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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
other: review BUA 1995
Rationale for reliability incl. deficiencies:
other: review: toxicokinetic data of MBTS (BUA 1993)

Data source

Referenceopen allclose all

Reference Type:
review article or handbook
Title:
2,2'-Dithio-bis-benzothiazole, BUA Report 26 (October 1993)
Author:
BUA
Year:
1995
Bibliographic source:
GDCh-Advisory Committee on Existing Chemicals of Environmental Relevance (BUA), S. Hirzel Wissenschaftliche Verlagsgesellschaft 1995
Reference Type:
publication
Title:
Disposition of 2-meraptobenzothiazole and 2-mercaptobenzothiazole disulfide in rats dosed intravenously, orally, and topically and in guinea pigs dosed topically
Author:
El Dareer, S., M.; et al.
Year:
1989
Bibliographic source:
Journal of Toxicology and Environmental Health, 27, 65-84
Reference Type:
study report
Title:
Unnamed
Year:
1986
Report Date:
1986
Reference Type:
study report
Title:
Unnamed
Year:
1986
Report Date:
1986
Reference Type:
study report
Title:
Unnamed
Year:
1987
Report Date:
1987

Materials and methods

Objective of study:
toxicokinetics
Principles of method if other than guideline:
other : review toxicokinetic data of MBTS

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
MBTS
Radiolabelling:
yes
Remarks:
14C

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male/female

Results and discussion

Main ADME resultsopen allclose all
Type:
absorption
Results:
MBTS is absorbed rapidly after oral administration, dermal absorption is slight.
Type:
excretion
Results:
MBTS is metabolized rapidly and eliminated in the urine, and to a lesser extent in the feces.

Metabolite characterisation studies

Details on metabolites:
MBTS is absorbed rapidly after oral administration, dermal absorption is slight. MBTS 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.

Any other information on results incl. tables

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 1986).

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 organism.

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).

In summary:

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.

Applicant's summary and conclusion