Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Old study covering only the metabolism, not comprehensive regarding all the possible metabolites but the partial results are valid.

Data source

Reference
Reference Type:
publication
Title:
The synthesis of mercapturic acids from diethyl sulphate and di-n- propyl sulphate in the rat
Author:
Kaye CM
Bibliographic source:
Xenobiotica 4(6): 329-336

Materials and methods

Objective of study:
metabolism
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
No guideline available at the time of the study.
Determination of some metabolites of DES in the urine of rats by paper chromatography
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Supplier: BDH chemicals (UK)
DES was redistilled at 136° and 60 mmHg before use.
Radiolabelling:
no

Test animals

Species:
rat
Strain:
other: CFE
Sex:
male

Administration / exposure

Route of administration:
other: subcutaneous, ip and gavage
Vehicle:
arachis oil
Duration and frequency of treatment / exposure:
1 treatment
Doses / concentrations
Remarks:
Doses / Concentrations:
1 mL of a solution at 5% (v/v) corresponding to ca 59 mg/ rat, by sc injection
No detail about the dose for the ip and oral routes.
No. of animals per sex per dose:
78 animals for the sc treatment, no data for the other routes
Control animals:
not specified

Results and discussion

Preliminary studies:
no data
Main ADME results
Type:
metabolism
Results:
identification of ethylmercapturic acid, a sulfoxide compound and no S-ethyl-cysteine in the urine

Toxicokinetic / pharmacokinetic studies

Details on absorption:
not tested
Details on distribution in tissues:
not tested
Details on excretion:
No comprehensive evaluation of the excretion process has been performed. Some metabolites of DES are excreted in the 24 h urine.

Metabolite characterisation studies

Metabolites identified:
yes
Details on metabolites:
identification of ethylmercapturic acid, a sulfoxide compound and no S-ethyl-cysteine in the urine disregarding the route of administration.
An attempt to quantify the ethylmercapturic acid was made: it would correspond to 2.4% of the DES administered.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): no data
identification of ethylmercapturic acid, a sulfoxide compound and no S-ethyl-cysteine in the urine disregarding the route of administration.
Executive summary:

Paper chromatography of urine of rats dosed subcutaneously, intra­peritoneally or orally with diethyl sulphate revealed the presence of ethyl­mercapturic acid.

After administration of diethyl sulphate to rats ethylmercapturic acid was isolated as its dicyclohexylammonium salt, in 2.4% yield from the urine.