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 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.

Recurrent pregnancy loss (RPL) is the termination of pregnancies, usually before 20 weeks of gestation, and is defined as the loss of two or more pregnancies. In Taiwan, after 2011 di-2-ethylhexyl phthalate (DEHP) exposure episode, more reproductive-aged women still expose to high levels of DEHP and di-butyl phthalate (DBP) than have women of other age groups. Phthalates might be involved in the RPL pathogenesis. This study assessed the association of phthalate exposure with RPL risk in reproductive-aged Taiwanese women.This study recruited 103 patients diagnosed by a physician with RPL of unknown etiology and 76 controls from the Department of Obstetrics and Gynecology at a medical center in southern Taiwan between August 2013 and August 2017. Urine samples were analyzed for 11 phthalate metabolites through liquid chromatography–tandem mass spectrometry; subsequently, principal component analysis (PCA) and hierarchical clustering analysis were performed to determine the main sources of phthalate exposure. Finally, multivariate logistic regression was used to determine the RPL risk.The creatinine-unadjusted median levels of mono-iso-butyl phthalate (MiBP), mono-n-butyl phthalate (MnBP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP) in RPL/control were 9.8/5.3, 27.2/13.1, 11.4/8.1, and 12.9/9.5 ng/mL, respectively; furthermore, ΣDBPm and ΣDEHPm in RPL/control were 0.18/0.10 and 0.15/0.12 nmol/mL, respectively. PCA revealed three primary components of phthalate exposure: diethyl phthalates (DEP), DEHP, and DBP. Plastic food container use and medication were identified as the main phthalate exposure sources. After adjustment for potential confounding factors (urinary creatinine, age, age at menarche, education, and plastic food container use), we found that the urinary level of ΣDBPm was significantly associated with elevated risk for RPL (OR = 2.85, p = 0.045).Our findings supported the hypothesis that exposure to phthalates increases RPL risk. The development of a strategy to reduce phthalate exposure among reproductive-aged women should be emphasized.

Metal pollution is a severe environmental issue in China, which has been recently linked with the risk of hypertension. However, relevant epidemiological studies are limited. The present exploratory study was conducted to assess the associations of environmental exposure to metals with the odds of hypertension as well as blood pressure (BP) levels using urine samples in a Chinese general population. From May 2016 to April 2017, a total of 823 eligible participants were consecutively enrolled in our study in Wuhan, China. Hypertension was defined as systolic BP (SBP) of ≥140 mmHg or diastolic BP (DBP) of ≥90 mmHg, a self-reported physician diagnosis, or current use of antihypertensive medication. We used urine samples as biomarkers to reflect the levels of environmental exposure to 20 metals. Multivariable regression models were applied to assess the potential association. Multi-metal models were conducted to investigate the impacts of co-exposure to various metals. Based on the results from various models, positive trends for increased odds of hypertension with increasing quartiles of vanadium (V), iron (Fe), zinc (Zn) and selenium (Se) were suggested. Compared with those in the lowest quartiles, participants in the highest quartiles of V, Fe, Zn and Se had a 4.4-fold, 4.9-fold, 4.2-fold and 2.5-fold increased odds of having hypertension, respectively. High urinary Hg level was found to increase the levels of DBP. Individuals in the highest group of Hg were found to have a 4.3 mmHg higher level of DBP. Our findings suggest that environmental exposure to V, Fe, Zn, Se and Hg might increase the risk of hypertension or elevate the levels of BP. These findings warrant further prospective studies in a larger population.

To characterize the source contributions of chemicals of emerging concern (CECs) from different aquatic environments of Taiwan, we collected water samples from different aquatic systems, which were screened for 30 pharmaceuticals and illicit drugs. The total estimated mass loadings of CECs were 23.1 g/d in southern aquatic systems and 133 g/d in central aquatic systems. We developed an analytical framework combining pollutant fingerprinting, hierarchical cluster analysis (HCA), and principal component analysis with multiple linear regression (PCA-MLR) to infer the pharmaco-signature and source contributions of CECs. Based on this approach, we estimate source contributions of 62.2% for domestic inputs, 16.9% for antibiotics application, and 20.9% for drug abuse/medication in southern aquatic system, compared with 47.3% domestic, 35.1% antibiotic, and 17.6% drug abuse/medication inputs to central aquatic systems. The proposed pharmaco-signature method provides initial insights into the profile and source apportionment of CECs in complex aquatic systems, which are of importance for environmental management.

The association between residential traffic exposure and change in C-reactive protein over 2-years was evaluated using multivariate linear regression including interaction models for traffic and diabetes medication use/type (insulin vs. oral hypoglycemic agents (OHAs)).The study population was Puerto Rican adults (n = 356) residing in greater Boston with type 2 diabetes. Traffic was characterized as proximity to roads with >20,000 weekday traffic volumes, and multi-directional traffic density.Increases in CRP concentration were significantly associated with residence ≤100 m of a roadway (p = 0.009) or near multiple roadways (p < 0.001), vs. further away, for individuals using insulin in stratified models, with consistent results in interaction models (p = 0.071 and p = 0.002). CRP was significantly lower with highest traffic density exposure in stratified (p = 0.03) and interaction models (p = 0.024) for individuals using OHAs.Individuals on insulin experienced increased CRP concentrations with traffic exposure over a 2-year study period, while those using OHAs did not experience increases.