Charlotta Fred

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With the increasing emphasis on identification and low level control of potentially genotoxic impurities (GTIs), there has been increased use of structure-based assessments including application of computerized models. To date many publications have focused on the ability of computational models, either individually or in combination, to accurately predict(More)
In cancer tests with 1,3-butadiene (BD), the mouse is much more sensitive than the rat. This is considered to be related to the metabolism of BD to the epoxide metabolites, 1,2-epoxy-3-butene (EB), 1,2:3,4-diepoxybutane, and 1,2-epoxy-3,4-butanediol. This study evaluates whether the large difference in outcome in cancer tests with BD could be predicted(More)
The reduced state of vitamin B(12), cob(I)alamin, acts as a supernucleophile that reacts ca. 10(5) times faster than standard nucleophiles, for example, thiols. Methods have been developed for trapping electrophilically reactive compounds by exploiting this property of cob(I)alamin. 1,3-Butadiene (BD) has recently been classified as a group 1 human(More)
A molecularly imprinted polymer, MIP, was prepared and evaluated as SPE sorbent for a cyclicized adduct formed to N-terminal valine (Pyr-Val) in hemoglobin from 1,2:3,4-diepoxybutane (DEB). This metabolite plays an important role in the carcinogenesis of 1,3-butadiene. The hydrazide of Pyr-Val, formed after hydrazinolysis of hemoglobin, as well as necessary(More)
Analytical methods facilitating studies of electrophilically reactive and genotoxic compounds in vitro and in vivo are needed. The strong nucleophile, cob(I)alamin, formed by reduction of Vitamin B12 [cob(III)alamin], may be used for trapping and analysis of 1,2-epoxides and other electrophiles. In the present study, cob(I)alamin is evaluated as an(More)
1,3-Butadiene and isoprene (2-methyl-1,3-butadiene) are chemically related substances that are carcinogenic to rodents. The overall aim of this work is to elucidate the role of the genotoxic action of diepoxide metabolites in the carcinogenesis of the dialkenes. In vivo doses of the diepoxide metabolites were measured through reaction products with(More)
1,3-Butadiene, a common air pollutant formed in the combustion of organic matter, has been assessed by the U.S. EPA to be a strongly carcinogenic compound. This risk assessment is very uncertain because of the lack of information on the dose of the powerful carcinogenic metabolite diepoxybutane (DEB). This report presents an analytical method for in vivo(More)
For cancer risk assessment of 1,3-butadiene from rodent cancer test data, the in vivo doses of formed 1,2:3,4-diepoxybutane (DEB) should be known. In vivo doses of DEB were measured through a specific reaction product with hemoglobin (Hb), a ring-closed adduct, N,N-(2,3-dihydroxy-1,4-butadiyl)valine (Pyr-Val), to N-terminal valines. An analytical method(More)
Isoprene (2-methylbuta-1,3-diene) is a multi-site carcinogen in rodents. To evaluate the role of the diepoxide metabolite (1,2:3,4-diepoxy-2-methylbutane) in carcinogenesis, measurements of in vivo doses of the diepoxide are needed. The in vivo dose may be inferred from levels of reaction products with hemoglobin (Hb adducts). This report presents in vitro(More)