Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data

Data source

Reference
Reference Type:
review article or handbook
Title:
Patty's Toxicology Volumes 1-9 5th ed
Author:
Bingham, E.; Cohrssen, B.; Powell, C.H.;
Year:
2001
Bibliographic source:
John Wiley & Sons. New York, N.Y. p. V5 932

Materials and methods

Objective of study:
excretion
metabolism
Test guideline
Qualifier:
no guideline required
Principles of method if other than guideline:
Diphenyl Ether was injected into the rabbit. Urine was recolted and analysed to determine metabolites.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
not specified
Specific details on test material used for the study:
Not Specified
Radiolabelling:
no

Test animals

Species:
rabbit
Strain:
not specified
Details on species / strain selection:
Not Specified
Sex:
not specified
Details on test animals and environmental conditions:
Not Specified

Administration / exposure

Route of administration:
other: injection
Vehicle:
not specified
Details on exposure:
Not Specified
Duration and frequency of treatment / exposure:
Not Specified
No. of animals per sex per dose:
Not Specified
Control animals:
not specified
Positive control:
Not Specified
Details on study design:
Not Specified
Details on dosing and sampling:
Not Specified
Statistics:
Not Specified

Results and discussion

Preliminary studies:
Not Specified

Toxicokinetic / pharmacokinetic studies

Details on absorption:
Not Specified
Details on distribution in tissues:
Not Specified
Details on excretion:
In the rabbit, no cleavage of the ether linkage /of phenyl ether occurs.

Metabolite characterisation studies

Metabolites identified:
yes
Details on metabolites:
The major metabolite was the p-hydroxylated ether, which is excreted both unconjugated (15%) and conjugated with glucuronic acid (63%) and sulfuric acid (12%). Another metabolite was also isolated from the rabbit urine and fairly well identified as di(p-hydroxyphenyl) ether.

Applicant's summary and conclusion

Conclusions:
Diphenyl Ether, when injected into the rabbit, was excreted in the urine as p-hydroxyphenyl phenyl ether and none was excreted as the unchanged ether.
Confirmation of these observation showed that in the rabbit no cleavage of the ether linkage occurs. The major metabolite was the p-hydroxylated ether, which is excreted both unconjugated (15%) and conjugated with glucuronic acid (63%) and sulfuric acid (12%). Another metabolite was also identified as di(p-hydroxyphenyl)-ether.
Executive summary:

Diphenyl Ether, when injected into the rabbit, was excreted in the urine as p-hydroxyphenyl phenyl ether and none was excreted as the unchanged ether.

Confirmation of these observation showed that in the rabbit no cleavage of the ether linkage occurs. The major metabolite was the p-hydroxylated ether, which is excreted both unconjugated (15%) and conjugated with glucuronic acid (63%) and sulfuric acid (12%). Another metabolite was also identified as di(p-hydroxyphenyl)-ether.