N-cyclohexylbenzothiazole-2-sulfenamide

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, well-documented study report, which meets scientific principles

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2007

Materials and methods

Objective of study:

toxicokinetics

Principles of method if other than guideline:

Kinetic study of acidic hydrolysis of CBS at pH 1 at 35°C

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

N-cyclohexylbenzothiazole-2-sulfenamide

EC Number:

202-411-2

EC Name:

N-cyclohexylbenzothiazole-2-sulfenamide

Cas Number:

95-33-0

Molecular formula:

C13H16N2S2

IUPAC Name:

N-(1,3-benzothiazol-2-ylsulfanyl)cyclohexanamine

Details on test material:

CBS commercial grade, active matter content: 97.7%

Test animals

Species:

other: in vitro

Results and discussion

Main ADME results

Main ADME results 1

Type:

other: Acidic hydrolysis of CBS

Results:

CBS is metabolised to MBTS in a two-step reaction

Main ADME results 2

Type:

other: Acidic hydrolysis of CBS

Results:

acid hydrolysis of CBS at pH 1 is nearly constant 9% per day for the first 6 to 7 days, rapid drop down to 2% per day for the following time

Any other information on results incl. tables

Within the first 6.5 days (=156 h) the rate of hydrolysis is nearly linear with about 9.0% over day based on the CBS amount at t = 0h and than drops to about 2.0% for the following 9.5 days (= 228 h). Parallel to this pH increase per day within the first 6.5 days is about 0.4 and than suddenly drops to about 0 for the following days.

A correlation of the CBS loss with the formation of MBTS shows that at the beginning the rate of hydrolysis is remarkably higher than the rate of MBTS formation which easily be explained with the low MBT concentration in this period. When there is enough MBT present, which at pH<5 is a precipitated solid like CBS and MBTS, the MBTS formation rate increases rapidly to slow down again after 8 to 9 days (= 216 h) to nearly the same rate than that of the CBS hydrolysis. The trend of the sums of the MBT moieties of CBS and MBTS shows that within analytical accuracy all hydrolyzed CBS is metabolized to MBTS in two steps; in the beginning free mercaptobenzothiazole (MBT) and cyclohexylamine appeared. The free MBT then reacted directly with the starting substance CBS leading to dimeric MBT (mercaptobenzothiazyl disulfide, MBTS) and cyclohexylamine. The interim formed MBT was not measured as it is dissolved during work-up of the sample.

Applicant's summary and conclusion

Executive summary:

Within the first 6.5 days (=156 h) the rate of hydrolysis is nearly linear with about 9.0% over day based on the CBS amount at t = 0h and than drops to about 2.0% for the following 9.5 days (= 228 h). Parallel to this pH increase per day within the first 6.5 days is about 0.4 and than suddenly drops to about 0 for the following days.

A correlation of the CBS loss with the formation of MBTS shows that at the beginning the rate of hydrolysis is remarkably higher than the rate of MBTS formation which easily be explained with the low MBT concentration in this period. When there is enough MBT present, which at pH<5 is a precipitated solid like CBS and MBTS, the MBTS formation rate increases rapidly to slow down again after 8 to 9 days (= 216 h) to nearly the same rate than that of the CBS hydrolysis. The trend of the sums of the MBT moieties of CBS and MBTS shows that within analytical accuracy all hydrolyzed CBS is metabolized to MBTS in two steps; in the beginning free mercaptobenzothiazole (MBT) and cyclohexylamine appeared. The free MBT then reacted directly with the starting substance CBS leading to dimeric MBT (mercaptobenzothiazyl disulfide, MBTS) and cyclohexylamine. The interim formed MBT was not measured as it is dissolved during work-up of the sample.