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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1985
Report Date:
1985
Reference Type:
publication
Title:
Pharmacokinetics of halogenated ethylenes in rats
Author:
Filser JG, Bolt HM
Year:
1979
Bibliographic source:
Arch. Toxicol. 42: 123-136

Materials and methods

Objective of study:
metabolism
Principles of method if other than guideline:
Metabolic elimination of vinylidene fluoride vapour was studied by monitoring the disappearance of VDF from the air in a closed loop whole body respiratory exposure system, using a Miran infrared analyser at a wavelength of 7700 nm and analysed with the simplified zeor and first order elimination model of Filser and Bolt (1979).
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Radiolabelling:
no

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River, Wilmington, USA
- Housing: 5 to a stainless steel wire mesh cage
- Individual metabolism cages: no
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21±1
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:
inhalation: gas
Vehicle:
unchanged (no vehicle)
Details on exposure:
Five rats were placed on a perforated support plate in a glass dessicator jar which was part of a closed loop system. Urine and faeces were collected in the area under the support plate. This area was cooled with tap water in order to remove caloric energy and water vapour excreted by the animals. The closed loop system further consisted of a CO2 absorber (soda lime), a rubber diaphragm pump for circulating the air through the loop system and the gas cell of a Miran 1A infrared analyzer. Oxygen was supplied by an overflow system. Oxygen flow was measured with an anemometer which acted as a sensitive leak detector. The pressure in the loop was about + 1 cm H2O with respect to the atmosphere. A thermometer was placed in the dessicator jar to check the temperature of the test atmosphere (19.7ºC ± 1.1).
The concentration in the test atmosphere as analyzed by the Miran 1A was continuously recorded with an x-t recorder. For the calculations the read out of the digital voltmeter taken every quarter of an hour was used.
Duration and frequency of treatment / exposure:
Ranging from 6 to 23 hours
Doses / concentrations
Remarks:
Doses / Concentrations:
Ranging from 20 to 1800 ppm
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
Five untreated rats were placed in a dessicator jar. Immediately after checking the system for leaks, the volume of vinylidene fluoride gas necessary for the target concentration was injected into the loop system. Most of the exposures were terminated after six hours. Two experiments were continued overnight. In one of these experiments the elimination of vinylidene fluoride was followed for 23 hours in order to study the stability of the elimination and measurement over a prolonged period. In the other experiment we flushed and cleaned the closed loop system from vinylidene fluoride after the six hours of elimination test and replaced the exposed rats into the dessicator jar.

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:
When replacing rats (cumulative weights 1442.5 g), which had been exposed for six hours to approximately 100 ppm VDF , into the cleaned closed loop respiratory exposure system, an increase of the VDF air concentration of about 1 ppm was observed within the first 15 minutes, after which the VDF concentration stabilized.
From this change in concentration it is concluded that considerably more than 1 percent of the test material had been absorbed in fur and tissues of the rats during the 6 h exposure period, as the rats were washing out during flushing and cleaning of the closed loop system.
Toxicokinetic parametersopen allclose all
Toxicokinetic parameters:
other: Maximum metabolic elimination rate of vinylidene fluoride (Vmax) = 3.2 ± 0.6 µmol/hr/kg body weight.
Toxicokinetic parameters:
other: First order metabolic elimination rate (k1) = 0.18 ± 0.09 L/hr/kg body weight.
Toxicokinetic parameters:
other: Saturation point of metablolism (Sp) = 402 ± 210 ppm

Metabolite characterisation studies

Metabolites identified:
no
Details on metabolites:
none

Applicant's summary and conclusion