Dibutyl phthalate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: well documented, scientifically acceptable study. Comparable to guideline, with certain restrictions

Data source

Reference

Title:

No information

Author:

NTP Report

Year:

1995

Bibliographic source:

CHEM00324, 29-Mar-1995

Materials and methods

Objective of study:

toxicokinetics

Principles of method if other than guideline:

Method: other

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Automatically generated during migration to IUCLID 6, no data available

IUPAC Name:

Automatically generated during migration to IUCLID 6, no data available

Details on test material:

IUCLID4 Test substance: other TS: Dibutylphthalate, purity: > 99%

TS-Freetext:
Dibutylphthalate, purity: > 99%

Test animals

Species:

other: Wistar Rats, Syrian Hamster, B6C3F1 Mice

Administration / exposure

Route of administration:

other: iv or gavage

Vehicle:

CMC (carboxymethyl cellulose)

Duration and frequency of treatment / exposure:

7 day(s)

Results and discussion

Toxicokinetic / pharmacokinetic studies

Toxicokinetic parameters

Toxicokinetic parameters 1

Toxicokinetic parameters:

half-life 2nd:

Toxicokinetic parameters 2

Toxicokinetic parameters:

half-life 1st:

Toxicokinetic parameters 3

Toxicokinetic parameters:

half-life 3rd:

Any other information on results incl. tables

RS-Freetext:
The toxicokinetic studies were conducted to define the oral  bioavailability of DBP when administered as a bolus dose in aqueous  methylcellulose and to establish a dose range over which plasma kinetics  are linear. Based on the ratios of AUC for iv and oral studies,  accounting for relative dose, bioavailability was 0.90 (mice), 0 .62  (rats), and 1 .01 (hamsters) at 83, 50, and 67 mg DBP/kg, respectively .  Maximum plasma concentrations at these doses were 77, 21, and 40 µg  MBP/ml for mice, rats and hamsters, respectively. Based on examination of  plasma concentration vs. time profiles and associated kinetic parameters,  the mid and high doses appeared to be associated with nonlinear  dispositional processes. 

For mice, the Cmax and AUC values for the 166 mg/kg oral dose in the  toxicokinetic study were 107% and 89%, respectively. Maximum  concentrations obtained in the SD rat toxicokinetic study were  approximately 3-fold greater than expected but remained lower than  predicted by the prestart WF rat study. Plasma concentrations for  hamsters in the toxicokinetic studies were well predicted by those  observed in the prestart study. Obviously, the greater number of animals  used in the toxicokinetic studies (n=3/timepoint) make this data more  reliable than the prestart data (1 animal/timepoint) .

In previous studies with diethylhexylphthalate in rats, it was necessary  to administer the dose in a plasma vehicle intraarterially versus  intravenously to avoid pulmonary toxicity. The pulmonary toxicity' was  attributed to trapping of the iv dose in the lung with resultant  hemorrhagic lesions. An analogous sequestration phenomenon may have  occurred following iv administration of DBP to mice in the prestart study  wherein plasma concentrations began to increase 120 min following iv  administration . In fact, in all three species, clinical signs of  lethargy were observed for various time periods following iv  administration (prestart and toxicokinetic studies) despite efforts to  deliver as dilute a dosing solution as possible. In both rats and mice,  secondary increases in plasma concentrations were apparent in several of  the data sets. DBP and MBP are known to undergo extensive enterohepatic  recirculation which could account for the observed plasma kinetics.