Registration Dossier

Toxicological information

Basic toxicokinetics

Currently viewing:

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:
other: Acceptable, well documented publication which meets basic scientific principles

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Species differences in the biotransformation of ethyl chloride: I. Cytochrome P450-dependent metabolism
Author:
Fedtke, N. et al.
Year:
1994
Bibliographic source:
Arch. Toxicol. 68:217-223
Reference Type:
secondary source
Title:
Chloroethane CAS: 75-00-3
Author:
OECD SIDS
Year:
2006
Bibliographic source:
SIDS Initial Assessment Report for SIAM 22

Materials and methods

Objective of study:
metabolism
Principles of method if other than guideline:
The role of oxidation by Cytochrome P-450 dependent monooxygenases was examined in rats and mice exposed 6 hours/day for 5 days to 15000 ppm chloroethane or to air.
GLP compliance:
not specified

Test material

Constituent 1
Chemical structure
Reference substance name:
Chloroethane
EC Number:
200-830-5
EC Name:
Chloroethane
Cas Number:
75-00-3
Molecular formula:
C2H5Cl
IUPAC Name:
chloroethane
Details on test material:
- Name of test material (as cited in study report): ethyl chloride
- Analytical purity: > 99%
Radiolabelling:
no

Test animals

Species:
other: rat and mouse
Strain:
other: Fischer 344 rats and B6C3F1 mice
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, Sulzfeld, Germany
- Weight study initiation: rats: females 195 g, males 238 g; mice: females 24 g, males 29 g
- Housing: in one set of all-glass metabolic cages (EBECO) during exposure and in another set of metabolic cages after exposure
- Diet: ad libitum Ssniff R 10 diet (Ssniff Spezialitäten GmbH, Soest, Germany)
- Water: ad libitum tap water


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 1
- Humidity (%): 30 - 70



Administration / exposure

Route of administration:
inhalation: gas
Vehicle:
unchanged (no vehicle)
Details on exposure:
TYPE OF INHALATION EXPOSURE: whole body

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: metabolic cages connected to a supply of an chloroethane/air mixture by teflon tubings.
- Source and rate of air: 2 L per minute and metabolic cage; the air flow was supplied from a tank containing compresed synthetic air (Messer Griesheim)



Duration and frequency of treatment / exposure:
6 hours/day for 5 days
Doses / concentrations
Dose / conc.:
15 000 ppm (nominal)
Remarks:
mean actual exposure concentrations: 14090 and 14393 ppm for male and female rats, and 15025 and 14879 ppm for male and female mice
No. of animals per sex per dose / concentration:
3 exposure groups of 2 rats or 10 mice of the same sex
Control animals:
other: air treatment
Details on dosing and sampling:
PHARMACOKINETIC STUDY
- Tissues and body fluids sampled: collection of blood (from the arteria carotis in EDTA containing vials); livers, lungs, kidneys and uteri were removed
From pretreated rats only the livers were removed.
- Time and frequency of sampling: at the end of the last exposure


METABOLITE CHARACTERISATION STUDIES
The chloroethane metabolism by liver microsomes was examined. In addition, blood serum and urine samples were analysed for the metabolite acetaldehyde.
- Method type(s) for identification: determination of acetaldehyd by isotope dilution mass spectrometry (GC-MS)


Statistics:
two sided t-test; alpha = 0.05, 0.01

Results and discussion

Metabolite characterisation studies

Metabolites identified:
yes
Details on metabolites:
The formed metabolite was identified as acetaldehyde.

Applicant's summary and conclusion