Cyclophosphamide (CP) is an antineoplastic drug widely used in chemotherapy treatments with high consumption rates and that has been detected in the aquatic environment. After being released into the aquatic environment, CP may cause adverse effects on aquatic organisms since antineoplastics are well-known cytotoxic, genotoxic, mutagenic and teratogenic drugs. Moreover, predicted environmental changes, such as the temperature rising, may alter the impacts caused by CP on organisms. Thus, the present study aimed to assess the effects caused by CP chronic exposure in the mussel Mytilus galloprovincialis, under actual and predicted warming scenarios. Organisms were exposed for 28 days to different concentrations of CP (10, 100, 500 and 1000 ng/L) at control (17 ± 1.0 °C) and increased (21 ± 1.0 °C) temperatures. Biochemical responses related to metabolic capacity, energy reserves, oxidative stress and neurotoxicity were assessed. The results showed that the organisms were able to maintain their metabolic capacity under all exposure conditions. However, their antioxidant defense mechanisms were activated mostly at higher CP concentrations being able to prevent cellular damage, even under the warming scenario. Overall, the present findings suggest that temperature rise may not alter the impacts of CP towards M. galloprovincialis.

Short-term exposure to air pollution has pro-thrombotic effects and triggers thrombo-embolic events such as myocardial infarction or stroke in adults. This study evaluates the association between short-term variation in air pollution and treatments for acute thrombo-embolic events among the whole Belgian population. In a bidirectional time-stratified case-crossover design, we included 227,861 events treated with endovascular intervention and 74,942 with antithrombotic enzymes that were reimbursed by the Belgian Social Security between January 1st, 2009 and December 31st, 2013. We compared the concentrations of particulate matter (PM) air pollution (PM₁₀ and PM₂.₅), as estimated at the municipality level on the day of the event (lag 0) and two days earlier (lag 1 and lag 2) with those of control days from the same month, matched by temperature and accounting for day of the week (weekend vs week days). We applied conditional logistic regression models to obtain odds ratios (OR) and their 95% CI for an increase of 10 μg/m³ (PM₁₀) or 5 μg/m³ (PM₂.₅) in pollutant concentrations over three lag days (lag 0, 1 and 2). We observed significant associations of PM₁₀ and PM₂.₅ with treatment of acute thrombo-embolic events at the three lags. The strongest associations were observed for air pollution concentrations on the day of the event (lag0). Increases of 10 μg/m³ PM₁₀ and 5 μg/m³ PM₂.₅ on lag0 increased the odds of events treated with endovascular intervention by 2.7% (95%CI:2.3%–3.2%) and 1.3% (95%CI:1%–1.5%), respectively, and they increased the odds of events treated with antithrombotic enzymes by 1.9% (95%CI:1.1–2.7%) and 1.2% (95%CI:0.7%–1.6%), respectively. The associations were generally stronger during autumn months and among children. Our nationwide study confirms that acute exposure to outdoor air pollutants such as PM₁₀ or PM₂.₅ increase the use of medication and interventions to treat thrombo-embolic events.

Limited research has examined the impacts of coal mine fire smoke on human health. The aim of this study was to assess the association between prolonged smoke PM₂.₅ exposure from a brown coal mine fire that burned over a seven week period in 2014 and medications dispensed across five localities in South-eastern Victoria, Australia. Spatially resolved PM₂.₅ concentrations were retrospectively estimated using a dispersion model coupled with a chemical transport model. Data on medications dispensed were collected from the national Pharmaceutical Benefits Schedule database for 2013–2016. Poisson distributed lag time series analysis was used to examine associations between daily mine fire-related PM₂.₅ concentrations and daily counts of medications dispensed for respiratory, cardiovascular or psychiatric conditions. Factors controlled for included: seasonality, long-term trend, day of the week, maximum ambient temperature and public holidays. Positive associations were found between mine fire-related PM₂.₅ and increased risks of medications dispensed for respiratory, cardiovascular and psychiatric conditions, over a lag range of 3–7 days. A 10 μg/m³ increase in coal mine fire-related PM₂.₅ was associated with a 25% (95%CI 19–32%) increase in respiratory medications, a 10% (95%CI 7–13%) increase in cardiovascular medications and a 12% (95%CI 8–16%) increase in psychiatric medications dispensed. These findings have the potential to better prepare for and develop more appropriate public health responses in the event of future coal mine fires.

The increasing consumption of anticancer drugs through single and/or combinatory chemotherapy worldwide raised concern regarding their toxicity burden in coastal zones. The toxicity of a mixture of three compounds involving the drugs cisplatin (CisPt), cyclophosphamide (CP) and tamoxifen (TAM) was determined on the marine polychaete Nereis diversicolor exposed to an increasing range of their concentrations, respectively: Mix A: 0.1 + 10 + 0.1 ng L−1; Mix B: 10 + 100 + 10 ng L−1; Mix C: 100 + 500 + 25 ng L−1; Mix D: 100 + 1000 + 100 ng L−1. Different endpoints were assessed, including disturbance in the burrowing behaviour, neurotoxicity (acetylcholinesterase – AChE activity), antioxidant enzymes (superoxide dismutase – SOD; catalase – CAT; selenium-dependent glutathione peroxidase – Se-GPx and total glutathione peroxidases T-GPx activities), biotransformation metabolism (glutathione-S-transferases - GST), lipid peroxidation (LPO) and genotoxicity (DNA damage). Biological effects of the mixtures of anticancer compounds on N. diversicolor were compared with previous studies about effects on the same biological model under single-drug exposure conducted with the same molecules. Regarding SOD activity, TAM showed an antagonist effect over CisPt and CP in mixtures C and D. In Mix D, there was a synergistic effect of TAM and CisPt that inhibited CAT activity and an additive interaction of CisPt and CP on the Phase II biotransformation enzyme. Drugs in Mix A also suppressed polychaetes' GST activity, although different from the respective single-drug responses, besides able to induce T-GPx activity, that was not sufficient to avoid oxidative damage and mid-grade DNA damage. Due to the absence of burrowing impairment in Mix A, mechanisms involved in neurotoxicity were other than the one driven by AChE alterations. At the intermediary concentrations (Mix B and C), only LPO occurred. Data from drugs individually may not predict the risks provided by mixtures.

Congenital heart defects (CHDs) are a major cause of death in infancy and childhood. Major risk factors for most CHDs, particularly those resulting from the combination of environmental exposures with social determinants and behaviors, are still unknown. This study evaluated the main effect of maternal environmental tobacco smoke (ETS), and its interaction with social-demographics and environmental factors on CHDs in China. A population-based, matched case-control study of 9452 live-born infants and stillborn fetuses was conducted using the Guangdong Registry of Congenital Heart Disease data (2004–2014). The CHDs were evaluated by obstetrician, pediatrician, or cardiologist, and confirmed by cardia tomography/catheterization. Controls were randomly chosen from singleton newborns without any malformation, born in the same hospital as the cases and 1:1 matched by infant sex, time of conception, and parental residence (same city and town to ensure sufficient geographical distribution for analyses). Face-to-face interviews were conducted to collect information on demographics, behavior patterns, maternal disease/medication, and environmental exposures. Conditional logistic regression was used to estimate odds ratios and 95% confidence intervals of ETS exposure on CHDs while controlling for all risk factors. Interactive effects were evaluated using a multivariate delta method for maternal demographics, behavior, and environmental exposures on the ETS-CHD relationship. Mothers exposed to ETS during the first trimester of pregnancy were more likely to have infants with CHD than mothers who did not (aOR = 1.44, 95% CI 1.25–1.66). We also observed a significant dose-response relationship when mothers were exposed to ETS and an increasing number of risk factors and CHDs. There were greater than additive interactions for maternal ETS and migrant status, low household income and paternal alcohol consumption on CHDs. Maternal low education also modified the ETS-CHD association on the multiplicative scale. These findings may help to identify high-risk populations for CHD, providing an opportunity for targeted preventive interventions.

The use of chemotherapy agents has been growing worldwide, due to the increase number of cancer cases. In several countries, mainly in Europe countries, these drugs have been detected in hospitals and municipal wastewaters. In Brazil this issue is poorly explored. The main goal of this study was to assess the presence of three anti-cancer drugs, 5-fluorouracil (5-FU), gemcitabine (GEM) and cyclophosphamide (CP), and two metabolites, alpha-fluoro-beta-alanine (3-NH₂-F) and 2′-deoxy-2′,2′-difluorouridine (2-DOH-DiF), in effluents from a large cancer hospital, in the municipal wastewater treatment plant (WWTP) influent and effluent, and also to evaluate toxicity of the mixtures of these compounds by ecotoxicological testing in zebrafish. The sample collections were performed in Barretos Cancer Hospital of the large cancer center in Brazil. After each collection, the samples were filtered for subsequent Liquid Chromatography Mass Spectrometry analysis. The presence of CP, GEM, and both metabolites (3-NH₂-F and 2-DOH-DiF) were detected in the hospital wastewater and the WWTP influent. Three drugs, GEM, 2-DOH-DiF and CP, were detected in the WWTP effluent. Two drugs were detected below the limit of quantification, 2-DOH-DiF: <LOQ (above 1400 ng L⁻¹) and CP: <LOQ (above 300 ng L⁻¹), and GEM was quantified at 420 ng L⁻¹. Furthermore, 2-DOH-DiF (116,000 ng L⁻¹) was detected at the highest level in the hospital wastewater. There were no zebrafish deaths at any of the concentrations of the compounds used. However, we observed histological changes, including aneurysms and edema in the gills and areas of necrosis of the liver. In summary, we found higher concentrations of CP, GEM and both metabolites (3-NH₂-F and 2-DOH-DiF) were detected for the first time. There is currently no legislation regarding the discharge of anti-cancer drugs in effluents in Brazil. This study is first to focus on effluents from specific treatments from a large cancer hospital located in small city in Brazil.

Evidence of health effects following early life exposure to short-to-medium duration of high pollution levels is extremely limited.We aimed to evaluate the associations between: 1. intrauterine exposure to fine particulate matter (PM2.5) from coal mine fire emissions and the frequencies of general practitioner attendances and dispensations of prescribed asthma inhalers, steroid skin creams, and antibiotics during the first year of life; 2. infant exposure and those outcomes during the year following the fire.All participants were recruited from the Latrobe Valley of Victoria, Australia. Participants’ 24-h average and hourly peak mine fire-specific PM2.5 exposures from 09/02/2014 to 31/03/2014 were estimated using chemical transport modelling. Outcome data were obtained from the Australian Medicare Benefits Schedule and Pharmaceutical Benefits Scheme from each child’s birth to 31/12/2016. We used negative binomial and logistic regression models to independently assess risks of the outcomes associated with every 10 and 100 μg m−3 increase in average or peak PM2.5 exposure, respectively, while adjusting for potential confounders.We included 286 of 311 children whose parents consented to be linked, comprising 77 with no exposure, 88 with intrauterine exposure and 121 with exposure in infancy. 10- and 100- μg m−3 increases in average and peak PM2.5 exposure during infancy were associated with greater incidence of antibiotics being dispensed during the year following the fire: the adjusted incidence rate ratios were 1.24 (95% CI 1.02, 1.50, p = 0.036) and 1.14 (1.00, 1.31, p = 0.048) respectively. No other significant associations were observed.Exposure to coal mine fire emissions during infancy was associated with increased dispensing of antibiotics. This could reflect increased childhood infections or increased prescriptions of antibiotics in the year following the fire.

This study addresses the occurrences and natural fates of chemotherapeutics and controlled drugs when found together in hospital effluents and surface waters. The results revealed the presence of 11 out of 16 drugs in hospital effluents, and the maximum detected concentrations were at the μg L−1 level in the hospital effluents and the ng L−1 level in surface waters. The highest concentrations corresponded to meperidine, morphine, 5-fluorouracil and cyclophosphamide. The sunlight photolysis of the target compounds was investigated, and the results indicated that morphine and codeine can be significantly attenuated, with half-lives of 0.27 and 2.5 h, respectively, in natural waters. Photolysis can lower the detected environmental concentrations, also lowering the estimated environmental risks of the target drugs to human health. Nevertheless, 5-fluorouracil and codeine were found to have a high risk quotient (RQ), demonstrating the high risks of directly releasing hospital wastewater into the environment.

Antibiotics are among the most successful drugs used for human therapy. However, since they can challenge microbial populations, they must be considered as important pollutants as well. Besides being used for human therapy, antibiotics are extensively used for animal farming and for agricultural purposes. Residues from human environments and from farms may contain antibiotics and antibiotic resistance genes that can contaminate natural environments. The clearest consequence of antibiotic release in natural environments is the selection of resistant bacteria. The same resistance genes found at clinical settings are currently disseminated among pristine ecosystems without any record of antibiotic contamination. Nevertheless, the effect of antibiotics on the biosphere is wider than this and can impact the structure and activity of environmental microbiota. Along the article, we review the impact that pollution by antibiotics or by antibiotic resistance genes may have for both human health and for the evolution of environmental microbial populations. The article reviews the current knowledge on the effects that pollution by antibiotics and antibiotic resistance genes may have for the microbiosphere.

The long-term associations between multiple metals and incident diabetes are uncertain. We aimed to examine the relationship between plasma concentrations of 23 metals and the incidence of type 2 diabetes among Chinese senior adults. We quantified fasting plasma concentrations of 23 metals by inductively coupled plasma mass spectrometry among 1039 incident diabetes cases and 1039 controls (age and sex matched) nested in a prospective study, the Dongfeng-Tongji cohort. Both cases and controls were free of diabetes at baseline (2008–2010), incident diabetes were identified using the following criteria: fasting glucose ≥ 7.0 mmoL/l; or hemoglobin A1c (HbA1c) ≥ 6.5%; or self-reported physician diagnosis of diabetes or use of anti-diabetic medication during the follow-up visits in 2013. In the conditional logistic regression models, the multivariable adjusted ORs (95% CIs) of diabetes across quartiles (Q1–Q4) of metal concentrations were as follows: titanium, 1.00, 0.92, 1.31, 1.38 (1.00–1.91, Ptrend = 0.011); selenium, 1.00, 1.08, 1.45, 1.27 (0.93–1.74, Ptrend = 0.05); and antimony, 1.00, 0.79, 0.77, 0.60 (0.44–0.83, Ptrend = 0.002). Arsenic was significantly associated with diabetes in the crude model (ORs comparing extreme quartiles 1.30; 1.02–1.65; Ptrend = 0.006), but was not significant after adjustment for socio-demographic factors. No significant associations were found for other metals. In conclusion, titanium and selenium were positively while antimony was negatively associated with incident diabetes.