Clinical Implications of New Drinking Water Regulation for "Forever Chemicals".

This Viewpoint describes new maximum contaminant levels set by the Environmental Protection Agency for specific perfluoroalkyl and polyfluoroalkyl substances (PFASs) and discusses the role clinicians can play in addressing their patients' PFAS health concerns.

Microplastics occurrence in sea cucumbers and impacts on sea cucumbers & human health: A systematic review.

Microplastics (MPs) are a developing concern in marine environments, with scientists concentrating more on their effects on various creatures. Sea cucumbers (SCs), as suspension and deposit feeders, are expected to be exposed to and consume MPs in their habitat. The purpose of this methodical review is to gather and integrate accessible research on the presence and effects of MPs on SCs. A systematic search of relevant databases yielded relevant papers exploring the occurrence of MPs in SC habitats as well as the possible effects of MP intake on SCs. Bibliometric analysis was also conducted to collect and analyze a large volume of data. Then the papers were sorted (a total of 249) related to the occurrence and effects of MPs in SCs. Finally, targeted data were collected from the articles for the study. The review emphasizes the ubiquity of MPs in SC ecosystems, citing studies that found high quantities in coastal areas and sediment. MPs have a variety of effects on SCs, with some studies indicating that they lower eating efficiency, affect behavior, and cause tissue damage. However, there is still no unanimity on the overall effects of MP exposure on SCs. This review gives a complete summary of the present state of information about the incidence and impact of MPs on SCs, highlighting the need for additional study in this area. Understanding the possible dangers of MPs on SCs is critical for the survival of these ecologically significant creatures.

Progress in the prevention and control of water-borne arsenicosis in China.

In this report, we provided an overview of the prevalence, control, and prevention of water-borne arsenicosis in China during 2001-2016. Random sampling was continuously performed during 2001-2010 to find villages having high levels of arsenic (>50 µg/L) in drinking water. The high-arsenic-exposure villages with more geographically dispersed water supplies were subsequently analyzed for characteristics of arsenic distribution, and villages with relatively large populations were investigated for arsenicosis. The results showed that among 32,673,677 inhabitants in 36,820 villages, 1,894,587 inhabitants in 2,476 villages were at risk of high arsenic exposure. Among the 33,318 drinking water sources surveyed in 625 high-arsenic-exposure villages, 9,807 drinking water sources that contained high levels of arsenic (>50 µg/L) were identified. The overall prevalence rate of arsenicosis was 1.93%. Further, some representative villages were chosen to monitor arsenicosis annually, showing that the prevalence rate of arsenicosis was lower in villages with arsenic-safe water supplies than in villages without arsenic-safe water supplies. To the best of our knowledge, this report provides the most comprehensive assessment of the distribution of high arsenic exposure and arsenicosis in China until now.

A review of the toxicity in fish exposed to antibiotics.

Antibiotics are widely used in the treatment of human and veterinary diseases and are being used worldwide in the agriculture industry to promote livestock growth. However, a variety of antibiotics that are found in aquatic environments are toxic to aquatic organisms. Antibiotics are not completely removed by wastewater treatment plants and are therefore released into aquatic environments, which raises concern about the destruction of the ecosystem owing to their non-target effects. Since antibiotics are designed to be persistent and work steadily in the body, their chronic toxicity effects have been studied in aquatic microorganisms. However, research on the toxicity of antibiotics in fish at the top of the aquatic food chain is relatively poor. This paper summarizes the current understanding of the reported toxicity studies with antibiotics in fish, including zebrafish, to date. Four antibiotic types; quinolones, sulfonamides, tetracyclines, and macrolides, which are thought to be genetically toxic to fish have been reported to bioaccumulate in fish tissues, as well as in aquatic environments such as rivers and surface water. The adverse effects of these antibiotics are known to cause damage to developmental, cardiovascular, and metabolic systems, as well as in altering anti-oxidant and immune responses, in fish. Therefore, there are serious concerns about the toxicity of antibiotics in fish and further research and strategies are needed to prevent them in different regions of the world.

Association of arsenic with recurrence of urinary bladder cancer.

Arsenic is known to be an important aetiological factor for the development of urinary bladder cancer. It is known to be found excessively in ground water in certain geographical areas, including West Bengal. We have studied patients with recurrent bladder cancer from different areas of this Indian state and correlated arsenic as a causative aetiological factor for development and aggressiveness of the biological behaviour of urinary cancer. We included 31 patients from various parts of West Bengal state with recurrent bladder cancer who were operated in our institute. Their clinical and residential data and their arsenic content of tumour tissue were measured. Statistical analysis was performed to test the association of tissue arsenic with clinicopathological features of recurrent disease. We found very high levels of arsenic in tumour tissue in all residents of the districts with high prevalence of arsenic in the drinking water. We also observed more aggressive clinicopathological progression and early recurrence in patients with high arsenic content. We conclude that arsenic is a causal factor in the clinicopathological progression of recurrent urinary bladder cancer. Measures to decrease the level of arsenic in drinking water should be taken as this may both improve clinicopathological outcomes in the recurrence of urinary bladder carcinoma, as well as reducing its overall incidence.

Mediation of oxidative stress toxicity induced by pyrethroid pesticides in fish.

Organophosphate and organochlorine pesticides are banned in most countries because they cause high toxicity and bioaccumulation in non-target organisms. Pyrethroid pesticides have been applied to agriculture and aquaculture since the 1970s to replace traditional pesticides. However, pyrethroids are approximately 1000 times more toxic to fish than to mammals and birds. Fish-specific organs such as the gills and their late metabolic action against this type of pesticide make fish highly susceptible to the toxicity of pyrethroid pesticides. Oxidative stress plays an important role in the neurological, reproductive, and developmental toxicity caused by pyrethroids. Deltamethrin, cypermethrin, and lambda-cyhalothrin are representative pyrethroid pesticides that induce oxidative stress in tissues such as the gills, liver, and muscles of fish and cause histopathological changes. Although they are observed in low concentrations in aquatic environments such as rivers, lakes, and surface water they induce DNA damage and apoptosis in fish. Pyrethroid pesticides cause ROS-mediated oxidative stress in fish species including carp, tilapia, and trout. They also cause lipid peroxidation and alter the state of DNA, proteins, and lipids in the cells of fish. Moreover, changes in antioxidant enzyme activity following pyrethroid pesticide exposure make fish more susceptible to oxidative stress caused by environmental pollutants. In this review, we examine the occurrence of pyrethroid pesticides in the aquatic environment and oxidative stress-induced toxicity in fish exposed to pyrethroids.

Ammonia toxicity in the yellow catfish (Pelteobagrus fulvidraco): The mechanistic insight from physiological detoxification to poisoning.

Ammonia is toxic to fishes. Different fish have different defense strategies against ammonia, so the mechanism of ammonia poisoning is different. In this study, yellow catfish were exposed to three levels of ammonia (0, 5.70 and 57.00 mg L-1) for 96 h. The results showed that ammonia poisoning could lead to free amino acid imbalance (ornithine and citrulline contents declined; arginine content elevated), urea cycle enzymes deficiency (carbamyl phosphate synthetase and arginase contents declined), oxidative stress (superoxide dismutase, catalase and glutathione peroxidase activities declined), immunosuppression (lysozyme activity, 50% hemolytic complement and total immunoglobulin contents and phagocytic index declined) and cytokines release (TNF, IL 1 and IL 8 contents elevated). In addition, ammonia poisoning could induce up-regulation of antioxidant enzymes (Cu/Zn-SOD, Mn-SOD, CAT and GPx), cytokines (TNFα, IL 1 and IL 8) and apoptosis (p53, Bax, cytochrome c, Caspase 3 and Caspase 9) genes transcription. This study suggesting that the urea cycle and glutamine synthesis both were involved in the ammonia detoxification of yellow catfish, and the immunosuppression, inflammation and apoptotic induced by ammonia poisoning in yellow catfish are related to oxidative stress.

Diagnosing Microcystin Intoxication of Canines: Clinicopathological Indications, Pathological Characteristics, and Analytical Detection in Postmortem and Antemortem Samples.

In the summer of 2018, six dogs exposed to a harmful algal bloom (HAB) of Microcystis in Martin County Florida (USA) developed clinicopathological signs of microcystin (MC) intoxication (i.e., acute vomiting, diarrhea, severe thrombocytopenia, elevated alanine aminotransferase, hemorrhage). Successful supportive veterinary care was provided and led to survival of all but one patient. Confirmation of MC intoxication was made through interpretation of clinicopathological abnormalities, pathological examination of tissues, microscopy (vomitus), and analytical MC testing of antemortem/postmortem samples (vomitus, blood, urine, bile, liver, kidney, hair). Gross and microscopic examination of the deceased patient confirmed massive hepatic necrosis, mild multifocal renal tubular necrosis, and hemorrhage within multiple organ systems. Microscopy of a vomitus sample confirmed the presence of Microcystis. Three analytical MC testing approaches were used, including the MMPB (2-methyl-3-methoxy-4-phenylbutyric acid) technique, targeted congener analysis (e.g., liquid chromatography tandem-mass spectrometry of MC-LR), and enzyme-linked immunosorbent assay (ELISA). Total Adda MCs (as MMPB) were confirmed in the liver, bile, kidney, urine, and blood of the deceased dog. Urinalysis (MMPB) of one surviving dog showed a high level of MCs (32,000 ng mL-1) 1-day post exposure, with MCs detectable >2 months post exposure. Furthermore, hair from a surviving dog was positive for MMPB, illustrating another testable route of MC elimination in canines. The described cases represent the first use of urine as an antemortem, non-invasive specimen to diagnose microcystin toxicosis. Antemortem diagnostic testing to confirm MC intoxication cases, whether acute or chronic, is crucial for providing optimal supportive care and mitigating MC exposure.

Global geographical and historical overview of cyanotoxin distribution and cyanobacterial poisonings.

Cyanobacteria are photoautotrophic organisms which occur in aquatic and terrestrial environments. They have the potential to produce toxins which pose a threat to human and animal health. This review covers the global distribution of the common cyanotoxins and related poisoning cases. A total of 468 selected articles on toxic cyanobacteria, dating from the earliest records until 2018, were reviewed. Most of the articles were published after 2000 (72%; 337 out of 468), which is consistent with the recent growth in interest in the analysis, toxinology and ecotoxicology of cyanotoxins. Animal and/or human poisoning cases were described in more than a third of the overall publications (38%; 177 out of 468). The reviewed publications showed that there were 1118 recorded identifications of major cyanotoxins in 869 freshwater ecosystems from 66 countries throughout the world. Microcystins were the most often recorded cyanotoxins worldwide (63%; 699 out of 1118), followed by cylindrospermopsin (10%; 107 out of 1118), anatoxins (9%; 100 out of 1118), and saxitoxins (8%; 93 out of 1118). Nodularins were the most rarely recorded cyanotoxins (2%; 19 out of 1118); however, there were also reports where cyanotoxins were not analysed or specified (9%; 100 out of 1118). The most commonly found toxic cyanobacterial genera were Microcystis spp. (669 reports), Anabaena spp. (397 reports), Aphanizomenon spp. (100 reports), Planktothrix spp. (98 reports), and Oscillatoria spp. (75 reports). Furthermore, there were 183 recorded cyanotoxin poisonings of humans and/or animals. Out of all toxic cyanobacterial blooms reviewed in this paper, the highest percentage of associated poisonings was found in North and Central America (39%; 69 cases out of 179), then Europe (20%; 35 out of 179), Australia including New Zealand (15%; 27 out of 179), and Africa (11%; 20 out of 179), while the lowest percentage was related to Asia (8%; 14 cases out of 179) and South America (8%; 14 cases out of 179). Events where only animals were known to have been affected were 63% (114 out of 182), whereas 32% (58 out of 182) of the investigated events involved only humans. A historical overview of human and animal poisoning episodes associated with cyanobacterial blooms is presented. Further, geographical data on the occurrence of cyanotoxins and related poisonings based on the available literature are shown. Some countries (mainly European) have done very intensive research on the occurrence of toxic cyanobacteria and cyanotoxins, and reported related ecotoxicological observations, while in some countries the lack of data is apparent. The true global extent of cyanotoxins and associated poisonings is likely to be greater than found in the available literature, and it can be assumed that ecotoxicological and hygienic problems caused by toxic cyanobacteria may occur in more environments.

Steroidal and phenolic endocrine disrupting chemicals (EDCs) in surface water of Bahe River, China: Distribution, bioaccumulation, risk assessment and estrogenic effect on Hemiculter leucisculus.

This study investigated selected steroidal and phenolic endocrine disrupting compounds (EDCs) in the surface water of the Bahe River (China) using gas chromatography mass spectrometry (GC-MS). Their effect on the wild sharpbelly Hemiculter leucisculus was investigated. The concentrations of 4-t-octylphenol, nonylphenol, bisphenol-A, estrone, 17 ß-estradiol, 17 α-Ethinylestradiol, and estriol were up to 126.0, 634.8, 1573.1, 55.9, 23.9, 31.5, and 5.2 ng L-1 in the surface water, and up to 26.4, 103.5, 146.9, 14.2, 9.3, 13.8, and 1.3 ng g-1 in the fish muscle tissue, respectively. High estrogen equivalent levels and hazard quotients were found in the middle and lower reaches of the river, and the pollution in these regions caused enhanced growth conditions, inhibition of gonad growth, and suppression of spermatogenesis in H. leucisculus. The up-regulation of Vitellogenin mRNA expression in male fish, collected from relatively heavily EDCs contaminated areas, indicates a potential estrogenic effect. The differential expression profiles of genes related to steroidogenesis at all sampling sites suggests that these endpoints may play an important role for the pollution monitoring of estrogenic EDCs in the Bahe River.

Widespread anatoxin-a detection in benthic cyanobacterial mats throughout a river network.

Benthic algae fuel summer food webs in many sunlit rivers, and are hotspots for primary and secondary production and biogeochemical cycling. Concerningly, riverine benthic algal assemblages can become dominated by toxic cyanobacteria, threatening water quality and public health. In the Eel River in Northern California, over a dozen dog deaths have been attributed to cyanotoxin poisonings since 2000. During the summers of 2013-2015, we documented spatial and temporal patterns of cyanotoxin concentrations in the watershed, showing widespread distribution of anatoxin-a in benthic cyanobacterial mats. Solid phase adsorption toxin tracking (SPATT) samplers were deployed weekly to record dissolved microcystin and anatoxin-a levels at 10 sites throughout the watershed, and 187 Anabaena-dominated or Phormidium-dominated cyanobacterial mat samples were collected from 27 locations to measure intracellular anatoxin-a (ATX) and microcystins (MCY). Anatoxin-a levels were higher than microcystin for both SPATT (mean MCY = 0.8 and ATX = 4.8 ng g resin-1 day-1) and cyanobacterial mat samples (mean MCY = 0.074 and ATX = 1.89 µg g-1 DW). Of the benthic mats sampled, 58.9% had detectable anatoxin-a (max = 70.93 µg g-1 DW), while 37.6% had detectable microcystins (max = 2.29 µg g-1 DW). SPATT cyanotoxin levels peaked in mid-summer in warm mainstem reaches of the watershed. This is one of the first documentations of widespread anatoxin-a occurrence in benthic cyanobacterial mats in a North American watershed.

The blood of my veins - mercury, Minamata and the soul of Japan.

The methylmercury contamination of Minamata Bay during the WWII postwar period resulted in thousands of Japanese citizens suffering horrific neurological injury. Fear and miscommunication destroyed and changed family and social structure. In addition, the Minamata poisoning caused momentous changes in the civic discourse in Japan and was an instrumental event in the democratization of the country. This manuscript describes the effects that the environmental contamination and human poising had in the transition of Japan from a feudal society to a democratic one.

Four phases of the Flint Water Crisis: Evidence from blood lead levels in children.

The Flint Water Crisis (FWC) is divisible into four phases of child water-lead exposure risk: Phase A) before the switch in water source to the Flint River (our baseline); Phase B) after the switch in water source, but before boil water advisories; Phase C) after boil water advisories, but before the switch back to the baseline water source of the Detroit Water and Sewerage Department (DWSD); and Phase D) after the switch back to DWSD. The objective of this work is to estimate water-lead attributable movements in child blood lead levels (BLLs) that correspond with the four phases in the FWC. With over 21,000 geo-referenced and time-stamped blood lead samples from children in Genesee County drawn from January 01, 2013 to July 19, 2016, we develop a series of quasi-experimental models to identify the causal effect of water-lead exposure on child BLLs in Flint. We find that the switch in water source (transitioning from phase A to B) caused mean BLLs to increase by about 0.5µg/dL, and increased the likelihood of a child presenting with a BLL ≥ 5µg/dL by a factor of 1.91-3.50, implying an additional 561 children exceeding 5µg/dL. We conservatively estimate cohort social costs (through lost earnings alone) of this increase in water-lead exposed children at $65 million, contrasted with expected annual savings of $2 million from switching water source. On the switch from Phase B to C, we find BLLs decreased about 50% from their initial rise following boil water advisories and subsequent water avoidance behaviors by households. Finally, the return to the baseline source water (Phase D) returned child BLLs to pre-FWC levels further implicating water-lead exposure as a causal source of child BLLs throughout the FWC.

Vertical transmission of microcystins to Nile crocodile (Crocodylus niloticus) eggs.

Cyanobacteria or blue green algae are known for their extensive and highly visible blooms in eutrophic, stagnant freshwater bodies. Climate change and global warming have also contributed to a rise in toxic cyanobacterial blooms. One of the most important cyanobacteria is Microcystis aeruginosa, which can synthesize various microcystins that can affect the health of terrestrial and aquatic animals. Commercial Nile crocodile (Crocodylus niloticus) farming in South Africa is based on keeping breeders (adult males and females) in big dams on farms (captive-bred approach). Unfortunately, cyanobacterial blooms in the breeder dams are a concern to farm owners, managers and veterinarians. The main objectives of this research project were to determine if microcystins were present in the contents of crocodile eggs and the liver and yolk of dead hatchlings, and to determine if the reduced hatchability on commercial farms might be caused by these toxins. Furthermore, the concentration of microcystins in the breeder dam was monitored on a monthly basis spanning the ovulation and egg laying period. During the hatching season microcystin concentrations in unfertilised eggs, egg shell membranes and in the yolk and liver of dead hatchlings were determined using liquid chromatography-high resolution mass spectrometry (LC-HRMS). Microcystins were detected in Nile crocodile egg and hatchling samples. Microcystin (MC-LR, MC-RR, MC-YR) concentrations in the crocodile egg and hatchling samples collected from clutches with a good hatching rate (≥90%) ranged between 0 and 1.76 ng g-1, with the highest concentration in the egg shell membranes. Microcystin concentrations in samples collected from clutches with a bad hatching rate (≤10%) ranged from 0 - 1.63 ng g-1 with the highest concentration detected in the hatchling yolk. However, the concentrations were probably underestimated as the percentage recovery from spiked samples was very low with the extraction method employed. Bayesian analysis suggests that the liver, yolk and unfertilised egg all have similar microcystin concentrations, while the membranes have (with moderate to high certainty) higher microcystin concentrations. There appears to be no difference in microcystin concentrations among good and bad clutches across all tissue types or within a specific tissue type, but due to the small sample size, it was not possible to determine whether microcystin affected the hatchability of Nile crocodile eggs. However, vertical transmission of microcystin variants to the Nile crocodile egg does occur and the possible implications for the survival of wild Nile crocodile populations should be ascertained.

Identification of risk factors in epidemiologic study based on ROC curve and network.

This article proposes a new non-parametric approach for identification of risk factors and their correlations in epidemiologic study, in which investigation data may have high variations because of individual differences or correlated risk factors. First, based on classification information of high or low disease incidence, we estimate Receptor Operating Characteristic (ROC) curve of each risk factor. Then, through the difference between ROC curve of each factor and diagonal, we evaluate and screen for the important risk factors. In addition, based on the difference of ROC curves corresponding to any pair of factors, we define a new type of correlation matrix to measure their correlations with disease, and then use this matrix as adjacency matrix to construct a network as a visualization tool for exploring the structure among factors, which can be used to direct further studies. Finally, these methods are applied to analysis on water pollutants and gastrointestinal tumor, and analysis on gene expression data in tumor and normal colon tissue samples.

Dose-Response Relationship between Inorganic Arsenic Exposure and Lung Cancer among Arseniasis Residents with Low Methylation Capacity.

Background: Exposure to inorganic arsenic (InAs) has been documented as a risk factor for lung cancer. This study examined the association between InAs exposure, its metabolism, and lung cancer occurrence.Methods: We followed 1,300 residents from an arseniasis area in Taiwan, determined urinary InAs metabolites, and identified 39 lung cancer cases. Cox proportional hazards model was performed.Results: The results demonstrated that participants with either the primary methylation index [monomethylarsonic acid (MMA)/InAs] or the secondary methylation index [dimethylarsenic acid (DMA)/MMA] lower than their respective median values were at a higher risk of lung cancer (HRs from 3.41 to 4.66) than those with high methylation capacity. The incidence density of lung cancer increased from 79.9/100,000 (year-1) to 467.4/100,000 (year-1) for residents with low methylation capacity and from 0 to 158.5/100,000 (year-1) for residents with high methylation capacity when the arsenic exposure dose increased from 2 to 10 ppb to ≥200 ppb, respectively. The analyses revealed a dose-response relationship between lung cancer occurrence and increasing arsenic concentrations in drinking water as well as cumulative arsenic exposure (monotonic trend test; P < 0.05 and P < 0.05, respectively) among the residents with low methylation capacity. The relationship between arsenic exposure and lung cancer among high methylators was not statistically significant.Conclusions: Hypomethylation responses to InAs exposure may dose dependently increase lung cancer occurrence.Impact: The high-risk characteristics observed among those exposed should be considered in future preventive medicine and research on arsenic carcinogenesis. Cancer Epidemiol Biomarkers Prev; 26(5); 756-61. ©2016 AACR.

Perchlorate and Diet: Human Exposures, Risks, and Mitigation Strategies.

Perchlorate is an endocrine-disrupting chemical that interferes with the normal functioning of the thyroid gland. Maternal thyroid dysfunction during gestation may alter fetal brain development. Perchlorate contamination is widespread: it is present in the body of all Americans tested and the majority of foods tested. The main sources of food contamination appear to be hypochlorite bleach, a disinfectant and sanitizer, that when poorly managed quickly degrades to perchlorate and perchlorate-laden plastic food packaging for dry food or localized contamination from manufacturing or processing of the chemical. Eliminating perchlorate from food packaging and improving bleach management, such as reducing concentration and storage time and temperature, would result in reduced perchlorate contamination of food and water.

Perchlorate in Water Supplies: Sources, Exposures, and Health Effects.

Perchlorate exposure occurs from ingestion of natural or man-made perchlorate in food or water. Perchlorate is used in a variety of industrial products including missile fuel, fireworks, and fertilizers, and industrial contamination of drinking water supplies has occurred in a number of areas. Perchlorate blocks iodide uptake into the thyroid and decreases the production of thyroid hormone, a critical hormone for metabolism, neurodevelopment, and other physiologic functions. Occupational and clinical dosing studies have not identified clear adverse effects, but may be limited by small sample sizes, short study durations, and the inclusion of mostly healthy adults. Expanding evidence suggests that young children, pregnant women, fetuses, and people co-exposed to similarly acting agents may be especially susceptible to perchlorate. Given the ubiquitous nature of perchlorate exposure, and the importance of thyroid hormone for brain development, studying the impact of perchlorate on human health could have far-reaching public health implications.