7.9 ± Gavage: 62.5, 125, No effects on standard 0.95nm 42d (M) 250 250 parameters in a rats 52d (F) Hong et al. combined 2014 reproductive/ developmental tox study. 20 nm Gavage: 500 - Reduction in food intake (18%) and 81 d body weight gain Ebabe Elle (20%), total & ↑ et al. 2013 LDL-cholesterol, ↑ liver inflammatory markers. 56 ± F344 rats Gavage: 30, 125, Clinical chemistry & liver histology 1.46nm 90 d 500 30 Kim et al. indicative of liver 2010 effects at mid- and high- dose. 19.0 ± 4.6 Gavage: 257.6, NOAEL: serum ALP & ↑ Ca, lymphocyte nm 91 d 515.3 and 515.3 Yu et al. infiltration into liver rats 1030.5 2015 & kidney at high dose Humans Diet 0.007 NOEL: No effects: - Metabolic mixed oral 0.007 markers, product syringe): 14d (only dose haematology, tested) (25-40 nm) urinalysis - Pulmonary reactive oxygen Munger et species or al. 2013, Smock et cytokines - Platelet al. 2014, aggregation Munger et - Sputum induction al. 2015 - Serum P450 enzyme activity - Complete physical examination, including chest & abdomen MRI Commercial Weanling Diet (feed): ~ 0.6, 0.9 NOAEL: Feed intake highest in 0.9 colloidal pigs 35d 0.9 mg/kg/d product (60-100 Fondevila No effects: nm) - Growth et al. 2009 - Dietary digestibility - Intestinal histology 14, 36 nm Wistar rats Diet (drinking 157.4 - Mild changes to haematology & water): et clinical chemistry. 55 d al. 2013
mixed 7.9 ± 0.95nm rats Gavage: 42d (M) 52d (F) 62.5, 125, 250 250 No effects on standard parameters in a combined reproductive/ developmental tox study. Hong et al. 2014 20 nm Gavage: 81 d 500 - Reduction in food intake (18%) and body weight gain (20%), ↑ total & LDL-cholesterol, ↑ liver inflammatory markers. Ebabe Elle et al. 2013 56 ± 1.46nm F344 rats Gavage: 90 d 30, 125, 500 30 Clinical chemistry & liver histology indicative of liver effects at mid- and high- dose. Kim et al. 2010 19.0 ± 4.6 nm rats Gavage: 91 d 257.6, 515.3 and 1030.5 NOAEL: 515.3 ↑ serum ALP & Ca, lymphocyte infiltration into liver & kidney at high dose Yu et al. 2015 product (25-40 nm) Humans Diet oral syringe): 14d 0.007 NOEL: 0.007 (only dose tested) No effects: - Metabolic markers, haematology, urinalysis - Pulmonary reactive oxygen species or cytokines - Platelet aggregation - Sputum induction - Serum P450 enzyme activity - Complete physical examination, including chest & abdomen MRI Munger et al. 2013, Smock et al. 2014, Munger et al. 2015 Commercial colloidal product (60-100 nm) Weanling pigs Diet (feed): 35d ~ 0.6, 0.9 NOAEL: 0.9 Feed intake highest in 0.9 mg/kg/d No effects: - Growth - Dietary digestibility - Intestinal histology Fondevila et al. 2009 14, 36 nm Wistar rats Diet (drinking water): 55 d 157.4 - Mild changes to haematology & clinical chemistry. et al. 2013
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