Decahydronaphthalene

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

May - August 1996

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Unnamed

Year:

2005

Reference 2

Reference Type:

publication

Title:

Single administration toxicokinetic studies of decalin (decahydronaphthalene) in rats and mice

Author:

Dill JA, Fuciarelli AF, Lee KM, Mellinger KM, Chan PC, Burka LT and Roycroft JH

Year:

2003

Bibliographic source:

Toxicol. Sci. 72, 210-222

Materials and methods

Objective of study:

toxicokinetics

Principles of method if other than guideline:

NTP method detailed in the report

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Decahydronaphthalene

EC Number:

202-046-9

EC Name:

Decahydronaphthalene

Cas Number:

91-17-8

Molecular formula:

C10H18

IUPAC Name:

decahydronaphthalene

Constituent 2

Reference substance name:

Dekalin

IUPAC Name:

Dekalin

Details on test material:

Decalin
Purity >99%
Supplier: Sigma Aldrich Fluka Bulk Chemicals (St Louis, USA)

Radiolabelling:

no

Test animals

Species:

other: rat and mice

Strain:

other: F344/N rats and B6C3F1 mice.

Sex:

male/female

Administration / exposure

Route of administration:

inhalation: vapour

Vehicle:

unchanged (no vehicle)

Duration and frequency of treatment / exposure:

single 6-hour whole body inhalation exposure

Doses / concentrations

Remarks:

Doses / Concentrations:
25, 100, or 400 ppm

Control animals:

no

Positive control reference chemical:

no positive control

Details on dosing and sampling:

Heparinized blood was collected from the retroorbital plexus (rats) or supraorbital sinus (mice) under 70% carbon
dioxide (in room air) anesthesia after exposure. Each animal was bled twice, once in each eye (except rats, which
were sampled three times at less than 5 minutes after exposure, 60 minutes, and approximately 1440 minutes after
exposure). Rats from all exposure groups were bled at 5 minutes or less and at 10, 20, 30, 60, 120, 240, 480, and
1440 minutes postexposure. Mice from the 25 ppm group were bled at 5 minutes or less and at 10, 20, 40, 60, 120,
240, and 360 minutes postexposure. Mice from the 100 and 400 ppm groups were bled at less than 5 minutes and
at 10, 20, 40, 60, 180, 360, and 480 minutes postexposure. Samples were stored at –70° C until analyses.

Results and discussion

Toxicokinetic / pharmacokinetic studies

Toxicokinetic parameters

Toxicokinetic parameters 1

Test no.:

#1

Toxicokinetic parameters:

half-life 1st: 23.0-26.6 min

Toxicokinetic parameters 2

Test no.:

#1

Toxicokinetic parameters:

half-life 2nd: 418-511 min

Toxicokinetic parameters 3

Test no.:

#1

Toxicokinetic parameters:

AUC: 2.18-5.26 µg min/g ppm

Any other information on results incl. tables

Decalin exhibited biexponential blood elimination kinetics in rats and mice after a single 6-hour whole body inhalation exposure. A rapid initial phase (") representing elimination from blood and rapidly perfused tissues such as liver, lung, and kidney was followed by a slower phase ($) representing elimination from slowly perfused tissues such as muscle and fat. The biexponential curves, weighted using [mean decalin blood concentrations]–2, that were used to model the data and to estimate toxicokinetic parameters for rats are presented in Figures M1 and M2; parameter estimates, A0, ", B0, and $, were obtained from these models. The biexponential curves, weighted using [mean decalin blood concentration]–1, that were used to model the data and to estimate toxicokinetic parameters for mice are presented in Figures M2 and M3; parameter estimates, A0, ", B0, and $, were obtained from these models . The parameter estimates, A0, ", B0, and $ were used to calculate t½", t½$, C0, and AUC4.

Applicant's summary and conclusion

Conclusions:

Decahydronaphthalene is rapidly eliminated by rats or mice following a single inhalation exposure. No sex differences were noted.
Therefore, no significant bioaccumulation potential is expected based on the study results.

Executive summary:

The single exposure inhalation study was designed to estimate toxicokinetic parameters relevant to the elimination

of decalin from the blood of F344/N rats and B6C3F1 mice. Male and female F344/N rats and B6C3F1 mice

received a single 6-hour whole body inhalation exposure to 25, 100, or 400 ppm decahydronaphthalene. Postexposure blood

samples were analyzed for decalin, and the results were used to estimate toxicokinetic parameters.

The half-lives for the initial elimination phase were not significantly different between sexes for rats and mice.

Differences in the terminal phase half-lives as a function of exposure concentration were also not significant

between sexes for rats or mice. At each decalin exposure concentration, no significant differences in the initial or

terminal half-lives as a function of sex for either species was observed. Half-lives for the initial elimination phase

were approximately 1.1 to 6.0 times shorter in mice than those in rats. Half-lives for the terminal elimination

phase in mice were approximately 3.4 to 5.4 times shorter than those in rats.

There are several conclusions that can be drawn from the PBPK model. First, it is not possible to detect any

differences in the metabolism of decalin between male and female mice in these data. There are significant

differences between male and female rats driven by the difference in kidney decalin concentrations. Second, the

model predicts a higher rate of metabolism for mice, but this metabolism pathway saturates at a lower

concentration than that in rats. Third, the model indicates that the highest dose (400 ppm) selected for the study

was at a concentration where metabolism was saturated. Finally, it is not possible to determine if the metabolism

and permeability parameters for male and female rats are the same; the only difference between the sexes were

parameters associated with the binding to alpha-2u-globulin.