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Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Public literature, no detailed study report available

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Distribution and Excretion of BisGMA in Guinea Pigs
Author:
Reichl
Year:
2008
Bibliographic source:
J. Dent. Res. 87 (4): 378-380, 2008
Reference Type:
publication
Title:
Distribution and Excretion of BisGMA in Guinea Pigs, Appendix
Author:
Reichl
Year:
2008
Bibliographic source:
J. Dent. Res. 87 (4): 378-380, 2008, i-v

Materials and methods

Objective of study:
other: distribution and excretion
Principles of method if other than guideline:
The uptake, distribution and excretion of radio labeled BisGMA applied via gastric and intravenous administration were examined in vivo in guinea pigs.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
bisGMA is the main constituent of Small Vinyl Ester and Modified Small Vinyl Ester.B[14C]BisGMA was purchased from Perkin Elmer.
Radiolabelling:
yes
Remarks:
14-C

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male
Details on test animals and environmental conditions:
Adult male guinea pigs (400 g). Each animal was put into a separate metabolic cage 3 days before the start of the study, and food was removed 12 hours before the start of the treatment. No details were provided on the environmental conditions.

Administration / exposure

Route of administration:
other: gavage and intravenous
Vehicle:
DMSO
Duration and frequency of treatment / exposure:
Single exposure.
Details on study design:
In situ experiment:Guinea pigs were randomized and allotted to 3 groups of 4 animals each. The ductus cysticus was ligated, and a cannula was placed in the bile duct. A 1 ml/kg quantity of BisGMA, dissolved in DMSO (final concentration DMSO 1%) was injected via the jugular vein (0.02 µmol/kg bw, labeled with a tracer dose of [14C]BisGMA (0.3 kBq/g bw). Control animals received either 0.9% NaCl solution or DMSO (final concentration 1% DMSO in 0.9% NaCl). In vivo ExperimentsTwelve guinea pigs were allotted to 3 groups of 4 animals each. Each animal received BisGMA (0.02 µmol/kg bw, dissolved in 1% DMSO), labeled with a tracer dose of [14CBisGMA (0.3 kBq/g bw), via gavage. Control animals received either 0.9% NaCl solution or DMSO (final concentration 1% DMSO in 0.9% NaCl). The volume for the application through the gastric tube was 4 ml/kg. A second set of 12 guinea pigs was treated as described above, with the addition, that each animal was kept in a closed chamber with controlled air flow.
Details on dosing and sampling:
In situ experiment:Blood was withdrawn form the carotid artery. Samples of the bile (0.4 ml) and blood (0.2 ml) were taken every 10 minutes. The experimental period was 60 minutes. The organs and their contents were immediately removed and their [14C]-radioactivity measured. In vivo experiment:Feces and urine were collected at 1, 2, 4, 6, 8, 12, and 24 hours after [14C]BisGMA administration, and the [14C]-radioactivity was measured. Twenty four hours after the beginning of the experiment, the animals were killed in ether. The organs and their contents were immediately removed and their [14C]-radioactivity measured. From the animals kept in the closed chamber, the exhaled air was captured during the 24-hour experimental period, in addition to the collection of urine and feces for 24 hours and analysis of organs. Guinea pig organs:For all experiments the following organs were taken: liver, kidney, blood, skin, brain, heart, spleen, lung, muscle, testes, eyes, bone, nerve tissue, spinal cord, wall of stomach, content of stomach, wall and content of ileum and jejunum, wall and content of colon, wall and content of caecum, wall of gall bladder and fat tissue. Organs were immediately washed with 2 x 10 ml distilled H2O, the wash-water was saved, and then the tissues were weighed and homogenized. Determination of Radioactivity:Tissues were dissolved in TEAH (20%) in aqueous solution with Omni-Szintisol. Radioactivity was determined with a liquid scintillation counter.
Statistics:
Data were presented as means +/- SEM. Statisticall significance of the differences between the experimental groups was determined by the Bonferroni-Holm t test.

Results and discussion

Any other information on results incl. tables

During the first hour after [14C]BisGMA intravenous injection, about 12% of the radio label was excreted via the bile, and about 50% reamined in the tissues at 1 hour, the time the guinea pigs were killed. Radio label was rapidly removed from the blood. No significant change in bile flux was observed during the 60 minutes in guinea pigs that had received radio labeled BisGMA, when compared to controls. One hour after intravenous injection, radio activity found in the l ungs was about 8% and in the brain 1% of the administered radio label (per gram organ). Radio activity in other organs was lower than 0.4% (per gram organ).

In the total blood, radio activity was foudn to be about 4% of the dose, 10 minutes after intravenous administration. From these data a plasma half-life period for BisGMA can be calculated that must be lower than 10 minutes.

In vivo experiments:

Duirng the first 24 hours after radio labelled BisGMA oral gavage, guinea pigs exhaled 14CO2 equivalent to about 65% fo the radio label administered. About 7% of the radiolabel was excreted via urine, 5% was excreted via feces, and about 6% remained in the tissues at 24 hours, the time the animals were killed. The total recovery was about 85% of the radio label administered. During the 24 hours, the amount of feces and urine excreted was not changed when compared to control animals. Radio label in organs ans walls and/or contents of organs in guinea pigs at 24 hours, was found in lungs about 0.035% and in the brain about 0.002% of the administered radio label.

Applicant's summary and conclusion