TABLE 3.

Toxicological adverse effects of Zinc oxide nanoparticles (ZnO‐NPs) in some animal species

Laboratory animal	ZnO‐NPs dose	Toxicological adverse effect	References
Lambs	20 mg/kg body weight	‐Changed normal liver and kidney function tests ‐Altered normal liver and kidney histopathology	Najafzadeh et al. (2013)
Mice	50 and 300 mg/kg body weight	‐Acted as testicular toxicant that affected spermatogenesis and testicular histopathology	Talebi et al. (2013)
	500 mg/kg body weight	‐Decreased body weight, increased weights of the pancreas, brain, and lungs as well as serum alanine aminotransferase, enhanced expression of genes related to Zn metabolism, and accumulated significant amount of Zn in the liver, pancreas, kidneys, and bones	Wang et al. (2016)
	50 mg/ml	‐Induced marked changes in 8‐OHdG formation ‐Reduced viability of L929 cells in vitro	Syama et al. (2013)
	100 μg/ml	‐Inhibited DNA repair, killed macrophage, and inhibited superoxide dismutase, catalase, and reactive oxygen species	Pati et al. (2016)
	500 mg/kg body weight	‐Induced DNA damage in the bone marrow and blood cells, produced high inflammation and destruction of liver, lungs, and kidneys, and reduced body weight and induced mortality	Pati et al. (2016)
	10, 20, and 30 μg/ml	‐Caused in vitro cytotoxicity in ovarian germ cells through enhancing reactive oxygen species generation, significant increasing in the expression of pre‐meiotic germ cells markers, and decreasing in meiotic and post‐meiotic markers	Saber et al. (2021)
	25 mg/kg body weight	‐Decreased mitochondrial membrane potential, induced reactive oxygen species generation, and apoptosis ‐In bone marrow cells, reduced mitochondrial membrane potential, increased oxidative stress, arrested G0/G1 cell cycle, chromosome aberrations, and micronuclei formation ‐In the liver cells, caused DNA damage, induced oxidative stress, and decreased the inhibition of antioxidant enzymes	Ghosh et al. (2016)
Rats	536.8 mg/kg body weight	‐Decreased body weight and showed significant alterations in haematological tests especially those related to anaemia with various degrees of pancreatitis	Seok et al. (2013)
	30 mg/kg body weight	‐Increased the formation of mitotic figures in the liver with multifocal acute injuries and dark brown pigment in the lungs	Choi et al. (2015)
	500 mg/kg body weight	‐Caused pathological changes including acinar cell apoptosis and ductular hyperplasia, periductular lymphoid cell infiltration, and an increased number of regenerative acinar cells in the pancreas with inflammation and oedema in the stomach mucosa, excessive salivation, and retinal atrophy of the eye ‐Decreased haematocrit, mean cell volume, mean cell haemoglobin and mean cell haemoglobin concentration ‐Decreased total protein and albumin	Park et al. (2014)
	200 mg/kg body weight	‐Increased total oxidant status and decreased total antioxidant capacity significantly ‐Impacted on sperm quality and quantity ‐Induced histopathological changes in liver and kidney tissues	Abbasalipourkabir et al. (2015)
	100 mg/kg body weight	‐Significantly increased MDA and decreased catalase and superoxide dismutase activities in the brain ‐Induced brain histological changes that caused behavioural changes	Rahdar et al. (2020)
	4.0 mg/kg body weight	‐Attenuated the spatial learning and memory capacity through alteration in synaptic plasticity	Han et al. (2011)
	500 mg/kg body weight	‐Reduced number of born‐alive pups, decreased body weights of pups and increased fetal resorption	Jo et al. (2013)
	200 mg/kg body weight	‐Increased in the corpus luteum, follicular cysts, inflammatory cell infiltration, and fibrosis ‐Induced epithelial destruction and hyperplasia of endometrial glands ‐Decreased the serum concentrations of reproductive hormone, oestrogen, and progesterone	Mohammad et al. (2019)
Fish	1000 mg/kg feed	‐Induced accumulation of Zn in the gill, intestine, and liver of rainbow trout fish ‐Developed oxidative stress and impaired the metabolism	Connolly et al. (2016)
	2.16 g/aquarium	‐Accumulated high amount of Zn in the liver and brain of fish, induced reactive oxygen species with a greater challenge to the antioxidant defense system of goldfish	Yin et al. (2017)
	500 mg/kg feed	‐Disturbed the homeostasis and proteins of the haematological and the immune system of juvenile common carp	Chupani et al. (2017)
	10 mg/L	‐Induced epicardial and yolk‐sac oedema, Influenced inflammation and the immune system‐related genes in the Zebrafish embryos	Choi et al. (2016)
	760 μg/L	‐Increased oxidative stress, behavioural changes, and genotoxic effects in grass carp	Estrela et al. (2021)