Registration Dossier

Administrative data

Endpoint:
dermal absorption 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, comparable to guideline study

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

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 427 (Skin Absorption: In Vivo Method)
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

Type of coverage:
occlusive
Vehicle:
other: tetrahydrofuran
Duration of exposure:
up to 96 h
Doses:
0.0361 mg (0.00501 mCi)/animal
No. of animals per group:
4 per dose and sex
Control animals:
no

Results and discussion

Percutaneous absorptionopen allclose all
Dose:
0.0361 mg (0.00501 mCi)/animal
Parameter:
percentage
Absorption:
16.1 %
Remarks on result:
other: 96 h
Remarks:
male rat
Dose:
0.0361 mg (0.00501 mCi)/animal
Parameter:
percentage
Absorption:
17.5 %
Remarks on result:
other: 96 h
Remarks:
female rats

Any other information on results incl. tables

Animal morbidity and mortality were also checked daily during the experiment. No mortality and no evidence of morbidity were observed.

By washing of the site of application, more radioactivity from [14C] MBT and [14C] MBTS was removed from guinea pigs than from rats. Amounts of [14C] MBT removed from the site of application by washing were 6.07, 9.01, and 38.2 % of the dose for male rats, female rats, and guinea pigs, respectively.

After washing of the skin radioactivity from [14C] MBT remaining at the site of application was 61.5, 51.6, and

15.2% of the dose for male rats, female rats, and guinea pigs, respectively.

Guinea pigs absorbed more radioactivity from [14C] MBT and [14C] MBTS than rats; and, for both species, absorption of [14C] MBT was more extensive than that for [14C] MBTS. In 96 hr, 16.1, 17.5, and 38.4% of the dose of [14C] MBT was absorbed by male rats, female rats, and guinea pigs, respectively. Rats and guinea pigs absorbed about 2.5-fold more [14C] MBT than [14C] MBTS.

For male and female rats dosed topically with [14C] MBT, there were no values for the same type of sample that did not have overlapping standard deviations.

For male rats, female rats, and guinea pigs dosed with [14C] MBT, the concentration

of radioactivity in whole blood relative to that in plasma was 12.7-, 12.9-, and 7.3-fold greater, respectively

For both [14C] MBT and [14C] MBTS, urine was the primary route for excretion of absorbed radioactivity. Of the absorbed dose of [14C] MBT, the amounts excreted in urine were 74% by male rats, 77% by female rats, and 87% by guinea pigs.

Similarly for [14C] MBTS, 54% was excreted in urine by male rats, 68% by female rats, and 73% by guinea pigs. For both compounds, the percentage of the dose excreted in the urine of guinea pigs was 2.1-2.8-fold that for rats, suggesting that in these species, MBT and MBTS follow the same excretory pattern.

In contrast, more radioactivity (2-3-fold) from [14C] MBT was excreted in the feces by rats than by guinea pigs. This route of excretion was minor, however accounting for less than 7% of the absorbed dose.

Total recovery of radioactivity ranged from 81.9 to 94.4% of the dose of [14C] MBT and from 76.8 to 88.7% of the dose of [14C] MBTS.

Applicant's summary and conclusion