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EC number: 200-867-7
CAS number: 75-38-7
Only toxicokinetic studies with
animals via the respiratory route are present in the available database.
In rats, relative absorption after
respiratory exposure is considerably more than 1% of the VDF available
in a closed exposure system, but could not be quantified more exactly,
based on the available data. The rate of absorption and distribution of
VDF are relatively high, steady state blood levels of VDF are reached
within 15 minutes after onset of respiratory exposure.
Distribution into tissues
In the rat, the rapid obtainment of
steady state concentrations and the equally rapid decrease of blood
concentrations after cessation of exposure suggest that VDF has limited
solubility in tissues of varying lipid and aqueous content. VDF
tissue/air partition coefficients were determined experimentally to be
0.07, 0.18, 0.8, 1.0, and 0.29 for water, blood, liver, fat, and muscle,
respectively. In view of these data, bio-accumulation of VDF in the rat
Transfer into organs
No data are available, but
accumulation in organs is unlikely in view of the results obtained on
distribution into tissues.
In rats, after cessation of exposure,
blood levels of VDF decreased to 10% of steady-state levels within 1
hour. This indicates excretion is a rather rapid process. The
quantitative importance of faecal and urinary excretion cannot be
addressed based on the available data. However, judging by the rapid
equilibration with ambient air, faecal and urinary excretion are
probably of little quantitative significance.
In the rat, no metabolites of VDF were
identified. After respiratory exposure, rats exhaled acetone (between
1.2 and 2.5 μmol/h/kg bw when exposed to 500 ppm VDF for 8 hours).
However, whether it is a de facto metabolite of VDF or the result
of inhibition of citric acid cycle enzyme(s) by a true VDF metabolite,
e.g. fluoroacetate, is still undecided based on the available data.
Based on the scant information
presented above and considerations regarding the chemical structure of
VDF, the following metabolic reactions were putatively proposed:
- epoxidation of the ethylene double
- rearrangement to the halogenated
acetaldehyde or halogenated acyl halide;
- partial transformation of the latter
to halogenated acetic acid.
Although, in the rat, respiratory
uptake of VDF increases linearly with its concentration in air,
metabolism may be saturated from a certain exposure concentration
upward. However, different results were obtained with respect to the
saturation point of the metabolism. Zwart (1985) calculated a saturation
point of ca. 400 ± 200 ppm in air, while Filser et al. (1982) found it
to be 100 ppm, in a different rat strain. Using the kinetic data of
Filser et al. (1982) in a PBPK-model, which correctly predicted VDF
blood concentrations, Medinsky et al. (1988) calculated a saturation
point of 2000 ppm. As the PBPK-model correctly predicted VDF blood
levels, providing some validation of the model and its underlying data,
2000 ppm seems to be the best estimate of the metabolic
saturation point. Estimations of Vmax for metabolic elimination in the
rat varied between 1.1 μM/h/kg bw and 3.2 μmol/h/kg bw. (As it is not
clear from the SIDS summary of the OECD to which volume the unit
expressed in μM is related, both units cannot be interconverted to
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