Skeletal pathology and bone mineral density changes in wild muskrats (Ondatra zibethicus) and red squirrels (Tamiasciurus hudsonicus) inhabiting arsenic polluted areas of Yellowknife, Northwest Territories (Canada): A radiographic densitometry study.

The City of Yellowknife is a known hotspot of arsenic contamination and there is a growing body of evidence suggesting that local wildlife in the vicinity of the abandoned Giant Mine site may be at risk of decreased bone mineralization and various bone disorders. The purpose of this study was to preliminarily measure bone mineral density (BMD) changes and investigate the incidence, pattern, and severity of bone lesions in wild muskrats and red squirrels breeding in three (3) catchment areas at different distances from the Giant Mine Site in Yellowknife, Northwest Territories (Canada): ~2 km (location 1), ~18 km (location 2), and ~40-100 km (location 3). Full femoral bones of 15 muskrats and 15 red squirrels were collected from the three sampling locations (5 from each location) and subjected to radiographic analysis and densitometric measurements. The patterns and severities of bone lesions, including changes in bone mineral density, were evaluated and compared between groups. As levels were significantly higher in the bones of muskrats caught from location 1 and 2, relative to location 3. Further, As and Cd levels were significantly higher in the bones of squirrels caught from locations 1 and 2 relative to squirrels caught from location 3. The preliminary results from bones revealed that radiographic abnormalities such as bone rarefaction, osteopenia, and thinning of the femoral shafts with significant ossific cystic lesions and bowing were the most common skeletal pathologies found in bones of red squirrels from the three locations. Radiographic appearances of massive sclerosis and dysplasia, including severe osteocondensation and osteopathia striata-like abnormalities, were found in the bones of muskrats from all the sampling locations. Densitometric evaluation showed no significant differences between the three locations in the bone parameters measured. However, there was a statistically significant correlation between As content in the bones of muskrats and percent fat content in the femur samples, which suggests that accumulation of As could have been a causal factor for a change in percent fat in femurs of muskrats.

On Placental Toxicology Studies and Cerium Dioxide Nanoparticles.

The human placenta is a transient organ essential for pregnancy maintenance, fetal development and growth. It has several functions, including that of a selective barrier against pathogens and xenobiotics from maternal blood. However, some pollutants can accumulate in the placenta or pass through with possible repercussions on pregnancy outcomes. Cerium dioxide nanoparticles (CeO2 NPs), also termed nanoceria, are an emerging pollutant whose impact on pregnancy is starting to be defined. CeO2 NPs are already used in different fields for industrial and commercial applications and have even been proposed for some biomedical applications. Since 2010, nanoceria have been subject to priority monitoring by the Organization for Economic Co-operation and Development in order to assess their toxicity. This review aims to summarize the current methods and models used for toxicology studies on the placental barrier, from the basic ones to the very latest, as well as to overview the most recent knowledge of the impact of CeO2 NPs on human health, and more specifically during the sensitive window of pregnancy. Further research is needed to highlight the relationship between environmental exposure to CeO2 and placental dysfunction with its implications for pregnancy outcome.

"Bisphenol a: an emerging threat to male fertility".

BACKGROUND: Among the factors causing male infertility, one of the most debated is the exposure to environmental contaminants. Recently, the chemical compound Bisphenol A (BPA) has drawn attention from the reproductive science community, due to its ubiquitous presence in day-to-day life. Its toxic action appears to mainly affect the male reproductive system, directly impacting male fertility. MAIN: The purpose of this review is to investigate current research data on BPA, providing an overview of the findings obtained from studies in animal and human models, as well as on its supposed mechanisms of action. CONCLUSION: A clear understanding of BPA action mechanisms, as well as the presumed risks deriving from its exposure, is becoming crucial to preserve male fertility. The development and validation of methodologies to detect BPA toxic effects on reproductive organs can provide greater awareness of the potential threat that this chemical represents.

Assessment of Endothelial Dysfunction with Methylated Arginines and L-arginine in Cadmium-Exposed People: a Pilot Study.

BACKGROUND: Workers can be exposed to cadmium (Cd) in various industries. On the other hand, another potential source for Cd exposure is the food chain and smoking. Environmental pollution to Cd plays an important role in the development of atherosclerosis. Asymmetric dimethyl arginine (ADMA) levels promote the development of endothelial dysfunction and atherosclerosis-related diseases such as hypertension, acute coronary syndrome, congestive heart failure, and peripheral vascular diseases. The aim of this study is to evaluate the cardiovascular risks of non-symptomatic cadmium-exposed workers and to promote the value of methylated arginines in screening of toxic exposures. METHODS: A total 176 participants were included in the study which has been separated as control group (n = 79) and Cd-exposed group (n = 94). Inductively Coupled Plasma Mass Spectrometry (ICP-MS) was used for toxicological analysis of Cd levels. Also, liquid Chromatography-Mass Spectrometry (LC-MS/MS) was used for levels of methylated arginines such as ADMA, symmetric dimethylarginine (SDMA), NG-monomethyl-L-arginine (L-NM-MA), homoarginine, and citrulline. RESULTS: Statistically significant differences were observed for control and Cd-exposed groups, respectively as follows: Cd levels (0.25 ± 0.13 µg/L and 1.33 ± 0.61 µg/L), ADMA (0.16 ± 0.04 µmol/L and 0.22 ± 0.11 µmol/L), SDMA (0.21 ± 0.06 µmol/L and 0.27 ± 0.07 µmol/L), L-NMMA(0.02 ± 0.01 µmol/L and 0.03 ± 0.01µmol/L), and arginine/ADMA levels (695.82 ± 620.63 and 478.30 ± 432.61). CONCLUSIONS: Our results suggest that workers chronically exposed to Cd showed imbalances in endothelial parameters.

Ambient temperature and pesticide poisoning: a time-series analysis.

Limited studies have explored the association between ambient temperature and the disease burden of pesticide poisoning. Our study aims to estimate associations between daily mean temperature and pesticide poisoning incidence with lag effect. A distributed lag nonlinear model with Poisson distribution was used to examine the nonlinear lagged effects of ambient temperature on pesticide poisoning incidence. Overall, the estimated effects of temperature on pesticide poisoning incidence were non-linear, with higher relative risks (RRs) at hotter temperatures. It was found that the high temperature had acute and short-term effects and then declined rapidly along the lag days with the maximum risk occurring 0 day of exposure. Considering the 5-day cumulative RR for daily mean temperature, the temperature generally showed a positive association with the pesticide poisoning incidence, achieving the maximum risk at 31°C. In general, pesticide poisoning incidence increased with higher temperatures, with the strongest effects occurring shortly.

Psychoactive pharmaceuticals at environmental concentrations induce in vitro gene expression associated with neurological disorders.

BACKGROUND: A number of researchers have speculated that neurological disorders are mostly due to the interaction of common susceptibility genes with environmental, epigenetic and stochastic factors. Genetic factors such as mutations, insertions, deletions and copy number variations (CNVs) are responsible for only a small subset of cases, suggesting unknown environmental contaminants play a role in triggering neurological disorders like idiopathic autism. Psychoactive pharmaceuticals have been considered as potential environmental contaminants as they are detected in the drinking water at very low concentrations. Preliminary studies in our laboratory identified gene sets associated with neuronal systems and human neurological disorders that were significantly enriched after treating fish brains with psychoactive pharmaceuticals at environmental concentrations. These gene expression inductions were associated with changes in fish behavior. Here, we tested the hypothesis that similar treatments would alter in vitro gene expression associated with neurological disorders (including autism) in human neuronal cells. We differentiated and treated human SK-N-SH neuroblastoma cells with a mixture (fluoxetine, carbamazepine and venlafaxine) and valproate (used as a positive control to induce autism-associated profiles), followed by transcriptome analysis with RNA-Seq approach. RESULTS: We found that psychoactive pharmaceuticals and valproate significantly altered neuronal gene sets associated with human neurological disorders (including autism-associated sets). Moreover, we observed that altered expression profiles in human cells were similar to gene expression profiles previously identified in fish brains. CONCLUSIONS: Psychoactive pharmaceuticals at environmental concentrations altered in vitro gene expression profiles of neuronal growth, development and regulation. These expression patterns were associated with potential neurological disorders including autism, suggested psychoactive pharmaceuticals at environmental concentrations might mimic, aggravate, or induce neurological disorders.

Preclinical antitoxic properties of Spirulina (Arthrospira).

CONTEXT: Spirulina (Arthrospira) exerts a wide spectrum of pharmacological activities which are mainly attributed to its antioxidant effect. However, Spirulina has also been reported (both in preclinical and in clinical scenarios) to exhibit other bioactive effects, including an antitoxic potential. OBJECTIVE: We performed a systematic review of the literature, conducted in TOXNET, PubMed/MEDLINE, and Science Direct-Scopus; all available years were included. Searching criteria included the effects of Spirulina on experimental poisonings from arsenic, cadmium, carbon tetrachloride, deltamethrin, fluoride, hexachlorocyclohexane, iron, lead, lindane, and mercury. RESULTS: In all cases, it was established that the blue-green alga, and its isolated compounds, effectively counteracted these pollutants toxic effects on the exposed organisms. Some molecular mechanisms are proposed, although they have not been fully elucidated yet. CONCLUSION: Spirulina could be a useful coadjuvant agent within clinical practice for treatment of these or other pollutants poisonings.

[Effects of organochloride pesticides on dyslipidemias].

Dyslipidemias is one important risk factor associated with chronic diseases. Persistent organic pollutants are resistant to degradation and can be bio-accumulated and magnified through the food chain. Recently, the relation between dyslipidemias and organochlorine pesticides has attracted more attentions. In this review, we explored the distribution of organochloride pesticides in the environment and human body, as well as the possible underlying mechanisms of the association between dyslipidemias and organochloride pesticides, including accumulation and release of organochloride, simulation of estrogen, impact on PPARs, the metabolic fingerprint, and the inflammatory reaction.

A Critical Review about Human Exposure to Polychlorinated Dibenzo-p-Dioxins (PCDDs), Polychlorinated Dibenzofurans (PCDFs) and Polychlorinated Biphenyls (PCBs) through Foods.

Dioxins include polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and part of polychlorinated biphenyls (PCBs). Only the compounds that are chlorinated at the 2,3,7, and 8 positions have characteristic dioxin toxicity. PCDDs, PCDFs and PCBs accumulate in the food chain due to their high lipophilicity, high stability, and low vapor pressure. They are not metabolized easily; however their hydroxylated metabolites are detected in feces. They cause a wide range of endocrine disrupting effects in experimental animals, wildlife, and humans. Endocrine related effects of PCDDs, PCDFs and PCBs on thyroid hormones, neurodevelopment and reproductive development were referenced. In addition, some studies of contamination of foods, bioaccumulation, dietary exposure assessment, as well as challenges of scientific research in these compounds were reviewed.

Suspected flunixin poisoning of a wild Eurasian Griffon Vulture from Spain.

Exposure to residues of the nonsteroidal anti-inflammatory drug (NSAID) diclofenac present in livestock carcasses has caused extensive declines in 3 Gyps vulture species across Asia. The carcass of a wild Eurasian Griffon Vulture (Gyps fulvus) was found in 2012 on an Andalucian (Spain) game hunting reserve and examined forensically. The bird had severe visceral gout, a finding consistent with Gyps vultures from Asia that have been poisoned by diclofenac. Liver and kidney samples from this Eurasian Griffon Vulture contained elevated flunixin (an NSAID) levels (median = 2.70 and 6.50 mg/kg, respectively). This is the first reported case of a wild vulture being exposed to and apparently killed by an NSAID outside Asia. It is also the first reported instance of mortality in the wild resulting from environmental exposure to an NSAID other than diclofenac.

Cancer and non-cancer excess mortality resulting from mixed exposure to polychlorinated biphenyls and polychlorinated dibenzofurans from contaminated rice oil: "Yusho".

PURPOSE: In 1968, rice oil contaminated with polychlorinated biphenyls and polychlorinated dibenzofurans caused a severe outbreak of food poisoning in Japan and was termed locally as "Yusho" (oil disease). In our previous study, we found that area-based standardized mortality ratios (SMRs) of some diseases were elevated shortly after the incident. This previous study, however, was unable to determine whether these elevated SMRs were a result of other area-specific factors. To overcome this limitation, we obtained mortality data from the 5 years before the incident and conducted an area-based study using vital statistics records dating from 1963 to 2002. METHODS: The population of Nagasaki Prefecture was set as the reference population for calculating SMRs. We also included data on cause-specific mortality attributable to cancer and expanded the population to encompass two severely exposed areas where contaminated rice oil was distributed (namely Tamanoura and Naru). We also calculated SMRs in the remainder of the Shimo-Goto region, excluding the exposed area, which was used as a comparison area. RESULTS: Even after considering the time trends in mortality before the incident, mortality due to diabetes mellitus and heart disease, as well as all-cause mortality, was found to be elevated shortly afterward. Additionally, mortalities due to uterine cancer in Tamanoura and leukemia were also elevated at 30-34 and 10-59 years after the event in both exposed areas, respectively. SMRs for leukemia in Tamanoura were as high as 3.0 (95% confidence interval 1.4-6.2) and 2.4 (1.2-4.8) 10-19 years later. In this period, SMRs for leukemia in the comparison area were not elevated. CONCLUSIONS: Further epidemiological studies are needed regarding this rice-oil, "Yusho" outbreak, especially with regard to cancer and non-cancer mortality.

VIGILANCE POISON: Illegal poisoning and lead intoxication are the main factors affecting avian scavenger survival in the Pyrenees (France).

A specific surveillance program has been set up to monitor avian scavenger populations in the French Pyrenean Mountains, hosting a high proportion of the French populations. The two main purposes of the study were to identify all causes of death and to investigate poisoning cases. All 170 birds found dead during the 7-year program were submitted to full necropsy, X-Ray, parasitological investigations and consistent analytical toxicology screenings (Cholinesterase inhibitors, anticoagulant rodenticides, organochlorine insecticides, Pb, Cd). Over the study period, 8 Bearded Vultures, 120 Griffon Vultures, 8 Egyptian Vultures and 34 Red kites were eventually collected. Mortality events were often multifactorial, but poisoning was by far the most common cause of death (24.1%), followed by trauma/fall (12%), bacterial diseases and starvation (8%) and electrocution (6%). Illicit use of banned pesticides was identified as a common cause of poisoning (53% of all poisoning cases) and lead poisoning was also identified as a significant toxicant issue (17% of all poisoning cases). Lead isotopic signature could be associated primarily with ammunition. Last, a positive association between trauma and lead contamination was detected, indicating that lead could be a significant contributor to different causes of death. These results urge for severe restrictions on the use of lead ammunition to prevent scavengers from detrimental exposure.

Assessment of blood lead levels among children aged ≤ 5 years--Zamfara State, Nigeria, June-July 2012.

Since 2010, Nigerian state and federal governments and the international community have been responding to an outbreak of lead poisoning caused by the processing of lead-containing gold ore in Zamfara State, Nigeria, that resulted in the deaths of approximately 400 children aged ≤ 5 years. Widespread education, surveys of high-risk villages, testing of blood lead levels (BLLs), medical treatment, and environmental cleanup all have been implemented. To evaluate the success of these remediation efforts in reducing the prevalence of lead poisoning and dangerous work practices, a population-based assessment of children's BLLs and ore processing techniques was conducted during June-July 2012. The assessment found few children in need of medical treatment, significantly lower BLLs, and substantially less exposure of children to dangerous work practices. Public health strategies designed to identify and treat children with lead poisoning, clean up existing environmental hazards, and prevent children from being exposed to dangerous ore processing techniques can produce a sustained reduction in BLLs.

Gene-environment interactions in heavy metal and pesticide carcinogenesis.

Cancer is a complex disease involving a sequence of gene-environment interactions. Lifestyle, genetics, dietary factors, and environmental pollutants can increase the risk of cancer. Gene-environment interactions have been studied by a candidate-gene approach focusing on metabolism, DNA repair, and apoptosis. Here, we review the influence of gene-environment interactions in carcinogenesis, with emphasis on heavy metal and pesticide exposures.

Follow-up study of genotoxic effects in individuals exposed to oil from the tanker Prestige, seven years after the accident.

The accident with the oil tanker Prestige in November 2002 resulted in a major spill of about 63,000 tons of heavy fuel oil. More than 300,000 people participated in the clean-up activities, which lasted for up to 10 months. Previous studies reported increases in genotoxicity endpoints in individuals exposed to Prestige oil, both at the moment of exposure [DNA breakage, micronuclei (MN), sister chromatid exchange] and two years later (chromosomal aberrations). In this work we carried out for the first time the follow-up of genotoxic effects in subjects exposed to an oil spill seven years after the exposure. The main objective was to determine the possible persistence of genotoxic damage in individuals exposed to Prestige oil seven years after the accident. The exposed group was composed of 54 residents of Galician villages in Spain that were heavily affected by the spill. This group was involved in clean-up labor for at least two months in the period November 2002-September 2003. They were compared with 50 matched controls. Primary DNA damage was evaluated by the comet assay, mutagenicity by the T-cell receptor (TCR) mutation assay, and MN frequency was determined both by the cytokinesis-block test and by flow cytometry. The results obtained showed no significant differences between the exposed and the controls in the comet assay, the TCR mutation assay and the cytokinesis-block MN test. An unexpected and significant decrease was observed in the exposed group for the results of the MN test evaluated by flow cytometry, probably influenced by modifying factors - other than age, sex and smoking - not considered in this study. Our results show no evidence of the persistence of genotoxic damage in individuals exposed to Prestige oil seven years later. Nevertheless, the need to plan biomonitoring studies on people participating in clean-up activities in case a new oil spill occurs should be established.

Assessing the health risks of natural CO2 seeps in Italy.

Industrialized societies which continue to use fossil fuel energy sources are considering adoption of Carbon Capture and Storage (CCS) technology to meet carbon emission reduction targets. Deep geological storage of CO(2) onshore faces opposition regarding potential health effects of CO(2) leakage from storage sites. There is no experience of commercial scale CCS with which to verify predicted risks of engineered storage failure. Studying risk from natural CO(2) seeps can guide assessment of potential health risks from leaking onshore CO(2) stores. Italy and Sicily are regions of intense natural CO(2) degassing from surface seeps. These seeps exhibit a variety of expressions, characteristics (e.g., temperature/flux), and location environments. Here we quantify historical fatalities from CO(2) poisoning using a database of 286 natural CO(2) seeps in Italy and Sicily. We find that risk of human death is strongly influenced by seep surface expression, local conditions (e.g., topography and wind speed), CO(2) flux, and human behavior. Risk of accidental human death from these CO(2) seeps is calculated to be 10-8 year-1 to the exposed population. This value is significantly lower than that of many socially accepted risks. Seepage from future storage sites is modeled to be less that Italian natural flux rates. With appropriate hazard management, health risks from unplanned seepage at onshore storage sites can be adequately minimized.

[Health risks from pest control products]. / Gesundheitliche Risiken durch Schädlingsbekämpfungsmittel.

According to European biocide legislation, pest control products require assessment and authorization by the responsible national or European authorities. Biocidal products can only be authorized if they have no unacceptable effects on human health. The health risk assessment performed for authorization comprises (a) the derivation of reference values for the active substances and substances of concern contained in the biocidal product and (b) an exposure assessment. These parameters are required for risk characterization. No unacceptable health risks are expected if the determined exposure is less than the relevant reference value. In addition, the toxicological information is used for classification of the biocidal product. The assessment may, where necessary, result in specific conditions for use or other restrictions aimed at minimizing risk. The risk to human health from pest control products is mainly based on the toxicological properties of their active substances. Commonly, the coformulants used in pest control products are of less concern than the active substances (e.g., food ingredients and animal feed products). For example, most rodenticides belong to the group of anticoagulants, which are also effective in humans. Regarding intoxications through insecticides, the group of pyrethroids is of particular importance. Fumigants containing metal phosphides, hydrogen cyanide, or sulfuryl difluoride are particularly toxic. This toxicity is linked to the high acute inhalation toxicity of the gaseous active substances themselves or, in the case of phosphides, of the released gas phosphane. The aim of health risk assessment for the authorization of biocidal products is to ensure their safe application for users and all other persons involved, assuming an adequate and label-compliant use.

Non-viral environmental risk factors for nasopharyngeal carcinoma: a systematic review.

This review aims to systematically summarize the epidemiological studies on nasopharyngeal carcinoma (NPC) conducted over the past half century, covering descriptive epidemiological studies and reports on non-viral risk factors. Multiple lines of epidemiologic evidence for established risk factors are systematically presented in comprehensive tables. The potential interactions among environmental factors and genetic components, and also the impacts of parallel sequencing technology on the aetiology of NPC are discussed. Finally, we propose a modified model for the pathogenesis of nasopharyngeal carcinoma based on the current knowledge.