The association of co-exposure to polycyclic aromatic hydrocarbons (PAHs) and phthalates (PAEs) with blood cell-based inflammatory biomarkers is largely unknown. We conducted a panel study of 144 children aged 4–12 years, with up to 3 repeated visits across 3 seasons. For each visit, we collected the first-morning urine for 4 consecutive days and fasting blood on the day of physical examination. We developed a gas chromatography/tandem mass spectrometry method to detect the metabolites of 10 PAHs (OH-PAHs) and 10 PAEs (mPAEs) in urine samples. We employed linear mixed-effects models to evaluate the individual associations of each OH-PAH and mPAE with blood cell-based inflammatory biomarkers over different lag times. Bayesian kernel machine regression (BKMR) and quantile g-computation were used to evaluate the overall associations of OH-PAHs and mPAEs mixtures with blood cell-based inflammatory biomarkers. After multiple adjustments, we found positive associations of summed hydroxylphenanthrene (∑OHPHE), summed OH-PAHs, and mono-n-butyl phthalate with inflammatory biomarkers such as neutrophil count, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and the systemic immune-inflammation index (SII) at lag 0 (the day of physical examination). Each 1% increase in ∑OHPHE was related to a 0.18% (95% confidence interval: 0.10%, 0.25%) increase in SII, which was the strongest among the above associations. The results of BKMR and quantile g-computation suggested that co-exposure to PAHs and PAEs mixture was associated with an elevated white blood cell count, neutrophil count, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and SII, to which ∑OHPHE and 1-hydroxypyrene (1-OHPYR) might be the major contributors. In addition, gender and age modified the associations of ∑OHPHE and 1-OHPYR with inflammatory biomarkers, where girls and younger children were more susceptible. In conclusion, co-exposure to PAHs and PAEs was associated with elevated inflammation in children, in which ∑OHPHE and 1-OHPYR might play important roles.

Insufficient evidence exists regarding the visible physiological toxic endpoints of MPs exposures on zebrafish larvae due to their small sizes. Herein, the impacts of micro-polystyrene particles (μ-PS) and 100 nm polystyrene particles (n-PS) on the toxicity of cadmium (Cd) through altering neutrophil expressions were identified and quantified in the transgenic zebrafish (Danio rerio) larvae Tg(lyz:DsRed2), and the effects were size-dependent. When exposed together with μ-PS, the amount of neutrophils in Cd treated zebrafish larvae decreased by 25.56% through reducing Cd content in the larvae. By contrast, although n-PS exposure caused lower Cd content in the larvae, the expression of neutrophils under their combined exposure remained high. The mechanism of immune toxicity was analyzed based on the results of metabonomics. n-PS induced high oxidative stress in the larvae, which promoted taurine metabolism and unsaturated fatty biosynthesis in n-PS + Cd treatment. This observation was accordance with the significant inhibition of the activities of superoxide dismutase and catalase enzymes detected in their combined treatment. Moreover, n-PS promoted the metabolic pathways of catabolic processes, amino acid metabolism, purine metabolism, and steroid hormone biosynthesis in Cd treated zebrafish larvae. Nanoplasctis widely coexist with other pollutants in the environment at relatively low concentrations. We conclude that more bio-markers of immune impact should be explored to identify their toxicological mechanisms and mitigate the effects on the environment.

Individuals with metabolic disorders exhibit enhanced susceptibility to the cardiovascular health effects of particulate air pollution, but the underlying mechanisms are not yet understood. We aim to assess whether changes in proinflammatory lipid signals are associated with fine particulate matter (PM₂.₅) exposure in individuals with and without prediabetes. A longitudinal panel study was conducted in Beijing, China, and included 120 participants followed up over 589 clinical visits from August 2013 to February 2015. We measured 12 lipids derived from arachidonic acid pathways in blood samples of the participants via targeted lipidomic analyses. Ambient PM₂.₅ concentrations were continuously monitored at a station for associations with the lipids. Among the 120 participants, 110 (mean [SD] age at recruitment, 56.5 [4.2] years; 31 prediabetics) who visited the clinic at least twice over the follow-up period were assigned exposure values of the outdoor residential PM₂.₅ concentrations during the 1–14 days preceding each clinical visit. With an interquartile range increase in the 1-day-lag PM₂.₅ exposure (64.0 μg/m³), the prediabetic group had consistently greater increases in the concentration of arachidonate metabolites derived from the cytochrome P450 (CYP450) pathway (5,6-DHET, 15.8% [95% CI, 3.5–29.7%]; 8,9-DHET, 9.7% [95% CI, 0.6–19.6%]; 11,12-DHET, 8.3% [95% CI, 1.9–15.1%]; 14,15-DHET, 7.4% [95% CI, 0.9–14.4%]; and 20-HETE, 8.9% [95% CI, 1.0–17.5%]), compared with the healthy group. Among CYP450-derived lipids, 14,15-DHET and 20-HETE significantly mediated 8% and 8% of the PM₂.₅-associated increase in white blood cells, 10% and 13% of that in neutrophils, and 20% and 23% of that in monocytes, respectively, in the prediabetic group. In conclusion, proinflammatory lipid signals from CYP450 pathways triggered the health effects of particulate air pollution in individuals with prediabetes, suggesting that targeting lipid metabolism has therapeutic potential to attenuate or prevent the cardiovascular effects of air pollution in susceptible populations.

The number of deaths from air pollution worldwide is estimated at 8.8 million per year, more than the number of deaths from smoking. Air pollutants, such as PM₂.₅, are known to induce respiratory and cardiovascular diseases by inducing oxidative stress. Thioredoxin (Trx) is a 12-kDa endogenous protein that exerts antioxidant activity by promoting dithiol disulfide exchange reactions. We previously synthesized human serum albumin-fused thioredoxin (HSA-Trx), which has a longer half-life in plasma compared with Trx, and demonstrated its efficacy against various diseases including respiratory diseases. Here, we examined the effect of HSA-Trx on urban aerosol-induced lung injury in mice. Urban aerosols induced lung injury and inflammatory responses in ICR mice, but intravenous administration of HSA-Trx markedly inhibited these responses. We next analyzed reactive oxygen species (ROS) production in murine lungs using an in vivo imaging system. The results show that intratracheal administration of urban aerosols induced ROS production that was inhibited by intravenously administered HSA-Trx. Finally, we found that HSA-Trx inhibited the urban aerosol-induced increase in levels of neutrophilic extracellular trap (NET) indicators (i.e., double-stranded DNA, citrullinated histone H3, and neutrophil elastase) in bronchoalveolar lavage fluid (BALF). Together, these findings suggest that HSA-Trx prevents urban aerosol-induced acute lung injury by suppressing ROS production and neutrophilic inflammation. Thus, HSA-Trx may be a potential candidate drug for preventing the onset or exacerbation of lung injury caused by air pollutants.

Indium tin oxide (ITO) is an important semiconductor material, because of increasing commercial products consumption and potentially exposed workers worldwide. So, urgently we need to assess and manage potential health risks of ITO. Although the Occupational Exposure Limit (OEL) has been established for ITO exposure, there is still a lack of distinguishing the risks of exposure to particles of different sizes. Therefore, obtaining toxicological data of small-sized particles will help to improve its risk assessment data. Important questions raised in quantitative risk assessments for ITO particles are whether biodistribution of ITO particles is affected by particle size and to what extent systematic adverse responses is subsequently initiated. In order to determine whether this toxicological paradigm for size is relevant in ITO toxic effect, we performed comparative studies on the toxicokinetics and sub-acute toxicity test of ITO in mice. The results indicate both sized-ITO resided in the lung tissue and slowly excreted from the mice, and the smaller size of ITO being cleared more slowly. Only a little ITO was transferred to other organs, especially with higher blood flow. Two type of ITO which deposit in the lung mainly impacts respiratory system and may injure liver or kidney. After sub-acute exposure to ITO, inflammation featured by neutrophils infiltration and fibrosis with both dose and size effects have been observed. Our findings revealed toxicokinetics and dose-dependent pulmonary toxicity in mice via oropharyngeal aspiration exposure, also replenish in vivo risk assessment of ITO. Collectively, these data indicate that under the current OEL, there are potential toxic effects after exposure to the ITO particles. The observed size-dependent biodistribution patterns and toxic effect might be important for approaching the hazard potential of small-sized ITO in an occupational environment.

In recent years, numerous studies paid more attention to the molecular mechanisms associated with fluoride toxicity. However, the detailed mechanisms of fluoride immunotoxicity in bovine neutrophils remain unclear. Neutrophil extracellular traps (NETs) is a novel immune mechanism of neutrophils. We hypothesized that sodium fluoride (NaF) can trigger NETs activation and release, and investigate the related molecular mechanisms during the process. We exposed peripheral blood neutrophils to 1 mM NaF for 120 min in bovine neutrophils. The results showed that NaF exposure triggered NET-like structures decorated with histones and granule proteins. Quantitative measurement of NETs content correlated positively with the concentration of NaF. Mechanistically, NaF exposure increased reactive oxygen species (ROS) levels and phosphorylation levels of ERK, p38, whereas inhibiting the activities of superoxide dismutase (SOD) and catalase (CAT) compared with control neutrophils. NETs formation is induced by NaF and this effect was inhibited by the inhibitors diphenyleneiodonium chloride (DPI), U0126 and SB202190. Our findings described the potential importance of NaF-triggered NETs related molecules, which might help to extend the current understanding of NaF immunotoxicity.

Lead (Pb) and polycyclic aromatic hydrocarbon (PAH) exposure is positively associated with cardiovascular disease (CVD), and the possible potential mechanism may be caused by damage to the endothelium by modulation of inflammatory processes. No comprehensive research shows co-exposure of Pb and PAH on cardiovascular endothelial inflammation in electronic waste (e-waste) exposed populations. Given this, the aim of this study is to provide evidence for a relationship between Pb and PAH co-exposure and cardiovascular endothelial inflammation, in an e-waste-exposed population, to delineate the link between a potential mechanism for CVD and environmental exposure. We recruited 203 preschool children (3–7 years) were enrolled from Guiyu (e-waste-exposed group, n = 105) and Haojiang (reference group, n = 98). Blood Pb levels and urinary PAH metabolites were measured. Percentages of T cells, CD4⁺ T cells and CD8⁺ T cells, complete blood counts, endothelial inflammation biomarker (serum S100A8/A9), and other inflammatory biomarkers [serum interleukin (IL)-6, IL-12p70, gamma interferon-inducible protein 10 (IP-10)] levels were evaluated. Blood Pb, total urinary hydroxylated PAH (ΣOHPAH), total hydroxynaphthalene (ΣOHNap) and total hydroxyfluorene (ΣOHFlu) levels, S100A8/A9, IL-6, IL-12p70 and IP-10 concentrations, absolute counts of monocytes, neutrophils, and leukocytes, as well as CD4⁺ T cell percentages were significantly higher in exposed children. Elevated blood Pb, urinary 2-hydroxynaphthalene (2-OHNap) and ΣOHFlu levels were associated with higher levels of IL-6, IL-12p70, IP-10, CD4⁺ T cell percentages, neutrophil and monocyte counts. Mediator models indicated that neutrophils exert the significant mediation effect on the relationship between blood Pb levels and S100A8/A9. IL-6 exerts a significant mediation effect on the relationship between blood Pb levels and IP-10, as well as the relationship between urinary ΣOHFlu levels and IP-10. Our results indicate that children with elevated exposure levels of Pb and PAHs have exacerbated vascular endothelial inflammation, which may indicate future CVD risk in e-waste recycling areas.

Recently, health damage to children exposed to synthetic polyurethane (PU) running tracks has aroused social panic in China. Some possible toxic volatiles may be responsible for these damages. However, the exact cause remains unclear. We have detected a low concentration of sulfur dioxide (SO₂; 1.80–3.30 mg/m³) on the surface of the PU running track. Surprisingly, we found that SO₂ was generated from the PU running track, and even such a low concentration of SO₂ could induce severe lung inflammation with hemorrhage, inflammatory cell infiltration, and inflammatory factor secretion in mice after 2-week exposure. Prolonged exposure (5 weeks) to the SO₂ caused chronic pulmonary inflammation and pulmonary fibrosis in the mice. Peripheral hemogram results showed that platelet concentration increased significantly in the SO₂ group compared to that in the control group, and the proportion of blood neutrophils and monocytes among total leukocytes was more imbalanced in the SO₂ group (16.6%) than in the control group (8.0%). Further histopathology results of sternal marrow demonstrated that hematopoietic hyperplasia was severely suppressed with increased reticular stroma and adipocytes under SO₂ exposure. These data indicate that a low concentration of SO₂ generated spontaneously from PU running track outdoors as a secondary product is still harmful to health, as it impairs the respiratory system, hematopoiesis, and immunologic function. This indicates that the low-concentration SO₂ could be a major cause of diseases induced by air pollution, such as chronic obstructive pulmonary disease.

In this study, we explore whether altered global histone modifications respond to low-level benzene exposure as well as their association with the hematotoxicity. We recruited 147 low-level benzene-exposed workers and 122 control workers from a petrochemical factory in Maoming City, Guangdong Province, China. The internal exposure marker level, urinary S-phenylmercapturic acid (SPMA), in benzene-exposed workers was 1.81-fold higher than that of the controls (P < 0.001). ELISA method was established to examine the specific histone modifications in human peripheral blood lymphocytes (PBLCs) of workers. A decrease in the counts of white blood cells (WBC), neutrophils, lymphocytes, and monocytes appeared in the benzene-exposed group (all P < 0.05) compared to the control group. Global trimethylated histone 3 lysine 4 (H3K4me3) modification was enhanced in the benzene-exposed group (P < 0.05) and was positively associated with the concentration of urinary SPMA (β = 0.103, P = 0.045) and the extent of DNA damage (% Tail DNA: β = 0.181, P = 0.022), but was negatively associated with the leukocyte count (WBC: β = −0.038, P = 0.023). The in vitro study revealed that H3K4me3 mark was enriched in the promoters of several DNA damage responsive (DDR) genes including CRY1, ERCC2, and TP53 in primary human lymphocytes treated with hydroquinone. Particularly, H3K4me3 modification was positively correlated with the expression of CRY1 in the PBLCs of benzene-exposed workers. These observations indicate that H3K4me3 modification might mediate the transcriptional regulation of DDR genes in response to low-dose benzene exposure.

Exposure to Particulate Matter (PM) could function as an adjuvant depending on the city of origin in mice allergic asthma models. Therefore, our aim was to determine whether inhalation of fine particles (PM2.5) from Mexico City could act as an adjuvant inducing allergic sensitization and/or worsening the asthmatic response in guinea pig, as a suitable model of human asthma. Experimental groups were Non-Sensitized (NS group), sensitized with Ovalbumin (OVA) plus Aluminum hydroxide (Al(OH)3) as adjuvant (S + Adj group), and sensitized (OVA) without adjuvant (S group). All the animals were exposed to Filtered Air (FA) or concentrated PM2.5 (5 h/daily/3 days), employing an aerosol concentrator system, PM2.5 composition was characterized. Lung function was evaluated by barometric plethysmography (Penh index). Inflammatory cells present in bronchoalveolar lavage were counted as well as OVA-specific IgG1 and IgE were determined by ELISA assay. Our results showed in sensitized animals without Al(OH)3, that the PM2.5 exposure (609 ± 12.73 μg/m3) acted as an adjuvant, triggering OVA-specific IgG1 and IgE concentration. Penh index increased ∼9-fold after OVA challenge in adjuvant-sensitized animals as well as in S + PM2.5 group (∼6-fold), meanwhile NS + FA and S + FA lacked response. S + Adj + PM2.5 group showed an increase significantly of eosinophils and neutrophils in bronchoalveolar lavage. PM2.5 composition was made up of inorganic elements and Polycyclic Aromatic Hydrocarbons, as well as endotoxins and β-glucan, all these components could act as adjuvant. Our study demonstrated that acute inhalation of PM2.5 acted as an adjuvant, similar to the aluminum hydroxide effect, triggering allergic asthma in a guinea pig model. Furthermore, in sensitized animals with aluminum hydroxide an enhancing influence of PM2.5 exposure was observed as specific-hyperresponsiveness to OVA challenge (quickly response) and eosinophilic and neutrophilic airway inflammation. Fine particles from Mexico City is a complex mix, which play a significant role as adjuvant in allergic asthma.