Human Biomonitoring of Mycotoxins in Blood, Plasma and Serum in Recent Years: A Review

Abstract

This manuscript reviews the state-of-the-art regarding human biological monitoring (HBM) of mycotoxins in plasma serum and blood samples. After a comprehensive and systematic literature review, with a focus on the last five years, several aspects were analyzed and summarized: a) the biomarkers analyzed and their encountered levels, b) the analytical methodologies developed and c) the relationship between biomarker levels and some illnesses. In the literature reviewed, aflatoxin B1-lysine (AFB1-lys) and ochratoxin A (OTA) in plasma and serum were the most widely studied mycotoxin biomarkers for HBM. Regarding analytical methodologies, a clear increase in the development of methods for the simultaneous determination of multiple mycotoxins has been observed. For this purpose, the use of liquid chromatography (LC) methodologies, especially when coupled with tandem mass spectrometry (MS/MS) or high resolution mass spectrometry (HRMS), has grown. A high percentage of the samples analyzed for OTA or aflatoxin B1 (mostly as AFB1-lys) in the reviewed papers were positive, demonstrating human exposure to mycotoxins. This review confirms the importance of mycotoxin human biomonitoring and highlights the important challenges that should be faced, such as the inclusion of other mycotoxins in HBM programs, the need to increase knowledge of mycotoxin metabolism and toxicokinetics, and the need for reference materials and new methodologies for treating samples. In addition, guidelines are required for analytical method validation, as well as equations to establish the relationship between human fluid levels and mycotoxin intake.

Keywords: HBM; blood; mycotoxins; plasma; serum.

Figure 1

Structures of the studied analytes in the retrieved articles. AFB1: aflatoxin B1; AFB2: aflatoxin B2; AFG1: aflatoxin G1; AFG2: aflatoxin G2; AFM1: aflatoxin M1; AFM2: aflatoxin M2; AFOH: aflatoxicol; AFB1-lys: adduct of AFB1 with lysine; STER: sterigmatocystin; OTA: ochratoxin A; OTα: ochratoxin α; OTB: ochratoxin B; 10-OH-OTA: 10-hydroxyochratoxin A; 2´R-OTA: 2’R-ochratoxin A; GLIO: gliotoxin; CIT: citrinin; DH-CIT: dihydrocitrinone; PAT: patulin; DON: deoxynivalenol; 3-ADON: 3-acetyldeoxynivalenol; 15-ADON: 15-acetyldeoxynivalenol; DON-3-GlcA: deoxynivalenol-3-glucuronide; DON-15-GlcA: deoxynivalenol-15-glucuronide; DOM-1: deepoxy-deoxynivalenol; T-2: T-2 toxin; HT-2: HT-2 toxin; HT-2-4-GlcA: HT-2-toxin-4-glucuronide. Modified from PubChem (https://pubchem.ncbi.nlm.nih.gov).

Figure 2

Structures of the studied analytes in the retrieved articles. ZEA: zearalenone; α-ZEL: α-zearalenol; β-ZEL: β-zearalenol; α-ZAL: α-zearalanol; β-ZAL: β-zearalanol; ZEA-14-GlcA: zearalenone-14- glucuronide; ZAN: zearalanone; ZAN-14-GlcA: zearalanone-14- glucuronide; FB1: fumonisin B1; FB2: fumonisin B2; NIV: nivalenol; FUS-X: fusarenon-X; DAS: diacetoxyscirpenol; EnA: enniatin A; EnA1: enniatin A1; EnB: enniatin B; EnB1: enniatin B1; BEA: beauvericin; ALT: altenuene; AME: alternariol monomethyl ether; AOH: alternariol. Modified from PubChem (https://pubchem.ncbi.nlm.nih.gov).

Figure 3

Extraction (A) and detection techniques (B) for mycotoxin determination in human blood/plasma/serum according to the articles reviewed on these matrices. The percentage of articles using each technique is indicated. IAC: immunoaffinity columns; LLE: liquid–liquid extraction; QuEChERS: Quick Easy Cheap Effective Rugged and Safe; SPE: solid-phase extraction.

Figure 4

Use of different analytical techniques for mycotoxin determination in human blood/plasma/serum across the years (in relation to the articles reviewed). The percentage of articles using each technique is shown.

Figure 5

Biomarkers of mycotoxins detected in human plasma or serum samples (according to the articles reviewed). The percentage of the retrieved papers that analyze each of the biomarkers is shown. AFB1: aflatoxin B1; AFB1-lys: adduct of AFB1; BEA: beauvericin; CIT: citrinin; DON: deoxynivalenol; Ens: enniatins; FBs: fumonisins; GLIO: gliotoxin; OTA: ochratoxin A; PAT: patulin; STER: sterigmatocystin; ZEA: zearalenone.

Figure 6

Comparison between estimated daily intake (EDI) of mean and maximum values and TDI for OTA exposure. Each dot corresponds to the EDI mean (blue) or EDI max (red) for the different exposure studies retrieved for OTA. A total of 15 studies were evaluated. The black line represents the most recent TDI established for OTA [136].

Figure 7

Flow diagram of excluded and included studies based on PRISMA Statement. MeSH: Medical Subject Headings.