Huuskonen, P., Karakitsios, S., Scholten, B., Westerhout, J., Sarigiannis, D.A.,
Santonen, T., 2022. Health risk assessment of ortho-toluuidine utilising human
biomonitoring data of workers and the general population. Toxics 10, 217.

Huuskonen, P., Porras, S.P., Scholten, B., Portengen, L., Uuksulainen, S., Ylinen, K.,
Santonen, T., 2023. Occupational Exposure and Health Impact Assessment of
Diisocyanates in Finland. Toxics 11, 229.

Ibrahim, M., MacFarlane, E.M., Matteo, G., Hoyee, M.P., Rick, K.R., Farokhi, S.,
Copley, C.M., O'Dwyer, S., Bruin, J.E., 2020. Functional cytochrome P450 1A
enzymes are induced in mouse and human islets following pollutant exposure.
Diabetologia 63, 162-178.

ICCVAM. Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM). in: Service N.T.P.U.S.D.o.H.a.H., ed. 2023.

Jones, K., Galea, K.S., Scholten, B., Loikala, M., Porras, S.P., Bousoumah, R., Ndaw, S.,
Leese, E., Louro, H., Silva, M.J., 2022. HBM4EU diisocyanates study—research
protocol for a collaborative European human biological monitoring study on
occupational exposure. Int. J. Environ. Res. Public Health 19, 8811.

Kavlock, R.J., Bahadori, T., Barton-Maclaren, T.S., Gwinn, M.R., Rasenberg, M.,
Thomas, R.S., 2018. Accelerating the pace of chemical risk assessment. Chem. Res.
Toxicol. 31, 287-290.

Koch, H.M., Aylward, L.L., Hays, S.M., Smolders, R., Moos, R.K., Cocker, J., Jones, K.,
Warren, N., Levy, L., Bevan, R., 2014b. Inter-and intra-individual variation in
urinary biomarker concentrations over a 6-day sampling period. Part 2: personal
care product ingredients. Toxicol. Lett. 231, 261-269.

Koch, H., Bader, M., Weiss, T., Koslitz, S., Schütze, A., Käfferlein, H.-U., Brüning, T.,
2014a. Metabolism and elimination of N-ethyl-2-pyrrolidone (NEP) in human males
after oral dosage. Arch. Toxicol. 88, 893-899.

Koch, H.M., Lorber, M., Christensen, K.L., Pälmke, C., Koslitz, S., Brüning, T., 2013a.
Identifying sources of phthalate exposure with human biomonitoring: results of a 48
h fastening study with urine collection and personal activity patterns. Int. J. Hyg.
Environ. Health 216, 672-681.

Koch, H.M., Schütze, A., Pälmke, C., Angerer, J., Brüning, T., 2013b. Metabolism of the
plasticizer and phthalate substitute diisonoroyl-cyclohexane-1, 2-dicarboxylate
(DINCH®) in humans after single oral doses. Arch. Toxicol. 87, 799-806.

Kohsuwan, K., Intayoung, U., Khachananda, S., Sapbamrner, R.,
Koonrungsesomboon, N., Techatoei, S., Wunnapuk, K., 2022. Urinary glyphosate
kinetics after occupational exposure. Int. J. Hyg. Environ. Health 245, 114021.

Kolossa-Gehring, M., Fiddicke, U., Leng, G., Angerer, J., Wolz, G., 2017. New human
biomonitoring methods for chemicals of concern—the German approach to enhance
relevance. Int. J. Hyg. Environ. Health 220, 103-112.

Kortenkamp, A., Scholze, M., Ermler, S., Priskorn, L., Jørgensen, N., Andersson, A.-M.,
Frederiksen, H., 2022. Combined exposures to bisphenols, polychlorinated dioxins,
paracetamol, and phthalates as drivers of deteriorating semen quality. Environ. Int.
165, 107322.

Krause, S., Goss, K.-U., 2018. In vitro-in vivo extrapolation of hepatic metabolism for
different scenarios-a toolbox. Chem. Res. Toxicol. 31, 1195-1202.

Krause, S., Goss, K.-U., 2021. Prediction of unbound fractions for in vitro-in vivo
extrapolation of biotransformation data. Chem. Res. Toxicol. 34, 7-11.

Lamkarkach, F., Ougier, E., Garnier, R., Viau, C., Kolossa-Gehring, M., Lange, R., Apel, P.,
2021. Human biomonitoring initiative (HBM4EU): Human biomonitoring guidance
values (HBM-GVs) derived for cadmium and its compounds. Environ. Int. 147,
106337.

Lamkarkach, F., Meslin, M., Kolossa-Gehring, M., Apel, P., Garnier, R., 2022. Human
biomonitoring initiative (HBM4EU): human biomonitoring guidance values derived
for dimethylformamide. Toxics 10, 298.

Lange, R., Apel, P., Rousselle, C., Charles, S., Sissoko, F., Kolossa-Gehring, M., Ougier, E.,
2021. The European Human Biomonitoring Initiative (HBM4EU): Human
biomonitoring guidance values for selected phthalates and a substitute plasticizer.
Int. J. Hyg. Environ. Health 234, 113722.

Laroche, C., Aggarwal, M., Bender, H., Benndorf, P., Birk, B., Crozier, J., Dal Negro, G.,
De Gaetano, F., Desaintes, C., Gardner, I., 2018. Finding synergies for
3Rs-Toxicokinetics and read-across: Report from an EPAA partners' Forum. Regul.
Toxicol. Pharm. 99, 5-21.

Lessmann, F., Schütze, A., Weiss, T., Langsch, A., Otter, R., Brüning, T., Koch, H.M.,
2016. Metabolism and urinary excretion kinetics of di (2-ethylhexyl) terephthalate
(DEHTP) in three male volunteers after oral dosage. Arch. Toxicol. 90, 1659-1667.

Li, L., Arnot, J.A., Wania, F., 2019. How are humans exposed to organic chemicals
released to indoor air? Environ. Sci. Tech. 53, 11276-11284.

Litsa, E.E., Das, P., Kavraki, L.E., 2021. Machine learning models in the prediction of
drug metabolism: Challenges and future perspectives. Expert Opin. Drug Metab.
Toxicol. 17, 1245-1247.

Loizou, G.D., Jones, K., Akrill, P., Dyne, D., Cocker, J., 1999. Estimation of the dermal
absorption of m-xylene vapor in humans using breath sampling and physiologically
based pharmacokinetic analysis. Toxicol. Sci. Off. J. Soc. Toxicol. 48, 170-179.

López, M.E., Góen, T., Mol, H., Nübler, S., Haji-Abbas-Zarrabi, K., Koch, H.M., Kasper-
Sonnenberg, M., Dvorakova, D., Hajslova, J., Antignac, J.-P., 2021. The European
human biomonitoring platform-Design and implementation of a laboratory quality
assurance/quality control (QA/QC) programme for selected priority chemicals. Int.
J. Hyg. Environ. Health 234, 113740.

Louisse, J., de Jong, E., van de Sandt, J.J., Blaauboer, B.J., Woutersen, R.A., Piersma, A.
H., Rietjens, I.M., Verwei, M., 2010. The use of in vitro toxicity data and
physiologically based kinetic modeling to predict dose-response curves for in vivo
developmental toxicity of glycol ethers in rat and man. Toxicol. Sci. 118, 470-484.

Louisse, J., Alewiijn, M., Peijnenburg, A.A., Cnubben, N.H., Heringa, M.B., Coecke, S.,
Punt, A., 2020. Towards harmonization of test methods for in vitro hepatic clearance
studies. Toxicol. In Vitro 63, 104722.

Louro, H., Heinälä, M., Bessems, J., Buekers, J., Vermeire, T., Woutersen, M., van
Engelen, J., Borges, T., Rousselle, C., Ougier, E., 2019. Human biomonitoring in
health risk assessment in Europe: Current practices and recommendations for the
future. Int. J. Hyg. Environ. Health 222, 727-737.

Lu, K., Hsiao, Y.-C., Liu, C.-W., Schoeny, R., Gentry, R., Starr, T.B., 2021. A Review of
Stable Isotope Labeling and Mass Spectrometry Methods to Distinguish Exogenous
from Endogenous DNA Adducts and Improve Dose-Response Assessments. Chem.
Res. Toxicol. 35, 7-29.

Luijten, M., Vlaanderen, J., Kortenkamp, A., Antignac, J.-P., Barouki, R., Bil, W., van den
Brand, A., den Braver-Sewradj, S., van Klaveren, J., Mengelers, M., 2023. Mixture
risk assessment and human biomonitoring: Lessons learnt from HBM4EU. Int. J. Hyg.
Environ. Health 249, 114135.

Madden, J.C., Enoch, S.J., Paini, A., Cronin, M.T., 2020. A review of in silico tools as
alternatives to animal testing: principles, resources and applications. Altern. Lab.
Anim. 48, 146-172.

Mann, S., Droz, P., Vahter, M., 1996. A physiologically based pharmacokinetic model for
arsenic exposure: I. Development in hamsters and rabbits. Toxicol. Appl. Pharmacol.
137, 8-22.

Manno, M., Viau, C., Cocker, J., Colosio, C., Lowry, L., Mutti, A., Nordberg, M., Wang, L.,
2010. Biomonitoring for occupational health risk assessment (BOHRA). Toxicol. Lett.
192, 3-16.

Marx-Stoeting, P., Rivière, G., Luijten, M., Aiello-Holden, K., Bandom, N., Baken, L.,
Canas, A., Castano, A., Denys, S., Fillol, C., 2023. A walk in the PARC: developing
and implementing 21st century chemical risk assessment in Europe. Arch. Toxicol.
1-16.

McNally, K., Sams, C., Hogg, A., Lumen, A., Loizou, G., 2021. Development, testing,
parameterisation and calibration of a human ppbk model for the plasticiser, di-(2-
propylheptyl) phthalate (dphp) using in silico, in vitro and human biomonitoring
data. Front. Pharmacol. 12, 692442.

Meslin, M., Beausoleil, C., Zeman, F.A., Antignac, J.-P., Kolossa-Gehring, M.,
Rousselle, C., Apel, P., 2022. Human Biomonitoring Guidance Values (HBM-GVs) for
Bisphenol S and Assessment of the Risk Due to the Exposure to Bisphenols A and S in
Europe. Toxics 10, 228.

Nakayama, S.F., St-Amand, A., Pollock, T., Apel, P., Bamai, Y.A., Barr, D.B., Bessems, J.,
Calafat, A.M., Castaño, A., Covaci, A., 2023. Interpreting biomonitoring data:
Introducing the international human biomonitoring (i-HBM) working group's
health-based guidance value (HB2GV) dashboard. Int. J. Hyg. Environ. Health 247,
114046.

Nehring, A., Bury, D., Kling, H.-W., Weiss, T., Brüning, T., Koch, H.M., 2019.
Determination of human urinary metabolites of the plasticizer di (2-ethylhexyl)
adipate (DEHA) by online-SPE-HPLC-MS/MS. J. Chromatogr. B 1124, 239-246.

Nehring, A., Bury, D., Ringbeck, B., Kling, H.-W., Otter, R., Weiss, T., Brüning, T.,
Koch, H.M., 2020. Metabolism and urinary excretion kinetics of di (2-ethylhexyl)
adipate (DEHA) in four human volunteers after a single oral dose. Toxicol. Lett. 321,
95-102.

NRC. National Research Council, Science and Decisions: Advancing Risk Assessment
ed's. Washington, DC: The National Academies Press; 2009.

OECD. No. 28 Guidance Document for the Conduct of Skin Absorption Studies. ENV/JM/
MONO(2004);2004a.

OECD. Test No. 428: Skin Absorption: In Vitro Method ed's; 2004b.

OECD. Test No. 417: Toxicokinetics ed's; 2010.

OECD. Guidance Document on Good In Vitro Method Practices (GIVIMP) ed's; 2018a.

OECD. GUIDANCE DOCUMENT ON THE DETERMINATION OF IN VITRO INTRINSIC
CLEARANCE USING CRYOPRESERVED HEPATOCYTES (RTHEP) OR LIVER S9 SUB-
CELLULAR FRACTIONS (RT-S9) FROM RAINBOW TROUT AND EXTRAPOLATION
TO IN VIVO INTRINSIC CLEARANCE SERIES ON TESTING AND ASSESSMENT- No.
280. ENV/JM/MONO(2018)12; 2018b.

OECD. Guidance document on the characterisation, validation and reporting of
Physiologically Based Kinetic (PBK) models for regulatory purposes. OECD Series on
Testing and Assessment, Environment,Health and Safety,Environment Directorate
2021No. 331. 2021.

OECD. Test No. 319A: Determination of in vitro intrinsic clearance using cryopreserved
rainbow trout hepatocytes (RT-HEP) ed's; 2018c.

OECD. Test No. 319B: Determination of in vitro intrinsic clearance using rainbow trout
liver S9 sub-cellular fraction (RT-S9) ed's; 2018d.

Olsen, A.K., Li, D., Li, L., 2023. Explore the Dosimetric Relationship between the Intake
of Chemical Contaminants and Their Occurrence in Blood and Urine. Environ. Sci.
Tech.

Ougier, E., Zeman, F., Antignac, J.-P., Rousselle, C., Lange, R., Kolossa-Gehring, M.,
Apel, P., 2021. Human biomonitoring initiative (HBM4EU): Human biomonitoring
guidance values (HBM-GVs) derived for bisphenol A. Environ. Int. 154, 106563.

Paini, A., Tan, Y.-M., Sachana, M., Worth, A., 2021. Gaining acceptance in next
generation PBK modelling approaches for regulatory assessments-An OECD
international effort. Comput. Toxicol. 18, 100163.

Pallocca, G.; Moné, M.J.; Kamp, H.; Luijten, M.; Van de Water, B.; Leist, M. Next-
generation risk assessment of chemicals-rolling out a human-centric testing strategy
to drive 3R implementation: the RISK-HUNT3R project perspective. 2022.

PARC. Development of the strategy for mixture risk assessment using HBM data and its
application to prioritised mixtures. in: Chemicals P.f.t.A.o.R.f., ed. Additional
Deliverable AD65. P-A-R-C HORIZON-HLTH-2021-ENVHLTH-03 CONTRACT N.
101057014; 2023a.

PARC. Periodic report on available supporting materials for HBM studies. in: Chemicals
P.f.t.A.o.R.f., ed. Additional Deliverable AD41. P-A-R-C HORIZON-HLTH-2021-
ENVLTH-03; 2023b.

Pletz, J., Blakeman, S., Paini, A., Parissis, N., Worth, A., Andersson, A.-M.,
Frederiksen, H., Sakhi, A.K., Thomsen, C., Bopp, S.K., 2020. Physiologically based
Huuskonen, P., Karakitsios, S., Scholten, B., Westerhout, J., Sarigiannis, D.A.,
Santonen, T., 2022. Health risk assessment of ortho-toluuidine utilising human
biomonitoring data of workers and the general population. Toxics 10, 217.

Huuskonen, P., Porras, S.P., Scholten, B., Portengen, L., Uuksulainen, S., Ylinen, K.,
Santonen, T., 2023. Occupational Exposure and Health Impact Assessment of
Diisocyanates in Finland. Toxics 11, 229.

Ibrahim, M., MacFarlane, E.M., Matteo, G., Hoyeck, M.P., Rick, K.R., Farokhi, S.,
Copley, C.M., O'Dwyer, S., Bruin, J.E., 2020. Functional cytochrome P450 1A
enzymes are induced in mouse and human islets following pollutant exposure.
Diabetologia 63, 162-178.

ICCVAM. Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM). in: Service N.T.P.U.S.D.o.H.a.H., ed. 2023.

Jones, K., Galea, K.S., Scholten, B., Loikala, M., Porras, S.P., Bousoumah, R., Ndaw, S., Leese, E., Louro, H., Silva, M.J., 2022. HBM4EU diisocyanates study—research protocol for a collaborative European human biological monitoring study on occupational exposure. Int. J. Environ. Res. Public Health 19, 8811.

Kavlock, R.J., Bahadori, T., Barton-Maclaren, T.S., Gwinn, M.R., Rasenberg, M.,
Thomas, R.S., 2018. Accelerating the pace of chemical risk assessment. Chem. Res.
Toxicol. 31, 287-290.

Koch, H.M., Aylward, L.L., Hays, S.M., Smolders, R., Moos, R.K., Cocker, J., Jones, K.,
Warren, N., Levy, L., Bevan, R., 2014b. Inter-and intra-individual variation in
urinary biomarker concentrations over a 6-day sampling period. Part 2: personal
care product ingredients. Toxicol. Lett. 231, 261-269.

Koch, H., Bader, M., Weiss, T., Koslitz, S., Schütze, A., Käfferlein, H.-U., Brüning, T.,
2014a. Metabolism and elimination of N-ethyl-2-pyrrolidone (NEP) in human males
after oral dosage. Arch. Toxicol. 88, 893-899.

Koch, H.M., Lorber, M., Christensen, K.L., Pälmke, C., Koslitz, S., Brüning, T., 2013a.
Identifying sources of phthalate exposure with human biomonitoring: results of a 48
h fastening study with urine collection and personal activity patterns. Int. J. Hyg.
Environ. Health 216, 672-681.

Koch, H.M., Schütze, A., Pälmke, C., Angerer, J., Brüning, T., 2013b. Metabolism of the plasticizer and phthalate substitute diisonoroyl-cyclohexane-1, 2-dicarboxylate (DINCH®) in humans after single oral doses. Arch. Toxicol. 87, 799-806.

Kohsuwan, K., Intayoung, U., Khachananda, S., Sapbamrner, R.,
Koonrungsesomboon, N., Techatoei, S., Wunnapuk, K., 2022. Urinary glyphosate
kinetics after occupational exposure. Int. J. Hyg. Environ. Health 245, 114021.

Kolossa-Gehring, M., Fiddicke, U., Leng, G., Angerer, J., Wolz, G., 2017. New human
biomonitoring methods for chemicals of concern—the German approach to enhance
relevance. Int. J. Hyg. Environ. Health 220, 103-112.

Kortenkamp, A., Scholze, M., Ermler, S., Priskorn, L., Jørgensen, N., Andersson, A.-M.,
Frederiksen, H., 2022. Combined exposures to bisphenols, polychlorinated dioxins,
paracetamol, and phthalates as drivers of deteriorating semen quality. Environ. Int.
165, 107322.

Krause, S., Goss, K.-U., 2018. In vitro-in vivo extrapolation of hepatic metabolism for
different scenarios-a toolbox. Chem. Res. Toxicol. 31, 1195-1202.

Krause, S., Goss, K.-U., 2021. Prediction of unbound fractions for in vitro-in vivo
extrapolation of biotransformation data. Chem. Res. Toxicol. 34, 7-11.

Lamkarkach, F., Ougier, E., Garnier, R., Viau, C., Kolossa-Gehring, M., Lange, R., Apel, P.,
2021. Human biomonitoring initiative (HBM4EU): Human biomonitoring guidance
values (HBM-GVs) derived for cadmium and its compounds. Environ. Int. 147,
106337.

Lamkarkach, F., Meslin, M., Kolossa-Gehring, M., Apel, P., Garnier, R., 2022. Human
biomonitoring initiative (HBM4EU): human biomonitoring guidance values derived
for dimethylformamide. Toxics 10, 298.

Lange, R., Apel, P., Rousselle, C., Charles, S., Sissoko, F., Kolossa-Gehring, M., Ougier, E.,
2021. The European Human Biomonitoring Initiative (HBM4EU): Human
biomonitoring guidance values for selected phthalates and a substitute plasticizer.
Int. J. Hyg. Environ. Health 234, 113722.

Laroche, C., Aggarwal, M., Bender, H., Benndorf, P., Birk, B., Crozier, J., Dal Negro, G.,
De Gaetano, F., Desaintes, C., Gardner, I., 2018. Finding synergies for
3Rs-Toxicokinetics and read-across: Report from an EPAA partners' Forum. Regul.
Toxicol. Pharm. 99, 5-21.

Lessmann, F., Schütze, A., Weiss, T., Langsch, A., Otter, R., Brüning, T., Koch, H.M.,
2016. Metabolism and urinary excretion kinetics of di (2-ethylhexyl) terephthalate
(DEHTP) in three male volunteers after oral dosage. Arch. Toxicol. 90, 1659-1667.

Li, L., Arnot, J.A., Wania, F., 2019. How are humans exposed to organic chemicals
released to indoor air? Environ. Sci. Tech. 53, 11276-11284.

Litsa, E.E., Das, P., Kavraki, L.E., 2021. Machine learning models in the prediction of
drug metabolism: Challenges and future perspectives. Expert Opin. Drug Metab.
Toxicol. 17, 1245-1247.

Loizou, G.D., Jones, K., Akrill, P., Dyne, D., Cocker, J., 1999. Estimation of the dermal
absorption of m-xylene vapor in humans using breath sampling and physiologically
based pharmacokinetic analysis. Toxicol. Sci. Off. J. Soc. Toxicol. 48, 170-179.

López, M.E., Góen, T., Mol, H., Nübler, S., Haji-Abbas-Zarrabi, K., Koch, H.M., Kasper-
Sonnenberg, M., Dvorakova, D., Hajslova, J., Antignac, J.-P., 2021. The European
human biomonitoring platform-Design and implementation of a laboratory quality
assurance/quality control (QA/QC) programme for selected priority chemicals. Int.
J. Hyg. Environ. Health 234, 113740.

Louisse, J., de Jong, E., van de Sandt, J.J., Blaauboer, B.J., Woutersen, R.A., Piersma, A.
H., Rietjens, I.M., Verwei, M., 2010. The use of in vitro toxicity data and
physiologically based kinetic modeling to predict dose-response curves for in vivo
developmental toxicity of glycol ethers in rat and man. Toxicol. Sci. 118, 470-484.

Louisse, J., Alewiijn, M., Peijnenburg, A.A., Cnubben, N.H., Heringa, M.B., Coecke, S.,
Punt, A., 2020. Towards harmonization of test methods for in vitro hepatic clearance
studies. Toxicol. In Vitro 63, 104722.

Louro, H., Heinälä, M., Bessems, J., Buekers, J., Vermeire, T., Woutersen, M., van
Engelen, J., Borges, T., Rousselle, C., Ougier, E., 2019. Human biomonitoring in
health risk assessment in Europe: Current practices and recommendations for the
future. Int. J. Hyg. Environ. Health 222, 727-737.

Lu, K., Hsiao, Y.-C., Liu, C.-W., Schoeny, R., Gentry, R., Starr, T.B., 2021. A Review of
Stable Isotope Labeling and Mass Spectrometry Methods to Distinguish Exogenous
from Endogenous DNA Adducts and Improve Dose-Response Assessments. Chem.
Res. Toxicol. 35, 7-29.

Luijten, M., Vlaanderen, J., Kortenkamp, A., Antignac, J.-P., Barouki, R., Bil, W., van den
Brand, A., den Braver-Sewradj, S., van Klaveren, J., Mengelers, M., 2023. Mixture
risk assessment and human biomonitoring: Lessons learnt from HBM4EU. Int. J. Hyg.
Environ. Health 249, 114135.

Madden, J.C., Enoch, S.J., Paini, A., Cronin, M.T., 2020. A review of in silico tools as
alternatives to animal testing: principles, resources and applications. Altern. Lab.
Anim. 48, 146-172.

Mann, S., Droz, P., Vahter, M., 1996. A physiologically based pharmacokinetic model for
arsenic exposure: I. Development in hamsters and rabbits. Toxicol. Appl. Pharmacol.
137, 8-22.

Manno, M., Viau, C., Cocker, J., Colosio, C., Lowry, L., Mutti, A., Nordberg, M., Wang, L.,
2010. Biomonitoring for occupational health risk assessment (BOHRA). Toxicol. Lett.
192, 3-16.

Marx-Stoeting, P., Rivière, G., Luijten, M., Aiello-Holden, K., Bandom, N., Baken, L.,
Canas, A., Castano, A., Denys, S., Fillol, C., 2023. A walk in the PARC: developing
and implementing 21st century chemical risk assessment in Europe. Arch. Toxicol.
1-16.

McNally, K., Sams, C., Hogg, A., Lumen, A., Loizou, G., 2021. Development, testing,
parameterisation and calibration of a human ppbk model for the plasticiser, di-(2-
propylheptyl) phthalate (dphp) using in silico, in vitro and human biomonitoring
data. Front. Pharmacol. 12, 692442.

Meslin, M., Beausoleil, C., Zeman, F.A., Antignac, J.-P., Kolossa-Gehring, M.,
Rousselle, C., Apel, P., 2022. Human Biomonitoring Guidance Values (HBM-GVs) for
Bisphenol S and Assessment of the Risk Due to the Exposure to Bisphenols A and S in
Europe. Toxics 10, 228.

Nakayama, S.F., St-Amand, A., Pollock, T., Apel, P., Bamai, Y.A., Barr, D.B., Bessems, J.,
Calafat, A.M., Castaño, A., Covaci, A., 2023. Interpreting biomonitoring data:
Introducing the international human biomonitoring (i-HBM) working group's
health-based guidance value (HB2GV) dashboard. Int. J. Hyg. Environ. Health 247,
114046.

Nehring, A., Bury, D., Kling, H.-W., Weiss, T., Brüning, T., Koch, H.M., 2019.
Determination of human urinary metabolites of the plasticizer di (2-ethylhexyl)
adipate (DEHA) by online-SPE-HPLC-MS/MS. J. Chromatogr. B 1124, 239-246.

Nehring, A., Bury, D., Ringbeck, B., Kling, H.-W., Otter, R., Weiss, T., Brüning, T.,
Koch, H.M., 2020. Metabolism and urinary excretion kinetics of di (2-ethylhexyl)
adipate (DEHA) in four human volunteers after a single oral dose. Toxicol. Lett. 321,
95-102.

NRC. National Research Council, Science and Decisions: Advancing Risk Assessment
ed's. Washington, DC: The National Academies Press; 2009.

OECD. No. 28 Guidance Document for the Conduct of Skin Absorption Studies. ENV/JM/
MONO(2004);2004a.

OECD. Test No. 428: Skin Absorption: In Vitro Method ed's; 2004b.

OECD. Test No. 417: Toxicokinetics ed's; 2010.

OECD. Guidance Document on Good In Vitro Method Practices (GIVIMP) ed's; 2018a.

OECD. GUIDANCE DOCUMENT ON THE DETERMINATION OF IN VITRO INTRINSIC
CLEARANCE USING CRYOPRESERVED HEPATOCYTES (RTHEP) OR LIVER S9 SUB-
CELLULAR FRACTIONS (RT-S9) FROM RAINBOW TROUT AND EXTRAPOLATION
TO IN VIVO INTRINSIC CLEARANCE SERIES ON TESTING AND ASSESSMENT- No.
280. ENV/JM/MONO(2018)12; 2018b.

OECD. Guidance document on the characterisation, validation and reporting of
Physiologically Based Kinetic (PBK) models for regulatory purposes. OECD Series on
Testing and Assessment, Environment,Health and Safety,Environment Directorate
2021No. 331. 2021.

OECD. Test No. 319A: Determination of in vitro intrinsic clearance using cryopreserved
rainbow trout hepatocytes (RT-HEP) ed's; 2018c.

OECD. Test No. 319B: Determination of in vitro intrinsic clearance using rainbow trout
liver S9 sub-cellular fraction (RT-S9) ed's; 2018d.

Olsen, A.K., Li, D., Li, L., 2023. Explore the Dosimetric Relationship between the Intake
of Chemical Contaminants and Their Occurrence in Blood and Urine. Environ. Sci.
Tech.

Ougier, E., Zeman, F., Antignac, J.-P., Rousselle, C., Lange, R., Kolossa-Gehring, M.,
Apel, P., 2021. Human biomonitoring initiative (HBM4EU): Human biomonitoring
guidance values (HBM-GVs) derived for bisphenol A. Environ. Int. 154, 106563.

Paini, A., Tan, Y.-M., Sachana, M., Worth, A., 2021. Gaining acceptance in next
generation PBK modelling approaches for regulatory assessments-An OECD
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Pallocca, G., Moné, M.J.; Kamp, H.; Luijten, M.; Van de Water, B.; Leist, M. Next-
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Pletz, J., Blakeman, S., Paini, A., Parissis, N., Worth, A., Andersson, A.-M.,
Frederiksen, H., Sakhi, A.K., Thomsen, C., Bopp, S.K., 2020. Physiologically based
kinetic (PBK) modelling and human biomonitoring data for mixture risk assessment. Environ. Int. 143, 105978.

Polet, T., Schlosser, P., Rodriguez, C., Parod, R., Rodwell, D., Kirman, C., 2016. Using physiologically based pharmacokinetic modeling and benchmark dose methods to derive an occupational exposure limit for N-methylpyrrolidone. Regul. Toxicol. Pharm. 76, 102–112.

Punt, A., Bouwmeester, H., Blaumober, B.J., Coecke, S., Hakkert, B., Hendriks, D.F., Jennings, P., Kramer, N.I., Neuhoff, S., Masereeuw, R., 2020. New approach methodologies (NAMs) for human-relevant biokinetics predictions: Meeting the paradigm shift in toxicology towards an animal-free chemical risk assessment. ALTEX-Alternatives to Animal Experimentation 37, 607–622.

Quignot, N., Wieczek, W., Amzal, B., Dorne, J.-L., 2018. "TKplate": A web-based platform for toxicokinetic modelling in food safety. Toxicol. Lett. 295, S248.

Ring, C.L., Pearce, R.G., Setzer, R.W., Wetmore, B.A., Wambaugh, J.F., 2017. Identifying populations sensitive to environmental chemicals by simulating toxicokinetic variability. Environ. Int. 106, 105–118.

Rostami-Hojdegan, A., Bois, F.Y., 2021. Opening a debate on open-source modeling tools: pouring fuel on fire versus extinguishing the flare of a healthy debate. CPT: Pharmacometrics & Systems. Pharmacology 10, 420–427.

Rotloff, D.M., Wetmore, B.A., Dix, D.J., Ferguson, S.S., Clewell, H.J., Houck, K.A., LeCluyse, E.L., Andersen, M.E., Judson, R.S., Smith, C.M., 2010. Incorporating human dosimetry and exposure into high-throughput in vitro toxicity screening. Toxicol. Sci. 117, 348–358.

Rotter, S., Beronius, A., Boobis, A., Hanberg, A., Van Klaveren, J., Luijten, M., Machera, K., Nikolopoulou, D., Van Der Voet, H., Ziliacus, J., 2018. Overview on legislation and scientific approaches for risk assessment of combined exposure to multiple chemicals: the potential EuroMix contribution. Crit. Rev. Toxicol. 48, 796–814.

Santonen, T., Porras, S.P., Bocca, B., Bousoumah, D., Duca, R.C., Galea, K.S., Godgeris, L., Göen, T., Hardy, E., Iavicoli, I., 2022. HBM4EU chromates study-Overall results and recommendations for the biomonitoring of occupational exposure to hexavalent chromium. Environ. Res. 204, 111984.

Santonen, T., Mahiout, S., Alvito, P., Apel, P., Bessemes, J., Bil, W., Borges, T., Bose-O'Reilly, S., Buekers, J., Portilla, A.I.C., 2023. How to use human biomonitoring in chemical risk assessment: Methodological aspects, recommendations, and lessons learned from HBM4EU. Int. J. Hyg. Environ. Health 249, 114139.

Scher, D.P., Alexander, B.H., Adgate, J.L., Eberly, L.E., Mandel, J.S., Aquavella, J.F., Bartels, M.J., Brzak, K.A., 2007. Agreement of pesticide biomarkers between morning void and 24-h urine samples from farmers and their children. J. Eposure Sci. Environ. Epidemiol. 17, 350–357.

Schettgen, T., Dewes, P., Kraus, T., 2016. A method for the simultaneous quantification of eight metabolites of synthetic pyrethroids in urine of the general population using gas chromatography-tandem mass spectrometry. Anal. Bioanal. Chem. 408, 5467–5478.

Schlüter, U., Meyer, J., Ahrens, A., Borghi, F., Clerc, F., Delmaar, C., Di Guardo, A., Dudzina, T., Fantke, P., Fransman, W., 2022. Exposure modelling in Europe: how to pave the road for the future as part of the European Exposure Science Strategy 2020–2030. J. Eposure Sci. Environ. Epidemiol. 32, 499–512.

Schmidt, C.W., 2006. Signs of the times: biomarkers in perspective. Nat. Inst. Environ. Health Sci.

Schütze, A., Pälmke, C., Angerer, J., Weiss, T., Brüning, T., Koch, H.M., 2012. Quantification of biomarkers of environmental exposure to di (isononyl) cyclohexane-1, 2-dicarboxylate (DINCH) in urine via HPLC-MS/MS. J. Chromatogr. B 895, 123–130.

Schütze, A., Gries, W., Kolossa-Gehring, M., Apel, P., Schröter-Kermani, C., Fiddicke, U., Leng, G., Brüning, T., Koch, H., 2015. Bis-(2-propylheptyl) phthalate (DPHP) metabolites emerging in 24 h urine samples from the German Environmental Specimen Bank (1999–2012). Int. J. Hyg. Environ. Health 218, 559–563.

Schütze, A., Otter, R., Modick, H., Langsch, A., Brüning, T., Koch, H.M., 2017. Additional oxidized and alkyl chain breakdown metabolites of the plasticizer DINCH in urine after oral dosage to human volunteers. Arch. Toxicol. 91, 179–188.

Stanfield, Z., Setzer, R.W., Hull, V., Sayre, R.R., Isaacs, K.K., Wambaugh, J.F., 2022. Bayesian inference of chemical exposures from NHANES urine biomonitoring data. J. Eposure Sci. Environ. Epidemiol. 32, 833–846.

Steckling, N., Gotti, A., Bose-O'Reilly, S., Chapizanis, D., Costopoulou, D., De Vocht, F., Garf, M., Grimalt, J.O., Heath, E., Hiscock, R., 2018. Biomarkers of exposure in environment-wide association studies—Opportunities to decode the exposome using human biomonitoring data. Environ. Res. 164, 597–624.

Tan, Y.-M., Leonard, J.A., Edwards, S., Teegarden, J., Paini, A., Egegy, P., 2018. Aggregate exposure pathways in support of risk assessment. Current Opinion in Toxicology 9, 8–13.

Teegarden, J.G., Tan, Y.-M., Edwards, S.W., Leonard, J.A., Anderson, K.A., Corley, R.A., Kile, M.L., Simonich, S.M., Stone, D., Tanguay, R.L., 2016. Completing the link between exposure science and toxicology for improved environmental health decision making: the aggregate exposure pathway framework. ACS Publications.

Terry, C., Hays, S., McCoy, A.T., McFadden, L.G., Aggarwal, M., Rasoulpour, R.J., Juberg, D.R., 2016. Implementing a framework for integrating toxicokinetics into human health risk assessment for agrochemicals. Regul. Toxicol. Pharm. 75, 89–104.

Thomas, R.S., Paules, R.S., Simeonov, A., Fitzpatrick, S.C., Crofton, K.M., Casey, W.M., Mendrick, D.L., 2018. The US Federal Tox21 Program: A strategic and operational plan for continued leadership. ALTEX 35, 163.

Thomas, R.S., Bahadori, T., Buckley, T.J., Cowden, J., Deisenroth, C., Dionisio, K.L., Frithsen, J.B., Grulke, C.M., Gwinn, M.R., Harrill, J.A., 2019. The next generation blueprint of computational toxicology at the US Environmental Protection Agency. Toxicol. Sci. 169, 317–332.

Thompson, C.V., Firman, J.W., Goldsmith, M.R., Grulke, C.M., Tan, Y.-M., Paini, A., Penson, P.E., Sayre, R.R., Webb, S., Madden, J.C., 2021. A systematic review of published physiologically-based kinetic models and an assessment of their chemical space coverage. Altern. Lab. Anim. 49, 197–208.

Tyzack, J.D., Kirchmann, J., 2019. Computational methods and tools to predict cytochrome P450 metabolism for drug discovery. Chem. Biol. Drug Des. 93, 377–386.

Ulrich, E.M., Sobus, J.R., Grulke, C.M., Richard, A.M., Newton, S.R., Strynar, M.J., Mansouri, K., Williams, A.J., 2019. EPA's non-targeted analysis collaborative trial (ENTAC): genesis, design, and initial findings. Anal. Bioanal. Chem. 411, 853–866.

USEPA. Strategic Plan to Promote the Development and Implementation of Alternative Test Methods Within the TSCA Program. EPA Document# EPA-740-R1-8004. U.S. Environmental Protection Agency, Office of Chemical Safety and Pollution Prevention, Washington, DC; 2018.

USEPA. EPA New Approach Methods Work Plan (v2). EPA/600/X-21/209. U.S. Environmental Protection Agency, Washington, DC; 2021.

Van Den Brand, A.D., Bajard, L., Steffensen, I.-L., Brantsæter, A.L., Dirven, H.A., Louisse, J., Peijnenburg, A., Ndw, S., Mantovani, A., De Santis, B., 2022. Providing Biological Plausibility for Exposure-Health Relationships for the Mycotoxins Deoxynivalenol (DON) and Fumonisin B1 (FB1) in Humans Using the AOP Framework. Toxins 14, 279.

Viegas, S.; Zare Jeddi, M.; B. Hopf, N.; Bessemes, J., Palmen, N.; S. Galea, K.; Jones, K.; Kujath, P.; Duca, R.-C.; Verhagen, H. Biomonitoring as an underused exposure assessment tool in occupational safety and health context—Challenges and way forward. International Journal of Environmental Research and Public Health 2020; 17:5884.

Vineis, P., Robinson, O., Chadeau-Hyam, M., Dehghan, A., Mudway, I., Dagnino, S., 2020. What is new in the exposome? Environ. Int. 143, 105887.

Wambaugh, J.F., Hughes, M.F., Ring, C.L., MacMillan, D.K., Ford, J., Fennell, T.R., Black, S.R., Snyder, R.W., Sipes, N.S., Wetmore, B.A., 2018. Evaluating in vitro-in vivo extrapolation of toxicokinetics. Toxicol. Sci. 163, 152–169.

Wambaugh, J.F., Bare, J.C., Carignan, C.C., Dionisio, K.L., Dodson, R.E., Jolliet, O., Liu, X., Meyer, D.E., Newton, S.R., Phillips, K.A., 2019a. New approach methodologies for exposure science. Current Opinion in Toxicology 15, 76–92.

Wambaugh, J.F., Wetmore, B.A., Ring, C.L., Nicolas, C.I., Pearce, R.G., Honda, G.S., Dinallo, R., Angus, D., Gilbert, J., Sierra, T., 2019b. Assessing toxicokinetic uncertainty and variability in risk prioritization. Toxicol. Sci. 172, 235–251.

Wangia, R.N., Githanga, D.P., Xue, K.S., Tang, L., Anzala, O.A., Wang, J.-S., 2019. Validation of urinary sphingolipid metabolites as biomarker of effect for fumonins exposure in Kenyan children. Biomarkers 24, 379–388.

Warner, R.M., Sweeney, L.M., Hayhurst, B.A., Mayo, M.L., 2022. Toxicokinetic Modeling of Per-and- Polyfluoroalkyl Substance Concentrations within Developing Zebrafish (Danio rerio) Populations. Environ. Sci. Tech. 56, 13189–13199.

Weschler, C.J., Bekö, G., Koch, H.M., Salthammer, T., Schripp, T., Toftum, J., Clausen, G., 2015. Transdermal uptake of diethyl phthalate and di (n-butyl) phthalate directly from air: experimental verification. Environ. Health Perspect. 123, 928–934.

Westmoreland, C., Bender, H.J., Doe, J.E., Jacobs, M.N., Kass, G.E., Madia, F., Mahony, C., Manou, I., Maxwell, G., Prieto, P., 2022. Use of New Approach Methodologies (NAMs) in regulatory decisions for chemical safety: Report from an EPA Deep Dive Workshop. Regul. Toxicol. Pharm. 135, 105261.

Wetmore, B.A., Wambaugh, J.F., Ferguson, S.S., Sochaski, M.A., Rotroff, D.M., Freeman, K., Clewell III, H.J., Dix, D.J., Andersen, M.E., Houck, K.A., 2012. Integration of dosimetry, exposure, and high-throughput screening data in chemical toxicity assessment. Toxicol. Sci. 125, 157–174.

Wrobel, S.A., Bury, D., Hayden, H., Koch, H.M., Brüning, T., Käfferlein, H.U., 2022. Human metabolism and urinary excretion of seven neonicotinoids and neonicotinoid-like compounds after controlled oral dosages. Arch. Toxicol. 96, 121–134.

Zare Jeddi, M., Hopf, N.B., Louro, H., Viegas, S., Galea, K.S., Pasanen-Kase, R., Santonen, T., Mustieles, V., Fernandez, M.F., Verhagen, H., 2022. Developing human biomonitoring as a 21st century toolbox within the European exposure science strategy 2020–2030. Environ. Int. 168, 107476.

Zare Jeddi, M., Hopf, N.B., Louro, H., Viegas, S., Galea, K.S., Pasanen-Kase, R., Santonen, T., Mustieles, V., Fernandez, M.F., Verhagen, H., 2022. Developing human biomonitoring as a 21st century toolbox within the European exposure science strategy 2020–2030. Environ. Int. 168, 107476.

Zbinden, G., 1991. Predictive value of animal studies in toxicology. Regul. Toxicol. Pharm. 14, 167–177.

Zoller, O., Rhyn, P., Zarn, J.A., Dudler, V., 2020. Urine glyphosate level as a quantitative biomarker of oral exposure. Int. J. Hyg. Environ. Health 228, 113526.

Further reading

European Food Safety Authority; Álvarez, F.; Arena, M.; Auteri, D.; Binaglia, M.; Castoldi, A.F.; Chiusolo, A.; Crivellente, F.; Egmose, M.; Fait, G. Peer review of the pesticide risk assessment of the active substance glyphosate. EFSA Journal 2023;21:e08164.

Creton, S., Saghir, S.A., Bartels, M.J., Billington, R., Bus, J.S., Davies, W., Dent, M.P., Hawksworth, G.M., Parry, S., Travis, K.Z., 2012. Use of toxicokinetics to support chemical evaluation: Informing high dose selection and study interpretation. Regul. Toxicol. Pharm. 62, 241–247.

EC. Review Report for the Active Substance Glyphosate. Finalised in the Standing Committee on Plant Health at its Meeting on 29 June 2001 in View of the Inclusion of Glyphosate in Annex I of Directive 91/414/EEC. European Commission, Health & Consumer Protection Directorate-General, Brussels, 56 p.; 2002.
kinetic (PBK) modelling and human biomonitoring data for mixture risk assessment. Environ. Int. 143, 105978.

Polet, T., Schlosser, P., Rodriguez, C., Parod, R., Rodwell, D., Kirman, C., 2016. Using physiologically based pharmacokinetic modeling and benchmark dose methods to derive an occupational exposure limit for N-methylpyrrolidone. Regul. Toxicol. Pharm. 76, 102-112.

Punt, A., Bouwmeester, H., Blaumober, B.J., Coecke, S., Hakkert, B., Hendriks, D.F., Jennings, P., Kramer, N.I., Neuhoff, S., Masereeuw, R., 2020. New approach methodologies (NAMs) for human-relevant biokinetics predictions: Meeting the paradigm shift in toxicology towards an animal-free chemical risk assessment. ALTEX-Alternatives to Animal Experimentation 37, 607-622.

Quignot, N., Wieczek, W., Amzal, B., Dorne, J.-L., 2018. "TKplate": A web-based platform for toxicokinetic modelling in food safety. Toxicol. Lett. 295, S248.

Ring, C.L., Pearce, R.G., Setzer, R.W., Wetmore, B.A., Wambaugh, J.F., 2017. Identifying populations sensitive to environmental chemicals by simulating toxicokinetic variability. Environ. Int. 106, 105-118.

Rostami-Hojdejan, A., Bois, F.Y., 2021. Opening a debate on open-source modeling tools: pouring fuel on fire versus extinguishing the flare of a healthy debate. CPT: Pharmacometrics & Systems. Pharmacology 10, 420-427.

Rotloff, D.M., Wetmore, B.A., Dix, D.J., Ferguson, S.S., Clewell, H.J., Houck, K.A., LeCluyse, E.L., Andersen, M.E., Judson, R.S., Smith, C.M., 2010. Incorporating human dosimetry and exposure into high-throughput in vitro toxicity screening. Toxicol. Sci. 117, 348-358.

Rotter, S., Beronius, A., Boobis, A., Hanberg, A., Van Klaveren, J., Luijten, M., Machera, K., Nikolopoulou, D., Van Der Voet, H., Ziliacus, J., 2018. Overview on legislation and scientific approaches for risk assessment of combined exposure to multiple chemicals: the potential EuroMix contribution. Crit. Rev. Toxicol. 48, 796-814.

Santonen, T., Porras, S.P., Bocca, B., Bousoumah, D., Duca, R.C., Galea, K.S., Godgeris, L., Göen, T., Hardy, E., Iavicoli, I., 2022. HBM4EU chromates study-Overall results and recommendations for the biomonitoring of occupational exposure to hexavalent chromium. Environ. Res. 204, 111984.

Santonen, T., Mahiout, S., Alvito, P., Apel, P., Bessemes, J., Bil, W., Borges, T., Bose-O'Reilly, S., Buekers, J., Portilla, A.I.C., 2023. How to use human biomonitoring in chemical risk assessment: Methodological aspects, recommendations, and lessons learned from HBM4EU. Int. J. Hyg. Environ. Health 249, 114139.

Scher, D.P., Alexander, B.H., Adgate, J.L., Eberly, L.E., Mandel, J.S., Aquavella, J.F., Bartels, M.J., Brzak, K.A., 2007. Agreement of pesticide biomarkers between morning void and 24-h urine samples from farmers and their children. J. Eposure Sci. Environ. Epidemiol. 17, 350-357.

Schettgen, T., Dewes, P., Kraus, T., 2016. A method for the simultaneous quantification of eight metabolites of synthetic pyrethroids in urine of the general population using gas chromatography-tandem mass spectrometry. Anal. Bioanal. Chem. 48, 5467-5478.

Schlüter, U., Meyer, J., Ahrens, A., Borghi, F., Clerc, F., Delmaar, C., Di Guardo, A., Dudzina, T., Fantke, P., Fransman, W., 2022. Exposure modelling in Europe: how to pave the road for the future as part of the European Exposure Science Strategy 2020-2030. J. Eposure Sci. Environ. Epidemiol. 32, 499-512.

Schmidt, C.W., 2006. Signs of the times: biomarkers in perspective. Nat. Inst. Environ. Health Sci.

Schütze, A., Pälmke, C., Angerer, J., Weiss, T., Brüning, T., Koch, H.M., 2012. Quantification of biomarkers of environmental exposure to di (isononyl) cyclohexane-1, 2-dicarboxylate (DINCH) in urine via HPLC-MS/MS. J. Chromatogr. B 895, 123-130.

Schütze, A., Gries, W., Kolossa-Gehring, M., Apel, P., Schröter-Kermani, C., Fiddicke, U., Leng, G., Brüning, T., Koch, H., 2015. Bis-(2-propylheptyl) phthalate (DPHP) metabolites emerging in 24 h urine samples from the German Environmental Specimen Bank (1999-2012). Int. J. Hyg. Environ. Health 218, 559-563.

Schütze, A., Otter, R., Modick, H., Langsch, A., Brüning, T., Koch, H.M., 2017. Additional oxidized and alkyl chain breakdown metabolites of the plasticizer DINCH in urine after oral dosage by human volunteers. Arch. Toxicol. 91, 179-188.

Stanfield, Z., Setzer, R.W., Hull, V., Sayre, R.R., Isaacs, K.K., Wambaugh, J.F., 2022. Bayesian inference of chemical exposures from NHANES urine biomonitoring data. J. Eposure Sci. Environ. Epidemiol. 32, 833-846.

Steckling, N., Gotti, A., Bose-O'Reilly, S., Chapizanis, D., Costopoulou, D., De Vocht, F., Garf, M., Grimalt, J.O., Heath, E., Hiscock, R., 2018. Biomarkers of exposure in environment-wide association studies—Opportunities to decode the exposome using human biomonitoring data. Environ. Res. 164, 597-624.

Tan, Y.-M., Leonard, J.A., Edwards, S., Teegarden, J., Paini, A., Egephy, P., 2018. Aggregate exposure pathways in support of risk assessment. Current Opinion in Toxicology 9, 8-13.

Teegarden, J.G., Tan, Y.-M., Edwards, S.W., Leonard, J.A., Anderson, K.A., Corley, R.A., Kile, M.L., Simonich, S.M., Stone, D., Tanguay, R.L., 2016. Completing the link between exposure science and toxicology for improved environmental health decision making: the aggregate exposure pathway framework. ACS Publications.

Terry, C., Hays, S., McCoy, A.T., McFadden, L.G., Aggarwal, M., Rasoulpour, R.J., Juberg, D.R., 2016. Implementing a framework for integrating toxicokinetics into human health risk assessment for agrochemicals. Regul. Toxicol. Pharm. 75, 89-104.

Thomas, R.S., Paules, R.S., Simeonov, A., Fitzpatrick, S.C., Crofton, K.M., Casey, W.M., Mendrick, D.L., 2018. The US Federal Tox21 Program: A strategic and operational plan for continued leadership. ALTEX 35, 163.

Thomas, R.S., Bahadori, T., Buckley, T.J., Cowden, J., Deisenroth, C., Dionisio, K.L., Frithsen, B., Grulke, C.M., Gwinn, M.R., Harrill, J.A., 2019. The next generation blueprint of computational toxicology at the US Environmental Protection Agency. Toxicol. Sci. 169, 317-332.

Thompson, C.V., Firman, J.W., Goldsmith, M.R., Grulke, C.M., Tan, Y.-M., Paini, A., Penson, P.E., Sayre, R.R., Webb, S., Madden, J.C., 2021. A systematic review of published physiologically-based kinetic models and an assessment of their chemical space coverage. Altern. Lab. Anim. 49, 197-208.

Tyzack, J.D., Kirchmann, J., 2019. Computational methods and tools to predict cytochrome P450 metabolism for drug discovery. Chem. Biol. Drug Des. 93, 377-386.

Ulrich, E.M., Sobus, J.R., Grulke, C.M., Richard, A.M., Newton, S.R., Strynar, M.J., Mansouri, K., Williams, A.J., 2019. EPA's non-targeted analysis collaborative trial (ENTAC): genesis, design, and initial findings. Anal. Bioanal. Chem. 411, 853-866.

USEPA. Strategic Plan to Promote the Development and Implementation of Alternative Test Methods Within the TSCA Program. EPA Document# EPA-740-R1-8004. U.S. Environmental Protection Agency, Office of Chemical Safety and Pollution Prevention, Washington, DC; 2018.

USEPA. EPA New Approach Methods Work Plan (v2). EPA/600/X-21/209. U.S. Environmental Protection Agency, Washington, DC; 2021.

Van Den Brand, A.D., Bajard, L., Steffensen, I.-L., Brantsæter, A.L., Dirven, H.A., Louisse, J., Peijnenburg, A., Ndw, S., Mantovani, A., De Santis, B., 2022. Providing Biological Plausibility for Exposure-Health Relationships for the Mycotoxins Deoxynivalenol (DON) and Fumonisin B1 (FB1) in Humans Using the AOP Framework. Toxins 14, 279.

Viegas, S.; Zare Jeddi, M.; B. Hopf, N.; Bessemes, J., Palmen, N.; S. Galea, K.; Jones, K.; Kujath, P.; Duca, R.-C.; Verhagen, H. Biomonitoring as an underused exposure assessment tool in occupational safety and health context—Challenges and way forward. International Journal of Environmental Research and Public Health 2020; 17:5884.

Vineis, P., Robinson, O., Chadeau-Hyam, M., Dehghan, A., Mudway, I., Dagnino, S., 2020. What is new in the exposome? Environ. Int. 143, 105887.

Wambaugh, J.F., Hughes, M.F., Ring, C.L., MacMillan, D.K., Ford, J., Fennell, T.R., Black, S.R., Snyder, R.W., Sipes, N.S., Wetmore, B.A., 2018. Evaluating in vitro-in vivo extrapolation of toxicokinetics. Toxicol. Sci. 163, 152-169.

Wambaugh, J.F., Bare, J.C., Carignan, C.C., Dionisio, K.L., Dodson, R.E., Jolliet, O., Liu, X., Meyer, D.E., Newton, S.R., Phillips, K.A., 2019a. New approach methodologies for exposure science. Current Opinion in Toxicology 15, 76-92.

Wambaugh, J.F., Wetmore, B.A., Ring, C.L., Nicolas, C.I., Pearce, R.G., Honda, G.S., Dinallo, R., Angus, D., Gilbert, J., Sierra, T., 2019b. Assessing toxicokinetic uncertainty and variability in risk prioritization. Toxicol. Sci. 172, 235-251.

Wangia, R.N., Githanga, D.P., Xue, K.S., Tang, L., Anzala, O.A., Wang, J.-S., 2019. Validation of urinary sphingolipid metabolites as biomarker of effect for fumonisins exposure in Kenyan children. Biomarkers 24, 379-388.

Warner, R.M., Sweeney, L.M., Hayhurst, B.A., Mayo, M.L., 2022. Toxicokinetic Modeling of Per-and- Polyfluoroalkyl Substance Concentrations within Developing Zebrafish (Danio rerio) Populations. Environ. Sci. Tech. 56, 13189-13199.

Weschler, C.J., Bekö, G., Koch, H.M., Salthammer, T., Schripp, T., Toftum, J., Clausen, G., 2015. Transdermal uptake of diethyl phthalate and di (n-butyl) phthalate directly from air: experimental verification. Environ. Health Perspect. 123, 928-934.

Westmoreland, C., Bender, H.J., Doe, J.E., Jacobs, M.N., Kass, G.E., Madia, F., Mahony, C., Manou, I., Maxwell, G., Prieto, P., 2022. Use of New Approach Methodologies (NAMs) in regulatory decisions for chemical safety: Report from an EPA Deep Dive Workshop. Regul. Toxicol. Pharm. 135, 105261.

Wetmore, B.A., Wambaugh, J.F., Ferguson, S.S., Sochaski, M.A., Rotroff, D.M., Freeman, K., Clewell III, H.J., Dix, D.J., Andersen, M.E., Houck, K.A., 2012. Integration of dosimetry, exposure, and high-throughput screening data in chemical toxicity assessment. Toxicol. Sci. 125, 157-174.

Wrobel, S.A., Bury, D., Hayden, H., Koch, H.M., Brüning, T., Käfferlein, H.U., 2022. Human metabolism and urinary excretion of seven neonicotinoids and neonicotinoid-like compounds after controlled oral dosages. Arch. Toxicol. 96, 121-134.

Zare Jeddi, M., Hopf, N.B., Louro, H., Viegas, S., Galea, K.S., Pasanen-Kase, R., Santonen, T., Mustieles, V., Fernandez, M.F., Verhagen, H., 2022. Developing human biomonitoring as a 21st century toolbox within the European exposure science strategy 2020-2030. Environ. Int. 168, 107476.

Zare Jeddi, M., Hopf, N.B., Louro, H., Viegas, S., Galea, K.S., Pasanen-Kase, R., Santonen, T., Mustieles, V., Fernandez, M.F., Verhagen, H., 2022. Developing human biomonitoring as a 21st century toolbox within the European exposure science strategy 2020-2030. Environ. Int. 168, 107476.

Zbinden, G., 1991. Predictive value of animal studies in toxicology. Regul. Toxicol. Pharm. 14, 167-177.

Zoller, O., Rhyn, P., Zarn, J.A., Dudler, V., 2020. Urine glyphosate level as a quantitative biomarker of oral exposure. Int. J. Hyg. Environ. Health 228, 113526.

Further reading

European Food Safety Authority; Álvarez, F.; Arena, M.; Auteri, D.; Binaglia, M.; Castoldi, A.F.; Chiusolo, A.; Crivellente, F.; Egmose, M.; Fait, G. Peer review of the pesticide risk assessment of the active substance glyphosate. EFSA Journal 2023;21:e08164.

Creton, S., Saghir, S.A., Bartels, M.J., Billington, R., Bus, J.S., Davies, W., Dent, M.P., Hawksworth, G.M., Parry, S., Travis, K.Z., 2012. Use of toxicokinetics to support chemical evaluation: Informing high dose selection and study interpretation. Regul. Toxicol. Pharm. 62, 241-247.

EC. Review Report for the Active Substance Glyphosate. Finalised in the Standing Committee on Plant Health at its Meeting on 29 June 2001 in View of the Inclusion of Glyphosate in Annex I of Directive 91/414/EEC. European Commission, Health & Consumer Protection Directorate-General, Brussels, 56 p.; 2002.