Analytical methodology for unveiling human exposure to (micro)plastic additives

1 Elec onic Supplemen a y Ma e ial Analy ical me hodology o un eiling human exposu e o (mic o)plas ic addi i es And ea Es é ez-Dan a a, Juan F. Ayala-Cab e a b,c,*, Ja ie López-Vázquez a, Mikel Musa adi b,c, Rosa Mon es a,*, Nes o E xeba ia b,c, José Beni o Quin ana a, Mai ane Oli a es b,c, Aile e P ie o b,c, Rosa io Rodil a, Manuel Mi ó d,*and Ola z Zuloaga b,c a Depa men o Analy ical Chemis y, Nu i ion and Food Science, Ins i u e o Resea ch on Chemical and Biological Analysis (IAQBUS), Uni e sidade de San iago de Compos ela (USC), San iago de Compos ela, Spain b Depa men o Analy ical Chemis y, Uni e si y o he Basque Coun y (UPV/EHU), Leioa, Spain c Resea ch Cen e o Expe imen al Ma ine Biology and Bio echnology, Uni e si y o he Basque Coun y (PiE- UPV/EHU), Plen zia, Spain d FI-TRACE G oup, Depa men o Chemis y, Uni e si y o he Balea ic Islands (UIB), Palma de Mallo ca, Spain Co esponding au ho s: D . Juan F. Ayala Cab e a ([email p o ec ed]) D . Rosa Ma ía Mon es Goyanes ([email p o ec ed]) D . Manuel Mi ó Lladó (manuel.[email p o ec ed]) Table o Con en s Suppo ing Tables ...................................................................................................................................... 2 Table S1. Lis o plas ic addi i es and plas ic cons i uen s, including con en ional and al e na i e plas icize s, lame- e a dan s an ioxidan s and bisphenol compounds, along wi h hei main phase-I me aboli es included in his e iew (* e e s o me aboli es no discussed in his e iew). ...................................................................................................................... 2 Table S2. Human o al bioaccessibili y da a o plas ic addi i es using di e en in- i o physiologically based ex ac ion es s. (See Table S1 o he ull names o he compounds). ..................................................................................................................... 6 Table S3. O e iew o he main me aboli es o plas ic- ela ed chemicals and hei espec i e 24- hou exc e ion a es. ......................................................................................................... 7 Table S4. Concen a ion le els o plas icize s, bisphenols, lame e a dan s and an ioxidan s in human biomoni o ing app oaches as applied o u ine, b eas milk and plasma (2019- 2023). (See Table S1 o he ull names o compounds, he “m” e e s o “me aboli e o ”) ....................................................................................................................................... 8 Suppo ing Figu es ................................................................................................................................... 17 Figu e S1. O e iew o physiologically-based ex ac ion es s o he in es iga ion o he gas oin es inal, de mal and lung bioaccessibili y o plas ic- ela ed chemicals. In o al bioaccessibili y, unde lined chemicals and expe imen al condi ions a e hose ecommended by Ruby e al. (2002). The emaining condi ions a e bo h applied o UBM and RIVM. ..................................................................................................................... 17 Figu e S2. Top phase I me aboli es moni o ed in human biomoni o ing pape s (2019-2023) included in his e iew and gi en as he numbe o imes hey ha e been analyzed in biological samples: a) p ima y and seconda y ph hala e es e me aboli es, b) p ima y and seconda y phase-I me aboli es o al e na i e plas icize s, and c) p ima y phase-I me aboli es o o ganophospha e lame- e a dan s. (See Table S1 o he ull names o compounds as well as he in o ma ion ela ed o he pa en compound). ..................................................... 18 Re e ences ................................................................................................................................................. 19 2 Suppo ing Tables Table S1. Lis o plas ic addi i es and plas ic cons i uen s, including con en ional and al e na i e plas icize s, lame- e a dan s an ioxidan s and bisphenol compounds, along wi h hei main phase- I me aboli es included in his e iew (* e e s o me aboli es no discussed in his e iew). Ph hala e Es e s (PAEs) Pa en P ima y Phase I me aboli e Seconda y Phase I me aboli e DMP dime hyl ph hala e MMP monome hyl ph hala e n. .a DEP die hyl ph hala e MEP monoe hyl ph hala e n. .a DP P dip opyl ph hala e MnP P mono-n-p opyl ph hala e MCPP (cx-MP P) mono(3-ca boxyp opyl) ph hala e DiP P di-isop opyl ph hala e MiPP mono-isop opyl ph hala e n. .a DAP diallyl ph hala e MAP* monoallyl ph hala e* n. .a DMEP di(2-me hoxye hyl) ph hala e MMEP* monome hoxye hyl ph hala e* MAA* me hoxyace ic acid DEEP di(e hoxye hyl) ph hala e MEEP* monoe hoxye hyl ph hala e* n. .a DnBP di-n-bu yl ph hala e MnBP mono-n-bu yl ph hala e 3OH-MnBP mono(3-hyd oxybu yl) ph hala e MCPP mono (3-ca boxyp opyl) ph hala e DiBP di-isobu yl ph hala e MiBP mono-isobu yl ph hala e 2OH-MiBP mono(2-hyd oxy-isobu yl) ph hala e DnPeP dipen yl ph hala e MnPeP (MPP) mono-n-pen yl ph hala e cx-MPeP mono(5-ca boxypen yl) ph hala e OH-MPeP mono(4-hyd oxypen yl) ph hala e DiPeP di-isopen yl ph hala e MiPeP mono-isopen yl ph hala e 4OH-MiPeP mono(4-hyd oxy-isopen yl) ph hala e DBEP di(2-bu oxye hyl) ph hala e n. .a n. .a BBzP bu yl benzyl ph hala e MBzP monobenzyl ph hala e n. .a DnHP di-n-hexyl ph hala e MHxP monohexyl ph hala e 5OH-MHxP mono(5-hyd oxyhexyl) ph hala e DMPP di(4-me hyl-2-pen yl) ph hala e n. .a n. .a DCHP dicyclohexyl ph hala e MCHP monocyclohexyl ph hala e n. .a DEHP di(2-e hylhexyl) ph hala e MEHP mono(2-e hylhexyl) ph hala e cx-MEPP mono(2-e hyl-5-ca boxypen yl) ph hala e MEHHP mono(2-e hyl-5-hyd oxyhexyl) ph hala e MEOHP mono(2-e hyl-5-oxohexyl) ph hala e cx-MMHP mono[(2-ca boxyme hyl)hexyl] ph hala e DP HP di(2-p opylhep yl) ph hala e cx-MPHxP mono(2-p opyl-6- ca boxyhexyl) ph hala e n. .a DHpP di-n-hep yl ph hala e MnHpP mono-n-hep yl ph hala e 6OH-MnHpP mono(6-hyd oxyhep yl) ph hala e DnOP di-n-oc yl ph hala e MnOP mono-n-oc yl ph hala e cx-MiOP mono(ca boxy-iso-oc yl) ph hala e MCPP mono(3-ca boxyp opyl) ph hala e DnNP di-nonyl ph hala e MnNP Mono-n-nonylph hala e n. .a DiNP di-isononyl ph hala e MiNP mono-isononyl ph hala e cx-MiNP mono(ca boxy-isononyl) ph hala e OH-MiNP mono(hyd oxy-isononyl) ph hala e oxo-MiNP mono(oxo-isononyl) ph hala e nPiPP n-pen yl-isopen yl ph hala e n. .a n. .a DiDP di-isodecyl ph hala e MiDP (MPHP) mono-isodecyl ph hala e cx-MiDP mono(ca boxy-isodecyl) ph hala e OH-MiDP mono(hyd oxy-isodecyl) ph hala e oxo-MiDP mono(oxo-isodecyl) ph hala e a No epo ed. 3 Table S1 (con ). Lis o plas ic addi i es and plas ic cons i uen s, including con en ional and al e na i e plas icize s, lame- e a dan s an ioxidan s and bisphenol compounds, along wi h hei main phase-I me aboli es included in his e iew (* e e s o me aboli es no discussed in his e iew). Al e na i e plas icize s (APs) Pa en P ima y Phase I me aboli e Seconda y Phase I me aboli e DMTP dime hyl e eph hala e MMTP monome hyl e eph hala e n. .a DETP die hyl e eph hala e METP monoe hyl e eph hala e n. .a DTBTP di- e -bu yl e eph hala e MTBTP mono- e -bu yl e eph hala e n. .a BBzTP bu yl benzyl e eph hala e MBzTP monobenzyl e eph hala e n. .a DEHTP di(e hylhexyl) e eph hala e TPA e eph halic acid n. .a MEHTP mono(2-e hylhexyl) e eph hala e 2cx-MMHTP mono-(2-ca boxyl-me hyl-hexyl) benzene-1,4-dica boxyla e 5cx-MEPTP mono(2-e hyl-5-ca boxypen yl) e eph hala e MEHHTP mono(2-e hyl-5-hyd oxyhexyl) e eph hala e MEOHTP mono(2-e hyl-5-oxo-hexyl) e eph hala e DINCH di(isononyl)cyclohexane- 1,2- dica boxyla e MCOCH cyclohexane-1,2-dica boxylic acid monoca boxyisooc yl es e n. .a MINCH mono-isononyl-cyclohexane-1,2- dica boxyla e cx-MINCH Mono-(7-ca boxy-4-me hyl- oc yl) cyclohexane-1,2- dica boxyla e OH-MINCH Mono-(4-me hyl-7-hyd oxy- oc yl) cyclohexane-1,2- dica boxyla e oxo-MINCH Mono-(4-me hyl-7-oxo-oc yl) cyclohexane-1,2-dica boxyla e DEHA di(2-e hylhexyl) adipa e MEPA mono(2-e hylpexyl) adipa e 5cx-MEPA mono(5-ca boxy-2-e hylpen yl) adipa e MEHA mono(2-e hylhexyl) adipa e 5OH-MEHA mono(2-e hyl-5-hyd oxyhexyl) adipa e 5oxo-MEHA mono(2-e hyl-5-oxohexyl) adipa e TOTM (TEHTM) i(2-e hylhexyl) imelli a e 1-MEHTM 1-mono-(2-e hylhexyl) imelli a e 5cx-1-MEPTM 1-mono(2-e hyl-5- ca boxypen yl) imelli a e 5OH-1-MEHTM 1-mono(2-e hyl-5-hyd oxyhexyl) imelli a e 5oxo-1-MEHTM 1-mono(2-e hyl-5-oxohexyl) imelli a e 2-MEHTM 2-mono-(2-e hylhexyl) imelli a e 5cx-2-MEPTM 2-mono(2-e hyl-5- ca boxypen yl) imelli a e 5OH-2-MEHTM 2-mono(2-e hyl-5-hyd oxyhexyl) imelli a e 5oxo-2-MEHTM 2-mono(2-e hyl-5-oxohexyl) imelli a e 4-MEHTM 4-mono-(2-e hylhexyl) imelli a e n. .a DiPGDB dip opylene glycol dibenzoa e DiPGDB- M194 3-(3-hyd oxyp opoxy)p opyl benzoa e n. .a ATBC Ace yl ibu yl ci a e ADBC* ace yl dibu yl ci a e* AMBC* ace yl monobu yl ci a e* DBC* dibu yl ci a e* a No epo ed. 4 Table S1 (con ). Lis o plas ic addi i es and plas ic cons i uen s, including con en ional and al e na i e plas icize s, lame- e a dan s an ioxidan s and bisphenol compounds, along wi h hei main phase-I me aboli es included in his e iew (* e e s o me aboli es no discussed in his e iew). O ganophospha e Flame Re a dan s (OPFRs) Pa en P ima y Phase I me aboli e Seconda y Phase I me aboli e TMP ime hyl phospha e DMP dime hyl phospha e n. .a TEP ie hyl phospha e DEP die hyl phospha e n. .a TP P ip opyl phospha e DP P dip opyl phospha e n. .a TnBP i-n-bu yl phospha e DBP di-n-bu yl phospha e n. .a 3OH-TNBP di-n-bu yl-3-hyd oxybu yl phospha e n. .a TiBP i-iso-bu yl phospha e DIBP diisobu yl phospha e n. .a TBzP ibenzyl phospha e DBzP dibenzyl phospha e n. .a TCP ic esyl phospha e DoCP di-o-c esyl phospha e n. .a BMPP di(2-me hylhexyl) phospha e n. .a DpCP di-p-c esyl phospha e n. .a TPHP iphenyl phospha e MPHP Monophenyl phospha e n. .a DPHP diphenyl phospha e 3OH-DPHP 3-hyd oxyphenyl phenyl phospha e 4OH-DPHP 4-hyd oxyphenyl phenyl phospha e 3OH-TPHP 3-hyd oxyphenyl diphenyl phospha e n. .a 4OH-TPHP 4-hyd oxyphenyl diphenyl phospha e n. .a TPPO iphenylphosphine oxide n. .a n. .a TMPP ime hylp opane phospah e n. .a n. .a TEHP i(2-e hylhexyl) phospha e BEHP di(2-e hylhexyl) phospha e n. .a TBOEP i(2-bu oxye hyl) phospha e BBOEP di(2-bu oxye hyl) phospha e n. .a BBOEHEP di(2-bu oxye hyl) 2-hyd oxye hyl phospha e n. .a 3OH-TBOEP di(2-bu oxye hyl) 3-hyd oxyl-2- bu oxye hyl phospha e n. .a TIPPP i(isop opylphenyl) phospha e IPPPP isop opylphenyl phenyl phospha e n. .a EHDPHP 2-ehylhexyldiphenyl phospha e EHPHP 2-e hylhexyl phenyl phospha e n. .a 5OH-EHDPHP 2-e hyl-5-hyd oxyhexyl diphenyl phospha e n. .a TClEP i(2-chlo oe hyl) phospha e BClEP di(2-chlo oe hyl) phospha e n. .a TClPP i(1-chlo o-2-p opyl) phospha e BClPP di(1-chlo o-2-p opyl) phospha e n. .a TDCIPP i(1,3-dichlo o-2-p opyl) phospha e BDCIPP di(1,3-dichlo o-2-p opyl) phospha e n. .a TCIPP i(2-chlo oisop opyl) phospha e BCIPP di(2-chlo op opyl) hyd ogen phospha e n. .a BCIPHIPP di(1-chlo o-2-p opyl) 1-hyd oxy-2- p opyl phospha e n. .a TBP i(2,3-dib omop opyl) phospha e BDBPP di(2,3-dib omop opyl) phospha e n. .a TBB 2-e hylhexyl-2,3,4,5- e ab omobenzoa e TBBA 2,3,4,5- e ab omobenzoic acid n. .a BDMEPPP bis( e -bu yphenyl) phenylphospha e BPPP e -bu ylphenyl phenyl phospha e n. .a O he Flame Re a dan s (FRs) n. .a n. .a TBBPA e ab omobisphenol 2,4-DBP 2,4-dib omophenol n. .a HBCD hexab omocyclodecane OH-HBCD* monohyd oxy- hexab omocyclodecane* n. .a a No epo ed. 5 Table S1 (con ). Lis o plas ic addi i es and plas ic cons i uen s, including con en ional and al e na i e plas icize s, lame- e a dan s an ioxidan s and bisphenol compounds, along wi h hei main phase-I me aboli es included in his e iew (* e e s o me aboli es no discussed in his e iew). Syn he ic an ioxidan s compounds (SAs) Pa en P ima y Phase I me aboli e BHT 2,6-di- e -bu yl-4-me hylphenol BHT-OH 2,6-di- e -bu yl-4-(hyd oxyme hyl)phenol BHT-CHO 3,5-di- e -bu yl-4-hyd oxybenzaldehyde BHT-COOH 3,5-di- e -bu yl-4-hyd oxybenzoic acid BHT-Q 2,6-di- e -bu ylcyclohexa-2,5-diene-1,4-dione BHT-quinol 3,5-di- e -bu yl-4-hyd oxy-4-hyd oxy-4-me hyl-2,5- cyclohexadione 2-BHAa 2- e -bu yl-4-hyd oxyanisole 2-BHAa 2- e -bu yl-4-hyd oxyanisole 3-BHAa 3- e -bu yl-4-hyd oxyanisole 3-BHAa 3- e -bu yl-4-hyd oxyanisole 6PDD N-(1,3-Dime hylbu yl)-N′-phenyl-p-phenylenediamine 6PDD-Q 6PDD-Quinone Bisphenols BPA Bisphenol A n. .b BPC Bisphenol C n. .b BPF Bisphenol F n. .b BPG Bisphenol G n. .b BPS Bisphenol S n. .b BPAF Bisphenol AF n. .b a Isome s. b No epo ed. 6 Table S2. Human o al bioaccessibili y da a o plas ic addi i es using di e en in- i o physiologically based ex ac ion es s. (See Table S1 o he ull names o he compounds). O al bioaccessibili y Re e ences [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] PBET me hods Fas ed (mod. Ruby, 1996)b Fas ed (mod. Ruby, 1996)b Fas ed (CE-mod. Ruby, 1996)b Fas ed (Ruby, 1996)b Fas ed (Ruby, 1996)b Fas ed (Ruby, 1996)b Fas ed (UBM) Fas ed (UBM) Fed (RIVM me hod) Fas ed (UBM) and ed (RIVM) me hods Fas ed (UBM) and ed (RIVM) me hods Fas ed (UBM) and ed (FOREhST) me hods Plas ic addi i es % Bioaccessibili y DMP 32 17-27 73-94 60-80 70-72 81-87 55-83 DEP 25 17-27 50-75 56-74 84-87 40-68 DnBP 15 1-5 45-50 18-27 80-100 12-32 BzBP 13 2-13 2-10 40-55 12-16 60-80 5-28 DEHP 10 2-13 1-5 20-40 <LOQa 30-40 5-32 DnOP 14 2-13 30-50 <LOQa 20-30 6-25 DiNP 2-13 30-50 2-22 BPA 30-43 80-99 48-51 37-67 TCEP 53-57 50-80 71-98 TClPP 53-94 50-57 41-82 16-52 TDClPP 48-99 15-27 9-57 <LOQa TPP 7-8 5-24 TPhP 61-95 a Limi o quan i ica ion. b Ruby, M. V., Da is, A., Schoo , R., Ebe le, S., and Sells one, C. M. 1996. Es ima ion o lead and a senic bioa ailabili y using a physiologically based ex ac ion es . En i on. Sci. Technol. 30:422–430. 7 Table S3. O e iew o he main me aboli es o plas ic- ela ed chemicals and hei espec i e 24-hou exc e ion a es. Pa en Me aboli e A e age pe cen age o exc e ion (24 h) a,b Re e ences Dime hyl ph hala e (DMP) Monome hyl ph hala e (MMP) 69 [13]a Die hyl ph hala e (DEP) Monoe hyl ph hala e (MEP) 69 Di-isobu yl ph hala e (DiBP) Mono-isobu yl ph hala e (MiBP) 71 Di-n-bu yl ph hala e (DnBP) Mono-n-bu yl ph hala e (MnBP) 63 Bu yl benzyl ph hala e (BBzP) Monobenzyl ph hala e (MBzP) 73 Di(2-e hylhexyl) ph hala e (DEHP) Mono(2-e hyl-5-hyd oxyhexyl) ph hala e (MEHHP) 16 Mono(2-e hyl-oxohexyl) ph hala e (MEOHP) 11 Mono(2-e hyl-5-ca boxypen yl) ph hala e (cx-MEPTP) 14 Di-isononyl ph hala e (DiNP) Mono(hyd oxy-isononyl) ph hala e (MHINP) 20.2 [14] Mono(oxo-isononyl) ph hala e (oxo-MiNP) 10.6 Mono(ca boxy-isononyl) ph hala e (cx-MiNP) 10.7 Di-isodecyl ph hala e (DiDP) Mono(ca boxy-isodecyl) ph hala e (cx-MiDP) 10.7 Di(2-e hylhexyl) e eph hala e (DEHTP) Mono(2-e hyl-5-hyd oxyhexyl) e eph hala e (MEHHTP) 1.8 [15] Mono(2-e hyl-5-oxohexyl) e eph hala e (MEOHTP) 1.0 Mono(2-e hyl-5-ca boxypen yl) e eph hala e (cx-MEPTP) 13 Di(isononyl)cyclohexane-1,2- dica boxyla e (DINCH) Mono-isononyl-cyclohexane-1,2-dica boxyla e (MINCH) 0.65 [15] Mono-(7-ca boxy-4-me hyl-oc yl) cyclohexane- 1,2-dica boxyla e (cx-MINCH) 1.67 Mono-(4-me hyl-7-hyd oxy-oc yl) cyclohexane- 1,2-dica boxyla e (OH-MINCH) 9.55 Mono-(4-me hyl-7-oxo-oc yl) cyclohexane-1,2- dica boxyla e (oxo-MINCH) 1.85 Bisphenol A (BPA) Bisphenol A Monosul a e (BPA-S) 3 / 12 [16,17] Bisphenol A β-D-Glucu onide (BPA-G) 87 / 64 Bisphenol S (BPS) Bisphenol S β-D-Glucu onide (BPS-G) 54 [18] T i(2-bu oxye hyl) phospha e (TBOEP) Di(2-bu oxye hyl) phospha e (BBOEP) 0.75 [18] Di(2-bu oxye hyl) 3-hyd oxyl-2-bu oxye hyl phospha e (OH-TBOEP) 0.02 Di(2-bu oxye hyl) 2-hyd oxye hyl phospha e (BBOEHEP) 5.77 a Ob ained om cu a ed me as udies, whene e possible. b A e age co esponding o he sum o he exc e ion o he phase I me aboli e and i s phase II conjuga e a e being enzyma ically deconjuga ed, excep o BPA and BPS, which co espond o phase-II me aboli es. 8 Table S4. Concen a ion le els o plas icize s, bisphenols, lame e a dan s and an ioxidan s in human biomoni o ing app oaches as applied o u ine, b eas milk and plasma (2019-2023). (See Table S1 o he ull names o compounds, he “m” e e s o “me aboli e o ”) Compound Family Nº compounds Region/ Coun y Ma ix Nº Samples S udied popula ion Concen a ion ange pe amily (ng/mL) Analy e ound a highes concen a ion Re . Plas icize s PAEs, mPAEs, APs and mAPs 50 Guangzhou, China B eas milk 64 B eas - eeding women PAEs: 2.12-34.1 ( ange) DEHP [19] mPAEs: 4.41-138 ( ange) MnBP APs 0.252-16.1 ( ange) DEHTP mAPs: 0.02-5.52 ( ange) MEHTP mPAEs and mAPs 40 Copenhagen , Denma k U ine 300 Young Danish men (18-30 yea s, 2009- 2017) mPAEs: <LOD-6255 (max) o <LOD-85 (median) o <LOD-233 (75% P.) o <LOD-1565 (95% P.) (osmolali y adjus ed) MEP [20] mAPs: 0.8-908 (max) o <LOD-3.79 (median) o <LOD-9.53 (75% P.) o <LOD-42.5 (95% P.) (osmolali y adjus ed) 5cx-MEPTP and OH-MINCH mPAEs and mAPs 17 Copenhagen , Denma k U ine 349 Danish newbo ns and hei pa en s (In an s, n = 144; mo he s n = 127; a he s n = 118) In an s: mPAEs: <LOD-381; mAPs: <LOD-583 ( anges, osmolali y adjus ed) MEP and ∑mDINCH (mola sum o OH-MiNCH and cx- MiNCH exp essed as DINCH) [21] Mo he s: mPAEs: <LOD-1022; mAPs: <LOD- 440 ( anges, osmolali y adjus ed) ∑mDiNP (mola sum o MiNP, OH-MiNP, oxo-MiNP and cx- MiOP exp essed as DiNP) and ∑mDEHTP (mola sum o MEHHTP, MEOHTP, 5cx- MEPTP and 2cx-MMHTP exp essed as DEHTP) Fa he s: mPAEs: <LOD-1162(Range); mAPs: 0.19-334 ( anges, osmolali y adjus ed) mPAEs 11 No way U ine 254 Gene al popula ion (2016-2017) n. .a Dibu yl ph hala e me aboli es (mDBPs) [22] mAPs (mDINCH) 3 Ge many U ine 300 Young adul s (2000-2017) <0.05-72.4 ( ange, c ea inine adjus ed, ng/mL) OH-MINCH [23] mPAEs 6 C e e, G eece U ine 100 P egnan women (22-44 yea s) 4.9-2256.6 ( ange, unadjus ed) MiBP [24] mPAEs and mAPs (mDINCH) 23 Ko ea and Thailand U ine 183 P egnan women (<14 weeks o ges a ion) Ko ea: mPAEs (2.0-18.3); mDINCH (0.3-0.6) (GMb o mPAEs and 75% P. o mDINCH, SG adjus edc) cx-MEPP, MEP and OH- MINCH [25] Thailand: mPAEs (1.2-33); mDINCH (0.5) (GM o mPAEs and 75% P. o mDINCH, SG adjus edc) mPAEs 19 Riyadh, Saudi A abia U ine 109 Child en (3-9 yea s) 0.8-277.5 (GMb, unadjus ed) MEP [26] a No epo ed; b Geome ic mean; c Speci ic g a i y adjus ed. 9 Table S4 (con .). Concen a ion le els o plas icize s, bisphenols, lame e a dan s and an ioxidan s in human biomoni o ing app oaches as applied o u ine, b eas milk and plasma (2019-2023). (See Table S1 o he ull names o compounds, he “m” e e s o “me aboli e o ”) Compound Family Nº compounds Region/ Coun y Ma ix Nº Samples S udied popula ion Concen a ion ange pe amily (ng/mL) Analy e ound a highes concen a ion Re e ences Plas icize s mPAEs and mAPs 32 Indonesia, Saudi A abia and Thaliand U ine 302 Child en (3-11 yea s) Indonesia: mPAEs (<LOQ-77.8); mAPs (<LOQ-3.6) (GMb, unadjus ed) 5cx-MEPP and 5cx-MEPTP [27] Saudi A abia: mPAEs (1.2-270.5); mAPs (<LOQ-139.6) (GMb, unadjus ed) MEP and 5cx-MEPTP Thailand: mPAEs (<LOQ-43.6); mAPs (<LOQ-8) (GMb, unadjus ed) MnBP and 5cx-MEPTP mPAEs 11 Senzhen, China U ine 309 Was e incine a ion plan wo ke s (cases, n = 104) and gene al popula ion 8 km away om he incine a o plan (con ols, n = 205) Cases: 217-3480 ( ange, unadjus ed) MEP and MnBP [28] Con ols: n.d.-1850 ( ange, unadjus ed) MnBP mPAEs 18 Kyo o, Japan U ine 132 Gene al popula ion (1993-2016) <LOD-2508 ( ange, c ea inine adjus ed, µg/g) MEP [29] mPAEs 16 Aichi Region, Japan U ine 1023 Toddle s (1.5-yea -old) 41-34696 nmol/L ( ange) o 496 nmol/L (GMb) (unadjus ed) cx-MEPP [30] mPAEs and mAPs 19 Illinois, USA U ine 482 P egnan women (18-40 yea s, 2013- 2018) mPAEs: 0.7-25 (median) o 0.4-12.6 (25% P.) o 1.5-46.5 (75% P.) (unadjus ed) MEP [31] mAPs: 9.2-69.2 (median) o 4.0-24.7 (25% P.) o 20.7-146 (75% P.) (unadjus ed) cx-MEPTP mPAEs and mAPs (mDINCH) 10 Liege, Belgium U ine 251 Gene al popula ion (2015 and 2018) mPAEs: <LOQ-21.25 (median) o 1.10- 62.85 (75% P.) o 2.4-689.67 (95% P.) (unadjus ed) MEP [32] mAPs: <LOQ (median) o <LOQ-4.76 (75% P.) o 9.13-35.99 (95% P.) (unadjus ed) OH-MINCH mPAEs 16 Jalisco, Mexico U ine 90 P egnan women (< 20 weeks o ges a ion) <LOD- 1830 ( ange, unadjus ed) o 0.3 - 55.8 (GMb, unadjus ed) o 2.1 - 48.6 (median, unadjus ed) o 1.7-55.8 (GMb, c ea inine adjus ed, µg/g) MEP [33] mPAEs 21 Ge many U ine 2256 Child en and eenage s (2014-2017) 0.6 - 27.0 ( ange) o 0.6 - 26.1 (GMb) (Unadjus ed) MiBP [34] b Geome ic mean; c Speci ic g a i y adjus ed. 16 Table S5. (con .). Su ey o Co ec ion Fac o s (CFs) and es ima ed exposu e o se e al plas ic- ela ed chemicals by WBE. (See Table S1 o he ull names o compounds). Class Compound Bioma ke CF Es ima ed exposu e (µg inh-1 day-1) Loca ion Re . Bisphenols BPA BPA-S 24.7 43 ± 9 - 407 ± 183 2 ci ies Belgium, 1 ci y Spain, 1 ci y C oa ia [61] Bisphenols BPA BPA-S 0.45 4 – 6 1 ci y, USA [62] BPS F ee BPS (1) 91 ± 59 Bisphenols BPA BPA-S 0.45 0.16 0.97±0.1 - 157±16 (4) 0.35 ±0.03 - 46.2 ±5.6 (4) 5 WWTP, UK [63] Flame e a dan s TBOEP BBOEHEP 13.9 395 ± 60 - 1783 ± 830 2 ci ies Belgium, 1 ci y Spain, 1 ci y C oa ia [61] Flame e a dan s TBOEP BBOEP OH-TBOEP BBOEHEP (1) (3) 5 ci ies, Eu ope [64] TPHP DPHP (2) OH-DPHP (1) (3) TDCIPP BDCIPP (1) (3) EHDPHP DPHP (2) OH-EHDPHP EHPHP (1) (3) TCIPP BCIPP BCIPHIPP (1) (3) TClEP F ee TClEP (1) (3) Flame e a dan s TClPP BClPP 45-47 1 ci y, Spain [65] Flame e a dan s TCIPP BCIPHIPP 1.8-3.3 4 ci ies, Belgium [66] TCEP F ee TClEP 18-108 EHDPHP DPHP (2) EHPHP 5OH-EHDPHP 18-175 38-393 0.6-2.7 TBOEP BBOEHEP 3OH-TBOEP 6.9-35 12-61 TPHP DPHP (2) 18-175 (1) No co ec ion ac o was applied. (2) bioma ke o exposu e o mo e han 1 pa en compound (3) Da a epo ed in igu es (4) Loads epo ed as µg day-1 kg-1. 17 Suppo ing Figu es Figu e S1. O e iew o physiologically-based ex ac ion es s o he in es iga ion o he gas oin es inal, de mal and lung bioaccessibili y o plas ic- ela ed chemicals. In o al bioaccessibili y, unde lined chemicals and expe imen al condi ions a e hose ecommended by Ruby e al. (2002). The emaining condi ions a e bo h applied o UBM (Uni ied Bioaccessibili y Me hod) and RIVM (Du ch Ins i u e o Public Heal h and he En i onmen Me hod). ALF: A i icial Lysosomal Fluid, SSSM: Syn he ic Swea and Sebum Mix u e. Condi ionsIno g. sal s Condi ionsIno g. sal s O g. species Biomolecules KCl KSCN NaH2PO4 Na2SO4 NaCl NaHCO3(RIVM) NaOH (UBM) U ea U ic acid α-Amylase Mucin pH = 6.8 ± 0.2 10 s 37°C KCl NaH2PO4 Na2SO4 NaCl CaCl2 NH4Cl HCl U ea D+ Glucose D- Glucu onic acid D- Glucosamine Mucin BSA Pepsin pH = 1.30 ± 0.02 1 h (UBM) 2 h (RIVM) pH = 2.0 1 h (Ruby e al) 37°C Mou h KCl NaCl NaHCO3 KH2PO4 MgCl2 CaCl2 HCl U ea BSA Panc ea in Lipase Bile sal s pH = 8.1 ± 0.2 4 h (UBM) 2 h (RIVM) pH = 7.5 3 h (Ruby e al.) 37°C S omach Small in es ine Colon (Tils on, 2011) KCl NaCl NaHCO3 MgSO4 KH2PO4 K2HPO4 CaCl2 L-Cys eine Haemin Mucin Bile sal s pH = 6.5 8 h 37°C MgCl2 NaCl Na2HPO4 Na2SO4 CaCl2 NaOH (ALF) NaHCO3 (Gamble) KCl (Gamble) Sodium ci a e Ci ic acid (ALF) Glycine (ALF) Na2Ta a e (ALF) NaLac a e (ALF) NaPy u a e (ALF) Sodium ace a e (Gamble) pH = 4.5 (ALF) 7.4 (Gamble) 96 h 37°C Na2SO4 NaCl NH4OH NH4Cl NaHCO3 Na2HPO4 KCl MgCl2 CaCl2 CuCl2 FeSO4 Ace ic acid Bu y ic acid D+ Glucose Lac ic acid U ea C ea inine Squalene Palmi yl Palmi a e T iolein Choles e yl Olea e pH = 5.3 ± 0.1 1 h 32°C Lung (Gamble and ALF me hods) De mal (SSSM me hod) O al (UBM, RIVM, Ruby and Tils on me hods) O g. species Gas oin es inal 18 Figu e S2. 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