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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
publication
Title:
Evidence of chloroethylene oxide being the reactive metabolite of vinyl chloride towards DNA: comparative studies with 2,2' -dichlorodiethylether
Author:
Gwinner, L.M., Laib, R.J., Filser, J.G., Bolt, H.M.
Year:
1983
Bibliographic source:
Carcinogenesis, 11:1483-1486

Materials and methods

Objective of study:
distribution
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
- Principle of test: Inhalation exposure to radiolabelled DCEE in a closed all-glass exposure system
- Short description of test conditions: A single dose corresponding to 0.25 mCi/animal (final uptake) was given to three rats. The rats were sacrificed after 24h.
- Parameters analysed / observed: distribution in organs
GLP compliance:
no
Remarks:
pre-GLP

Test material

Constituent 1
Chemical structure
Reference substance name:
Bis(2-chloroethyl) ether
EC Number:
203-870-1
EC Name:
Bis(2-chloroethyl) ether
Cas Number:
111-44-4
Molecular formula:
C4H8Cl2O
IUPAC Name:
1-chloro-2-(2-chloroethoxy)ethane
Test material form:
liquid
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Name (as cited): 2,2'-Dichlorodiethylether (BCEE)
- Purity: 99%
- Source of test material: Merck-Schuchard

RADIOLABELLED TEST MATERIAL
- Name (as cited): [1-14C]2,2'-Dichlorodiethylether
- Radiochemical purity: no specified
- Source of test material: NEN Chemicals
- Specific activity: 1.42 mCi/mmol
Radiolabelling:
yes

Test animals

Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Ivanovas, Kissleg, FRG
- Age at study initiation: not specified
- Weight at study initiation: 200g
- Diet: ad libitum
- Water: ad libitum

Administration / exposure

Route of administration:
inhalation: vapour
Vehicle:
unchanged (no vehicle)
Duration and frequency of treatment / exposure:
At the start of the experiment the glass chamber, where the three rats were housed, was filled with vapor of radiolabelled BCEE. After 18 h exposure > 95% of the administered BCEE was taken up by the animals. Uptake was 0.25 mCi/animal.
Doses / concentrations
Dose / conc.:
125.9 mg/kg bw (total dose)
Remarks:
Calculated based on the specific activity of radiolabelled BCEE (1.42 mCi/mmol), the uptake of test animals (0.25 mCi/animal) and the animal weight (200 g).
No. of animals per sex per dose / concentration:
3 animals
Control animals:
no
Details on dosing and sampling:
TOXICOKINETIC / PHARMACOKINETIC STUDY
- Test chamber: closed all-glass exposure system
- Dose: 0.25 mCi/animal
- Time of sampling: 24 h post-exposure
- Tissues sampled: Liver, kidney, spleen, lung, small intestine and muscle tissues
- Sample storage: - 80°C
- Parameter measured: irreversible binding of radioactive metabolites of [1-14C]BCEE to tissue proteins
- Other: The decline of BCEE vapor in the inhalation chamber was measured by gas chromatography. After 18 h exposure >95% of the administered BCEE was taken up by the animals.

Results and discussion

Main ADME results
Type:
distribution
Results:
Irreversibly protein bound radiolabelled BCEE was mainly found in the liver. Smaller amounts were found in kidney, small intetsine, lung and spleen.

Any other information on results incl. tables

The relative distribution of irreversible protein binding in different rat tissues after exposure of the animals to [14C]BCEE as observed in this study is presented in the table below:

 Tissue  % of radioactivity irreversibly bound per g tissue protein (n = 4)
 Liver  0.32 +/- 0.016
 Lung  0.07 +/- 0.015
 Spleen  0.06 +/- 0.014
 Kidney  0.17 +/- 0.024
 Small intestine  0.12 +/- 0.017
 Muscle

 0.01 +/- 0.003

Applicant's summary and conclusion

Conclusions:
3 male rats were exposed to radiolabelled BCCE by inhalation (dose: approc. 125.9 mg/kg BCEE). After 18 h exposure > 95% of the administered BCEE was taken up by the animals. Radiolabbed BCEE irreversibly bound to protein was mainly found in the rat liver. Smaller amounts were found in kidney, small intestine, lung and spleen.
Executive summary:

The objective of this study was to evaluate the role of vinyl chloride metabolites (namely chloroethylene oxyde (CEO) an chloroacetaldehyde (CAA)) in the carcinogenicity of vinyl chloride (VC). 2,2' dichlorodiethyl ether (BCEE) was studied as a metabolite precusor of CAA. Following exposure to vapour of radiolabelled VC and BCEE, the distribution of radioactiviy in various tissues following covalent binding to protein was studied. The carcinogenic potential of exposure to these substance was evaluated by the occurrence of nucleic acid (RNA and DNA) alkylation and the potency of the two chemicals to induce preneoplastic ATPase-deficient foci in rat liver.

After 18 h exposure > 95% of the administered BCEE was taken up by the animals. Both chemicals displayed similar distribution in rat tissues. Radiolabbed BCEE irreversibly bound to protein was mainly found in the rat liver. Smaller amounts were found in kidney, small intestine, lung and spleen.