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EC number: 204-424-9
CAS number: 120-78-5
Metabolism, Toxicokinetics (cited in BUA 1995):
After a single oral dose of 0.438 or 51.1 mg 14C-MBTS/kg bw to male and
female F-344 rats, maximum 14C radioactivity was reached in the total
blood and plasma within 8 hours. After 96 hours 0.4% to 2% of the 14C
radioactivity was still detectable in erythrocytes; this also explained
the relatively slight decline of the 14C radioactivity in the total
blood compared to the plasma. Due to the relatively high 14C
concentration in the total blood and plasma in animals in the low dose
group, the authors concluded that the reaction was saturated. The
elimination from total blood and plasma was biphasic, with a rapid
alpha-phase and slower beta-phase. More than 50% of the absorbed 14C
radioactivity had already been excreted in the urine after 24 hours, and
after 96 hours the excretion was considerably >80%. In comparison,
excretion in the feces was relatively slight (>18%). The 8-hour urine
revealed 2 main and 5 metabolites (not identified), but no 14C-MBTS (CMA
El Dareer (1989) obtained comparable results in a follow-up study with
F-344 rats (males and females) and Hartley guinea pigs (females). After
daily oral doses of 0.547 mg/kg bw for 14 days and a subsequent single
oral dose of 0.73 mg 14C-MBTS/ kg bw to rats, the substance was
distributed rapidly in the organism. After 8 hours the highest 14C
radioactivity was measured in the kidneys, thyroid gland, liver, total
blood and plasma; after 96 hours only the 14C radioactivity in the
thyroid gland and total blood was still elevated compared to the other
tissues. According to the authors the substance was probably bound
covalently to the erythrocyte membrane (after 96 hours 1.2 to 1.7% of
the 14C radioactivity was still detectable in the erythrocytes); the
elimination was also biphasic (single oral dose 0.73 mg/kg bw: males:
alpha/beta phase 4.32/102 h; females: 3.91/138 h). Within 96 hours the
excretion in the urine was about 61% for male animals and about 82% for
females; the amount of administered 14C radioactivity eliminated in the
feces was 7% and 3% respectively.
No MBTS was detected in the 8-hour urine. Since two MBT metabolites (a
thioglucuronide and probably a sulfonic acid derivate) were detected,
which also occurred after oral MBT administration, the authors (El
Dareer et al. 1989) concluded that MBTS is metabolized to MBT in the
After a single intravenous dose of 0.571 mg 14C-MBTS/kg bw, rats again
showed a binding to the erythrocyte membrane (after 96 hours 1.5 to 2%
of the 14C radioactivity was still detectable in the erythrocytes), as
well as biphasic elimination (males alpha/beta phase: 1.29/18.9 h;
females: 0.64/13.2 h). Within 72 hours the elimination in the urine was
about 93% for male animals and about 101% in females; excretion of the
administered 14C radioactivity in the feces amounted to about 10 and 5%
respectively (El Dareer, 1989).
After 96-hours dermal application of 0.0336 mg 14C-MBTS/animal
(application surface: rat 2 cm2, guinea pig 5 cm2) 6-8% of the
administered dose was absorbed by male and female F-344 rats and 12% by
female Hartley guinea pigs. In this experiment most of the absorbed 14C
radioactivity was again eliminated within 96 hours in the urine (88% to
92% for rats; 97% for guinea pigs) and only a very small amount (4 to 9
% and 1 to 2%, respectively) in the feces (El Dareer 1989).
Whereas MBTS is absorbed rapidly after oral administration, dermal
absorption is slight. The test substance is metabolized rapidly and
eliminated in the urine, and to a lesser extent in the feces. Metabolism
to MBT seems likely, since glucuronic acid derivatives of MBT have been
detected in urine.
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