Simultaneous analysis of naphthols, phenanthrols, and 1-hydroxypyrene in urine as biomarkers of polycyclic aromatic hydrocarbon exposure: intraindividual variance in the urinary metabolite excretion profiles caused by intervention with β-naphthoflavone induction in the rat

Elovaara, Eivor; Väänänen, Virpi; Mikkola, Jouni

doi:10.1007/s00204-003-0436-0

Cited by 50 publications

(23 citation statements)

References 42 publications

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“…1-Naphthol and 2-naphthol are detected in urine of Wistar rats administered naphthalene intraperitoneally (Elovaara et al, 2003). However, these naphthols have also been detected in cases of exposure to environmental polycyclic aromatic hydrocarbons in humans and animals.…”

Section: Discussionmentioning

confidence: 99%

In Vitro Metabolism of Naphthalene by Human Liver Microsomal Cytochrome P450 Enzymes

Cho

Rose²,

Hodgson³

2005

Drug Metab Dispos

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ABSTRACT:The polycyclic aromatic hydrocarbon naphthalene is an environmental pollutant, a component of jet fuel, and, since 2000, has been reclassified as a potential human carcinogen. Few studies of the in vitro human metabolism of naphthalene are available, and these focus primarily on lung metabolism. The current studies were performed to characterize naphthalene metabolism by human cytochromes P450. Naphthalene metabolites from pooled human liver microsomes (pHLMs) were trans-1,2-dihydro-1,2-naphthalenediol (dihydrodiol), 1-naphthol, and 2-naphthol. Metabolite production generated K m values of 23, 40, and 116 M and V max values of 2860, 268, and 22 pmol/mg protein/min, respectively. P450 isoform screening of naphthalene metabolism identified CYP1A2 as the most efficient isoform for producing dihydrodiol and 1-naphthol, and CYP3A4 as the most effective for 2-naphthol production. Metabolism of the primary metabolites of naphthalene was also studied to identify secondary metabolites. Whereas 2-naphthol was readily metabolized by pHLMs to produce 2,6-and 1,7-dihydroxynaphthalene, dihydrodiol and 1-naphthol were inefficient substrates for pHLMs. A series of human P450 isoforms was used to further explore the metabolism of dihydrodiol and 1-naphthol. 1,4-Naphthoquinone and four minor unknown metabolites from 1-naphthol were observed, and CYP1A2 and 2D6*1 were identified as the most active isoforms for the production of 1,4-naphthoquinone. Dihydrodiol was metabolized by P450 isoforms to three minor unidentified metabolites with CYP3A4 and CYP2A6 having the greatest activity toward this substrate. The metabolism of dihydrodiol by P450 isoforms was lower than that of 1-naphthol. These studies identify primary and secondary metabolites of naphthalene produced by pHLMs and P450 isoforms.

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Section: Discussionmentioning

confidence: 99%

In Vitro Metabolism of Naphthalene by Human Liver Microsomal Cytochrome P450 Enzymes

Cho

Rose²,

Hodgson³

2005

Drug Metab Dispos

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“…The predictors of 1-naphthol in urine (lnNAPurine) are more consistent with exposure to naphthalene, which together with phenanthrene and pyrene dominate PAH mixtures (Elovaara et al, 2003), than with exposure to the insecticide carbaryl. Tending a wood stove or fireplace the day before sampling (FIRE, yes or no), using gasolinepowered equipment (EQUIPMENT), spending time in a workshop (WORKSHOP, min), smoking cigarettes (CI-GARETS), and using mothballs (MOTHBALLS, yes or no) all correspond with known sources of naphthalene exposure, which include wood and tobacco smoke, fuel exhaust, and moth repellent (ATSDR, 1995).…”

Section: Multiple Regression Analysismentioning

confidence: 93%

Determinants of temporal variability in NHEXAS-Maryland environmental concentrations, exposures, and biomarkers

Egeghy

Quackenboss

Catlin

et al. 2004

J Expo Sci Environ Epidemiol

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The longitudinal NHEXAS-Maryland study measured metals, PAHs, and pesticides in several media to capture temporal variability. Questionnaires were concurrently administered to identify factors that influenced changes in contaminant levels over time. We constructed mixed-effects regression models for lead, phenanthrene, and chlorpyrifos (including metabolites) in indoor air, dust, dermal wipes, and biological fluids. Significant predictors represented time-varying activities as well as unchanging housing and demographic factors. There was little overlap among the models, with predictors generally reflecting the diverse characteristics of the target compounds. We estimated between-and within-person variance components to evaluate the reliability of the measurements. While only one measurement of lead in blood or chlopyrifos in dust was needed for a dependable estimate of an individual's average level, three to eight measurements were needed for most other compound/exposure medium combinations because of considerable temporal variability. Measurements in biological fluids and dust were generally more consistent than those in indoor air. The significant covariates in the full models preferentially reduced the between-person variance component. Since the regression models explained only 1-37% of the within-person variance, the questionnaires in this study provided only modest insight into the factors responsible for the temporal variability in the contaminant levels.

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“…Over the past years several analytical methods for the determination of either 1-naphthol or 2-naphthol, or even both together, in human or animal urine have been developed. Apart from one method that used thin-layer chromatography (Bieniek and Wilczok 1986), the techniques were based on high-pressure liquid chromatography (Elovaara et al 2003;Hansen et al 1992a;Kim et al 1999Kim et al , 2001Lee et al 2001;Massey et al 1995;Thompson et al 1996) and gas chromatography (Bieniek 1996(Bieniek , 1997(Bieniek , 1998Bouchard et al 2001;Hill et al 1995b;Hung et al 1992;Jansen et al 1995;Keimig and Morgan 1986;Kilanowicz et al 1999;Serdar et al 2003;Smith et al 2002;Yang et al 1999).…”

Section: Occupational Exposure To Naphthalenementioning

confidence: 99%

Naphthalene?an environmental and occupational toxicant

Preuss

Angerer

Drexler

2003

International Archives of Occupational and Environmental Health

281

149

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For many years naphthalene had been considered as a non-carcinogenic polycyclic aromatic hydrocarbon (PAH). Airborne naphthalene concentrations have always been observed to be below the limit values of various national committees, such as the threshold limit value (TLV) of the American Conference of Governmental Industrial Hygienists (ACGIH) and the MAK of the Deutsche Forschungsgemeinschaft (DFG) (10 ppm). Since 2000, when the US National Toxicology Program revealed clear evidence of the carcinogenic activity of naphthalene in rats, international agencies [the International Agency for Research on Cancer (IARC), the US Environmental Protection Agency (US EPA), DFG] have reclassified naphthalene as a potential human carcinogen, and the European Union (EU) is currently preparing a new risk assessment report. It is presently unknown how to protect humans from health risks resulting from occupational and environmental naphthalene exposure. Knowledge about the external and internal exposure of humans serves as the key determinant in a comprehensive risk assessment. We review here ambient monitoring studies concerning the external naphthalene exposure that results from ubiquitous environmental sources (indoor and outdoor air, water, soil, food) and from a variety of critical workplaces (coking plants, creosote impregnation, distillation of coal tar and naphthalene, manufacture of refractories, graphite electrodes, aluminium and mothballs). Based on results of ambient monitoring studies published so far, a new hygiene-based exposure limit of 1.5 mg naphthalene per cubic metre of air (0.3 ppm) is proposed. Furthermore, results from biological monitoring studies are summarised in this article. The internal burden was almost exclusively determined by means of the urinary metabolites 1-naphthol and 2-naphthol, but it is currently not possible for one to evaluate a biological tolerance level (BAT) or a biological exposure index (BEI). Based on the toxicokinetics and metabolism of naphthalene, the central question on its carcinogenicity is briefly sketched. Naphthoquinones play an important role in this context. Their adducts with macromolecules may be the parameters of choice for the estimation of effects to human health.

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Simultaneous analysis of naphthols, phenanthrols, and 1-hydroxypyrene in urine as biomarkers of polycyclic aromatic hydrocarbon exposure: intraindividual variance in the urinary metabolite excretion profiles caused by intervention with β-naphthoflavone induction in the rat

Cited by 50 publications

References 42 publications

In Vitro Metabolism of Naphthalene by Human Liver Microsomal Cytochrome P450 Enzymes

In Vitro Metabolism of Naphthalene by Human Liver Microsomal Cytochrome P450 Enzymes

Determinants of temporal variability in NHEXAS-Maryland environmental concentrations, exposures, and biomarkers

Naphthalene?an environmental and occupational toxicant

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