Deciphering the Role of the Gut Microbiota in Exposure to Emerging Contaminants and Diabetes: A Review.

Emerging pollutants, a category of compounds currently not regulated or inadequately regulated by law, have recently become a focal point of research due to their potential toxic effects on human health. The gut microbiota plays a pivotal role in human health; it is particularly susceptible to disruption and alteration upon exposure to a range of toxic environmental chemicals, including emerging contaminants. The disturbance of the gut microbiome caused by environmental pollutants may represent a mechanism through which environmental chemicals exert their toxic effects, a mechanism that is garnering increasing attention. However, the discussion on the toxic link between emerging pollutants and glucose metabolism remains insufficiently explored. This review aims to establish a connection between emerging pollutants and glucose metabolism through the gut microbiota, delving into the toxic impacts of these pollutants on glucose metabolism and the potential role played by the gut microbiota.

Emerging Contaminants: An Emerging Risk Factor for Diabetes Mellitus.

Emerging contaminants have been increasingly recognized as critical determinants in global public health outcomes. However, the intricate relationship between these contaminants and glucose metabolism remains to be fully elucidated. The paucity of comprehensive clinical data, coupled with the need for in-depth mechanistic investigations, underscores the urgency to decipher the precise molecular and cellular pathways through which these contaminants potentially mediate the initiation and progression of diabetes mellitus. A profound understanding of the epidemiological impact of these emerging contaminants, as well as the elucidation of the underlying mechanistic pathways, is indispensable for the formulation of evidence-based policy and preventive interventions. This review systematically aggregates contemporary findings from epidemiological investigations and delves into the mechanistic correlates that tether exposure to emerging contaminants, including endocrine disruptors, perfluorinated compounds, microplastics, and antibiotics, to glycemic dysregulation. A nuanced exploration is undertaken focusing on potential dietary sources and the consequential role of the gut microbiome in their toxic effects. This review endeavors to provide a foundational reference for future investigations into the complex interplay between emerging contaminants and diabetes mellitus.

Relationship of individual and mixed urinary metals exposure with liver function in the China National Human Biomonitoring (CNHBM) of Zhejiang Province.

BACKGROUND: Heavy metals have been reported to affect liver function. However, there is currently little and inconsistent knowledge about the effects of combined and individual urinary metals on specific parameters of liver function in the general population. Therefore, this study aimed to investigate their associations. METHODS: This study involved 807 general population from the China National Human Biomonitoring of Zhejiang Province 2017-2018. Concentrations of urinary metals, including Chromium (Cr), Cobalt (Co), Nickle (Ni), Arsenic (As), Selenium (Se), Molybdenum (Mo), Cadmium (Cd), Thallium (Tl) and Lead (Pb) were measured. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), total protein (TP), albumin (ALB), direct bilirubin (DBIL), total bilirubin (TBIL) as liver function biomarkers. Multivariable linear regression and weighted quantile sum (WQS) regression were employed to explore the associations of urinary metals with liver function biomarkers. Subgroup analysis stratified by gender and age, excluding smokers and drinkers for sensitivity analysis. RESULTS: Both statistical models indicated that urinary metals were positively associated with ALT and AST, while negatively with TP, ALB, DBIL and TBIL. In the WQS analysis, each quartile increase in the ln-transformed levels of metal mixtures was associated with 4.11 IU/L (95% CI: 1.07, 7.15) higher ALT and 3.00 IU/L (95% CI: 1.75, 4.25) higher AST, as well as, with 0.67 g/L (95% CI: 1.24, -0.11) lower TP, 0.74 g/L (95% CI: 1.09, -0.39) lower ALB, 0.38 µmol/L (95% CI: 0.67, -0.09) lower DBIL, and 1.56 µmol/L (95% CI: 2.22, -0.90) lower TBIL. The association between urinary metals and ALT was primarily driven by Cd (55.8%), Cr contributed the most to the association with AST (20.2%) and TBIL (45.2%), while the association with TP was primarily driven by Ni (38.2%), the association with ALB was primarily driven by As (32.8%), and the association with DBIL was primarily driven by Pb (30.9%). The associations between urinary metals and liver function might differ by sex and age. CONCLUSION: Urinary metals were significantly associated with liver function parameters. Further studies are required to clarify the relationship between heavy metals and liver function.

Association of urinary bisphenols with thyroid function in the general population: a cross-sectional study of an industrial park in China.

Bisphenols (BPs) are potential thyroid disruptors that are widely used in many consumer products, leading to their widespread exposure in the general population. Current cross-sectional and case-control studies have found associations between exposure to BPs and serum thyroid function, but the results were contradictory. The objectives of this study are to describe demographic characteristics, BP exposure levels, and thyroid function measurements in potentially exposed and control districts and to investigate the association of urinary BPs with thyroid function. Data were collected from a general population aged 3-79 years (N = 281) recruited by the Zhejiang Human Biomonitoring Program (ZJHBP). The concentrations of 10 kinds of BPs in urine and serum free triiodothyronine (FT3), total triiodothyronine (TT3), free thyroxine (FT4), total thyroxine (TT4), thyroid-stimulating hormone (TSH), thyroglobulin (Tg), thyroglobulin antibodies (TgAb), thyroid peroxidase antibodies (TPOAb), and thyrotropin receptor antibody (TRAb) in serum were measured. Multiple linear regression and weighted quantile sum (WQS) regression were used to estimate the relationship between single and mixed exposure of BPs and thyroid function. Bisphenol A (BPA), bisphenol S (BPS), and bisphenol P (BPP) were detected, respectively, in 82.73%, 94.24%, and 55.40% of the population in the exposed area and 81.69%, 61.27%, and 43.66% of the population in the control area. Among adult females, serum TT3 was negatively associated with urinary BPA (ß = -0.033, 95% CI = -0.071, -0.008, P = 0.021). Among minor females, FT4 and Tg levels were negatively associated with the urinary BPA (ß = -0.026, 95% CI = -0.051, -0.002, P = 0.032 for FT4; ß = -0.129, 95% CI = -0.248, -0.009, P = 0.035 for Tg), and TPOAb was positively associated with urinary BPA (ß = 0.104, 95% CI = 0.006, 0.203, P = 0.039). In WQS models, BPs mixture was positively associated with FT3 (ßWQS = 0.022, 95% CI = 0.002, 0.042) and TT3 (ßWQS = 0.033, 95% CI = 0.004, 0.062), and negatively associated with FT4 (ßWQS = -0.024, 95% CI = -0.044, 0.004). We found widespread exposure to BPA, BPS, and BPP in the general population of Zhejiang province and found an association between BPA and thyroid hormones. This association is gender- and age-dependent and needs to be confirmed in further studies.

Serum Iodine as a Potential Individual Iodine Status Biomarker: A Cohort Study of Mild Iodine Deficient Pregnant Women in China.

Iodine deficiency during pregnancy is a widespread public health concern, but indicators and methods for assessing iodine nutritional status are lacking. Serum iodine concentration (SIC) is an important iodine metabolism biomarker and can, to some extent, predict the risk of thyroid diseases, making it a potential biomarker for assessing individual iodine nutrition levels. Our study aimed to analyze the relationship between SIC and thyroid function in a cohort of mild iodine deficient pregnant women in China in order to explore the potential of SIC as a biomarker of individual iodine status in pregnancy. A total of 1540 early pregnant women (gestation < 10 weeks) aged 18 to 45 years old were included in the final study from a Zhejiang multicenter population-based mother and child cohort. Repeated measures of SIC, urinary iodine concentration (UIC), and thyroid function were taken at approximately 10, 17, and 32 weeks of gestation. The SIC was statistically correlated with all thyroid function indexes in the first trimester, and a very strong positive correlation with FT4 over three trimesters (r = 0.449, 0.550, and 0.544, respectively). Pregnant women with an SIC < 72.4 µg/L were at a higher risk of hypothyroxinemia (adjusted OR = 8.911, 95% CI = 5.141-15.447) and iodine deficiency (adjusted OR = 1.244, 95% CI = 1.031-1.502), while those with an SIC > 93.9 µg/L were at a higher risk of thyrotoxicosis (adjusted OR = 11.064, 95% CI = 6.324-19.357) and excessive iodine (adjusted OR = 11.064, 95% CI = 6.324-19.357). In contrast, the UIC was not correlated with thyroid diseases (p > 0.05). These findings indicate that the SIC is a potential biomarker for assessing individual iodine nutrition and thyroid dysfunction in pregnant women.

Are Microplastics Toxic? A Review from Eco-Toxicity to Effects on the Gut Microbiota.

Emerging studies have presented an initial picture of the toxic effects of exposure to environmental micro- and nanoplastics. They have indicated that micro- and nanoplastics may induce toxicity by leading to oxidative stress, energy metabolism disorders, gene damage, and so forth in environmental organisms, marine invertebrates and vertebrates, and laboratory mouse models. In recent years, micro- and nanoplastics have been discovered in human fecal samples, placentas, lung tissue, and even blood; thus, micro- and nanoplastics pose an alarming and ever-increasing threat to global public health. However, current research on the health effects of micro- and nanoplastics and the possible adverse outcomes in humans has only presented the tip of the iceberg. More robust clinical data and basic experiments are still warranted to elucidate the specific relationships and mechanisms. In this paper, we review studies on micro- and nanoplastic toxicity from the perspectives of eco-toxicity, the adverse effects on invertebrates and vertebrates, and the impact of micro- and nanoplastics on the gut microbiota and its metabolites. In addition, we evaluate the toxicological role of micro- and nanoplastic exposure and its potential implications in respect to human health. We also summarize studies regarding preventive strategies. Overall, this review provides insights on micro- and nanoplastic toxicity and its underlying mechanisms, opening up scientific avenues for future in-depth studies.

Pollution Characteristics and Health Risk Assessment of Heavy Metals in Agricultural Soils over the Past Five Years in Zhejiang, Southeast China.

Heavy metal contamination in agricultural soils has attracted increasing attention in recent years. In this study, 1999 agricultural soil samples were collected from 11 cities in Zhejiang Province from 2016 to 2020, and the spatial and temporal variation characteristics of 3 of the most important heavy metals, i.e., lead (Pb), cadmium (Cd), and chromium (Cr) were analyzed. The results showed that Cd had a slightly higher sample over-standard rate of 12.06%. Spatial distribution and temporal trends showed that the Pb concentrations overall increased from 2016 to 2020 and mainly accumulated in southern Zhejiang. In addition, multiple exposure routes were evaluated for human health risks. Children are more susceptible to the adverse effects of heavy metals in agricultural soils, and oral ingestion was the major exposure route. Cr poses higher human health risks to humans than Pb and Cd in agricultural soils. Therefore, more rigid environmental monitoring and related soil remediation counter-measures for some sites with high concentrations of heavy metals are necessary to limit the potential threat to human health.

Low Iodine Intake May Decrease Women's Fecundity: A Population-Based Cross-Sectional Study.

Salt iodization is one of the most cost-effective strategies to eliminate iodine deficiency disorders (IDD). However, China's dismantling of salt monopoly has reduced the availability of iodized salt in the susceptible population in pregnancy, which might cause IDD and have adverse health effects on both themselves and their offspring. The aim of our study was therefore to explore the association between IDD and women's reproductive health. This is a population-based cross-sectional study conducted in 2018 in Zhejiang Province, China. A total of 1653 pregnant women participated in this study. Median urinary iodine concentration (UIC) in the population was used to assess iodine intake. Cox regression analyses were used to estimate the association between iodine intake and time to pregnancy, which was indicated with fecundability ratio (FR) and 95% confidence interval (CI). The percentage of participants with iodine deficiency who had been waiting longer than 13 months to get pregnant (20%; median UIC 119.6 µg/L) was significantly higher than those with iodine sufficiency (14%; median UIC 147.1 µg/L). A significant decrease in fecundity was observed in participants with iodine deficiency (FR, 0.820; 95% CI, 0.725-0.929) than those with iodine sufficiency. These findings indicate the importance of ongoing monitoring of iodine nutrition in women of reproductive age. Keeping a safe and optimal level of iodine nutrition during pregnancy should be emphasized.

Geographical influences on thyroid abnormalities in adult population from iodine-replete regions: a cross-sectional study.

The studies on the increasing incidence of thyroid abnormalities are scarce. The aim of this current study was to ascertain the effects of geographical region on thyroid abnormalities under the context of universal salt iodization (USI). We randomly selected 1255 participants residing in inland and 1248 in coast, with the determination of urinary iodine concentration (UIC) and functional and morphological abnormalities of thyroid gland. The median UIC was significantly higher for the inland participants (188.5 µg/L) than the coastal participants (128.5 µg/L; p < 0.001), indicating iodine sufficiency in both populations according to the recommended assessment criteria by the World Health Organization. However, the spectrum of thyroid abnormalities varied between regions, with hypothyroidism prevalent in inland and thyroid nodules in coast. The associations between region and thyroid abnormalities via binary logistic regression models showed that the coastal participants were at a higher risk of total thyroid abnormalities than those from the inland (OR 1.216, 95% CI 1.020-1.449), after the adjustment of ten confounders (demographical characteristics, smoking status, metabolism syndrome, and hyperuricemia). These results indicated that further investigations of the adverse effects of hypothyroidism and thyroid nodules on health burden is urgently needed to sustain USI program.

Induction of peripheral blood T follicular helper cells expressing ICOS correlates with antibody response to hepatitis B vaccination.

T follicular helper (TFH) cells, a critical subset of CD4+ T cells, provide help to B cells during the procession of the humoral immune response in the germinal center (GC) and extrafollicular sites. CXCR5+ CD4+ T cells in human circulating blood, referred to herein as peripheral TFH (pTFH) cells, share phenotypes and functional properties with TFH cells in GC. Hepatitis B vaccine protects about 60% of the chronic hepatitis C patients from hepatitis B. The immunological bases that lead to the induction of protective antibody response is not well understood. In the present study, the pTFH cells subsets were determined in 18 healthy controls (anti-HBs ≥ 100 mIU/mL; HC), 21 nonresponders (anti-HBs < 10 mIU/mL; NR), and 23 weak responders (10 mIU/mL ≤ anti-HBs < 100 mIU/mL; WR) of chronic hepatitis patients upon routine hepatitis B vaccination. Though the frequency of the pTFH cell was equivalent in HC, WR, and NR, ICOS+ pTFH cells in HC underwent expansion with increased IL-21 secretion and production of serum anti-HBs response at 4 weeks after a full course of hepatitis B vaccination. These changes were not shown in both NR and WR. Analysis of ICOS+ pTFH cells represents a novel cellular determinant of the hepatitis B vaccine-induced humoral immune response, which may have relevance for design of hepatitis B vaccine.

Poor Iodine Knowledge, Coastal Region, and Non-Iodized Salt Consumption Linked to Low Urinary Iodine Excretion in Zhejiang Pregnant Women.

BACKGROUND: Iodine deficiency in pregnant women, defined as a median urinary iodine concentration (UIC) of less than 150 µg/L, is an important public health issue. To improve their iodine intake, it is important to understand the knowledge and practices regarding iodine. METHODS: A cross-sectional investigation was conducted on 2642 pregnant women during 2016⁻2017 in Zhejiang province, China. A 3-point Likert scale questionnaire was used to record knowledge. The UIC and iodine content in household salt were determined. RESULTS: Coastal participants were iodine deficient (median UIC 127.6 µg/L) while inland participants were iodine sufficient (median UIC 151.0 µg/L). The average knowledge scores were significantly lower for the coastal participants (24.2 points vs. 25 points for the inland participants; p < 0.001). The percentage for iodized salt consumption was significantly lower for the coastal participants (88.9% vs. 96.0% for those inland; p < 0.001). A generalized linear model analysis showed that non-iodized salt consumption, coastal region, and low knowledge scores were independently associated with a low UIC. CONCLUSIONS: Comprehensive interventional strategies are needed to develop to achieve an optimal iodine status. We recommend that coastal pregnant women should take iodine supplements based on the consumption of iodized salt, and improvement of iodine-related knowledge.

Iodine Deficiency in Zhejiang Pregnant Women in the Context of Universal Salt Iodization Programme.

Zhejiang introduced universal salt iodization (USI) programme in 1995 and has achieved the goal of elimination of iodine deficiency disorders (IDD) since 2011. However, no systematical data of iodine nutritional status in population in pregnancy is available. In this cross-sectional study, pregnant women were interviewed to complete questionnaires in addition to handing in samples of urine and household table salt between March 2016 to February 2017. Date of birth, age of pregnancy, ethnicity and dietary iodine habits were recorded. The overall median urinary iodine concentration in 8561 pregnant women was 130.47 µg/L, which was lower than the cut-off value of iodine sufficiency of 150 µg/L recommended by the WHO. Participants using non-iodized salt, taking non-iodine-containing supplements, in coastal and in Han group were independently associated with iodine deficiency. The current USI programme did not supply Zhejiang pregnant women with sufficient iodine intake. They are generally iodine deficient, which have great public health importance since even mild IDD in pregnancy have adverse effects on fetal neurodevelopment. We strongly recommend urgent measures to improve iodine intake in pregnancy.

HEK293 cells exposed to microcystin-LR show reduced protein phosphatase 2A activity and more stable cytoskeletal structure when overexpressing α4 protein.

Microcystin-LR (MC-LR) is one of the most toxic members of microcystins released by freshwater cyanobacterial. The major mechanism of MC-LR toxicity has been attributed to its inhibition of protein phosphatases 1 (PP1) and 2A (PP2A). In our prior research, α4 protein, a regulator of PP2A, was found not only crucial for PP2A regulation but also for the overall response of HEK 293 cells encountering MC-LR. To explore the role of α4 in MC-LR toxicity via PP2A regulation, here, HEK 293 cells overexpressing α4 protein were exposed to MC-LR and PP2A, cytoskeletal organization, and cytoskeleton-related proteins were investigated. The results showed that PP2A activity decreased and PP2A/C subunit expression and phosphorylation at Tyr307 increased significantly in the group exposed to high MC-LR. Vimentin IF became concentrated and formed perinuclear bundles. However, the assembly of actin filament and microtubules remained unchanged and the expression and phosphorylation of the cytoskeleton-related proteins HSP27 and VASP did not increase significantly. Some of these results differ from those of our previous study in which normal HEK293 cells were exposed to MC-LR. Our results indicate that elevated α4 expression confers some resistance to MC-LR-induced cytoskeletal change These new findings provide helpful insights into the mechanism of MC-LR toxicity and the role of α4 in regulating PP2A function. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 255-264, 2017.

Microcystin-LR induces a wide variety of biochemical changes in the A549 human non-small cell lung cancer cell line: Roles for protein phosphatase 2A and its substrates.

Our previous studies have described the toxic effects of microcystin-LR (MC-LR) in various normal cell lines and human hepatoma SMMC-7721 cells, but the specific effects of MC-LR in other types of cancer cells with respect to protein phosphatase 2A (PP2A) have not been fully elaborated. A549 human lung adenocarcinoma cells have been identified to express organic anion-transporting polypeptides (OATP) involved in cellular uptake of MC-LR, and thus probably make an appropriate in vitro model to assess MC-LR's cytotoxicity. Hence, in our present study, A549 cells were treated with various concentrations of MC-LR for 24 h. The presence of MC-LR in A549 cells was confirmed, and PP2A activity, PP2A substrates, cytoskeleton, apoptosis, and proliferation were subsequently explored. The results showed that 5-10 µM MC-LR inhibited PP2A activity significantly but 0.5-1 µM MC-LR did not change PP2A activity dramatically. The inhibition could result from the hyperphosphorylation of PP2A/C at Tyr307, an elevation in the total PP2A/C expression and the dissociation of α4/PP2A/C complexes. Moreover, MC-LR led to rearrangements of filamentous actin and microtubules, which might be correlated with the hyperphosphorylation of Ezrin, VASP and HSP27 due to PP2A inhibition and mitogen-activated protein kinase (MAPK) activation. However, exposure to MC-LR for 24 h failed to trigger either apoptosis or proliferation, which might be related to PP2A-inhibition-induced hyperphosphorylation of Bcl-2 and Bad and the activation status of Akt. In conclusion, our data indicated that MC-LR induced extensive molecular and cellular alterations in A549 cells through a PP2A-centered pathway, which differed in some respects from our previous study in SMMC-7721 cells. To our knowledge, this is the first report comprehensively demonstrating the effects of MC-LR in A549 cells, and our findings provide insights into the mechanism of MC-LR toxicity in cancer cells. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1065-1078, 2017.

Polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs) and polychlorinated biphenyls (PCBs) in Zhejiang foods (2006-2015): Market basket and polluted areas.

In this study, we measured the levels of polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs) and polychlorinated biphenyls (PCBs) in 620 foods collected during 2006-2015 from Zhejiang market, a municipal waste incinerator (MWI) and E-waste disassembling areas. For market retail foods, the levels of PCDD/F TEQs, PCDD/F plus dioxin-like PCB (DL-PCB) TEQs, and the concentrations of six indicator PCBs were generally below the EU ML. The average TEQ values for the 13 food groups were 42% of EU ML for PCDD/Fs and 32% for PCDD/Fs+DL-PCBs. Some foods of animal origin were close to the corresponding EU ML: pork (PCDD/F TEQ, 79% of ML; PCDD/F+DL-PCB TEQ, 84% of ML); infant formula (90% of PCDD/F ML) and beef (96% of PCDD/F ML; PCDD/F+DL-PCB TEQ, 78% of ML). The estimated dietary intake for the general population was 22.0pgTEQ(kgbody weight (bw))-1month-1, which was below the standard of 70pgTEQ(kgbw)-1month-1 set by the Joint FAO/WHO Expert Committee on Food Additives (JECFA). For the MWI and E-waste disassembling sites, high concentrations of PCDD/Fs and PCBs were measured in all foods tested. The corresponding TEQ in (1) freshwater fish, (2) chicken egg, (3) chicken meat and (4) chicken liver was (1) 1.4-fold (MWI, PCDD/F TEQ), (2) 11.2-fold (MWI,) and 1.6-fold (E-waste disassembling sites), (3) 20.7-fold and (4) 3.3-fold greater than EU ML, respectively. Considering the worst situation (highly polluted foods were consumed), the estimated dietary intake for local residents were 244 (MWI) and 240pgTEQ(kgbw)-1month-1 (E-waste disassembling sites), approximately 3.5-fold greater compared to the standard 70pgTEQ(kgbw)-1month-1 set by JECFA, indicating high risk could have been imposed on the health of local residents.

[An analysis of characteristics of exposure to nanoparticles in a workplace manufacturing iron oxide nanoparticles].

OBJECTIVE: To investigate the characteristics of exposure to iron oxide nanoparticles in workplace. METHODS: The real-time particle number (NC), surface area (SAC), and mass (MC) concentrations of nanoparticles were measured in various locations of a selected workplace manufacturing iron oxide nanoparticles. The collected particles were analyzed for morphology and elemental composition. RESULTS: The average NCs and SACs in milling site (16,566 pt/cm3, 106.082 µm2/cm3), packaging site (12,386 pt/cm3, 89.861 µm2/cm3), shipping site (13,808 pt/cm3, 102.071 µm2/cm3), and product storage room (17,192 pt/cm, 115.044 µm2/cm3) of the yellow powder (α-Fe2O3 . nH2O) were all significantly higher than the workplace background concentrations (11,420 pt/cm3, 85.026 µm2/cm3) (all P<0.05). The NC was highly correlated with the SAC (r= 0.784), while both NC and SAC were loosely correlated with the MC (r1=0.323, r2=0.331). Scanning electron microscopy revealed a spindle-like shape of the iron oxide nanoparticle; the chemical composition of the collected particles contained 19.33 weight percent iron (Fe). CONCLUSION: The milling site and product storage room of the yellow powder are exposed to a higher concentration of nanoparticles, which are mainly composed of iron oxide nanoparticles. The NC is highly correlated with the SAC.

Relationships between number, surface area, and mass concentrations of different nanoparticles in workplaces.

No consistent metric for measuring exposure to nanoparticles has yet been agreed upon internationally. This study seeks to examine the relationship between the number concentration (NC), surface area concentration (SAC), and mass concentration (MC) of nanoparticles in workplaces. Real-time NC20-1000 nm, SAC10-1000 nm, and respirable MC100-1000 nm were determined for different nanoparticles. Concentration ratio (CR, activity: background), exposure ranking (ER), and between-metric correlation coefficients (R) were used to analyze the relationships between the three metrics. The ratio of cumulative percentage by number (APN) and cumulative percentage by mass (APM) was used to analyze whether the nanoparticle number is predominant, as compared with the nanoparticle mass. The CRs of NC20-1000 nm and SAC10-1000 nm for different nanoparticles at the corresponding work sites were higher than those of respirable MC100-1000 nm. The ERs of NC20-1000 nm for nano-Fe2O3 and nano-Al2O3 were the same as those of SAC10-1000 nm, but were inconsistent with those of respirable MC100-1000 nm. The order of correlation coefficients between NC20-1000 nm, SAC10-1000 nm, and respirable MC100-1000 nm was: RSAC and NC > RSAC and MC > RNC and MC. The ratios of APN and APM for nano-Al2O3 and grinding-wheel particles (less than 100 nm) at the same work site were 2.03 and 1.65, respectively. NC and SAC metrics are significantly distinct from the MC in characterizing exposure to airborne nanoparticles. Simultaneous measurements of the NC, SAC, and MC should be conducted as part of nanoparticle exposure assessment strategies and epidemiological studies.

Exposure characteristics of ferric oxide nanoparticles released during activities for manufacturing ferric oxide nanomaterials.

The exposure characteristics of Fe2O3 nanoparticles (NPs) released in a factory were investigated, as exposure data on this type of NP is absent. The nature of the particles was identified in terms of their concentrations [i.e. number concentration (NC(20-1000 nm)), mass concentration (MC(100-1000 nm)), surface area concentration (SAC(10-1000 nm))], size distribution, morphology and elemental composition. The relationships between different exposure metrics were determined through analyses of exposure ranking (ER), concentration ratios (CR), correlation coefficients and shapes of the particle concentration curves. Work activities such as powder screening, material feeding and packaging generated higher levels of NPs as compared to those of background particles (p < 0.01). The airborne Fe2O3 NPs exhibited a unimodal size distribution and a spindle-like morphology and consisted predominantly of the elements O and Fe. Periodic and activity-related characteristics were noticed in the temporal variations in NC(20-1000 nm) and SAC(10-1000 nm). The modal size of the Fe2O3 NPs remained relatively constant (ranging from 10 to 15 nm) during the working periods. The ER, CR values and the shapes of NC(20-1000 nm) and SAC(10-1000 nm) curves were similar; however, these were significantly different from those for MC(100-1000 nm). There was a high correlation between NC(20-1000 nm) and SAC(10-1000 nm), and relatively lower correlations between the two and MC(100-1000 nm). These findings suggest that the work activities during the manufacturing processes generated high levels of primary Fe2O3 NPs. The particle concentrations exhibited periodicity and were activity dependent. The number and SACs were found to be much more relevant metrics for characterizing NPs than was the mass concentration.

Workplace exposure to airborne alumina nanoparticles associated with separation and packaging processes in a pilot factory.

Workplace exposure to airborne Al2O3 nanoparticles in a pilot factory was characterised by particle concentrations, size distribution, morphology and chemical composition, compared with background particles. Real-time variations in number concentration (NC20-1000 nm), respirable mass concentration (MC100-1000 nm), active surface area concentration (SAC10-1000 nm) and particle size were measured at production locations involved in separation and packaging activities. Measurements during stable production periods showed significant increases in the various concentrations of agglomerated Al2O3 nanoparticles (about 305 nm) at separation locations, compared to those of background particles (p < 0.01). The size distribution model for separation processes might switch to primary nanoparticles (21-26 nm) during periods of unstable production. Packaging activities also caused significant increases in different concentrations of Al2O3 nanoparticles (about 90 nm) compared to background particles (p < 0.01). These particles exhibited a bimodal size distribution and floccus or cloudy-like agglomerates of primary nanoparticles. NC20-1000 nm and active SAC10-1000 nm variations showed the same trend, and were temporally consistent with particle emission scenarios or worker activities, but differed from that for respirable MC100-1000 nm. There was strong correlation between active SAC10-1000 nm and NC20-1000 nm (r = 0.823), moderate correlation between active SAC10-1000 nm and respirable MC100-1000 nm (r = 0.666) and relatively weak correlation between NC20-1000 nm and respirable MC100-1000 nm (r = 0.361). These findings from the pilot factory suggest significant exposure to Al2O3 nanoparticles or their agglomerates, associated with separation and packaging processes. The number and active surface area concentrations may be distinct from mass concentration and might be more appropriate for characterizing exposure to airborne nanoparticles.

[Toxicity of intragastrically administered N, N-dimethylformamide in female Wistar rats].

OBJECTIVE: To investigate the toxicity of intragastrically administered N, N-dimethylformamide (DMF) in female Wistar rats, and to provide experimental data for the overall evaluation of DMF toxicity under different ways of exposure. METHODS: Forty female Wistar rats weighing 150∼180 g were randomly divided into four groups: control group (treated with water) and three DMF exposure groups with doses of 50 mg/kg, 100 mg/kg, and 200 mg/kg. After oral administration of DMF once a day for 14 consecutive days, the rats were weighed and sacrificed. The liver, kidney, brain, and uterus were weighed to calculate organ indices. The pathological changes in the liver were examined by HE staining. The protein expression of HSP70 in the liver, kidney, and brain was determined. Finally, peripheral lymphocytes were collected from the arteria cruralis to determine DNA damage by comet assay. RESULTS: Fourteen days after DMF exposure, the body weight and organ indices of the kidney, brain, and uterus showed no significant changes. However, the liver index showed concentration-dependent increase in all DMF exposed groups (3.52±0.21, 3.55±0.13, and 3.88±0.22 in the low-, medium-, and high-dose groups, respectively), as compared with the control group (3.24±0.28) (P < 0.05 or P < 0.01). The pathological damage in the liver also showed a concentration-dependent manner. Inflammatory cell infiltration and granular degeneration in centrilobular hepatocytes were observed in the high-dose group. No significant change in protein expression of HSP70 was observed in the liver, kidney, or brain of DMF-exposed rats (P > 0.05). DNA damage was induced by DMF, and the DNA percentage of lymphocyte comet tail, average tail length, and tail moment in exposed groups were all significantly increased as compared with the control group (P < 0.05 or P < 0.01). CONCLUSION: Gavaged DMF can induce liver injury and DNA damage in lymphocytes in rats 14 days after administration. There is no significant change in protein expression of HSP70 in the liver, brain, or kidney after DMF exposure.