Trimethylamin, N-oxid

454 mg/mL

Soluble in water

Soluble (in ethanol)

Liquid

Colorless solid; Highly hygroscopic; [Merck Index]

Solid

Colourless to yellow solid; Odourless

Danger

H302 (71.8%): Harmful if swallowed [Warning Acute toxicity, oral]

P264, P264+P265, P270, P273, P280, P301+P317, P302+P352, P305+P354+P338, P317, P321, P330, P332+P317, P362+P364, P391, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 188 reports by companies from 6 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Warning

H302+H332 (31.5%): Harmful if swallowed or if inhaled [Warning Acute toxicity, oral; acute toxicity, inhalation]

Commission Regulation (EC) No 1565/2000 (Repealed by Com. Implementing Reg. (EU) No 872/2012)

Methanamine, N,N-dimethyl-, N-oxide is listed on the EPA's Chemical Data Reporting (CDR) system. Manufacturers and importers of Methanamine, N,N-dimethyl-, N-oxide are required to report information about their production and use of this chemical to the EPA under the Toxic Substances Control Act (TSCA). (40 eCFR Part 711)

Status: Active Update: 03-04-2023 https://echa.europa.eu/registration-dossier/-/registered-dossier/25104

Methanamine, N,N-dimethyl-, N-oxide: Does not have an individual approval but may be used under an appropriate group standard

Amines, C12-16-alkyldimethyl, N-oxides: Does not have an individual approval but may be used as a component in a product covered by a group standard. It is not approved for use as a chemical in its own right.

Acute Tox. 4 (57.6%)

Acute Tox. 4 (71.8%)

Kidney dialysis is usually needed to relieve the symptoms of uremic syndrome until normal kidney function can be restored. Treatments for atherosclerosis may include lifestyle changes (exercise, eating fruits and vegetables), medicines (statins), and medical procedures or surgery (angioplasty).

High endogenous levels of TMAO in the blood (>100 uM) can lead to uremia which can lead to a number of conditions including renal damage, chronic kidney disease and cardiovascular disease. Chronically high levels of TMAO in the blood can also lead to the development of atherosclerosis and atherosclerotic plaques.

Uremic toxins such as TMAO are actively transported into the kidneys via organic ion transporters (especially OAT3). Increased levels of uremic toxins can stimulate the production of reactive oxygen species. This seems to be mediated by the direct binding or inhibition by uremic toxins of the enzyme NADPH oxidase (especially NOX4 which is abundant in the kidneys and heart) (5). Reactive oxygen species can induce several different DNA methyltransferases (DNMTs) which are involved in the silencing of a protein known as KLOTHO. KLOTHO has been identified as having important roles in anti-aging, mineral metabolism, and vitamin D metabolism. A number of studies have indicated that KLOTHO mRNA and protein levels are reduced during acute or chronic kidney diseases in response to high local levels of reactive oxygen species (6). TMAO appears to contribute to the development of atherosclerosis in part by promoting cholesterol accumulation within macrophages, perhaps by inducing scavenger receptors such as CD36 and SRA1, both of which are involved in the uptake of modified lipoproteins (A15344).

As a uremic toxin, TMAO can cause uremic syndrome. Uremic syndrome may affect any part of the body and can cause nausea, vomiting, loss of appetite, and weight loss. It can also cause changes in mental status, such as confusion, reduced awareness, agitation, psychosis, seizures, and coma. Abnormal bleeding, such as bleeding spontaneously or profusely from a very minor injury can also occur. Heart problems, such as an irregular heartbeat, inflammation in the sac that surrounds the heart (pericarditis), and increased pressure on the heart can be seen in patients with uremic syndrome. Shortness of breath from fluid buildup in the space between the lungs and the chest wall (pleural effusion) can also be present. Symptoms of atherosclerosis include angina, chest pain, breathlessness, nausea, dizziness, leg pains, weakness or numbness in the legs, erectile dysfunction, hairloss on legs or feet and leg sores that never heal.

Trimethylamine-N-oxide is biosynthesized in the liver from trimethylamine (TMA), which is derived from choline. Flavin monooxygenase 3 (FMO3) has been implicated in the oxidation of TMA since individuals with mutations in FMO3 present with accumulation of TMA levels, causing fish malodor syndrome. TMAO is secreted in the urine and is not metabolized any further.

Present in marine organisms; Used in organic synthesis (oxidizing agent); [Merck Index] Used to make quaternary ammonium compounds, as an insect attractant, and a warning agent for flammable gas; [ChemIDplus] Used as flavoring agent or adjuvant; [FDA]

TMAO is produced endogenously in the body. High levels are found in fish. It is a uremic toxic and an atherotoxin or atherogenic. It is also an osmolyte.

Flavouring Agent -> FLAVOURING_AGENT -> JECFA Functional Classes

Flavoring Agents -> JECFA Flavorings Index

Not Known or Reasonably Ascertainable

Methanamine, N,N-dimethyl-, N-oxide: ACTIVE