Registration Dossier
Registration Dossier
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EC number: 214-675-6 | CAS number: 1184-78-7
Toxicological Summary
Administrative data
Workers - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
DNEL related information
Workers - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
Workers - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- no hazard identified
Additional information - workers
- Acute toxicity: toxicologically significant effect observed for oral and dermal exposure
- Irritation/corrosion: no toxicological effect observed
- Sensitisation: no toxicological effect observed
- Repeated dose toxicity: no toxicologically significant effect observed
- Genetic toxicity: inconclusive effect observed but toxicologically significant effect not anticipated, further investigation required
- Toxicity to reproduction: no toxicologically significant effect observed
Risk characeterisation of TMAO.
Physiochemical Danger
Trimethylamine N-oxide is a white solid powder with a bulk density of 1.16 g/cm³ at 22 °C and a MMAD of 414.329 µm and a D10 of 161.713 µm. It has a melting point of 100 °C and a boiling point of 158 °C at 1013 hPa. The measured vapour pressure is 23.5 Pa at 20 °C. TMAO is very water soluble with a measured water solubility of 793 g/L and a corresponding measured log Pow of -2.79.
TMAO is not considered as a pyrophoric solid nor a flammable solid. Additionally, TMAO is not considered to possess explosive (thermal sensitivity) or oxidizing properties. There is no known potential for a dust explosion hazard (i.e., not a known or expected combustible dust).
There are no known physicochemical hazards associated with TMAO. The likelihood and severity of an event occurring due to the physicochemical properties of TMAO is negligible; therefore, no further risk management measures (RMMs) are required.
Environmental Danger
Trimethylamine N-oxide is considered to be readily biodegradable meeting the OECD TG 301 10-day window criteria. Additionally, experimental data from fish, daphnia, and algae indicate a lack of toxic effect at the maximum concentration tested and TMAO does not meet the classification criteria of EC 1272/2008 (as amended) for environmental hazards.
There are no known environmental hazards associated with TMAO. The likelihood and severity of an event occurring due to the environmental properties of TMAO is negligible; therefore, no further risk management measures (RMMs) are required.
Danger to the Human Population
The scope of the chemical safety assessment under REACH covers only what could be described as “normal operations” for the manufacture and/or use under foreseeable operational conditions. Neither fault nor accident conditions should be considered in the assessment.
Under REACH, risk characterisation needs not be conducted for all relevant health effects, but only for the leading health effect(s); that is risk characterisation needs only be conducted where a toxicological effect is observed. This means the toxicological effect that results in the most critical hazard for a given exposure pattern (duration, frequency, route and exposure to human populations) associated with an exposure scenario needs to be identified and considered for the risk characterisation.
Toxicological investigations for endpoints relevant for the human population have been conducted and the outcomes are summarized below:
Results of a GLP-compliant OECD TG 490 study using the mouse lymphoma L5178Y test system indicate in the absence of S9-mix the test item, trimethylamine N-oxide dihydrate, induced increases in the mutant frequency after the short (3 hour) treatment period. Given the available genetic toxicity results were only positive for gene mutation in the absence of metabolic activation (i.e., S9-mix), it is anticipated that TMAO will be negative for genotoxicity potential; a testing proposal for further in vivo genetic toxicity testing has been submitted to the ECHA. Therefore, at this time, the likelihood and severity of an event occurring due to genetic toxicity properties of TMAO is negligible; therefore, no further risk management measures (RMMs) are required. Therefore, the only toxicologically significant effect observed, and therefore the leading health effect(s), is acute toxicity.
Acute toxicity (CLP Category 4) is the leading health effect and there is no basis for setting a DNEL or DMEL; therefore, a qualitative risk characterisation is presented. The general approach when no DNEL for an endpoint is available aims at reducing/avoiding contact with the substance. However, implementation of risk management measures (RMMs) and operational conditions (OCs) needs to be proportional to the degree of concern for the health hazard presented by the substance.
Acute toxicity in CLP Categories 1 and 2 are allocated to the high hazard band on the basis that exposure to such very acutely toxic substances should be strictly contained. Substances classified for acute toxicity in Category 3 according to CLP are allocated to the moderate hazard band on the basis that exposure to such acutely toxic substances should be well-controlled. As TMAO is classified as acutely toxic Category 4 according to CLP, it is allocated to the low hazard band for acute/short-term exposure on the basis that good industrial and personal hygiene measures are sufficient to control the risk.
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
DNEL related information
General Population - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
General Population - Hazard via oral route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
DNEL related information
General Population - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- no hazard identified
Additional information - General Population
- Acute toxicity: toxicologically significant effect observed for oral and dermal exposure
- Irritation/corrosion: no toxicological effect observed
- Sensitisation: no toxicological effect observed
- Repeated dose toxicity: no toxicologically significant effect observed
- Genetic toxicity: inconclusive effect observed but toxicologically significant effect not anticipated, further investigation required
- Toxicity to reproduction: no toxicologically significant effect observed
Risk characeterisation of TMAO.
Physiochemical Danger
Trimethylamine N-oxide is a white solid powder with a bulk density of 1.16 g/cm³ at 22 °C and a MMAD of 414.329 µm and a D10 of 161.713 µm. It has a melting point of 100 °C and a boiling point of 158 °C at 1013 hPa. The measured vapour pressure is 23.5 Pa at 20 °C. TMAO is very water soluble with a measured water solubility of 793 g/L and a corresponding measured log Pow of -2.79.
TMAO is not considered as a pyrophoric solid nor a flammable solid. Additionally, TMAO is not considered to possess explosive (thermal sensitivity) or oxidizing properties. There is no known potential for a dust explosion hazard (i.e., not a known or expected combustible dust).
There are no known physicochemical hazards associated with TMAO. The likelihood and severity of an event occurring due to the physicochemical properties of TMAO is negligible; therefore, no further risk management measures (RMMs) are required.
Environmental Danger
Trimethylamine N-oxide is considered to be readily biodegradable meeting the OECD TG 301 10-day window criteria. Additionally, experimental data from fish, daphnia, and algae indicate a lack of toxic effect at the maximum concentration tested and TMAO does not meet the classification criteria of EC 1272/2008 (as amended) for environmental hazards.
There are no known environmental hazards associated with TMAO. The likelihood and severity of an event occurring due to the environmental properties of TMAO is negligible; therefore, no further risk management measures (RMMs) are required.
Danger to the Human Population
The scope of the chemical safety assessment under REACH covers only what could be described as “normal operations” for the manufacture and/or use under foreseeable operational conditions. Neither fault nor accident conditions should be considered in the assessment.
Under REACH, risk characterisation needs not be conducted for all relevant health effects, but only for the leading health effect(s); that is risk characterisation needs only be conducted where a toxicological effect is observed. This means the toxicological effect that results in the most critical hazard for a given exposure pattern (duration, frequency, route and exposure to human populations) associated with an exposure scenario needs to be identified and considered for the risk characterisation.
Toxicological investigations for endpoints relevant for the human population have been conducted and the outcomes are summarized below:
Results of a GLP-compliant OECD TG 490 study using the mouse lymphoma L5178Y test system indicate in the absence of S9-mix the test item, trimethylamine N-oxide dihydrate, induced increases in the mutant frequency after the short (3 hour) treatment period. Given the available genetic toxicity results were only positive for gene mutation in the absence of metabolic activation (i.e., S9-mix), it is anticipated that TMAO will be negative for genotoxicity potential; a testing proposal for further in vivo genetic toxicity testing has been submitted to the ECHA. Therefore, at this time, the likelihood and severity of an event occurring due to genetic toxicity properties of TMAO is negligible; therefore, no further risk management measures (RMMs) are required. Therefore, the only toxicologically significant effect observed, and therefore the leading health effect(s), is acute toxicity.
Acute toxicity (CLP Category 4) is the leading health effect and there is no basis for setting a DNEL or DMEL; therefore, a qualitative risk characterisation is presented. The general approach when no DNEL for an endpoint is available aims at reducing/avoiding contact with the substance. However, implementation of risk management measures (RMMs) and operational conditions (OCs) needs to be proportional to the degree of concern for the health hazard presented by the substance.
Acute toxicity in CLP Categories 1 and 2 are allocated to the high hazard band on the basis that exposure to such very acutely toxic substances should be strictly contained. Substances classified for acute toxicity in Category 3 according to CLP are allocated to the moderate hazard band on the basis that exposure to such acutely toxic substances should be well-controlled. As TMAO is classified as acutely toxic Category 4 according to CLP, it is allocated to the low hazard band for acute/short-term exposure on the basis that good industrial and personal hygiene measures are sufficient to control the risk.
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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