Tributyl phosphate

Basic toxicokinetics

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

Test material information

Constituent 1

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.