Safety evaluation of certain food additives - ipcs inchem

492 FURAN-SUBSTITUTED ALIPHATIC HYDROCARBONS
Figure 2. Summary of metabolic options for furyl derivatives
Alkyl-substituted furans and furan ketones
O
R1
O
R2
R1
O
O
O
O
O
S
S S
O R
R2
O
O
SH
O
R1
R1
O
R2
R2
O
R1
O
O
Furan-substituted aldehydes, carboxylic acids and related esters
O
O
H R2
HO
R2
R3
O
R1
R3 O
R1
O
O
O R
Furan-substituted ethers
O
O
OH
O
OH
SOH
R2
OH
Furan-substituted sulfides, disulfides and thioesters
O
(>70%) of the absorbed dose was eliminated by direct conjugation of the
administered substance, whereas in humans, >70% was hydroxylated before
conjugation. The authors speculated that the benzarone glucuronic acid conjugate
was excreted directly into the bile more readily in rats and dogs than in humans,
thereby minimizing further hydroxylation in the liver (Wood et al., 1987).
Two healthy male volunteers were administered a single oral daily dose of
100 mg benzbromarone [(3,5-dibromo-4-hydroxyphenyl) (2-ethyl-3-benzofuranyl)
methanone] for 8 consecutive days (DeVries et al., 1993). The major metabolites
were formed by C1-hydroxylation to yield the corresponding
1-hydroxybenzbromarone and by hydroxylation of the benzene side-chain to yield
6-hydroxybenzbromarone. The corresponding C1 ketone formed by oxidation of the
1-hydroxy group was also identified in the urine. The ratio of C1 enantiomers of
O
O
O
SO 2 H
OH
O SSG O S-Cys
+
O
SO 3 H
Metabolites form
conjugates and are
readily excreted