Diphenly Poisoning in Fruit Paper Production

Häkkinen, Ilona; Siltanen, Eero; Hernberg, Sven; Seppäläinen, Anna Maria; Karli, Pauli; Vikkula, Esko

doi:10.1080/00039896.1973.10666226

Cited by 29 publications

(11 citation statements)

References 2 publications

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“…Toxic effects to humans after prolonged exposure to air containing biphenyl and after cutaneous application are known (14). Some biphenyl derivatives also are suspected carcinogens and have estrogenic activity (21,33,39).…”

mentioning

confidence: 99%

Biotransformation of Biphenyl by Paecilomyces lilacinus and Characterization of Ring Cleavage Products

Gesell

Hammer

Specht

et al. 2001

Appl Environ Microbiol

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We examined the pathway by which the fungicide biphenyl is metabolized in the imperfect fungus Paecilomyces lilacinus. The initial oxidation yielded the three monohydroxylated biphenyls. Further hydroxylation occurred on the first and the second aromatic ring systems, resulting in the formation of five di-and trihydroxylated metabolites. The fungus could cleave the aromatic structures, resulting in the transformation of biphenyl via ortho-substituted dihydroxybiphenyl to six-ring fission products. All compounds were characterized by gas chromatography-mass spectroscopy and proton nuclear magnetic resonance spectroscopy. These compounds include 2-hydroxy-4-phenylmuconic acid and 2-hydroxy-4-(4-hydroxyphenyl)-muconic acid, which were produced from 3,4-dihydroxybiphenyl and further transformed to the corresponding lactones 4-phenyl-2-pyrone-6-carboxylic acid and 4-(4-hydroxyphenyl)-2-pyrone-6-carboxylic acid, which accumulated in large amounts. Two additional ring cleavage products were identified as (5-oxo-3-phenyl-2,5-dihydrofuran-2-yl)-acetic acid and [5-oxo-3-(4-hydroxyphenyl)-2,5-dihydrofuran-2-yl]-acetic acid. We found that P. lilacinus has a high transformation capacity for biphenyl, which could explain this organism's tolerance to this fungicide.

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mentioning

confidence: 99%

Biotransformation of Biphenyl by Paecilomyces lilacinus and Characterization of Ring Cleavage Products

Gesell

Hammer

Specht

et al. 2001

Appl Environ Microbiol

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“…Under improper conditions, it has been toxic to production workers. 27,28) Diphenylmethane is also used as a dye carrier and synthetic intermediate, similarly to diphenyl. Diphenyl is metabolized to hydroxylated diphenyls.…”

Section: Activation Of Diphenyl and Related Compounds By The Cyp1a1/2mentioning

confidence: 99%

Metabolic Activation of Proestrogens in the Environment by Cytochrome P450 System

Kawa

Sugihara

Sanoh

et al. 2008

JOURNAL OF HEALTH SCIENCE

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Liver microsome-mediated activation of proestrogens in the environment is reviewed here. Proestrogens such as methoxychlor, trans-stilbene, diphenyl, diphenylmethane, 2,2-diphenylpropane, benzo[a]pyrene, benzophenone, 2-nitrofluorene (NF), chalcone, trans-4-phenyl-3-buten-2-one and styrene oligomers are negative in in vitro estrogen screening tests. However, those proestrogens exhibit estrogenic activity after metabolic activation by the microsomal cytochrome P450 system. In these cases, hydroxylated derivatives of the compounds are formed as major metabolites, and these metabolites exhibit significant estrogenic activities. Thus, the estrogenic activities of proestrogenic compounds are a consequence of metabolism of the parent compounds. Various candidates for proestrogens among medicines and insecticides are also discussed.

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“…Under poor hygienic conditions, its production caused the toxicity for workers. 7,8) It is known to induce calculi and tumors in the urinary bladder of rats. 9) Diphenylmethane (DPM) is also used as a dye carrier and synthetic intermediate, similarly to DP.…”

Section: Introductionmentioning

confidence: 99%

Metabolic Activation of Proestrogenic Diphenyl and Related Compounds by Rat Liver Microsomes

Kawa

Sanoh

Kohta

et al. 2003

JOURNAL OF HEALTH SCIENCE

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In this study, liver microsome-mediated activation of diphenyl (DP), diphenylmethane (DPM) and 2,2-diphenylpropane (DPP) to estrogens was demonstrated. These three compounds were negative in estrogen reporter assay using estrogen-responsive human breast cancer cell line MCF-7. However, they exhibited estrogenic activity after incubation with liver microsomes of 3-methylcholanthrene-treated rats in the cases of DP and DPM, or of phenobarbital-treated rats in the cases of DP and DPP, in the presence of NADPH. When these compounds were incubated with liver microsomes in the presence of NADPH, monohydroxyl and dihydroxyl derivatives were formed. These hydroxylated metabolites, 4-hydroxydiphenyl, 3-hydroxydiphenyl, 2-hydroxydiphenyl, 4-hydroxydiphenylmethane, 2-(4-hydroxyphenyl)-2-phenylpropane (4-OH-DPP), 4,4′-dihydroxydiphenyl, 4,4′-dihydroxydiphenylmethane and 2,2-bis(4-hydroxyphenyl)propane (bisphenol A), all exhibited estrogenic activity in MCF-7 cells. Binding assay of these hydroxylated compounds with rat uterus estrogen receptor was also positive. These results suggest that the estrogenic activities of DP, DPM and DPP were due to the formation of hydroxylated metabolites by the liver cytochrome P450 system.Key words ---diphenyl, estrogenic activity, metabolic activation, human breast cancer cell line MCF-7, endocrine disruption, cytochrome P450 exert biological effects. Many so-called xenoestrogens produce a wide variety of toxic effects in animals. They may be playing a role in the increasing incidence of hormonally related cancers such as breast cancer and testicular cancer, and other problems of the reproductive system in humans. It is therefore important to screen environmental contaminants for estrogenic activity. Their metabolites also need to be identified and screened. We recently showed that trans-stilbene, which is the parent compound of diethylstilbestrol, and trans-stilbene oxide were not estrogenic, but exhibited a potent estrogenic activity after metabolic activation by a liver microsomal oxidation system. 4,5) In that report, we suggested that the estrogenic activity was due to the hydroxylated metabolites, trans-4-hydroxystilbene and trans-4,4′-dihydroxystilbene, formed by cytochrome P450 1A1/2. Furthermore, we demonstrated that styrene oligomers were metabolically activated to estrogens by rat liver microsomes, especially cytochrome P450 2B1.6) These results demonstrate the importance of considering proestrogenic potential, when screening for xenoestrogens in the environment.

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Diphenly Poisoning in Fruit Paper Production

Cited by 29 publications

References 2 publications

Biotransformation of Biphenyl by Paecilomyces lilacinus and Characterization of Ring Cleavage Products

Biotransformation of Biphenyl by Paecilomyces lilacinus and Characterization of Ring Cleavage Products

Metabolic Activation of Proestrogens in the Environment by Cytochrome P450 System

Metabolic Activation of Proestrogenic Diphenyl and Related Compounds by Rat Liver Microsomes

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