1,1-difluoroethylene

Basic toxicokinetics

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

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1985

Report date:

1985

Reference 2

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

Test material information

Constituent 1

Reference substance name:

1,1-difluoroethylene

EC Number:

200-867-7

EC Name:

1,1-difluoroethylene

Cas Number:

75-38-7

Molecular formula:

C2H2F2

IUPAC Name:

1,1-difluoroethene

Radiolabelling:

no

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system 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 / concentration:

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 parameters

Toxicokinetic parameters 1

Toxicokinetic parameters:

other: Maximum metabolic elimination rate of vinylidene fluoride (Vmax) = 3.2 ± 0.6 µmol/hr/kg body weight.

Toxicokinetic parameters 2

Toxicokinetic parameters:

other: First order metabolic elimination rate (k1) = 0.18 ± 0.09 L/hr/kg body weight.

Toxicokinetic parameters 3

Toxicokinetic parameters:

other: Saturation point of metablolism (Sp) = 402 ± 210 ppm

Metabolite characterisation studies

Metabolites identified:

no

Details on metabolites:

none