral toxicity in rats was lower for oMDA (LD500,7 g/kg bw, BASF AG 1973) than for 4,4’-MDA (LD500.444 g/kg bw, BASF AG 1975).
- both isoforms are non irritating on skin and mucosa
- subcutaneous injections of 3- and 4-ring fractions of MDA into rats resulted in a significantly lower acute toxicity (LD502.5 g/kg bw) than 4,4’-MDA (LD500.2 g/kg bw, Bayer AG 1969). In the same study chronic subcutaneous injections of 3- and 4-ring fractions of MDA were tolerated way better than 4,4’-MDA. Life expectancy and tumour incidence of animals injected with a high total dose of 11.2 g/kg of 3- and 4-ring fractions of MDA was approximately identical to the animals injected with a lower total dose of 1.41 g/kg 4,4’-MDA. This trend of decreasing systemic toxicity with increasing number of aromatic rings in the amine molecule was supported by chronic subcutaneous injections of a 8-ring fraction of MDA.
Justification on read-across of data for the 4,4´-isomer of MDA for oligomeric MDA in the scope of REACH.
Oligomeric MDA is produced by a condensation reaction between aniline and formaldehyde. The main component of the crude product is 4,4’-MDA, which makes up 25 -85 %. Further, the crude product contains methylene-2,4’-dianiline, minor amounts of methylene-2,2’-dianiline and 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=4-6; 4 to 6 aniline with 3-5 formaldehyde). The mean number of additional rings in the oMDA (>2-ring) is m=0.33 (range 0.1-0.6).
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 number500-036-1.
Table 1: Concentration ranges of MDA-isoforms [%]:
CONTENT |
4,4’-MDA |
oligomeric MDA |
4,4’-MDA |
75 – 100 |
25 – 85 |
2,4’-MDA |
0 – 20 |
1 – 50 |
2,2’-MDA |
0 - 5 |
0.01 – 10 |
Formaldehyde, oligomeric reaction products with aniline |
0 - 15 |
5 - 60 |
2,4'-methylenedianiline: CAS number 1208-52-2,EC number214-900-8
2,2'-methylenedianiline: CAS number 6582-52-1,EC number229-512-4
Table 2: Comparison of physico-chemical properties of MDA-isoforms.
|
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 |
Since 4,4’-MDA is the main constituent of both isoforms, toxicological properties of the incompletely tested oMDA can be extrapolated from this isomer by means of a worst case consideration. All isomers and homologues have primary aromatic amino groups as a common property.
The leading health effects of 4,4’-MDA are liver toxicity, carcinogenicity and sensitization. These effects may, at least partly, be driven by the bifunctional diamine-structure of the 2-ring molecule in 4,4´-position. In higher-ring compounds it may be predicted that this functionality, at least partly and to an alleviated extend, still exists.
Taking into account the higher degree of saturation of functional groups and the altered physico-chemical properties (higher molecular weight, decreased vapour pressure, decreased water solubility, unchanged / decreased logPowat physiological pH) a lower reactivity and bioavailability of oMDA can be anticipated.
As a proof of concept data from dated industrial hygiene studies and a chronic study in rats can be used:
Even though the quality of the cited studies does not comply with current guideline requirements, these considerations support the thesis that 4,4’-MDA can be taken as a reference molecule for oMDA. The data gained on 4,4’-MDA can therefore be considered representative for the category for the purpose of hazard evaluation and risk assessment. Accordingly, the classification of oMDA can be adapted from 4,4’-MDA by means of a worst case consideration:
DSD:
Carc. Cat. 2; R45
Muta. Cat. 3; R68
T; R39/23/24/25
Xn; R48/20/21/22
R43
GHS:
carc. cat. 1B
muta. cat. 2
STOT single exp. cat 1
STOT rep. exp. cat 2
skin sens. cat.1
In order to support the legal classification key studies of 4,4’-MDA for all relevant end point were included into the oMDA IUCLID.
General Population - Hazard via inhalation route
Systemic effects
Acute/short term exposure
DNEL related information
Local effects
Acute/short term exposure
DNEL related information
General Population - Hazard via dermal route
Systemic effects
Acute/short term exposure
DNEL related information
General Population - Hazard via oral route
Systemic effects
Acute/short term exposure
DNEL related information
General Population - Hazard for the eyes
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.
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