Choksi, N.Y., Truax, J., Layton, A., Matheson, J., Mattie, D., Varney, T., Tao, J.,
Yozzo, K., McDougal, A.J., Merrill, J., Lowther, D., Barroso, J., Linke, B., Casey, W.,
Allen, D., 2019. United States regulatory requirements for skin and eye irritation
testing. Cutan. Ocul. Toxicol. 38, 141–155.

Clerbaux, L.-A., Paini, A., Lumen, A., Osman-Ponchet, H., Worth, A.P., Fardel, O., 2019.
Membrane transporter data to support kinetically-informed chemical risk assessment
using non-animal methods: Scientific and regulatory perspectives. Environ. Int. 126
659–671.

Coecke, S., Balls, M., Bowe, G., Davis, J., Gstraunthaler, G., Hartung, T., Hay, R.,
Merten, O., Price, A., Schechtman, L., Stacey, G., Stokes, W., 2005. Second ECVAM
Task Force on Good Cell Culture Practice Guidance on good cell culture practice.
a report of the second ECVAM task force on good cell culture practice. Altern. Lab.
Anim. 33, 261–287.

Cote, I., Anastas, P.T., Birnbaum, L.S., Clark, R.M., Dix, D.J., Edwards, S.W., Preuss, P.W.,
2012. Advancing the next generation of health risk assessment. Environ. Health
Perspect. 120, 1499–1502.

Daniel, A.B., Strickland, J., Allen, D., Casati, S., Zuang, V., Barroso, J., Whelan, M.,
Régimbald-Krnel, M.J., Kojima, H., Nishikawa, A., Park, H.K., Lee, J.K., Kim, T.S.,
Delgado, I., Rios, L., Yang, Y., Wang, G., Kleinstreuer, N., 2018. International
regulatory requirements for skin sensitization testing. Regul. Toxicol. Pharm. 95
52–65.

Daston, G., Knight, D.J., Schwarz, M., Gocht, T., Thomas, R.S., Mahony, C., Whelan, M.,
2015. SEURAT: safety evaluation ultimately replacing animal
testing—recommendations for future research in the field of predictive toxicology.
Arch. Toxicol. 89, 15–23.

Daston, G.P., Mahony, C., Thomas, R.S., Vinken, M., 2022. Assessing safety without
animal testing: The road ahead. Toxicol. Sci.

de Jong, E., van der Voet, H., Marx-Stoeling, P., Bennekou, S.H., Sprong, C., Bloch, D.,
Burchardt, A., Lasch, A., Opialla, T., Rotter, S., Wedebye, E.B., Zwartsen, A., Leys, A.,
Jeddi, M.Z., Wolterink, G., Kruisselbrink, J., de Boer, W., van Klaveren, J., 2022.
Roadmap for action on risk assessment of combined exposure to multiple chemicals
(RACEMAC). EFSA Support. Publicat. 19, 7555E.

Dent, M., Amaral, R.T., Da Silva, P.A., Ansell, J., Boisleve, F., Hatao, M., Hirose, A.,
Kasai, Y., Kern, P., Kreiling, R., Milstein, S., Montemayor, B., Oliveira, J., Richarz, A.,
Taalman, R., Vaillancourt, E., Verma, R., Posada, N.V.O.R.C., Weiss, C., Kojima, H.,
2018. Principles underpinning the use of new methodologies in the risk assessment
of cosmetic ingredients. Computat. Toxicol. 7, 20–26.

Doak, S.H., Clift, M.J., Costa, A., Delmaar, C., Gosens, I., Halappanavar, S., Kelly, S.,
Pejinenburg, W.J., Rothen-Rutishauser, B., Schins, R.P., Stone, V., Tran, L.,
Vijver, M.G., Vogel, U., Wohlleben, W., Cassee, F.R., 2022. The road to achieving the
european commission's chemicals strategy for nanomaterial sustainability—a patrols
perspective on new approach methodologies. Small 2200231.

Eccles, K.M., Karmaus, A.L., Kleinstreuer, N.C., Parham, F., Rider, C.V., Wambaugh, J.F.,
Messier, K.P., 2023. A geospatial modeling approach to quantifying the risk of
exposure to environmental chemical mixtures via a common molecular target. Sci.
Total Environ. 855, 158905.

ECHA, 2019. General Report 2018.

ECHA, 2020a. Annual Report 2019.

ECHA, 2020b. The use of alternatives to testing on animals for the REACH regulation.
Report under Article 117(3) of the REACH Regulation: European Chemicals Agency
Helsinki, Finland.

ECHA, 2021a. Annual Report 2020.

ECHA, 2021b. Transparent progress in addressing substances of concern - Integrated
Regulatory Strategy Annual Report 2021.

EFSA, Products, Panel o.P.P., Residues, t., Hernández-Jerez, A., Adriaanse, P., Aldrich,
A., Berny, P., Coja, T., Duquesne, S., Focks, A., Marinovich, M., Millet, M.,
Pelkonen, O., Pieper, S., Tiktag, A., Topping, C., Widenfalk, A., Wilks, M.,
Wolterink, G., Crofton, K., Hougaard Bennekou, S., Paparella, M., Tzoulaki, I.,
2021. Development of Integrated Approaches to Testing and Assessment (IATA) case
studies on developmental neurotoxicity (DNT) risk assessment. EFSA J. 19, e06599.

EFSA, 2018. EFSA Scientific Colloquium 24 – ‘omics in risk assessment: state of the art and next steps. EFSA Supporting Publications 15, 1512E.

EFSA, 2020. Cumulative dietary risk characterisation of pesticides that have chronic effects on the thyroid. EFSA J.18, e06088.

EFSA, 2021. Guidance Document on Scientific criteria for grouping chemicals into
assessment groups for human risk assessment of combined exposure to multiple
chemicals. EFSA J. 19, e07033.

EFSA, 2022. Theme (Concept) paper - Application of OMICS and BIOINFORMATICS
Approaches: Towards Next Generation Risk Assessment. EFSA Supporting
Publications 19, E200506E.

Escher, S.E., Kamp, H., Bennekou, S.H., Bitsch, A., Fisher, C., Graepel, R., Hengstler, J.G.,
Herzler, M., Knight, D., Leist, M., Norinder, U., Ouedraogo, G., Pastor, M., Stuard, S.,
White, A., Zdrasil, B., van de Water, B., Kroese, D., 2019. Towards grouping concepts
based on new approach methodologies in chemical hazard assessment: the read-
across approach of the EU-ToxRisk project. Arch. Toxicol. 93, 3643–3667.

Escher, B.I., Lamoree, M., Antignac, J.-P., Scholze, M., Herzler, M., Hamers, T., Jensen, T.
K., Audebert, M., Busquet, F., Maier, D., Oelgeschläger, M., Valente, M.J., Boye, H.,
Schmeisser, S., Dervilly, G., Piumatti, M., Motteau, S., König, M., Renko, K.,
Margalef, M., Cariou, R., Ma, Y., Treschow, A.F., Kortenkamp, A., Vinggaard, A.M.,
2022. Mixture Risk Assessment of complex real-life mixtures—The PANORAMIX
project. Int. J. Environ. Res. Public Health 19, 12990.

European Commission. Regulation (EC) No 1907/2006 of the European Parliament and of the Council of 18 December 2006 concerning the registration, evaluation, authorisation and restriction of chemicals (REACH), establishing a European Chemicals Agency, amending Directive 1999/45/EC and repealing Council Regulation (EEC) No 793/93 and Commission Regulation (EC) No 1488/94 as well

as Council Directive 76/769/EEC and Commission Directives 91/155/EEC, 93/67/
EEC, 93/105/EC and 2000/21/EC. Official Journal of the European Union 2006;
396:1-849.

European Commission, 2019. J.R.C.J. EURL ECVAM dataset on alternative methods to
animal experimentation (DB-ALM). European Commission, Joint Research Centre
(JRC).

European Commission. Chemicals Strategy for Sustainability Towards a Toxic-Free
Environment. European Commission Brussels, Belgium; 2020.

Fischer, I., Milton, C., Wallace, H., 2020. Toxicity testing is evolving! Toxicol. Res. 9,
67–80.

Gerberick, F., Aleksic, M., Basketter, D., Casati, S., Karlberg, A.-T., Kern, P., Kimber, I.,
Lepoittevin, J.P., Natsch, A., Ovigne, J.M., Rovida, C., Sakaguchi, H., Schultz, T.,
2008. Chemical reactivity measurement and the predictive identification of skin
sensitisers: The report and recommendations of ECVAM Workshop 64. Altern. Lab.
Anim. 36, 215–242.

Gocht, T., Berggren, E., Ahr, H.J., Cotgreave, I., Cronin, M.T., Daston, G., Hardy, B.,
Heinzle, E., Hescheler, J., Knight, D.J., Mahony, C., Peschanski, M., Schwarz, M.,
Thomas, R.S., Verfaillie, C., White, A., Whelan, M., 2015. The SEURAT-1 approach
towards animal free human safety assessment. ALTEX 32, 9–24.

Goodman, J.I., 2018. Goodbye to the bioassay. Toxicol. Res. 7, 558–564.

Gwinn, W.M., Auerbach, S.S., Parham, F., Stout, M.D., Waidyanatha, S., Mutlu, E.,
Collins, B., Paules, R.S., Merrick, B.A., Ferguson, S., Ramanahari, S., Bucher, J.R.,
Sparrow, B., Toy, H., Gorospe, J., Machesky, N., Shah, R.R., Balik-Meisner, M.R.,
Mav, D., Phadke, D.P., Roberts, G., DeVito, M.J., 2020. Evaluation of 5-day in vivo
rat liver and kidney with high-throughput transcriptomics for estimating benchmark
doses of apical outcomes. Toxicol. Sci. 176, 343–354.

Hareng, L., Pellizzer, C., Bremer, S., Schwarz, M., Hartung, T., 2005. The integrated
project ReProTect: a novel approach in reproductive toxicity hazard assessment.
Repro. Toxicol. 20, 441–452.

Harrill, J.A., Viant, M.R., Yauk, C.L., Sachana, M., Gant, T.W., Auerbach, S.S., Beger, R.
D., Bouhifd, M., O'Brien, J., Burgoon, L., Caiment, F., Carpi, D., Chen, T., Chorley, B.
N., Colbourne, J., Corvi, R., Debrauwer, L., O'Donovan, C., Ebbels, T.M.D.,
Ekman, D.R., Faulhammer, F., Gribaldo, L., Hilton, G.M., Jones, S.P., Kende, A.,
Lawson, T.N., Leite, S.B., Leonardas, P.E.G., Luijten, M., Martin, A., Moussa, L.,
Rudaz, S., Schmitz, O., Sobanski, T., Strauss, V., Vaccari, M., Vijay, V., Weber, R.J.
M., Williams, A.J., Williams, A., Thomas, R.S., Whelan, M., 2021. Progress towards
an OECD reporting framework for transcriptomics and metabolomics in regulatory
toxicology. Regul. Toxicol. Pharm. 125, 105020.

Hartung, T., van Vliet, E., Jaworska, J., Bonilla, L., Skinner, N., Thomas, R., 2012.
Systems Toxicology. ALTEX - Alternatives to animal experimentation 29, 119–128.

Hartung, T., Hoffmann, S., Stephens, M., 2013b. Food for thought...Mechanistic
validation. ALTEX 30, 119–130.

Hartung, T., McBride, M., 2011. Food for thought... on mapping the human toxome.
ALTEX-Alternat. Anim. Exp. 28, 83–93.

Hartung, T., Tsatsakis, A.M., 2021. The state of the scientific revolution in toxicology.
ALTEX – Alternat. Anim. Exp. 38, 379–386.

Hartung, T., Luechtefeld, T., Maertens, A., Kleensang, A., 2013c. Food for thought... integrated testing strategies for safety assessments. ALTEX 30, 3.

Hartung, T., FitzGerald, R.E., Jennings, P., Mirams, G.R., Peitsch, M.C., Rostami-
Hodjegan, A., Shah, I., Wilks, M.F., Sturla, S.J., 2017. Systems toxicology: real world
applications and opportunities. Chem. Res. Toxicol. 30, 870–882.

Hartung, T., de Vries, R., Hoffmann, S., Hogberg, H.T., Smirnova, L., Tsaioun, K.,
Whaley, P., Leist, M., 2019. Toward good in vitro reporting standards. ALTEX –
Alternat. Anim. Exp. 36, 3–17.

Herzler, M., Marx-Stoeling, P., Pirow, R., Riebeling, C., Luch, A., Tralau, T.,
Schwerdtle, T., Hensel, A., 2021. The, “EU chemicals strategy for sustainability”
sitions regulatory toxicology as we know it: is it all rooted in sound scientific
evidence? Arch. Toxicol. 95, 2589–2601.

Herzler, M., Marx-Stoeling, P., Pirow, R., Riebeling, C., Luch, A., Tralau, T.,
Schwerdtle, T., Hensel, A., 2022. Reply to the opinion paper “The EU chemicals
strategy for sustainability: an opportunity to develop new approaches for hazard
assessment” by Scholz, et al. Arch. Toxicol. 96, 2387–2390.

Iccvam, 2018. A Strategic roadmap for establishing new approaches to evaluate the
safety of chemicals and medical products in the United States. Natl. Toxicol. Progr.
Natl. Inst. Environ. Health ...

Jacobs, M.N., Colacci, A., Corvi, R., Vaccari, M., Aguila, M.C., Corvaro, M., Delrue, N.,
Desaulniers, D., Ertych, N., Jacobs, A., Luijten, M., Madia, F., Nishikawa, A.,
Ogawa, K., Ohmori, K., Paparella, M., Sharma, A.K., Vasseur, P., 2020. Chemical
carcinogen safety testing: OECD expert group international consensus on the
development of an integrated approach for the testing and assessment of chemical
non-genotoxic carcinogens. Arch. Toxicol. 94, 2899–2923.

Karmaus, A.L., Mansouri, K., To, K.T., Blake, B., Fitzpatrick, J., Strickland, J.,
Patiewicz, G., Allen, D., Casey, W., Kleinstreuer, N., 2022. Evaluation of variability
across rat acute oral systemic toxicity studies. Toxicol. Sci. 188, 34–47.

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.

Kleinstreuer, N.C., Ceger, P.C., Allen, D.G., Strickland, J., Chang, X., Hamm, J.T.,
Casey, W.M., 2016. A curated database of rodent uterotrophic bioactivity. Environ.
Health Perspect. 124, 556–562.

Kleinstreuer, N.C., Hoffmann, S., Alépée, N., Allen, D., Ashikaga, T., Casey, W.,
Clouet, E., Cluzel, M., Desprez, B., Gellatly, N., Göbel, C., Kern, P.S., Klaric, M.,
Kühnl, J., Martinozzi-Teissier, S., Mewes, K., Miyazawa, M., Strickland, J., van
Vliet, E., Zang, Q., Petersohn, D., 2018. Non-animal methods to predict skin
sensitization (II): an assessment of defined approaches (*). Crit. Rev. Toxicol. 48,
359–374.
Choksi, N.Y., Truax, J., Layton, A., Matheson, J., Mattie, D., Varney, T., Tao, J.,
Yozzo, K., McDougal, A.J., Merrill, J., Lowther, D., Barroso, J., Linke, B., Casey, W.,
Allen, D., 2019. United States regulatory requirements for skin and eye irritation
testing. Cutan. Ocul. Toxicol. 38, 141–155.

Clerbaux, L.-A., Paini, A., Lumen, A., Osman-Ponchet, H., Worth, A.P., Fardel, O., 2019.
Membrane transporter data to support kinetically-informed chemical risk assessment
using non-animal methods: Scientific and regulatory perspectives. Environ. Int. 126,
659–671.

Coecke, S., Balls, M., Bowe, G., Davis, J., Gstraunthaler, G., Hartung, T., Hay, R.,
Merten, O., Price, A., Schechtman, L., Stacey, G., Stokes, W., 2005. Second ECVAM
Task Force on Good Cell Culture Practice Guidance on good cell culture practice.
a report of the second ECVAM task force on good cell culture practice. Altern. Lab.
Anim. 33, 261–287.

Cote, I., Anastas, P.T., Birnbaum, L.S., Clark, R.M., Dix, D.J., Edwards, S.W., Preuss, P.W.,
2012. Advancing the next generation of health risk assessment. Environ. Health
Perspect. 120, 1499–1502.

Daniel, A.B., Strickland, J., Allen, D., Casati, S., Zuang, V., Barroso, J., Whelan, M.,
Régimbald-Krnel, M.J., Kojima, H., Nishikawa, A., Park, H.K., Lee, J.K., Kim, T.S.,
Delgado, I., Rios, L., Yang, Y., Wang, G., Kleinstreuer, N., 2018. International
regulatory requirements for skin sensitization testing. Regul. Toxicol. Pharm. 95,
52–65.

Daston, G., Knight, D.J., Schwarz, M., Gocht, T., Thomas, R.S., Mahony, C., Whelan, M.,
2015. SEURAT: safety evaluation ultimately replacing animal
testing—recommendations for future research in the field of predictive toxicology.
Arch. Toxicol. 89, 15–23.

Daston, G.P., Mahony, C., Thomas, R.S., Vinken, M., 2022. Assessing safety without
animal testing: The road ahead. Toxicol. Sci.

de Jong, E., van der Voet, H., Marx-Stoeling, P., Bennekou, S.H., Sprong, C., Bloch, D.,
Burchardt, A., Lasch, A., Opialla, T., Rotter, S., Wedebye, E.B., Zwartsen, A., Leys, A.,
Jeddi, M.Z., Wolterink, G., Kruisselbrink, J., de Boer, W., van Klaveren, J., 2022.
Roadmap for action on risk assessment of combined exposure to multiple chemicals
(RACEMAC). EFSA Support. Publicat. 19, 7555E.

Dent, M., Amaral, R.T., Da Silva, P.A., Ansell, J., Boisleve, F., Hatao, M., Hirose, A.,
Kasai, Y., Kern, P., Kreiling, R., Milstein, S., Montemayor, B., Oliveira, J., Richarz, A.,
Taalman, R., Vaillancourt, E., Verma, R., Posada, N.V.O.R.C., Weiss, C., Kojima, H.,
2018. Principles underpinning the use of new methodologies in the risk assessment
of cosmetic ingredients. Computat. Toxicol. 7, 20–26.

Doak, S.H., Clift, M.J., Costa, A., Delmaar, C., Gosens, I., Halappanavar, S., Kelly, S.,
Pejinenburg, W.J., Rothen-Rutishauser, B., Schins, R.P., Stone, V., Tran, L.,
Vijver, M.G., Vogel, U., Wohlleben, W., Cassee, F.R., 2022. The road to achieving the
european commission's chemicals strategy for nanomaterial sustainability—a patrols
perspective on new approach methodologies. Small 2200231.

Eccles, K.M., Karmaus, A.L., Kleinstreuer, N.C., Parham, F., Rider, C.V., Wambaugh, J.F.,
Messier, K.P., 2023. A geospatial modeling approach to quantifying the risk of
exposure to environmental chemical mixtures via a common molecular target. Sci.
Total Environ. 855, 158905.

ECHA, 2019. General Report 2018.

ECHA, 2020a. Annual Report 2019.

ECHA, 2020b. The use of alternatives to testing on animals for the REACH regulation.
Report under Article 117(3) of the REACH Regulation: European Chemicals Agency
Helsinki, Finland.

ECHA, 2021a. Annual Report 2020.

ECHA, 2021b. Transparent progress in addressing substances of concern - Integrated
Regulatory Strategy Annual Report 2021.

EFSA, Products, Panel o.P.P., Residues, t., Hernández-Jerez, A., Adriaanse, P., Aldrich,
A., Berny, P., Coja, T., Duquesne, S., Focks, A., Marinovich, M., Millet, M.,
Pelkonen, O., Pieper, S., Tiktak, A., Topping, C., Widenfalk, A., Wilks, M.,
Wolterink, G., Crofton, K., Hougaard Bennekou, S., Paparella, M., Tzoulaki, I.,
2021. Development of Integrated Approaches to Testing and Assessment (IATA) case
studies on developmental neurotoxicity (DNT) risk assessment. EFSA J. 19, e06599.

EFSA, 2018. EFSA Scientific Colloquium 24 – ‘omics in risk assessment: state of the art and next steps. EFSA Supporting Publications 15, 1512E.

EFSA, 2020. Cumulative dietary risk characterisation of pesticides that have chronic
effects on the thyroid. EFSA J.18, e06088.

EFSA, 2021. Guidance Document on Scientific criteria for grouping chemicals into
assessment groups for human risk assessment of combined exposure to multiple
chemicals. EFSA J. 19, e07033.

EFSA, 2022. Theme (Concept) paper - Application of OMICS and BIOINFORMATICS
Approaches: Towards Next Generation Risk Assessment. EFSA Supporting
Publications 19, E200506E.

Escher, S.E., Kamp, H., Bennekou, S.H., Bitsch, A., Fisher, C., Graepel, R., Hengstler, J.G.,
Herzler, M., Knight, D., Leist, M., Norinder, U., Ouedraogo, G., Pastor, M., Stuard, S.,
White, A., Zdrasil, B., van de Water, B., Kroese, D., 2019. Towards grouping concepts
based on new approach methodologies in chemical hazard assessment: the read-
across approach of the EU-ToxRisk project. Arch. Toxicol. 93, 3643–3667.

Escher, B.I., Lamoree, M., Antignac, J.-P., Scholze, M., Herzler, M., Hamers, T., Jensen, T.
K., Audebert, M., Busquet, F., Maier, D., Oelgeschläger, M., Valente, M.J., Boye, H.,
Schmeisser, S., Dervilly, G., Piumatti, M., Motteau, S., König, M., Renko, K.,
Margalef, M., Cariou, R., Ma, Y., Treschow, A.F., Kortenkamp, A., Vinggaard, A.M.,
2022. Mixture Risk Assessment of complex real-life mixtures—The PANORAMIX
project. Int. J. Environ. Res. Public Health 19, 12990.

European Commission. Regulation (EC) No 1907/2006 of the European Parliament and of the Council of 18 December 2006 concerning the registration, evaluation, authorisation and restriction of chemicals (REACH), establishing a European Chemicals Agency, amending Directive 1999/45/EC and repealing Council Regulation (EEC) No 793/93 and Commission Regulation (EC) No 1488/94 as well

as Council Directive 76/769/EEC and Commission Directives 91/155/EEC, 93/67/
EEC, 93/105/EC and 2000/21/EC. Official Journal of the European Union 2006;
396:1-849.

European Commission, 2019. J.R.C.J. EURL ECVAM dataset on alternative methods to
animal experimentation (DB-ALM). European Commission, Joint Research Centre
(JRC).

European Commission. Chemicals Strategy for Sustainability Towards a Toxic-Free
Environment. European Commission Brussels, Belgium; 2020.

Fischer, I., Milton, C., Wallace, H., 2020. Toxicity testing is evolving! Toxicol. Res. 9,
67–80.

Gerberick, F., Aleksic, M., Basketter, D., Casati, S., Karlberg, A.-T., Kern, P., Kimber, I.,
Lepoittevin, J.P., Natsch, A., Ovigne, J.M., Rovida, C., Sakaguchi, H., Schultz, T.,
2008. Chemical reactivity measurement and the predictive identification of skin
sensitisers: The report and recommendations of ECVAM Workshop 64. Altern. Lab.
Anim. 36, 215–242.

Gocht, T., Berggren, E., Ahr, H.J., Cotgreave, I., Cronin, M.T., Daston, G., Hardy, B.,
Heinzle, E., Hescheler, J., Knight, D.J., Mahony, C., Peschanski, M., Schwarz, M.,
Thomas, R.S., Verfaillie, C., White, A., Whelan, M., 2015. The SEURAT-1 approach
towards animal free human safety assessment. ALTEX 32, 9–24.

Goodman, J.I., 2018. Goodbye to the bioassay. Toxicol. Res. 7, 558–564.

Gwinn, W.M., Auerbach, S.S., Parham, F., Stout, M.D., Waidyanatha, S., Mutlu, E.,
Collins, B., Paules, R.S., Merrick, B.A., Ferguson, S., Ramanahari, S., Bucher, J.R.,
Sparrow, B., Toy, H., Gorospe, J., Machesky, N., Shah, R.R., Balik-Meisner, M.R.,
Mav, D., Phadke, D.P., Roberts, G., DeVito, M.J., 2020. Evaluation of 5-day in vivo
rat liver and kidney with high-throughput transcriptomics for estimating benchmark
doses of apical outcomes. Toxicol. Sci. 176, 343–354.

Hareng, L., Pellizzer, C., Bremer, S., Schwarz, M., Hartung, T., 2005. The integrated
project ReProTect: a novel approach in reproductive toxicity hazard assessment.
Repro. Toxicol. 20, 441–452.

Harrill, J.A., Viant, M.R., Yauk, C.L., Sachana, M., Gant, T.W., Auerbach, S.S., Beger, R.
D., Bouhifd, M., O'Brien, J., Burgoon, L., Caiment, F., Carpi, D., Chen, T., Chorley, B.
N., Colbourne, J., Corvi, R., Debrauwer, L., O'Donovan, C., Ebbels, T.M.D.,
Ekman, D.R., Faulhammer, F., Gribaldo, L., Hilton, G.M., Jones, S.P., Kende, A.,
Lawson, T.N., Leite, S.B., Leonardas, P.E.G., Luijten, M., Martin, A., Moussa, L.,
Rudaz, S., Schmitz, O., Sobanski, T., Strauss, V., Vaccari, M., Vijay, V., Weber, R.J.
M., Williams, A.J., Williams, A., Thomas, R.S., Whelan, M., 2021. Progress towards
an OECD reporting framework for transcriptomics and metabolomics in regulatory
toxicology. Regul. Toxicol. Pharm. 125, 105020.

Hartung, T., van Vliet, E., Jaworska, J., Bonilla, L., Skinner, N., Thomas, R., 2012.
Systems Toxicology. ALTEX - Alternatives to animal experimentation 29, 119–128.

Hartung, T., Hoffmann, S., Stephens, M., 2013b. Food for thought...Mechanistic
validation. ALTEX 30, 119–130.

Hartung, T., McBride, M., 2011. Food for thought... on mapping the human toxome.
ALTEX-Alternat. Anim. Exp. 28, 83–93.

Hartung, T., Tsatsakis, A.M., 2021. The state of the scientific revolution in toxicology.
ALTEX – Alternat. Anim. Exp. 38, 379–386.

Hartung, T., Luechtefeld, T., Maertens, A., Kleensang, A., 2013c. Food for thought...
integrated testing strategies for safety assessments. ALTEX 30, 3.

Hartung, T., FitzGerald, R.E., Jennings, P., Mirams, G.R., Peitsch, M.C., Rostami-
Hodjegan, A., Shah, I., Wilks, M.F., Sturla, S.J., 2017. Systems toxicology: real world
applications and opportunities. Chem. Res. Toxicol. 30, 870–882.

Hartung, T., de Vries, R., Hoffmann, S., Hogberg, H.T., Smirnova, L., Tsaioun, K.,
Whaley, P., Leist, M., 2019. Toward good in vitro reporting standards. ALTEX –
Alternat. Anim. Exp. 36, 3–17.

Herzler, M., Marx-Stoeling, P., Pirow, R., Riebeling, C., Luch, A., Tralau, T.,
Schwerdtle, T., Hensel, A., 2021. The “EU chemicals strategy for sustainability”
sitions regulatory toxicology as we know it: is it all rooted in sound scientific
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Luechtedfeld, T., Maertens, A., Russo, D.P., Rovida, C., Zhu, H., Hartung, T., 2016. Global analysis of publicly available safety data for 9,801 substances registered under REACH from 2008–2014. ALTEX 33, 95.

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Maertens, A., Golden, E., Luechtedfeld, T.H., Hoffmann, S., Tsaioun, K., Hartung, T., 2022. Probabilistic risk assessment—the keystone for the future of toxicology. ALTEX 39, 3.

Mahony, C., Ashton, R.S., Birk, B., Boobis, A.R., Cull, T., Daston, G.P., Ewart, L., Knudsen, T.B., Manou, I., Maurer-Stroh, S., Margiotta-Casaluci, L., Müller, B.P., Nordlund, P., Roberts, R.A., Steger-Hartmann, T., Vandenbossche, E., Viant, M.R., Vinken, M., Whelan, M., Zvonimir, Z., Cronin, M.T.D., 2020. New ideas for non-animal approaches to predict repeated-dose systemic toxicity: report from an EPA Blue Sky Workshop. Regul. Toxicol. Pharm. 114, 104668.

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Marx, U., Akabane, T., Andersson, T.B., Baker, E., Beilmann, M., Beken, S., Brendler-Schwaab, S., Cirit, M., David, R., Dehne, E.M., Durieux, I., Ewart, L., Fitzpatrick, S.C., Frey, O., Fuchs, F., Griffith, L.G., Hamilton, G., Hartung, T., Hoeng, J., Hogberg, H., Hughes, D.J., Ingber, D.E., Iskandar, A., Kanamori, T., Kojima, H., Kuehnl, J., Leist, M., Li, B., Loskill, P., Mendrick, D.L., Neumann, T., Pallocca, G., Rusyn, I., Smirnova, L., Steger-Hartmann, T., Tagle, D.A., Tonevitsky, A., Tsyb, S., Trapecer, M., Van de Water, B., Van den Eijden-van Raaij, J., Vulto, P., Watanabe, K., Wolf, A., Zhou, X., Roth, A., 2020. Biology-inspired microphysiological systems to advance patient benefit and animal welfare in drug development. ALTEX 37, 365–394.

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Leist, M., Hasiwa, N., Daneshian, M., Hartung, T., 2012. Validation and quality control of replacement alternatives-current status and future challenges. Toxicol. Res. 1, 8-22.

Leist, M., Hasiwa, N., Rovida, C., Daneshian, M., Basketter, D., Kimber, I., Clewell, H., Gocht, T., Goldberg, A., Busquet, F., Rossi, A.-M., Schwarz, M., Stephens, M., Taalman, R., Knudsen, T.B., McKim, J., Harris, G., Pamies, D., Hartung, T., 2014. Consensus report on the future of animal-free systemic toxicity testing. ALTEX – Alternat. Anim. Exp. 31, 341–356.

Leist, M., Ghallab, A., Graepel, R., Marchan, R., Hassan, R., Bennekou, S.H., Limonciel, A., Vinken, M., Schildknecht, S., Waldmann, T., Danen, E., van Ravenzwaay, B., Kamp, H., Gardner, I., Godoy, P., Bois, F.Y., Braeuning, A., Reif, R., Oesch, F., Drasdo, D., Höhme, S., Schwarz, M., Hartung, T., Braunbeck, T., Beltman, J., Vrieling, H., Sanz, F., Forsby, A., Gadaleta, D., Fisher, C., Kelm, J., Fluri, D., Ecker, G., Zdrazil, B., Terron, A., Jennings, P., van der Burg, B., Dooley, S., Meijer, A.H., Willighagen, E., Martens, M., Elova, M., Mombelli, E., Taboureau, O., Mantovani, A., Hardy, J., Koch, F., Escher, S., van Thriel, C., Cadenas, C., Kroese, D., van de Water, B., Hengstler, J.G., 2017. Adverse outcome pathways: opportunities, limitations and open questions. Arch. Toxicol. 91, 3477–3505.

Leonard, J.A., 2019. Supporting systems science through in silico applications: a focus on informing metabolic mechanisms. Curr. Opin. Toxicol. 16, 1-8.

Li, T., Tong, W., Roberts, R., Liu, Z., Thakkar, S., 2020. Deep Learning on High-
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Lichtenstein, D., Mentz, A., Schmidt, F.F., Luckert, C., Buhrke, T., Marx-Stoelting, P., Kalinowski, J., Albaum, S.P., Joos, T.O., Poetz, O., Braeuning, A., 2020. Transcript and protein marker patterns for the identification of steatotic compounds in human HepaRG cells. Food Chem. Toxicol. 145, 111690.

Linkov, I., Massey, O., Keisler, J., Rusyn, I., Hartung, T., 2015. From, “weight of evidence” to quantitative data integration using multicriteria decision analysis and Bayesian methods. ALTEX – Alternat. Anim. Experiment. 32, 3-8.

Luechtedfeld, T., Maertens, A., Russo, D.P., Rovida, C., Zhu, H., Hartung, T., 2016. Global analysis of publicly available safety data for 9,801 substances registered under REACH from 2008–2014. ALTEX 33, 95.

Luechtedfeld, T., Marsh, D., Rowlands, C., Hartung, T., 2018. Machine learning of toxicological big data enables read-across structure activity relationships (RASAR) outperforming animal test reproducibility. Toxicol. Sci. 165, 198-212.

Luijten, M., Corvi, R., Mehta, J., Corvaro, M., Delrue, N., Felter, S., Haas, B., Hewitt, N.J., Hilton, G., Holmes, T., Jacobs, M.N., Jacobs, A., Lamplmair, F., Lewis, D., Madia, F., Manou, I., Melching-Kollmuss, S., Schorsch, F., Schütte, K., Sewell, F., Strup, C., van der Laan, J.W., Wolf, D.C., Wolterink, G., Woutersen, R., Zvonar, Z., Heusinkveld, H., Braakhuis, H., 2020. A comprehensive view on mechanistic approaches for cancer risk assessment of non-genotoxic agrochemicals. Regul. Toxicol. Pharm. 118, 104789.

Luijten, M., Sprong, R.C., Rorije, E., van der Ven, L.T.M., 2022. Prioritization of chemicals in food for risk assessment by integrating exposure estimates and new approach methodologies: a next generation risk assessment case study. Front. Toxicol. 4.

Lupu, D., Andersson, P., Bornehag, C.G., Demenee, B., Fritsche, O., Eennings, C.,
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Ma, Y., Taxvig, C., Rodríguez-Carrillo, A., Mustieles, V., Reiber, L., Kiesow, A., Michelle Löbl, N., Fernández, M.F., Vicky Alstrup Hansen, T., João Valente, M., Kolossa-Gehring, M., David, M., Marie Vinggaard, A., 2023. Human risk associated with exposure to mixtures of antiandrogenic chemicals evaluated using in vitro hazard and human biomonitoring data. Environ. Int. 107815.

Maertens, A., Golden, E., Luechtedfeld, T.H., Hoffmann, S., Tsaioun, K., Hartung, T., 2022. Probabilistic risk assessment—the keystone for the future of toxicology. ALTEX 39, 3.

Mahony, C., Ashton, R.S., Birk, B., Boobis, A.R., Cull, T., Daston, G.P., Ewart, L., Knudsen, T.B., Manou, I., Maurer-Stroh, S., Margiotta-Casaluci, L., Müller, B.P., Nordlund, P., Roberts, R.A., Steger-Hartmann, T., Vandenbossche, E., Viant, M.R., Vinken, M., Whelan, M., Zvonimir, Z., Cronin, M.T.D., 2020. New ideas for non-animal approaches to predict repeated-dose systemic toxicity: report from an EPA Blue Sky Workshop. Regul. Toxicol. Pharm. 114, 104668.

Malinowska, J.M., Palosaari, T., Sund, J., Carpi, D., Bouhifd, M., Weber, R.J.M., Whelan, M., Viant, M.R., 2022. Integrating in vitro metabolomics with a 96-well high-throughput screening platform. Metabolomics 18, 11.

Marx, U., Andersson, T.B., Bahinski, A., Beilmann, M., Beken, S., Cassee, F.R., Cirit, M., Daneshian, M., Fitzpatrick, S., Frey, O., Gaertner, C., Giese, C., Griffith, L., Hartung, T., Heringa, M.B., Hoeng, J., de Jong, W.H., Kojima, H., Kuehnl, J., Leist, M., Luch, A., Maschmeyer, I., Sakharov, D., Sips, A.J., Steger-Hartmann, T., Tagle, D.A., Tonevitsky, A., Tralau, T., Tsyb, S., van de Stolpe, A., Vandebriel, R., Vulto, P., Wang, J., Wiest, J., Rodenburg, M., Roth, A., 2016. Biology-inspired microphysiological system approaches to solve the prediction dilemma of substance testing. ALTEX 33, 272–321.

Marx, U., Akabane, T., Andersson, T.B., Baker, E., Beilmann, M., Meken, S., Brendler-Schwaab, S., Cirit, M., David, R., Dehne, E.M., Durieux, I., Ewart, L., Fitzpatrick, S.C., Frey, O., Fuchs, F., Griffith, L.G., Hamilton, G., Hartung, T., Hoeng, J., Hogberg, H., Hughes, D.J., Ingber, D.E., Iskandar, A., Kanamori, T., Kojima, H., Kuehnl, J., Leist, M., Li, B., Loskill, P., Mendrick, D.L., Neumann, T., Pallocca, G., Rusyn, I., Smirnova, L., Steger-Hartmann, T., Tagle, D.A., Tonevitsky, A., Tsyb, S., Trapecer, M., Van de Water, B., Van den Eijden-van Raaij, J., Vulto, P., Watanabe, K., Wolf, A., Zhou, X., Roth, A., 2020. Biology-inspired microphysiological systems to advance patient benefit and animal welfare in drug development. ALTEX 37, 365-394.

Marx-Stoelting, P., Braeuning, A., Buhrke, T., Lampen, T., Niemann, L.,
Oelgeschlæger, M., Rieke, S., Schmidt, F., Heise, T., Pfeil, R., Solecki, R., 2015.
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