Registration Dossier

Toxicological information

Basic toxicokinetics

Currently viewing:

Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: well conducted and sufficient documented

Data source

Referenceopen allclose all

Reference Type:
secondary source
Title:
Unnamed
Year:
1974
Reference Type:
publication
Title:
The metabolism of 14C o-chlorotoluene in the rat
Author:
Wold JS, Emmerson JL
Year:
1974
Bibliographic source:
The Pharmacologist 16, 196

Materials and methods

Objective of study:
metabolism
Principles of method if other than guideline:
uniformly ring-labeled 14C o-chlorotoluene was administered by gavage to rats at a dose of 320 mg/kg bw. Expired air, urine and faeces were examined for metabolites
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
uniformly ring-labeled 14C o-chlorotoluene
Radiolabelling:
yes

Test animals

Species:
rat
Strain:
not specified
Sex:
not specified

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
not specified
Duration and frequency of treatment / exposure:
single application
Doses / concentrations
Remarks:
Doses / Concentrations:
320 mg/kg
No. of animals per sex per dose:
no data
Control animals:
not specified

Results and discussion

Preliminary studies:
no data

Toxicokinetic / pharmacokinetic studies

Details on absorption:
no data
Details on distribution in tissues:
no data
Details on excretion:
the recovery of radioactivity at 48 h averaged 11 % in the expired air, 81 % in urine, and 4 % in feces; radioactivity in expired air was identified as unchanged o-chlorotoluene; urinary metabolites (as % of dose) were: o-chlorohippuric acid (16- 20 %), a mercapturic acid conjugate of o-chlorotoluene (20- 24 %) and polar metabolites (36-43 %); enzymatic hydrolysis of rat urine indicated that the polar metabolites included the glucuronide conjugate of the phenolic hydroxylation product of o-chlorotoluene; unchanged o-chlorotoluene was not present in urine or feces of treated rats

Metabolite characterisation studies

Metabolites identified:
yes
Details on metabolites:
o-chlorohippuric acid, mercapturic acid conjugate of o-chlorotoluene, glucuronide conjugate of the phenolic hydroxylation product of o-chlorotoluene

Any other information on results incl. tables

unchanged o-chlorotoluene was not present in urine or feces of treated rats

Applicant's summary and conclusion

Executive summary:

Uniformly ring-labeled 14C o-chlorotoluene was administered by gavage to rats at a dose of 320 mg/kg bw. Expired air, urine and faeces were examined for metabolites.

The recovery of radioactivity at 48 h averaged 11 % in the expired air, 81 % in urine, and 4 % in feces; radioactivity in expired air was identified as unchanged o-chlorotoluene; urinary metabolites (as % of dose) were: o-chlorohippuric acid (16- 20 %), a mercapturic acid conjugate of o-chlorotoluene (20- 24 %) and polar metabolites (36-43 %); enzymatic hydrolysis of rat urine indicated that the polar metabolites included the glucuronide conjugate of the phenolic hydroxylation product of o-chlorotoluene; unchanged o-chlorotoluene was not present in urine or feces of treated rats