Toxics — Open Access Journal

Industrial advances have led to generation of multi-component chemicals, materials and pharmaceuticals which are directly or indirectly affecting the environment. Although toxicity data are available for individual chemicals, generally there is no toxicity data of chemical mixtures. Most importantly, the nature of toxicity of these studied mixtures is completely different to the single components, which makes the toxicity evaluation of mixtures more critical and challenging. Interactions of individual chemicals in a mixture can result in multifaceted and considerable deviations in the apparent properties of its ingredients. It results in synergistic or antagonistic effects as opposed to the ideal case of additive behavior i.e., concentration addition (CA) and independent action (IA). The CA and IA are leading models for the assessment of joint activity supported by pharmacology literature. Animal models for toxicity testing are time- and money-consuming as well as unethical. Thus, computational approaches are already proven efficient alternatives for assessing the toxicity of chemicals by regulatory authorities followed by industries. In silico methods are capable of predicting toxicity, prioritizing chemicals, identifying risk and assessing, followed by managing, the risk. In many cases, the mechanism behind the toxicity from species to species can be understood by in silico methods. Until today most of the computational approaches have been employed for single chemical’s toxicity. Thus, only a handful of works in the literature and methods are available for a mixture’s toxicity prediction employing computational or in silico approaches. Therefore, the present review explains the importance of evaluation of a mixture’s toxicity, the role of computational approaches to assess the toxicity, followed by types of in silico methods. Additionally, successful application of in silico tools in a mixture’s toxicity predictions is explained in detail. Finally, future avenues towards the role and application of computational approaches in a mixture’s toxicity are discussed. Full article

Aristolochic acids (AAs) are nitrophenanthrene carboxylic acids naturally produced by Aristolochia plants. These plants were widely used to prepare herbal remedies until AAs were observed to be highly nephrotoxic and carcinogenic to humans. Although the use of AA-containing Aristolochia plants in herbal medicine is prohibited in countries worldwide, emerging evidence nevertheless has indicated that AAs are the causative agents of Balkan endemic nephropathy (BEN), an environmentally derived disease threatening numerous residents of rural farming villages along the Danube River in countries of the Balkan Peninsula. This perspective updates recent findings on the identification of AAs in food as a result of the root uptake of free AAs released from the decayed seeds of Aristolochia clematitis L., in combination with their presence and fate in the environment. The potential link between AAs and the high prevalence of chronic kidney diseases in China is also discussed. Full article

Environmental research has widely utilized the ambient concentrations of hazardous air pollutants (HAPs) modeled by the National-Scale Air Toxics Assessment (NATA) program; however, limited studies have evaluated the model’s performance. This study aims to evaluate the model-to-monitor agreement of the 2011 NATA data with the monitoring data reported to the U.S. Environmental Protection Agency’s (EPA) Air Quality System (AQS). Concentrations of 27 representative HAPs measured at 274 sites in the U.S. in 2011 were merged with NATA data by census tract. The comparison consisted of two steps for each HAP: first, the model-monitor difference at each site was compared with the limit of quantitation (LOQ); second, the modeled annual average was compared to the 95% confidence interval of the monitored annual average. Nationally, NATA could predict national medians of most HAPs well; however, it was unable to capture high concentrations. At individual sites, a large portion of model-monitor differences was below the LOQs, indicating they were unquantifiable. Model-to-monitor agreement displayed inconsistent patterns in terms of chemical groups or EPA regions and was strongly impacted by the comparison methods. The substantial non-agreements of NATA predictions with monitoring data require caution in environmental epidemiology and justice studies that are based on NATA data. Full article

Silver nanoparticles (AgNPs) are used intensively in medical and industrial applications. Environmental concerns have arisen from the potential release of this material into aquatic ecosystems. The aims of this research were to evaluate the potential accumulation of silver in the whole body of organisms and analyze the effects of AgNPs on the survival and reproduction of the snail Biomphalaria glabrata. Results show slow acute toxicity with a 10-day LC₅₀ of 18.57 mg/L and an effective decrease in the eggs and egg clutches per organism exposed to tested concentrations. Based on these data, the No Observed Effect Concentration (NOEC) observed was <1 mg/L for snail reproduction. For silver accumulation, we observed that uptake was faster than elimination, which was very slow and still incomplete 35 days after the end of the experiment. However, the observed accumulation was not connected with a concentration/response relationship, since the amount of silver was not equivalent to a higher reproductive effect. The data observed show that AgNPs are toxic to B. glabrata, and suggest that the snail has internal mechanisms to combat the presence of Ag in its body, ensuring survival and reduced reproduction and showing that the species seems to be a potential indicator for Ag presence in contaminated aquatic ecosystems. Full article

Preterm birth is an obstetric condition associated with a high risk of infant mortality and morbidities in both the neonatal period and later in life, which has also a significant public health impact because it carries an important societal economic burden. As in many cases the etiology is unknown, it is important to identify environmental factors that may be involved in the occurrence of this condition. In this review, we report all the studies published in PubMed and Scopus databases from January 1992 to January 2019, accessible as full-text articles, written in English, including clinical studies, original studies, and reviews. We excluded articles not written in English, duplicates, considering inappropriate populations and/or exposures or irrelevant outcomes and patients with known risk factors for preterm birth (PTB). The aim of this article is to identify and summarize the studies that examine environmental toxicants exposure associated with preterm birth. This knowledge will strengthen the possibility to develop strategies to reduce the exposure to these toxicants and apply clinical measures for preterm birth prevention. Full article

Background: The efficacy of chemotherapy is undermined by adverse side effects and chemoresistance of target tissues. Developing a drug delivery system can reduce off-target side effects and increase the efficacy of drugs by increasing their accumulation in target tissues. Inorganic salts have several advantages over other drug delivery vectors in that they are non-carcinogenic and less immunogenic than viral vectors and have a higher loading capacity and better controlled release than lipid and polymer vectors. Methods: MgF₂ crystals were fabricated by mixing 20 mM MgCl₂ and 10 mM NaF and incubating for 30 min at 37 °C. The crystals were characterized by absorbance, dynamic light scattering, microscopic observance, pH sensitivity test, SEM, EDX and FTIR. The binding efficacy to doxorubicin was assessed by measuring fluorescence intensity. pH-dependent doxorubicin release profile was used to assess the controlled release capability of the particle-drug complex. Cellular uptake was assessed by fluorescence microscopy. Cytotoxicity of the particles and the drug-particle complex were assessed using MTT assay to measure cell viability of MCF-7 cells. Results and Discussion: Particle size on average was estimated to be <200 nm. The crystals were cubic in shape. The particles were pH-sensitive and capable of releasing doxorubicin in increasing acidic conditions. MgF₂ nanocrystals were safe in lower concentrations, and when bound to doxorubicin, enhanced its uptake. The protein corona formed around MgF₂ nanoparticles lacks typical opsonins but contains some dysopsonins. Conclusion: A drug delivery vector in the form of MgF₂ nanocrystals has been developed to transport doxorubicin into breast cancer cells. It is pH-sensitive (allowing for controlled release), size-modifiable, simple and cheap to produce. Full article

Opiate use during pregnancy has been an increasing problem over the last two decades, making it an important social and health concern. The use of such substances may have serious negative outcomes in the newborn, and clinical and cognitive conditions have been reported, including neonatal abstinence syndrome, developmental problems, and lower cognitive performance. These conditions are common when opiates are used during pregnancy, making the prescription of these kinds of drugs problematic. Moreover, the mother may develop opiate addiction, thus, increasing the likelihood of the infant being born with any of those conditions. This paper reviews the use of opiates during pregnancy and focuses mainly on the neonatal abstinence syndrome. First, the commonly prescribed opiates will be identified, namely those usually involved in cases of addiction and/or neonatal abstinence syndrome. Second, published approaches to deal with those problems will be presented and discussed, including the treatment of both the mother and the infant. Finally, we will outline the treatments that are safest and most efficient, and will define future goals, approaches, and research directions for the scientific community regarding this problem. Full article

A simple microextraction method, magnetic stirring assisted demulsification dispersive liquid–liquid microextraction, for preconcentration of five polycyclic aromatic hydrocarbons (fluorene, phenanthrene, anthracene, fluoranthrene, and pyrene) was investigated prior to analysis by high performance liquid chromatography. In this method, a mixture of extraction solvent and disperser solvent was rapidly injected into sample solution. The magnetic stirrer agitator aided the dispersion of the extraction solvent into the sample solution. After the formation of an emulsion, the demulsifier was added, resulting in the rapid separation of the mixture into two phases. No centrifugation step was required. Several parameters affecting the extraction efficiency of the proposed method were studied, including addition of salt, kind and volume of extraction solvent, volume of demulsifier solvent, and extraction times. Under the optimum conditions, high enrichment factor, low limit of detections (LODs) and good precision were gained. The proposed method was successfully applied to analysis of polycyclic aromatic hydrocarbon residues in grilled pork samples. Full article

The general population is exposed to the genotoxic carcinogen glycidol via food containing refined edible oils where glycidol is present in the form of fatty acid esters. In this study, internal (in vivo) doses of glycidol were determined in a cohort of 50 children and in a reference group of 12 adults (non-smokers and smokers). The lifetime in vivo doses and intakes of glycidol were calculated from the levels of the hemoglobin (Hb) adduct N-(2,3-dihydroxypropyl)valine in blood samples from the subjects, demonstrating a fivefold variation between the children. The estimated mean intake (1.4 μg/kg/day) was about two times higher, compared to the estimated intake for children by the European Food Safety Authority. The data from adults indicate that the non-smoking and smoking subjects are exposed to about the same or higher levels compared to the children, respectively. The estimated lifetime cancer risk (200/10⁵) was calculated by a multiplicative risk model from the lifetime in vivo doses of glycidol in the children, and exceeds what is considered to be an acceptable cancer risk. The results emphasize the importance to further clarify exposure to glycidol and other possible precursors that could give a contribution to the observed adduct levels. Full article

Particulate matter (PM) exposure and metabolic syndrome (MetSyn) are both significant global health burdens. PM exposure has been implicated in the pathogenesis of MetSyn and cardiopulmonary diseases. Individuals with pre-existing MetSyn may be more susceptible to the detrimental effects of PM exposure. Our aim was to provide a narrative review of MetSyn/PM-induced systemic inflammation in cardiopulmonary disease, with a focus on prior studies of the World Trade Center (WTC)-exposed Fire Department of New York (FDNY). We included studies (1) published within the last 16-years; (2) described the epidemiology of MetSyn, obstructive airway disease (OAD), and vascular disease in PM-exposed individuals; (3) detailed the known mechanisms of PM-induced inflammation, MetSyn and cardiopulmonary disease; and (4) focused on the effects of PM exposure in WTC-exposed FDNY firefighters. Several investigations support that inhalation of PM elicits pulmonary and systemic inflammation resulting in MetSyn and cardiopulmonary disease. Furthermore, individuals with these preexisting conditions are more sensitive to PM exposure-related inflammation, which can exacerbate their conditions and increase their risk for hospitalization and chronic disease. Mechanistic research is required to elucidate biologically plausible therapeutic targets of MetSyn- and PM-induced cardiopulmonary disease. Full article

Endocrine Disruptor Compounds (EDCs) are synthetic or natural molecules in the environment that promote adverse modifications of endogenous hormone regulation in humans and/or in wildlife animals. In the present paper, we review the potential mechanisms of EDCs and point out the similarities and differences between EDCs and hormones. There was only one mechanism, out of nine identified, in which EDCs acted like hormones (i.e., binding and stimulated hormone receptor activity). In the other eight identified mechanisms of action, EDCs exerted their effects either by affecting endogenous hormone concentration, or its availability, or by modifying hormone receptor turn over. This overview is intended to classify the various EDC mechanisms of action in order to better appreciate when in vitro tests would be valid to assess their risks towards humans and wildlife. Full article

In Taiwan and other countries, glyphosate has been used widely as a non-selective herbicide over 40 years in crop lands and non-crop lands. However, public concerns about its environmental and health risks have increased rapidly because the International Agency for Research on Cancer (IARC) reclassified it as Group 2A (probably carcinogenic to humans) in 2015. From the viewpoints of environmental quality, food security and human health, it is necessary to regulate the release of glyphosate into the environment due to its massive use. The purpose of this case study was to analyze the historical consumption of glyphosate in Taiwan and also summarize its current regulatory measures through multi-ministerial levels. It showed that the sales quantities of glyphosate in Taiwan can be grouped into three stages, which include a ramping period (1984–1992), a stable period (1992–2007), and a declining period (2007–2016). These variations can be correlated with the annual price, manufacturers’ promotion and other non-selective herbicide competitors (i.e., paraquat and glufosinate), as well as the excellent action features of glyphosate. It should be noted that its sales quantities significantly increased from 3200 metric tons in 2015 to 4535 metric tons in 2016 mainly due to the official announcement of paraquat ban effective in February 2019. The core regulations for protecting food security and water quality from the use of glyphosate are based on its residual limits and standards under the authorization of the Food Sanitation Management Act (FSMA) and the Water Pollution Control Act (WPCA), respectively. More importantly, there are occasional reports of contamination by herbicides (including glyphosate) in drinking water sources. Unfortunately, glyphosate is not yet considered among chemical items when evaluating drinking water quality standards in Taiwan. Full article

The uptake of trace elements by wild herbaceous plants in a multiple trace element-contaminated site was investigated. The bioaccumulation factor (BF) of trace elements was markedly variable among the different plant species. On average, the BF for various trace elements was in the following decreasing order: Zn > Cu > Mn > Ni > As > Pb > Cr. The translocation factor among the investigated plant species was also considerably variable and showed the following decreasing order: Mn > Zn > Ni > Cu > Cr > As > Pb. Several hyperaccumulating plants were identified: Artemisia vulgaris for As, Mn and Zn, Phalaris arundinacea for Mn and Ni, Heracleum sphondylium for Cr and Zn, and Bistorta officinalis for Mn and Zn. The marked accumulation of trace elements in the plant tissue suggests that the site may not be suitable for urban agricultural production. The plant tissue-borne trace elements could affect microbial activities and consequently interfere with the ecosystem functioning in the affected areas. Full article

The four heat-induced coffee contaminants—acrylamide, furfuryl alcohol (FA), furan and 5-hydroxymethylfurfural (HMF)—were analyzed in a collective of commercial samples as well as in Coffea arabica seeds roasted under controlled conditions from very light Scandinavian style to very dark Neapolitan style profiles. Regarding acrylamide, average contents in commercial samples were lower than in a previous study in 2002 (195 compared to 303 µg/kg). The roasting experiment confirmed the inverse relationship between roasting degree and acrylamide content, i.e., the lighter the coffee, the higher the acrylamide content. However, FA, furan and HMF were inversely related to acrylamide and found in higher contents in darker roasts. Therefore, mitigation measures must consider all contaminants and not be focused isolatedly on acrylamide, specifically since FA and HMF are contained in much higher contents with lower margins of exposure compared to acrylamide. Full article

The execution of agricultural activities on an industrial scale has led to indiscriminate deposition of toxic xenobiotics, including organophosphates, in the biome. This has led to intoxication characterized by deleterious oxidative and neuronal changes. This study investigated the consequences of oxidative and neurogenic disruptions that follow exposure to a combination of two organophosphates, chlorpyrifos (CPF) and dichlorvos (DDVP), on neuro-cognitive performance and anxiety-like behaviors in rats. Thirty-two adult male Wistar rats (150–170 g) were randomly divided into four groups, orally exposed to normal saline (NS), DDVP (8.8 mg/kg), CPF (14.9 mg/kg), and DDVP + CPF for 14 consecutive days. On day 10 of exposure, anxiety-like behavior and amygdala-dependent fear learning were assessed using open field and elevated plus maze paradigms, respectively, while spatial working memory was assessed on day 14 in the Morris water maze paradigm, following three training trials on days 11, 12, and 13. On day 15, the rats were euthanized, and their brains excised, with the hippocampus and amygdala removed. Five of these samples were homogenized and centrifuged to analyze nitric oxide (NO) metabolites, total reactive oxygen species (ROS), and acetylcholinesterase (AChE) activity, and the other three were processed for histology (cresyl violet stain) and proliferative markers (Ki67 immunohistochemistry). Marked (p ≤0.05) loss in body weight, AChE depletion, and overproduction of both NO and ROS were observed after repeated exposure to individual and combined doses of CPF and DDVP. Insults from DDVP exposure appeared more severe owing to the observed greater losses in the body weights of exposed rats. There was also a significant (p ≤0.05) effect on the cognitive behaviors recorded from the exposed rats, and these deficits were related to the oxidative damage and neurogenic cell loss in the hippocampus and the amygdala of the exposed rats. Taken together, these results provided an insight that oxidative and neurogenic damage are central to the severity of neuro-cognitive dysfunction and increased anxiety-like behaviors that follow organophosphate poisoning. Full article

This study was undertaken to determine whether exposure of operating room personnel to inhalation anesthetics, nitrous oxide, isoflurane, and sevoflurane was associated with any hematological changes. This historical cohort study was performed in 2018 at a large public hospital in Shiraz, where 52 operating room personnel and 52 administrative staff were investigated. The blood sample was taken from all individuals for Complete Blood Count. Furthermore, demographic information was collected through questionnaires. Mean atmospheric concentrations of nitrous oxide, isoflurane, and sevoflurane, to which subjects were exposed, were 850.92, 2.40, and 0.18 ppm, respectively. The hematological parameters were within the normal range in both groups. However, the mean values of hemoglobin, hematocrit, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, and red blood cell count in the exposed group were significantly lower than the control group. No significant differences were noted between the two groups as far as other hematological factors were concerned. These findings provide circumstantial evidence to further substantiate the notion that occupational exposure to inhalation anesthetics, under the exposure scenario explained in this study, is associated with subtle, subclinical, prepathologic hematological changes. Long-term consequence and ramifications of these effects require further investigation. The range of exposure levels to anesthetic gases in operating rooms. Full article

A novel method was developed for the sensitive, cheap and fast quantitation of 10 phthalates in non-alcoholic beverages by liquid–liquid extraction (LLE) combined with gas chromatography tandem mass spectrometry (GC-MS/MS). The best results were obtained when n-hexane was used as extraction solvent. A central composite design (CCD) was applied to select the most appreciated operating condition. The method performance was evaluated according to the SANTE/11945/2015 guidelines and was linear in the 0.1 to 200 µg/L range for 10 phthalate compounds, with r² > 0.996 and individual residuals <15%. Repeatability (RSD_r), within-laboratory reproducibility (RSD_wr), and the trueness range were from 2.7 to 9.1%, from 3.4 to 14.3% and from 91.5 to 118.1%, respectively. The limit of detection (LOD) was between 0.5 to 1.0 ng/L and the limit of quantitation (LOQ) was between 1.5 to 3.0 ng/L for all 10 compounds. The developed method was successfully applied to the analysis of non-alcoholic beverages. Full article

Air pollution has become an emerging invisible killer in recent years and is a major cause of morbidity and mortality globally. More than 90% of the world’s children breathe toxic air every day. India is among the top ten most highly polluted countries with an average PM₁₀ level of 134 μg/m³ per year. It is reported that 99% of India’s population encounters air pollution levels that exceed the World Health Organization Air Quality Guideline, advising a PM_2.5 permissible level of 10 μg/m³. Maternal exposure to air pollution has serious health outcomes in offspring because it can affect embryonic phases of development during the gestation period. A fetus is more prone to effects from air pollution during embryonic developmental phases due to resulting oxidative stress as antioxidant mechanisms are lacking at that stage. Any injury during this vulnerable period (embryonic phase) will have a long-term impact on offspring health, both early and later in life. Epidemiological studies have revealed that maternal exposure to air pollution increases the risk of development of airway disease in the offspring due to impaired lung development in utero. In this review, we discuss cellular mechanisms involved in maternal exposure to air pollution and how it can impact airway disease development in offspring. A better understanding of these mechanisms in the context of maternal exposure to air pollution can offer a new avenue to prevent the development of airway disease in offspring. Full article