Biopersistence and translocation to extrapulmonary organs of titanium dioxide nanoparticles after subacute inhalation exposure to aerosol in adult and elderly rats

Gaté, Laurent; Disdier, Clémence; Cosnier, Frédéric; Gagnaire, François; Devoy, Jérôme; Saba, Wadad; Brun, Émilie; Chalansonnet, Monique; Mabondzo, Aloı̈se

doi:10.1016/j.toxlet.2016.11.009

Cited by 53 publications

(37 citation statements)

References 52 publications

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“…NR8383 cells are relevant due to their immune functions and their ability of contact with foreign bodies (Hussain et al 2012). In addition, experimental rat or mouse models have been validated by many studies as toxicity paradigm of airways (Ganguly et al 2017;Gaté et al 2017;Wallin et al 2017). Moreover, in order to respect the three "R" of the ethical approach described by Russel and Burch in 1959 for reducing, replacing, and refining the use of animal testing, it seems important to develop in vitro models (Tannenbaum and Bennett 2015).…”

Section: Introductionmentioning

confidence: 99%

Protein and lipid homeostasis altered in rat macrophages after exposure to metallic oxide nanoparticles

et al. 2019

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Metal oxide nanoparticles (NPs), such as ZnO, ZnFe 2 O 4 , and Fe 2 O 3 , are widely used in industry. However, little is known about the cellular pathways involved in their potential toxicity. Here, we particularly investigated the key molecular pathways that are switched on after exposure to sub-toxic doses of ZnO, ZnFe 2 O 4 , and Fe 2 O 3 in the in vitro rat alveolar macrophages (NR8383). As in our model, the calculated IC 50 were respectively 16, 68, and more than 200 μg/mL for ZnO, ZnFe 2 O 4 , and Fe 2 O 3 ; global gene and protein expression profiles were only analyzed after exposure to ZnO and ZnFe 2 O 4 NPs. Using a rat genome microarray technology, we found that 985 and 1209 genes were significantly differentially expressed in NR8383 upon 4 h exposure to ¼ IC 50 of ZnO and ZnFe 2 O 4 NPs, respectively. It is noteworthy that metallothioneins were overexpressed genes following exposure to both NPs. Moreover, Ingenuity Pathway Analysis revealed that the top canonical pathway disturbed in NR8383 exposed to ZnO and ZnFe 2 O 4 NPs was eIF2 signaling involved in protein homeostasis. Quantitative mass spectrometry approach performed from both NR8383 cell extracts and culture supernatant indicated that 348 and 795 proteins were differentially expressed upon 24 h exposure to ¼ IC 50 of ZnO and ZnFe 2 O 4 NPs, respectively. Bioinformatics analysis revealed that the top canonical pathways disturbed in NR8383 were involved in protein homeostasis and cholesterol biosynthesis for both exposure conditions. While VEGF signaling was specific to ZnO exposure, iron homeostasis signaling pathway was specific to ZnFe 2 O 4 NPs. Overall, the study provides resource of transcriptional and proteomic markers of response to ZnO and ZnFe 2 O 4 NP-induced toxicity through combined transcriptomics, proteomics, and bioinformatics approaches.

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Section: Introductionmentioning

confidence: 99%

Protein and lipid homeostasis altered in rat macrophages after exposure to metallic oxide nanoparticles

et al. 2019

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“…In several studies, nanoparticles were detected in the liver, heart, kidneys, pancreas, spleen, brain or blood after inhalation and translocation through the lung barrier. 31,[35][36][37][38] Nevertheless, this phenomenon does not appear to be predominant as the translocation rate is slower than the lung clearance rate. 39 In conclusion, inhaled nanoparticles can be found in the lungs.…”

Section: Inhalation Exposurementioning

confidence: 99%

Safety of titanium dioxide nanoparticles in cosmetics

Dréno¹,

Chuberre

et al. 2019

Acad Dermatol Venereol

176

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Titanium dioxide (TiO2) is widely used in a variety of products including cosmetics. TiO2 in its nanoparticle form (nano‐TiO2) is now the only form used as an ultraviolet (UV) filter in sunscreens, but also in some day creams, foundations and lip balms. While its efficacy as a UV filter is proven in the prevention of skin cancers and sunburns, some concerns have been raised about its safety. Indeed, considering its small size, nano‐TiO2 is suspected to penetrate dermal, respiratory or gastrointestinal barriers, disseminate in the body and therefore constitute a potential risk to the consumer. At the skin level, most studies performed in humans or animals showed that nano‐TiO2 did not penetrate beyond the outer layers of stratum corneum to viable cells and did not reach the general circulation, either in healthy or in compromised skin. The Scientific Committee on Consumer Safety (SCCS) considers nano‐TiO2 as a non‐sensitizer and as mild‐ or non‐irritant to skin and concludes in no evidence of carcinogenicity (supported by the European Chemicals Agency), mutagenicity or reproductive toxicity after dermal exposure to nano‐TiO2. According to the SCCS, nano‐TiO2 from sunscreens does not present any health risk when applied on the skin at a concentration up to 25%. However, the SCCS does not recommend the use of nano‐TiO2 in formulations that may lead to exposure of the consumer's lungs by inhalation (sprayable products and powders). Indeed, even if human data are sparse and inconsistent, lung inflammation was reported in animals. In 2016, the EU Cosmetic Regulation made nano‐TiO2 as an authorized UV filter, except in products that could lead to exposure of the lungs. After oral exposure, nano‐TiO2 absorption and toxicity are limited. The incidental oral exposure to nano‐TiO2 contained in lip balms is thus not expected to induce adverse health effects.

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“…A number of animal inhalation studies demonstrated that the exposure to carbon nanotubes induced lung cancers . In addition, translocation and accumulation of inhaled nanoparticles in other organs such as brain, kidneys, and liver have been reported . Considering the situation, the notification titled “Tentative preventive measure to avoid the exposure of nanomaterials in the manufactured nanomaterial‐handling workplace” was imposed upon employers and workers of the nanomaterial‐related factories by the Ministry of Health, Labour and Welfare.…”

Section: Nanomaterials and Its Occupational Health Managementmentioning

confidence: 99%

“…60,61 In addition, translocation and accumulation of inhaled nanoparticles in other organs such as brain, kidneys, and liver have been reported. [62][63][64] Considering the situation, the notification titled "Tentative preventive measure to avoid the exposure of nanomaterials in the manufactured nanomaterial-handling workplace" was imposed upon employers and workers of the nanomaterial-related factories by the Ministry of Health, Labour and Welfare. Because the harmfulness of nanomaterials is not clearly identified, the management procedures are implemented as a precautionary approach.…”

Section: Its Occupational Health Managementmentioning

confidence: 99%

Update of occupational lung disease

Suganuma

Natori

Kurosawa

et al. 2019

Journal of Occupational Health

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Objective Occupational Lung Disease is an oldest but still a biggest problem in occupational health. Methods Steering Committee members of the Japan Society for Occupational Health (JSOH) Occupational Lung Disease Study Group selected and summarized current topics on occupational lung diseases based on expert opinion, as informed by governmental regulation, public health concerns, and frequently discussed in related academic conferences. Results The topics included in this review are professional education in medical screening skills, 2014 update of Helsinki Criteria, respiratory diseases found in the earthquake and tsunami affected regions, newly recognized occupational lung diseases, and potential respiratory health hazards. Discussions Although occupational lung diseases seem to stay as one of the major concerns in occupational health, screening tools and control measures are standardized for the better prevention of the diseases. As this health problem usually occurs in where the most actively economically developing area is, the patients tend to increase in emerging economic powers with huge population.

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Biopersistence and translocation to extrapulmonary organs of titanium dioxide nanoparticles after subacute inhalation exposure to aerosol in adult and elderly rats

Cited by 53 publications

References 52 publications

Protein and lipid homeostasis altered in rat macrophages after exposure to metallic oxide nanoparticles

Protein and lipid homeostasis altered in rat macrophages after exposure to metallic oxide nanoparticles

Safety of titanium dioxide nanoparticles in cosmetics

Update of occupational lung disease

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