First order risk assessment for nanoparticle inhalation exposure during injection molding of polypropylene composites and production of tungsten-carbide-cobalt fine powder based upon pulmonary inflammation and surface area dose

AbstractInhalation exposure to low toxicity and biodurable particles has shown to induce polymorphonuclear neutrophilia (PMN) in the lungs, which is a strong indicator for lung inflammation. Recently, Schmid and Stoeger (2016; http://dx.doi.org/10.1016/j.jaerosci.2015.12.006) reviewed mice and rat intratracheal instillation studies and assessed the relation between particles dry powder BET surface area dose and PMN influx for granular biodurable particles (GBPs) and transition metal oxides. In this study, we measured workers alveolar lung deposited surface area (LDSA) concentrations (μm2 cm−3) during injection molding of polypropylene (PP) car bumpers and production of tungsten-carbide-cobalt (WCCo) fine grade powder using diffusion chargers. First order risk assessment was performed by comparing the doses calculated from measured LDSA concentrations during an 8-h work day with the NOEL1/100, the one hundredth of no observed effect level, assigned for GBPs (0.11cm2g−1) and transition metal oxide particles (9×10−3cm2g−1). During the injection molding of PP car bumpers, LDSA concentrations varied from 23 to 39.8μm2cm−3. During 8-h exposure PP, particle doses were at a maximum of 1.4×10−3cm2g−1, which was a factor 100 lower compared to the NOEL1/100 assigned for GBPs. In the WCCo fine powder production plant, the LDSA concentrations were below 18.7μm2cm−3, which corresponds to the 8-h dose of 2.7×10−3cm2g−1. This is 3 times lower than the NOEL1/100 assigned for transition metal oxide particles. The LDSA concentrations were generally low compared to urban background levels of 44.2μm2cm−3 in European cities

First order risk assessment for nanoparticle inhalation exposure during injection molding of polypropylene composites and production of tungsten-carbide-cobalt fine powder based upon pulmonary inflammation and surface area dose

AbstractInhalation exposure to low toxicity and biodurable particles has shown to induce polymorphonuclear neutrophilia (PMN) in the lungs, which is a strong indicator for lung inflammation. Recently, Schmid and Stoeger (2016; http://dx.doi.org/10.1016/j.jaerosci.2015.12.006) reviewed mice and rat intratracheal instillation studies and assessed the relation between particles dry powder BET surface area dose and PMN influx for granular biodurable particles (GBPs) and transition metal oxides. In this study, we measured workers alveolar lung deposited surface area (LDSA) concentrations (μm2 cm−3) during injection molding of polypropylene (PP) car bumpers and production of tungsten-carbide-cobalt (WCCo) fine grade powder using diffusion chargers. First order risk assessment was performed by comparing the doses calculated from measured LDSA concentrations during an 8-h work day with the NOEL1/100, the one hundredth of no observed effect level, assigned for GBPs (0.11cm2g−1) and transition metal oxide particles (9×10−3cm2g−1). During the injection molding of PP car bumpers, LDSA concentrations varied from 23 to 39.8μm2cm−3. During 8-h exposure PP, particle doses were at a maximum of 1.4×10−3cm2g−1, which was a factor 100 lower compared to the NOEL1/100 assigned for GBPs. In the WCCo fine powder production plant, the LDSA concentrations were below 18.7μm2cm−3, which corresponds to the 8-h dose of 2.7×10−3cm2g−1. This is 3 times lower than the NOEL1/100 assigned for transition metal oxide particles. The LDSA concentrations were generally low compared to urban background levels of 44.2μm2cm−3 in European cities

Hematological Changes in Women and Infants Exposed to an AZT-Containing Regimen for Prevention of Mother-to-child-transmission of HIV in Tanzania.

Tanzanian guidelines for prevention of mother-to-child-transmission of HIV (PMTCT) recommend an antiretroviral combination regimen involving zidovudine (AZT) during pregnancy, single-dosed nevirapine at labor onset, AZT plus Lamivudine (3TC) during delivery, and AZT/3TC for 1-4 weeks postpartum. As drug toxicities are a relevant concern, we assessed hematological alterations in AZT-exposed women and their infants. A cohort of HIV-positive women, either with AZT intake (n = 82, group 1) or without AZT intake (n = 62, group 2) for PMTCT during pregnancy, was established at Kyela District Hospital, Tanzania. The cohort also included the infants of group 1 with an in-utero AZT exposure ≥4 weeks, receiving AZT for 1 week postpartum (n = 41), and infants of group 2 without in-utero AZT exposure, receiving a prolonged 4-week AZT tail (n = 58). Complete blood counts were evaluated during pregnancy, birth, weeks 4-6 and 12. For women of group 1 with antenatal AZT intake, we found a statistically significant decrease in hemoglobin level, red blood cells, white blood cells, granulocytes, as well as an increase in red cell distribution width and platelet count. At delivery, the median red blood cell count was significantly lower and the median platelet count was significantly higher in women of group 1 compared to group 2. At birth, infants from group 1 showed a lower median hemoglobin level and granulocyte count and a higher frequency of anemia and granulocytopenia. At 4-6 weeks postpartum, the mean neutrophil granulocyte count was significantly lower and neutropenia was significantly more frequent in infants of group 2. AZT exposure during pregnancy as well as after birth resulted in significant hematological alterations for women and their newborns, although these changes were mostly mild and transient in nature. Research involving larger cohorts is needed to further analyze the impact of AZT-containing regimens on maternal and infant health

Occupational exposure during handling and loading of halloysite nanotubes – A case study of counting nanofibers

Halloysite nanotubes (HNTs) are abundant naturally-occurring hollow aluminosilicate clay mineral fibers with a typical diameter  3 and in length > 2 μm. These particles were agglomerated and/or aggregated particles where the longest individual fiber was 2 μm in length. The occupational exposure limits for refractory mineral fibers vary from 0.1 to 2 fibers cm−3. Following standard protocols for fiber analysis, detection of 0.1 fibers cm−3 would require analysis on 4 × 104 images when the filter loading is good. Thus, the fiber sampling and quantification procedures needs to be improved significantly if nanofibers <100 nm in diameter are included in regulatory exposure assessment. Due to very limited toxicological information of HNTs we recommend avoiding inhalation exposure

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes

Airport emission particles:Exposure characterization and toxicity following intratracheal instillation in mice

Background: Little is known about the exposure levels and adverse health effects of occupational exposure to airplane emissions. Diesel exhaust particles are classified as carcinogenic to humans and jet engines produce potentially similar soot particles. Here, we evaluated the potential occupational exposure risk by analyzing particles from a non-commercial airfield and from the apron of a commercial airport. Toxicity of the collected particles was evaluated alongside NIST standard reference diesel exhaust particles (NIST2975) in terms of acute phase response, pulmonary inflammation, and genotoxicity after single intratracheal instillation in mice. Results: Particle exposure levels were up to 1 mg/m3 at the non-commercial airfield. Particulate matter from the non-commercial airfield air consisted of primary and aggregated soot particles, whereas commercial airport sampling resulted in a more heterogeneous mixture of organic compounds including salt, pollen and soot, reflecting the complex occupational exposure at an apron. The particle contents of polycyclic aromatic hydrocarbons and metals were similar to the content in NIST2975. Mice were exposed to doses 6, 18 and 54 μg alongside carbon black (Printex 90) and NIST2975 and euthanized after 1, 28 or 90 days. Dose-dependent increases in total number of cells, neutrophils, and eosinophils in bronchoalveolar lavage fluid were observed on day 1 post-exposure for all particles. Lymphocytes were increased for all four particle types on 28 days post-exposure as well as for neutrophil influx for jet engine particles and carbon black nanoparticles. Increased Saa3 mRNA levels in lung tissue and increased SAA3 protein levels in plasma were observed on day 1 post-exposure. Increased levels of DNA strand breaks in bronchoalveolar lavage cells and liver tissue were observed for both particles, at single dose levels across doses and time points. Conclusions: Pulmonary exposure of mice to particles collected at two airports induced acute phase response, inflammation, and genotoxicity similar to standard diesel exhaust particles and carbon black nanoparticles, suggesting similar physicochemical properties and toxicity of jet engine particles and diesel exhaust particles. Given this resemblance as well as the dose-response relationship between diesel exhaust exposure and lung cancer, occupational exposure to jet engine emissions at the two airports should be minimized.publishedVersionPeer reviewe

Adherence to Combination Prophylaxis for Prevention of Mother-to-Child-Transmission of HIV in Tanzania

BACKGROUND: Since 2008, Tanzanian guidelines for prevention of mother-to-child-transmission of HIV (PMTCT) recommend combination regimen for mother and infant starting in gestational week 28. Combination prophylaxis is assumed to be more effective and less prone to resistance formation compared to single-drug interventions, but the required continuous collection and intake of drugs might pose a challenge on adherence especially in peripheral resource-limited settings. This study aimed at analyzing adherence to combination prophylaxis under field conditions in a rural health facility in Kyela, Tanzania. METHODS AND FINDINGS: A cohort of 122 pregnant women willing to start combination prophylaxis in Kyela District Hospital was enrolled in an observational study. Risk factors for decline of prophylaxis were determined, and adherence levels before, during and after delivery were calculated. In multivariate analysis, identified risk factors for declining pre-delivery prophylaxis included maternal age below 24 years, no income-generating activity, and enrolment before 24.5 gestational weeks, with odds ratios of 5.8 (P = 0.002), 4.4 (P = 0.015) and 7.8 (P = 0.001), respectively. Women who stated to have disclosed their HIV status were significantly more adherent in the pre-delivery period than women who did not (P = 0.004). In the intra- and postpartum period, rather low drug adherence rates during hospitalization indicated unsatisfactory staff performance. Only ten mother-child pairs were at least 80% adherent during all intervention phases; one single mother-child pair met a 95% adherence threshold. CONCLUSIONS: Achieving adherence to combination prophylaxis has shown to be challenging in this rural study setting. Our findings underline the need for additional supervision for PMTCT staff as well as for clients, especially by encouraging them to seek social support through status disclosure. Prophylaxis uptake might be improved by preponing drug intake to an earlier gestational age. Limited structural conditions of a healthcare setting should be taken into serious account when implementing PMTCT combination prophylaxis