Table 1.

Categories and subcategories in the AEP-AOP based taxonomy of chemical interactions from Price and Leonard (2019) and example interactions.

Category	Example	Reference
Category 1. Interactions occurring during environmental exposure processes, including emissions, transport and transformation, and exposure processes. Chemical X may interact with a chemical Y by either:
1A. Influencing the movement of chemical Y between environmental KESs	Effects of acids on the mobility of metals in soils and aquatic systems	Spurgeon et al. (2010)
1B. Changing the conversion rate of chemical Y in an environmental KES	Reducing the conversion of ammonia to nitrate in soil by dicyandiamide	Rose et al. (2018)
1C. Creating a new conversion KTR that involves chemicals X and Y in an environmental KES	Photochemical reaction of nitrogen oxide and methane to produce formaldehyde in the atmosphere	Luecken et al. (2018)
Category 2. Interactions during the toxicokinetic processes. Chemical X may interact with chemical Y by either:
2A. Influencing the movement of chemical X between KESs in an organism	Increased of dermal absorption of disinfection-by-products by sodium lauryl sulfate	Trabaris et al. (2012)
2B. Changing the conversion rate of chemical X in an organism’s KES	Ethanol’s ability to inhibit the metabolism of methanol by competitive inhibition of alcohol dehydrogenase	Tephly (1991)
2C. Creating a new conversion KTR that involves chemicals X and Y in an organism’s KES	The ability of melamine and cyanuric acid to form insoluble chemical complexes in the kidney leading to nephrotoxicity	Puschner et al. (2007), Dorne et al. (2013)
Category 3. Chemical Interactions that involve chemicals with MIEs on a common AOP network
3A. Chemicals X and Y have one or more common MIEs	Thyroid hormone disruption caused by sodium-iodide symporter (NIS) inhibitors such as perchlorate, thiocyanate, and nitrates.	Hines et al. (2019)
3B. Chemicals X and Y have different MIEs but have one or more common intermediate KEs	Stimulation of estrogen receptor by bisphenol A and inhibition of androgen receptor by diethyl hexyl phthalate both leading to common KEs and a common AO of reduced fertility	De Falco et al. (2015)
3C. Chemicals X and Y have different MIEs, different intermediate KEs, and a common AO	Pulmonary fibrosis that is caused by nickel oxide nanoparticles and cigarette smoke	Bai et al. (2018) and Checa et al. (2016)
Category 4. Interactions leading to an adverse outcome in a population due to population- or ecosystem-mediated interactions.
4A. Chemicals X and Y have different MIEs for AOs that occur in different portions of a receptor population	Flubenzuron a larvicide for juvenile sea lice and pyrethroids are pesticides that affect adult sea lice	Van Geest et al. (2014)
4B. Chemicals X and Y have different AOs in different species in an ecosystem, but the AOs lead to a joint effect in a receptor population	Turbufos causes direct toxicity cladocerans while atrazine reduces the levels of food (algae) for the planktonic animals	Choung et al. (2013)