Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics
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: acceptable, well-documented publication and study report which meets basic scientific principles

Data source

Reference
Reference Type:
publication
Title:
Comparative metabolism and toxicokinetics of 14C-Resorcinol Bis-Diphenylphosphate (RDP) in the rat, mouse, and monkey
Author:
Freudenthal RI., McDonald LJ., Johnson JV., McCormick DL. and Henrich RT
Year:
2000
Bibliographic source:
International Journal of Toxicology 19: 233-242

Materials and methods

Objective of study:
absorption
distribution
toxicokinetics
Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 417 (Toxicokinetics)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
Nonradiolabeled RDP was obtained from Akzo NobelChemicals (Dobbs Ferry, NY).14C-RDP was purchased from DuPont/New England Nuclear (Boston, MA). It had a specific cactivity of 48.6 mCi/mmole. The radiolabeled RDP was repurified prior to use, to achieve a minimum radiochemical purity of 99.0%.

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:
The RDP was present in significant amounts only in the feces of animals exposed by inhalation or gavage; this appears to reflect unabsorbed ingested material. Dermal absorption of RDP in the rat was relatively low 83% and 20% absorption by the oral and dermal route, respectively.
Details on distribution in tissues:
The brain, mesenteric fat, kidneys, liver, lungs, testes/ovaries, and spleen were removed, weighed, and homogenized. Measured aliquots of the tissue homogenates, and of the residual carcass, were solubilized and then the radioactivity therein was quantified by scintillation counting.
Details on excretion:
Significant quantitative differences were observed for the radioactivity eliminated in the feces, the primary route of excretion. The largest fraction of the administered dose eliminated in the feces was seen in rats that received RDP via oral dosing. In these animals, approximately 80% of the dose was excreted during the first day after administration. Fecal excretion of radiolabel by rats exposed to RDP by other routes was considerably slower. Animals that received RDP by the inhalation, intravenous, and dermal routes had 60%, 48%, and 32% of the administered dose in their feces. Regardless of the route of exposure, fecal excretion was at least threefold greater than urinary excretion of total radiolabel. The expired air was a minor route of excretion, regardless of route of dosing. A comparison of the parameters obtained after intravenous injection of RDP to primates and rats showed similar concentration versus time profiles, and both species demonstrated two-compartment toxicokinetics. In both species, the primary route of excretion was via the feces. After dermal exposure, there was significantly less absorption by the primate as compared to the rat.
Toxicokinetic parametersopen allclose all
Test no.:
#1
Toxicokinetic parameters:
AUC: 1895.0 ± 213 µg equiv × h/mL (monkey i.v.)
Test no.:
#2
Toxicokinetic parameters:
Cmax:
Test no.:
#3
Toxicokinetic parameters:
Tmax:

Applicant's summary and conclusion