Download PDF
Suchttherapie 2024; 25(03): 120-128
DOI: 10.1055/a-2340-7514
Schwerpunktthema

Bedeutung neuer Alkoholbiomarker in der Eignungsbegutachtung von Verkehrsteilnehmern

New Alcohol Biomarkers when Checking Apitude in Road Traffic
Frank Musshoff
1   Forensisch Toxikologisches Centrum GmbH, München, Germany
› Author Affiliations
› Further Information
Also available at
    Permissions and Reprints

Zusammenfassung

Die direkten Alkoholkonsummarker Ethylglucuronid (EtG) in Urin und Haaren sowie Phosphatidylethanol (PEth) im Blut sind die Biomarker der Wahl bei einer Überprüfung einer Eignung gerade auch im Straßenverkehr. Die Bestimmung von EtG im Urin kann nur für unvorhersehbar anberaumte Abstinenzkontrollen eingesetzt werden, erlaubt aber keine weiterführende Interpretation bzgl. eines Konsumverhaltens. Die Bestimmung von EtG im Haar kann bei einem Cutoff von 5 pg/mg als Abstinenzkontrolle erfolgen, bis unter 30 pg/mg kann man ansonsten von einem moderaten, sozial angepasstem Konsumverhalten ausgehen. PEth im Blut eignet sich mit einem Cutoff von 20 ng/mL ebenfalls für Abstinenzkontrollen, Werte ab 210 ng/mL sprechen für einen übermäßigen Alkoholkonsum. PEth, das viel schneller auf Änderungen des Konsumverhaltens reagiert, als die Konzentration von EtG im Haar, wird auch eingesetzt in der analytischen Begleitung des Kontrollierten Trinkens nach Körkel. Der derzeitig dafür propagierte Cutoff von 100 ng/mL ist ggf. noch nach unten zu korrigieren. Möglichkeiten und Grenzen dieser Alkoholkonsummarker werden vorgestellt und diskutiert.

Abstract

The direct alcohol consumption markers ethyl glucuronide (EtG) in urine and hair as well as phosphatidylethanol (PEth) in blood are the biomarkers of choice when checking aptitude, especially in road traffic. The determination of EtG in urine can only be used for unannounced abstinence checks but does not allow any further interpretation regarding the consumption behavior. The determination of EtG in hair can be carried out for abstinence purposes using a cutoff of 5 pg/mg; otherwise, up to less than 30 pg/mg, a moderate, socially adapted consumption behavior can be assumed. With a cutoff of 20 ng PEth/mL blood, this marker is also suitable for checking abstinence; values above 210 ng/mL indicate excessive alcohol consumption. PEth, which reacts much more quickly to changes in consumption behavior compared to the concentration of EtG in hair, is also used in the analytical support of controlled drinking according to Körkel. The cutoff of 100 ng PEth/mL blood currently suggested for this purpose may need to be revised downwards. The possibilities and limitations of these alcohol consumption markers are presented and discussed.

Schlüsselwörter

Alkoholkonsummarker - Fahreignung - Ethylglucuronid - Phosphatidylethanol

Keywords

alcohol biomarker - driving ability - ethylglucuronide - phosphytidylethanol


Publication History

Article published online:
12 August 2024

© 2024. Thieme. All rights reserved.

Georg Thieme Verlag
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • Literatur

  • 1 Mußhoff F. Aktuelles zu Alkoholkonsummarkern in der Fahreignungsdiagnostik. Zeitschrift für Verkehrssicherheit 2017; 63: 125-135
    PubMedGoogle Scholar
  • 2 Andresen-Streichert H, Müller A. et al. Alkoholmarker bei klinischen und forensischen Fragestellungen. Dtsch Ärztebl Int 2018; 11: 309-315
    PubMedGoogle Scholar
  • 3 Skopp G, Mußhoff F. Aktuelles zu Alkoholkonsummarkern bei forensischen und suchtmedizinischen Fragestellungen. Sucht 2020; 66: 329-338
    CrossrefPubMedGoogle Scholar
  • 4 AWMF, DGPPN & DG Sucht (Hrsg.) S3-Leitlinie „Screening, Diagnose und Behandlung alkoholbezogener Störungen“, AWMF-Register Nr. 076-001 https://register.awmf.org/assets/guidelines/076-001l_S3-Screening-Diagnose-Behandlung-alkoholbezogene-Stoerungen_2021-02.pdf (abgerufen am 20.06.24)
    PubMed
  • 5 Heier C, Xie H, Zimmermann R. Nonoxidative ethanol metabolism in humans – from biomarkers to bioactive lipids. Int Union Biochem Mol Biol 2016; 68: 916-923
    PubMedGoogle Scholar
  • 6 Helander A, Böttcher M. et al. Detection times for urinary ethyl glucuronide and ethyl sulfate in heavy drinkers during alcohol detoxification. Alcohol Alcohol 2009; 44: 55-61
    CrossrefPubMedGoogle Scholar
  • 7 Albermann E, Musshoff F. et al. Preliminary investigations on ethyl glucuronide and ethyl sulfate cutoffs for detecting alcohol consumption on the basis of an ingestion experiment and on data from withdrawal treatment. Int J Legal Med 2012; 126: 757-764
    CrossrefPubMedGoogle Scholar
  • 8 Deutsche Gesellschaft für Verkehrspsychologie (DGVP) & Deutsche Gesellschaft für Verkehrsmedizin (DGVM) Urteilsbildung in der Fahreignungsbegutachtung – Beurteilungskriterien, 4. Aufl. Bonn: Kirschbaum Verlag; 2022
    Google Scholar
  • 9 Musshoff F, Albermann E, Madea B. Ethyl glucuronide and ethyl sulfate in urine after consumption of various beverages and foods – misleading results?. Int J Legal Med 2010; 124: 623-630
    CrossrefPubMedGoogle Scholar
  • 10 Costantino A, Di Gregorio EJ. et al. The effect of the use of mouthwash on ethylglucuronide concentrations in urine. J Anal Toxicol 2006; 30: 659-662
    CrossrefPubMedGoogle Scholar
  • 11 Arndt T, Beyreiss R. et al. Cross-reaction of propyl and butyl alcohol glucuronides with an ethyl glucuronide enzyme immunoassay. Forensic Sci Int 2014; 241: 84-86
    CrossrefPubMedGoogle Scholar
  • 12 Arndt T, Schrofel S. et al. Inhalation but not transdermal resorption of hand sanitizer ethanol causes positive ethyl glucuronide findings in urine. Forensic Sci Int 2014; 237: 126-130
    CrossrefPubMedGoogle Scholar
  • 13 Gessner S, Below E. et al. Ethanol and ethyl glucuronide urine concentrations after ethanol-based hand antisepsis with and without permitted alcohol consumption. Am J Infect Control 2016; 44: 999-1003
    CrossrefPubMedGoogle Scholar
  • 14 Bützer P (2009. Dermale Aufnahme von Ethanol https://docplayer.org/32670435-Dermale-aufnahme-von-ethanol.html https://www.researchgate.net/publication/237263370_Dermale_Aufnahme_von_Ethanol_Dermal_uptake_of_ethanol/link/02e7e5319dfa1227ac000000/download (abgerufen am 10.01.2024).
    PubMed
  • 15 Reisfield GM, Teitelbaum SA. et al. Blood phosphatidylethanol concentrations following regular exposure to an alcohol-based mouthwash. J Anal Toxicol 2021; 45: 950-956
    PubMedGoogle Scholar
  • 16 Herzog J, Skopp G, Musshoff F. Development and validation of seven phosphatidylethanol-homologues in dried blood spots including preliminary results after excessive use of an ethanol-based hand sanitizer. J Anal Toxicol 2023; 47: 245-252
    CrossrefPubMedGoogle Scholar
  • 17 Helander A, Olsson I, Dah H. Postcollection synthesis of ethyl glucuronide by bacteria in urine may cause false identification of alcohol consumption. Clin Chem 2007; 53: 1855-1857
    CrossrefPubMedGoogle Scholar
  • 18 Thierauf A, Wohlfarth A. et al. Urine tested positive for ethyl glucuronide and ethyl sulfate after the consumption of yeast and sugar. Forensic Sci Int 2010; 202: e45-e47
    CrossrefPubMedGoogle Scholar
  • 19 Helander A, Dahl H. Urinary tract infection: a risk factor for false-negative urinary ethyl glucuronide but not ethyl sulfate in the detection of recent alcohol consumption. Clin Chem 2005; 51: 1728-1730
    CrossrefPubMedGoogle Scholar
  • 20 Baranowski S, Serr A. et al. In vitro study of bacterial degradation of ethyl glucuronide and ethyl sulphate. Int J Legal Med 2008; 122: 389-393
    CrossrefPubMedGoogle Scholar
  • 21 Thierauf A, Serr A. et al. Influence of preservatives on the stability of ethyl glucuronide and ethyl sulphate in urine. Forensic Sci Int 2008; 182: 41-45
    CrossrefPubMedGoogle Scholar
  • 22 Redondo AH, Körber C. et al. Inhibition of bacterial degradation of EtG by collection as dried urine spots (DUS). Anal Bioanal Chem 2012; 402: 2417-2424
    CrossrefPubMedGoogle Scholar
  • 23 Wurst FM, Dresen S. et al. Ethyl sulphate: a direct ethanol metabolite reflecting recent alcohol consumption. Addiction 2006; 101: 204-211
    CrossrefPubMedGoogle Scholar
  • 24 Graw M, Musshoff F, Seidl J. Alkohol und Drogen. Zeitschrift für Verkehrssicherheit 2017; 63: 76-78
    PubMedGoogle Scholar
  • 25 Sachs H. Drogennachweis in Haaren. In: Kijewski, H. (Hrsg.) Das Haar als Spur - Spur der Haare. Schmidt-Römhild, Lübeck. 1995: 119-133
    Google Scholar
  • 26 Pragst F, Yegles M. Determination of fatty acid ethyl esters (FAEE) and ethyl glucuronide (EtG) in hair: a promising way for retrospective detection of alcohol abuse during pregnancy?. Ther Drug Mon 2008; 30: 255-263
    CrossrefPubMedGoogle Scholar
  • 27 Tsanaclis L, Kingston R, Wicks J. Testing for alcohol use in hair. Is ethyl glucuronide (EtG) stable in hair?. Ann Toxicol Anal 2009; 21: 67-71
    CrossrefPubMedGoogle Scholar
  • 28 Pragst F, Rothe M. et al. Combined use of fatty acid ethyl esters and ethyl glucuronide in hair for diagnosis of alcohol abuse: interpretation and advantages. Forensic Sci Int 2010; 196: 101-110
    CrossrefPubMedGoogle Scholar
  • 29 Fosen JT, Høiseth G. et al. Hair EtG: Alterations in segment levels accompanying hair growth. Drug Test Anal 2019; 11: 112-118
    CrossrefPubMedGoogle Scholar
  • 30 Crunelle CL, Yegles M. et al. Influence of repeated permanent coloring and bleaching on ethyl glucuronide concentrations in hair from alcohol-dependent patients. Forensic Sci Int 2015; 247: 18-22
    CrossrefPubMedGoogle Scholar
  • 31 Martins Ferreira L, Binz T, Yegles M. The influence of ethanol containing cosmetics on ethyl glucuronide concentration in hair. Forensic Sci Int 2012; 218: 123-125
    CrossrefPubMedGoogle Scholar
  • 32 Sporkert F, Kharbouche H. et al. Positive EtG findings in hair as a result of a cosmetic treatment. Forensic Sci Int 2012; 218: 97-100
    CrossrefPubMedGoogle Scholar
  • 33 Arndt T, Schrofel S, Stemmerich K. Ethyl glucuronide identified in commercial hair tonics. Forensic Sci Int 2013; 231: 195-198
    CrossrefPubMedGoogle Scholar
  • 34 Scholz C, Baumgartner MR, Madry MM. Use of ethanol-based hand desinfectants: Source of increased ethyl glucuronide levels in hair?. Alcohol Alcohol 2021; 56: 38-41
    CrossrefPubMedGoogle Scholar
  • 35 Pötsch L, Skopp G. Inkorporation von Fremdsubstanzen in Haare. In: Madea, B. & Musshoff, F. (Hrsg.): Haaranalytik: Technik und Interpretation in Medizin und Recht. Köln: Deutscher Ärzte-Verlag; pp 2004: 29-98
    Google Scholar
  • 36 Kronstrand R, Brinkhagen L, Nystrom FH. Ethyl glucuronide in human hair after daily consumption of 16 or 32 g of ethanol for 3 months. Forensic Sci Int 2012; 215: 51-55
    CrossrefPubMedGoogle Scholar
  • 37 Crunelle CL, Cappelle D. et al. Ethyl glucuronide concentrations in hair: a controlled alcohol-dosing study in healthy volunteers. Anal Bioanal Chem 2016; 408: 2019-2025
    CrossrefPubMedGoogle Scholar
  • 38 Society of Hair Testing (SOHT) (2019). 2019 Consensus for the use of alcohol markers in hair for supporting the assessment of abstinence and chronic alcohol consumption https://www.soht.org/images/pdf/Revision_2019_Alcoholmarkers.pdf (abgerufen am 10.1.2024).
    PubMed
  • 39 Mueller A, Jungen H. et al. Determination of ethyl glucuronide in human hair samples: A multivariate analysis of the impact of extraction conditions on quantitative results. Forensic Sci Int 2016; 271: 43-48
    CrossrefPubMedGoogle Scholar
  • 40 Salomone A, Baumgartner MR. et al. Effects of various sample pretreatment procedures on ethyl glucuronide quantification in hair samples: Comparison of positivity rates and appraisal of cut-off values. Forensic Sci Int 2016; 267: 60-65
    CrossrefPubMedGoogle Scholar
  • 41 Pragst F, Auwaerter V. et al. Analysis of fatty acid ethyl esters in hair as possible markers of chronically elevated alcohol consumption by headspace solid-phase microextraction (HS-SPME) and gas chromatography-mass spectrometry (GC-MS). Forensic Sci Int 2001; 121: 76-88
    CrossrefPubMedGoogle Scholar
  • 42 Gnann H, Engelmann C. et al. Identification of 48 homologues of phosphatidylethanol in blood by LC-ESI-MS/MS. Anal Bioanal Chem 2010; 396: 2415-2423
    CrossrefPubMedGoogle Scholar
  • 43 Ulwelling W, Smith K. The PEth blood test in the security environment: what it is; why it is important; and interpretative guidelines. J Forensic Sci 2018; 63: 1634-1640
    CrossrefPubMedGoogle Scholar
  • 44 Luginbühl M, Wurst FW. et al. Consensus for the use of the alcohol biomarker phosphatidylethanol (PEth) for the assessment of abstinence and alcohol consumption in clinical and forensic practice (2022 Consensus of Basel). Drug Test Anal 2022; 14: 1800-1802
    CrossrefPubMedGoogle Scholar
  • 45 Musshoff F, Böttcher M. et al. Comment on the upper cutoff level for the alcohol biomarker phosphatidylethanol (PEth) for the assessment of alcohol consumption in forensic practice. Drug Test Anal 2023; 15: 791-792
    CrossrefPubMedGoogle Scholar
  • 46 Schröck A, Pfäffli M. et al. Application of phosphatidylethanol (PEth) in whole blood in comparison to ethyl glucuronide in hair (hEtG) in driving aptitude assessment (DAA). Int J Legal Med 2016; 130: 1527-1533
    CrossrefPubMedGoogle Scholar
  • 47 Stöth F, Kotzerke E. et al. Can PEth be detected with a cutoff of 20 ng/mL after single alcohol consumption?. J Anal Toxicol 2023; 46: e232-e238
    CrossrefPubMedGoogle Scholar
  • 48 Herzog J, Skopp G, Musshoff F. et al. Formation of phosphatidylethanol and ethylglucuronide after low to moderate alcohol consumption in volunteers with a previous three-week alcohol abstinence. Alcohol Alcohol 2023; 58: 599-605
    CrossrefPubMedGoogle Scholar
  • 49 Aboutara N, Szewczyk A. et al. Phosphatidylethanol in patients with liver diseases of different etiologies: Analysis of six homologues and comparison with other alcohol markers. Clin Chem Acta 2022; 524: 171-178
    CrossrefPubMedGoogle Scholar
  • 50 Aboutara N, Jungen H. et al. PEth 16:0/18:1 and 16:0/18:2 after consumption of low doses of alcohol-A contribution to cutoff discussion. Drug Test Anal 2023; 15: 104-114
    CrossrefPubMedGoogle Scholar
  • 51 Reisfield GM, Teitelbaum SA. et al. Blood phosphatidylethanol concentrations following regular exposure to an alcohol-based mouthwash. J Anal Toxicol 2021; 45: 950-956
    CrossrefPubMedGoogle Scholar
  • 52 Schröck A, Thierauf-Emberger A, Schürch S. et al. Phosphatidylethanol (PEth) detected in blood for 3 to 12 days after single consumption of alcohol-a drinking study with 16 volunteers. Int J Legal Med 2017; 131: 153-160
    CrossrefPubMedGoogle Scholar
  • 53 Gnann H, Weinmann W, Thierauf A. Formation of phosphatidylethanol and its subsequent elimination during an extensive drinking experiment over 5 days. Alcohol: Clin Exp Res 2012; 36: 1507-1511
    CrossrefPubMedGoogle Scholar
  • 54 Snozek CLH, Kinard TN. et al. Artificial elevation of phosphatidylethanol due to red blood cell transfusion. Clin Biochem 2023; 120: 110651
    CrossrefPubMedGoogle Scholar
  • 55 Årving A, Hilberg T. et al. Falsely low phosphatidylethanol may be associated with biomarkers of haemolytic disease. Basic Clin Pharmacol Toxicol 2023; 132: 223-230
    CrossrefPubMedGoogle Scholar
  • 56 Aradottir S, Seidl S. et al. Phosphatidylethanol in human organs and blood: A study on autopsy material and influences by storage conditions. Alcohol.: Clin Exp Res 2004; 28: 1718-1723
    CrossrefPubMedGoogle Scholar
  • 57 Aboutara N, Jungen H. et al. Stability of PEth 16:0/18:1, 16:0/18:2, 16:0/20:4, 18:0/18:1, 18:0/18:2, and 18:1/18:1 2024
    PubMed
  • 58 Herzog J, Skopp G, Musshoff F. et al. Storage stability of phosphatidylethanol homologues in whole blood and dried blood spots of non-alcoholics at different temperatures over 60 days. Drug Test Anal. 2024 Im Druck
    PubMedGoogle Scholar
  • 59 Beck O, Mellring M. et al. Measurement of the alcohol biomarker phosphatidylethanol (PEth) in dried blood spots and venous blood-importance of inhibition of post-sampling formation from ethanol. Anal Bioanal Chem 2021; 413: 5601-5606
    CrossrefPubMedGoogle Scholar
  • 60 Faller A, Richter B. et al. LC-MS/MS analysis of phosphatidylethanol in dried blood spots versus conventional blood specimens. Anal Bioanal Chem 2011; 401: 1163-1166
    CrossrefPubMedGoogle Scholar
  • 61 Faller A, Richter B. et al. Stability of phosphatidylethanol species in spiked and authentic whole blood and matching dried blood spots. Int J Legal Med 2013; 127: 603-610
    CrossrefPubMedGoogle Scholar
  • 62 Kummer N, Ingels A-S. et al. Quantification of phosphatidylethanol 16:0/18:1, 18:1/18:1, and 16:0/16:0 in venous blood and venous and capillary dried blood spots from patients in alcohol withdrawal and control volunteers. Anal Bioanal Chem 2016; 408: 825-838
    CrossrefPubMedGoogle Scholar
  • 63 Luginbühl M, Young RSE. et al. Variation in the relative isomer abundance of synthetic and biologically derived phosphatidylethanols and its consequences for reliable quantification. J Anal Toxicol 2021; 45: 76-83
    CrossrefPubMedGoogle Scholar
  • 64 Körkel J. Kontrolliertes Trinken: Aktueller Forschungsstand – Implikationen für Beurteilungskriterien, Begutachtung (MPU) und verkehrspsychologische Interventionen. Zeitschrift für Verkehrssicherheit 2018; 111-115
    PubMedGoogle Scholar
  • 65 Körkel J, Wagner T. Abstinenz oder kontrolliertes Trinken? Eine evidenzbasierte Betrachtung zur notwendigen Verhaltensänderung bei alkoholauffälligen Kraftfahrern. Blutalkohol 2021; 58: 211-228
    PubMedGoogle Scholar
  • 66 Bischof G, Lange N. et al. Stellungnahme Dachgesellschaft Sucht: reduziertes Trinken und Schadensminderung bei der Behandlung von Alkoholkonsumstörungen. Sucht 2019; 65: 115-134
    CrossrefPubMedGoogle Scholar
  • 67 Musshoff F, Wagner T. Kontrolliertes Trinken – Alkoholkonsummarker PEth und EtG. Zeitschrift für Verkehrssicherheit 2023; 68: 138-140
    PubMedGoogle Scholar
  • 68 Skråstad RB, Aamo TO. et al. Quantifying alcohol consumption in the general population by analysing phosphatidylethanol concentrations in whole blood: Results from 24.574 subjects included in the HUNT4 Study. Alcohol Alcohol 2023; 58: 258-265
    CrossrefPubMedGoogle Scholar
  • 69 Herzog J, Skopp G, Musshoff F. Monitoring of phosphatidylethanol in dried blood spots and of ethyl glucuronide in hair over 6 months of alcohol consumption. Drug Test Anal 2024; 16: 359-368
    CrossrefPubMedGoogle Scholar