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EC number: 214-675-6 | CAS number: 1184-78-7
- 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)
Description of key information
In accordance with Annex VIII, Column 1, 8.8.1, of Regulation (EC) 1907/2006 and with ‘Guidance on information requirements and chemical safety assessment Chapter R.7c: Endpoint specific guidance’ (ECHA, 2017), an assessment of the toxicokinetic behaviour of the target substance TMAO (Trimethylamine N-oxide; CAS #62637-93-8) was conducted to the extent that can be derived from the relevant available information. This comprises a qualitative assessment of the available substance specific data on physico-chemical and toxicological properties according to the Chapter R.7c Guidance document (ECHA, 2017) and taking into account further available information from source substances. The substance TMAO is a monoconstituent.
Physico-chemical properties
TMAO has a molecular weight 75.11 g/mol. It is a solid at 20 °C with a melting point at 100°C, a boiling point at 158°C and a water solubility of 793 g/L at 20 °C. The log Pow was measured to be -2.79 and the vapour pressure 23.5 Pa at 20 °C.
Absorption and distribution
Absorption is a function of the potential for a substance to diffuse across biological membranes. The most useful parameters providing information on this potential are the molecular weight, the octanol/water partition coefficient (log Pow) value and the water solubility. The log Pow value provides information on the relative solubility of the substance in water and lipids (ECHA, 2017).
Oral
In general, molecular weights below 500 and log Pow values between -1 and 4 are favourable for absorption via the gastrointestinal (GI) tract, provided that the substance is sufficiently water soluble (> 1 mg/L). Lipophilic compounds can be taken up by micellar solubilisation by bile salts, but this mechanism may be of particular importance for highly lipophilic compounds (log Pow > 4), in particular for those that are poorly soluble in water (≤ 1 mg/L) as these would otherwise be poorly absorbed. Solids must be dissolved before absorption; the degree depends on the water solubility (Aungst and Shen, 1986; ECHA, 2017).
Some of the physico-chemical characteristics (molecular weight and water solubility) of the substance are in a range that indicate a good absorption from the gastrointestinal (GI-) tract following oral ingestion, while the log Pow may limit the uptake. TMAO is a water-soluble substance and will readily dissolve into the gastrointestinal fluids. As a very hydrophilic substance, absorption by passive diffusion may be limited by the rate at which the substance partitions out of the gastrointestinal fluid. However, as the molecular weight is low (less than 200) the substance may pass through aqueous pores or be carried through the epithelial barrier by the bulk passage of water.
No in-vivo toxicity data is available on TMAO, but some indications exists with the source substance trimethylamine (TMA; CAS 75-50-3) that shows some acute toxicity (Oral LD50 rat gavage = 766 mg/kg). In a study in which rats were administered TMA by oral gavage for 42 days up to 200 mg/kg bw/d, mortality and clinical signs were observed. However it is not completely clear if the effects observed are evidence of systemic absorption or of local effects.
The potential of a substance to be absorbed in the GI-tract may be influenced by several parameters, like: chemical changes taking place in GI-fluids, as a result of metabolism by GI-flora, by enzymes released into the GI-tract or by hydrolysis. These changes will alter the physico-chemical characteristics of the substance and hence predictions based on the physico-chemical characteristics of the parent substance may in some cases no longer apply (ECHA, 2017).
Dermal
The dermal uptake of liquids and substances in solution is higher than that of dry particulates, since dry particulates need to dissolve into the surface moisture of the skin before uptake can begin. Molecular weights below 100 g/mol favour dermal uptake, while for those above 500 g/mol the molecule may be too large. Dermal uptake is anticipated to be low if the water solubility is < 1 mg/L; low to moderate if it is between 1-100 mg/L; and moderate to high if it is between 100-10000 mg/L. However, if water solubility is above 10,000 mg/l and the log P value below 0 the substance may be too hydrophilic to cross the lipid rich environment of the stratum corneum; dermal uptake for these substances will be low. Log Pow values in the range of 1 to 4 (values between 2 and 3 are optimal) are favourable for dermal absorption, in particular if the water solubility is high. For substances with a log Pow above 4, the rate of penetration may be limited by the rate of transfer between the stratum corneum and the epidermis, but uptake into the stratum corneum will be high. Log Pow values above 6 reduce the uptake into the stratum corneum and decrease the rate of transfer from the stratum corneum to the epidermis, thus limiting dermal absorption. For substances with log P values <0, poor lipophilicity will limit penetration into the stratum corneum and hence dermal absorption. Values <–1 suggest that a substance is not likely to be sufficiently lipophilic to cross the stratum corneum, therefore dermal absorption is likely to be low (ECHA, 2017).
The target substance TMA has a molecular weight of 75.11 g/mol, which indicates a potential for dermal absorption. In contrast, the substance has a very high water solubility and therefore a low dermal absorption potential might be assumed (ECHA, 2017). Moreover the log Pow is < 1, which means that the uptake into the stratum corneum is predicted to be low (ECHA, 2017).
If a substance shows skin irritating or corrosive properties, damage to the skin surface may enhance penetration. The available toxicity data on TMAO shows no indications for skin irritating effects. In an acute dermal toxicity study with the source substance TMA, the LD50 was determined at > 5000 mg/kg bw (irritation was observed). If the substance has been identified as a skin sensitizer then some uptake must have occurred although it may only have been a small fraction of the applied dose (ECHA, 2017); no skin sensitising effects were noted in the in-vitro skin sensitisation studies performed with TMAO.
Based on the available information, it can be anticipated that the dermal absorption of TMAO will be low.
Inhalation
TMAO is a solid with low vapour pressure (23.5 Pa at 20 °C) and high boiling point (above 150°C), and therefore a low volatility. Therefore, under normal use and handling conditions, inhalation exposure and availability for respiratory absorption of the substance in the form of particles will depend on the aerodynamic particle size (ECHA, 2017). The substance may also be available for inhalatory absorption after inhalation of aerosols, if the substance is sprayed (e.g. as a formulated product). In humans, particles with aerodynamic diameters below 100 μm have the potential to be inhaled. Particles with aerodynamic diameters below 50 μm may reach the thoracic region and those below 15 μm the alveolar region of the respiratory tract. Particles deposited in the nasopharyngeal/thoracic region will mainly be cleared from the airways by the mucocilliary mechanism and swallowed. According to the data available on TMAO, the MMAD is at 414 µm, with D10 = 161 µm, D50 = 404 µm and D90 = 859 µm, indicating the TMAO as dry solid are mainly not inhalable/respirable particles.
The Log Pow is not particularly favorable to respiratory absorption (value < -1). However as TMAO is very hydrophilic, vapours may be retained within the mucus.
Due to the limited information available a worst case approach is applied, and absorption via inhalation is assumed to be as equivalent to the oral route.
Distribution and Accumulation
Distribution of a compound within the body depends on the physico-chemical properties of the substance; particularly the molecular weight, the lipophilic character and the water solubility. In general, the smaller the molecule, the wider the distribution. If the molecule is lipophilic, it is likely to distribute into cells and the intracellular concentration may be higher than extracellular concentration, particularly in fatty tissues (ECHA, 2017).
TMAO is a small water-soluble molecule and ions will diffuse through aqueous channels and pores. However it is a very hydrophilic molecule and is rat of diffusion across membranes could limit its distribution. No specific organ toxicity was observed in the animal studies with TMA.
No accumulation is expected due to the high water solubility and low Log Pow.
Metabolism
No data is available on the metabolism of TMAO.
According to the data available on the source substance TMA, TMA is metabolized to TMAO and mainly excreted as such, without additional transformation.
Excretion
No data is available on the excretion of TMAO.
According to the data available on the source substance TMA, TMA is metabolized to TMAO and mainly excreted as such in urine. Other routes of excretion are negligible.
Key value for chemical safety assessment
- Bioaccumulation potential:
- no bioaccumulation potential
Additional information
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.

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