The consequences of time-varying or repeated exposures can be explained and simulated by the TKTD model. Carry-over toxicity as well as delayed effects can be simulated, whether the carry-over toxicity is due to TK or TD or both.Ashauer et al. 2010 In this way, TKTD models can quantify risks from pulsed or fluctuating exposures. Organism recovery time depends on the time course of TK and TD, which makes the TKTD models suitable for calculating organism recovery time. TKTD models have the potential to predict effects of mixtures and also be used as mechanism-based extrapolation to untested toxicants or untested species . Linking TKTD models with Individual Based Models (IBM) may improve risk assessment of toxicants by simulating temporal aspects as well as ecological aspects. References Ashauer R, Escher B. 2010. Advantages of Toxicokinetic and Toxicodynamic modeling in aquatic ecotoxicology and risk assessment. Journal of Environmental Monitoring 12: 2056-2061. Ashauer R, Hintermeister A, Caravatti I, Kretschmann A, Escher B. 2010. Toxicokinetic and toxicodynamic modeling explains carry-over toxicity from exposure to Diazinon by slow organism recovery. Environmental Science and Technology 44: 3963-3971. Ashauer R, Albert C, Augustine S, Cedergreen N, Charles, S, Ducrot V, Focks A, Gabsi, F, Gergs, A, Goussen, B, Jager, T, Kramer, N. I, Nyman, A.-M, Poulsen, V, Reichenberger, S, Schäfer, R.B, Van den Brink, P.J, Veltman, K, Vogel, S, Zimmer, E.I, Preuss, T. G. 2016. Modelling survival: exposure pattern, species sensitivity and uncertainty. Scientific Reports 6:29178 DOI: 10.1038/srep29178 ATSDR. Agency for Toxic Substances and Disease Registry. ToxFAQs™ for Polychlorinated Biphenyls (PCBs). Web. URL Blaauboer B. 2003. Biokinetic and Toxicodynamic modeling and its role in toxicological research and risk assessment. Alternatives to Laboratory Animals 31: 277-281. Boelsterli, Urs. Mechanistic Toxicology: The molecular basis of how chemicals disrupt biological targets. New York: Taylor & Francis, 2003. 258-263. Print. Choi, S.M., Yoo, S.D., Lee, B.M. 2010. Toxicological Characteristics of Endocrine-Disrupting Chemicals: Developmental Toxicity, Carcinogenicity, and Mutagenicity. Journal of Toxicology and Environmental Health, Part B: Critical Reviews, 7:1, 1-23 Clotfelter, E.D., Bell, A.M. and Levering, K.R. 2004. The role of animal behaviour in the study of endocrine-disrupting chemicals. Animal Behaviour 68, 665-676. Colborn, T., Saal, F.S.V. and Soto, A.M. 1993. Developmental effects of endocrine-disrupting chemicals in wildlife and humans. Environmental Health Perspectives 101, 378-384.  Guillette, L.J., Crain, D.A., Gunderson, M.P., Kools, S.A.E., Milnes, M.R., Orlando, E.F., Rooney, A.A. and Woodward, A.R. 2000. *Alligators and endocrine disrupting contaminants: A current perspective. American Zoologist 40, 438-452. Jager T, Albert C, Preuss T, Ashauer R. 2011. General unified threshold model of survival – a Toxicokinetic-Toxicodynamic framework for ecotoxicology. Environmental Science and Technology 45: 2529-2540. Manibusan MK, Odin M, Eastmond DA. 2007. Postulated Carbon Tetrachloride Mode of Action: A Review. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 25(3): 185-209. National Toxicology Program (NTP). 2011. Carbon Tetrachloride: Report on Carcinogens (12th ed.). URL Newman, M. C. (2010). Fundamentals of Ecotoxicology (3rd ed.). Boca Raton, FL: CRC Press. Pait, A.S. and J.O. Nelson. 2002. Endocrine Disruption in Fish: An Assessment of Recent Research and Results. NOAA Tech. Memo. NOS NCCOS CCMA 149. Silver Spring, MD:NOAA, NOS, Center for Coastal Monitoring and Assessment. 55. 4-5. Perrin, William. Encyclopedia of Marine Mammals. 2nd ed. New York: Academic Press, 2009. 894. eBook. Rabergh C.M.I. and Lipsky M.M. 1997. Toxicity of Chloroform and Carbon Tetrachloride in Primary Cultures of Rainbow Trout Hepatocytes. Aquat Toxicol. 37: 169-182. Rand, G.M. (1995). Fundamentals of Aquatic Toxicology: Effects, Environmental Fate, and Risk Assessment (2nd ed.). Washington, D.C.: Taylor and Francis. Tabb, M.M. and Blumberg, B. 2006. New modes of action for endocrine-disrupting chemicals. Molecular Endocrinology 20, 475-482. VanDelft J.H.M., Van Agen E, Van Breda S.G.J., Herwijnen M.H., Staal Y.C.M., Kleinjans J.C.S. 2004. Discrimination of Genotoxic from Non-genotoxic Carcinogens by Gene Expression Profiling. Carcinogenesis. 25:1265-1276.
The consequences of time-varying or repeated exposures can be explained and simulated by the TKTD model. Carry-over toxicity as well as delayed effects can be simulated, whether the carry-over toxicity is due to TK or TD or both.Ashauer et al. 2010 In this way, TKTD models can quantify risks from pulsed or fluctuating exposures. Organism recovery time depends on the time course of TK and TD, which makes the TKTD models suitable for calculating organism recovery time. TKTD models have the potential to predict effects of mixtures , including both environmental and chemical stressors and also be used as mechanism-based extrapolation to untested toxicants or untested species Goussen et al, 2020. Linking TKTD models with Individual Based Models (IBM) may improve risk assessment of toxicants by simulating temporal aspects as well as ecological aspects. References Ashauer R, Escher B. 2010. Advantages of Toxicokinetic and Toxicodynamic modeling in aquatic ecotoxicology and risk assessment. Journal of Environmental Monitoring 12: 2056-2061. Ashauer R, Hintermeister A, Caravatti I, Kretschmann A, Escher B. 2010. Toxicokinetic and toxicodynamic modeling explains carry-over toxicity from exposure to Diazinon by slow organism recovery. Environmental Science and Technology 44: 3963-3971. Ashauer R, Albert C, Augustine S, Cedergreen N, Charles, S, Ducrot V, Focks A, Gabsi, F, Gergs, A, Goussen, B, Jager, T, Kramer, N. I, Nyman, A.-M, Poulsen, V, Reichenberger, S, Schäfer, R.B, Van den Brink, P.J, Veltman, K, Vogel, S, Zimmer, E.I, Preuss, T. G. 2016. Modelling survival: exposure pattern, species sensitivity and uncertainty. Scientific Reports 6:29178 DOI: 10.1038/srep29178 ATSDR. Agency for Toxic Substances and Disease Registry. ToxFAQs™ for Polychlorinated Biphenyls (PCBs). Web. URL Blaauboer B. 2003. Biokinetic and Toxicodynamic modeling and its role in toxicological research and risk assessment. Alternatives to Laboratory Animals 31: 277-281. Boelsterli, Urs. Mechanistic Toxicology: The molecular basis of how chemicals disrupt biological targets. New York: Taylor & Francis, 2003. 258-263. Print. Choi, S.M., Yoo, S.D., Lee, B.M. 2010. Toxicological Characteristics of Endocrine-Disrupting Chemicals: Developmental Toxicity, Carcinogenicity, and Mutagenicity. Journal of Toxicology and Environmental Health, Part B: Critical Reviews, 7:1, 1-23 Clotfelter, E.D., Bell, A.M. and Levering, K.R. 2004. The role of animal behaviour in the study of endocrine-disrupting chemicals. Animal Behaviour 68, 665-676. Colborn, T., Saal, F.S.V. and Soto, A.M. 1993. Developmental effects of endocrine-disrupting chemicals in wildlife and humans. Environmental Health Perspectives 101, 378-384. Goussen, B., Rendal, C., Sheffield, D., Butler, E., Price, O.R. and Ashauer, R. 2020. Bioenergetics modelling to analyse and predict the joint effects of multiple stressors: Meta-analysis and model corroboration. Science of the Total Environment 749, 141509 DOI: doi:10.1016/j.scitotenv.2020.141509 Guillette, L.J., Crain, D.A., Gunderson, M.P., Kools, S.A.E., Milnes, M.R., Orlando, E.F., Rooney, A.A. and Woodward, A.R. 2000. *Alligators and endocrine disrupting contaminants: A current perspective. American Zoologist 40, 438-452. Jager T, Albert C, Preuss T, Ashauer R. 2011. General unified threshold model of survival – a Toxicokinetic-Toxicodynamic framework for ecotoxicology. Environmental Science and Technology 45: 2529-2540. Manibusan MK, Odin M, Eastmond DA. 2007. Postulated Carbon Tetrachloride Mode of Action: A Review. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 25(3): 185-209. National Toxicology Program (NTP). 2011. Carbon Tetrachloride: Report on Carcinogens (12th ed.). URL Newman, M. C. (2010). Fundamentals of Ecotoxicology (3rd ed.). Boca Raton, FL: CRC Press. Pait, A.S. and J.O. Nelson. 2002. Endocrine Disruption in Fish: An Assessment of Recent Research and Results. NOAA Tech. Memo. NOS NCCOS CCMA 149. Silver Spring, MD:NOAA, NOS, Center for Coastal Monitoring and Assessment. 55. 4-5. Perrin, William. Encyclopedia of Marine Mammals. 2nd ed. New York: Academic Press, 2009. 894. eBook. Rabergh C.M.I. and Lipsky M.M. 1997. Toxicity of Chloroform and Carbon Tetrachloride in Primary Cultures of Rainbow Trout Hepatocytes. Aquat Toxicol. 37: 169-182. Rand, G.M. (1995). Fundamentals of Aquatic Toxicology: Effects, Environmental Fate, and Risk Assessment (2nd ed.). Washington, D.C.: Taylor and Francis. Tabb, M.M. and Blumberg, B. 2006. New modes of action for endocrine-disrupting chemicals. Molecular Endocrinology 20, 475-482. VanDelft J.H.M., Van Agen E, Van Breda S.G.J., Herwijnen M.H., Staal Y.C.M., Kleinjans J.C.S. 2004. Discrimination of Genotoxic from Non-genotoxic Carcinogens by Gene Expression Profiling. Carcinogenesis. 25:1265-1276.
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