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Toxicological information

Basic toxicokinetics

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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:
1982
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
Name:
Unnamed
Type:
Constituent
Details on test material:
- Source: Matheson Chemical Co., Newark, CA, USA
- No further details
Radiolabelling:
no

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals 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.