Table Info

Table 3.

In vivo toxicity studies for different NPs and relevant European legislation

NP	Testing material	Toxicity	Purpose in food	Reference	European legislation applicable to NMs in food
Ag NPs	Nitrifying bacteria, human colon carcinoma cells, human umbilical vein, endothelial cells	Oxidative stress is associated to decrease viability, inhibition of mitochondrial activity, and initiation of apoptosis	Food contact, packaging materials, and food additives	[96, 97]	Regulation (EC) No 1333/2008: for food additives; Regulation (EU) No 528/2012: biocides
TiO₂ NPs	Anaerobic gut bacteria, human gastric epithelial cells, human peripheral blood, mononuclear cells	Potentially carcinogenic, DNA damage, oxidative stress, chromatin condensation, and eventual cell death via apoptosis	Food additive (E171 or INS171)	[98–100]	Regulation (EC) No 1334/2008: on food flavourings
ZnO NPs	Human pulmonary adenocarcinoma cell, male IRC mice	Oxidative stress, mitochondrial dysfunction	Food packaging	[101, 102]	Regulation (EC) No 2283/2015: on novel foods
SiO₂ NPs	Sprague-Dawley rats, human bronchoalveolar carcinoma cells	Fibrotic lung disease, lung cancer, emphysema and pulmonary tuberculosis, autoimmune disease, systemic sclerosis, rheumatoid arthritis, lupus, and chronic renal disease	Packaging additive (E551)	[103–105]	Regulation (EC) No 450/2009^*: active and intelligent materials intended to come into contact with food
NOMs to encapsulate bioactive compounds	Cells obtained from liver tissue of patient with hepatocellular carcinoma	Prevent cell division, hinder cell proliferation, damage DNA and biological systems, eventually lead to cell death; raising concerns over acute and chronic toxicity and related problems	Food encapsulation, food processing, food supplement, active material intended to meet contact to food	[36, 106, 107]	Regulation (EC) No 1925/2006: for fortified foods
Fe₂O₃	Blood lymphocytes from healthy humans	Generation of ROS, changes in function of vital organs, in cellular morphology, and induction of apoptosis	Food additive, enzyme immobilization	[108]	Regulation (EU) No 10/2011^*: on plastic materials and articles intended to come into contact with food; Regulation (EC) No 1332/2008: on food enzyme

EC: European Commission; EU: European Union; ^* Although both regulations are not directly applicable to NMs there is a reference to “New technologies that engineer substances in particle sizes that exhibit chemical and physical properties significantly different from those at a larger scale, for example NPs, should be assessed on a case-by-case basis as regards their risk until more information is known about such new technology. Therefore, they should not be covered by the functional barrier concept.”

Declarations

Author contributions

NV: Investigation, Data curation, Visualization, Writing––original draft. MJV: Conceptualization, Methodology, Project administration, Writing––review & editing. ÁR: Conceptualization, Resources, Funding acquisition, Supervision, Writing––review & editing.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

The work is funded by the Spanish Ministry of Science and Innovation (MICINN) Grants [PID2019-104381GB-I00]; Regional Government of Castilla-La Mancha (JCCM) Grants [SBPLY/17/180501/000188].

Copyright

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