Ten years of research on synergisms and antagonisms in chemical mixtures: A systematic review and quantitative reappraisal of mixture studies

Mixture prioritization and testing: the importance of toxicokinetics

“…toxicokinetic interference. Of note, this is in accordance with observations from the pharmaceutical field demonstrating that pharmacokinetic interference is a major cause of undesired drug-drug interactions (Martin et al 2021 ).…”

“…Martin et al ( 2021 ) have recently published a systematic review article on experimental analysis of chemical mixtures. The authors conclude that the dose addition concept appears to be suitable for most mixtures, while nonetheless the potential of some classes of chemicals to produce non-additive, especially synergistic mixture effects, should not be disregarded.…”

The “EU chemicals strategy for sustainability” questions regulatory toxicology as we know it: is it all rooted in sound scientific evidence?

“…Given that the mechanistic and quantitative requirements for additive (or synergistic/antagonistic) effects are well established, the occurrence of combination effects should not be a default assumption, unless there are data supporting such mechanisms to be potentially relevant. In these cases, recent reviews show that if combination effects occur, they generally concur in size with the prediction made by the dose/concentration addition model rather than exceeding it (Cedergreen 2014; Martin et al 2021).…”

Next Generation Reproductive and Developmental Toxicology: Crosstalk Into the Future

“…Pioneer work on endocrine disrupting chemicals made clear that chemicals, which individually exert no or small effects, might induce marked responses in concert (Hass et al, 2007). This was later confirmed in several studies (Martin et al, 2020). Also, non-chemical stressors might enhance developmental adversity of chemicals (Hougaard and Hansen, 2007;Sobolewski et al, 2018).…”