Purpose The widespread use of nanoparticles (NPs) in industrial and biomedical applications has prompted growing concern regarding their potential toxicity and impact on human health. This study therefore investigated the subchronic, systemic oral toxicity and no-observed-adverse-effect level (NOAEL) of 20 nm, negatively charged zinc oxide (ZnO SM20(−) ) NPs in Sprague Dawley rats for 90 days. Methods The high-dose NP level was set at 500 mg/kg of bodyweight, and the mid- and low-dose levels were set at 250 and 125 mg/kg, respectively. The rats were observed during a 14-day recovery period after the last NP administration for the persistence or reduction of any adverse effects. Toxicokinetic and distribution studies were also conducted to determine the systemic distribution of the NPs. Results No rats died during the test period. However, ZnO SM20(−) NPs (500 mg/kg) induced changes in the levels of anemia-related factors, prompted acinar cell apoptosis and ductular hyperplasia, stimulated periductular lymphoid cell infiltration and excessive salivation, and increased the numbers of regenerative acinar cells in the pancreas. In addition, stomach lesions were seen at 125, 250, and 500 mg/kg, and retinal atrophy was observed at 250 and 500 mg/kg. The Zn concentration was dose-dependently increased in the liver, kidney, intestines, and plasma, but not in other organs investigated. Conclusion A ZnO SM20(−) NP NOAEL could not be established from the current results, but the lowest-observed-adverse-effect level was 125 mg/kg. Furthermore, the NPs were associated with a number of undesirable systemic actions. Thus, their use in humans must be approached with caution.

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Aims:The effect of EVCO, containing about 57.48% triglycerides, 26.88% diglycerides, 1.51% monoglycerides and 14.13% free fatty acids, against clinical mastitis pathogens, bought from American Type Cultures Collection (ATCC), was investigated. The present study aims to determine the efficacy of EVCO against three potent mastitis causal agents, namely S. aureus (ATCC 31885), S. agalactiae (ATCC 12927) and S. dysagalactiae (ATCC 27957). Methodology and results:The In-vitro study showed that EVCO can act as a potent agent to inhibit the growth of Staphylococcus aureus (ATCC 31885), Streptococcus agalactiae (ATCC 12927) and Streptococcus dysgalactiae (ATCC 27957). A time kill study showed that EVCO at 2.5% is able to kill both Streptococcus spp. (ATCC 12927 & ATCC 27957) in 5 min of incubation time. Among three mastitis pathogens, S. aureus was the most difficult to eradicate and required at least 5% EVCO for 100% inhibition after 30 min of treatment. The In-vivo study on mastitis-induced lactating cows showed the amount of EVCO introduced into the infected mammary gland was considered over dosage; 50% concentration of EVCO was over dosage, even though it reduced the growth of pathogens from 10 4 to 10 0 . The acidic characteristics of EVCO caused the protein in milk to clot and the udders to swell, even after several days of treatment. Conclusion, significance and impact study: The EVCO had shown its antimicrobial efficacy against three potent mastitis causal agents. The amount of EVCO used to treat mastitis-induced cows and the number of treatments applied needed to be reduced to avoid the milk clotting and udders swelling as a result of the acidic characteristics of EVCO.

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