Ethanethiol

Endpoint summary

Description of key information

No studies are available on the toxicokinetics of ethanethiol. 

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

No in vitro or in vivo toxicokinetic studies are available for ethanethiol.

The following summary has therefore been prepared based on the physicochemical properties of the substance.Ethanethiol is a volatile liquid and exposure via the inhalation route is therefore likely to be of most significance to humans. In practice, however, the substance is used and handled under strictly controlled conditions and exposure is therefore not relevant.

Absorption

Oral and Dermal:The water solubility (8860 mg/l) and log K_ow (1.5) of ethanethiol suggest that the substance will be absorbed effectively. Clinical signs and necropsy findings in an acute oral toxicity study are indicative of absorption. In an acute dermal toxicity study no effects were observed therefore absorption cannot be confirmed for this route.

 

Inhalation:The water solubility and log K_ow of ethanethiol suggest that it will be dissolved in the mucous of the respiratory tract lining, but the log K_ow is optimal for absorption, so it could be passively absorbed from the mucous. Clinical signs and necropsy findings in acute inhalation studies support the assumption that the substance is absorbed following inhalatory exposure.

 

Distribution

The log K_ow of the substance means that it is likely to distribute into cells and the intracellular concentration might be higher than the extracellular concentration particularly in fatty tissues. Toxicity studies provide evidence for distribution to various organs.

Metabolism

There are no measured data on the metabolism of ethanethiol. 

Simple thiol flavouring agents have been assessed by the Joint FAO/WHO Expert Committee on Food Additives (JECFA, 2000). Metabolic pathways for thiols are described in detail in that document:

Simple aliphatic and aromatic thiols undergoS-methylation in mammals to produce the corresponding ethyl thioether or sulfide. Methylation is catalysed by thiopurine methyltransferase in the cytoplasm and thiol methyltransferase in microsomes, and both reactions requireS-adenosyl-l-methionine as a methyl group donor. Thiopurine methyltransferase is present in human liver, kidney, and erythrocytes; preferential substrates for this enzyme include aromatic and heterocyclic thiols. S-Methylation of aliphatic thiols is catalysed by microsomal thiol methyltransferase, and the resulting methyl thioether (sulfide) metabolite would undergoS-oxidation to give the methyl sulfoxide and methyl sulfone analogues as urinary products.

Thiols may react with glutathione and other endogenous thiol substances to form mixed disulfides. Both microsomal and cytoplasmic thioltransferases have been reported to catalyse the formation of mixed disulfides. The resulting mixed disulfides can undergo reduction back to thiols, oxidative desulfuration, or oxidation to a sulfonic acid via the intermediate thiosulfinate and sulfinic acids. The principalS-Glucuronidation of aromatic thiols has been reported, and this may be a pathway for the metabolism of aromatic thiols (thiophenols) (Nos 525 and 528-531) and simple aromatic disulfides (Nos 576 and 578; subgroup vii) after their reduction (see below). Glucuronyl transferases behave similarly towards hydroxyl and sulfydryl groups, and the two activities have the same subcellular location and optimal pH. Thiols may be oxidized to form sulfenic acids (RSOH), which are unstable and readily undergo further oxidation to sulfinic (RSO₂H) and sulfonic (RSO₃H) acids or combine with nucleophiles. The sulfonic acid group is a highly polar centre and makes molelcules highly soluble in water. In general, sulfonic acids are stable to metabolism.

Alkyl thiols of low relative molecular mass undergo oxidative desulfuration in vivoto yield CO₂and SO₄⁼. This reaction has been shown, for example, for methanethiol (methyl mercaptan). Whereas the carbon atom from thiols may be used in the biosynthesis of amino acids, the sulfur atom is not used significantly in the synthesis of sulfur-containing amino acids.

Excretion

The high water solubility and molecular weights of the substance mean that, once absorbed, they are likely to be excreted by the kidneys into urine. Due to the high volatility of the substance, excretion in exhaled breath is also likely.