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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
October 3, 1989 - August 21, 1991
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991
Report Date:
1991

Materials and methods

Objective of study:
toxicokinetics
Test guideline
Qualifier:
according to
Guideline:
EPA OPP 85-1 (Metabolism and Pharmacokinetics)
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Radiolabelling:
yes

Test animals

Species:
rat
Strain:
CD-1
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Duration and frequency of treatment / exposure:
13 days
Doses / concentrations
Remarks:
Doses / Concentrations:
Males: 50 and 500 mg/kg
Females: 50 and 500 mg/kg
No. of animals per sex per dose:
Males: 15 Females: 15
Control animals:
yes

Results and discussion

Main ADME resultsopen allclose all
Type:
excretion
Results:
54.76-66.16% of orally dosed radioactivity was excreted in the feces
Type:
excretion
Results:
27.2-38.09% was excreted in the urine

Toxicokinetic / pharmacokinetic studies

Details on absorption:
Absorbed PB appears to be quantitatively degraded since little or no parent material was found in the urine.
Details on excretion:
There was no meaninful difference between males and females at any dosage regimen with regard to the percent of administered dose excreted in the urine, the ratio of polar to nonpolar metabolites was greater in the male rats.

Metabolite characterisation studies

Metabolites identified:
yes
Details on metabolites:
The metabolic profile revealed that PB was extensively metabolized. Eight metabolites were isolated from urine or feces and characterized by mass spectrometry. These metabolites were formed through the oxidation and subsequent cleavage of the eather side chain and/or the methylene bridge on the benzodioxole ring.

Any other information on results incl. tables

In all tests, approximately 55 to 66% of recovered radioactivity was found in the faeces and 27 to 39% was
found in the urine.  The mean 14C-residues in tissues plus
carcass were less than 1.5% of the administered dose.  No
differences were noted in the ADME pattern between males and
females, between low and high doses, or between single and
repeated dosing.  Recoveries ranged from 92 to 100%.

Applicant's summary and conclusion

Conclusions:
No bioaccumulation potential based on study results
Based upon the results of this study, dosage patterns (quantity or number of doses) and the sex of the rat has very little or no affect on the excretion patterns of orally administered 14C Piperonyl butoxide. In addition, the data indicate that bioaccumation of piperonyl butoxide or its degradates in tissues in unlikely following oral administration of 14C piperonyl butoxide.