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EC number: 248-948-6 | CAS number: 28299-41-4
Basic toxicokinetics
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:
- 1 983
- 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:
- 1 940
- 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:
- 1 953
- 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:
- 1 986
- 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:
- 1 983
- 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
- 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
Constituent 1
- 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.
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