Globally 113 702 confirmed (4125 new) 4012 deaths (203 new) China 80 924 confirmed (20 new) 3140 deaths (17 new) Outside of China 32 778 confirmed (4105 new) 872 deaths (186 new) 109 countries/territories/ areas (5 new) WHO RISK ASSESSMENT China Very High Regional Level Very High Global Level Very High HIGHLIGHTS • 5 new countries/territories/areas (Brunei Darussalam, Mongolia, Cyprus, Guernsey and Panama) have reported cases of COVID-19 in the past 24 hours. 1 https://www.iatatravelcentre.com/international-travel-document-news/1580226297.htm 2 https://pandemic.internationalsos.com/2019-ncov/ncov-travel-restrictions-flight-operations-and-screening 3 https://www.iata.org/en/pressroom/pr/2020-03-02-01/ 4 https://www.who.int/ith/2019-nCoV_advice_for_international_traffic-rev/en/

Background: Engineered nanomaterials (ENMs) have potential benefits, but they also present safety concerns for human health. Interlaboratory studies in rodents using standardized protocols are needed to assess ENM toxicity.Methods: Four laboratories evaluated lung responses in C57BL/6 mice to ENMs delivered by oropharyngeal aspiration (OPA), and three labs evaluated Sprague-Dawley (SD) or Fisher 344 (F344) rats following intratracheal instillation (IT). ENMs tested included three forms of titanium dioxide (TiO2) [anatase/rutile spheres (TiO2-P25), anatase spheres (TiO2-A), and anatase nanobelts (TiO2-NBs)] and three forms of multiwalled carbon nanotubes (MWCNTs) [original (O), purified (P), and carboxylic acid “functionalized” (F)]. One day after treatment, bronchoalveolar lavage fluid was collected to determine differential cell counts, lactate dehydrogenase (LDH), and protein. Lungs were fixed for histopathology. Responses were also examined at 7 days (TiO2 forms) and 21 days (MWCNTs) after treatment.Results: TiO2-A, TiO2-P25, and TiO2-NB caused significant neutrophilia in mice at 1 day in three of four labs. TiO2-NB caused neutrophilia in rats at 1 day in two of three labs, and TiO2-P25 and TiO2-A had no significant effect in any of the labs. Inflammation induced by TiO2 in mice and rats resolved by day 7. All MWCNT types caused neutrophilia at 1 day in three of four mouse labs and in all rat labs. Three of four labs observed similar histopathology to O-MWCNTs and TiO2-NBs in mice.Conclusions: ENMs produced similar patterns of neutrophilia and pathology in rats and mice. Although interlaboratory variability was found in the degree of neutrophilia caused by the three types of TiO2 nanoparticles, similar findings of relative potency for the three types of MWCNTs were found across all laboratories, thus providing greater confidence in these interlaboratory comparisons.

The growing use of silver nanoparticles (AgNPs) in consumer products raises concerns about potential health effects. This study investigated the persistence and clearance of 2 different size AgNPs (20 and 110 nm) delivered to rats by single nose-only aerosol exposures (6 h) of 7.2 and 5.4 mg/m(3), respectively. Rat lung tissue was assessed for silver accumulations using inductively-coupled plasma mass spectrometry (ICP-MS), autometallography, and enhanced dark field microscopy. Involvement of tissue macrophages was assessed by scoring of silver staining in bronchoalveolar lavage fluid (BALF). Silver was abundant in most macrophages at 1 day post-exposure. The group exposed to 20 nm AgNP had the greatest number of silver positive BALF macrophages at 56 days post-exposure. While there was a significant decrease in the amount of silver in lung tissue at 56 days post-exposure compared with 1 day following exposure, at least 33% of the initial delivered dose was still present for both AgNPs. Regardless of particle size, silver was predominantly localized within the terminal bronchial/alveolar duct junction region of the lung associated with extracellular matrix and within epithelial cells. Inhalation of both 20 and 110 nm AgNPs resulted in a persistence of silver in the lung at 56 days post-exposure and local deposition as well as accumulation of silver at the terminal bronchiole alveolar duct junction. Further the smaller particles, 20 nm AgNP, produced a greater silver burden in BALF macrophages as well as greater persistence of silver positive macrophages at later timepoints (21 and 56 days).

Inhaled multiwalled carbon nanotubes (MWCNTs) may cause adverse pulmonary responses due to their nanoscale, fibrous morphology and/or biopersistance. This study tested multiple factors (dose, time, physicochemical characteristics, and administration method) shown to affect MWCNT toxicity with the hypothesis that these factors will influence significantly different responses upon MWCNT exposure. The study is unique in that (1) multiple administration methods were tested using particles from the same stock; (2) bulk MWCNT formulations had few differences (metal content, surface area/functionalization); and (3) MWCNT retention was quantified using a specialized approach for measuring unlabeled MWCNTs in rodent lungs. Male Sprague–Dawley rats were exposed to original (O), purified (P), and carboxylic acid functionalized (F) MWCNTs via intratracheal instillation and inhalation. Blood, bronchoalveolar lavage fluid (BALF), and lung tissues were collected at postexposure days 1 and 21 for quantifying biological responses and MWCNTs in lung tissues by programmed thermal analysis. At day 1, MWCNT instillation produced significant BALF neutrophilia and MWCNT-positive macrophages. Instilled O- and P-MWCNTs produced significant inflammation in lung tissues, which resolved by day 21 despite MWCNT retention. MWCNT inhalation produced no BALF neutrophilia and no significant histopathology past day 1. However, on days 1 and 21 postinhalation of nebulized MWCNTs, significantly increased numbers of MWCNT-positive macrophages were observed in BALF. Results suggest (1) MWCNTs produce transient inflammation if any despite persistence in the lungs; (2) instilled O-MWCNTs cause more inflammation than P- or F-MWCNTs; and (3) MWCNT suspension media produce strikingly different effects on physicochemical particle characteristics and pulmonary responses.

BackgroundSilver nanowires (Ag NWs) are increasingly being used to produce touchscreens for smart phones and computers. When applied in a thin film over a plastic substrate, Ag NWs create a transparent, highly-conductive network of fibers enabling the touch interface between consumers and their electronics. Large-scale application methods utilize techniques whereby Ag NW suspensions are deposited onto substrates via droplets. Aerosolized droplets increase risk of occupational Ag NW exposure. Currently, there are few published studies on Ag NW exposure-related health effects. Concerns have risen about the potential for greater toxicity from exposure to high-aspect ratio nanomaterials compared to their non-fibrous counterparts. This study examines whether Ag NWs of varying lengths affect biological responses and silver distribution within the lungs at different time-points.MethodsTwo different sizes of Ag NWs (2 μm [S-Ag NWs] and 20 μm [L-Ag NWs]) were tested. Male, Sprague-Dawley rats were intratracheally instilled with Ag NWs (0, 0.1, 0.5, or 1.0 mg/kg). Broncho-alveolar lavage fluid (BALF) and lung tissues were obtained at 1, 7, and 21 days post exposure for analysis of BAL total cells, cell differentials, and total protein as well as tissue pathology and silver distribution.Results and conclusionsThe two highest doses produced significant increases in BAL endpoints. At Day 1, Ag NWs increased total cells, inflammatory polymorphonuclear cells (PMNs), and total protein. PMNs persisted for both Ag NW types at Day 7, though not significantly so, and by Day 21, PMNs appeared in line with sham control values. Striking histopathological features associated with Ag NWs included 1) a strong influx of eosinophils at Days 1 and 7; and 2) formation of Langhans and foreign body giant cells at Days 7 and 21. Epithelial sloughing in the terminal bronchioles (TB) and cellular exudate in alveolar regions were also common. By Day 21, Ag NWs were primarily enclosed in granulomas or surrounded by numerous macrophages in the TB-alveolar duct junction. These findings suggest short and long Ag NWs produce pulmonary toxicity; thus, further research into exposure-related health effects and possible exposure scenarios are necessary to ensure human safety as Ag NW demand increases.Electronic supplementary materialThe online version of this article (doi:10.1186/s12989-014-0052-6) contains supplementary material, which is available to authorized users.

TiO2 is one of the most widely used nanomaterials, valued for its highly refractive, photocatalytic and pigmenting properties. TiO2 is also classified by the International Agency for Research on Cancer (IARC) as a possible human carcinogen. The objectives of this study were to establish a lowest observed effect level (LOEL) for nano-scale TiO2, determine TiO2 uptake in the lungs, and estimate toxicity based on physico-chemical properties and retention in the lungs. In vivo lung toxicity of nano-scale TiO2 using varying forms of well-characterized, highly-dispersed TiO2 was assessed. Anatase/rutile P25 spheres (TiO2-P25), pure anatase spheres (TiO2-A), and anatase nanobelts (TiO2-NB) were tested. To determine the effects of dose and particle characteristics, male Sprague-Dawley rats were given TiO2 (0, 20, 70, or 200 µg) via intratracheal instillation. Broncho-alveolar lavage fluid (BALF) and lung tissue were obtained for analysis 1 and 7 days post exposure. Despite abundant TiO2 inclusions in all exposed animals, only TiO2-NB elicited any significant degree of inflammation seen in BALF at the 1-day time-point. This inflammation resolved by 7 days; although, TiO2 particles had not cleared from alveolar macrophages recovered from the lung. Histological examination showed TiO2-NB caused cellular changes at day 1 which were still evident at day 7. We conclude TiO2-NB is the most inflammatory with a lowest observable effect level of 200 µg at 1 day post instillation.

3-D anatomic evidence of intraosseous arterial distribution of the femoral head and the high frequency with which the inferior retinacular arteries remained patent after femoral neck fracture lead us to consider the necessity of drilling and placing internal implants closer to the central region of the femoral head during surgery. Future controlled studies might evaluate this proposition.

Background:Silver nanoparticles (AgNP) are present in personal, commercial, and industrial products, which are often aerosolized. Current understanding of the deposition, translocation, and health-related impacts of AgNP inhalation is limited.Objectives:We determined a) the deposition and retention of inhaled Ag in the nasal cavity from nose-only exposure; b) the timing for Ag translocation to and retention/clearance in the olfactory bulb (OB); and c) whether the presence of Ag in the OB affects microglial activity.Methods:Male Sprague-Dawley rats were exposed nose-only to citrate-buffered 20- or 110-nm AgNP (C20 or C110, respectively) or citrate buffer alone for 6 hr. The nasal cavity and OB were examined for the presence of Ag and for biological responses up to 56 days post-exposure (8 weeks).Results:The highest nasal Ag deposition was observed on Day 0 for both AgNP sizes. Inhalation of aerosolized C20 resulted in rapid translocation of Ag to the OB and in microglial activation at Days 0, 1, and 7. In contrast, inhalation of C110 resulted in a gradual but progressive transport of Ag to and retention in the OB, with a trend for microglial activation to variably be above control.Conclusions:The results of this study show that after rats experienced a 6-hr inhalation exposure to 20- and 110-nm AgNP at a single point in time, Ag deposition in the nose, the rate of translocation to the brain, and subsequent microglial activation in the OB differed depending on AgNP size and time since exposure.Citation:Patchin ES, Anderson DS, Silva RM, Uyeminami DL, Scott GM, Guo T, Van Winkle LS, Pinkerton KE. 2016. Size-dependent deposition, translocation, and microglial activation of inhaled silver nanoparticles in the rodent nose and brain. Environ Health Perspect 124:1870–1875; http://dx.doi.org/10.1289/EHP234