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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Toxicological information

Basic toxicokinetics

Currently viewing:

Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: read -across with diphenyl ether as surrogate

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Disposition and metabolism of diphenylether in rats
Author:
Law FCP, Song YY, Chakrabarti S
Year:
1983
Bibliographic source:
Xenobiotica 13, 627-633
Reference Type:
publication
Title:
Metabolism of the parent compounds of some of the simpler synthetic estrogenic hydrocarbons
Author:
Stroud SW
Year:
1940
Bibliographic source:
J Endocrinol 2, 55-62
Reference Type:
publication
Title:
The metabolism of ethers in the rabbit. I. Anisole and diphenyl ether
Author:
Bray HG, James SP, Thorpe WV, Wasdell MR
Year:
1953
Bibliographic source:
Biochem J 54, 547-551
Reference Type:
publication
Title:
Biotransformation of diphenyl ether by trout and guinea-pigs after intraperitoneal administration
Author:
Poon G, Chui YC, Law FCP
Year:
1986
Bibliographic source:
Xenobiotica 16, 795-800
Reference Type:
publication
Title:
Irreversible binding of 14C-diphenyl ether-derived radioactivity to liver microsomes in vitro and tissue proteins in vivo
Author:
Law FCP
Year:
1983
Bibliographic source:
Drug Chem Toxicol 6, 285-294

Materials and methods

Objective of study:
metabolism
Principles of method if other than guideline:
metabolism of diphenyl ether was examined in rats, rabbits, and guinea pigs
GLP compliance:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Diphenyl ether
EC Number:
202-981-2
EC Name:
Diphenyl ether
Cas Number:
101-84-8
Molecular formula:
C12H10O
IUPAC Name:
1,1'-oxydibenzene
Details on test material:
diphenyl ether was used as surrogate
Radiolabelling:
other: radiolabelled and not radiolabelled

Test animals

Species:
other: rat, rabbit, and guinea pig
Strain:
not specified
Sex:
not specified

Administration / exposure

Route of administration:
other: intragastric (i.g.) or i.p. administration
Vehicle:
other: undiluted, with sesame oil or water
Duration and frequency of treatment / exposure:
single treatment or repeated dose for metabolism studies
Doses / concentrations
Remarks:
Doses / Concentrations:
variable doses from 5 mg/kg up to 500 mg/kg
No. of animals per sex per dose / concentration:
no. of animals not specified
Control animals:
not specified

Results and discussion

Preliminary studies:
no data

Toxicokinetic / pharmacokinetic studies

Details on absorption:
diphenyl ether is absorbed readily by various rat tissues after i.p. or i.g. administration. The absorption rate constant following a single oral dose of diphenyl ether is about 0.024/h (Law, 1983)
Details on distribution in tissues:
after i.p. administration of [14C]diphenyl ether (5 mg/kg) to rats, radioactivity was detected in all organs and tissues (Law, 1983)
Details on excretion:
more than 90% of the intragastrically administered dose was excreted in urine and faeces within 3 days; > 80 % dose was in the urine (Law, 1983)
Toxicokinetic parameters
Toxicokinetic parameters:
half-life 1st: ca. 1.5 hours after i.g. application

Metabolite characterisation studies

Metabolites identified:
yes
Details on metabolites:
in the urine of all animals 4-hydroxydiphenyl ether was found as main metabolite and in smaller amounts 4,4'-dihydroxydiphenyl ether , both metabolites as free metabolites and as conjugated substances. As additional metabolites 2-hydroxydiphenyl ether, 4-methoxymonohydroxydiphenyl ether and 4-methoxydihydroxydiphenyl ether were found in the urine of rats and rabbits

Any other information on results incl. tables

no evidence was seen for a species difference in animals in the metabolism of diphenyl ether

Applicant's summary and conclusion

Conclusions:
Interpretation of results: bioaccumulation potential cannot be judged based on study results as intermediates for the hydroxylation step the formation of arene oxides are presumed.
Executive summary:

Metabolism of diphenyl ether was examined in rats, rabbits, and guinea pigs. In the urine of these animals 4-hydroxydiphenyl ether was found as main metabolite and in smaller amounts 4,4'-dihydroxydiphenyl ether, both metabolites as free as well as conjugated substances. As additional metabolites 2-hydroxydiphenyl ether, 4-methoxymonohydroxydiphenyl ether and 4-methoxydihydroxydiphenyl ether was found in the urine of rats and rabbits. Investigations with radiolabelled [14C]diphenyl ether indicated a biological half-life of about 1.5 hours after i.g. application.