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EC number: 229-962-1 | CAS number: 6864-37-5
- 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
Endpoint summary
Administrative data
Link to relevant study record(s)
- Endpoint:
- dermal absorption, other
- Type of information:
- (Q)SAR
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Scientifically acceptable calculation.
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- QSAR calculation using SkinPerm v1.03
- GLP compliance:
- no
- Remarks on result:
- other: maximal absorption: 0.00257 mg/cm2/h
Reference
Description of key information
Based on physico-chemical properties, oral, inhalative and dermal absorption and distribution through-out the body is expected. These assumptions are supported by the results of single and repeated-dose toxicity studies in vivo were systemic effects are reported and target organs are identified. Bioaccumulation of the substance is not expected after continuous exposure. The test substance and/or its metabolites are expected to be predominantly excreted partially via urine but also via feces.
Key value for chemical safety assessment
- Bioaccumulation potential:
- no bioaccumulation potential
Additional information
2,2'-dimethyl-4,4'-methylenebis(cyclohexylamine) is a colorless/yellowish liquid with a molecular weight of 238.4 g/mol. The test item has a water solubility of 2.01 g/L at 20°C. The log Pow is measured to be 2.3at 25°C (pH 10) and the vapor pressure is 0.0008 hPa at 20°C. The substance has a measured melting point of -7.1°C and a boiling point of 342°C at 1013 hPa.
Absorption
Oral
Absorption is a property of a substance to diffuse across biological membranes.Generally, oral absorption is favored for molecular weights below 500 g/mol and log Pow values between -1 and 4. In the GI tract absorption of small water-soluble molecules (molecular weight up to around 200 g/mol) occurs through aqueous pores or carriage of such molecules across membranes with the bulk passage of water. Based on the physico-chemical properties of the substance, it can be considered as likely that 2,2'-dimethyl-4,4'-methylenebis(cyclohexylamine) becomes bioavailable following the oral route. Since the substance has a pKa value of 10.3, it is deprotonated in acid environments like the stomach and diffusion of non-ionized substances across biological membranes is likely.
Oral uptake is confirmed by results of acute oral and repeated dose reproductive/developmental oral toxicity studies where clinical signs up to mortality were observed indicating systemic bioavailability. In a subchronic oral toxicity study with rats (OECD TG 408), the liver, white and red blood cells, kidneys, adrenal glands and heart were the target organs for toxic effect, showing also histopathological alterations. At the high dose level (60 mg/kg bw/day) body weight development/food consumption was clearly impaired and the general state of health was poor. Comparable effects were observed in the other repeated dose toxicity studies.
Inhalation
Absorption via the respiratory route also depends on physico-chemical properties like vapor pressure, log Powand water solubility. In general, highly volatile substances are those with a vapor pressure greater than 25 kPa or boiling point below 50°C. Substances with log Powvalues between -1 and 4 are favored for absorption directly across the respiratory tract epithelium by passive diffusion. Moderate water solubility will enhance penetration to the lower respiratory tract. Based on the water solubility of 2.01 g/L and log Powof 2.3 inhalative absorption can be assumed. On the other hand, due to the low vapor pressure of 0.0008 hPa only minor availability of vapors for inhalative absorption is anticipated.
However, in a well conducted 90-day inhalation study (OECD 413) performed in rats systemic effects have been observed after repeated inhalative exposure indicating that absorption occurred. Here, body weight development was impaired and target organ toxicity indicative of a mild anemic effect as well as effects on the liver and kidneys were seen at 48 mg/m3.
Dermal
In general, dermal absorption is favored by small molecular weights and high water solubility of the substance. Log Powvalues between 1 and 4 favor dermal absorption, particularly if water solubility is high. However, if water solubility is between 1-100 mg/L absorption is anticipated to be low to moderate.
In anacute dermal toxicity study, systemic effects were observed indicating dermal absorption. In addition, gross necropsy revealed effects on the heart (acutely dilated, right; acute congestion), lungs (notable congestion, in some animals edema) and liver (gray-white lobular periphery broader). Since the substance is classified for skin corrosion, severe damage to the skin will enhance the penetration of the substance. Nevertheless, internal exposure through dermal contact was calculated using IH SkinPerm model (AIHA) showing a maximal dermal absorption of 0.00257 mg/cm2/h indicating that dermal absorption is slow.
Distribution
In general, the smaller the molecule the wider is its distribution. Small water-soluble molecules will diffuse through aqueous channels and pores in the membranes. After being absorbed into the body, 2,2'-dimethyl-4,4'-methylenebis(cyclohexylamine) is expected to distribute throughout the body water. In repeated dose toxicity studies target tissues like liver, kidney and skeletal muscle have been identified which indicates distribution of the substance.
Due to its low log Pow the test item is unlikely to bioaccumulate in tissue,and there are no other physicochemical properties indicating bioaccumulating properties. A passage over the placental barrier is not expected since in the developmental toxicity study no teratogen or specific embryotoxic effects were reported.
Metabolism
Metabolic transformation of 2,2'-dimethyl-4,4'-methylenebis(cyclohexylamine) may occur in the liver and may partially be catalysed by cytochrom P-450 enzymes. Phase I reactions may include oxidation or hydroxylation. Most probably metabolism will not render the parent compound more toxic. This assumption is supported by results obtained in the Ames test. The assay shows that there is no significant difference in toxicity, in absence or presence of a rodent microsomal S9-fraction. This clearly indicates that the formation of reactive metabolites is rather unlikely. Phase II reactions may include sulfatation and glucuronidation as well as other conjugation reactions. It is likely that metabolism of the substance will render the molecule more polar, leading to faster excretion via urine and bile (following conjugation).
Excretion
In general, urinary excretion in favored by low molecular weight (below 300 g/mol in the rat) good water solubility, and ionization of the molecule. Substances that are excreted in the bile tend to have higher molecular weights or may be conjugated as glucuronides or glutathione derivates. Therefore, 2,2'-dimethyl-4,4'-methylenebis(cyclohexylamine) is expected to be excreted partially via urine but also via feces.
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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