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EC number: 700-584-3 | CAS number: 1217271-02-7
- 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:
- basic toxicokinetics
- Type of information:
- other: Expert statement
- Adequacy of study:
- key study
- Study period:
- 2014-05-06
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Expert statement, no study available
- Qualifier:
- according to guideline
- Guideline:
- other: Expert statement
- Principles of method if other than guideline:
- Expert statement
- GLP compliance:
- yes
- Details on test animals or test system and environmental conditions:
- not applicable
- Details on exposure:
- not applicable
- Duration and frequency of treatment / exposure:
- not applicable
- Remarks:
- Doses / Concentrations:
not applicable - No. of animals per sex per dose / concentration:
- not applicable
- Positive control reference chemical:
- not applicable
- Details on study design:
- not applicable
- Details on dosing and sampling:
- not applicable
- Statistics:
- not applicable
- Preliminary studies:
- not applicable
- Details on absorption:
- Generally, oral absorption is facilitated for molecular weights below 500 g/mol. The relatively low water solubility may limit oral absorption by the inability of the substance to dissolve in the gastro-intestinal fluids, which in turn hinders contact with the mucosal surface. However, Sika Hardener MI will be hydrolysed after being in contact with an aqueous solution and the degradation products have physicochemical properties (higher water solubility) facilitating oral absorption. Administered without a vehicle in an acute oral toxicity study performed on rats, Sika Hardener MI lead to a LD50 of > 2000 mg/kg bw. Neither clinical signs during the entire study period nor pathological changes could be observed after the observation period of 14 days. Additionally, no adverse effects were observed in the sub-acute repeated dose toxicity study after oral administration. These findings indicate that the compound or its hydrolysis products do not become bioavailable or, in case of absorption, are of low toxicity.
Based on the low vapour pressure of 0.00533 Pa at 20 °C, exposure to Sika Hardener MI via inhalation is expected to be unlikely.
The assumptions concerning absorption of Sika Hardener MI and its hydrolysis products based on the physicochemical properties are supported by the results achieved from the LLNA, showing skin sensitising properties. Thus, a small amount of the compound or its hydrolysis products might penetrate the skin. Since Sika Hardener MI induces dermal irritation increased penetration after long term application cannot be excluded. - Details on distribution in tissues:
- Assuming that Sika Hardener MI is absorbed into the body following oral intake, it may be distributed into the interior part of cells due to its lipophilic properties and in turn the intracellular concentration may be higher than extracellular concentration particularly in adipose tissues. In contrast distribution via the blood stream is expected for the hydrolysis products due to their higher water solubility. Although the estimated BCF value of Sika Hardener MI is above 2000 L/kg wet-wt. no bioaccumulation potential is expected since the compound is hydrolysed very fast and both degradation products are highly water soluble and have low log Pow values.
- Details on excretion:
- As discussed above, Sika Hardener MI will be hydrolysed after being in contact with an aqueous solution and will probably not be excreted in its unhydrolysed form. Based on the low molecular weights and the high water solubility, the hydrolysis products are assumed to be excreted via urine. Generally, in the rat renal excretion is facilitated for water-soluble molecules with a molecular weight below 300 g/mol.
- Details on metabolites:
- Based on the structure of the molecule, Sika Hardener MI and its hydrolysis products may be metabolized by Phase I enzymes while undergoing functionalization reactions aiming to increase the compound’s hydrophilicity. Furthermore, Phase II conjugation reactions may covalently link an endogenous substrate to the parent compound or the Phase I metabolite in order to ultimately facilitate excretion. Metabolism to more toxic metabolites is not expected based on the results obtained in the in vitro bacterial reverse mutation test (Ames test) as well as the HPRT and in the chromosome aberration test in the presence of a metabolic activation system.
- Bioaccessibility (or Bioavailability) testing results:
- Taken together, physicochemical properties and experimental data indicate bioavailability of Sika Hardener MI via oral and dermal route albeit to a small amount.
- Conclusions:
- No bioaccumulation potential is expected based on study results.
- Executive summary:
Based on physicochemical characteristics, particularly water solubility absorption via oral and dermal route is expected to be low. If absorbed, intracellular concentration is likely to be higher than extracellular due to the lipophilicity of SIKA Hardener MI. Hydrolytic and metabolic conversion is expected and conjugation of Phase I-metabolites may further increase hydrophilicity. Excretion via urine is assumed to be the main excretion pathway of degradation products and metabolites formed due to their expected lower molecular weight and higher water solubility. Based on hydrolytical degradation bioaccumulation of SIKA Hardener MI is considered unlikely based on the physicochemical properties of the hydrolysis products.
Reference
Description of key information
Based on physicochemical characteristics, particularly water solubility absorption via oral and dermal route is expected to be low. If absorbed, intracellular concentration is likely to be higher than extracellular due to the lipophilicity of Sika Hardener MI. Hydrolytic and metabolic conversion is expected and conjugation of Phase I-metabolites may further increase hydrophilicity. Excretion via urine is assumed to be the main excretion pathway of degradation products and metabolites formed due to their expected lower molecular weight and higher water solubility. Based on hydrolytical degradation bioaccumulation of Sika Hardener MI is considered unlikely based on the physicochemical properties of the hydrolysis products.
Key value for chemical safety assessment
- Bioaccumulation potential:
- no bioaccumulation potential
Additional information
Toxicokinetic Assessment of N-[3-({[2,2-dimethyl-3-(morpholin-4-yl)propylidene]amino}methyl)-3,5,5-trimethylcyclohexyl]-2,2-dimethyl-3-(morpholin-4-yl)propan-1-imine (Sika Hardener MI)
Toxicological profile of Sika Hardener MI
An acute oral toxicity study conducted with Sika Hardener MI using rats revealed a LD50 value of > 2000 mg/kg bw. In an acute dermal toxicity study the LD50 value was also determined to be greater than 2000 mg/kg bw. No acute inhalation toxicity study was conducted with Sika Hardener MI since the vapour pressure of the substance is low and inhalation exposure is considered unlikely. In an in vitro skin irritation study conducted with Sika Hardener MI a skin irritating effect was observed when applied on a human skin model. A BCOP test revealed that Sika Hardener MI does not induce severe eye damage. An in vivo test on eye irritation is currently conducted. In a LLNA test a skin sensitising potential of Sika Hardener MI was observed when applied on the ear of mice. Sika Hardener MI did not induce reverse mutations in a bacterial reverse mutation test (Ames test) with five Salmonella typhimurium strains in the absence and presence of a metabolic activation system. An in vitro gene mutation assay and an in vitro cytogenetic assay on mammalian cells have been conducted to further assess genetic toxicity. Sika Hardener MI did not induce gene mutation or chromosome aberrations in these tests. Furthermore, a combined repeated dose toxicity study with the reproduction/developmental toxicity screening test was performed revealing no adverse effects up to a limit concentration of 1000 mg/kg bw/day.
Toxicokinetics of Sika Hardener MI
Sika Hardener MI is a colourless liquid at room temperature and has a molecular weight of 476.74 g/mol. Since Sika Hardener MI has two stereogenic carbon atoms the substance is an unspecific mixture of cis and trans diastereomers, with each of the stereoisomers assumed to be present as a mixture of E/Z isomers (E,E; E,Z; Z,Z). Water solubility of ca. 1 g/L at 25 °C and a log Pow value of 2.1 at 25 °C were determined. The BCF value was estimated to be 2721 L/kg wet-wt. The vapour pressure of Sika Hardener MI is 0.00533 Pa at 20 °C. In an aqueous solution, Sika Hardener MI is degraded quickly hydrolytically into 2,2-dimethyl-3-(morpholin-4-yl)propanal (Aldehyde M) and 3-Aminomethyl-3,5,5-trimethylcyclohexylamine (Isophorone diamine). Both substances have a higher water solubility (≥ 500 g/L) and a lower log Pow value (1.7 and 0.99, respectively) than Sika Hardener MI itself.
Absorption
Generally, oral absorption is facilitated for molecular weights below 500 g/mol. The relatively low water solubility may limit oral absorption by the inability of the substance to dissolve in the gastro-intestinal fluids, which in turn hinders contact with the mucosal surface. However, Sika Hardener MI will be hydrolysed after being in contact with an aqueous solution and degradation products have physicochemical properties (higher water solubility) facilitating oral absorption. Administered without a vehicle in an acute oral toxicity study performed on rats, Sika Hardener MI lead to a LD50 of > 2000 mg/kg bw. Neither clinical signs during the entire study period nor pathological changes could be observed after the observation period of 14 days. Additionally, no adverse effects were observed in the sub-acute repeated dose toxicity study after oral administration. These findings indicate that the compound or its hydrolysis products do not become bioavailable or, in case of absorption, are of low toxicity.
Based on the low vapour pressure of 0.00533 Pa at 20 °C exposure to Sika Hardener MI via inhalation is expected to be unlikely.
Dermal absorption of Sika Hardener MI is expected to occur based on physicochemical properties. This assumption is supported by the results achieved from the LLNA showing skin sensitising properties. Thus, a small amount of the compound or its hydrolysis products might penetrate the skin. Since Sika Hardener MI induces dermal irritation increased penetration after long term application cannot be excluded.
Taken together, physicochemical properties and experimental data indicate bioavailability of Sika Hardener MI via oral and dermal route albeit to a small amount.
Distribution
Assuming that Sika Hardener MI is absorbed into the body following oral intake, it may be distributed into the interior part of cells due to its lipophilic properties and in turn the intracellular concentration may be higher than extracellular concentration particularly in adipose tissues. In contrast distribution via the blood stream is expected for the hydrolysis products due to their higher water solubility. Although the estimated BCF value of Sika Hardener MI is above 2000 L/kg wet-wt. no bioaccumulation potential is expected since the compound is hydrolysed very fast and both degradation products are highly water soluble and have low log Pow values.
Metabolism
Based on the structure of the molecule, Sika Hardener MI and its hydrolysis products may be metabolized by Phase I enzymes while undergoing functionalization reactions aiming to increase the compound’s hydrophilicity. Furthermore, Phase II conjugation reactions may covalently link an endogenous substrate to the parent compound or the Phase I metabolite in order to ultimately facilitate excretion. Metabolism to more toxic metabolites is not expected based on the results obtained in the in vitro bacterial reverse mutation test (Ames test) as well as the HPRT and in the chromosome aberration test in the presence of a metabolic activation system.
Excretion
As discussed above, Sika Hardener MI will be hydrolysed after being in contact with an aqueous solution and will probably not be excreted in its unhydrolysed form. Based on the low molecular weights and the high water solubility hydrolysis products are assumed to be excreted via urine. Generally, in the rat renal excretion is facilitated for water-soluble molecules with a molecular weight below 300 g/mol.
Summary
Based on physicochemical characteristics, particularly water solubility and log Pow absorption via oral and dermal route is expected to be moderate to high. If absorbed, intracellular concentration is likely to be higher than extracellular due to the lipophilicity of Sika Hardener MI. Hydrolytic and metabolic conversion is expected and conjugation of Phase I-metabolites may further increase hydrophilicity. Excretion via urine is assumed to be the main excretion pathway of degradation products and metabolites formed due to their expected lower molecular weight and higher water solubility. Based on hydrolytical degradation bioaccumulation of Sika Hardener MI is considered unlikely based on the physicochemical properties of the hydrolysis products.
References
ECHA (2012), Guidance on information requirements and chemical safety assessment, Chapter R.7c: Endpoint specific guidance.
Marquardt H., Schäfer S. (2004). Toxicology. Academic Press, San Diego, USA, 2nd Edition 688-689.
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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