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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: taken from NTP Technical Report

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
2005

Materials and methods

Objective of study:
metabolism
Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
taken from NTP Technical Report
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Radiolabelling:
yes
Remarks:
14C-Anthraquinone

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male

Administration / exposure

Details on exposure:
Labelled 14C-Anthraquinone was administered to animals by intravenous injection at 0.35 mg/kg body weight or by gavage at doses ranging from 0.35 to 350 mg/kg.
Control animals:
not specified

Results and discussion

Metabolite characterisation studies

Metabolites identified:
yes
Details on metabolites:
1-hydroxyanthraquinone
2-hydroxyanthraquinone

Any other information on results incl. tables

Following oral administration, Anthraquinone was absorbed from the gastrointestinal tract and distributed to tissues. Although the highest concentration of Anthraquinone was initially found in adipose tissue, no indication of bioaccumulation was apparent in any tissue. The majority of the radiolabel was eliminated in the feces and the urine by 24 hours after dosing at all four concentrations. At 96 hours after dosing, less than 5% of the administered dose remained in major tissues.

Elimination of over 50% of the administered radioactivity in the feces suggested substantial excretion of parent and/or metabolites in the bile. This was confirmed by administering Anthraquinone to bile-duct cannulated rats. During the 6-hour period of sample collection, 35% of the administered dose was recovered in bile. Analysis of the bile samples indicated that less than 3% of the radioactivity collected was present as the parent compound, suggesting extensive hepatic metabolism. Analysis of urine from dosed rats by high performance liquid chromatography revealed the presence of as many as 11 metabolites. Two of the metabolites identified were 1-hydroxyanthraquinone and 2-hydroxyanthraquinone.

Applicant's summary and conclusion

Conclusions:
Based on available data, Anthraquinone was absorbed from the gastrointestinal tract and distributed to tissues. No indication of Anthraquinone bioaccumulation was apparent in any tissue. The majority of the radiolabel was eliminated in the feces and the urine. At 96 hours after dosing, less than 5% of the administered dose remained in major tissues. Elimination of over 50% of the administered radioactivity was found in the feces. There seemed to be an extensive hepatic metabolism of Anthraquinone. Analysis of urine revealed the presence of 11 metabolites, with 1-hydroxyAnthraquinone and 2-hydroxy Anthraquinone being the major ones.