M.Th.M. Tulp

The metabolism of 4,4′-dichlorobiphenyl in rats and frogs

Abstract The metabolism of 4,4′-dichlorobiphenyl in the rat has been investigated in detail and four monohydroxy-, four dihydroxy- and two trihydroxy metabolites were detected. The structures of the metabolites - except for the trihydroxy compounds - were ascertained by GC-MS studies and by comparison with synthetic compounds. Metabolism experiments in frog resulted in the isolation and characterisation of four metabolites. The structure of the major metabolites in both the rat and the frog are consistent with epoxidation of the biphenyl nucleus followed by epoxide ring opening accompanied by a 1,2-chlorine shift (NIH-shift). The formation of one minor rat metabolite, 4-chloro-3t-biphenylol can only be explained by reductive dechlorination.

The bacterial metabolism of 4,4′-dichlorobiphenyl, and its suppression by alternative carbon sources

Abstract The metabolism of 4,4′-dichlorobiphenyl by mixed cultures of bacteria, isolated from activated sludge, was studied in shake cultures and in soil, both in presence and absence of alternative carbon sources. When 4,4′-dichlorobiphenyl was used as sole carbon source, 4-chlorobenzoic acid and 4,4′-dichloro-2,3-biphenyldiol could be isolated from the culture medium. Polar metabolites however, could not be detected in soil and in media in which alternative carbon sources such as glucose, glycerol, peptone, yeast-extract, humic acid or activated sludge were present. No hydroxylated or carboxylic acid derivatives could be isolated when 2,4′, 5-tri-, 2,2′,5,5′,-textra-, 2,2′,3,4,5′-penta-, 2,2′,3,4,5,5′-hexa- and decachlorobiphenyl were used as the sole carbon sources for incubation with bacteria in shake culture.

Environmental chemistry of PCB-replacement compounds - III - the metabolism of 4-chloro-4′-isopropylbiphenyl and 2,5-dichloro-4′-isopropylbiphenyl in the rat

Abstract 4-Chloro-4′-isopropylbiphenyl and 2,5-dichloro-4′-isopropylbiphenyl, two model compounds for alkylated chlorobiphenyls (Chloralkylenes), are metabolized in the rat by two major routes. One pathway proceeds by stepwise oxidation of the isopropyl group to chlorobiphenyl carboxylic acid via intermediate keto- and carboxylic acid derivatives, and the other by hydroxylation of the chlorine substituted phenyl ring. A number of metabolites formed from either one or a combination of both pathways were identified by gas chromatography - mass spectrometry and synthesis.

Environmental chemistry of PCB-replacement compounds - VI - composition and metabolism of Wemcol ®, an isopropylbiphenyl formulation

Abstract Wemcol is a technical isopropylbiphenyl formulation that is used as a substitute for polychlorobiphenyl. According to the producer Wemcol is 4-isopropylbiphenyl, but we found our sample to consist of 60.3% 3-isopropylbiphenyl, 38.6% 4-isopropylbiphenyl and 3,5-, 3,3′-, 3,4′- and 4,4′-diisopropylbiphenyl in amounts of 0.3%, 0.4%, 0.2% and 0.1% respectively. The two major components of the mixture are metabolized in the rat by two routes : oxidation of the isopropyl group and hydroxylation of the aromatic nuclei. Rats fed the technical mixture retained 3- and 4-isopropylbiphenyl in a ratio 4.3 : 1 in their abdominal fat, whilst the ratio in the mixture is 1.6 : 1. One week after the simultaneous feeding of equal amounts of Wemcol, 4,4′-dichlorobiphenyl, 2,4′,5-trichlorobiphenyl and 2,2′,5,5′-tetrachlorobiphenyl, the isopropylbiphenyls, in contrast to the chlorobiphenyls, could no longer be detected in the abdominal fat of rats.

Reductive dechlorination of chlorobiphenylols by rats

Dechlorinated products were isolated from the urine of rats that were administered chlorobiphenylols, the primary hydroxylated metabolites of PCB in mammals. The mechanism of chlorine loss from chlorobiphenylols is different from the mechanism of dechlorination via arene oxides whereby concomitant hydroxylation is always observed.

Structure Elucidation of Hydroxylated Metabolites of Polychlorinated Aromatic Compounds by GC-MS Investigation of Their Methyl Ethers

In recent years polychlorinated aromatic hydrocarbons have been the subject of growing concern and much research is focussed on these compounds, for two main reasons. Firstly, a number of them have been, and to a certain extent still are, produced in large quantities, due to their favourable physico-chemical properties, that permit a broad spectrum of applications.