Phenolic compounds carvacrol, thymol, eugenol, and vanillin are four of the most thoroughly investigated essential oil components given their relevant biological properties. These compounds are generally considered safe for consumption and have been used in a wide range of food and non-food applications. Significant biological properties, including antimicrobial, antioxidant, analgesic, anti-inflammatory, anti-mutagenic, or anti-carcinogenic activity, have been described for these components. They are versatile molecules with wide-ranging potential applications whose use may substantially increase in forthcoming years. However, some in vitro and in vivo studies, and several case reports, have indicated that carvacrol, thymol, and eugenol may have potential toxicological effects. Oxidative stress has been described as the main mechanism underlying their cytotoxic behavior, and mutagenic and genotoxic effects have been occasionally observed. In vivo studies show adverse effects after acute and prolonged carvacrol and thymol exposure in mice, rats, and rabbits, and eugenol has caused pulmonary and renal damage in exposed frogs. In humans, exposure to these three compounds may cause different adverse reactions, including skin irritation, inflammation, ulcer formation, dermatitis, or slow healing. Toxicological vanillin effects have been less reported, although reduced cell viability after exposure to high concentrations has been described. In this context, the possible risks deriving from increased exposure to these components for human health and the environment should be thoroughly revised. Graphical Abstract

The toxicological properties of different silica particles functionalised with essential oil components (EOCs) were herein assessed using the in vivo model C. elegans. In particular, the effects of the acute and long-term exposure to three silica particle types (SAS, MCM-41 micro, MCM-41 nano), either bare or functionalised with eugenol or vanillin, were evaluated on different biological parameters of nematodes. Acute exposure to the different particles did not reduce nematodes survival, brood growth or locomotion, but reproduction was impaired by all the materials, except for vanillin-functionalised MCM-41 nano. Moreover, long-term exposure to particles led to strongly inhibited nematodes growth and reproduction. The eugenol-functionalised particles exhibited higher functionalisation yields and had the strongest effects during acute and long-term exposures. Overall, the vanillin-functionalised particles displayed milder acute toxic effects on reproduction than pristine materials, but severer toxicological responses for the 96-hour exposure assays. Our findings suggest that the EOC type anchored to silica surfaces and functionalisation yield are crucial for determining the toxicological effects of particles on C. elegans. The results obtained with this alternative in vivo model can help to anticipate potential toxic responses to these new materials for human health and the environment.