Table 2.

Summary of Krug and Wick study evaluation.

Nanomaterial Characterization Score	Criteria	In Vivo Studies									In Vitro Studies
		O’Connor 2014	Yanamala et al. 2014	Farcas et al. 2016	Shvedova et al. 2016	Catalan et al. 2017	Park et al. 2018	Ilves et al. 2018	TOTAL	%	Clift et al. 2011	Endes et al. 2014	Yanamala et al. 2016	Menas et al. 2017	Lopes et al. 2017	Ilves et al. 2018	TOTAL	%
	Chemical composition, purity, impurities	0	1	1	2	0	1	2	7	50%	0	1	1	1	1	2	6	50%
	Particle size and size distribution	2	2	2	2	2	2	2	14	100%	2	2	2	2	2	2	12	100%
	Specific surface	2	0	0	0	0	0	0	2	14%	0	0	0	0	0	0	0	0%
	Morphology (crystalline/amorphous, shape)	2	2	0	2	2	2	2	12	86%	2	2	0	2	2	2	10	83%
	Surface chemistry, coating, functionalization	1	0	0	1	2	0	1	5	36%	0	1	0	0	2	1	4	33%
	Degree of agglomeration/aggregation and particle size distribution under experimental conditions (for example, media with/without proteins)	0	0	0	0	0	0	0	0	0%	0	1	0	0	2	0	3	25%
	Surface reactivity and/or surface load (zeta potential)	0	0	0	2	2	0	2	6	43%	0	0	0	0	2	2	4	33%
	Characterization Score (out of 14)	7	5	3	9	8	5	9		47%	4	7	3	5	11	9		46%
Study Design Score	Criteria	In vivo studies									In vitro studies
		O’Connor 2014	Yanamala et al. 2014	Farcas et al. 2016	Shvedova et al. 2016	Catalan et al. 2017	Park et al. 2018	Ilves et al. 2018	TOTAL	%	Clift et al. 2011	Endes et al. 2014	Yanamala et al. 2016	Menas et al. 2017	Lopes et al. 2017	Ilves et al. 2018	TOTAL	%
	Applied concentration/dose, to be given in more than one unit.	0	0	0	0	0	0	2	2	17%	0	2	2	2	0	2	8	67%
	Doses should be clearly marked as “overload” or “non-overload”.	0	0	0	0	0	1	0	1	8%	NA	NA	NA	NA	NA	NA
	At least two different tests for each biological end point.	1	1	1	1	2	1	1	8	67%	0	0	1	1	1	1	4	33%
	Study should contain data on the dose–effect relationship of the acute toxic effects.	0	0	0	0	1	0	0	1	8%	1	1	0	1	1	1	5	42%
	Interference of the nanomaterials with the test system.	0	0	0	0	0	0	1	1	8%	2	0	0	0	0	1	3	25%
	Evaluation that contaminants or solvents not responsible for observed toxicity	0	0	0	0	1	0	1	2	17%	0	2	1	1	1	2	7	58%
	Are doses relevant to human exposures?	0	0	0	0	0	1	0	1	8%	0	0	0	1	0	0	1	8%
	Positive Control	0	2	0	0	2	2	2	8	67%	2	2	2	2	2	2	12	100%
	Negative Control	0	0	0	0	2	0	2	4	33%	2	0	0	1	2	2	7	58%
	Vehicle Control	0	0	0	0	2	2	2	6	50%	2	2	0	0	0	2	6	50%
	Study Design Score (out of 20/18)	1	3	1	1	10	7	11		28%	9	9	6	9	7	13		49%