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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Meets generally accepted scientific standards, sufficiently documented with acceptable restrictions

Data source

Reference
Reference Type:
publication
Title:
The metabolism of acenaphthene in the rat
Author:
Chang LH, Young L
Year:
1943
Bibliographic source:
J. Biol. Chem., 151, 87-91

Materials and methods

Objective of study:
excretion
Principles of method if other than guideline:
Method: other: metabolic study
GLP compliance:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Acenaphthene
EC Number:
201-469-6
EC Name:
Acenaphthene
Cas Number:
83-32-9
Molecular formula:
C12H10
IUPAC Name:
1,2-dihydroacenaphthylene
Details on test material:
Acenaphthene [CAS No. 83-32-9]
Radiolabelling:
no

Test animals

Species:
rat
Strain:
not specified
Sex:
male

Administration / exposure

Route of administration:
other: Oral feed or gavage
Vehicle:
other: Gavage: fine suspension of the TS in dilute starch solution
Duration and frequency of treatment / exposure:
up to 12 days
Doses / concentrations
Remarks:
Doses / Concentrations:
Males: approx. 0.45 g/(kg bw*d) in diet; approx. 0.3 g/kg bw by gavage every alternate day
No. of animals per sex per dose / concentration:
Number of animals 6 (oral feed) and 3 (gavage)
Control animals:
no
Positive control reference chemical:
no
Details on dosing and sampling:
TEST MATERIAL CONCENTRATIONS
Diet: 1 %; 
gavage: 0.1 g/ml suspension

EXPOSURE period No direct information available. From the total final amounts applied and  the doses administered, the exposure times can be estimated: 
Diet: Total ingested amount per 6 rats = 4.1 g ==> approx. 0.7 g/rat              
daily estimated dose approx. 0.15 g/d per rat ==> 4 - 5 days. 

Gavage: Total ingested amount per 3 rats = 1.8 g ==> 0.6 g/rat             
Dose on alternate days: 0.1 g per rat ==> 6 dosing days          => 12 exposure days 

SAMPLING: Urine and feces were daily collected separately. But only the  urine was collected for analysis and isolation.

SAMPLE PROCESSING and ANALYTCS Urine samples were made alkaline, extracted with ether. After acidification and resting for 1 hour, a precipitate formed. The total was extracted with dichloromethane. The combined extracts were  concentrated to a small volume by distillation and evaporated to dryness  under vacuum. The residue was treated with hot ethanol, the solution filtered and  cooled, while a precipitate formed (pale yellow needles), melting point:  268 °C. The identity of the compound was established through comparison with  phys.-chem. data of a reference substance, re-synthesis and  characteristic reactions

Results and discussion

Metabolite characterisation studies

Metabolites identified:
yes
Details on metabolites:
The amount of the metabolite was very small. The metabolite found in the urine on acidification was identified as naphthalic anhydride, the anhydride that readily forms from naphthalene-1,8-dicarboxylic acid (naphthalic acid).

Any other information on results incl. tables

The amount of the metabolite was very small: only 60 mg were obtained after administration of the gavage (dose: 1.8 g), only 215 mg were 

obtained after feeding (total dose: 4.1 g).
The metabolite which appeared on acidification of the urine was identified as naphthalic anhydride, the anhydride that readily forms from 

naphthalene-1,8-dicarboxylic acid (naphthalic acid).
    

Applicant's summary and conclusion

Conclusions:
This early study provides strong evidence that the primary metabolic reaction of acenaphthene starts with the oxidative cleavage of the 5-membered ring in acenaphthene in rat. No quantitative conclusions can be drawn from the work, because no complete analysis on the metabolite profile was performed (urine partly examined, feces dismissed).
Executive summary:

The primary metabolite that is excreted into the urine of rats was not identified, naphthalic acid or conjugates of it that are hydrolysed upon acidification. Whatever the nature of the compound(s) excreted into the urine, the study strongly suggests that the 5-membered carbon ring of acenaphthene undergoes oxidative fission in the rat.

 

 

This early study provides strong evidence that the primary metabolic reaction of acenaphthene starts with the oxidative cleavage of the 5-membered ring in acenaphthene in rat.