ReviewBiomonitoring of polycyclic aromatic hydrocarbons in human urine
Introduction
It is well-documented that polycyclic aromatic hydrocarbons (PAH) represent a class of compounds many of which are potent carcinogens for mammals [1], [2], [3]. Their significance as environmental and occupational carcinogens [4] has been proven by a series of studies on balancing the carcinogenic potential of various environmental matrices (vehicle exhaust, diesel exhaust extract, tobacco smoke condensate, hard-coal combustion condensate, used motor oil) and fractions thereof [5], [6], [7], [8], [9], [10], [11], [12]. At least for these matrices it has been shown that PAH containing more than three aromatic rings account for 70–90% of the total carcinogenic effect. According to the formation of PAH during all kinds of incomplete combustion processes they are widespread in the environment and reach high concentrations at certain workplaces. Hence, they have to be considered as a serious occupational burden. Although no direct experimental evidence is available that PAH are carcinogenic for humans, occupational studies strongly indicate that there is a correlation between PAH exposure and cancer incidence for various human tissues such as lung, skin and bladder. As a result of these findings a regular control of the PAH concentrations at various workplaces became mandatory. However, great inter-individual differences of the actual exposure were found for persons working at the same area and even at the same workplace [219], [220]. Physiological (breathing behaviour) and working habits (application of breathing masks etc.) were found to be responsible for this variability.
A more realistic parameter for the individual exposure, therefore, may be obtained by measuring the excretion of the incorporated PAH and their metabolites formed by a number of different enzymes, e.g. in the liver, lung and bladder. In the past, 1-hydroxypyrene (1-OHP) has been used as a representative PAH metabolite in occupational studies, and more recently further analytes (phanthrene metabolites, 3-hydroxybenzo[a]pyrene) have additionally been brought up [51], [81], [91], [96], [100], [122], [123], [125], [161], [183], [184].
Section snippets
Occupational studies
There are various industrial workplaces for which a significant increase of certain cancer diseases has been found that may be attributed to an unusually high exposure to PAH. For instance, PAH exposure is high in coke plants, coal tar and pitch producing and manufacturing industries, aluminium plants, iron and steel foundries, creosote-, rubber-, mineral oil-, soot- and carbon black-producing or manufacturing companies. As highly exposed occupational groups, chimney sweeps, roadmen
Exposure to PAH
For a basic burden of the general, non-occupationally exposed population, ambient air, water and food may be relevant. Presently, limit values of 1 or 10 ng benzo[a]pyrene per m3 air are recommended or mandatory in various countries (e.g. Italy or Germany). Actually, these concentrations are seldom found or exceeded nowadays in ambient air of rural or even of urban living areas. Elevated concentrations may be expected in areas with dense vehicle traffic, in road tunnels or in areas near to
Metabolism, elimination and excretion of PAH
After incorporation PAH are enzymatically converted primarily to arene-oxides which upon spontaneous isomerisation may give phenols or upon microsomal epoxide hydrolase-mediated addition of water may form trans-dihydrodiols. For the first step more or less regio-specifically operating cytochrome P450(CYP)-dependent monooxygenases are responsible, among which predominantly CYP1A1, 1A2, 1B1 and 3A4 are involved in the metabolic activation of PAH. Once formed, dihydrodiols may be further oxidised
Biomonitoring of PAH and their metabolites
Initial approaches to utilize the mutagenic potential of urine as a measure for the exposure to PAH led to inconsistent and unsatisfactory results [77], [78], [79], [80], [81], [82] which are based on the low sensitivity and the lack of specificity of the method. Actually the parameter measured cannot be unequivocally attributed to PAH or their metabolites.
Accordingly, methods were developed to directly measure the concentration of specific PAH metabolites excreted in urine. The obtained data
Conclusions
Measurement of PAH metabolites in human urine is the method of choice to determine recent exposure of an individual to PAH, in particular, when multiple routes of exposure have to be taken into account. 1-OHP excreted in urine is a sensitive biomarker for and significantly correlates with PAH exposure, although a wide interindividual variation occurs frequently. Despite the fact that this interindividual variation in urinary 1-OHP concentration also among similar exposed subjects reflects major
- Prof. Dr. Jürgen JACOB
- 1936
born in Hamburg
- 1955
matura examination
- 1955–1961
final examination for chemist (diploma)
- 1963
PhD at the university of Bonn; assistant of Prof. R. Tschesche. Subsidiary subject of the PhD: Pharmacology
- since 1963
scientific assistant at the Biochemical Institute for Environmental Carcinogens (BIU) in Großhansdorf, near Hamburg (director: Prof. Dr. G. Grimmer). Working fields: Lipid metabolism; skin lipids; occurrence, synthesis and metabolism of polycyclic aromatic
References (221)
- et al.
Cancer Lett.
(1987) - et al.
Cancer Lett.
(1983) - et al.
Cancer Lett.
(1984) - et al.
Cancer Lett.
(1985) - et al.
Cancer Lett.
(1988) - et al.
Chemosphere
(1997) - et al.
J. Chrom.
(1987) Toxicol. Lett.
(1982)- et al.
Cancer Lett.
(1989) - et al.
Mutat. Res.
(1983)
Mutat. Res.
Mutat. Res.
J. Chromatogr.
J. Chromatogr.
Sci. Total Environ.
IPCS Environmental Health Criteria 202. Selected Non-heterocyclic Polycyclic Aromatic Hydrocarbons
Pure Appl. Chem.
J. Natl. Cancer Inst.
J. Natl. Cancer Inst.
Int. Arch. Occup. Environ. Health
J. Occup. Med.
Br. J. Ind. Med.
J. Air Pollut. Control Assoc.
Ann. NY Acad. Sci.
Long-term Mortality Experience of Steelworkers
Zur Frage des Berufskrebses bei Beschäftigten der Gasindustrie — Kohortenstudie
Br. J. Ind. Med.
J. Occup. Environ. Med.
Scand. J. Work Environ. Health
Polynuclear aromatic hydrocarbons: physical and biological chemistry
J. Occup. Med.
J. Occup. Med.
Am. J. Public Health
Am. J. Epidemiol.
J. Occup. Med.
Arch. Malad. prof. Mèd. Trav. Sécurité Soc.
J. Environ. Pathol. Toxicol.
Vopr. Onkol.
Br. J. Ind. Med.
Chirurgical Observations Relative to the Cataract, the Polypus of the Nose, the Cancer of the Scrotum, the Different Kinds of Ruptures, and the Mortification of the Toes and Feet
J. Work Environ. Health
Staub Reinhalt. Luft
Br. J. Ind. Med.
Br. J. Ind. Med.
Scand. J. Work Environ. Health
Int. J. Epidemiol.
Cited by (228)
Research progress in human biological monitoring of aromatic hydrocarbon with emphasis on the analytical technology of biomarkers
2023, Ecotoxicology and Environmental SafetyStudy of the long-finned pilot whale (Globicephala melas) bile content - An indicator of ocean health
2023, Marine Pollution BulletinFine particulate matter and vasoactive 20-hydroxyeicosatetraenoic acid: Insights into the mechanisms of the prohypertensive effects of particulate air pollution
2022, Science of the Total EnvironmentCitation Excerpt :The robust association between OC and the 20-HETE concentration can be explained by the central roles of CYP in the metabolization of xenobiotics (e.g., nonpolar organics) and endobiotics (e.g., lipids). For instance, CYP family 1 (CYP1) in the phase I detoxification system is mainly responsible for metabolic activation of PAH in mammals (Jacob and Seidel, 2002). Animal toxicological studies suggest that CYP4 is involved in the metabolism of nonpolar carbon species, including pyrene, petroleum hydrocarbon, and organochlorine pesticides (Du et al., 2015; Chen et al., 2012).
- Prof. Dr. Jürgen JACOB
- 1936
born in Hamburg
- 1955
matura examination
- 1955–1961
final examination for chemist (diploma)
- 1963
PhD at the university of Bonn; assistant of Prof. R. Tschesche. Subsidiary subject of the PhD: Pharmacology
- since 1963
scientific assistant at the Biochemical Institute for Environmental Carcinogens (BIU) in Großhansdorf, near Hamburg (director: Prof. Dr. G. Grimmer). Working fields: Lipid metabolism; skin lipids; occurrence, synthesis and metabolism of polycyclic aromatic hydrocarbons; enzyme induction (CYP 450-dependent monoxygenases)
- since 1969
Director of the biochemistry division of BIU
- 1973
Habilitation at the university of Hamburg. Lecturer at the university.
- 1975
Chairman of the expert commission ‘Polynuclear Aromatic Hydrocarbons – Reference Materials’ of the European Community in Brussels
- since 1975
various activities by the order of the EU (BCR)
- 1978
Professor at the University of Hamburg
- 1979
Director at BIU
- 1987
Associated Member of the IUPAC
- 1990
Member of the Editorial Boards of ‘Polycyclic Aromatic Compounds’ (Gordon and Breach Science Publs.)
Publications:J. Jacob: Sulfur analogues of polycyclic aromatic hydrocarbons (thiaarenes). Cambridge Monographs on Cancer Research, Cambridge University Press (1990)
Contributions:Various contributions to scientific books and more than 300 publications in scientific journals (list of publication on demand)
- Dr. Albrecht SEIDEL
- 1954
born in Northeim/Hann
- 1972
Abitur
- 1972–1978
Studies of Chemistry
- 1979
Diploma in Chemistry
- 1980–1989
Ph.D. student/Research Assistant, Johannes Gutenberg-University of Mainz, Institute of Organic Chemistry and Institute of Toxicology
- 1989
Ph.D. (summa cum laude) in Chemistry, Johannes Gutenberg-Universität Mainz, supervisors: Prof. Dr. H. Kunz and Prof. Dr. F. Oesch
- 1990–1995
Research Associate at the University of Mainz, Project Leader in the center core grant SFB 302 (“Control factors of tumorigenesis”) at the University of Mainz
- 1996–1998
Research associate and teaching assistant (C1) at the Institute of Toxicology at the University of Mainz (Director: Prof. Dr. F. Oesch)
- since 1999
CEO of the “Biochemical Insitute of Environmental Carcinogens – Prof. Dr. Gernot Grimmer-Foundation” in Grosshansdorf/Hamburg
- 2000
Habilitation at the Johannes Gutenberg-Universität Mainz; Faculty of “Theoretical Medicine”; Priv.-Doz. “venia legendi for Toxicology”
- Honors:
1981–1984 Scholarship of the Herman Schlosser Foundation (Degussa AG, Germany). 1982–1984 Scholarship for exceptional talented Ph.D. Students (awarded by the “German National Scholarship Foundation”)
Research interests:Synthesis of reactive metabolites of polycyclic aromatic compounds (PAC); in vitro metabolism of PAC by human enzymes; molecular mechanisms of mutagenesis and carcinogenesis of PAC; methods for human biomonitoring of polycyclic aromatic hydrocarbons; analysis of PAC in environmental samples
Publications:Numerous book chapters and more than 100 publications in scientific journals
Membership of Scientific Societies:Gesellschaft Deutscher Chemiker (GDCh); American Chemical Society (ACS) Deutsche Gesellschaft für Pharmakologie und Toxikologie (DGPT); Gesellschaft für Umwelt- und Mutationsforschung (GUM); International Society of Polycyclic Aromatic Compounds (ISPAC); International Society for the Study of Xenobiotics (ISSX); International Society of Environmental Medicine (ISEM).