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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study, test protocol reviewed by the EPA

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1987
Report Date:
1987
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

Materials and methods

Objective of study:
excretion
metabolism
Principles of method if other than guideline:
other: other: toxicokinetic study, test protocol reviewed by the EPA
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
MBT, purity: 98%
Radiolabelling:
yes
Remarks:
14C MBT

Test animals

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

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Duration and frequency of treatment / exposure:
daily
Doses / concentrations
Remarks:
Doses / Concentrations:
MBT: 0.509 mg/kg, 14C MBT: 0.503 mg/kg (0.0586 mCi/kg)
No. of animals per sex per dose:
4 rats per sex and dose
Control animals:
no

Results and discussion

Main ADME resultsopen allclose all
Type:
excretion
Results:
6 h after aministration of [14C] MBT >90% were excreted with the urine, excretion with the feces was minor (5.22 to 9.99%)
Type:
metabolism
Results:
Two major metabolites were found in urine, the major one being a glucuronide derivate of MBT

Toxicokinetic / pharmacokinetic studies

Details on excretion:
96 h after aministration of [14C] MBT >90% were excreted with the urine, excretion with the feces was minor (5.22 to 9.99%)

Metabolite characterisation studies

Details on metabolites:
Two major metabolites were found in urine, the major one being a glucuronide derivate of MBT

Any other information on results incl. tables

Males and females administered with [14C] MBT excreted in the urine 96 h after dosing 90.7% and 101% of the radioactivity, respectively. Simularly, 9.99% and 5.22% of the dose, respectively, was excreted in the feces in 96 h. A small portion of the administered radiosctivity (1.20 to 1.53% of dose) remains associated with the erythrocytes at 96 h after dosing. Most of this radioactivity was bound to the erythrocyte membranes.

Half-lives of elimination from the plasma have been calculated to be 4.7 to 8.56 h and 5780 to 6000 h for the alpha and beta phases, respectively.

At 96 h after dosing, only trace amounts of radioactivity remain in other tissues. Of these tissues, thyroid contains the highest concentration. No intact MBT or MBTS was seen in the urine. Only two metabolites appeared in the urine at 8 hours. The major one was a glucuronide derivate of MBT. The other metabolite was not subject to hydrolysis by acid, beta-glucuronidase, or sulfarase, and therefore is probably not a conjugate.

The authors conclude, that radioactivity from [14C] MBT appears to be excreted in a similar manner by male and female rats dosed previously for 14 days with unlabeled MBT. With the exception of whole blood and thyroid, retention of radioactivity from [14C] MBT in tissues is negligible. Excretion is primarily in the urine, with relative small amounts appearing in the feces. Only two metabolites were found in the urine, the major one being a glucuronide derivate of MBT.

Applicant's summary and conclusion