Particulate matter (PM) can strongly affect redox biochemistry and therefore induce the response of the immune system and aggravate the course of autoimmune diseases. Nanoparticles containing transition metal compounds possessing semiconductor properties (TiO2, ZnO) may act as photocatalysts and accelerate the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS). In this study, the NIST standard reference material, SRM 1648a, has been analyzed in terms of this consideration. Organic compounds present in SRM 1648a were removed by cold oxygen plasma treatment. Samples of SRM 1648a with removed organic content (<2% of organic carbon, <1% of nitrogen) were obtained within 2 h of this treatment. The treatment did not affect the morphology of the powder. The reference material and PM2.5 collected in Kraków are composed of smaller particles and nanoparticles forming aggregates. The efficiency of (photo)generation of hydroxyl radicals and singlet oxygen was compared for original and organics-free samples. The analyzed samples showed the highest activity towards ROS generation when exposed to UV-vis-NIR light, moderate under UV irradiation, and the lowest in dark. Data collected in the present study suggest that the organic fraction is mostly responsible for singlet oxygen generation, as almost twice higher efficiency of 1O2 generation was observed for the original NIST sample compared to the material without the organic fraction. However, particulate matter collected in Kraków was found to have a five times higher activity in singlet oxygen generation (compared for original NIST and Kraków dust samples).

Di-isononyl phthalate (DINP) is used as a substitute for traditional phthalates, in a wide range of applications. However, there is growing concern regarding its toxicity. Studies have indicated that DINP is related to thyroid hormone disorder and that phthalates can affect thyroid normal function. In this study, we aim to determine any effects of DINP exposure on autoimmune thyroid disease (AITD), the most common autoimmune disease, and to understand the underlying causal mechanism. AITD model Wistar rats were exposed to 0.15 mg/kg, 1.5 mg/kg or 15 mg/kg DINP. We assessed the thyroid globulin antibody levels, Th1/Th2 balance, histopathological changes and caspase-3 levels in the thyroid. The data show that exposure to DINP does indeed aggravate AITD. To explore the underlying mechanisms, we examined the levels of microtubule-associated protein 1 light chain 3 B (LC3B), Sequestosome 1 (SQSTM1) and the appearance of autophagosomes or autolysosomes to assess autophagy in the thyroid. The results show that DINP can suppress normal autophagy. We found that DINP induced an exacerbation of oxidative stress and the activation of the Akt/mTOR pathway, indicating that oxidative stress and activation of mTOR may play a key role in these processes. Moreover, the activation of mTOR also promoted the expression of IL-17. Importantly, blocking oxidative stress with VE or blocking Akt/mTOR with rapamycin mitigated the exacerbation of AITD and the suppression of normal autophagy. All these results indicate that exposure to DINP, especially high doses of DINP, can aggravate oxidative stress and activate the Akt/mTOR pathway. This exposure then leads to a suppression of normal autophagy and expression of IL-17 in the thyroid, resulting in an eventual exacerbation of AITD.

Emerging pollutants are a group of substances involved in environmental contamination resulting mostly from incomplete drug metabolism, associated with inadequate disposal and ineffective effluent treatment techniques. Methotrexate (MTX), for instance, is excreted at high concentrations in unchanged form through the urine. Although the MTX is still effective in cancer and autoimmune disease treatment, this drug shows the ability of bioaccumulation and toxicity to the organism. Thus, the present work aimed to evaluate the adsorption of the MTX drug onto magnetic nanocomposites containing different amounts of incorporated magnetite (1:1, 1:5, and 1:10 wt%), combining the theoretical–experimental study as well as the in vitro cytotoxicity. Moreover, equilibrium studies (Langmuir, Freundlich, Temkin, Dubinin-Radushkevich, Hill, Redlich-Peterson, and Sips), kinetic (PFO, PSO, and IPD), and thermodynamic (ΔG°, ΔH°, and ΔS°) were used to describe the experimental data, and ab initio simulations were employed in the theoretical study. Magnetic nanocomposites were synthesized by the co-precipitation method using only FeCl₂ as the iron precursor. Adsorbents were characterized by FTIR, XRD, Raman, SEM–EDS, BET, and VSM analysis. Meanwhile, cytotoxic effects on L929 and A375 cell lines were evaluated through MTT, NR, and LDH assays. The adsorption of the MTX was carried out in a typical batch system, exploring the different experimental conditions. The theoretical study suggests the occurrence of chemisorption between CS·Fe₃O₄-MTX. The maximum adsorption capacity of MTX was 285.92 mg g⁻¹, using 0.125 g L⁻¹ of CS·Fe₃O₄ 1:1, with an initial concentration of the MTX (50 mg L⁻¹), pH 4.0 at 293 ± 1.00 K. The best adjustment of equilibrium and kinetic data were the Sips (low values for statistical errors) and PSO (qₑ = 96.73 mg g⁻¹) models, respectively. Thermodynamic study shows that the adsorption occurred spontaneously (ΔG° < 0), with exothermic (ΔH° = − 4698.89 kJ mol⁻¹) and random at the solid-solution interface (ΔS° = 1,476,022.00 kJ mol⁻¹ k⁻¹) behavior. Finally, the in vitro study shows that magnetic nanomaterials exhibit higher cytotoxicity in melanoma cells. Therefore, the magnetic nanocomposite reveals to be not only an excellent tool for water remediation studies but also a promising platform for drug delivery.

Celiac disease (CD) is an autoimmune disease with increasing prevalence in the USA. CD leads to decreased absorption of many nutrients including certain divalent metals. On the other hand, recent cross-sectional studies suggest the associations between trace heavy metal exposure and autoimmunity. We aimed to determine if there is an association between CD autoimmunity and blood levels of heavy metals in the general US population. We used nationally representative data from National Health and Nutrition Examination Survey, 2009–2012. Our study comprised 3643 children (ages 6–17 years) and 11,040 adults (age ≥18 years). Children with CD seropositivity had significantly lower blood lead (0.56 versus 0.80 μg/dL, P = 0.001) and mercury levels (0.47 versus 0.64 μg/L, P = 0.001). In the linear regression model, CD seropositivity was associated with lower levels of blood lead and mercury in children (β = −0.14, P = 0.03 for lead and β = −0.22, P = 0.008 for mercury), but not in adults. These findings of CD-heavy metals association are, to our knowledge, novel, and we conclude that decreased levels of heavy metals in blood are most likely a consequence of CD in the US children.

The immune system can be the target of many chemicals, with potentially severe adverse effects on the host’s health. In the literature, carbamate (CM) pesticides have been implicated in the increasing prevalence of diseases associated with alterations of the immune response, such as hypersensitivity reactions, some autoimmune diseases and cancers. CMs may initiate, facilitate, or exacerbate pathological immune processes, resulting in immunotoxicity by induction of mutations in genes coding for immunoregulatory factors and modifying immune tolerance. In the present study, direct immunotoxicity, endocrine disruption and inhibition of esterases activities have been introduced as the main mechanisms of CMs-induced immune dysregulation. Moreover, the evidence on the relationship between CM pesticide exposure, dysregulation of the immune system and predisposition to different types of cancers, allergies, autoimmune and infectious diseases is criticized. In addition, in this review, we will discuss the relationship between immunotoxicity and cancer, and the advances made toward understanding the basis of cancer immune evasion.

Background, aim, and scope Anti-tumour agents and their metabolites are largely excreted into effluent, along with other pharmaceuticals. In the past, investigations have focused on the input and analysis of pharmaceuticals in surface and ground water. The two oxazaphosphorine compounds, cyclophosphamide and ifosfamide are important cytostatic drugs used in the chemotherapy of cancer and in the treatment of autoimmune diseases. Their mechanism of action, involving metabolic activation and unspecific alkylation of nucleophilic compounds, accounts for genotoxic and carcinogenic effects described in the literature and is reason for environmental concern. The anti-tumour agents cyclophosphamide (CP) and ifosfamide (IF) were not biodegraded in biodegradation tests. They were not eliminated in municipal sewage treatment plants. Degradation by photochemically formed HO radicals may be of some relevance only in shallow, clear, and nitrate-rich water bodies but could be further exploited for elimination of these compounds by advanced oxidation processes, i.e. in a treatment of hospital waste water. Therefore, CP and IF are assumed to persist in the aquatic environment and to enter drinking water via surface water. The risk to humans from input of CP and IF into surface water is not known. Materials and methods The local and regional, i.e. nationwide predicted environmental concentration (PEClocal, PECregional) of CP and IF was calculated for German surface water. Both compounds were measured in hospital effluents, and in the influent and effluent of a municipal treatment plant. Additionally, published concentrations in the effluent of sewage treatment plants and surface water were used for risk assessment. Excretion rates were taken into account. For a worst-case scenario, maximum possible ingestion of CP or IF by drinking 2 L a day of unprocessed surface water over a life span of 70 years was calculated for adults. Elimination in drinking water processing was neglected, as no data is available. This intake was compared with intake during anti-cancer treatment. Results and discussion Intake of CP and IF for anti-cancer treatment is typically 10 g within a few months. Under such conditions, a relative risk of 1.5 for the carcinogenic compounds CP and IF is reported in the literature. In the worst case, the maximum possible intake by drinking water is less than 10⁻³ (IF) and 10⁻⁵ (CP) of this amount, based on highest measured local concentrations. On a nationwide average, the factor is approx. 10⁻⁶ or less. Conclusions The additional intake of CP and IF due to their emission into surface water and its use without further treatment as drinking water is low compared to intake within a therapy. This approach has shortcomings. It illustrates the current lack of methodology and knowledge for the specific risk assessment of carcinogenic pharmaceuticals in the aquatic environment. IF and CP are directly reacting with the DNA. Therefore, with respect to health effects a safe threshold concentration for these compounds cannot be given. The resulting risk is higher for newborns and children than for adults. Due to the lack of data the risk for newborns and children cannot be assessed fully. The data presented here show that according to present knowledge the additional risk of cancer cannot be fully excluded, especially with respect to children. Due to the shortage of data for effects of CP and IF in low doses during a whole lifespan, possible effects were assessed using data of high doses of CP and IF within short-term ingestion, i.e. therapy. This remains an unresolved issue. Anyway, the risk assessment performed here could give a rough measure of the risks on the one hand and the methodological shortcomings on the other hand which are connected to the assessment of the input of genotoxic and carcinogenic pharmaceuticals such as CP and IF into the aquatic environment. Therefore, we recommend to take measures to reduce the input of CP and IF and other carcinogenic pharmaceuticals. We hope that our manuscript further stimulates the discussion about the human risk assessment for carcinogenic pharmaceuticals in the aquatic environment. Recommendations and perspectives CP and IF are carcinogens. With respect to newborn and children, reduction of the emission of CP and IF into effluent and surface water is recommended at least as a precautionary measure. The collection of unused and outdated drugs is a suitable measure. Collection of patients' excreta as a measure of input reduction is not recommended. Data suitable for the assessment of the risk for newborn and children should be collected in order to perform a risk assessment for these groups. This can stimulate discussion and give new insights into risk assessment for pharmaceuticals in the environment. Our study showed that in the long term, effective risk management for the reduction of the input of CP and IF are recommendable.