Zinc di(benzothiazol-2-yl) disulphide

Basic toxicokinetics

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

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1987

Report date:

1987

Reference 2

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

Test material information

Constituent 1

Reference substance name:

Benzothiazole-2-thiol

EC Number:

205-736-8

EC Name:

Benzothiazole-2-thiol

Cas Number:

149-30-4

Molecular formula:

C7H5NS2

IUPAC Name:

1,3-benzothiazole-2-thiol

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 / concentration:

4 rats per sex and dose

Control animals:

no

Results and discussion

Main ADME results

Main ADME results 1

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%)

Main ADME results 2

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.