Registration Dossier
Registration Dossier
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EC number: 200-816-9 | CAS number: 74-86-2
Basic toxicokinetics
Administrative data
- Endpoint:
- basic toxicokinetics
- 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 animal experimental study, published in peer reviewed literature, limitations in reporting but otherwise adequate for assessment
Data source
Reference
- Reference Type:
- publication
- Title:
- Destruction of cytochrome P-450 by vinyl fluoride, fluroxene and acetylene. Evidence for a radical intermediate in olefin oxidation
- Author:
- Ortiz de Montellano PR, Kunze KL, Beilan HS and Wheeler C
- Year:
- 1 982
- Bibliographic source:
- Biochemistry, 21, 1331-1339
Materials and methods
- Objective of study:
- metabolism
- Principles of method if other than guideline:
- The interaction of acetylene with hepatic P-450 was investigated in vitro and in vivo
- GLP compliance:
- not specified
Test material
- Reference substance name:
- Acetylene
- EC Number:
- 200-816-9
- EC Name:
- Acetylene
- Cas Number:
- 74-86-2
- Molecular formula:
- C2H2
- IUPAC Name:
- acetylene
- Details on test material:
- - Source: Matheson Chemical Co., Newark, CA, USA
- No further details
Constituent 1
- Radiolabelling:
- no
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Weight: 250±25 g
- No further details
Administration / exposure
- Route of administration:
- inhalation: gas
- Vehicle:
- other: air
- Details on exposure:
- Animals were pre-treated for 4 days with 80 mg/kg/day phenobarbital in aqueous solution by injection.
- Details on dosing and sampling:
- - In-vitro experiment: pre-treated rats were decapitated and hepatic microsomes were prepared
- Acetylene was mixed with air and incubated with the microsomes for up to 30 min, control incubations were performed
- The Cytochrome P-450 activity was measured using a spectrophotometric method
- Abnormal porphyrins were purified and isolated by chromatography and then characterised using MS and NMR
- In-vivo experiment: rats were exposed to acetylene by inhalation, P-450 activity and porphyrins were analysed as above
Results and discussion
Metabolite characterisation studies
- Metabolites identified:
- yes
- Details on metabolites:
- The identity of the abnormal porphyrin was determined to be N-(2-oxoethyl) protoporphyrin IX; this is probably generated by reaction of a free radical metabolite of acetylene formed during oxidation by cytochrome P-450.
Applicant's summary and conclusion
- Executive summary:
Oxidation of acetylene by cytochrome P-450 results in a reactive metabolite which reacts with the prosthetic heme resulting in loss of enzyme activity.
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