title: Gas chromatography-mass spectrometry determination of ethylenethiourea hemoglobin adducts: a possible indicator of exposure to ethylene bis dithiocarbamate pesticides.
abstract: Ethylenebisdithiocarbamates (EBDC) are an important class of fungicides used to control crop diseases and prevent mold. Ethylenethiourea (ETU), reported to be their main degradation and metabolic product in animals and man, may have teratogenic and carcinogenic properties. The feasibility of monitoring exposure to ETU on the basis of the formation of adducts to hemoglobin (Hb) was investigated. Rats given a single oral dose of ETU (from 62.5 to 500 mg/kg body wt) formed stable covalent ETU-Hb adducts. Mild acid hydrolysis of the protein regenerated ETU, allowing its detection by isotope dilution gas chromatography-mass spectrometry (GC-MS). The amount of released ETU increased with the dose. The dose-response curve fitted a linear model only between 62.5 mg/kg and 250 mg/kg. Acid-releasable ETU was also positively identified in the hemoglobin of workers exposed to Mancozeb, an EBDC formulation. In the exposed group, 40% had ETU-Hb adducts levels ranging from 0.5 to 1.42 pmol ETU/mg Hb. Such adducts might be useful for measuring EBDC exposure in humans.
authors.affiliation: Laboratory of Molecular Toxicology, Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Pastorelli
authors.forename: R
authors.initials: R
authors.lastname: Allevi
authors.forename: S
authors.initials: S
authors.lastname: Romagnano
authors.forename: G
authors.initials: G
authors.lastname: Meli
authors.forename: R
authors.initials: R
authors.lastname: Fanelli
authors.forename: L
authors.initials: L
authors.lastname: Airoldi
mesh_terms: D000328:Adult; D000818:Animals; D005028:Ethylenebis(dithiocarbamates) / Q000032:analysis*; D005031:Ethylenethiourea / Q000032:analysis / Q000378:metabolism*; D008401:Gas Chromatography-Mass Spectrometry; D006454:Hemoglobins / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010575:Pesticides / Q000032:analysis*; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D005028:Ethylenebis(dithiocarbamates); D006454:Hemoglobins; D010575:Pesticides; D005031:Ethylenethiourea