Fate of dipropyl sulphide and dipropyl sulphoxide in rat

Abstract

1. Dipropyl [35S]-sulphide and dipropyl [35S]-sulphoxide were administered by gavage (4.24 mM/4 ml/kg body wt) to adult male Wistar rats following an overnight fast. 2. Urine was the major route of excretion for both compounds, with more radioactivity appearing during the second day (c. 43%) than the first (c. 26%). Only small amounts were found in the faeces (c. 5%). Biliary excretion played an important role with substantial amounts of the dose (c. 25%) passing through the bile duct during 0-48 h. Following ingestion of the sulphide large quantities of radioactivity (18%) were detected in exhaled air. Near total recoveries were achieved for both compounds, although 13% of the radioactivity remained within the carcass 3 days after administration of the sulphoxide. 3. Absorption and elimination half-lives were in the region of 5 and 8 h, respectively, for both compounds, with the sulphoxide plasma profile showing a prolonged plateau region. 4. Metabolism was limited to oxidation of the sulphur with the formation of the sulphoxide and sulphone, and trace amounts of inorganic sulphate.

Joint FAO/WHO Expert Committee on Food Additives (JECFA)

“…Monosulfides are expected to undergo oxidation, mainly to the corresponding sulfoxide and sulfone. Sulfoxides and sulfones are physiologically stable and are excreted unchanged in the urine (McBain & Menn, 1969;Nickson & Mitchell, 1994;Nickson et al, 1995;Nnane & Damani, 1995).…”

Scientific Opinion on Flavouring Group Evaluation 8, Revision 3 (FGE.08Rev3): Aliphatic and alicyclic mono‐, di‐, tri‐, and polysulphides with or without additional oxygenated functional groups from chemical groups 20 and 30

“…Based on the numerous examples of successive oxidation of sulphides to sulphoxides and sulphones by FMO and P450 enzymes in a variety of test systems (Cashman & Williams, 1990;Cashman et al, 1995a;Cashman et al, 1995b;Elfarra et al, 1995) and (Nnane & Damani, 1995;Rettie et al, 1990;Sadeque et al, 1992;Sadeque et al, 1995;Yoshihara & Tatsumi, 1990), it is concluded that the oxidation pathway is the major route of biotransformation of (mono)sulphides in humans (Ziegler, 1980;Nickson & Mitchell, 1994). The same applies to sulphides containing an oxygenated functional group (i.e., alcohol, aldehyde, acid or ketone function); indeed, although C-oxidation and/or conjugation may compete with Soxidation, sulphoxide formation is usually the major metabolic pathway.…”

“…Urinary metabolites collected during the first 24 hours included the sulphoxide (92.5 %), sulphone (5 %) and sulphate (3 %). On days 2 and 3, the sulphoxide accounted for more than 98 % of daily urinary metabolites (Nickson & Mitchell, 1994).…”

Scientific Opinion on Flavouring Group Evaluation 17, Revision 3 (FGE.17Rev3): Pyrazine derivatives from chemical group 24

“…The reactive lone pair of electrons on divalent sulphur in thiols and monosulphides permits rapid oxidation. Alkyl and aromatic sulphides, such as the candidate substances 2-isopropyl-3-methylthiopyrazine ] and 2-methyl-3-methylthiopyrazine ], can be oxidised to sulphoxides and then to sulphones (Hoodi and Damani, 1984;Nickson and Mitchell, 1994;Nickson et al, 1995). The oxidation to sulphoxides is catalysed by at least two enzyme systems, cytochrome P-450s and the flavincontaining monooxygenases (FMO) (Cashman and Williams, 1990;Cashman et al, 1995a;Cashman et al, 1995b;Elfarra et al, 1995) and (Hoodi and Damani, 1984;Nnane and Damani, 1995;Rettie et al, 1990;Sadeque et al, 1992;Sadeque et al, 1995;Yoshihara and Tatsumi, 1990;Ziegler, 1980).…”