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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:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report date:
1992

Materials and methods

Objective of study:
toxicokinetics
Test guideline
Qualifier:
according to guideline
Guideline:
EPA OTS 795.2280 (Oral/Dermal Pharmacokinetics)
Principles of method if other than guideline:
Plasma concentrations of tributyl phosphate were measured in rats as a function of time using radiolabeled TBP and following different doses and 3 routes of exposure: 1. intravenous 2. dermal (low and hig doses, 10 and 350 mg/kg), and 3. oral (single and multiple doses at both low and hig doses).
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Tributyl phosphate
EC Number:
204-800-2
EC Name:
Tributyl phosphate
Cas Number:
126-73-8
Molecular formula:
C12H27O4P
IUPAC Name:
tributyl phosphate
Details on test material:
purity of the labeled TBP was 99%, specific activity was 112.6 µCi/mg
Radiolabelling:
yes
Remarks:
14C-TBP

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female

Administration / exposure

Route of administration:
other: iv, dermal, or oral
Vehicle:
unchanged (no vehicle)
Duration and frequency of treatment / exposure:
single or in the multiple dose group for 7 days
Doses / concentrations
Remarks:
Doses / Concentrations:
intravenous: 5 mg/kg
dermal: 10 or 350 mg/kg
single oral: 10 or 350 mg/kg
multiple oral: 10 or 350 mg/kg
No. of animals per sex per dose / concentration:
4 males and 4 femals/dose/group
Control animals:
not specified

Results and discussion

Preliminary studies:
no data

Toxicokinetic / pharmacokinetic studies

Details on absorption:
The extent of absorption was about 40% in the low dermal dose group and about 56% in the high dermal dose group. The extent of absorption did not change between the single oral and multiple oral dose groups; it was about 100% in all oral dose groups
Details on distribution in tissues:
no data
Details on excretion:
intravenous administration was followed by a rapid removal of TBP from plasma with a half-life of about 1.3 hr in both males and females. Based on the urinary excretion data , the mean terminal half-live was considerably higher (~ 29 h). This suggests that TBP/metabolites rapidly disappear from plasma due to tissue uptake, followed by slower excretion into the urine.
for the oral single or multiple dose a bioavailability of 100 % was found, with a half-life of about 25 h. urinary excretion data from dermal application demonstrated a mean terminal half-life of about 20 h.
Toxicokinetic parameters
Toxicokinetic parameters:
half-life 1st: 1.3 hours after intravenous administration

Metabolite characterisation studies

Metabolites identified:
no
Details on metabolites:
no data

Any other information on results incl. tables

Gender did not affect the pharmacokinetics of TBP

Applicant's summary and conclusion

Conclusions:
Interpretation of results no bioaccumulation potential based on study results
Executive summary:

Plasma concentrations of tributyl phosphate were measured in rats as a function of time using radiolabeled TBP and following different doses and 3 routes of exposure: 1. intravenous 2. dermal (low and hig doses, 10 and 350 mg/kg), and 3. oral (single and multiple doses at both low and hig doses). Intravenous administration was followed by a rapid removal of TBP from plasma with a half-life of about 1.3 hr in both males and females. Based on the urinary excretion data , the mean terminal half-live was considerably higher (~ 29 h). This suggests that TBP/metabolites rapidly disappear from plasma due to tissue uptake, followed by slower excretion into the urine.

For the oral single or multiple dose a bioavailability of 100 % was found, with a half-life of about 25 h. Urinary excretion data from dermal application demonstrated a mean terminal half-life of about 20 h.The extent of absorption was about 40% in the low dermal dose group and about 56% in the high dermal dose group.