Registration Dossier
Registration Dossier
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EC number: 212-611-1 | CAS number: 831-82-3
Endpoint summary
Administrative data
Link to relevant study record(s)
- 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
- Objective of study:
- excretion
- metabolism
- 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
- Specific details on test material used for the study:
- Not Specified
- Radiolabelling:
- no
- Species:
- rabbit
- Strain:
- not specified
- Details on species / strain selection:
- Not Specified
- Sex:
- not specified
- Details on test animals or test system and environmental conditions:
- Not Specified
- 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 / concentration:
- Not Specified
- Control animals:
- not specified
- Positive control reference chemical:
- Not Specified
- Details on study design:
- Not Specified
- Details on dosing and sampling:
- Not Specified
- Statistics:
- Not Specified
- Preliminary studies:
- Not Specified
- 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.
- 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.
- 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.
Reference
Description of key information
- Phase I : enzymes introduce reactive or polar group into xenobiotics to convert lipophilic compounds into hydrophilic products that are readily excreted.
- Phase II ; the modified compounds are conjugated to polar compounds (these reactions are catalysed by transferase enzymes such as glutathione S-transferases).
Dermal Absorption
After semi-occlusive application to the clipped skin of rats, almost 20 % of the Diphenyl Ether dose was absorbed as measured by the amount excreted in urine. However, in a diffusion in vitro experiment, only 0.3 % (rat skin) or 0.2 % (human skin) of diphenyl ether penetrated the skin in vitro. The higher absorption in the in vivo experiment may have been caused by the vehicle (diethyl phthalate).
As indicated in basic Toxicokinetics data, due the -OH fragment, 4 -PhenoxyPhenol is more soluble in water than Diphenyl Ether. Therefore, the percentage of the dermal dose absorbed for 4 -Phenoxyphenol is expected lower than the Diphenyl Ether percentage (20%)
Toxicokinetics
In organism, metabolism is divided into two phases:
The 4-PhenoxyPhenol has a polar group in addition to Diphenyl Ether, this suggests that 4-PhenoxyPhenol is the breakdown product of Diphenyl Ether after the phase I.
The study “Basic toxicokinetics-2-Patty's-2001” confirms this point and that 4-PhenoxyPhenol are modified by the phase II and it is the principal metabolic of the Diphenyl Ether.
Key value for chemical safety assessment
- Absorption rate - dermal (%):
- 20
Additional information
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