Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 212-658-8 | CAS number: 838-88-0
- 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
Carcinogenicity
Administrative data
- Endpoint:
- carcinogenicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Meets generally accepted scientific standards, well documented and acceptable for assessment
Data source
Reference
- Reference Type:
- publication
- Title:
- Experimental neoplasia in rats from oral administration of 3,3'-dichlorobenzidine, 4,4'-methylene-bis- (2-chloroaniline), and 4,4'-methylene-bis(2-methylaniline)
- Author:
- Stula EF, Sherman H, Zapp JA Jr, Clayton JW Jr
- Year:
- 1 975
- Bibliographic source:
- Toxicol Appl Pharmacol 31: 159-176
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 451 (Carcinogenicity Studies)
- Deviations:
- yes
- GLP compliance:
- no
Test material
- Reference substance name:
- 4,4'-methylenedi-o-toluidine
- EC Number:
- 212-658-8
- EC Name:
- 4,4'-methylenedi-o-toluidine
- Cas Number:
- 838-88-0
- Molecular formula:
- C15H18N2
- IUPAC Name:
- 4-[(4-amino-3-methylphenyl)methyl]-2-methylaniline
- Details on test material:
- - Name of test material (as cited in study report): 4,4'-Methylene-bis (2-methylaniline) (Me-MDA)
- Analytical purity: not specified
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Strain: ChR-CD rats (Charles River Cesarean Derived, Sprague-Dawley origin, barrier sustained, random bred albino)
- Source: Charles River Breeding Laboratories, Wilmington, MA
- Age at study initiation: 38 days
- Housing: The rats were housed two to a suspended stainless-steel cage in an air-conditioned room
- Diet (ad libitum): Standard diet of ground Purina Laboratory Chow containing 1% added corn oil
- Water: ad libitum
ENVIRONMENTAL CONDITIONS
Artificial lighting of the room was for 8 hr of each day.
Administration / exposure
- Route of administration:
- oral: feed
- Vehicle:
- corn oil
- Analytical verification of doses or concentrations:
- no
- Duration of treatment / exposure:
- Average exposure period for males 388 days and for females 482 days
Six rats per group were sacrificed after 1 year on test for an interim evaluation - Frequency of treatment:
- continously, 5 days/week
Doses / concentrations
- Remarks:
- Doses / Concentrations:
200 ppm
Basis:
actual ingested
- No. of animals per sex per dose:
- 50
- Control animals:
- yes, concurrent no treatment
Examinations
- Observations and examinations performed and frequency:
- No analysis of clinical chemisty and hematology was performed. Data on body weight changes and organ weights were not given.
- Sacrifice and pathology:
- A necropsy was performed on all rats, and a set of 30 organs was sampled for histologic examination even if there was no gross evidence of tumor formation. Rats found moribund were sacrificed in order to obtain satisfactory tissue sections. Six rats per group were sacrificed after 1 year on test for an interim evaluation. When a group size was reduced to six rats, a terminal sacrifice was conducted on that group. When a rat had multiple primary tumors of one histologic type, they were counted as one tumor.
- Statistics:
- The chi-square method was used for a statistical analysis of the tumor incidence data.
Results and discussion
Any other information on results incl. tables
A terminal sacrifice on male rats of the treatment group was conducted after 16 months, whereas the females were terminated after 19 months. Average exposure period of the control group for males and females was reported to be 564 days (range: 63-731 days) and 628 days (range: 306-733), respectively. Average exposure period of animals treated with the test substance for males and females was reported be 388 days (range: 109-481 days) and 482 days (range: 259-580 days), respectively.
Number of animals evaluated for tumor formation was 44, since the 6 animals sacrificed after 1 year were excluded. Data on body weight changes and organ weights were not given.
Liver tumors observed in both sexes consisting in hepatocellular ademoma (M, F 6/44; control 0/44 each), hepataocellular carcinoma (M 8/44; F 19/44; control 0/44 each) and cholangiocarcinoma (F 2/44) were statistically significant from control group. Furthermore, males treated with the test substance showed statistically significant increase in skin fibroma (13/44; control 2/44) and mammary fibroadenoma (14/44; control 1/44).
Nonneoplastic liver changes from exposure to the test substance were reported as hepatocytomegaly, fatty change, necrosis, bile duct proliferation, and fibrosis.
Applicant's summary and conclusion
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.