Chloroethane

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Data source

Reference

Reference 1

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 2

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

Test material information

Constituent 1

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.