Immunotoxicological effects induced by engineered nanomaterials

Engineered nanomaterials (ENM) are widely used in the industry as their unique characteristics improve competitiveness and potential for innovations in the different sectors of industry: It has been estimated that the market size of nanotechnological innovations will exceed 2 trillion euros in 2015. However, the toxicological hazard and risk assessment of different nanomaterials is far from complete. There is a concern that nanomaterials cause toxic outcomes, and more research efforts are put into hazard assessment of nanomaterials. However, the huge amount of differently modified nanomaterials poses a challenge for toxicologists who will have to develop new, quicker and cheaper, approaches for hazard and risk assessment to guarantee the human health. The human body is protected from foreign material by its immune system. The most common routes for foreign materials to enter the human body are via inhalation, digestion or dermal penetration, and these routes are protected by physical barrier. The physical barrier accompanied with phagocytosing cells are part of the innate immunity: Rapid and non-specific immune system. Phagocytosing cells scavenge foreign material in the body cavities and secrete signaling molecules to further activate other cells of immunity, such as T or B cells, to form a specific immune response. In this thesis, an immunotoxicological approach was used to compare effects of different types of ENM in the phagocytosing cells or in the disease model of atopic dermatitis. Studies performed with metal oxide nanoparticles and carbon nanotubes (CNT) showed that surface treatment or shape of nanomaterial modify their toxic properties in vitro. Mechanistical studies performed with CNT clearly demonstrated that long, rigid carbon nanotubes resemble asbestos fibers in their toxicity whereas other types of CNT showed less toxicity. In addition, the effects of either bulk-sized or nano-sized ZnO particles commonly used in cosmetics were compared in the mouse atopic dermatitis disease model. The results clearly showed that ZnO particles were able to suppress local inflammation, however, there was also an induction of systemic antibody levels. These outcomes were clearly higher if the mice skin had been treated with nano-ZnO shown also to penetrate into the deeper layers on mouse allergic skin. The results suggest that material size, shape and surface modifications are important parameters in their toxicity. Therefore the risk assessment of differently modified nanomaterials shall be performed separately despite the previously performed risk assessment of the bulk-sized form of the same material. These results also underline factors that should be taken into account in the planning of the future studies.Teollisesti tuotetut nanomateriaalit ovat laajassa käytössä eri toimialoilla, sillä niiden ainutlaatuiset ominaisuudet parantavat tuotteiden kilpailukykyä ja mahdollistavat niihin liittyviä innovaatioita: nanoteknologiaa hyödyntävien innovaatioiden markkinakoko on yli 2 biljoonaa euroa vuonna 2015. Nanomateriaalien vaarallisuuden tutkimus laahaa kuitenkin jäljessä, sillä tuhansia erilaisia nanomateriaaleja käytetään tuotannossa ilman tarkkaa tietoa niiden terveydelle haitallisista ominaisuuksista. Valtava määrä eri tavalla muunneltuja nanomateriaaleja asettaa haasteen kehittää uusia, nopeampia ja halvempia vaaranarviointimenetelmiä ihmisten terveyden turvaamiseksi. Immuunijärjestelmä on kehon puolustusjärjestelmä vieraita aineita vastaan. Yleisimmin vieraat materiaalit kulkeutuvat kehoon hengitysteitse, ruuansulatuskanavan tai ihon kautta, ja niissä onkin tehokas fyysinen suoja. Fyysinen suoja yhdessä syöjäsolujen kanssa muodostavat tärkeän osan synnynnäistä immuniteettia, nopeaa ja epäspesifistä tulehdusreaktiota. Syöjäsolut siivoavat kehon onkaloita vierasmateriaaleista ja erittävät viestinvälitysmolekyylejä, jotka aktivoivat muita tulehdusvasteen soluja muodostamaan spesifisen tulehdusvasteen. Väitöskirjassa vertailtiin erilaisien nanomateriaalien vaikutuksia syöjäsoluissa ja atooppisen ihottuman tautimallissa. Solumalleilla tehdyt tutkimukset näyttävät, että metallioksidien pintakäsittely ja hiilinanoputkien muoto vaikuttavat voimakkaasti niiden haitallisiin ominaisuuksiin. Mekanistinen solututkimus erilaisilla hiilinanoputkilla osoittaa, että ainoastaan pitkät ja jäykät hiilinanoputket muistuttivat vaaraominaisuuksiltaan asbestikuituja ehdottaen, että kaikki hiilinanoputket eivät ole yhtä haitallisia. Tutkimus kosmetiikassa käytettävien erikokoisten ZnO hiukkasten vaikutusta hiiren atooppisen ihottuman tautimallissa osoittaa, että ZnO hiukkaset alentavat paikallista tulehdusta ihossa, mutta aiheuttavat nousua veren vasta-ainetasoissa: Nanokokoiset ZnO hiukkaset tunkeutuivat syvemmälle ihoon ja niiden vaikutukset olivat suuremmat kuin mikrokokoisilla ZnO hiukkasilla. Väitöskirjassa osoitetaan, että hiukkasten koko, muoto ja pintakäsittely vaikuttavat voimakkaasti niiden vaaraominaisuuksiin. Tämä aiheuttaa sen, että eri tavoin muunneltujen nanokokoisten materiaalien aiheuttama terveysriski on arvioitava erikseen, huolimatta siitä, onko isomman hiukkaskoon riskinarviointi jo suoritettu. Tulokset auttavat myös ottamaan huomioon tekijöitä, jotka ovat tärkeitä suunniteltaessa ja toteutettaessa uusia toksisuustutkimuksia

Multimorbidity and overall comorbidity of sleep apnoea: a Finnish nationwide study

The prevalence of sleep apnoea is increasing globally; however, population-based studies have reported a wide variation of prevalence estimates, and data on incidence of clinically diagnosed sleep apnoea are scant. Data on the overall burden of comorbidities or multimorbidity in individuals with incident sleep apnoea are scarce, and the pathways to multimorbidity have only marginally been studied. To study the current epidemiology of sleep apnoea in Finland, overall burden of comorbidities, and multimorbidity profiles in individuals with incident sleep apnoea, we conducted a register-based, nationwide, retrospective study of data from January 2016 to December 2019. The prevalence of clinically diagnosed sleep apnoea was 3.7% in the Finnish adult population; 1-year incidence was 0.6%. Multimorbidity was present in 63% of individuals at the time of sleep apnoea diagnosis. Of those with incident sleep apnoea, 34% were heavily multimorbid (presenting with four or more comorbidities). The three most common chronic morbidities before sleep apnoea diagnosis were musculoskeletal disease, hypertension and cardiovascular disease. In multimorbid sleep apnoea patients, hypertension and metabolic diseases including obesity and diabetes, cardiovascular diseases, musculoskeletal diseases and dorsopathies, in different combinations, encompassed the most frequent disease pairs preceding a sleep apnoea diagnosis. Our study adds to the few population-based studies by introducing overall and detailed figures on the burden of comorbidities in sleep apnoea in a nationwide sample and provides up-to-date information on the occurrence of sleep apnoea as well as novel insights into multimorbidity in individuals with incident sleep apnoea

Hiilinanoputkien aiheuttamien terveysvaikutusten karakterisointi systeemitoksikologian avulla

Hiilinanoputket ovat monikäyttöisiä teollisia nanomateriaaleja, jotka soveltuvat lukuisiin teollisuusaloihin. Hiilinanoputkien asbestin kaltainen muoto on kuitenkin nostanut esiin kysymyksiä niiden turvallisuudesta.1

A call for action: Improve reporting of research studies to increase the scientific basis for regulatory decision-making

Publisher's version (útgefin grein)This is a call for action to scientific journals to introduce reporting requirements for toxicity and ecotoxicity studies. Such reporting requirements will support the use of peer‐reviewed research studies in regulatory decision‐making. Moreover, this could improve the reliability and reproducibility of published studies in general and make better use of the resources spent in research.Nordic Council of Minister

Evaluation of the health effects of carbon nanotubes

Recent studies have suggested that some types of multiwalled carbon nanotubes (MWCNTs) have similar effects as asbestos. This report shows that rigid, long and needle-like MWCNTs induce inflammation and DNA damage in the lungs and in cultured cells, while flexible, long and tangled MWCNTs do not. It appears that the rigidity of MWCNTs is a key feature in triggering a specific inflammatory reaction and in causing cellular alterations involved in cancer formation. These results provide new information on the adverse effects of MWCNTs and are useful in assessing which forms of MWCNTs require regulatory attention and special safety measures in occupational settings

Maternal verbal responsiveness and directiveness:consistency, stability, and relations to child early linguistic development

Abstract Maternal responsive and directive speech to children at ages 0;10 and 2;0 was investigated by applying a procedure first introduced by Flynn and Masur (2007) to a new language community (Finnish). The issues examined were consistency and stability over time, and also the role of responsiveness and directiveness in child linguistic development at 1;0 and 2;6. The measures of maternal speech from each age were used to predict the results of the subsequent linguistic assessment. Negative correlations between responsive and directive utterances were found at both ages. The frequencies of responsive utterances and supportive directives increased over time. Responsiveness was positively, and intrusive directiveness negatively, related to child early comprehensive skills and the use of symbolic actions and communicative gestures. By contrast, no relations were found between responsiveness and directiveness and children’s later linguistic capacities