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Toxicological information

Basic toxicokinetics

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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: Non GLP, non-guideline study published in peer reviewed literature, minor restrictions in reporting but otherwise adequate for assessment.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1995

Materials and methods

Objective of study:
toxicokinetics
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Toxicokinetics and adduct formation of 1-alkenes was investigated in rats.
GLP compliance:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Ethylene
EC Number:
200-815-3
EC Name:
Ethylene
Cas Number:
74-85-1
Molecular formula:
C2H4
IUPAC Name:
ethylene
Constituent 2
Reference substance name:
Ethene
IUPAC Name:
Ethene
Details on test material:
Ethene, >99.5% pure was supplied by HydroGas AS, Norway.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals or test system and environmental conditions:
Rats, 180-225 g were supplied by Mollegaard A/S, LI. Skensved, Denmark, housed 8 per cage and acclimatised for at least 5 days. Food and water was provided ad libitum except during exposure. The photoperiod was 14h light/10h dark. Temperature was 21±1°C and humidity 65±5%.

Administration / exposure

Route of administration:
inhalation: gas
Vehicle:
other: air
Details on exposure:
Exposure was performed during the light period in conical chambers with 10 air changes/hour. The atmosphere was generated using a 2-stage pressure regulator; concentrations were measured hourly by gas chromatography.
Duration and frequency of treatment / exposure:
12h/day for 3 consecutive days.
Doses / concentrations
Remarks:
Doses / Concentrations:
300 ppm (344.2 mg/m3)
No. of animals per sex per dose / concentration:
Up to 32
Control animals:
yes, sham-exposed
Details on dosing and sampling:
Samples of blood, brain, liver, kidney, lung and perirenal fat were taken from groups of 4 rats at the end of each 12h exposure period and at 12h after the final exposure; samples were analysed by gas chromatography for ethene. DNA adducts were measured in liver samples taken immediately after the final exposure. DNA and haemoglobin adducts were measured in lymphocytes and erythrocytes respectively from blood taken at the end of the last exposure. Haemoglobin adducts were determined using GC-MS; DNA adducts were measured using a [32P]-post labelling technique.

Results and discussion

Main ADME resultsopen allclose all
Type:
absorption
Results:
Steady state tissue concentrations were attained during the first exposure.
Type:
distribution
Results:
Immediately after the final exposure, mean tissue concentrations (µmol/kg) in blood: 0.3, liver: 0.4, lung: 2.3, brain: 0.7, kidneys: 0.7 and fat: 7; the concentration in fat had fallen to below the limit of detection by 12 hours after the final exposure.

Metabolite characterisation studies

Details on metabolites:
Mean concentrations of N-(2-hydroxyethyl) valine in haemoglobin was 2730±100 pmol/g.
Mean concentrations of 7-ethylguanine in lymphocytes and liver were 5.8±2.2 and 7.4±1.0 adducts/10^7 normal nucleotides, respectively.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): other: Exposure to ethylene results in formation of DNA and haemoglobin adducts