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PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
1982-8-7
pubmed:abstractText
Metabolic inactivation of chemicals may prevent toxic effects of reactive intermediates when present at low levels whereas inactivation may be overcome at high levels changing dose-effect relation. This is demonstrated in various in vitro test systems: a) Monooxygenase-mediated metabolism causes formation of reactive oxygen species which induce DNA repair in lymphoblastoid cells. DNA damage is suppressed in the presence of glutathione (GSH), catalase or superoxide dismutase. b) Chloroprene is mutagenic in Salmonella typhimurium but not carcinogenic, possibly due to inactivation by GSH-conjugations. c) Chlorodinitrobenzene is not mutagenic is Salmonella typhimurium in the presence of GSH. However it is increasingly mutagenic at concentrations exceeding those of the GSH. d) Suppression of glucuronidation and sulfation in isolated hepatocytes highly increases irreversible binding of naphthalene. It is concluded that information on the metabolism of chemicals is essential for interpretation of toxicity studies in animals and their relevance to man.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0065-2598
pubmed:author
pubmed:issnType
Print
pubmed:volume
136 Pt B
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1389-98
pubmed:dateRevised
2004-11-17
pubmed:meshHeading
pubmed:year
1981
pubmed:articleTitle
Threshold levels in toxicology: significance of inactivation mechanisms.
pubmed:publicationType
Journal Article