Exploring the Q-marker of "sweat soaking method" processed radix Wikstroemia indica: Based on the "effect-toxicity-chemicals" study.

PubMed

Feng, Guo; Chen, Yun-Long; Li, Wei; Li, Lai-Lai; Wu, Zeng-Guang; Wu, Zi-Jun; Hai, Yue; Zhang, Si-Chao; Zheng, Chuan-Qi; Liu, Chang-Xiao; He, Xin

2018-06-01

Radix Wikstroemia indica (RWI), named "Liao Ge Wang" in Chinese, is a kind of toxic Chinese herbal medicine (CHM) commonly used in Miao nationality of South China. "Sweat soaking method" processed RWI could effectively decrease its toxicity and preserve therapeutic effect. However, the underlying mechanism of processing is still not clear, and the Q-markers database for processed RWI has not been established. Our study is to investigate and establish the quality evaluation system and potential Q-markers based on "effect-toxicity-chemicals" relationship of RWI for quality/safety assessment of "sweat soaking method" processing. The variation of RWI in efficacy and toxicity before and after processing was investigated by pharmacological and toxicological studies. Cytotoxicity test was used to screen the cytotoxicity of components in RWI. The material basis in ethanol extract of raw and processed RWI was studied by UPLC-Q-TOF/MS. And the potential Q-markers were analyzed and predicted according to "effect-toxicity-chemical" relationship. RWI was processed by "sweat soaking method", which could preserve efficacy and reduce toxicity. Raw RWI and processed RWI did not show significant difference on the antinociceptive and anti-inflammatory effect, however, the injury of liver and kidney by processed RWI was much weaker than that by raw RWI. The 20 compounds were identified from the ethanol extract of raw product and processed product of RWI using UPLC-Q-TOF/MS, including daphnoretin, emodin, triumbelletin, dibutyl phthalate, Methyl Paraben, YH-10 + OH and matairesinol, arctigenin, kaempferol and physcion. Furthermore, 3 diterpenoids (YH-10, YH-12 and YH-15) were proved to possess the high toxicity and decreased by 48%, 44% and 65%, respectively, which could be regarded as the potential Q-markers for quality/safety assessment of "sweat soaking method" processed RWI. A Q-marker database of processed RWI by "sweat soaking method" was established according to the results and relationship of "effect-toxicity-chemicals", which provided a scientific evidence for processing methods, mechanism and the clinical application of RWI, also provided experimental results to explore the application of Q-marker in CHM. Copyright © 2018 Elsevier GmbH. All rights reserved.

Environmental Application, Fate, Effects, and Concerns of Ionic Liquids: A Review.

PubMed

Amde, Meseret; Liu, Jing-Fu; Pang, Long

2015-11-03

Ionic liquids (ILs) comprise mostly of organic salts with negligible vapor pressure and low flammability that are proposed as replacements for volatile solvents. ILs have been promoted as "green" solvents and widely investigated for their various applications. Although the utility of these chemicals is unquestionable, their toxic effects have attracted great attention. In order to manage their potential hazards and design environmentally benign ILs, understanding their environmental behavior, fate and effects is important. In this review, environmentally relevant issues of ILs, including their environmental application, environmental behavior and toxicity are addressed. In addition, also presented are the influence of ILs on the environmental fate and toxicity of other coexisting contaminants, important routes for designing nontoxic ILs and the techniques that might be adopted for the removal of ILs.

Perioperative pain control: a strategy for management.

PubMed

Cohen, Mitchell Jay; Schecter, William P

2005-12-01

A thorough understanding of the anatomy and neurophysiology of the pain response is necessary for the effective treatment of perioperative pain. This article describes the mechanisms that produce pain,including those related to inflammation. Other topics include the pharmacologies of nonopioid and opioid analgesics. Nonopioid analgesics can be separated into two categories: nonsteroidal anti-inflammatory drugs, such as salicylates, and acetaminophen. Opioids include morphine, fentanyl, and meperidine. The pharmacology of local anesthesia is discussed. The six major adverse reactions to local anesthetics are cardiac arrhythmias, hypertension, direct tissue toxicity, central nervous system toxicity, methemoglobinemia and allergic reactions. Methods for measuring pain are described.

Effects of soil type, prepercolation, and ageing on bioaccumulation and toxicity of zinc for the springtail Folsomia candida

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smit, C.E.; Van Gestel, C.A.M.

1998-06-01

Soil properties are a major influence on the bioavailability and toxicity of metals and represent one of the important factors that complicate the extrapolation of results from laboratory tests to field situations. The influence of soil characteristics and way of contamination on the bioaccumulation and toxicity of zinc was investigated for the springtail Folsomia candida, and the applicability of chemical extraction techniques for the prediction of zinc uptake and toxicity was evaluated. Bioaccumulation of zinc in F. candida was related to water-soluble zinc concentrations, and uptake was dependent on the test soil used. Effects of zinc for F. candida couldmore » not be fully explained by bioaccumulation. This indicates that the existence of a fixed internal threshold concentration of zinc above which physiological functions are impaired is not likely for F. candida. In freshly contaminated soils, zinc toxicity was related to organic matter and clay content of the soil; however, the use of these soils overestimated the effects of zinc for F. candida by a factor of 5 to 8 compared to a test soil that was subjected to ageing under field conditions for 1.5 years. Equilibration of the zinc contamination by percolating the soils with water before use in the toxicity experiment strongly reduced the difference in zinc toxicity between laboratory-treated and aged soils. Water-soluble concentrations are most appropriate to predict effects of zinc on reproduction of F. candida in soils with unknown contamination histories. For laboratory toxicity tests, it is recommended to percolate soils with water after contamination and to include an equilibration period prior to use to achieve a more realistic exposure situation.« less

Lead Levels in Landfill Areas and Childhood Exposure: An Integrative Review.

PubMed

Kim, M Angela; Williams, Kimberly A

2017-01-01

Landfills are high-risk areas for environmental lead exposure for children living in poverty stricken areas in many countries. This review examines landfills and lead toxicity in children. The review discusses the effects of lead toxicity, provides evidenced based recommendations to reduce lead exposure, and identify gaps in the evidence. A database search was conducted of articles in English from 1985 to 2014. Ten articles met the inclusion criteria. The Whittemore and Knafl framework and the John Hopkins Research Evidence Appraisal Tool © were used for reviewing the data. Elevated blood lead levels (BLLs) of children living near landfills were related to increased soil lead levels. Toxic effects of lead included adverse outcomes such as encephalopathy or death for children. Different approaches to decrease lead level include environmental surveillance, BLL screening, and soil abatement which are costly. Increased BLL through environmental exposure is connected with poor health outcomes and death among children. Evidence-based prevention included monitoring and screening and costly soil abatement. It is recommended that future studies focus on community education for exposure avoidance for children living near landfill areas. © 2016 Wiley Periodicals, Inc.

Oxygen toxicity.

PubMed

Stogner, S W; Payne, D K

1992-12-01

The objective of this article is to provide an overview of the biochemistry of oxygen metabolism, including the formation of free radicals and the role of endogenous antioxidants. Pathophysiologic correlates underlying the clinical manifestations of oxygen toxicity are reviewed and management strategies are outlined. References from basic science and clinical journals were selected from the authors' files and from a search of a computerized database of the biomedical literature. Articles selected for review included both historical and current literature concerning the biochemistry and pathophysiology of oxygen toxicity in animals and humans. The benefits of oxygen therapy have been known for many years; however, its potential toxicity has not been recognized until the last two decades. The lungs, the eyes, and, under certain conditions, the central nervous system are the organs most affected by prolonged exposure to hyperoxic environments. Free radical formation during cellular metabolism under hyperoxic conditions is recognized as the biochemical basis of oxygen injury to cells and organs. Endogenous antioxidants are a primary means of detoxifying reactive oxygen species and preventing hyperoxia-induced cellular damage. When this defense fails or is overwhelmed by the excessive production of hyperoxia-induced free-radical species, distinctive morphologic changes occur at the cellular level. The amount of hyperoxia required to cause cellular damage and the time course of these changes vary from species to species and from individual to individual within the same species. Age, nutritional status, presence of underlying diseases, and certain drugs may influence the development of oxygen toxicity. There is currently no reliably effective drug for preventing or delaying the development of oxygen toxicity in humans. Use of the lowest effective oxygen concentration, the avoidance of certain drugs, and attention to nutritional and metabolic factors remain the best means currently available to avoid or minimize oxygen toxicity. Research is continuing into more effective ways to prevent, diagnose, and treat this disorder.

Using passive sampling and zebrafish to identify developmental toxicants in complex mixtures.

PubMed

Bergmann, Alan J; Tanguay, Robert L; Anderson, Kim A

2017-09-01

Using effects-directed analysis, we investigated associations previously observed between polycyclic aromatic hydrocarbons (PAHs) and embryotoxicity in field-deployed low-density polyethylene (LDPE). We conducted effects-directed analysis using a zebrafish embryo assay and iterative fractionation of extracts of LDPE that were deployed in the Portland Harbor superfund megasite, Oregon (USA). Whole extracts induced toxicity including mortality, edema, and notochord distortion at 20% effect concentration (EC20) values of approximately 100, 100, and 10 mg LDPE/mL, respectively. Through fractionation, we determined that PAHs at concentrations similar to previous research did not contribute markedly to toxicity. We also eliminated pesticides, phthalates, musks, and other substances identified in toxic fractions by testing surrogate mixtures. We identified free fatty acids as lethal components of LDPE extracts and confirmed their toxicity with authentic standards. We found chromatographic evidence that dithiocarbamates are responsible for notochord and other sublethal effects, although exact matches were not obtained. Fatty acids and dithiocarbamates were previously unrecorded components of LDPE extracts and likely contribute to the toxicity of the whole mixture. The present study demonstrates the success of effects-directed analysis in nontargeted hazard identification using the zebrafish embryo test as a self-contained battery of bioassays that allows identification of multiple chemicals with different modes of action. This is the first effects-directed analysis to combine LDPE and zebrafish, approaches that are widely applicable to identifying developmental hazards in the bioavailable fraction of hydrophobic organic compounds. Environ Toxicol Chem 2017;36:2290-2298. © 2017 SETAC. © 2017 SETAC.

Workgroup Report: Implementing a National Occupational Reproductive Research Agenda—Decade One and Beyond

PubMed Central

Lawson, Christina C.; Grajewski, Barbara; Daston, George P.; Frazier, Linda M.; Lynch, Dennis; McDiarmid, Melissa; Murono, Eisuke; Perreault, Sally D.; Robbins, Wendie A.; Ryan, Megan A.K.; Shelby, Michael; Whelan, Elizabeth A.

2006-01-01

The initial goal of occupational reproductive health research is to effectively study the many toxicants, physical agents, and biomechanical and psychosocial stressors that may constitute reproductive hazards in the workplace. Although the main objective of occupational reproductive researchers and clinicians is to prevent recognized adverse reproductive outcomes, research has expanded to include a broader spectrum of chronic health outcomes potentially affected by reproductive toxicants. To aid in achieving these goals, the National Institute for Occupational Safety and Health, along with its university, federal, industry, and labor colleagues, formed the National Occupational Research Agenda (NORA) in 1996. NORA resulted in 21 research teams, including the Reproductive Health Research Team (RHRT). In this report, we describe progress made in the last decade by the RHRT and by others in this field, including prioritizing reproductive toxicants for further study; facilitating collaboration among epidemiologists, biologists, and toxicologists; promoting quality exposure assessment in field studies and surveillance; and encouraging the design and conduct of priority occupational reproductive studies. We also describe new tools for screening reproductive toxicants and for analyzing mode of action. We recommend considering outcomes such as menopause and latent adverse effects for further study, as well as including exposures such as shift work and nanomaterials. We describe a broad domain of scholarship activities where a cohesive system of organized and aligned work activities integrates 10 years of team efforts and provides guidance for future research. PMID:16507468

Prevention of dopaminergic toxicity of MPTP in mice by phenylethylamine, a specific substrate of type B monoamine oxidase.

PubMed Central

Melamed, E.; Youdim, M. B.

1985-01-01

N-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) is toxic to dopaminergic neurones in several mammalian species including mice. Combined treatment with phenylethylamine prevented in mice the long-term (30 days post-treatment) dopamine depletions in striatum induced by MPTP. Phenylethylamine, a naturally-occurring specific substrate of monoamine oxidase (MAO) type B, probably protects against effects of MPTP by competitively inhibiting the oxidative conversion of MPTP to its toxic metabolite N-methyl-4-phenylpyridinium ion catalysed by MAO-B. PMID:3877535

Inclusion of dosimetric data as covariates in toxicity-related radiogenomic studies : A systematic review.

PubMed

Yahya, Noorazrul; Chua, Xin-Jane; Manan, Hanani A; Ismail, Fuad

2018-05-17

This systematic review evaluates the completeness of dosimetric features and their inclusion as covariates in genetic-toxicity association studies. Original research studies associating genetic features and normal tissue complications following radiotherapy were identified from PubMed. The use of dosimetric data was determined by mining the statement of prescription dose, dose fractionation, target volume selection or arrangement and dose distribution. The consideration of the dosimetric data as covariates was based on the statement mentioned in the statistical analysis section. The significance of these covariates was extracted from the results section. Descriptive analyses were performed to determine their completeness and inclusion as covariates. A total of 174 studies were found to satisfy the inclusion criteria. Studies published ≥2010 showed increased use of dose distribution information (p = 0.07). 33% of studies did not include any dose features in the analysis of gene-toxicity associations. Only 29% included dose distribution features as covariates and reported the results. 59% of studies which included dose distribution features found significant associations to toxicity. A large proportion of studies on the correlation of genetic markers with radiotherapy-related side effects considered no dosimetric parameters. Significance of dose distribution features was found in more than half of the studies including these features, emphasizing their importance. Completeness of radiation-specific clinical data may have increased in recent years which may improve gene-toxicity association studies.

The effect of plants on the degradation and toxicity of petroleum contaminants in soil: a field assessment.

PubMed

Banks, M K; Schwab, P; Liu, B; Kulakow, P A; Smith, J S; Kim, R

2003-01-01

A field project located at the US Naval Base at Port Hueneme, California was designed to evaluate changes in contaminant concentrations and toxicity during phytoremediation. Vegetated plots were established in petroleum (diesel and heavy oil) contaminated soil and were evaluated over a two-year period. Plant species were chosen based on initial germination studies and included native California grasses. The toxicity of the impacted soil in vegetated and unvegetated plots was evaluated using Microtox, earthworm, and seed germination assays. The reduction of toxicity was affected more by contaminant aging than the establishment of plants. However, total petroleum hydrocarbon concentrations were lower by the end of the study in the vegetated plots when compared to the unvegetated soil. Although phytoremediation is an effective approach for cleaning-up of petroleum contaminated soil, a long-term management plan is required for significant reductions in contaminant concentrations.

Fight, Flight or Freeze: Common Responses for Follower Coping with Toxic Leadership.

PubMed

Webster, Vicki; Brough, Paula; Daly, Kathleen

2016-10-01

Sustained destructive leadership behaviours are associated with negative outcomes that produce serious workplace problems, yet there is scant research into how followers effectively cope with toxic leader behaviours. Despite numerous attempts to develop typologies of coping behaviours, there remains much to learn, especially in relation to this specific workplace stressor. This mixed method research investigates the coping strategies reported by 76 followers to cope with the psychological, emotional and physical consequences of their leader's adverse behaviour. Coping instances were categorized using two existing theoretical coping frameworks, and the ability of these frameworks to explain responses to real-world experiences with toxic leadership are discussed. Common coping strategies reported included assertively challenging the leader, seeking social support, ruminating, taking leave and leaving the organization. Organizational interventions to increase effectiveness of follower coping with the impact of toxic leadership are also discussed. Copyright © 2014 John Wiley & Sons, Ltd. Copyright © 2014 John Wiley & Sons, Ltd.

Synergistic Effects of Toxic Elements on Heat Shock Proteins

PubMed Central

Mahmood, Khalid; Mahmood, Qaisar; Irshad, Muhammad; Hussain, Jamshaid

2014-01-01

Heat shock proteins show remarkable variations in their expression levels under a variety of toxic conditions. A research span expanded over five decades has revealed their molecular characterization, gene regulation, expression patterns, vast similarity in diverse groups, and broad range of functional capabilities. Their functions include protection and tolerance against cytotoxic conditions through their molecular chaperoning activity, maintaining cytoskeleton stability, and assisting in cell signaling. However, their role as biomarkers for monitoring the environmental risk assessment is controversial due to a number of conflicting, validating, and nonvalidating reports. The current knowledge regarding the interpretation of HSPs expression levels has been discussed in the present review. The candidature of heat shock proteins as biomarkers of toxicity is thus far unreliable due to synergistic effects of toxicants and other environmental factors. The adoption of heat shock proteins as “suit of biomarkers in a set of organisms” requires further investigation. PMID:25136596

Toxic effects of chemical dispersant Corexit 9500 on water flea Daphnia magna.

PubMed

Toyota, Kenji; McNabb, Nicole A; Spyropoulos, Demetri D; Iguchi, Taisen; Kohno, Satomi

2017-02-01

In 2010, approximately 2.1 million gallons of chemical dispersants, mainly Corexit 9500, were applied in the Gulf of Mexico to prevent the oil slick from reaching shorelines and to accelerate biodegradation of oil during the Deepwater Horizon oil spill. Recent studies have revealed toxic effects of Corexit 9500 on marine microzooplankton that play important roles in food chains in marine ecosystems. However, there is still little known about the toxic effects of Corexit 9500 on freshwater zooplankton, even though oil spills do occur in freshwater and chemical dispersants may be used in response to these spills. The cladoceran crustacean, water flea Daphnia magna, is a well-established model species for various toxicological tests, including detection of juvenile hormone-like activity in test compounds. In this study, we conducted laboratory experiments to investigate the acute and chronic toxicity of Corexit 9500 using D. magna. The acute toxicity test was conducted according to OECD TG202 and the 48 h EC 50 was 1.31 ppm (CIs 0.99-1.64 ppm). The reproductive chronic toxicity test was performed following OECD TG211 ANNEX 7 and 21 days LOEC and NOEC values were 4.0 and 2.0 ppm, respectively. These results indicate that Corexit 9500 has toxic effects on daphnids, particularly during the neonatal developmental stage, which is consistent with marine zooplankton results, whereas juvenile hormone-like activity was not identified. Therefore, our findings of the adverse effects of Corexit 9500 on daphnids suggest that application of this type of chemical dispersant may have catastrophic impacts on freshwater ecosystems by disrupting the key food chain network. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Halogenated flame retardants: do the fire safety benefits justify the risks?

PubMed

Shaw, Susan D; Blum, Arlene; Weber, Roland; Kannan, Kurunthachalam; Rich, David; Lucas, Donald; Koshland, Catherine P; Dobraca, Dina; Hanson, Sarah; Birnbaum, Linda S

2010-01-01

Since the 1970s, an increasing number of regulations have expanded the use of brominated and chlorinated flame retardants. Many of these chemicals are now recognized as global contaminants and are associated with adverse health effects in animals and humans, including endocrine and thyroid disruption, immunotoxicity, reproductive toxicity, cancer, and adverse effects on fetal and child development and neurologic function. Some flame retardants such as polybrominated diphenyl ethers (PBDEs) have been banned or voluntarily phased out by manufacturers because of their environmental persistence and toxicity, only to be replaced by other organohalogens of unknown toxicity. Despite restrictions on further production in some countries, consumer products previously treated with banned retardants are still in use and continue to release toxic chemicals into the environment, and the worldwide use of organohalogen retardants continues to increase. This paper examines major uses and known toxic effects of commonly-used organohalogen flame retardants, replacements for those that have been phased out, their combustion by-products, and their effectiveness at reducing fire hazard. Policy and other solutions to maintain fire safety while reducing toxicity are suggested. The major conclusions are: (1) Flammability regulations can cause greater adverse environmental and health impacts than fire safety benefits. (2) The current options for end-of-life disposal of products treated with organohalogens retardants are problematic. (3) Life-cycle analyses evaluating benefits and risks should consider the health and environmental effects of the chemicals, as well as their fire safety impacts. (4) Most fire deaths and most fire injuries result from inhaling carbon monoxide, irritant gases, and soot. The incorporation of organohalogens can increase the yield of these toxic by-products during combustion. (5) Fire-safe cigarettes, fire-safe candles, child-resistant lighters, sprinklers, and smoke detectors can prevent fires without the potential adverse effects of flame retardant chemicals. (6) Alternatives to organohalogen flame retardant chemicals include using less flammable materials, design changes, and safer chemicals. To date, before evaluating their health and environmental impacts, many flame retardant chemicals have been produced and used, resulting in high levels of human exposure. As a growing literature continues to find adverse impacts from such chemicals, a more systematic approach to their regulation is needed. Before implementing new flammability standards, decision-makers should evaluate the potential fire safety benefit versus the health and environmental impacts of the chemicals, materials, or technologies likely to be used to meet the standard. Reducing the use of toxic or untested flame retardant chemicals in consumer products can protect human and animal health and the global environment without compromising fire safety.

Developmental toxicity study in Sprague-Dawley rats by whole-body exposure to N,N-diethylethanolamine vapor.

PubMed

Leung, H W; Murphy, S R

1998-01-01

Timed-pregnant Sprague-Dawley rats were exposed whole body to N,N-diethylethanolamine vapor for 6 h per day on gestational days (GD) 6-15 at targeted concentrations of 33, 66 or 100 ppm. Dams were sacrificed on GD 21. There was no maternal mortality in any exposed groups. Maternal toxicity observed in the 100 ppm group included dry rales, reduced body weight (9.5%) on GD 15 and reduced weight gain (48%) during exposure. Suppression of body weight gain was also noted in the 66 ppm group during GD 12-15. There were no effects of treatment on gestational parameters, including pre- and post-implantation loss or sex ratio. Mean fetal body weights in treated groups were comparable to controls. There was no increase in the incidence of total malformations (external, visceral or skeletal) or individually by category. The incidence of a single developmental variation (hypoplastic bones of the forepaw) in the 100 ppm groups was statistically significantly decreased relative to that of controls. The no-observed-adverse-effect level was 33 ppm for maternal toxicity but greater than 100 ppm for embryofetal toxicity and teratogenicity.

Application of dispersive solid phase extraction for trace analysis of toxic chemicals in foods.

PubMed

Neely, Sarah; Martin, Jordan; da Cruz, Natalia Ferreira; Piester, Gavin; Robinson, Morgan; Okoniewski, Richard; Tran, Buu N

2018-05-29

The objectives of this study were to develop and validate a method for the identification of toxic organic chemicals, including groups of controlled substances, alkaloids and pesticides that are highly toxic and considered threats to public health. This project aims to ensure our laboratory's readiness to respond to emergencies involving our food supply in cooperation with the Food Emergency Response Network (FERN) program. The food matrices were homogenized in a blender or food processor prior to extraction with an acetonitrile-water mixture using a QuEChERS (Quick, Easy, Cheap, Effective, Rugged, and Safe) procedure. The extracts were then analyzed by either gas chromatography-mass spectrometry (GC-MS) or liquid chromatography-electrospray tandem mass spectrometry (LC-ESI/MS/MS). Method validation was performed on a variety of food matrices including lettuce, grapes, milk, chicken, pork and beef. MDLs for the toxic compounds ranged from 0.01 to 0.66 mg/kg (ppm). The findings in this study will provide a valuable resource for the determination of toxic chemicals in food matrices for emergency response situations. Copyright © 2018. Published by Elsevier B.V.

Static renewal tests using Anodonta imbecillis (freshwater mussels). Anodonta imbecillis QA test 1, Clinch River-Environmental Restoration Program (CR-ERP)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Simbeck, D.J.

1993-12-31

Toxicity testing of split whole sediment samples using juvenile freshwater mussels (Anodonta imbecillis) was conducted by TVA and CR-ERP personnel as part of the CR-ERP biomonitoring study of Clinch River sediments to provide a quality assurance mechanism for test organism quality and overall performance of the test. In addition, testing included procedures comparing daily renewal versus non-renewal of test sediments. Testing of sediment samples collected July 15 from Poplar Creek Miles 6.0 and 5.1 was conducted from July 21--30, 1993. Results from this test showed no toxicity (survival effects) to fresh-water mussels during a 9-day exposure to the sediments. Sidemore » by side testing of sediments with daily sediment renewal and no sediment renewal showed no differences between methods. This may be due to the absence of toxicity in both samples and may not reflect true differences between the two methods for toxic sediment. Attachments to this report include: Chain of custody forms -- originals; Toxicity test bench sheets and statistical analyses; and Ammonia analysis request and results.« less

Relative toxicities of pure propylene and ethylene glycol and formulated deicers on plant species

DOE Office of Scientific and Technical Information (OSTI.GOV)

DuFresne, D.L.; Pillard, D.A.

1994-12-31

Propylene and ethylene glycol deicers are commonly used at airports in the US and other countries to remove and retard the accumulation of snow and ice on aircraft. Deicers may not only enter water bodies without treatment, due to excessive storm-related flow, but also may expose terrestrial organisms to high concentrations through surface runoff. Most available toxicity data are for aquatic vertebrates and invertebrate species; this study examined effects on terrestrial and aquatic plants. Terrestrial plant species included both a monocot (rye grass, Lolium perenne) and a dicot (lettuce, Lactuca saliva). Aquatic species included a single cell alga (Selenastrum capricomutum),more » and an aquatic macrophyte (duckweed, Lemna minor). Glycol deicers were obtained in the formulated mixtures used on aircraft. Pure ethylene and propylene glycol were obtained from Sigma{reg_sign}. Parameters measured included germination, root and shoot length, survival, and growth. Formulated deicers, like those used at airports, were generally more toxic than pure chemicals, based on glycol concentration. This greater toxicity of formulated deicers is consistent with results of tests using animal species.« less

Toxic metal(loid)-based pollutants and their possible role in autism spectrum disorder.

PubMed

Bjørklund, Geir; Skalny, Anatoly V; Rahman, Md Mostafizur; Dadar, Maryam; Yassa, Heba A; Aaseth, Jan; Chirumbolo, Salvatore; Skalnaya, Margarita G; Tinkov, Alexey A

2018-06-11

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social interaction, verbal and non-verbal communication, and stereotypic behaviors. Many studies support a significant relationship between many different environmental factors in ASD etiology. These factors include increased daily exposure to various toxic metal-based environmental pollutants, which represent a cause for concern in public health. This article reviews the most relevant toxic metals, commonly found, environmental pollutants, i.e., lead (Pb), mercury (Hg), aluminum (Al), and the metalloid arsenic (As). Additionally, it discusses how pollutants can be a possible pathogenetic cause of ASD through various mechanisms including neuroinflammation in different regions of the brain, fundamentally occurring through elevation of the proinflammatory profile of cytokines and aberrant expression of nuclear factor kappa B (NF-κB). Due to the worldwide increase in toxic environmental pollution, studies on the role of pollutants in neurodevelopmental disorders, including direct effects on the developing brain and the subjects' genetic susceptibility and polymorphism, are of utmost importance to achieve the best therapeutic approach and preventive strategies. Copyright © 2018 Elsevier Inc. All rights reserved.

[The toxicity variation of organic extracts in drinking water treatment processes].

PubMed

Mei, M; Wei, S; Zijian, W; Wenhua, W; Baohua, Z; Suxia, Z

2001-01-01

Source water samples and outlet water samples from different treatment processes of the Beijing Ninth Water Works were concentrated in situ with XAD-2 filled columns. GC-MS analysis and toxic assessment including acute toxicity evaluation by luminescent bacterium bioassay(Q67 strains) and mutagenicity assessment by Ames test(TA98 and TA100 strains with and without S9 addition) were conducted on these samples. The results showed that prechlorination caused the direct and indirect frame shift mutagenicity as well as indirect base pair substitute mutagenicity. Addition of coagulant may increase the base pair substitute mutagenic effects greatly. Sand and coal filtration and granular activated carbon filtration could effectively remove most of the formed mutagens. The rechlorination do not obviously increase the mutagenic effects. No mutagenic effect was observed in tap water. Acute toxicity showed the same variation with that of mutagenicity during the treatment processes. Sample from flocculation treatment process was found to be the most toxic sample. Results of GC-MS analysis showed that water in this plant was not contaminated by PCB. Concentrations of toluene, naphthalene and phenol increased in flocculation treatment process and in tap water. However, the concentrations of these substances were at the level of microgram/L, therefore, were not high enough to cause mutagenicity.

Cross-species extrapolation of toxicity information using the ...

EPA Pesticide Factsheets

In the United States, the Endocrine Disruptor Screening Program (EDSP) was established to identify chemicals that may lead to adverse effects via perturbation of the endocrine system (i.e., estrogen, androgen, and thyroid hormone systems). In the mid-1990s the EDSP adopted a two tiered approach for screening chemicals that applied standardized in vitro and in vivo toxicity tests. The Tier 1 screening assays were designed to identify substances that have the potential of interacting with the endocrine system and Tier 2 testing was developed to identify adverse effects caused by the chemical, with documentation of dose-response relationships. While this tiered approach was effective in identifying possible endocrine disrupting chemicals, the cost and time to screen a single chemical was significant. Therefore, in 2012 the EDSP proposed a transition to make greater use of computational approaches (in silico) and high-throughput screening (HTS; in vitro) assays to more rapidly and cost-efficiently screen chemicals for endocrine activity. This transition from resource intensive, primarily in vivo, screening methods to more pathway-based approaches aligns with the simultaneously occurring transformation in toxicity testing termed “Toxicity Testing in the 21st Century” which shifts the focus to the disturbance of the biological pathway predictive of the observable toxic effects. An example of such screening tools include the US Environmental Protection Agency’s

Mixtures of Chemical Pollutants at European Legislation Safety Concentrations: How Safe Are They?

PubMed Central

Carvalho, Raquel N.; Arukwe, Augustine; Ait-Aissa, Selim; Bado-Nilles, Anne; Balzamo, Stefania; Baun, Anders; Belkin, Shimshon; Blaha, Ludek; Brion, François; Conti, Daniela; Creusot, Nicolas; Essig, Yona; Ferrero, Valentina E. V.; Flander-Putrle, Vesna; Fürhacker, Maria; Grillari-Voglauer, Regina; Hogstrand, Christer; Jonáš, Adam; Kharlyngdoh, Joubert B.; Loos, Robert; Lundebye, Anne-Katrine; Modig, Carina; Olsson, Per-Erik; Pillai, Smitha; Polak, Natasa; Potalivo, Monica; Sanchez, Wilfried; Schifferli, Andrea; Schirmer, Kristin; Sforzini, Susanna; Stürzenbaum, Stephen R.; Søfteland, Liv; Turk, Valentina; Viarengo, Aldo; Werner, Inge; Yagur-Kroll, Sharon; Zounková, Radka; Lettieri, Teresa

2014-01-01

The risk posed by complex chemical mixtures in the environment to wildlife and humans is increasingly debated, but has been rarely tested under environmentally relevant scenarios. To address this issue, two mixtures of 14 or 19 substances of concern (pesticides, pharmaceuticals, heavy metals, polyaromatic hydrocarbons, a surfactant, and a plasticizer), each present at its safety limit concentration imposed by the European legislation, were prepared and tested for their toxic effects. The effects of the mixtures were assessed in 35 bioassays, based on 11 organisms representing different trophic levels. A consortium of 16 laboratories was involved in performing the bioassays. The mixtures elicited quantifiable toxic effects on some of the test systems employed, including i) changes in marine microbial composition, ii) microalgae toxicity, iii) immobilization in the crustacean Daphnia magna, iv) fish embryo toxicity, v) impaired frog embryo development, and vi) increased expression on oxidative stress-linked reporter genes. Estrogenic activity close to regulatory safety limit concentrations was uncovered by receptor-binding assays. The results highlight the need of precautionary actions on the assessment of chemical mixtures even in cases where individual toxicants are present at seemingly harmless concentrations. PMID:24958932

Saffron as an antidote or a protective agent against natural or chemical toxicities.

PubMed

Razavi, Bibi Marjan; Hosseinzadeh, Hossein

2015-05-01

Saffron (Crocus sativus) is an extensively used food additive for its color and taste. Since ancient times this plant has been introduced as a marvelous medicine throughout the world. The wide spectrum of saffron pharmacological activities is related to its major constituents including crocin, crocetin and safranal. Based on several studies, saffron and its active ingredients have been used as an antioxidant, antiinflammatory and antinociceptive, antidepressant, antitussive, anticonvulsant, memory enhancer, hypotensive and anticancer. According to the literatures, saffron has remarkable therapeutic effects. The protective effects of saffron and its main constituents in different tissues including brain, heart, liver, kidney and lung have been reported against some toxic materials either natural or chemical toxins in animal studies.In this review article, we have summarized different in vitro and animal studies in scientific databases which investigate the antidotal and protective effects of saffron and its major components against natural toxins and chemical-induced toxicities. Due to the lake of human studies, further investigations are required to ascertain the efficacy of saffron as an antidote or a protective agent in human intoxication.

Methamphetamine toxicity-induced calcineurin activation, nuclear translocation of nuclear factor of activated T-cells and elevation of cyclooxygenase 2 levels are averted by calpastatin overexpression in neuroblastoma SH-SY5Y cells.

PubMed

Chetsawang, Jirapa; Nudmamud-Thanoi, Sutisa; Phonchai, Ruchee; Abubakar, Zuroida; Govitrapong, Piyarat; Chetsawang, Banthit

2018-06-23

Methamphetamine (METH) is an addictive stimulant drug that has many negative consequences, including toxic effects to the brain. Recently, the induction of inflammatory processes has been identified as a potential contributing factor to induce neuronal cell degeneration. It has been demonstrated that the expression of inflammatory agents, such as cyclooxygenase 2 (COX-2), depends on the activation of calcineurin (CaN) and nuclear factor of activated T-cells (NFAT). Moreover, the excessive elevation in cytosolic Ca 2+ levels activates the cell death process, including calpain activation in neurons, which was diminished by the overexpression of the calpain inhibitor protein, calpastatin. However, it is unclear whether calpain mediates CaN-NFAT activation in the neurotoxic process. In the present study, we observed that the toxic high dose of METH-treated neuroblastoma SH-SY5Y cells significantly decreased cell viability but increased apoptotic cell death, the active cleaved form of calcineurin, the nuclear translocation of NFAT, and COX-2 levels. Nevertheless, these toxic effects were diminished in METH-treated calpastatin-overexpressing SH-SY5Y cells. These findings might emphasize the role of calpastatin against METH-induced toxicity by a mechanism related to calpain-dependent CaN-NFAT activation-induced COX-2 expression. Copyright © 2018. Published by Elsevier B.V.

Toxic Epidemics: Agent Orange Sickness in Vietnam and the United States.

PubMed

Uesugi, Tak

2016-01-01

Social scientists studying toxic epidemics have often endeavored to shed light on the differences between scientists' and nonscientists' epistemic perspectives. Yet, little attention has been paid to the processes through which a toxic epidemic emerges as a phenomenon. A Luoi Valley of Central Vietnam was extensively sprayed with chemical defoliants (including Agent Orange) during the Vietnam War. The latent toxic effects of these chemicals, however, went largely unnoticed until the late 1990s. By juxtaposing the history through which the notion of "Agent Orange Sickness" emerged in the United States with an ethnographic study of A Luoi, I explore the notion of poison under which Agent Orange became recognizable as a poison.

Biostimulation of Oil Sands Process-Affected Water with Phosphate Yields Removal of Sulfur-Containing Organics and Detoxification.

PubMed

Quesnel, Dean M; Oldenburg, Thomas B P; Larter, Stephen R; Gieg, Lisa M; Chua, Gordon

2015-11-03

The ability to mitigate toxicity of oil sands process-affected water (OSPW) for return into the environment is an important issue for effective tailings management in Alberta, Canada. OSPW toxicity has been linked to classical naphthenic acids (NAs), but the toxic contribution of other acid-extractable organics (AEOs) remains unknown. Here, we examine the potential for in situ bioremediation of OSPW AEOs by indigenous algae. Phosphate biostimulation was performed in OSPW to promote the growth of indigenous photosynthetic microorganisms and subsequent toxicity and chemical changes were determined. After 12 weeks, the AEO fraction of phosphate-biostimulated OSPW was significantly less toxic to the fission yeast Schizosaccharomyces pombe than unstimulated OSPW. Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) analysis of the AEO fraction in phosphate-biostimulated OSPW showed decreased levels of SO3 class compounds, including a subset that may represent linear arylsulfonates. A screen with S. pombe transcription factor mutant strains for growth sensitivity to the AEO fraction or sodium dodecylbenzenesulfonate revealed a mode of toxic action consistent with oxidative stress and detrimental effects on cellular membranes. These findings demonstrate a potential algal-based in situ bioremediation strategy for OSPW AEOs and uncover a link between toxicity and AEOs other than classical NAs.

Effect-Based Tools for Monitoring and Predicting the Ecotoxicological Effects of Chemicals in the Aquatic Environment

PubMed Central

Connon, Richard E.; Geist, Juergen; Werner, Inge

2012-01-01

Ecotoxicology faces the challenge of assessing and predicting the effects of an increasing number of chemical stressors on aquatic species and ecosystems. Herein we review currently applied tools in ecological risk assessment, combining information on exposure with expected biological effects or environmental water quality standards; currently applied effect-based tools are presented based on whether exposure occurs in a controlled laboratory environment or in the field. With increasing ecological relevance the reproducibility, specificity and thus suitability for standardisation of methods tends to diminish. We discuss the use of biomarkers in ecotoxicology including ecotoxicogenomics-based endpoints, which are becoming increasingly important for the detection of sublethal effects. Carefully selected sets of biomarkers allow an assessment of exposure to and effects of toxic chemicals, as well as the health status of organisms and, when combined with chemical analysis, identification of toxicant(s). The promising concept of “adverse outcome pathways (AOP)” links mechanistic responses on the cellular level with whole organism, population, community and potentially ecosystem effects and services. For most toxic mechanisms, however, practical application of AOPs will require more information and the identification of key links between responses, as well as key indicators, at different levels of biological organization, ecosystem functioning and ecosystem services. PMID:23112741

A combined evaluation of the characteristics and acute toxicity of antibiotic wastewater.

PubMed

Yu, Xin; Zuo, Jiane; Li, Ruixia; Gan, Lili; Li, Zaixing; Zhang, Fei

2014-08-01

The conventional parameters and acute toxicities of antibiotic wastewater collected from each treatment unit of an antibiotic wastewater treatment plant have been investigated. The investigation of the conventional parameters indicated that the antibiotic wastewater treatment plant performed well under the significant fluctuation in influent water quality. The results of acute toxicity indicated that the toxicity of antibiotic wastewater could be reduced by 94.3 percent on average after treatment. However, treated antibiotic effluents were still toxic to Vibrio fischeri. The toxicity of antibiotic production wastewater could be attributed to the joint effects of toxic compound mixtures in wastewater. Moreover, aerobic biological treatment processes, including sequencing batch reactor (SBR) and aerobic biofilm reactor, played the most important role in reducing toxicity by 92.4 percent. Pearson׳s correlation coefficients revealed that toxicity had a strong and positive linear correlation with organic substances, nitrogenous compounds, S(2-), volatile phenol, cyanide, As, Zn, Cd, Ni and Fe. Ammonia nitrogen (NH4(+)) was the greatest contributor to toxicity according to the stepwise regression method. The multiple regression model was a good fit for [TU50-15 min] as a function of [NH₄(+)] with the determination coefficient of 0.981. Copyright © 2014 Elsevier Inc. All rights reserved.

Snake Venom L-Amino Acid Oxidases: Trends in Pharmacology and Biochemistry

PubMed Central

Izidoro, Luiz Fernando M.; Sobrinho, Juliana C.; Mendes, Mirian M.; Costa, Tássia R.; Grabner, Amy N.; Rodrigues, Veridiana M.; da Silva, Saulo L.; Zanchi, Fernando B.; Zuliani, Juliana P.; Fernandes, Carla F. C.; Calderon, Leonardo A.; Stábeli, Rodrigo G.; Soares, Andreimar M.

2014-01-01

L-amino acid oxidases are enzymes found in several organisms, including venoms of snakes, where they contribute to the toxicity of ophidian envenomation. Their toxicity is primarily due to enzymatic activity, but other mechanisms have been proposed recently which require further investigation. L-amino acid oxidases exert biological and pharmacological effects, including actions on platelet aggregation and the induction of apoptosis, hemorrhage, and cytotoxicity. These proteins present a high biotechnological potential for the development of antimicrobial, antitumor, and antiprotozoan agents. This review provides an overview of the biochemical properties and pharmacological effects of snake venom L-amino acid oxidases, their structure/activity relationship, and supposed mechanisms of action described so far. PMID:24738050

Cancer Treatment Side Effects: A Meta-analysis of the Relationship Between Response Expectancies and Experience.

PubMed

Devlin, Elise J; Denson, Linley A; Whitford, Hayley S

2017-08-01

Although previous research has, overall, suggested a moderate relationship between response expectancies (REs) and cancer treatment-related side effects, empirical results have been mixed. We aimed to further explore these relationships, hypothesizing that REs would predict subsequent toxicities with the inclusion of more recent studies, across a broader range of side effects, while incorporating the impact of potential moderators including patients' experience with treatment and measurement methods. We further investigated the impact of REs across individual toxicities. A systematic search and analysis were conducted across four databases (PsychInfo, PubMed, CINAHL, and Embase) and reference lists, from 1985 to February 2016. This provided 27 eligible studies with 4474 participants, through which the main analysis, moderator analyses, and individual side-effect analyses were explored. REs were moderately related to side effects overall (r = 0.26), and effect sizes were significantly influenced by sample diagnostic homogeneity, whereas differences between type and timing of measurement showed trends. Of the 16 toxicities examined, 15 demonstrated significant relationships between REs and side-effect experience, with hair loss (r = 0.48) the strongest. No clear difference emerged between objective and subjective side effects; however, significant differences across individual toxicities were revealed. Findings support a relationship between REs and a wide range of subsequent side effects, yet differences between individual RE-toxicity associations emerged. These findings provide direction for the measurement of side effects and REs and support REs as potential targets for intervention during the informed consent process. Copyright © 2017 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Multiple factors govern the association between pharmacology and toxicity in a class of drugs: toward a unification of class effect terminology.

PubMed

Smith, Dennis A; Harrison, Anthony; Morgan, Paul

2011-04-18

The term class effect has gained in use to describe a side effect including toxicity common to a series of drugs. There is no definition of what constitutes a class effect, and it is not applied against a rigid set of criteria.Thus, the finding of toxicity in one of a series of drugs can raise the concern of a class effect, especially if one or more of the others shows findings even slightly related or at very much lower incidence. This is particularly problematic when the term is used loosely or speculatively on initial events that are themselves of low incidence and serious. This speculation exaggerates and distorts the scientific process in establishing the true benefit risk of the individual drugs and can lead to lengthy development times, or highly restrictive labeling, to the detriment of patient welfare. To provide better definition and application of the term, we suggest that the term class effect toxicity is only used when a clear mechanistic link has been established between a safety concern and drug class based on (I) where the primary pharmacology delivers a clear rationale for the observed findings and toxicities; and (II) where the secondary pharmacology is obligate to the class of the molecule and not subject to variation of structure, and the selectivity cannot be impacted significantly by variations in potency introduced by structural manipulation. With these categorizations, we believe class effect toxicity will be mainly confined to I with examples such as the tetracycline class of antibacterials which inhibit protein synthesis both as a mechanism of antibacterial activity and to produce hepatic injury by mitochondrial injury in the liver.

Ecotoxicological effect of ketamine: Evidence of acute, chronic and photolysis toxicity to Daphnia magna.

PubMed

Li, Shih-Wei; Wang, Yu-Hsiang; Lin, Angela Yu-Chen

2017-09-01

Ketamine has been increasingly used in medicine and has the potential for abuse or illicit use around the world. Ketamine cannot be removed by conventional wastewater treatment plants. Although ketamine and its metabolite norketamine have been detected to a significant degree in effluents and aquatic environments, their ecotoxicity effects in aquatic organisms remain undefined. In this study, we investigated the acute toxicity of ketamine and its metabolite, along with the chronic reproductive toxicity of ketamine (5-100μg/L) to Daphnia magna. Multiple environmental scenarios were also evaluated, including drug mixtures and sunlight irradiation toxicity. Ketamine and norketamine caused acute toxicity to D. magna, with half lethal concentration (LC 50 ) values of 30.93 and 25.35mg/L, respectively, after 48h of exposure. Irradiated solutions of ketamine (20mg/L) significantly increased the mortality of D. magna; pre-irradiation durations up to 2h rapidly increased the death rate to 100%. A new photolysis byproduct (M.W. 241) of norketamine that accumulates during irradiation was identified for the first time. The relevant environmental concentration of ketamine produced significant reproductive toxicity effects in D. magna, as revealed by the reduction of the number of total live offspring by 33.6-49.8% (p < 0.05). The toxicity results indicate that the environmental hazardous risks of the relevant ketamine concentration cannot be ignored and warrant further examination. Copyright © 2017 Elsevier Inc. All rights reserved.

Synergistic Effects of Nano-Sized Titanium Dioxide and Zinc on the Photosynthetic Capacity and Survival of Anabaena sp.

PubMed Central

Tang, Yulin; Li, Shuyan; Qiao, Junlian; Wang, Hongtao; Li, Lei

2013-01-01

Anabaena sp. was used to examine the toxicity of exposure to a nano-TiO2 suspension, Zn2+ solution, and mixtures of nano-TiO2 and Zn2+ suspensions. Typical chlorophyll fluorescence parameters, including effective quantum yield, photosynthetic efficiency and maximal electron transport rate, were measured by a pulse-amplitude modulated fluorometer. Nano-TiO2 particles exhibited no significant toxicity at concentrations lower than 10.0 mg/L. The 96 h concentration for the 50% maximal effect (EC50) of Zn2+ alone to Anabaena sp. was 0.38 ± 0.004 mg/L. The presence of nano-TiO2 at low concentrations (<1.0 mg/L) significantly enhanced the toxicity of Zn2+ and consequently reduced the EC50 value to 0.29 ± 0.003 mg/L. However, the toxicity of the Zn2+/TiO2 system decreased with increasing nano-TiO2 concentration because of the substantial adsorption of Zn2+ by nano-TiO2. The toxicity curve of the Zn2+/TiO2 system as a function of incremental nano-TiO2 concentrations was parabolic. The toxicity significantly increased at the initial stage, reached its maximum, and then decreased with increasing nano-TiO2 concentration. Hydrodynamic sizes, concentration of nano-TiO2 and Zn2+ loaded nano-TiO2 were the main parameters for synergistic toxicity. PMID:23852017

Effect of H+ ion activity and Ca2+ on the toxicity of metals in the environment.

PubMed Central

Hutchinson, T C; Collins, F W

1978-01-01

The role of acidity in determining and restricting plant distribution and performance is discussed. In soils especially, a key effect of H+ ion concentration is on the solubility of potentially toxic heavy metals such as aluminum, managenese, zinc, iron, copper, and nickel. Al has been reported from many studies since the 1920's as the key determining toxic factor in acid soils. Some acid-tolerant species have been shown to be especially tolerant of Al, and mechanisms of tolerance have been suggested. Mn is also a commonly toxic factor at soil pH less than 5.0. Calcium has been shown to alleviate Mn toxicity. Low pH soils are also generally low in Ca, K, Na, and P; all essential major elements for plant growth. In lakes and marine situations acidic waters are uncommon as the waters are buffered. Calcium is again ameliorative of metal toxicities. The pH, redox, and valency state are critical in determining nutrient availability and metal speciation. Recent increases in the H+ ion content of precipitation have caused increased acidities of freshwater lakes in Scandinavia and eastern North America, which have depleted biota, including fish populations. PMID:31277

The Role of Transporters in the Toxicity of Nucleoside and Nucleotide Analogs

PubMed Central

Koczor, Christopher A; Torres, Rebecca A

2013-01-01

Introduction Two families of nucleoside analogs have been developed to treat viral infections and cancer, but these compounds can cause tissue and cell-specific toxicity related to their uptake and subcellular activity which are dictated by host enzymes and transporters. Cellular uptake of these compounds requires nucleoside transporters that share functional similarities but differ in substrate specificity. Tissue-specific cellular expression of these transporters enables nucleoside analogs to produce their tissue specific toxic effects, a limiting factor in the treatment of retroviruses and cancer. Areas Covered This review discusses the families of nucleoside transporters and how they mediate cellular uptake of nucleoside analogs. Specific focus is placed on examples of known cases of transporter-mediated cellular toxicity and classification of the toxicities resulting. Efflux transporters are also explored as a contributor to analog toxicity and cell-specific effects. Expert Opinion Efforts to modulate transporter uptake/clearance remain long-term goals of oncologists and virologists. Accordingly, subcellular approaches that either increase or decrease intracellular nucleoside analog concentrations are eagerly sought and include transporter inhibitors and targeting transporter expression. However, additional understanding of nucleoside transporter kinetics, tissue expression, and genetic polymorphisms are required to design better molecules and better therapies. PMID:22509856

Assessment of toxic effects of triclosan on the terrestrial snail (Achatina fulica).

PubMed

Wang, Xiaonan; Liu, Zhengtao; Wang, Wanhua; Yan, Zhenguang; Zhang, Cong; Wang, Weili; Chen, Lihong

2014-08-01

Triclosan (TCS) is a broad-spectrum antimicrobial agent used in personal care products, and as a result, is widespread in the environment. Toxicity tests of TCS on aquatic organisms have been reported, but limited toxicity data on terrestrial species are available. In this study, the 28-d chronic toxicity of TCS on the biomass, shell diameter growth, and total food intake of the terrestrial snail Achatina fulica were tested. Moreover, biochemical responses, including changes in the activity of catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), and the content of malondialdehyde (MDA), were examined after 14-d and 28-d exposure. Results showed that TCS had toxic effects on the biomass, shell diameter growth, and total food intake of A. fulica with no observed effect concentration (NOEC) values of 24 mg kg(-1). As for the antioxidant enzymes, TCS caused significant oxidative stress even at the low concentration of 24 mg kg(-1). The CAT and POD activities at the high concentrations of 200 and 340 mg kg(-1), respectively, were significantly inhibited. The SOD and CAT activity in treatments below 118 mg kg(-1) and the MDA content in all treatments showed dose-effect relationships. This study demonstrated that TCS caused adverse effects on terrestrial invertebrates, and provided valuable information for the risk assessment imposed by TCS in the terrestrial environment. Copyright © 2014 Elsevier Ltd. All rights reserved.

Developmental and reproductive toxicity of inorganic arsenic: animal studies and human concerns.

PubMed

Golub, M S; Macintosh, M S; Baumrind, N

1998-01-01

Information on the reproductive and developmental toxicity of inorganic arsenic is available primarily from studies in animals using arsenite and arsenate salts and arsenic trioxide. Inorganic arsenic has been extensively studied as a teratogen in animals. Data from animal studies demonstrate that arsenic can produce developmental toxicity, including malformation, death, and growth retardation, in four species (hamsters, mice, rats, rabbits). A characteristic pattern of malformations is produced, and the developmental toxicity effects are dependent on dose, route, and the day of gestation when exposure occurs. Studies with gavage and diet administration indicate that death and growth retardation are produced by oral arsenic exposure. Arsenic is readily transferred to the fetus and produces developmental toxicity in embryo culture. Animal studies have not identified an effect of arsenic on fertility in males or females. When females were dosed chronically for periods that included pregnancy, the primary effect of arsenic on reproduction was a dose-dependent increase in conceptus mortality and in postnatal growth retardation. Human data are limited to a few studies of populations exposed to arsenic from drinking water or from working at or living near smelters. Associations with spontaneous abortion and stillbirth have been reported in more than one of these studies, but interpretation of these studies is complicated because study populations were exposed to multiple chemicals. Thus, animal studies suggest that environmental arsenic exposures are primarily a risk to the developing fetus. In order to understand the implications for humans, attention must be given to comparative pharmacokinetics and metabolism, likely exposure scenarios, possible mechanisms of action, and the potential role of arsenic as an essential nutrient.

Effect of temperature on heavy metal toxicity to juvenile crayfish, Orconectes immunis (Hagen).

PubMed

Khan, M A Q; Ahmed, S A; Catalin, Bogdon; Khodadoust, A; Ajayi, Oluwaleke; Vaughn, Mark

2006-10-01

The acute toxicity of four selected heavy metals to juvenile crayfish Orconectes immunis (Hagen) (1-2 g wet body wt. each) at room temperature increased in the following order: cadmium (x3) < copper (x10) < zinc (x2) < lead. The toxicity of these metals to crayfish acclimated at 17, 20, 23/24, and 27 degrees C increased with temperature (by 7-20% between 20 and 24 degrees C and 14-26% between 20 and 27 degrees C) as judged by the lowering of LT(50) (time to kill 50% of test animals at a fixed concentration) values. A 4 degrees C rise in temperature (from 20 to 24 degrees C), which increased the toxicity of copper by about 7%, increased the rate of oxygen consumption by about 34%. Heavy metals inhibited the rate of oxygen consumption at all temperatures. In 20 degrees C-acclimated crayfish, copper caused about 17% inhibition of oxygen consumption compared to about 7-12% by other metals including the most toxic cadmium. A 3-4 degrees C rise in temperature tripled the inhibitory effect of copper (20%), cadmium and zinc (26 and 18%, respectively), but not of lead, on oxygen consumption. A 7 degrees C-rise in temperature (from 20 to 27 degrees C) increased the inhibitory effect of heavy metals, including lead, on oxygen consumption by up to 54% in the case of copper. The data indicate that rising global temperatures (currently 0.60 degrees C) associated with climate change can have the potential to increase the sensitivity of aquatic animals to heavy metals in their environment.

An evaluation of benthic community measures using laboratory-derived sediment effect concentrations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dwyer, F.J.; Canfield, T.J.; Ingersoll, C.G.

1995-12-31

Sediment effect concentrations (SECs) are contaminant sediment concentrations which are frequently associated with sediment toxicity. Recently, a number of different SECs have been calculated from laboratory toxicity tests with field collected sediments using Chironomus tentans, Chironomus riparius, and Hyalella azteca. Toxicity endpoints included (depending upon species) lethality, growth and sexual maturation. The authors selected the Effect Range Median (ERM) calculated for 28-d Hyalella azteca as an SEC for evaluating six different benthic community measures as indicators of contaminated sediment. The benthic measures included: taxa richness, chironomid genera richness, percent chironomid deformity, chironomid biotic index, ratio of chironomids/oligochaetes, and oligochaete bioticmore » index. Benthic measures were obtained for 31 stations from the Great Lakes and 13 stations from Milltown Reservoir and Clark Fork River, MT. Each benthic measure was ranked from 1 to 100 and individual ranks and various combinations of ranks were plotted against the ratio of chemical concentration at the site/ERM calculated for that chemical (similar to a toxic unit approach) and the sum of the ERM ratios (sum of toxic units). Preliminary analysis indicates that, in general, benthic measures varied widely in relatively uncontaminated stations, confounding any underlying relationship that may have existed. The absence of chironomids, in areas with suitable habitat, seems to be indicative of grossly contaminated stations, but not an endpoint useful for discriminating stations with contaminant concentrations closer to the SEC. The usefulness of benthic measures as diagnostic tools for contaminated sediments and potential ways to improve these measures will be discussed.« less

The Developmental Toxicity of Complex Silica-Embedded Nickel Nanoparticles Is Determined by Their Physicochemical Properties

PubMed Central

Mahoney, Sharlee; Najera, Michelle; Bai, Qing; Burton, Edward A.; Veser, Götz

2016-01-01

Complex engineered nanomaterials (CENs) are a rapidly developing class of structurally and compositionally complex materials that are expected to dominate the next generation of functional nanomaterials. The development of methods enabling rapid assessment of the toxicity risk associated with this type of nanomaterial is therefore critically important. We evaluated the toxicity of three differently structured nickel-silica nanomaterials as prototypical CENs: simple, surface-deposited Ni-SiO2 and hollow and non-hollow core-shell Ni@SiO2 materials (i.e., ~1–2 nm Ni nanoparticles embedded into porous silica shells with and without a central cavity, respectively). Zebrafish embryos were exposed to these CENs, and morphological (survival and malformations) and physiological (larval motility) endpoints were coupled with thorough characterization of physiochemical characteristics (including agglomeration, settling and nickel ion dissolution) to determine how toxicity differed between these CENs and equivalent quantities of Ni2+ salt (based on total Ni). Exposure to Ni2+ ions strongly compromised zebrafish larva viability, and surviving larvae showed severe malformations. In contrast, exposure to the equivalent amount of Ni CEN did not result in these abnormalities. Interestingly, exposure to Ni-SiO2 and hollow Ni@SiO2 provoked abnormalities of zebrafish larval motor function, indicating developmental toxicity, while non-hollow Ni@SiO2 showed no toxicity. Correlating these observations with physicochemical characterization of the CENs suggests that the toxicity of the Ni-SiO2 and hollow Ni@SiO2 material may result partly from an increased effective exposure at the bottom of the well due to rapid settling. Overall, our data suggest that embedding nickel NPs in a porous silica matrix may be a straightforward way to mitigate their toxicity without compromising their functional properties. At the same time, our results also indicate that it is critical to consider modification of the effective exposure when comparing different nanomaterial configurations, because effective exposure might influence NP toxicity more than specific “nano-chemistry” effects. PMID:27031643

Influence factors of multicomponent mixtures containing reactive chemicals and their joint effects.

PubMed

Tian, Dayong; Lin, Zhifen; Yu, Jianqiao; Yin, Daqiang

2012-08-01

Organic chemicals usually coexist as a mixture in the environment, and the mixture toxicity of organic chemicals has received increased attention. However, research regarding the joint effects of reactive chemicals is lacking. In this study, we examined two kinds of reactive chemicals, cyanogenic toxicants and aldehydes and determined their joint effects on Photobacterium phosphoreum. Three factors were found to influence the joint effects of multicomponent mixtures containing reactive chemicals, including the number of components, the dominating components and the toxic ratios. With an increased number of components, the synergistic or antagonistic effects (interactions) will weaken to the additive effects (non-interactions) if the added component cannot yield a much stronger joint effect with an existing component. Contrarily, the joint effect of the mixture may become stronger instead of weaker if the added components can yield a much stronger joint effect than the existing joint effect of the multicomponent mixture. The components that yield the strongest interactions in their binary mixture can be considered the dominating components. These components contribute more to the interactions of multicomponent mixtures than other components. Moreover, the toxic ratios also influence the joint effects of the mixtures. This study provides an insight into what are the main factors and how they influence the joint effects of multicomponent mixtures containing reactive chemicals, and thus, the findings are beneficial to the study of mixture toxicology. Copyright © 2012 Elsevier Ltd. All rights reserved.

Pollutant Concentrations and Toxic Effects on the Red Alga Ceramium tenuicorne of Sediments from Natural Harbors and Small Boat Harbors on the West Coast of Sweden.

PubMed

Eklund, Britta; Hansson, Tomas; Bengtsson, Henrik; Eriksson Wiklund, Ann-Kristin

2016-04-01

This investigation set out to analyze the toxicity of surface sediments in a number of natural harbors and small boat harbors on the west coast of Sweden. This was done with the growth inhibition method with Ceramium tenuicorne. Also, concentrations of copper (Cu), lead (Pb), zinc (Zn), irgarol, organotin compounds, and polycyclic aromatic hydrocarbons (PAHs) in the sediments were analyzed. The small boat harbors were heavily polluted by Cu, Zn, butyltins, and PAHs, and to a lesser extent by Pb. The Cu, Pb, Zn, and butyltins probably originated from their past and/or present use in antifouling paints, whereas the PAHs probably had multiple sources, including boat motor exhausts. The measured toxicity of the sediment was generally related to their Cu, Zn, and butyltin content, although other toxic substances than those analyzed here probably contributed to the toxicity in some of the harbors. The natural harbor sediments contained less pollutants and were less toxic than the small boat harbor sediments. Nevertheless, our data indicate that the boating pressure today may be high enough to produce toxic effects even in natural harbors in pristine areas. The strongest relationship between toxicity and the major pollutants was obtained when the sediment toxicity was expressed as gram wet weight per liter compared with gram dry weight per liter and gram total organic carbon per liter. Hence, for pollutants that can be elutriated with natural sea water, sediment toxicity expressed as gram wet weight per liter appears preferable.

Toxicity assessment using different bioassays and microbial biosensors.

PubMed

Hassan, Sedky H A; Van Ginkel, Steven W; Hussein, Mohamed A M; Abskharon, Romany; Oh, Sang-Eun

2016-01-01

Toxicity assessment of water streams, wastewater, and contaminated sediments, is a very important part of environmental pollution monitoring. Evaluation of biological effects using a rapid, sensitive and cost effective method can indicate specific information on ecotoxicity assessment. Recently, different biological assays for toxicity assessment based on higher and lower organisms such as fish, invertebrates, plants and algal cells, and microbial bioassays have been used. This review focuses on microbial biosensors as an analytical device for environmental, food, and biomedical applications. Different techniques which are commonly used in microbial biosensing include amperometry, potentiometry, conductometry, voltammetry, microbial fuel cells, fluorescence, bioluminescence, and colorimetry. Examples of the use of different microbial biosensors in assessing a variety of environments are summarized. Copyright © 2016 Elsevier Ltd. All rights reserved.

Efficient, non-toxic anion transport by synthetic carriers in cells and epithelia

NASA Astrophysics Data System (ADS)

Li, Hongyu; Valkenier, Hennie; Judd, Luke W.; Brotherhood, Peter R.; Hussain, Sabir; Cooper, James A.; Jurček, Ondřej; Sparkes, Hazel A.; Sheppard, David N.; Davis, Anthony P.

2016-01-01

Transmembrane anion transporters (anionophores) have potential for new modes of biological activity, including therapeutic applications. In particular they might replace the activity of defective anion channels in conditions such as cystic fibrosis. However, data on the biological effects of anionophores are scarce, and it remains uncertain whether such molecules are fundamentally toxic. Here, we report a biological study of an extensive series of powerful anion carriers. Fifteen anionophores were assayed in single cells by monitoring anion transport in real time through fluorescence emission from halide-sensitive yellow fluorescent protein. A bis-(p-nitrophenyl)ureidodecalin shows especially promising activity, including deliverability, potency and persistence. Electrophysiological tests show strong effects in epithelia, close to those of natural anion channels. Toxicity assays yield negative results in three cell lines, suggesting that promotion of anion transport may not be deleterious to cells. We therefore conclude that synthetic anion carriers are realistic candidates for further investigation as treatments for cystic fibrosis.

Toxicity of food additives (excluding antioxidants). January 1978-November 1987 (citations from the Life Sciences Collection data base). Report for January 1978-November 1987

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1987-12-01

This bibliography contains citations concerning the toxicity of food additives (excluding antioxidants) and their effects on the liver, kidneys, bladder, and other organs. The carcinogenic and teratogenic properties of these substances are also considered. The synthetic sweeteners, particularly the saccharins and cyclamates, and other additives, including nitrates and nitrites are discussed. Methods to detect and quantitate these additives are also included. (This updated bibliography contains 340 citations, 132 of which are new entries to the previous edition.)

Toxic effects of brominated flame retardants in man and in wildlife.

PubMed

Darnerud, Per Ola

2003-09-01

Brominated flame retardants (BFRs) are ubiquitous industrial chemicals, and many of them are produced in large volumes. Due to this fact, several BFRs are found in quantifiable levels in wildlife, as well as in humans. However, we are still lacking information on the effects of BFR in wildlife and, especially, in man. This review summarises the biological effects of polybrominated diphenyl ethers (PBDEs), tetrabromobisphenol A (TBBPA) and derivates, hexabromocyclododecane (HBCD) and polybrominated biphenyls (PBBs), however excluding other aspects such as environmental levels. These BFR groups were selected because of a large volume production (PBDEs, TBBPA and derivates), and availability of some toxicity data in spite of much lower production volumes (HBCD and PBBs). In addition, the increase in levels of PBDEs in human (breast milk) and wildlife samples during later time made it especially interesting to include this BFR group. PBDES: The commercial PBDE products predominantly consist of so-called penta-, octa- and decabromodiphenyl ether products. Each product consists of a rather narrow range of congeners and is named after the dominating congener as regards the bromination pattern. Generally, the PentaBDEs seem to cause adverse effects at the comparably lowest dose, whereas much higher doses were needed for effects of the DecaBDEs. The critical effects of PentaBDEs are those on neurobehavioural development (from 0.6 mg/kg body weight) and, at somewhat higher dose, thyroid hormone levels in rats and mice, of OctaBDEs on fetal toxicity/teratogenicity in rats and rabbits (from 2 mg/kg body weight), and of DecaBDEs on thyroid, liver and kidney morphology in adult animals (from 80 mg/kg body weight). Carcinogenicity studies, only performed for DecaBDEs, show some effects at very high levels, and IARC (1990) evaluates DecaBDEs not classifiable as to its carcinogenicity to humans. TBBPA: The toxicity of TBBPA in the experimental in vivo studies is suggested to be low. In most reported studies, only doses in g/kg body weight were effective, but at least one study suggested renal effects at around 250 mg/kg body weight. Although difficult to include and interpret in a quantitative risk assessment, the in vitro effects on immunological and thyroid hormones, as well as binding to erythrocytes should be noted. Before a solid standpoint could be reached on TBBPA toxicity additional studies must be performed. This statement is even more valid regarding the TBBPA derivates, where there is an almost complete lack of toxicity data. HBCD: Also in the case of HBCD, relevant toxicity studies are lacking. Based on the present animal studies, a critical effect is seen in the liver and on thyroid hormones (LOAEL 100 mg/kg body weight/day). However, in a recent short paper behavioural effects in mice pups were observed already at 0.9 mg/kg body weight, and behavioural effects may be a sensitive endpoint for HBCD, as well as for other BFRs. PBBS: Due to the Michigan accident in 1973-1974, many toxicity studies on PBBs are available. The critical experimental effects are those on reproduction and carcinogenicity, and a NOAEL of 0.15 mg/kg body weight/day could be suggested based on the cancer effects. In man no unequivocal effects have been observed, although in some studies neurological and musculoskeletal symptoms were suggested. Based on the carcinogenic effects in animals, a human TDI of 0.15 microg/kg body weight has been presented. To conclude, the toxicity data are almost entirely based on experimental models. There are differences among the BFR groups, as well as within these groups, both regarding type of toxic effect and at what dose it appears. As BFRs will continue to appear both in industrial applications and, even if the production has ceased, in our environment, there is a continued need for effects studies on BFRs.

Bisphenol Analogues Other Than BPA: Environmental Occurrence, Human Exposure, and Toxicity-A Review.

PubMed

Chen, Da; Kannan, Kurunthachalam; Tan, Hongli; Zheng, Zhengui; Feng, Yong-Lai; Wu, Yan; Widelka, Margaret

2016-06-07

Numerous studies have investigated the environmental occurrence, human exposure, and toxicity of bisphenol A (BPA). Following stringent regulations on the production and usage of BPA, several bisphenol analogues have been produced as a replacement for BPA in various applications. The present review outlines the current state of knowledge on the occurrence of bisphenol analogues (other than BPA) in the environment, consumer products and foodstuffs, human exposure and biomonitoring, and toxicity. Whereas BPA was still the major bisphenol analogue found in most environmental monitoring studies, BPF and BPS were also frequently detected. Elevated concentrations of BPAF, BPF, and BPS (i.e., similar to or greater than that of BPA) have been reported in the abiotic environment and human urine from some regions. Many analogues exhibit endocrine disrupting effects, cytotoxicity, genotoxicity, reproductive toxicity, dioxin-like effects, and neurotoxicity in laboratory studies. BPAF, BPB, BPF, and BPS have been shown to exhibit estrogenic and/or antiandrogenic activities similar to or even greater than that of BPA. Knowledge gaps and research needs have been identified, which include the elucidation of environmental occurrences, persistence, and fate of bisphenol analogues (other than BPA), sources and pathways for human exposure, effects on reproductive systems and the mammary gland, mechanisms of toxicity from coexposure to multiple analogues, metabolic pathways and products, and the impact of metabolic modification on toxicity.

Skin toxicities and unmet supportive care needs of patients with cancer undergoing EGFR-inhibitor therapy

PubMed

Matzka, Martin; Stöhr, Doreen; Colditz, Alexandra; Köck-Hódi, Sabine; Koller, Martina; Mayer, Hanna

2017-01-01

Background: Targeted therapies, such as the EGFR (epidermal growth factor receptor) inhibitor therapy, are being used to treat patients with various solid and metastatic tumours. Skin toxicities are a common side effect of this therapy. Aim: The aim of this study was to assess the effects of skin toxicities on quality of life of patients with cancer undergoing EGFR inhibitor therapy, as well as their unmet supportive care needs. Method: Embedded design. A standardised quantitative survey was administered and analysed. In addition, memos and audiotaped material of insightful conversations with the patients after survey administration were included in the analyses. Results: Among the three domains of the effects of skin toxicities on quality of life, physical symptoms (e. g. itching skin, rash) were most frequently reported to impair quality of life, while associated emotional and functional impairments were less frequently reported. Patients don’t consider the management of skin toxicities to be a priority during their treatment, skin toxicities are rather perceived in context of the total symptom burden. Yet, we observed significant correlations between the assessed quality of life and unmet supportive care need domains, especially concerning physical and psychological needs. Conclusions: Although no clinically significant impairment of quality of life of patients undergoing EGFR inhibitor therapy was found, skin changes should be addressed in supportive interventions embedded in routine symptom management.

Assessment of the acute toxicity of triclosan and methyl triclosan in wastewater based on the bioluminescence inhibition of Vibrio fischeri.

PubMed

Farré, Marinella; Asperger, Daniela; Kantiani, Lina; González, Susana; Petrovic, Mira; Barceló, Damià

2008-04-01

In this work, the contributions of triclosan and its metabolite methyl triclosan to the overall acute toxicity of wastewater were studied using Vibrio fischeri. The protocol used in this paper involved various steps. First, the aquatic toxicities of triclosan and methyl triclosan were determined for standard substances, and the 50% effective concentrations (EC(50)) were determined for these compounds. Second, the toxic responses to different mixtures of triclosan, methyl triclosan, and surfactants were studied in different water matrices, i.e., Milli-Q water, groundwater and wastewater, in order to evaluate (i) the antagonistic or synergistic effects, and (ii) the influence of the water matrices. Finally, chemical analysis was used in conjunction with the toxicity results in order to assess the aquatic toxicities of triclosan and its derivative in wastewaters. In this study, the toxicities of 45 real samples corresponding to the influents and effluents from eight wastewater treatment works (WWTW) were analyzed. Thirty-one samples were from a wastewater treatment plant (WWTP) equipped with two pilot-scale membrane bioreactors (MBR), and the influent and the effluent samples after various treatments were characterized via different chromatographic approaches, including solid-phase extraction (SPE), liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS), and SPE coupled to gas chromatography-mass spectrometry (GC-MS). The toxicity was determined by measuring the bioluminescence inhibition of Vibrio fischeri. In order to complete the study and to extrapolate the results to different WWTPs, the toxicity to V. fischeri of samples from seven more plants was analyzed, as were their triclosan and methyl triclosan concentrations. Good agreement was established between the overall toxicity values and concentrations of the biocides, indicating that triclosan is one of the major toxic organic pollutants currently found in domestic wastewaters.

Reduced Toxicity Fuel Satellite Propulsion System Including Plasmatron

NASA Technical Reports Server (NTRS)

Schneider, Steven J. (Inventor)

2003-01-01

A reduced toxicity fuel satellite propulsion system including a reduced toxicity propellant supply for consumption in an axial class thruster and an ACS class thruster. The system includes suitable valves and conduits for supplying the reduced toxicity propellant to the ACS decomposing element of an ACS thruster. The ACS decomposing element is operative to decompose the reduced toxicity propellant into hot propulsive gases. In addition the system includes suitable valves and conduits for supplying the reduced toxicity propellant to an axial decomposing element of the axial thruster. The axial decomposing element is operative to decompose the reduced toxicity propellant into hot gases. The system further includes suitable valves and conduits for supplying a second propellant to a combustion chamber of the axial thruster. whereby the hot gases and the second propellant auto-ignite and begin the combustion process for producing thrust.

Azithromycin induced hepatocellular toxicity and hepatic encephalopathy in asymptomatic dilated cardiomyopathy

PubMed Central

Das, Bidyut Kumar

2011-01-01

Azithromycin is a widely used macrolide derivative and has generally been considered to be a very safe medication. Though gastrointestinal symptoms and reversible hearing loss are common, potentially serious side effects including angioedema and cholestatic jaundice occurred in less than one percent of patients. We report a case of asymptomatic dilated cardiomyopathy with Azithromycin induced severe hepatocellular toxicity and hepatic encephalopathy. PMID:22144789

DOE Office of Scientific and Technical Information (OSTI.GOV)

Walton, B.T.

In the present study, acute and chronic toxicities of five PAHs (naphthalene, anthracene, benz(a)anthracene, pyrene, and benzo(a)pyrene) and an oxygenated PAH derivative (anthrone) were determined in a terrestrial insect, Acheta domesticus (L.), with emphasis on the influence of route of entry on toxicity. Hexamethylphosphoric triamide (hempa) was included in the chronic tests since this chemosterilant is a useful reference compound for investigations of reproductive effects of chemicals in insects.

The effect of body condition on serum concentrations of two teratogenic alkaloids (anagyrine and ammodendrine) from Lupines (Lupinus spp.) that cause crooked calf disease.

USDA-ARS?s Scientific Manuscript database

Several species of lupine (Lupinus spp.) are toxic to livestock, causing death losses in sheep and cattle but more commonly “crooked calf disease” in pregnant range cows. The major toxic alkaloids in lupine are of the quinolizidine alkaloid group and include the teratogen anagyrine, which is primari...

Preparation of five 3-MCPD fatty acid esters and the effects of their chemical structures on acute oral toxicity in Swiss mice

USDA-ARS?s Scientific Manuscript database

Fatty acid esters of 3-monochloro-1, 2-propanediol (3-MCPDEs), including 1-stearic, 1-oleic, 1-linoleic, 1-linoleic-2-palmitic and 1-palmitic-2-linoleic acid esters, were synthetized and examined for their acute oral toxicities in Swiss mice. 3-MCPDEs were obtained through the reaction of 3-MCPD and...

A test strategy for the assessment of additive attributed toxicity of tobacco products.

PubMed

Kienhuis, Anne S; Staal, Yvonne C M; Soeteman-Hernández, Lya G; van de Nobelen, Suzanne; Talhout, Reinskje

2016-08-01

The new EU Tobacco Product Directive (TPD) prohibits tobacco products containing additives that are toxic in unburnt form or that increase overall toxicity of the product. This paper proposes a strategy to assess additive attributed toxicity in the context of the TPD. Literature was searched on toxicity testing strategies for regulatory purposes from tobacco industry and governmental institutes. Although mainly traditional in vivo testing strategies have been applied to assess toxicity of unburnt additives and increases in overall toxicity of tobacco products due to additives, in vitro tests combined with toxicogenomics and validated using biomarkers of exposure and disease are most promising in this respect. As such, tests are needed that are sensitive enough to assess additive attributed toxicity above the overall toxicity of tobacco products, which can associate assay outcomes to human risk and exposure. In conclusion, new, sensitive in vitro assays are needed to conclude whether comparable testing allows for assessment of small changes in overall toxicity attributed to additives. A more pragmatic approach for implementation on a short-term is mandated lowering of toxic emission components. Combined with risk assessment, this approach allows assessment of effectiveness of harm reduction strategies, including banning or reducing of additives. Copyright © 2016 Elsevier Ltd. All rights reserved.

Acute toxicity of copper, ammonia, and chlorine to glochidia and juveniles of freshwater mussels (Unionidae)

USGS Publications Warehouse

Wang, N.; Ingersoll, C.G.; Hardesty, D.K.; Ivey, C.D.; Kunz, J.L.; May, T.W.; Dwyer, F.J.; Roberts, A.D.; Augspurger, T.; Kane, C.M.; Neves, R.J.; Barnhart, M.C.

2007-01-01

The objective of the present study was to determine acute toxicity of copper, ammonia, or chlorine to larval (glochidia) and juvenile mussels using the recently published American Society for Testing and Materials (ASTM) Standard guide for conducting laboratory toxicity tests with freshwater mussels. Toxicity tests were conducted with glochidia (24- to 48-h exposures) and juveniles (96-h exposures) of up to 11 mussel species in reconstituted ASTM hard water using copper, ammonia, or chlorine as a toxicant. Copper and ammonia tests also were conducted with five commonly tested species, including cladocerans (Daphnia magna and Ceriodaphnia dubia; 48-h exposures), amphipod (Hyalella azteca; 48-h exposures), rainbow trout (Oncorhynchus mykiss; 96-h exposures), and fathead minnow (Pimephales promelas; 96-h exposures). Median effective concentrations (EC50s) for commonly tested species were >58 ??g Cu/L (except 15 ??g Cu/L for C. dubia) and >13 mg total ammonia N/L, whereas the EC50s for mussels in most cases were 40 ??g/L and above the FAV in the WQC for chlorine. The results indicate that the early life stages of mussels generally were more sensitive to copper and ammonia than other organisms and that, including mussel toxicity data in a revision to the WQC, would lower the WQC for copper or ammonia. Furthermore, including additional mussel data in 2007 WQC for copper based on biotic ligand model would further lower the WQC. ?? 2007 SETAC.

Gossypol Toxicity from Cottonseed Products

PubMed Central

Gadelha, Ivana Cristina N.; Fonseca, Nayanna Brunna S.; Oloris, Silvia Catarina S.; Melo, Marília M.

2014-01-01

Gossypol is a phenolic compound produced by pigment glands in cotton stems, leaves, seeds, and flower buds (Gossypium spp.). Cottonseed meal is a by-product of cotton that is used for animal feeding because it is rich in oil and proteins. However, gossypol toxicity limits cottonseed use in animal feed. High concentrations of free gossypol may be responsible for acute clinical signs of gossypol poisoning which include respiratory distress, impaired body weight gain, anorexia, weakness, apathy, and death after several days. However, the most common toxic effects is the impairment of male and female reproduction. Another important toxic effect of gossypol is its interference with immune function, reducing an animal's resistance to infections and impairing the efficiency of vaccines. Preventive procedures to limit gossypol toxicity involve treatment of the cottonseed product to reduce the concentration of free gossypol with the most common treatment being exposure to heat. However, free gossypol can be released from the bound form during digestion. Agronomic selection has produced cotton varieties devoid of glands producing gossypol, but these varieties are not normally grown because they are less productive and are more vulnerable to attacks by insects. PMID:24895646

RTECS database (on the internet). Online data

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

The Registry of Toxic Effects of Chemical Substances (RTECS (trademark)) is a database of toxicological information compiled, maintained, and updated by the National Institute for Occupational Safety and Health. The program is mandated by the Occupational Safety and Health Act of 1970. The original edition, known as the `Toxic Substances List,` was published on June 28, 1971, and included toxicologic data for approximately 5,000 chemicals. Since that time, the list has continuously grown and been updated, and its name changed to the current title, `Registry of Toxic Effects of Chemical Substances.` RTECS (trademark) now contains over 133,000 chemicals as NIOSHmore » strives to fulfill the mandate to list `all known toxic substances...and the concentrations at which...toxicity is known to occur.` This database is now available for searching through the Gov. Research-Center (GRC) service. GRC is a single online web-based search service to well known Government databases. Featuring powerful search and retrieval software, GRC is an important research tool. The GRC web site is at http://grc.ntis.gov.« less

Acute toxicity of nitrofurazone to channel catfish Ictalurus punctatus, and goldfish, Carassius auratus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wise, M.L.; Stiebel, C.L.; Grizzle, J.M.

1987-01-01

Nitrofurazone (5-nitro-2-furaldehyde semicarbazone) is a nitrofuran, a group of organic compounds which have inhibitory activity against many Gram-negative and Gram-positive bacteria and against some protozoan parasites. Although not approved by the United States Food and Drug Administration for use with food fish, nitrofurazone has been found effective in fish against external and internal infections by various species of Aeromonas, Pseudomonas and myxobacteria and can be administered either as a food additive or as a bath treatment. Attempts to control the microsporidian parasite Pleistophora ovariae in golden shiners, Notemigonus crysoleucas, with nitrofurazone met with equivocal results. The following experiment was performedmore » to determine acute toxicity, including lesions, of nitrofurazone to channel catfish, Ictalurus punctatus, and goldfish, carassius auratus, fingerlings. Toxicity of nitrofurazone to channel catfish was determined with low dissolved oxygen concentrations (2 mg/L) to simulate conditions frequently encountered in channel catfish culture. Information abut toxic levels of drugs and the lesions occurring in exposed fish is important to determine the safety of treatment levels and the effects of toxic concentrations.« less

A Hemorrhagic Factor (Apicidin) Produced by Toxic Fusarium Isolates from Soybean Seeds

PubMed Central

Park, Jun-Suk; Lee, Kyung-Rim; Kim, Jin-Cheol; Lim, Sun-Hee; Seo, Jeong-Ah; Lee, Yin-Won

1999-01-01

Fifty-two isolates of Fusarium species were obtained from soybean seeds from various parts of Korea and identified as Fusarium oxysporum, F. moniliforme, F. semitectum, F. solani, F. graminearum, or F. lateritium. These isolates were grown on autoclaved wheat grains and examined for toxicity in a rat-feeding test. Nine cultures were toxic to rats. One of these, a culture of Fusarium sp. strain KCTC 16677, produced apicidin, an antiprotozoal agent that caused toxic effects in rats (including body weight loss; hemorrhage in the stomach, intestines, and bladder; and finally death) when rats were fed diets supplemented with 0.05 and 0.1% apicidin. The toxin was toxic to brine shrimp (the 50% lethal concentration was 40 μg/ml) and was weakly cytotoxic to human and mouse tumor cell lines. PMID:9872769

Air toxics and epigenetic effects: ozone altered microRNAs in the sputum of human subjects

EPA Science Inventory

Ozone (03) is a criteria air pollutant that is associated with numerous adverse health effects, including altered respiratory immune responses. Despite its deleterious health effects, possible epigenetic mechanisms underlying 03-induced health effects remain understudied. MicroRN...

The time-dependent health and biochemical effects in rats exposed to stainless steel welding dust and its soluble form.

PubMed

Halatek, Tadeusz; Stanislawska, Magdalena; Kaminska, Irena; Cieslak, Malgorzata; Swiercz, Radoslaw; Wasowicz, Wojciech

2017-02-23

Welding processes that generate fumes containing toxic metals, such as hexavalent chromium (Cr(VI)), manganese (Mn), and nickel (Ni), have been implicated in lung injury, inflammation, and lung tumor promotion in animal models. The principal objective of this study was to determine the dynamics of toxic effects of inhalation exposure to morphologically rated welding dust from stainless steel welding and its soluble form in TSE System with a dynamic airflow. We assessed the pulmonary toxicity of welding dust in Wistar rats exposed to 60.0 mg/m 3 of respirable-size welding dust (mean diameter 1.17 µm) for 2 weeks (6 h/day, 5 days/week); the aerosols were generated in the nose-only exposure chambers (NOEC). An additional aim included the study of the effect of betaine supplementation on oxidative deterioration in rat lung during 2 weeks of exposure to welding dust or water-soluble dust form. The animals were divided into eight groups (n = 8 per group): control, dust, betaine, betaine + dust, soluble-form dust, soluble-form dust + betaine, saline and saline + betaine groups. Rats were euthanized 1 or 2 weeks after the last exposure for assessment of pulmonary toxicity. Differential cell counts, total protein concentrations and cellular enzyme (lactate dehydrogenase-LDH) activities were determined in bronchoalveolar lavage (BAL) fluid, and corticosterone and thiobarbituric acid reactive substances (TBARS) concentrations were assessed in serum. The increase in polymorphonuclear (PMN) leukocytes in BAL fluid (a cytological index of inflammatory responses of the lung) is believed to reflect pulmonary toxicity of heavy metals. Biomarkers of toxicity assessed in bronchoalveolar fluids indicate that the level of the toxic effect depends mainly on the solubility of studied metal compounds; biomarkers that showed treatment effects included: total cell, neutrophil and lymphocyte counts, total protein concentrations, and cellular enzyme (lactate dehydrogenase) activity. Betaine supplementation at 250 mg/kg/day in all study rats groups attenuated stress indices, and corticosterone and TBARS serum levels, and simultaneously stimulated increase of polymorphonuclear cells in BALF of rats. The study confirmed deleterious effect of transitory metals and particles during experimental inhalation exposure to welding dusts, evidenced in the lungs and brain by increased levels of total protein, higher cellular influx, rise of LDH in BALF, elevated TBARS and increased corticosterone in serum of rats. Our result confirm also the hypothesis about the effect of the welding dusts on the oxidative stress responsible for disturbed systemic homeostasis and impairment of calcium regulation.

DISTRIBUTED STRUCTURE-SEARCHABLE TOXICITY ...

EPA Pesticide Factsheets

The ability to assess the potential genotoxicity, carcinogenicity, or other toxicity of pharmaceutical or industrial chemicals based on chemical structure information is a highly coveted and shared goal of varied academic, commercial, and government regulatory groups. These diverse interests often employ different approaches and have different criteria and use for toxicity assessments, but they share a need for unrestricted access to existing public toxicity data linked with chemical structure information. Currently, there exists no central repository of toxicity information, commercial or public, that adequately meets the data requirements for flexible analogue searching, SAR model development, or building of chemical relational databases (CRD). The Distributed Structure-Searchable Toxicity (DSSTox) Public Database Network is being proposed as a community-supported, web-based effort to address these shared needs of the SAR and toxicology communities. The DSSTox project has the following major elements: 1) to adopt and encourage the use of a common standard file format (SDF) for public toxicity databases that includes chemical structure, text and property information, and that can easily be imported into available CRD applications; 2) to implement a distributed source approach, managed by a DSSTox Central Website, that will enable decentralized, free public access to structure-toxicity data files, and that will effectively link knowledgeable toxicity data s

Integration of biological responses from a suite of bioassays for the Venice Lagoon (Italy) through sediment toxicity index - part A: development and comparison of two methodological approaches.

PubMed

Losso, Chiara; Novelli, Alessandra Arizzi; De Salvador, Davide; Ghetti, Pier Francesco; Ghirardini, Annamaria Volpi

2010-12-01

Marine and coastal quality assessment, based on test batteries involving a wide array of endpoints, organisms and test matrices, needs for setting up toxicity indices that integrate multiple toxicological measures for decision-making processes and that classify the continuous toxicity response into discrete categories according to the European Water Framework Directive. Two toxicity indices were developed for the lagoon environment such as the Venice Lagoon. Stepwise procedure included: the construction of a database that identified test-matrix pairs (indicators); the selection of a minimum number of ecotoxicological indicators, called toxicological core metrics (CMs-tox) on the basis of specific criteria; the development of toxicity scores for each CM-tox; the integration of the CMs-tox into two indices, the Toxicity Effect Index (TEI), based on the transformation of Toxic Unit (TU) data that were integrated as logarithmic sum, and the Weighted Average Toxicity Index (WATI), starting from toxicity classes integrated as weighted mean. Results from the indices are compared; advantages and drawbacks of both approaches are discussed. Copyright © 2010. Published by Elsevier Ltd.

A bacterial bioreporter panel to assay the cytotoxicity of atmospheric particulate matter

NASA Astrophysics Data System (ADS)

Kessler, Nivi; Schauer, James J.; Yagur-Kroll, Sharon; Melamed, Sahar; Tirosh, Ofir; Belkin, Shimshon; Erel, Yigal

2012-12-01

Numerous studies have demonstrated that elevated concentrations of suspended atmospheric particulate matter (PM) are associated with adverse health effects. In order to minimize the adverse public health effects of atmospheric PM by exposure management, there is a need for a greater understanding of the toxic mechanisms and the components that are responsible for the toxic effects. The aim of this study was to utilize bioassay techniques to investigate these aspects. For this purpose a reporter panel of 9 genetically engineered bacterial (Escherichia coli) strains was composed. Each panel member was designed to report on a different stress condition with a measurable light signal produced by the luciferase enzyme. Toxic mechanisms and components were studied using six anthropogenic PM source samples, including two vehicle combustion particles, three coal fly ash (CFA) samples and an urban dust sample. The most prominent outcome of the panel exposure results were broad panel responses observed for two of the CFA samples, indicating oxidative stress, respiration inhibition and iron deficiency. These responses were relieved when the samples were treated with EDTA, a non-specific metal chelator, suggesting the involvement of metals in the observed effects. Bioavailability analysis of the samples suggests that chromium was related to the toxic responses induced by two of the CFA samples. Oxidative stress was also observed in several samples of ambient atmospheric aerosols and excess metal toxicity in an urban dust sample collected in a parking lot. The reporter panel approach, as demonstrated in this study, has the potential of providing novel insights as to the mechanisms of atmospheric PM toxicity. Furthermore, combining the panel's results with bioavailability data can enlighten about the role of different PM components in the observed toxicity.

Developmental Toxicology##

EPA Science Inventory

Developmental toxicology encompasses the study of developmental exposures, pharmacokinetics, mechanisms, pathogenesis, and outcomes potentially leading to adverse health effects. Manifestations of developmental toxicity include structural malformations, growth retardation, functi...

Pb Neurotoxicity: Neuropsychological Effects of Lead Toxicity

PubMed Central

Mason, Lisa H.; Harp, Jordan P.; Han, Dong Y.

2014-01-01

Neurotoxicity is a term used to describe neurophysiological changes caused by exposure to toxic agents. Such exposure can result in neurocognitive symptoms and/or psychiatric disturbances. Common toxic agents include heavy metals, drugs, organophosphates, bacterial, and animal neurotoxins. Among heavy metal exposures, lead exposure is one of the most common exposures that can lead to significant neuropsychological and functional decline in humans. In this review, neurotoxic lead exposure's pathophysiology, etiology, and epidemiology are explored. In addition, commonly associated neuropsychological difficulties in intelligence, memory, executive functioning, attention, processing speed, language, visuospatial skills, motor skills, and affect/mood are explored. PMID:24516855

In vitro functional screening as a means to identify new plasticizers devoid of reproductive toxicity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Boisvert, Annie; Jones, Steven; Issop, Leeyah

Plasticizers are indispensable additives providing flexibility and malleability to plastics. Among them, several phthalates, including di (2-ethylhexyl) phthalate (DEHP), have emerged as endocrine disruptors, leading to their restriction in consumer products and creating a need for new, safer plasticizers. The goal of this project was to use in vitro functional screening tools to select novel non-toxic plasticizers suitable for further in vivo evaluation. A panel of novel compounds with satisfactory plasticizer properties and biodegradability were tested, along with several commercial plasticizers, such as diisononyl-cyclohexane-1,2-dicarboxylate (DINCH®). MEHP, the monoester metabolite of DEHP was also included as reference compound. Because phthalates targetmore » mainly testicular function, including androgen production and spermatogenesis, we used the mouse MA-10 Leydig and C18-4 spermatogonial cell lines as surrogates to examine cell survival, proliferation, steroidogenesis and mitochondrial integrity. The most promising compounds were further assessed on organ cultures of rat fetal and neonatal testes, corresponding to sensitive developmental windows. Dose-response studies revealed the toxicity of most maleates and fumarates, while identifying several dibenzoate and succinate plasticizers as innocuous on Leydig and germ cells. Interestingly, DINCH®, a plasticizer marketed as a safe alternative to phthalates, exerted a biphasic effect on steroid production in MA-10 and fetal Leydig cells. MEHP was the only plasticizer inducing the formation of multinucleated germ cells (MNG) in organ culture. Overall, organ cultures corroborated the cell line data, identifying one dibenzoate and one succinate as the most promising candidates. The adoption of such collaborative approaches for developing new chemicals should help prevent the development of compounds potentially harmful to human health. - Highlights: • Phthalate plasticizers exert toxic effects on male reproduction. • Reproductive toxicity of new plasticizers was assessed by functional assays. • Mouse Leydig and germ cell lines, and rat perinatal testis cultures were used. • Survival, proliferation, steroidogenesis, abnormal germ cell formation were examined. • Reproductive toxic and innocuous plasticizer candidates were identified.« less

Enantioselective Effects of Chiral Pesticides on their Primary Targets and Secondary Targets.

PubMed

Yang, Ye; Zhang, Jianyun; Yao, Yijun

2017-01-01

Enantioselectivity has been well recognized in the environmental fate and effects of chiral pesticides. Enantiospecific action of the optical enantiomers on the biological molecules establishes the mechanistic basis for the enantioselective toxicity of chiral pesticides to both target and non-target organisms. We undertook a structured search of bibliographic databases for research literature concerning the enantioselective effects of chiral pesticides, including insecticides, herbicides and fungicides, on biomolecules in various species by using some key words. The results of the relevant literatures were reviewed in the text and summarized in tables. Pesticides generally exert their activity on the target organisms via disrupting the primary target biomolecules. In non-target species, effects of pesticides on the secondary targets distinguished from the primary ones make great contribution to their toxicity. Recent investigations have provided convincing evidence of enantioselective toxicity of chiral pesticides to both target and non-target species which is recognized to result from their enantiospecific action on the primary or secondary targets in organisms. This review confirms that chiral pesticides have enantiospecific effects on both primary and secondary target biomolecules in organisms. Future studies regarding toxicological effects of chiral pesticides should focus on the relationship between the enantiomeric difference in the compound-biomolecules interaction and the enantioselectivity in their toxicity.

Toxic stress and child refugees.

PubMed

Murray, John S

2018-01-01

The purpose of this article was to describe the phenomenon of toxic stress and its impact on the physical and mental health of child refugees. Almost two decades ago, researchers found that recurring adverse childhood events (ACEs; e.g., physical, psychological, and sexual abuse, neglect, and household dysfunction such as substance abuse, mental illness, and criminal behavior) were associated with a significant increase in serious illnesses during adulthood. Illnesses include heart, lung, and liver disease, cancer, and bone fractures. The scientists reported that experiencing four or more ACEs during childhood significantly increases the risk for toxic stress. Toxic stress is defined as the exposure to extreme, frequent, and persistent adverse events without the presence of a supportive caretaker. There is a paucity of literature related to toxic stress and child refugees. However, it has been clearly established that the prolonged brutal and traumatizing war in Syria is having a profound impact on the physical and mental health of child refugees at a distressing rate. Prevention of toxic stress should be a primary goal of all pediatric healthcare professionals working with child refugees. While this seems daunting given the population, and the seemingly insurmountable stressors they experience, some basic interventions should be considered. Providing basic anticipatory guidance to parents and caregivers of child refugees, to encourage positive parenting and strengthening support networks, will be highly effective in developing the requisite buffers that mitigate the effects of stress and avoid toxic stress. Efforts should also be focused on addressing caregiver stress and improving their ability to provide safe, reliable, and nurturing care that will help to mitigate any stress response experienced by a child. It is critical that greater awareness be placed on the effects of toxic stress on child refugees who are exposed to significant adverse events early in life. © 2017 Wiley Periodicals, Inc.

The Impact of Detoxification Costs and Predation Risk on Foraging: Implications for Mimicry Dynamics

PubMed Central

Skelhorn, John; Rowe, Candy; Ruxton, Graeme D.; Higginson, Andrew D.

2017-01-01

Prey often evolve defences to deter predators, such as noxious chemicals including toxins. Toxic species often advertise their defence to potential predators by distinctive sensory signals. Predators learn to associate toxicity with the signals of these so-called aposematic prey, and may avoid them in future. In turn, this selects for mildly toxic prey to mimic the appearance of more toxic prey. Empirical evidence shows that mimicry could be either beneficial (‘Mullerian’) or detrimental (‘quasi-Batesian’) to the highly toxic prey, but the factors determining which are unknown. Here, we use state-dependent models to explore how tri-trophic interactions could influence the evolution of prey defences. We consider how predation risk affects predators’ optimal foraging strategies on aposematic prey, and explore the resultant impact this has on mimicry dynamics between unequally defended species. In addition, we also investigate how the potential energetic cost of metabolising a toxin can alter the benefits to eating toxic prey and thus impact on predators’ foraging decisions. Our model predicts that both how predators perceive their own predation risk, and the cost of detoxification, can have significant, sometimes counterintuitive, effects on the foraging decisions of predators. For example, in some conditions predators should: (i) avoid prey they know to be undefended, (ii) eat more mildly toxic prey as detoxification costs increase, (iii) increase their intake of highly toxic prey as the abundance of undefended prey increases. These effects mean that the relationship between a mimic and its model can qualitatively depend on the density of alternative prey and the cost of metabolising toxins. In addition, these effects are mediated by the predators’ own predation risk, which demonstrates that, higher trophic levels than previously considered can have fundamental impacts on interactions among aposematic prey species. PMID:28045959

Reduced Toxicity Fuel Satellite Propulsion System Including Fuel Cell Reformer with Alcohols Such as Methanol

NASA Technical Reports Server (NTRS)

Schneider, Steven J. (Inventor)

2001-01-01

A reduced toxicity fuel satellite propulsion system including a reduced toxicity propellant supply for consumption in an axial class thruster and an ACS class thruster. The system includes suitable valves and conduits for supplying the reduced toxicity propellant to the ACS decomposing element of an ACS thruster. The ACS decomposing element is operative to decompose the reduced toxicity propellant into hot propulsive gases. In addition the system includes suitable valves and conduits for supplying the reduced toxicity propellant to an axial decomposing element of the axial thruster. The axial decomposing element is operative to decompose the reduced toxicity propellant into hot gases. The system further includes suitable valves and conduits for supplying a second propellant to a combustion chamber of the axial thruster, whereby the hot gases and the second propellant auto-ignite and begin the combustion process for producing thrust.

A study on toxicity of gasoline and GM-10 on liver of mice and it's amelioration by black tea extract.

PubMed

Verma, Ramtej Jayram; Dave, Manjeet; Mathuria, Neeta

2008-01-01

The aim of present study is to investigate the ameliorative effect of black tea extract on gasoline and GM-10 induced toxicity in liver of mice. Eighty healthy male mice weighing 38-40 g approximately were divided into eight groups which included untreated control and various treated groups. Mice were treated with Gasoline 462 mg/kg/day and GM-10 low dose (206 mg/kg/day) and high dose (412 mg/kg/day) subcutaneously for 30 days. Black tea extract was given as 2 g/100 mL drinking water (2% w/v) instead of pure drinking water. All the animals were sacrificed on 31st day by cervical dislocation and livers were isolated and weighed. Parameters such as lipid peroxidation, catalase, superoxide dismutase, glutathione peroxidase, glutathione and total ascorbic acid were studied. The results revealed dose-dependent toxicity of gasoline and GM-10 on liver. Administration of black tea extract ameliorates this toxicity of gasoline and GM-10 in liver of mice. This proves the effective ameliorative effect of black tea extract.

Toxicity prediction of compounds from turmeric (Curcuma longa L).

PubMed

Balaji, S; Chempakam, B

2010-10-01

Turmeric belongs to the ginger family Zingiberaceae. Currently, cheminformatics approaches are not employed in any of the spices to study the medicinal properties traditionally attributed to them. The aim of this study is to find the most efficacious molecule which does not have any toxic effects. In the present study, toxicity of 200 chemical compounds from turmeric were predicted (includes bacterial mutagenicity, rodent carcinogenicity and human hepatotoxicity). The study shows out of 200 compounds, 184 compounds were predicted as toxigenic, 136 compounds are mutagenic, 153 compounds are carcinogenic and 64 compounds are hepatotoxic. To cross validate our results, we have chosen the popular curcumin and found that curcumin and its derivatives may cause dose dependent hepatotoxicity. The results of these studies indicate that, in contrast to curcumin, few other compounds in turmeric which are non-mutagenic, non-carcinogenic, non-hepatotoxic, and do not have any side-effects. Hence, the cost-effective approach presented in this paper could be used to filter toxic compounds from the drug discovery lifecycle. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Medical effects of iodine disinfection products in spacecraft water

NASA Technical Reports Server (NTRS)

Sauer, Richard L.; Janik, Daniel S.; Thorstenson, Yvonne R.

1987-01-01

Various iodination products (IDPs), including iodinated and iodine-induced new compounds, will be present in the iodine-disinfected water that is expected to be used by crews on the NASA Space Station and on long duration missions. The metabolic intermediaries created by such a process may be more important to crew health than the parent IDPs, and reclamation and recycling may be expected to produce additional products. These medical effects may be expressed in crews as hypersensitivity, allergic, acute toxic, and chronic toxic reactions, as well as modifications of immune system response.

Effects-based spatial assessment of contaminated estuarine sediments from Bear Creek, Baltimore Harbor, MD, USA.

PubMed

Hartzell, Sharon E; Unger, Michael A; McGee, Beth L; Wilson, Sacoby M; Yonkos, Lance T

2017-10-01

Estuarine sediments in regions with prolonged histories of industrial activity are often laden to significant depths with complex contaminant mixtures, including trace metals and persistent organic pollutants. Given the complexity of assessing risks from multi-contaminant exposures, the direct measurement of impacts to biological receptors is central to characterizing contaminated sediment sites. Though biological consequences are less commonly assessed at depth, laboratory-based toxicity testing of subsurface sediments can be used to delineate the scope of contamination at impacted sites. The extent and depth of sediment toxicity in Bear Creek, near Baltimore, Maryland, USA, was delineated using 10-day acute toxicity tests with the estuarine amphipod Leptocheirus plumulosus, and chemical analysis of trace metals and persistent organic pollutants. A gradient of toxicity was demonstrated in surface sediments with 21 of 22 tested sites differing significantly from controls. Effects were most pronounced (100% lethality) at sites proximate to a historic industrial complex. Sediments from eight of nine core samples to depths of 80 cm were particularly impacted (i.e., caused significant lethality to L. plumulosus) even in locations overlain with relatively non-toxic surface sediments, supporting a conclusion that toxicity observed at the surface (top 2 cm) does not adequately predict toxicity at depth. In seven of nine sites, toxicity of surface sediments differed from toxicity at levels beneath by 28 to 69%, in five instances underestimating toxicity (28 to 69%), and in two instances overestimating toxicity (44 to 56%). Multiple contaminants exceeded sediment quality guidelines and correlated positively with toxic responses within surface sediments (e.g., chromium, nickel, polycyclic aromatic hydrocarbon (PAH), total petroleum hydrocarbon). Use of an antibody-based PAH biosensor revealed that porewater PAH concentrations also increased with depth at most sites. This study informs future management decisions concerning the extent of impact to Bear Creek sediments, and demonstrates the benefits of a spatial approach, relying primarily on toxicity testing to assess sediment quality in a system with complex contaminant mixtures.

Modeling Aquatic Toxicity through Chromatographic Systems.

PubMed

Fernández-Pumarega, Alejandro; Amézqueta, Susana; Farré, Sandra; Muñoz-Pascual, Laura; Abraham, Michael H; Fuguet, Elisabet; Rosés, Martí

2017-08-01

Environmental risk assessment requires information about the toxicity of the growing number of chemical products coming from different origins that can contaminate water and become toxicants to aquatic species or other living beings via the trophic chain. Direct toxicity measurements using sensitive aquatic species can be carried out but they may become expensive and ethically questionable. Literature refers to the use of chromatographic measurements that correlate to the toxic effect of a compound over a specific aquatic species as an alternative to get toxicity information. In this work, we have studied the similarity in the response of the toxicity to different species and we have selected eight representative aquatic species (including tadpoles, fish, water fleas, protozoan, and bacteria) with known nonspecific toxicity to chemical substances. Next, we have selected four chromatographic systems offering good perspectives for surrogation of the eight selected aquatic systems, and thus prediction of toxicity from the chromatographic measurement. Then toxicity has been correlated to the chromatographic retention factor. Satisfactory correlation results have been obtained to emulate toxicity in five of the selected aquatic species through some of the chromatographic systems. Other aquatic species with similar characteristics to these five representative ones could also be emulated by using the same chromatographic systems. The final aim of this study is to model chemical products toxicity to aquatic species by means of chromatographic systems to reduce in vivo testing.

Paradoxical toxicity of cardioplegic compounds on ischemic cardiomyocyte using optimal design strategy.

PubMed

Ferrera, René; Michel, Pierre; Ovize, Michel

2005-07-01

The aim of this study was to evaluate the effects of major components of cardioplegic solutions on myocardial tissue submitted to prolonged cold ischemia. Our methodology was based on the simultaneous testing in the same series of experiments of many compounds (19 in number), which were included in the composition of 20 established solutions. All the experiments were performed by a matricial-predefined protocol that allows the evaluation of the protective or toxic effects of each of these 19 compounds. Pig hearts were removed and left ventricular myocardiums were cut into 320 pieces. For each solution tested, 8 pieces of myocardial tissue were incubated at 4 degrees C for 24 hours and 8 other pieces were incubated for 72 hours. At the end of incubation period, tissue injury was assessed by measuring the leakage of myocardial enzymes(glutamic-oxaloacetic transaminase, lactate dehydrogenase, creatine phosphokinase) into the incubation medium. Initially, the effects of each solution were evaluated, and then a mathematical analysis was performed and the effects of each compound deduced. After the 24-hour incubation period, pyruvate (5 mmol/liter), polyethylene glycol (5 mmol/liter), Ala-Gln (20 mmol/liter), and reduced glutathione (3 mmol/liter) showed toxic effects, whereas ethanol (1%) and calcium chloride (2 mmol/liter) seemed to be protective. After 72 hours' incubation, similar data were obtained; dextran 70 (0.57 mmol/liter) was also found to be deleterious. The results revealed surprising myocardial toxicity (enzymatic release) from components included in cardioplegic solutions. Some components would induce metabolic activation during prolonged hypothermic ischemia, which may be inappropriated and which may perhaps exacerbate damages by increasing membrane ruptures. This concept confirms eventual discrepant effects of preservative compounds on cardiomyocyte membrane during deep hypothermia, according to the metabolic state of the cell.

Reduction of aflatoxins by Korean soybean paste and its effect on cytotoxicity and reproductive toxicity--Part 3. Inhibitory effects of Korean soybean paste (doen-jang) on aflatoxin toxicity in laying hens and aflatoxin accumulation in their eggs.

PubMed

Kim, Jong-Gyu; Lee, Yong-Wook; Kim, Pan-Gyi; Roh, Woo-Sup; Shintani, Hideharu

2003-05-01

This study was conducted to determine the effects of Korean soybean paste (doen-jang [dwen-jahng]) (at concentrations of 0.5, 1, and 5%) on the toxicity of 500 ppb of aflatoxin in the diets of 60 laying hens (Isa Brown) divided into five groups and treated from week 15 to week 67. The aflatoxin-treated hens exhibited many deleterious effects, including reduced body weight; increased relative organ weights; decreased egg production; aflatoxin accumulation in eggs; decreased serum calcium, phosphorus, and alanino amonotransferase (ALT) levels; increased serum gammaglutamil transferase and lactic dehydrogenase levels; and, most significantly, severely altered cell foci and sinusoid dilatation in the liver, relative to control hens. The feeding of 1% soybean paste to hens reduced the adverse effects of aflatoxin on body weight, relative organ weights, egg production, and aflatoxin accumulation in eggs and improved serum calcium and ALT levels and the histopathological lesions of the liver. The feeding of 5% soybean paste to hens resulted in higher levels of the same types of improvements, especially with regard to the histopathological findings for the liver. On the basis of these results, it was suggested that a diet including 5% (and in some cases only 1%) Korean soybean paste protected laying hens and their eggs from the major deleterious effects of 500 microg of aflatoxin per kg of diet and from aflatoxin accumulation. These results indicate that dietary supplementation with Korean soybean paste reduces aflatoxin toxicity in laying hens that ultimately produce human foods such as eggs and poultry.

Spray Toxicity and Risk Potential of 42 Commonly Used Formulations of Row Crop Pesticides to Adult Honey Bees (Hymenoptera: Apidae).

PubMed

Zhu, Yu Cheng; Adamczyk, John; Rinderer, Thomas; Yao, Jianxiu; Danka, Robert; Luttrell, Randall; Gore, Jeff

2015-12-01

To combat an increasing abundance of sucking insect pests, >40 pesticides are currently recommended and frequently used as foliar sprays on row crops, especially cotton. Foraging honey bees may be killed when they are directly exposed to foliar sprays, or they may take contaminated pollen back to hives that maybe toxic to other adult bees and larvae. To assess acute toxicity against the honey bee, we used a modified spray tower to simulate field spray conditions to include direct whole-body exposure, inhalation, and continuing tarsal contact and oral licking after a field spray. A total of 42 formulated pesticides, including one herbicide and one fungicide, were assayed for acute spray toxicity to 4-6-d-old workers. Results showed significantly variable toxicities among pesticides, with LC50s ranging from 25 to thousands of mg/liter. Further risk assessment using the field application concentration to LC1 or LC99 ratios revealed the risk potential of the 42 pesticides. Three pesticides killed less than 1% of the worker bees, including the herbicide, a miticide, and a neonicotinoid. Twenty-six insecticides killed more than 99% of the bees, including commonly used organophosphates and neonicotinoids. The remainder of the 13 chemicals killed from 1-99% of the bees at field application rates. This study reveals a realistic acute toxicity of 42 commonly used foliar pesticides. The information is valuable for guiding insecticide selection to minimize direct killing of foraging honey bees, while maintaining effective control of field crop pests. Published by Oxford University Press [on behalf of Entomological Society of America] 2015. This work is written by US Government employees and is in the public domain in the US.

Advances in the use of milk thistle (Silybum marianum).

PubMed

Post-White, Janice; Ladas, Elena J; Kelly, Kara M

2007-06-01

Milk thistle (Silybum marianum) is an herbal supplement used to treat liver and biliary disorders. Silymarin, a mixture of flavanoid complexes, is the active component that protects liver and kidney cells from toxic effects of drugs, including chemotherapy. Although milk thistle has not significantly altered the course of chronic liver disease, it has reduced liver enzyme levels and demonstrated anti-inflammatory and T cell-modulating effects. There is strong preclinical evidence for silymarin's hepatoprotective and anticarcinogenic effects, including inhibition of cancer cell growth in human prostate, skin, breast, and cervical cells. Milk thistle is considered safe and well-tolerated, with gastrointestinal upset, a mild laxative effect, and rare allergic reaction being the only adverse events reported when taken within the recommended dose range. More clinical trials of rigorous methodology, using standardized and well-defined products and dosages, are needed to evaluate the potential of silymarin against liver toxicity, chronic liver disease, and human cancers.

Skin toxicity from external beam radiation therapy in breast cancer patients: protective effects of Resveratrol, Lycopene, Vitamin C and anthocianin (Ixor®).

PubMed

Di Franco, Rossella; Calvanese, MariaGrazia; Murino, Paola; Manzo, Roberto; Guida, Cesare; Di Gennaro, Davide; Anania, Caterina; Ravo, Vincenzo

2012-01-30

This is an observational study and the aim is to evaluate the effect of dietary supplements based on Resveratrol, Lycopene, Vitamin C and Anthocyanins (Ixor®) in reducing skin toxicity due to external beam radiotherapy in patients affected by breast cancer. 71 patients were enrolled and they were divided in two different groups: a control group (CG) of 41 patients treated with prophylactic topical therapy based on hyaluronic acid and topical steroid therapy in case of occurrence of radiodermatitis, and a Ixor-Group (IG) of 30 patients treated also with an oral therapy based on Resveratrol, Lycopene, Vitamin C and Anthocyanin (Ixor®) at a dose of 2 tablets/day, starting from 10 days before the radiation treatment until 10 days after the end of treatment. Skin toxicity has been related to PTV, to breast volume that received a radiation dose equal or lower than 107%, included between 107% and 110%, or greater than 110% of the prescribed dose. Moreover it's been studied the relationship between skin toxicity and the chemotherapy schedule used before treatment. We calculated in both groups the percentage of patients who had a skin toxicity of grade 2 or 3 (according to RTOG scale). Absolute risk reduction (ARR), relative risk (RR) and odds ratio (OR) have been calculated for each relationship. Control Group (CG) patients with a PTV > 500 ml presented skin toxicity G2 + G3 in 30% of cases, versus 25% of Ixor-Group (IG) [OR 0.77]. In patients with a PTV < 500 ml G2 + G3 toxicity was 0% in the IG compared to 18% in CG (OR 0.23). When Dmax was less than or equal to 107% of the prescribed dose skin toxicity was G2 + G3 in 12.5% in CG, versus 0% in IG (OR 0.73), instead when Dmax was included between 107 and 110% of the prescribed dose, G2 + G3 skin toxicity was 35% in CG and 21% in IG (OR 0.50). In patients undergoing chemotherapy with anthracyclines and taxanes, G2 + G3 toxicity was 27% in CG, against 20% in IG (OR 0.68). The protective effect of Resveratrol, Lycopene, Vitamin C and Anthocyanin (Ixor®) is more detected in patients with PTV < 500 ml, when Dmax reaches values lower or equal to 107%, but not exceeding 110% of the prescribed dose, and in patients undergoing adjuvant chemotherapy with anthracyclines and taxanes.

Novel VEGF signalling inhibitors: how helpful are biomarkers in their early development?

PubMed

Wood, Joanna; Scott, Edwina; Thomas, Anne L

2009-11-01

The development of vascular endothelial growth factor (VEGF) inhibitors of tumour angiogenesis can only be described as prolific. It is therefore interesting to speculate which will reach the clinic. Of course, the most effective agents will succeed, but how is effectiveness measured? When presented with a summary of competitive compounds, it can be difficult to discriminate between their potency on target, toxicity and response rates. A comparison was undertaken between new small-molecule tyrosine kinase inhibitors with vascular endothelial growth factor receptor as one of their targets. Factors considered included mode of action (targets), toxicity and usefulness of biomarker data. We carried out a systematic review using PubMed, MEDLINE and American Society of Clinical Oncologist (ASCO) databases for articles (including abstracts) presented in 2007 - 2009. Search terms included 'angiogenesis inhibitors', 'tyrosine kinase inhibitors', 'VEGF' and 'biomarkers'. Nine compounds were selected for detailed comparison. The toxicity profiles of the compounds were similar. Many exposure biomarkers have been identified that have informed the dose and scheduling of these compounds in clinical trials. Progress has also been made in identifying potential efficacy and predictive biomarkers for these new agents; however, these are yet to be validated.

Review on toxicity testing with marine macroalgae and the need for method standardization--exemplified with copper and phenol.

PubMed

Eklund, Britta T; Kautsky, Lena

2003-02-01

Toxic effects on macroalgae have been compiled. Eighty-two articles have been found in literature during 1959-2000. A total of 120 substances were investigated using 65 different macroalgae species. About one-third of the tested compounds were organic substances (33%), another third metal-organic substances (35%), and the last third were oils (14%), metals (8%), detergents (7.5%) and other inorganic chemicals (2.5%). Half of the substances were only tested once on a single species. Likewise, toxicity data has only been reported for one chemical tested on a single occasion for about half of the 65 species. Thus little is known about the toxic effects on marine macroalgae. The objectives of the previous studies undertaken varied and therefore the toxicity data was presented in numerous ways, e.g. using different exposure times, temperature, light intensity, light regime, salinity, and nutrients, which makes a direct comparison of the data difficult. This review also shows that many stages in the lifecycle of macroalgae are often more sensitive to toxic substances than other aquatic organisms. Consequently, tests using macroalgae may discover toxicity earlier, which would in turn also protect the fauna. If toxic compounds have a negative affect on the distribution and growth of structurally and functionally dominating macroalgae, there may indirectly be a large and harmful influence on the whole marine coastal ecosystem. For this reason tests on macroalgae should be included in control programs along the coasts.

In vitro bioassays reveal that additives are significant contributors to the toxicity of commercial household pesticides.

PubMed

van de Merwe, Jason P; Neale, Peta A; Melvin, Steven D; Leusch, Frederic D L

2018-06-01

Pesticides commonly used around households can contain additives of unknown concentrations and toxicity. Given the likelihood of these chemicals washing into urban waterways, it is important to understand the effects that these additives may have on aquatic organisms. The aim of this study was to compare the toxicity of commercially available household pesticides to that of the active ingredient(s) alone. The toxicity of five household pesticides (three herbicides and two insecticides) was investigated using a bacterial cytotoxicity bioassay and an algal photosynthesis bioassay. The commercial products were up to an order of magnitude more toxic than the active ingredient(s) alone. In addition, two commercial products with the same listed active ingredients in the same ratio had a 600× difference in potency. These results clearly demonstrate that additives in commercial formulations are significant contributors to the toxicity of household pesticides. The toxicity of pesticides in aquatic systems is therefore likely underestimated by conventional chemical monitoring and risk assessment when only the active ingredients are considered. Regulators and customers should require more clarity from pesticide manufacturers about the nature and concentrations of not only the active ingredients, but also additives used in commercial formulations. In addition, monitoring programmes and chemical risk assessments schemes should develop a structured approach to assessing the toxic effects of commercial formulations, including additives, rather than simply those of the listed active ingredients. Copyright © 2018. Published by Elsevier B.V.

A systematic study on photocatalysis of antipyrine: Catalyst characterization, parameter optimization, reaction mechanism a toxicity evolution to plankton.

PubMed

Gong, Han; Chu, Wei; Chen, Meijuan; Wang, Qinxing

2017-04-01

The toxicity of antipyrine (AP) in the photodegradation using UV/CoFe 2 O 4 /TiO 2 was investigated by analyzing the characteristic of the catalyst, the effect of parameters (light source wavelength, catalyst dose, pH and initial AP concentration), the reaction mechanism (the organic intermediates, TOC reduction and inorganic ions release) and the newly proposed low-dosage-high-effective radical reaction approach. The catalyst shows the optimal removal efficiency under the conditions of wavelength at 350 nm, the catalyst dose at 0.5 g/L, and pH value at 5.5. Ten organic intermediates were identified, and five of them were newly reported in AP treatment process. Hydroxylation, demethylation and the cleavage of the pentacyclic ring were included in the decomposition pathways. The ring opening was certified by the 45% TOC reduction and 60% ammonia release during the process. The parent compound AP and its degradation products show positive effects on the growth of the algae. However, acute toxicity of AP was detected on brine shrimps Artemia salina. The toxicity was eliminated gradually with the decomposition of AP and the generation of the byproducts. The results indicate that the photocatalysis process is effective in AP removal, TOC reduction and toxicity elimination. Copyright © 2017 Elsevier Ltd. All rights reserved.

Predictions of sediment toxicity using consensus-based freshwater sediment quality guidelines

USGS Publications Warehouse

Ingersoll, C.G.; MacDonald, D.D.; Wang, N.; Crane, J.L.; Field, L.J.; Haverland, P.S.; Kemble, N.E.; Lindskoog, R.A.; Severn, C.; Smorong, D.E.

2001-01-01

The objectives of this study were to compare approaches for evaluating the combined effects of chemical mixtures on the toxicity in field-collected sediments and to evaluate the ability of consensus-based probable effect concentrations (PECs) to predict toxicity in a freshwater database on both a national and regional geographic basis. A database was developed from 92 published reports, which included a total of 1,657 samples with high-quality matching sediment toxicity and chemistry data from across North America. The database was comprised primarily of 10- to 14-day or 28- to 42-day toxicity tests with the amphipod Hyalella azteca (designated as the HA10 or HA28 tests) and 10- to 14-day toxicity tests with the midges Chironomus tentans or C. riparius (designated as the CS10 test). Mean PEC quotients were calculated to provide an overall measure of chemical contamination and to support an evaluation of the combined effects of multiple contaminants in sediments. There was an overall increase in the incidence of toxicity with an increase in the mean quotients in all three tests. A consistent increase in the toxicity in all three tests occurred at a mean quotient > 0.5, however, the overall incidence of toxicity was greater in the HA28 test compared to the short-term tests. The longer-term tests, in which survival and growth are measured, tend to be more sensitive than the shorter-term tests, with acute to chronic ratios on the order of six indicated for H. azteca. Different patterns were observed among the various procedures used to calculate mean quotients. For example, in the HA28 test, a relatively abrupt increase in toxicity was associated with elevated polychlorinated biphenyls (PCBs) alone or with elevated polycyclic aromatic hydrocarbons (PAHs) alone, compared to the pattern of a gradual increase in toxicity observed with quotients calculated using a combination of metals, PAHs, and PCBs. These analyses indicate that the different patterns in toxicity may be the result of unique chemical signals associated with individual contaminants in samples. Though mean quotients can be used to classify samples as toxic or nontoxic, individual quotients might be useful in helping identify substances that may be causing or substantially contributing to the observed toxicity. An increase in the incidence of toxicity was observed with increasing mean quotients within most of the regions, basins, and areas in North America for all three toxicity tests. The results of these analyses indicate that the consensus-based PECs can be used to reliably predict toxicity of sediments on both a regional and national basis.

Algal toxicity of the alternative disinfectants performic acid (PFA), peracetic acid (PAA), chlorine dioxide (ClO2) and their by-products hydrogen peroxide (H2O2) and chlorite (ClO2-).

PubMed

Chhetri, Ravi Kumar; Baun, Anders; Andersen, Henrik Rasmus

2017-05-01

Environmental effect evaluation of disinfection of combined sewer overflow events with alternative chemical disinfectants requires that the environmental toxicity of the disinfectants and the main by-products of their use are known. Many disinfectants degrade quickly in water which should be included in the evaluation of both their toxicity as determined in standardized tests and their possible negative effect in the water environment. Here we evaluated according to the standardized ISO 8692 test the toxicity towards the green microalgae, Pseudokirchneriella subcapitata, of three disinfectants: performic acid (PFA), peracetic acid (PAA) and chlorine dioxide (ClO 2 ) as well as two by-products of their use: hydrogen peroxide (H 2 O 2 ) and chlorite. All of the five chemicals investigated showed clear toxicity to the algae with well-defined dose response curves. The EC 50 values ranged from 0.16 to 2.9mg/L based on nominal concentrations leading to the labeling of the chemicals as either toxic or very toxic. The five investigated chemicals decreased in toxicity in the order chlorine dioxide, performic acid, peracetic acid, chlorite and hydrogen peroxide. The stability of the chemicals increased in the same order as the toxicity decrease. This indicates that even though ClO 2 has the highest environmental hazard potential, it may still be suitable as an alternative disinfectant due to its rapid degradation in water. Copyright © 2016 Elsevier GmbH. All rights reserved.

Decolorization of different textile dyes by Penicillium simplicissimum and toxicity evaluation after fungal treatment

PubMed Central

Bergsten-Torralba, L.R.; Nishikawa, M.M.; Baptista, D.F.; Magalhães, D.P.; da Silva, M.

2009-01-01

The objective of this study was to investigate the capacity of decolorization and detoxification of the textile dyes Reactive Red 198 (RR198), Reactive Blue 214 (RB214), Reactive Blue 21 (RB21) and the mixture of the three dyes (MXD) by Penicillium simplicissimum INCQS 40211. The dye RB21, a phthalocyanine, was totally decolorized in 2 days, and the others, the monoazo RR198, the diazo RB214 and MXD were decolorized after 7 days by P. simplicissimum. Initially the dye decolorization involved dye adsorption by the biomass followed by degradation. The acute toxicity after fungal treatment was monitored with the microcrustacean Daphnia pulex and measured through Effective Concentration 50% (EC50). P. simplicissimum reduced efficiently the toxicity of RB21 from moderately acutely toxic to minor acutely toxic and it also reduced the toxicity of RB214 and MXD, which remained minor acutely toxic. Nevertheless, the fungus increased the toxicity of RR198 despite of the reduction of MXD toxicity, which included this dye. Thus, P. simplicissimum INCQS 40211 was efficient to decolorize different textile dyes and the mixture of them with a significant reduction of their toxicity. In addition this investigation also demonstrated the need of toxicological assays associated to decolorization experiments. PMID:24031428

Diagnosis of toxic alcohols: limitations of present methods.

PubMed

Kraut, Jeffrey A

2015-01-01

Methanol, ethylene glycol, diethylene glycol, and propylene glycol intoxications are associated with cellular dysfunction and an increased risk of death. Adverse effects can develop quickly; thus, there is a need for methods for rapidly detecting their presence. To examine the value and limitations of present methods to diagnose patients with possible toxic alcohol exposure. I searched MEDLINE for articles published between 1969 and 2014 using the terms: toxic alcohols, serum osmolality, serum osmol gap, serum anion gap, metabolic acidosis, methanol, ethylene glycol, diethylene glycol, propylene glycol, and fomepizole. Each article was reviewed for additional references. The diagnosis of toxic alcohol exposure is often made on the basis of this history and physical findings along with an increase in the serum osmol and anion gaps. However, an increase in the osmol and/or anion gaps is not always present. Definitive detection in blood requires gas or liquid chromatography, laborious and expensive procedures which are not always available. Newer methods including a qualitative colorimetric test for detection of all alcohols or enzymatic tests for a specific alcohol might allow for more rapid diagnosis. Exposure to toxic alcohols is associated with cellular dysfunction and increased risk of death. Treatment, if initiated early, can markedly improve outcome, but present methods of diagnosis including changes in serum osmol and anion gap, and use of gas or liquid chromatography have important limitations. Development of more rapid and effective tests for detection of these intoxications is essential for optimal care of patients.

High-Content Analysis Provides Mechanistic Insights into the Testicular Toxicity of Bisphenol A and Selected Analogues in Mouse Spermatogonial Cells.

PubMed

Liang, Shenxuan; Yin, Lei; Shengyang Yu, Kevin; Hofmann, Marie-Claude; Yu, Xiaozhong

2017-01-01

Bisphenol A (BPA), an endocrine-disrupting compound, was found to be a testicular toxicant in animal models. Bisphenol S (BPS), bisphenol AF (BPAF), and tetrabromobisphenol A (TBBPA) were recently introduced to the market as alternatives to BPA. However, toxicological data of these compounds in the male reproductive system are still limited so far. This study developed and validated an automated multi-parametric high-content analysis (HCA) using the C18-4 spermatogonial cell line as a model. We applied these validated HCA, including nuclear morphology, DNA content, cell cycle progression, DNA synthesis, cytoskeleton integrity, and DNA damage responses, to characterize and compare the testicular toxicities of BPA and 3 selected commercial available BPA analogues, BPS, BPAF, and TBBPA. HCA revealed BPAF and TBBPA exhibited higher spermatogonial toxicities as compared with BPA and BPS, including dose- and time-dependent alterations in nuclear morphology, cell cycle, DNA damage responses, and perturbation of the cytoskeleton. Our results demonstrated that this specific culture model together with HCA can be utilized for quantitative screening and discriminating of chemical-specific testicular toxicity in spermatogonial cells. It also provides a fast and cost-effective approach for the identification of environmental chemicals that could have detrimental effects on reproduction. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

NMR-based metabonomics study on the effect of Gancao in the attenuation of toxicity in rats induced by Fuzi.

PubMed

Sun, Bo; Wang, Xubin; Cao, Ruili; Zhang, Qi; Liu, Qiao; Xu, Meifeng; Zhang, Ming; Du, Xiangbo; Dong, Fangting; Yan, Xianzhong

2016-12-04

Fuzi, the processed lateral root of Aconitum carmichaelii Debeaux, is a traditional Chinese medicine used for its analgesic, antipyretic, anti-rheumatoid arthritis and anti-inflammation effects; however, it is also well known for its toxicity. Gancao, the root of Glycyrrhiza uralensis Fisch., is often used concurrently with Fuzi to alleviate its toxicity. However, the mechanism of detoxication is still not well clear. In this study, the effect of Gancao on the metabolic changes induced by Fuzi was investigated by NMR-based metabonomic approaches. Fifty male Wistar rats were randomly divided into five groups (group A: control, group B: Fuzi decoction alone, group C: Gancao decoction alone, group D: Fuzi decoction and Gancao decoction simultaneously, group E: Fuzi decoction 5h after Gancao decoction) and urine samples were collected for NMR-based metabolic profiling analysis. Statistical analyses such as unsupervised PCA, t-test, hierarchical cluster, and pathway analysis were used to detect the effects of Gancao on the metabolic changes induced by Fuzi. The behavioral and biochemical characteristics showed that Fuzi exhibited toxic effects on treated rats (group B) and statistical analyses showed that their metabolic profiles were in contrast to those in groups A and C. However, when Fuzi was administered with Gancao, the metabolic profiles became similar to controls, whereby Gancao reduced the levels of trimethylamine N-oxide, betaine, dimethylglycine, valine, acetoacetate, citrate, fumarate, 2-ketoglutarate and hippurate, and regulated the concentrations of taurine and 3-hydroxybutyrate, resulting in a decrease in toxicity. Furthermore, important pathways that are known to be involved in the effect of Gancao on Fuzi, including phenylalanine, tyrosine and tryptophan biosynthesis, the synthesis and degradation of ketone bodies, and the TCA cycle, were altered in co-treated rats. Gancao treatment mitigated the metabolic changes altered by Fuzi administration in rats, demonstrating that dosing with Gancao could reduce the toxicity of Fuzi at the metabolic level. Fuzi and Gancao administered simultaneously resulted in improved toxicity reduction than when Gancao was administrated 5h prior to Fuzi. In summary, co-administration of Gancao with Fuzi reduces toxicity at the metabolic level. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Persistent toxic substances: sources, fates and effects.

PubMed

Wong, Ming H; Armour, Margaret-Ann; Naidu, Ravi; Man, Ming

2012-01-01

Persistent toxic substances (PTS) include the Stockholm persistent organic pollutants, like dichlorodiphenyltrichloroethane, polychlorinated biphenyls, dioxin/furan, etc., and organometallic compounds, like organomercury, organotin, and organolead, which all share the same characteristics of being persistent, toxic, bioaccumulative, and able to travel long distances through different media. The adverse health effects of some of the emerging chemicals like pentabromodiphenyl ether, bisphenol A, and di(2-ethylhexyl)phthalate, which are widely used in daily appliances (e.g., TVs, computers, mobile phones, plastic baby bottles), have become a public health concern due to more evidence now available showing their adverse effects like disturbance of the endocrine system and cancer. This article is an attempt to review the current status of PTS in our environment, citing case studies in China and North America, and whether our existing drinking water treatment and wastewater treatment processes are adequate in removing them from water. Some management issues of these emerging chemicals of concern are also discussed.

Global warming and environmental contaminants in aquatic organisms: the need of the etho-toxicology approach.

PubMed

Manciocco, Arianna; Calamandrei, Gemma; Alleva, Enrico

2014-04-01

Environmental contaminants are associated with a wide spectrum of pathological effects. Temperature increase affects ambient distribution and toxicity of these chemicals in the water environment, representing a potentially emerging problem for aquatic species with short-, medium- and long-term repercussions on human health through the food chain. We assessed peer-reviewed literature, including primary studies, review articles and organizational reports available. We focused on studies concerning toxicity of environmental pollutants within a global warming scenario. Existing knowledge on the effects that the increase of water temperature in a contaminated situation has on physiological mechanisms of aquatic organisms is presented. Altogether we consider the potential consequences for the human beings due to fish and shellfish consumption. Finally, we propose an etho-toxicological approach to study the effects of toxicants in conditions of thermal increase, using aquatic organisms as experimental models under laboratory controlled conditions. Copyright © 2014 Elsevier Ltd. All rights reserved.

Cisplatin-induced Kidney Dysfunction and Perspectives on Improving Treatment Strategies

PubMed Central

Oh, Gi-Su; Kim, Hyung-Jin; Shen, AiHua; Lee, Su Bin; Khadka, Dipendra; Pandit, Arpana

2014-01-01

Cisplatin is one of the most widely used and highly effective drug for the treatment of various solid tumors; however, it has dose-dependent side effects on the kidney, cochlear, and nerves. Nephrotoxicity is the most well-known and clinically important toxicity. Numerous studies have demonstrated that several mechanisms, including oxidative stress, DNA damage, and inflammatory responses, are closely associated with cisplatin-induced nephrotoxicity. Even though the establishment of cisplatin-induced nephrotoxicity can be alleviated by diuretics and pre-hydration of patients, the prevalence of cisplatin nephrotoxicity is still high, occurring in approximately one-third of patients who have undergone cisplatin therapy. Therefore it is imperative to develop treatments that will ameliorate cisplatin-nephrotoxicity. In this review, we discuss the mechanisms of cisplatin-induced renal toxicity and the new strategies for protecting the kidneys from the toxic effects without lowering the tumoricidal activity. PMID:25606044

Tidal river sediments in the Washington, D.C. area. 111 Biological effects associated with sediment contamination

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schlekat, C.E.; McGee, B.L.; Boward, D.M.

1994-06-01

Sediment toxicity and benthic marcroinvertebrate community structure were measured as one component of a study conceived to determine the distribution and effect of sediment contamination in tidal freshwater portions of the Potomac and Anacostia rivers in the Washington, D.C., area. Samples were collected at 15 sites. Analyses included a partial life cycle (28 d) whole sediment test using the amphipod Hyalella azteca (Talitridae) and an assessment of benthic community structure. Survival and growth (as estimated by amphipod length) were experimental endpoints for the toxicity test. Significant mortality was observed in 5 to 10 sites in the lower Anacostia River basinmore » and at the main channel Potomac River site. Sublethal toxicity, as measured by inhibition of amphipod growth, was not observed. Toxicity test results were in general agreement with synoptically measured sediment contaminant concentrations. Porewater total ammonia (NH{sub 3} + NH{sub 4}{sup +}) appears to be responsible for the toxicity of sediments from the Potomac River, while correlation analysis and simultaneously extracted metals: acid volatile sulfide (SEM:AVA) results suggest that the toxicity associated with Anacostia River sediments was due to organic compounds. Twenty-eight macroinvertebrate taxa were identified among all sites, with richness varying from 5 to 17 taxa per site. Groups of benthic assemblages identified by group-average cluster analysis exhibited variable agreement with sediment chemical and sediment toxicity results. Integration of toxicological, chemical, and ecological components suggests that adverse environmental effects manifest in lower Anacostia River benthos result from chemical contamination of sediment. 37 refs., 2 figs., 7 tabs.« less

Lead.

PubMed

Bellinger, David C

2004-04-01

Children differ from adults in the relative importance of lead sources and pathways, lead metabolism, and the toxicities expressed. The central nervous system effects of lead on children seem not to be reversible. Periods of enhanced vulnerability within childhood have not consistently been identified. The period of greatest vulnerability might be endpoint specific, perhaps accounting for the failure to identify a coherent "behavioral signature" for lead toxicity. The bases for the substantial individual variability in vulnerability to lead are uncertain, although they might include genetic polymorphisms and contextual factors. The current Centers for Disease Control and Prevention screening guideline of 10 micro g/dL is a risk management tool and should not be interpreted as a threshold for toxicity. No threshold has been identified, and some data are consistent with effects well below 10. Historically, most studies have concentrated on neurocognitive effects of lead, but higher exposures have recently been associated with morbidities such as antisocial behavior and delinquency. Studies of lead toxicity in experimental animal models are critical to the interpretation of nonexperimental human studies, particularly in addressing the likelihood that associations observed in the latter studies can be attributed to residual confounding. Animal models are also helpful in investigating the behavioral and neurobiological mechanisms of the functional deficits observed in lead-exposed humans. Studies of adults who have been exposed to lead are of limited use in understanding childhood lead toxicity because developmental and acquired lead exposure differ in terms of the maturity of the organs affected, the presumed mechanisms of toxicity, and the forms in which toxicities are expressed.

Alleviative effects of quercetin and onion on male reproductive toxicity induced by diesel exhaust particles.

PubMed

Izawa, Hiromi; Kohara, Machiko; Aizawa, Koichi; Suganuma, Hiroyuki; Inakuma, Takahiro; Watanabe, Gen; Taya, Kazuyoshi; Sagai, Masaru

2008-05-01

Diesel exhaust particles (DEPs) are particulate matter from diesel exhaust that contain many toxic compounds, such as polyaromatic hydrocarbons (PAHs). Some toxicities of PAH are thought to be expressed via aryl hydrocarbon receptors (AhRs). The male reproductive toxicity of DEPs might depend on AhR activation induced by PAHs. We hypothesized that AhR antagonists protect against the male reproductive toxicity of DEPs. Quercetin is a flavonoid and a well-known AhR antagonist, while onion contains many flavonoids, including quercetin. Hence, we examined whether quercetin and onion have alleviative effects against the male reproductive toxicity induced by DEPs. BALB/c male mice were fed quercetin- or onion-containing diets and received 10 injections of DEP suspension or vehicle into the dorsal subcutaneous layer over 5 weeks. The mice were euthanized at 2 weeks, after the last treatment, and their organs were collected. Daily sperm production and total incidence of sperm abnormalities were significantly affected in the DEP groups as compared with the vehicle group, but the total incidence of sperm abnormalities in the quercetin + DEP-treated mice was significantly reduced as compared with the DEP-treated mice. The numbers of Sertoli cells were significantly decreased in DEP-treated mice as compared with the vehicle-treated mice, but, the numbers of Sertoli cells were significantly increased in the quercetin and the onion + DEP-treated mice as compared with the DEP-treated mice. These results clearly indicate alleviative effects of quercetin and onion against the male reproductive toxicity induced by DEP.

Subchronic Toxicities of HZ1006, a Hydroxamate-Based Histone Deacetylase Inhibitor, in Beagle Dogs and Sprague-Dawley Rats.

PubMed

Zhang, Xiaofang; Zhang, Xiaodong; Yuan, Bojun; Ren, Lijun; Zhang, Tianbao; Lu, Guocai

2016-11-30

Histone deacetylase inhibitors (HDACIs), such as vorinostat and panobinostat, have been shown to have active effects on many hematologic malignancies, including multiple myeloma and cutaneous T-cell lymphoma. Hydroxamate-based (Hb) HDACIs have very good toxicity profiles and are currently being tested in phases I and II clinical trials with promising results in selected neoplasms, such as bladder carcinoma. One of the Hb-HDACIs, HZ1006, has been demonstrated to be a promising drug for clinical use. The aim of our study was to determine the possible target of toxicity and to identify a non-toxic dose of HZ1006 for clinical use. In our studies, the repeated dosage toxicity of HZ1006 in Beagle dogs and Sprague Dawley (SD) rats was identified. Dogs and rats received HZ1006 orally (0-80 and 0-120 mg/kg/day, respectively) on a continuous daily dosing agenda for 28 days following a 14-day dosage-free period. HZ1006's NOAEL (No Observed Adverse Effect Level) by daily oral administration for dogs and rats was 5 mg/kg and 60 mg/kg, respectively, and the minimum toxic dose was 20 and 120 mg/kg, respectively. All the side effects indicated that the digestive tract, the male reproductive tract, the respiratory tract and the hematological systems might be HZ1006 toxic targets in humans. HZ1006 could be a good candidate or a safe succedaneum to other existing HDACIs for the treatment of some solid tumor and hematologic malignancies.

Safety evaluation of the temporary consolidant based on a zebrafish embryo model.

PubMed

Zhang, Lu; Zhang, Xiao Yan; Hu, Yulan; Zhang, Bing Jian

2018-05-07

Temporary consolidants, such as cyclododecane, menthol, coumarin, and ethyl maltol, are proved to be effective for urgent conservation in archaeological field. However, the safety of these temporary consolidants is still unknown although they are always heavily used in archaeological field. Thus reports on the toxicity of these temporary consolidants are limited. Here, a zebrafish model was used for safety evaluation of these four temporary consolidants. In the present study, four temporary consolidants, including cyclododecane, menthol, coumarin, and ethyl maltol, at different concentrations were incubated with zebrafish embryos, and their biological toxic effects were firstly evaluated. It was shown that embryo exposure to temporary consolidants resulted in an increased mortality and malformation rate, and a decreased hatching rate. The order of embryo toxicity of the four types of temporary consolidants tested was menthol > coumarin > ethyl maltol > cyclododecane. Although the embryo toxicity of cyclododecane was minimal, some studies have indicated that this temporary consolidant could be bioaccumulated. The results also suggested that the zebrafish embryos can serve as a reliable model for the evaluation of embryo toxicity of temporary consolidants, as this model could offer the possibility to perform the rapid, medium throughput, cost-effective analyses. Copyright © 2018 Elsevier Ltd. All rights reserved.

Assessing neurodevelopmental effects of arsenolipids in pre-differentiated human neurons.

PubMed

Witt, Barbara; Ebert, Franziska; Meyer, Sören; Francesconi, Kevin A; Schwerdtle, Tanja

2017-11-01

In the general population exposure to arsenic occurs mainly via diet. Highest arsenic concentrations are found in seafood, where arsenic is present predominantly in its organic forms including arsenolipids. Since recent studies have provided evidence that arsenolipids could reach the brain of an organism and exert toxicity in fully differentiated human neurons, this work aims to assess the neurodevelopmental toxicity of arsenolipids. Neurodevelopmental effects of three arsenic-containing hydrocarbons (AsHC), two arsenic-containing fatty acids (AsFA), arsenite and dimethylarsinic acid (DMA V ) were characterized in pre-differentiated human neurons. AsHCs and arsenite caused substantial cytotoxicity in a similar, low concentration range, whereas AsFAs and DMA V were less toxic. AsHCs were highly accessible for cells and exerted pronounced neurodevelopmental effects, with neurite outgrowth and the mitochondrial membrane potential being sensitive endpoints; arsenite did not substantially decrease those two endpoints. In fully differentiated neurons, arsenite and AsHCs caused neurite toxicity. These results indicate for a neurodevelopmental potential of AsHCs. Taken into account the possibility that AsHCs might easily reach the developing brain when exposed during early life, neurotoxicity and neurodevelopmental toxicity cannot be excluded. Further studies are needed in order to progress the urgently needed risk assessment. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Percutaneous penetration and pharmacodynamics: Wash-in and wash-off of sunscreen and insect repellent.

PubMed

Rodriguez, Jocelyn; Maibach, Howard I

2016-01-01

Increased awareness of skin cancer and mosquito-transmitted diseases has increased use of insect repellents and sunscreens. The challenge in setting recommendations for use and reapplication, especially when used concomitantly, lies in finding the balance between applying a durable product effective in withstanding natural and physical factors such as water, sweat, temperature and abrasion, while limiting percutaneous absorption and decreasing risk of potential dermal and systemic toxicity. Inorganic sunscreens show no or little percutaneous absorption or toxic effects in comparison to organic sunscreens, which show varying levels of dermal penetration and cutaneous adverse effects. An alternative to N,N-diethyl-m-toluamide (DEET), the traditional gold standard compound in insect repellents, picaridin appears as efficacious, has lower risk of toxicity, and when used simultaneously with sunscreen may decrease percutaneous absorption of both compounds. Conversely, combined use of DEET and sunscreen results in significantly higher absorption of both compounds. It is important to increase consumer awareness of "washing in" of various compounds leading to increased risk of toxicity, as well as differences in reapplication need due to "washing off" caused by water, sweat and abrasion. Although much remains to be studied, to maximize efficacy and decrease toxicity, contemporary research tools, including dermatopharmokinetics, should aid these prospective advances.

An Evaluation of the NIDS (registered trademark) ACE (trademark) Test

DTIC Science & Technology

2014-06-30

included chemicals commonly used for drinking water disinfection (chlorine and chloramine), byproducts of cyanobacteria blooms (geosmin and 2...duration field toxicity test for Army drinking water . One component of the ESB the ACE Test) is an enzymatic assay designed to detect neurotoxicants...adverse health effects is the presence of toxic industrial chemicals (TICs) in drinking water . The current field water test kit – the water quality

Distributed structure-searchable toxicity (DSSTox) public database network: a proposal.

PubMed

Richard, Ann M; Williams, ClarLynda R

2002-01-29

The ability to assess the potential genotoxicity, carcinogenicity, or other toxicity of pharmaceutical or industrial chemicals based on chemical structure information is a highly coveted and shared goal of varied academic, commercial, and government regulatory groups. These diverse interests often employ different approaches and have different criteria and use for toxicity assessments, but they share a need for unrestricted access to existing public toxicity data linked with chemical structure information. Currently, there exists no central repository of toxicity information, commercial or public, that adequately meets the data requirements for flexible analogue searching, Structure-Activity Relationship (SAR) model development, or building of chemical relational databases (CRD). The distributed structure-searchable toxicity (DSSTox) public database network is being proposed as a community-supported, web-based effort to address these shared needs of the SAR and toxicology communities. The DSSTox project has the following major elements: (1) to adopt and encourage the use of a common standard file format (structure data file (SDF)) for public toxicity databases that includes chemical structure, text and property information, and that can easily be imported into available CRD applications; (2) to implement a distributed source approach, managed by a DSSTox Central Website, that will enable decentralized, free public access to structure-toxicity data files, and that will effectively link knowledgeable toxicity data sources with potential users of these data from other disciplines (such as chemistry, modeling, and computer science); and (3) to engage public/commercial/academic/industry groups in contributing to and expanding this community-wide, public data sharing and distribution effort. The DSSTox project's overall aims are to effect the closer association of chemical structure information with existing toxicity data, and to promote and facilitate structure-based exploration of these data within a common chemistry-based framework that spans toxicological disciplines.

Calculation and evaluation of sediment effect concentrations for the amphipod Hyalella azteca and the midge Chironomus riparius

USGS Publications Warehouse

Ingersoll, Christopher G.; Haverland, Pamela S.; Brunson, Eric L.; Canfield, Timothy J.; Dwyer, F. James; Henke, Chris; Kemble, Nile E.; Mount, David R.; Fox, Richard G.

1996-01-01

Procedures are described for calculating and evaluating sediment effect concentrations (SECs) using laboratory data on the toxicity of contaminants associated with field-collected sediment to the amphipod Hyalella azteca and the midge Chironomus riparius. SECs are defined as the concentrations of individual contaminants in sediment below which toxicity is rarely observed and above which toxicity is frequently observed. The objective of the present study was to develop SECs to classify toxicity data for Great Lake sediment samples tested with Hyalella azteca and Chironomus riparius. This SEC database included samples from additional sites across the United States in order to make the database as robust as possible. Three types of SECs were calculated from these data: (1) Effect Range Low (ERL) and Effect Range Median (ERM), (2) Threshold Effect Level (TEL) and Probable Effect Level (PEL), and (3) No Effect Concentration (NEC). We were able to calculate SECs primarily for total metals, simultaneously extracted metals, polychlorinated biphenyls (PCBs), and polycyclic aromatic hydrocarbons (PAHs). The ranges of concentrations in sediment were too narrow in our database to adequately evaluate SECs for butyltins, methyl mercury, polychlorinated dioxins and furans, or chlorinated pesticides. About 60 to 80% of the sediment samples in the database are correctly classified as toxic or not toxic depending on type of SEC evaluated. ERMs and ERLs are generally as reliable as paired PELs and TELs at classifying both toxic and non-toxic samples in our database. Reliability of the SECs in terms of correctly classifying sediment samples is similar between ERMs and NECs; however, ERMs minimize Type I error (false positives) relative to ERLs and minimize Type II error (false negatives) relative to NECs. Correct classification of samples can be improved by using only the most reliable individual SECs for chemicals (i.e., those with a higher percentage of correct classification). SECs calculated using sediment concentrations normalized to total organic carbon (TOC) concentrations did not improve the reliability compared to SECs calculated using dry-weight concentrations. The range of TOC concentrations in our database was relatively narrow compared to the ranges of contaminant concentrations. Therefore, normalizing dry-weight concentrations to a relatively narrow range of TOC concentrations had little influence on relative concentra of contaminants among samples. When SECs are used to conduct a preliminary screening to predict the potential for toxicity in the absence of actual toxicity testing, a low number of SEC exceedances should be used to minimize the potential for false negatives; however, the risk of accepting higher false positives is increased.

Hemolytic, anticancer and antigiardial activity of Palythoa caribaeorum venom.

PubMed

Lazcano-Pérez, Fernando; Zavala-Moreno, Ariana; Rufino-González, Yadira; Ponce-Macotela, Martha; García-Arredondo, Alejandro; Cuevas-Cruz, Miguel; Gómez-Manzo, Saúl; Marcial-Quino, Jaime; Arreguín-Lozano, Barbarín; Arreguín-Espinosa, Roberto

2018-01-01

Cnidarian venoms and extracts have shown a broad variety of biological activities including cytotoxic, antibacterial and antitumoral effects. Most of these studied extracts were obtained from sea anemones or jellyfish. The present study aimed to determine the toxic activity and assess the antitumor and antiparasitic potential of Palythoa caribaeorum venom by evaluating its in vitro toxicity on several models including human tumor cell lines and against the parasite Giardia intestinalis . The presence of cytolysins and vasoconstrictor activity of P. caribaeorum venom were determined by hemolysis, PLA 2 and isolated rat aortic ring assays, respectively. The cytotoxic effect was tested on HCT-15 (human colorectal adenocarcinoma), MCF-7 (human mammary adenocarcinoma), K562 (human chronic myelogenous leukemia), U251 (human glyoblastoma), PC-3 (human prostatic adenocarcinoma) and SKLU-1 (human lung adenocarcinoma). An in vivo toxicity assay was performed with crickets and the antiparasitic assay was performed against G. intestinalis at 24 h of incubation. P. caribaeorum venom produced hemolytic and PLA 2 activity and showed specific cytotoxicity against U251 and SKLU-1 cell lines, with approximately 50% growing inhibition. The venom was toxic to insects and showed activity against G. intestinalis in a dose-dependent manner by possibly altering its membrane osmotic equilibrium. These results suggest that P. caribaeorum venom contains compounds with potential therapeutic value against microorganisms and cancer.

Glycyl-alanyl-histidine protects PC12 cells against hydrogen peroxide toxicity.

PubMed

Shimura, Hideki; Tanaka, Ryota; Shimada, Yoshiaki; Yamashiro, Kazuo; Hattori, Nobutaka; Urabe, Takao

2017-11-22

Peptides with cytoprotective functions, including antioxidants and anti-infectives, could be useful therapeutics. Carnosine, β-alanine-histidine, is a dipeptide with anti-oxidant properties. Tripeptides of Ala-His-Lys, Pro-His-His, or Tyr-His-Tyr are also of interest in this respect. We synthesized several histidine-containing peptides including glycine or alanine, and tested their cytoprotective effects on hydrogen peroxide toxicity for PC12 cells. Of all these peptides (Gly-His-His, Ala-His-His, Ala-His-Ala, Ala-Ala-His, Ala-Gly-His, Gly-Ala-His (GAH), Ala-His-Gly, His-Ala-Gly, His-His-His, Gly-His-Ala, and Gly-Gly-His), GAH was found to have the strongest cytoprotective activity. GAH decreased lactate dehydrogenase (LDH) leakage, apoptosis, morphological changes, and nuclear membrane permeability changes against hydrogen peroxide toxicity in PC12 cells. The cytoprotective activity of GAH was superior to that of carnosine against hydrogen peroxide toxicity in PC12 cells. GAH also protected PC12 cells against damage caused by actinomycin D and staurosporine. Additionally, it was found that GAH also protected SH-SY5Y and Jurkat cells from damage caused by hydrogen peroxide, as assessed by LDH leakage. Thus, a novel tripeptide, GAH, has been identified as having broad cytoprotective effects against hydrogen peroxide-induced cell damage.

Carfilzomib and the cardiorenal system in myeloma: an endothelial effect?

PubMed Central

Rosenthal, A; Luthi, J; Belohlavek, M; Kortüm, K M; Mookadam, F; Mayo, A; Fonseca, R; Bergsagel, P L; Reeder, C B; Mikhael, J R; Stewart, A K

2016-01-01

Carfilzomib (Cfz) has been associated with an ~5% incidence of unexplained and unpredictable cardiovascular toxicity in clinical trials. We therefore implemented a detailed, prospective, clinical cardiac and renal evaluation of 62 Cfz-treated myeloma patients, including serial blood pressure (BP), creatinine, troponin, NT-proBNP and pre- and post-treatment echocardiograms, including ejection fraction (EF), average global longitudinal strain and compliance. Pre-treatment elevations in NT-proBNP and BP, as well as abnormal cardiac strain were common. A rise in NT-proBNP occurred frequently post-treatment often without corresponding cardiopulmonary symptoms. A rise in creatinine was common, lessened with hydration and often reversible. All patients had a normal EF pre-treatment. Five patients experienced a significant cardiac event (four decline in EF and one myocardial infarction), of which 2 (3.2%) were considered probably attributable to Cfz. None were rechallenged with Cfz. The ideal strategy for identifying patients at risk for cardiac events, and parameters by which to monitor for early toxicity have not been established; however, it appears baseline echocardiographic testing is not consistently predictive of toxicity. The toxicities observed suggest an endothelial mechanism and further clinical trials are needed to determine whether or not this represents a class effect or is Cfz specific. PMID:26771810

Class act: safety comparison of approved tyrosine kinase inhibitors for non-small-cell lung carcinoma.

PubMed

Burotto, Mauricio; Ali, Syed Abbas; O'Sullivan Coyne, Geraldine

2015-01-01

The past decade has seen the development and widespread use of tyrosine kinase inhibitors (TKIs) targeting a mutated EGFR (mEGFR) for the treatment of metastatic NSCLC. We discuss the main properties of the TKIs currently recommended for the treatment of mEGFR NSCLC: gefitinib, erlotinib and afatinib. The mechanism of action, pharmacodynamics and pharmacokinetics of these drugs, with emphasis on the historical context of their preclinical and clinical development, will be covered, including potential resistance mechanisms to these first-generation TKIs that has driven the trial design for second and third generations of EGFR inhibitors. Six Phase III clinical trials comparing these three TKIs with cisplatin-based chemotherapy upfront for mEGFR NSCLC provide the basis for the comparative safety and toxicity analysis between these agents. Class-related toxicity of these EGFR inhibitors, including life-threatening effects, will be discussed. Toxicity and safety analysis from the Phase III trials of these agents in mEGFR populations suggests that afatinib has more frequent and severe side effects. Given that an efficacy advantage has not yet been demonstrated for afatinib over erlotinib and gefitinib, the consistent class toxicity profile of these agents means that gefitinib and erlotinib are a safer first-line treatment recommendation.

Evaluation of “Dream Herb,” Calea zacatechichi, for Nephrotoxicity Using Human Kidney Proximal Tubule Cells

PubMed Central

Flynn, Thomas J.; Vohra, Sanah; Wiesenfeld, Paddy; Sprando, Robert L.

2016-01-01

A recent surge in the use of dietary supplements, including herbal remedies, necessitates investigations into their safety profiles. “Dream herb,” Calea zacatechichi, has long been used in traditional folk medicine for a variety of purposes and is currently being marketed in the US for medicinal purposes, including diabetes treatment. Despite the inherent vulnerability of the renal system to xenobiotic toxicity, there is a lack of safety studies on the nephrotoxic potential of this herb. Additionally, the high frequency of diabetes-associated kidney disease makes safety screening of C. zacatechichi for safety especially important. We exposed human proximal tubule HK-2 cells to increasing doses of this herb alongside known toxicant and protectant control compounds to examine potential toxicity effects of C. zacatechichi relative to control compounds. We evaluated both cellular and mitochondrial functional changes related to toxicity of this dietary supplement and found that even at low doses evidence of cellular toxicity was significant. Moreover, these findings correlated with significantly elevated levels of nephrotoxicity biomarkers, lending further support for the need to further scrutinize the safety of this herbal dietary supplement. PMID:27703475

Cutaneous effects of exposure to polybrominated biphenyls (PBBs): the Michigan PBB incident

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chanda, J.J.; Anderson, H.A.; Glamb, R.W.

1982-10-01

In 1973 an environmental accident occurred in northern Michigan in which 1000-2000 pounds of the toxic fire retardant polybrominated biphenyl (PBB) was added to the livestock food supply of much of northern Michigan. PBB is highly lipophilic, poorly metabolized, and biocumulative. It subsequently entered the human food chain of the entire state of Michigan. Health effects were noted in contaminated animals and among exposed farmers some months after the contamination; these often included cutaneous problems. Three years later a multidisciplinary study of the farming population was undertaken. Detected cutaneous abnormalities included halogen acne, hair loss, skin redness, skin peeling, andmore » scaling, itching, increased sweating, and increased growth of fingernails and toenails. The mechanisms underlying these effects are unknown. PBBs appear to be etiologically implicated for significant cutaneous toxicity.« less

Health Effects of Toxicants: Online Knowledge Support ...

EPA Pesticide Factsheets

Research in toxicology generates vast quantities of data which reside on the Web and are subsequently appropriated and utilized to support further research. This data includes a broad spectrum of information about chemical, biological and radiological agents which can affect health, the nature of the effects, treatment, regulatory measures, and more. Online resources are created and housed by a variety of institutions, including libraries and government agencies. This paper focuses on three such institutions and the tools they offer to the public: the National Library of Medicine (NLM) and its Toxicology and Environmental Health Information Program, the United States Environmental Protection Agency (EPA), and the Organisation for Economic Co-operation and Development (OECD). Reference is also made to other relevant organizations. A review of online public data sources and data resources on health effects of toxicants offered by NLM, EPA and OECD..

A quantitative weight of evidence methodology for the assessment of reproductive and developmental toxicity and its application for classification and labeling of chemicals.

PubMed

Dekant, Wolfgang; Bridges, James

2016-12-01

Hazard assessment of chemicals usually applies narrative assessments with a number of weaknesses. Therefore, application of weight of evidence (WoE) approaches are often mandated but guidance to perform a WoE assessment is lacking. This manuscript describes a quantitative WoE (QWoE) assessment for reproductive toxicity data and its application for classification and labeling (C&L). Because C&L criteria are based on animal studies, the scope is restricted to animal toxicity data. The QWoE methodology utilizes numerical scoring sheets to assess reliability of a publication and the toxicological relevance of reported effects. Scores are given for fourteen quality aspects, best practice receives the highest score. The relevance/effects scores (0 to four) are adjusted to the key elements of the toxic response for the endpoint and include weighting factors for effects on different levels of the biological organization. The relevance/effects scores are then assessed against the criteria dose-response, magnitude and persistence of effects, consistency of observations with the hypothesis, and relation of effects to human disease. The quality/reliability scores and the relevance/effect scores are then multiplied to give a numerical strength of evidence for adverse effects. This total score is then used to assign the chemical to the different classes employed in classification. Copyright © 2016 Elsevier Inc. All rights reserved.

Pharmaceuticals and Personal-Care Products in Plants.

PubMed

Bartrons, Mireia; Peñuelas, Josep

2017-03-01

Pharmaceuticals and personal-care products (PPCPs) derived from agricultural, urban, and industrial areas accumulate in plants at concentrations (ng to μg kg -1 ) that can be toxic to the plants. Importantly, the dietary intake of these PPCP-contaminated plants may also pose a risk to human health, but currently little is known about the fate of PPCPs in plants and their effect on or risk to the ecosystem. In this Opinion article we propose that in-depth research on the use of plants as a monitoring device for assessing the use and environmental presence of PPCPs is warranted. The toxicity of PPCPs to plants and their microbiota needs to be established, as well as any toxic effects on herbivores including humans. Copyright © 2016 Elsevier Ltd. All rights reserved.

Endocrine therapy toxicity: management options.

PubMed

Henry, N Lynn

2014-01-01

Treatment with adjuvant endocrine therapy, including tamoxifen and the aromatase inhibitors, has resulted in notable improvements in disease-free and overall survival for patients with hormone receptor-positive breast cancer. Despite their proven benefit, however, adherence to and persistence with the medications is poor in part because of bothersome side effects that can negatively affect quality of life. Retrospective analyses have identified possible predictors of development of toxicity. Reports have also suggested that development of toxicity may be a biomarker of better response to therapy. In addition, there has been considerable research investment into the management of these side effects, which may lead to improved adherence and persistence with therapy. However, although notable advances have been made, much more remains to be done to provide patients with truly personalized therapy for hormone receptor-positive breast cancer.

The Molecular Mechanisms of the Antibacterial Effect of Picosecond Laser Generated Silver Nanoparticles and Their Toxicity to Human Cells

PubMed Central

Korshed, Peri; Li, Lin; Liu, Zhu; Wang, Tao

2016-01-01

Silver nanoparticles (Ag NPs) are known to have antibacterial properties. They are commonly produced by chemical synthesis which involves the use of harmful reducing agents. Contras, the laser technique is able to generate high-purity Ag NPs in water with specified surface charge characteristics. In the past, the molecular mechanisms contributing to the bactericidal effects of Ag NPs have been investigated extensively, but little is known of the antibacterial and toxic effects and mechanisms involved in laser-generated Ag NPs. In the current study Ag NPs were generated by picosecond laser ablation. Their antibacterial activity was determined on the gram-negative bacteria E. coli and Pseudomonas aeruginosa, and the gram positive bacteria Staphylococcus aureus including the methicillin resistant strain MRSA. Results showed that the laser generated Ag NPs exhibited strong dose-dependent antibacterial activity against all the three bacterial strains tested. Using E.coli as a model system, the laser Ag NPs treatment induced significantly high levels of reactive oxygen species (ROS). These ROS did not include detectable hydroxyl radicals, suggesting for the first time the selective ROS induction in bacterial cells by laser generated Ag NPs. The increased ROS was accompanied by significantly reduced cellular glutathione, and increased lipid peroxidation and permeability, suggesting ROS related bacterial cell damage. The laser generated Ag NPs exhibited low toxicity (within 72 hours) to five types of human cells although a weak significant decrease in cell survival was observed for endothelial cells and the lung cells. We conclude that picosecond laser generated Ag NPs have a broad spectrum of antibacterial effects against microbes including MRSA with minimal human cell toxicity. The oxidative stress is likely the key mechanism underlying the bactericidal effect, which leads to lipid peroxidation, depletion of glutathione, DNA damages and eventual disintegration of the cell membrane. PMID:27575485

The Molecular Mechanisms of the Antibacterial Effect of Picosecond Laser Generated Silver Nanoparticles and Their Toxicity to Human Cells.

PubMed

Korshed, Peri; Li, Lin; Liu, Zhu; Wang, Tao

2016-01-01

Silver nanoparticles (Ag NPs) are known to have antibacterial properties. They are commonly produced by chemical synthesis which involves the use of harmful reducing agents. Contras, the laser technique is able to generate high-purity Ag NPs in water with specified surface charge characteristics. In the past, the molecular mechanisms contributing to the bactericidal effects of Ag NPs have been investigated extensively, but little is known of the antibacterial and toxic effects and mechanisms involved in laser-generated Ag NPs. In the current study Ag NPs were generated by picosecond laser ablation. Their antibacterial activity was determined on the gram-negative bacteria E. coli and Pseudomonas aeruginosa, and the gram positive bacteria Staphylococcus aureus including the methicillin resistant strain MRSA. Results showed that the laser generated Ag NPs exhibited strong dose-dependent antibacterial activity against all the three bacterial strains tested. Using E.coli as a model system, the laser Ag NPs treatment induced significantly high levels of reactive oxygen species (ROS). These ROS did not include detectable hydroxyl radicals, suggesting for the first time the selective ROS induction in bacterial cells by laser generated Ag NPs. The increased ROS was accompanied by significantly reduced cellular glutathione, and increased lipid peroxidation and permeability, suggesting ROS related bacterial cell damage. The laser generated Ag NPs exhibited low toxicity (within 72 hours) to five types of human cells although a weak significant decrease in cell survival was observed for endothelial cells and the lung cells. We conclude that picosecond laser generated Ag NPs have a broad spectrum of antibacterial effects against microbes including MRSA with minimal human cell toxicity. The oxidative stress is likely the key mechanism underlying the bactericidal effect, which leads to lipid peroxidation, depletion of glutathione, DNA damages and eventual disintegration of the cell membrane.

BLTK1 murine Leydig cells: a novel steroidogenic model for evaluating the effects of reproductive and developmental toxicants.

PubMed

Forgacs, Agnes L; Ding, Qi; Jaremba, Rosemary G; Huhtaniemi, Ilpo T; Rahman, Nafis A; Zacharewski, Timothy R

2012-06-01

Leydig cells are the primary site of androgen biosynthesis in males. Several environmental toxicants target steroidogenesis resulting in both developmental and reproductive effects including testicular dysgenesis syndrome. The aim of this study was to evaluate the effect of several structurally diverse endocrine disrupting compounds (EDCs) on steroidogenesis in a novel BLTK1 murine Leydig cell model. We demonstrate that BLTK1 cells possess a fully functional steroidogenic pathway that produces low basal levels of testosterone (T) and express all the necessary steroidogenic enzymes including Star, Cyp11a1, Cyp17a1, Hsd3b1, Hsd17b3, and Srd5a1. Recombinant human chorionic gonadotropin (rhCG) and forskolin (FSK) elicited concentration- and time-dependent induction of 3',5'-cyclic adenosine monophosphate, progesterone (P), and T, as well as the differential expression of Star, Hsd3b6, Hsd17b3, and Srd5a1 messenger RNA levels. The evaluation of several structurally diverse male reproductive toxicants including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), atrazine, prochloraz, triclosan, monoethylhexyl phthalate (MEHP), glyphosate, and RDX in BLTK1 cells suggests different modes of action perturb steroidogenesis. For example, prochloraz and triclosan antifungals reduced rhCG induction of T, consistent with published in vivo data but did not alter basal T levels. In contrast, atrazine and MEHP elicited modest induction of basal T but antagonized rhCG-mediated induction of T levels, whereas TCDD, glyphosate, and RDX had no effect on basal or rhCG induction of T in BLTK1 cells. These results suggest that BLTK1 cells maintain rhCG-inducible steroidogenesis and are a viable in vitro Leydig cell model to evaluate the effects of EDCs on steroidogenesis. This model can also be used to elucidate the different mechanisms underlying toxicant-mediated disruption of steroidogenesis.

Comparative assessment of three in vitro exposure methods for combustion toxicity.

PubMed

Lestari, Fatma; Markovic, Boban; Green, Anthony R; Chattopadhyay, Gautam; Hayes, Amanda J

2006-01-01

A comparative assessment of three approaches for the use of human cells in vitro to investigate combustion toxicity was conducted. These included one indirect and two direct (passive and dynamic) exposure methods. The indirect method used an impinger system in which culture medium was used to trap the toxicants, whilst the direct exposure involved the use of a Horizontal Harvard Navicyte Chamber at the air/liquid interface. The cytotoxic effects of thermal decomposition products were assessed using the MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay (Promega) on a selection of human cells including: HepG2, A549 and skin fibroblasts. A small scale laboratory fire test using a vertical tube furnace was designed for the generation of combustion products. Polymethyl methacrylate (PMMA) was selected as a model polymer to study the cytotoxic effects of combustion products. NOAEC (no observable adverse effect concentration), IC10 (10% inhibitory concentration), IC50 (50% inhibitory concentration) and TLC (total lethal concentration) values were determined from dose response curves. Assessment using the NRU (neutral red uptake) and ATP (adenosine triphosphate) assays on human lung derived cells (A549) was also undertaken. Comparison between in vitro cytotoxicity results against published toxicity data for PMMA combustion and predicted LC50 (50% lethal concentration) values calculated from identified compounds using GCMS (gas chromatography mass spectrometry) was determined. The results suggested that the indirect exposure method did not appear to simulate closely exposure via inhalation, whilst exposure at the air/liquid interface by using the dynamic method proved to be a more representative method of human inhalation. This exposure method may be a potential system for in vitro cytotoxicity testing in combustion toxicity. Copyright 2005 John Wiley & Sons, Ltd.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ema, Makoto, E-mail: ema-makoto@aist.go.jp; Gamo, Masashi; Honda, Kazumasa

We summarized significant effects reported in the literature on the developmental toxicity of engineered nanomaterials (ENMs) in rodents. The developmental toxicity of ENMs included not only structural abnormalities, but also death, growth retardation, and behavioral and functional abnormalities. Most studies were performed on mice using an injection route of exposure. Teratogenic effects were indicated when multi-walled carbon nanotubes (MWCNTs), single-walled carbon nanotubes (SWCNTs), and TiO{sub 2}-nanoparticles were administered to mice during early gestation. Reactive oxygen species levels were increased in placentas and malformed fetuses and their placentas after prenatal exposure to MWCNTs and SWCNTs, respectively. The pre- and postnatal mortalitiesmore » and growth retardation in offspring increased after prenatal exposure to ENMs. Histopathological and functional abnormalities were also induced in placentas after prenatal exposure to ENMs. Maternal exposure to ENMs induced behavioral alterations, histopathological and biochemical changes in the central nervous system, increased susceptibility to allergy, transplacental genotoxicity, and vascular, immunological, and reproductive effects in offspring. The size- and developmental stage-dependent placental transfer of ENMs was noted after maternal exposure. Silver accumulated in the visceral yolk sac after being injected with Ag-NPs during early gestation. Although currently available data has provided initial information on the potential developmental toxicity of ENMs, that on the developmental toxicity of ENMs is still very limited. Further studies using well-characterized ENMs, state-of the-art study protocols, and appropriate routes of exposure are required in order to clarify these developmental effects and provide information suitable for risk assessments of ENMs. - Highlights: • We review the developmental toxicity studies of engineered nanomaterials (ENMs). • Various developmental endpoints have been reported after exposure to ENMs. • Physico-chemical properties of ENMs are determinants of the developmental toxicity. • Oxidative stress/inflammation may be involved in the developmental toxicity of ENMs. • Further developmental toxicity studies of ENMs are needed to fill a data gap.« less

[The Effectiveness of Cooling Packaging Care in Relieving Chemotherapy-Induced Skin Toxicity Reactions in Cancer Patients Receiving Chemotherapy: A Systematic Review].

PubMed

Hsu, Ya-Hui; Hung, Hsing-Wei; Chen, Shu-Ching

2017-08-01

Anti-cancer chemotherapy may cause skin-toxicity reactions. Different types of cooling packages affect chemotherapy-induced skin toxicity reactions differently. To evaluate the effects of cooling packing care on chemotherapy-induced skin toxicity reactions in cancer patients receiving chemotherapy. A systematic review approach was used. Searches were conducted in databases including Cochrane Library, Embase, MEDLINE, PubMed and Airiti Library using the keywords "chemotherapy cutaneous toxicity", "chemotherapy skin reaction", "chemotherapy skin toxicity", "frozen glove", "frozen sock", "cooling packaging care", "ice gloves", "ice socks", "usual care", "severity", "comfort", "satisfaction", "severity", and "comfort". The search focused on articles published before December 2016. Based on the inclusion and exclusion criteria, 5 articles involving relevant randomized controlled trials were extracted for review. Elasto-Gel ice gloves or ice socks that were chilled to -25°C- -30°C and used for 15 mins during initial chemotherapy, for one hour during chemotherapy infusion, and for 15 mins after chemotherapy were shown to improve the frequency and severity of chemotherapy-induced skin toxicity reactions. Several studies were limited by small sample sizes and different types of cooling packing programs, temperature, timing, and frequency. Thus, further research is recommended to verify the effects of cooling packing care. Cancer patients who were treated with docetaxel or PLD and who used ice gloves or ice socks that were chilled to -25°C- -30°C for 15 mins during initial chemotherapy, for one hour during chemotherapy infusion, and for 15 mins after chemotherapy improved significantly in terms of the frequency and severity of their chemotherapy-induced skin toxicity reactions. Local cooling packing care is a non-pharmacotherapy approach that is low cost and free of side effects. This review is intended to provide a reference for clinical care.

Suppression of Calpain Expression by NSAIDs is Associated with Inhibition of Cell Migration in Rat Duodenum

PubMed Central

Silver, Kristopher; Littlejohn, A.; Thomas, Laurel; Bawa, Bhupinder; Lillich, James D.

2017-01-01

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for the alleviation of pain and inflammation, but these drugs are also associated with a suite of negative side effects. Gastrointestinal (GI) toxicity is particularly concerning since it affects an estimated 70% of individuals taking NSAIDs routinely, and evidence suggests the majority of toxicity is occurring in the small intestine. Traditionally, NSAID-induced GI toxicity has been associated with indiscriminate inhibition of cyclooxygenase isoforms, but other mechanisms, including inhibition of cell migration, intestinal restitution, and wound healing, are likely to contribute to toxicity. Previous efforts demonstrated that treatment of cultured intestinal epithelial cells (IEC) with NSAIDs inhibits expression and activity of calpain proteases, but the effects of specific inhibition of calpain expression in vitro or the effects of NSAIDs on intestinal cell migration in vivo remain to be determined. Accordingly, we examined the effect of suppression of calpain protease expression with siRNA on cell migration in cultured IECs and evaluated the effects of NSAID treatment on epithelial cell migration and calpain protease expression in rat duodenum. Our results show that calpain siRNA inhibits protease expression and slows migration in cultured IECs. Additionally, NSAID treatment of rats slowed migration up the villus axis and suppressed calpain expression in duodenal epithelial cells. Our results are supportive of the hypothesis that suppression of calpain expression leading to slowing of cell migration is a potential mechanism through which NSAIDs cause GI toxicity. PMID:28342779

Effects of heavy metals on sea urchin embryo development. Part 2. Interactive toxic effects of heavy metals in synthetic mine effluents.

PubMed

Kobayashi, Naomasa; Okamura, Hideo

2005-12-01

Interactive toxic effects between heavy metals were investigated using a sea urchin (Anthocidaris crassispina) bioassay. An effluent from an abandoned mine showed significant inhibitory effects on embryo development as well as producing specific malformations. The effects on the embryos were reproduced by synthetic polluted seawater consisting of eight metals (manganese, lead, cadmium, nickel, zinc, chromium, iron, and copper) at the concentrations detected in the mine effluent. This indicated that the heavy metals were responsible for the effects observed. Five heavy metals were ranked in decreasing order of toxicity as follows: Cu>Zn>Pb>Fe>Mn. Among these, zinc and manganese could cause malformation of the embryos. From bioassay results using 27 combinations of heavy metals, 16 combinations including zinc could produce specific malformations, such as radialized, exo-gastrulal, and spaceship Apollo-like gastrulal embryos. Zinc was one of the elements responsible for causing malformations and its effects were intensified by the presence of the other metals, such as manganese, lead, iron, and copper.

Lethal Dietary Toxicities of Environmental Contaminants and Pesticides to Coturnix

USGS Publications Warehouse

Hill, E.F.; Camardese, M.B.

1986-01-01

Five-day subacute dietary toxicity tests of 193 potential environmental contaminants, pesticides, organic solvents, and various adjuvants are presented for young coturnix (Japanese quail, Coturnix japonica Temminck and Schlegel). The report provides the most comprehensive data base available for avian subacute dietary toxicity tests and is primarily intended for use in ranking toxicities by a standard method that has a reasonable degree of environmental relevance. Findings are presented in two parts: Part I is a critique of selected drugs that includes discussion of subacute toxicity in relation to chemical class and structure, pesticide formulation, and age of animals; Part II is a summary of toxicologic findings for each test substance and provides a statistically basis for comparing toxicities. Data presented include the median lethal concentration (LC50), slope of the probit regression curve (dose-response curve), response chronology, and food consumption. We observed that: 1) fewer than 15% of the compounds were classed 'very' or 'highly' toxic (i.e, LC50 < 200 ppm) and all of these were either chlorinated hydrocarbons, organophosphates, or organometallics; 2) subacute toxicity may vary widely among structurally similar chemicals and between different formulations of the same chemical; therefore, conclusions about lethal hazard must be made cautiously until the actual formulation of inset has been tested: 3) inclusion of a general standard in each battery of tests is useful for detection of atypical trials and monitoring population changes but should not be used indiscriminantly for adjusting LC50's for intertest differences unless the chemicals of concern and the standard elicit their toxicities through the same action; 4) although other species have been tested effectively under the subacute protocol, coturnix were ideal for the stated purpose of this research because they are inexpensive, well-adapted to the laboratory environment, and yield good intertest reproducibility of response.

Aquatic toxicity information retrieval data base (aquire for non-vms) (on magnetic tape). Data file

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

The AQUIRE-AQUatic toxicity information REtrieval-data base was established in 1981 by the United States Environmental Protection Agency (US EPA), Office of Pesticide and Toxic Substances. AQUIRE continues to be updated and maintained at the US EPA Environmental Research Laboratory-Duluth. The purpose of AQUIRE is to provide scientists and managers quick access to a comprehensive, systematic, computerized compilation of aquatic toxic effects data for freshwater and marine organisms. The AQUIRE system is one of the foremost resources for the location of aquatic toxicity information and is commonly used to evaluate and prioritize the hazards of industrial chemicals and pesticides in themore » USA and abroad. Scientific papers published both nationally and internationally on the toxicity of chemicals to aquatic organisms and plants are collected and reviewed for AQUIRE. Independently compiled data files that meet AQUIRE parameter and quality assurance criteria are also included. Relevant toxicity test results and related test information for any individual chemicals analyzed using freshwater and marine organisms in laboratory and field conditions, are included in the database. Since 1994, nine data updates were made to the AQUIRE system. AQUIRE now contains 129,740 individual aquatic toxicity test results for 5,679 chemicals, 2,827 organisms, and over 160 endpoints reviewed from 7,517 publications. Over 16,000 of the AQUIRE records represent aquatic toxicity data reported in the literature for the publication years 1989-1991. AQUIRE offers data contributed through an international data exchange clearinghouse with the Organization for Economic Cooperation and Development (OECD) and the Borok Institute in Russia. The current release of AQUIRE delivers data submitted from Germany, The Netherlands, and Russia.« less

Acute Toxicity and Environmental Risks of Five Veterinary Pharmaceuticals for Aquatic Macroinvertebrates.

PubMed

Bundschuh, Mirco; Hahn, Torsten; Ehrlich, Bert; Höltge, Sibylla; Kreuzig, Robert; Schulz, Ralf

2016-02-01

Due to the high use of antibiotics and antiparasitics for the treatment of livestock, there is concern about the potential impacts of the release of these compounds into freshwater ecosystems. In this context, the present study quantified the acute toxicity of two antibiotics (sulfadiazine and sulfadimidine), and three antiparasitic agents (flubendazole, fenbendazole, ivermectin) for nine freshwater invertebrate species. These experiments revealed a low degree of toxicity for the sulfonamide antibiotics, with limited implications in the survival of all test species at the highest test concentrations (50 and 100 mg/L). In contrast, all three antiparasitic agents indicated on the basis of their acute toxicity risks for the aquatic environment. Moreover, chronic toxicity data from the literature for antiparasitics, including effects on reproduction in daphnids, support the concern about the integrity of aquatic ecosystems posed by releases of these compounds. Thus, these pharmaceuticals warrant further careful consideration by environmental risk managers.

Reduced Toxicity Fuel Satellite Propulsion System

NASA Technical Reports Server (NTRS)

Schneider, Steven J. (Inventor)

2001-01-01

A reduced toxicity fuel satellite propulsion system including a reduced toxicity propellant supply for consumption in an axial class thruster and an ACS class thruster. The system includes suitable valves and conduits for supplying the reduced toxicity propellant to the ACS decomposing element of an ACS thruster. The ACS decomposing element is operative to decompose the reduced toxicity propellant into hot propulsive gases. In addition the system includes suitable valves and conduits for supplying the reduced toxicity propellant to an axial decomposing element of the axial thruster. The axial decomposing element is operative to decompose the reduced toxicity propellant into hot gases. The system further includes suitable valves and conduits for supplying a second propellant to a combustion chamber of the axial thruster, whereby the hot gases and the second propellant auto-ignite and begin the combustion process for producing thrust.

The U. S. Environmental Protection Agency's inhalation RfD methodology: Risk assessment for air toxics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jarabek, A.M.; Menache, M.G.; Overton, J.H. Jr.

1990-10-01

The U.S. Environmental Protection Agency (U.S. EPA) has advocated the establishment of general and scientific guidelines for the evaluation of toxicological data and their use in deriving benchmark values to protect exposed populations from adverse health effects. The Agency's reference dose (RfD) methodology for deriving benchmark values for noncancer toxicity originally addressed risk assessment of oral exposures. This paper presents a brief background on the development of the inhalation reference dose (RfDi) methodology, including concepts and issues related to addressing the dynamics of the respiratory system as the portal of entry. Different dosimetric adjustments are described that were incorporated intomore » the methodology to account for the nature of the inhaled agent (particle or gas) and the site of the observed toxic effects (respiratory or extra-respiratory). Impacts of these adjustments on the extrapolation of toxicity data of inhaled agents for human health risk assessment and future research directions are also discussed.« less

U. S. Environmental Protection Agency's inhalation RFD methodology: Risk assessment for air toxics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jarabek, A.M.; Menache, M.G.; Overton, J.H.

1989-01-01

The U.S. Environmental Protection Agency (U.S. EPA) has advocated the establishment of general and scientific guidelines for the evaluation of toxicological data and their use in deriving benchmark values to protect exposed populations from adverse health effects. The Agency's reference dose (RfD) methodology for deriving benchmark values for noncancer toxicity originally addressed risk assessment of oral exposures. The paper presents a brief background on the development of the inhalation reference dose (RFDi) methodology, including concepts and issues related to addressing the dynamics of the respiratory system as the portal of entry. Different dosimetric adjustments are described that were incorporated intomore » the methodology to account for the nature of the inhaled agent (particle or gas) and the site of the observed toxic effects (respiratory or extrarespiratory). Impacts of these adjustments on the extrapolation of toxicity data of inhaled agents for human health risk assessment and future research directions are also discussed.« less

Principles for characterizing the potential human health effects from exposure to nanomaterials: elements of a screening strategy

PubMed Central

Oberdörster, Günter; Maynard, Andrew; Donaldson, Ken; Castranova, Vincent; Fitzpatrick, Julie; Ausman, Kevin; Carter, Janet; Karn, Barbara; Kreyling, Wolfgang; Lai, David; Olin, Stephen; Monteiro-Riviere, Nancy; Warheit, David; Yang, Hong

2005-01-01

The rapid proliferation of many different engineered nanomaterials (defined as materials designed and produced to have structural features with at least one dimension of 100 nanometers or less) presents a dilemma to regulators regarding hazard identification. The International Life Sciences Institute Research Foundation/Risk Science Institute convened an expert working group to develop a screening strategy for the hazard identification of engineered nanomaterials. The working group report presents the elements of a screening strategy rather than a detailed testing protocol. Based on an evaluation of the limited data currently available, the report presents a broad data gathering strategy applicable to this early stage in the development of a risk assessment process for nanomaterials. Oral, dermal, inhalation, and injection routes of exposure are included recognizing that, depending on use patterns, exposure to nanomaterials may occur by any of these routes. The three key elements of the toxicity screening strategy are: Physicochemical Characteristics, In Vitro Assays (cellular and non-cellular), and In Vivo Assays. There is a strong likelihood that biological activity of nanoparticles will depend on physicochemical parameters not routinely considered in toxicity screening studies. Physicochemical properties that may be important in understanding the toxic effects of test materials include particle size and size distribution, agglomeration state, shape, crystal structure, chemical composition, surface area, surface chemistry, surface charge, and porosity. In vitro techniques allow specific biological and mechanistic pathways to be isolated and tested under controlled conditions, in ways that are not feasible in in vivo tests. Tests are suggested for portal-of-entry toxicity for lungs, skin, and the mucosal membranes, and target organ toxicity for endothelium, blood, spleen, liver, nervous system, heart, and kidney. Non-cellular assessment of nanoparticle durability, protein interactions, complement activation, and pro-oxidant activity is also considered. Tier 1 in vivo assays are proposed for pulmonary, oral, skin and injection exposures, and Tier 2 evaluations for pulmonary exposures are also proposed. Tier 1 evaluations include markers of inflammation, oxidant stress, and cell proliferation in portal-of-entry and selected remote organs and tissues. Tier 2 evaluations for pulmonary exposures could include deposition, translocation, and toxicokinetics and biopersistence studies; effects of multiple exposures; potential effects on the reproductive system, placenta, and fetus; alternative animal models; and mechanistic studies. PMID:16209704

Toxicity testing of leachate from waste landfills using medaka (Oryzias latipes) for monitoring environmental safety.

PubMed

Osaki, Kae; Kashiwada, Shosaku; Tatarazako, Norihisa; Ono, Yoshiro

2006-06-01

To investigate the environmental safety of waste disposal landfill sites and of land reclaimed from such sites, we evaluated the toxicity of leachate from these sites by a combination of bioassays in the Japanese killifish medaka Oryzias latipes. We tested for lethal toxicity in adult and larval medaka and for hatching inhibition of embryos from eggs. As biochemical evidence of the effects of leachate exposure, CYP1A (EROD activity) and vitellogenin (Vtg) were induced. We also bioassayed water-treated leachate and downstream river water. Leachate solution was lethal to larval and adult medaka. Embryo hatchability was inhibited, and abnormal hatching, spinal deformity and anisophthalmia occurred in embryos exposed to leachate solution. CYP1A was induced by exposure to leachate solution diluted to 1.0%, and EROD activity was significantly higher than in control. Vtg and unknown proteins were induced in the sera of male medaka exposed to the diluted leachate solution. Conventional water treatments worked effectively to remove toxic compounds but did not work well to remove element ions, including heavy metals. Treated leachate produced neither lethal toxicity nor hatching abnormalities during the exposure period. Fish toxicity tests for leachate would be useful for monitoring the environmental safety of landfill sites.

Clinical aspects of percutaneous poisoning by the chemical warfare agent VX: effects of application site and decontamination.

PubMed

Hamilton, Murray G; Hill, Ira; Conley, John; Sawyer, Thomas W; Caneva, Duane C; Lundy, Paul M

2004-11-01

O-ethyl S-(2-diisopropylaminoethyl) methylphosphonothioate (VX) is an extremely toxic organophosphate nerve agent that has been weaponized and stockpiled in a number of different countries, and it has been used in recent terrorist events. It differs from other well-known organophosphate nerve agents in that its primary use is as a contact poison rather than as an inhalation hazard. For this reason, we examined the effects of application site and skin decontamination on VX toxicity in anesthetized domestic swine after topical application. VX applied to the surface of the ear rapidly resulted in signs of toxicity consistent with the development of cholinergic crisis, including apnea and death. VX on the epigastrium resulted in a marked delayed development of toxic signs, reduced toxicity, and reduction in the rate of cholinesterase depression compared with animals exposed on the ear. Skin decontamination (15 minutes post-VX on the ear) arrested the development of clinical signs and prevented further cholinesterase inhibition and death. These results confirm earlier work that demonstrates the importance of exposure site on the resultant toxicity of this agent and they also show that decontamination postexposure has the potential to be an integral and extremely important component of medical countermeasures against this agent.

Sulfur Mediated Alleviation of Mn Toxicity in Polish Wheat Relates to Regulating Mn Allocation and Improving Antioxidant System

PubMed Central

Sheng, Huajin; Zeng, Jian; Liu, Yang; Wang, Xiaolu; Wang, Yi; Kang, Houyang; Fan, Xing; Sha, Lina; Zhang, Haiqin; Zhou, Yonghong

2016-01-01

Sulfur (S) is an essential macronutrient that has been proved to play an important role in regulating plant responses to various biotic and abiotic stresses. The present study was designed to investigate the effect of S status on polish wheat plant response to Mn toxicity. Results showed that Mn stress inhibited plant growth, disturbed photosynthesis and induced oxidative stress. In response to Mn stress, polish wheat plant activated several detoxification mechanisms to counteract Mn toxicity, including enhanced antioxidant defense system, increased Mn distribution in the cell wall and up-regulated genes involved in S assimilation. Moderate S application was found to alleviate Mn toxicity mainly by sequestering excess Mn into vacuoles, inhibiting Mn translocation from roots to shoots, stimulating activities of antioxidant enzymes and enhancing GSH production via up-regulating genes involved in S metabolism. However, application of high level S to Mn-stressed plants did not significantly alleviated Mn toxicity likely due to osmotic stress. In conclusion, moderate S application is beneficial to polish wheat plant against Mn toxicity, S exerts its effects via stimulating the antioxidant defense system and regulating the translocation and subcellular distribution of Mn, in which processes GSH plays an indispensable role. PMID:27695467

Absence of subchronic oral toxicity and genotoxicity of rice koji with Aspergillus terreus.

PubMed

Yun, Jun-Won; Kim, Seung-Hyun; Kim, Yun-Soon; You, Ji-Ran; Cho, Eun-Young; Yoon, Jung-Hee; Kwon, Euna; Lee, Sang Ju; Kim, Seong Pil; Seo, Jae Hoon; In, Jae Pyung; Ahn, Jae Hun; Jang, Ja-June; Park, Jin-Sung; Che, Jeong-Hwan; Kang, Byeong-Cheol

2017-10-01

Koji products have been considered as an effective fermented food consumed in East Asia with many health benefits. Particularly, rice koji with Aspergillus terreus (RAT) has been reported to be able to prevent hyperlipidemia and hepatic steatosis through regulating cholesterol synthesis. Despite its biological activities, there is a lack of comprehensive information to give an assurance of its safety. Therefore, the objective of this study was to perform a series of toxicological studies (repeated dose oral toxicity and genotoxicity) according to test guidelines published by the Organization for Economic Cooperation and Development. Along with acute toxicity study using rats and beagle dogs, a 13-week toxicity study revealed no clear RAT-related toxic changes, including body weight, mortality, hematology, serum biochemistry, organ weight, and histopathology after oral administration at doses of 500, 1000, and 2000 mg/kg BW. The no-observed-adverse-effect level of RAT was considered to be more than 2000 mg/kg BW/day in rats of both genders. In addition, potential genotoxicity was evaluated using a standard battery of tests (Ames test, chromosome aberration assay, and micronucleus assay) which revealed that RAT showed no genotoxicity. Accordingly, these results suggest that RAT is a safe and non-toxic functional food for human consumption at proper dose. Copyright © 2017. Published by Elsevier Inc.

Mometasone Furoate Effect on Acute Skin Toxicity in Breast Cancer Patients Receiving Radiotherapy: A Phase 3 Double-Blind, Randomized Trial from the North Central Cancer Treatment Group N06C4

PubMed Central

Miller, Robert C.; Schwartz, David J.; Sloan, Jeff A.; Griffin, Patricia C.; Deming, Richard L.; Anders, Jon C.; Stoffel, Thomas J.; Haselow, Robert E.; Schaefer, Paul L.; Bearden, James D.; Atherton, Pamela J.; Loprinzi, Charles L.; Martenson, James A.

2010-01-01

Purpose A 2-arm, double-blinded, randomized trial to evaluate the effect of 0.1% mometasone furoate (MMF) on acute skin-related toxicity in patients undergoing breast or chest wall radiotherapy. Methods and Materials Patients with ductal carcinoma in situ or invasive breast carcinoma receiving external beam radiotherapy to breast or chest wall were randomly assigned to daily apply 0.1% MMF or placebo cream. Primary study end point was provider-assessed maximum grade of Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 radiation dermatitis. Secondary end points included provider-assessed CTCAE grade 3 or greater radiation dermatitis and adverse-event monitoring. Patient-reported outcome (PRO) measures included the Skindex-16, the Skin Toxicity Assessment Tool, a Symptom Experience Diary, and quality of life self-assessment. Assessment was performed at baseline, weekly during radiotherapy, and for 2 weeks after radiotherapy. Results In total, 176 patients were enrolled from September 21, 2007 through December 7, 2007. The provider-assessed primary end point showed no difference in mean maximum grade of radiation dermatitis by treatment arm (1.2 for MMF vs 1.3 for placebo; P=.18). CTCAE toxicity was greater in placebo group (P=.04), primarily from pruritus. For PRO measures, the maximum Skindex-16 score for MMF group showed less itching (P=.008), less irritation (P=.01), less symptom persistence or recurrence (P=.02), and less annoyance with skin problems (P=.04); the group's maximum Skin Toxicity Assessment Tool score showed less burning sensation (P=.02) and less itching (P=.002). Conclusion Patients receiving daily MMF during radiotherapy may experience reduced acute skin toxicity in comparison to placebo. PMID:20800381

Evaluating the Spatial Distribution of Toxic Air Contaminants in Multiple Ecosystem Indicators in the Sierra Nevada-Southern Cascades

NASA Astrophysics Data System (ADS)

Nanus, L.; Simonich, S. L.; Rocchio, J.; Flanagan, C.

2013-12-01

Toxic air contaminants originating from agricultural areas of the Central Valley in California threaten vulnerable sensitive receptors including surface water, vegetation, snow, sediments, fish, and amphibians in the Sierra Nevada-Southern Cascades region. The spatial distribution of toxic air contaminants in different ecosystem indicators depends on variation in atmospheric concentrations and deposition, and variation in air toxics accumulation in ecosystems. The spatial distribution of organic air toxics and mercury at over 330 unique sampling locations and sample types over two decades (1990-2009) in the Sierra Nevada-Southern Cascades region were compiled and maps were developed to further understand spatial patterns and linkages between air toxics deposition and ecological effects. Potential ecosystem impacts in the Sierra Nevada-Southern Cascades region include bioaccumulation of air toxics in both aquatic and terrestrial ecosystems, reproductive disruption, and immune suppression. The most sensitive ecological end points in the region that are affected by bioaccumulation of toxic air contaminants are fish. Mercury was detected in all fish and approximately 6% exceeded human consumption thresholds. Organic air toxics were also detected in fish yielding variable spatial patterns. For amphibians, which are sensitive to pesticide exposure and potential immune suppression, increasing trends in current and historic use pesticides are observed from north to south across the region. In other indicators, such as vegetation, pesticide concentrations in lichen increase with increasing elevation. Current and historic use pesticides and mercury were also observed in snowpack at high elevations in the study area. This study shows spatial patterns in toxic air contaminants, evaluates associated risks to sensitive receptors, and identifies data gaps. Future research on atmospheric modeling and information on sources is needed in order to predict which ecosystems are the most sensitive to toxic air contaminants in the Sierra Nevada-Southern Cascades region.

Curcumin Attenuates Amyloid-β Aggregate Toxicity and Modulates Amyloid-β Aggregation Pathway.

PubMed

Thapa, Arjun; Jett, Stephen D; Chi, Eva Y

2016-01-20

The abnormal misfolding and aggregation of amyloid-β (Aβ) peptides into β-sheet enriched insoluble deposits initiates a cascade of events leading to pathological processes and culminating in cognitive decline in Alzheimer's disease (AD). In particular, soluble oligomeric/prefibrillar Aβ have been shown to be potent neurotoxins. The naturally occurring polyphenol curcumin has been shown to exert a neuroprotective effect against age-related neurodegenerative diseases such as AD. However, its protective mechanism remains unclear. In this study, we investigated the effects of curcumin on the aggregation of Aβ40 as well as Aβ40 aggregate induced neurotoxicity. Our results show that the curcumin does not inhibit Aβ fibril formation, but rather enriches the population of "off-pathway" soluble oligomers and prefibrillar aggregates that were nontoxic. Curcumin also exerted a nonspecific neuroprotective effect, reducing toxicities induced by a range of Aβ conformers, including monomeric, oligomeric, prefibrillar, and fibrillar Aβ. The neuroprotective effect is possibly membrane-mediated, as curcumin reduced the extent of cell membrane permeabilization induced by Aβ aggregates. Taken together, our study shows that curcumin exerts its neuroprotective effect against Aβ induced toxicity through at least two concerted pathways, modifying the Aβ aggregation pathway toward the formation of nontoxic aggregates and ameliorating Aβ-induced toxicity possibly through a nonspecific pathway.

Gastroprotective effects of several H2RAs on ibuprofen-induced gastric ulcer in rats.

PubMed

Liu, Jing; Sun, Dan; He, Jinfeng; Yang, Chengli; Hu, Tingting; Zhang, Lijing; Cao, Hua; Tong, Ai-Ping; Song, Xiangrong; Xie, Yongmei; He, Gu; Guo, Gang; Luo, Youfu; Cheng, Ping; Zheng, Yu

2016-03-15

Ibuprofen is the first line of treatment for osteoarthritis and arthritis. The main side effects of ibuprofen especially in long-term treatment include gastric ulcer, duodenal ulcer and indigestion etc. Therefore, screening drugs with effective gastric protective effects and low toxicity for combination therapy with ibuprofen is necessary. The mechanism of gastric damage induced by ibuprofen is still unclear, however, cell damage caused by reactive oxygen species (ROS) is considered as the main reason. Preliminary screening of literature with the criteria of low toxicity led to four histamine-2 receptor antagonists (H2RAs): nizatidine, famotidine, lafutidine, and roxatidine acetate, which were selected for further investigation. These drugs were evaluated systemically by examining the gastric ulcer index, lipid peroxidation (LPO), membrane permeability, toxicity to main organs, and the influence on the activity of antioxidant enzymes, and myeloperoxidase (MPO). Nizatidine was found to be the best gastric protective agent. It exhibited excellent protective effect by increasing antioxidant enzyme activity, decreasing MPO activity, reducing LPO, and membrane permeability. Combination treatment with nizatidine and ibuprofen did not show any significant toxicity. Nizatidine was considered as a good option for combination therapy with ibuprofen especially for diseases that require long-term treatment such as arthritis and osteoarthritis. Copyright © 2016 Elsevier Inc. All rights reserved.

Synergistic ameliorative effects of sesame oil and alpha-lipoic acid against subacute diazinon toxicity in rats: hematological, biochemical, and antioxidant studies.

PubMed

Abdel-Daim, Mohamed M; Taha, Ramadan; Ghazy, Emad W; El-Sayed, Yasser S

2016-01-01

Diazinon (DZN) is a common organophosphorus insecticide extensively used for agriculture and veterinary purposes. DZN toxicity is not limited to insects; it also induces harmful effects in mammals and birds. Our experiment evaluated the protective and antioxidant potential of sesame oil (SO) and (or) alpha-lipoic acid (ALA) against DZN toxicity in male Wistar albino rats. DZN-treated animals exhibited macrocytic hypochromic anemia and significant increases in serum biochemical parameters related to liver injury, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), γ-glutamyl transferase (γGT), cholesterol, and triglycerides. They also had elevated levels of markers related to cardiac injury, such as lactate dehydrogenase (LDH) and creatine phosphokinase (CPK), and increased biomarkers of renal injury, urea and creatinine. DZN also increased hepatic, renal, and cardiac lipid peroxidation and decreased antioxidant biomarker levels. SO and (or) ALA supplementation ameliorated the deleterious effects of DZN intoxication. Treatment improved hematology and serum parameters, enhanced endogenous antioxidant status, and reduced lipid peroxidation. Importantly, they exerted synergistic hepatoprotective, nephroprotective, and cardioprotective effects. Our findings demonstrate that SO and (or) ALA supplementation can alleviate the toxic effects of DZN via their potent antioxidant and free radical-scavenging activities.

The efficacy of Pistacia Terebinthus soap in the treatment of cetuximab-induced skin toxicity.

PubMed

Tastekin, Didem; Tambas, Makbule; Kilic, Kemal; Erturk, Kayhan; Arslan, Deniz

2014-12-01

This open-labeled phase II, efficacy-finding study evaluated the efficiency and safety of Pistacia terebinthus soap in metastatic colorectal cancer patients who developed cetuximab induced skin toxicity. Patients who received cetuximab plus chemotherapy and developed Grade 2 or 3 skin toxicity were treated twice daily with a soap made of oil extracted from Pistacia terebinthus. During treatment, no topical or oral antibiotics, corticosteroids or other moisturizers were used. Patients were examined 1 week later and their photographs were taken. Fifteen mCRC patients who developed skin toxicity while receiving first-line CTX in combination with chemotherapy were included into the study. Eight patients were male and the median age was 58 (25-70). Sixty percent of the patients (n:9) had Grade 3 skin toxicity. Complete response rates in patients with Grade 2 and Grade 3 skin toxicities were 100 and 33%, respectively. In the remaining patients with Grade 3 toxicity the skin toxicity regressed to Grade 1. The objective response rate was 100%, and no delay, dose reduction or discontinuation of CTX treatment due to skin toxicity was necessary. Skin toxicity reoccurred in all patients when patients stopped administering the soap and therefore they used it throughout the cetuximab treatment. Pistacia terebinthus soap seemed to be used safely and effectively in the treatment of skin toxicity induced by Cetuximab.

Studies with the USF/NASA toxicity screening test method - Exercise wheels and oxygen replenishment

NASA Technical Reports Server (NTRS)

Hilado, C. J.; Cumming, H. J.

1977-01-01

Continuing efforts to improve the University of San Francisco/NASA toxicity screening test method have included the addition of exercise wheels to provide a different measure of incapacitation, and oxygen replenishment to offset any effect of oxygen depletion by the test animals. The addition of exercise wheels limited the number of animals in each test and doubled the required number of tests without any significant improvement in reproducibility. Oxygen replenishment appears to have an effect on survival in the last 5 minutes of the 30-minute test, but the effect is expected to be similar for most materials.

Developmental immunotoxicity of chemicals in rodents and its possible regulatory impact.

PubMed

Hessel, Ellen V S; Tonk, Elisa C M; Bos, Peter M J; van Loveren, Henk; Piersma, Aldert H

2015-01-01

Around 25% of the children in developed countries are affected with immune-based diseases. Juvenile onset diseases such as allergic, inflammatory and autoimmune diseases have shown increasing prevalences in the last decades. The role of chemical exposures in these phenomena is unclear. It is thought that the developmental immune system is more susceptible to toxicants than the mature situation. Developmental immunotoxicity (DIT) testing is nowadays not or minimally included in regulatory toxicology requirements. We reviewed whether developmental immune parameters in rodents would provide relatively sensitive endpoints of toxicity, whose inclusion in regulatory toxicity testing might improve hazard identification and risk assessment of chemicals. For each of the nine reviewed toxicants, the developing immune system was found to be at least as sensitive or more sensitive than the general (developmental) toxicity parameters. Functional immune (antigen-challenged) parameters appear more affected than structural (non-challenged) immune parameters. Especially, antibody responses to immune challenges with keyhole limpet hemocyanine or sheep red blood cells and delayed-type hypersensitivity responses appear to provide sensitive parameters of developmental immune toxicity. Comparison with current tolerable daily intakes (TDI) and their underlying overall no observed adverse effect levels showed that for some of the compounds reviewed, the TDI may need reconsideration based on developmental immune parameters. From these data, it can be concluded that the developing immune system is very sensitive to the disruption of toxicants independent of study design. Consideration of including functional DIT parameters in current hazard identification guidelines and wider application of relevant study protocols is warranted.

Protective effect of thymoquinone, the active constituent of Nigella sativa fixed oil, against ethanol toxicity in rats

PubMed Central

Hosseini, Sayed Masoud; Taghiabadi, Elahe; Abnous, Khalil; Hariri, Alireza Timcheh; Pourbakhsh, Hamed; Hosseinzadeh, Hossein

2017-01-01

Objective(s): Long term consumption of ethanol may induce damage to many organs. Ethanol induces its noxious effects through reactive oxygen species production, and lipid peroxidation and apoptosis induction in different tissues and cell types. Previous experiments have indicated the antioxidant characteristics of thymoquinone, the active constituent of Nigella sativa fixed oil, against biologically dangerous reactive oxygen species. This experiment was planned to evaluate the protective effect of thymoquinone against subchronic ethanol toxicity in rats. Materials and Methods: Experiments were performed on six groups. Each group consisted of six animals, including control group (saline, gavage), ethanol-receiving group (3 g/kg/day, gavage), thymoquinone (2.5, 5, 10 mg/Kg/day, intraperitoneally (IP)) plus ethanol and thymoquinone (10 mg/Kg/day, IP) groups. Treatments were carried out in four weeks. Results: Thymoquinone reduced the ethanol-induced increase in the lipid peroxidation and severity of histopathological alteration in liver and kidney tissues. In addition it improved the levels of proinflammatory cytokines in liver tissue. Furthermore, thymoquinone corrected the liver enzymes level including alanine transaminase, aspartate transaminase and alkaline phosphatase in serum and glutathione content in liver and kidney tissues. Other experiments such as Western blot analysis and quantitative real-time RT-PCR revealed that thymoquinone suppressed the expression of Bax/Bcl-2 ratio (both protein and mRNA level), and caspases activation pursuant to ethanol toxicity. Conclusion: This study indicates that thymoquinone may have preventive effects against ethanol toxicity in the liver and kidney tissue through reduction in lipid peroxidation and inflammation, and also interrupting apoptosis. PMID:29085585

Ecotoxicological evaluation of propranolol hydrochloride and losartan potassium to Lemna minor L. (1753) individually and in binary mixtures.

PubMed

Godoy, Aline A; Kummrow, Fábio; Pamplin, Paulo Augusto Z

2015-07-01

Antihypertensive pharmaceuticals, including the beta-blockers, are one of the most detected therapeutic classes in the environment. The ecotoxicity of propranolol hydrochloride and losartan potassium was evaluated, both individually and combined in a binary mixture, by using the Lemna minor growth inhibition test. The endpoints evaluated in the single-pharmaceutical tests were frond number, total frond area and fresh weight. For the evaluation of the mixture toxicity, the selected endpoint was frond number. Water quality criteria values (WQC) were derived for the protection of freshwater and saltwater pelagic communities regarding the effects induced by propranolol and losartan using ecotoxicological data from the literature, including our data. The risks associated with both pharmaceutical effects on non-target organisms were quantified through the measured environmental concentration (MEC)/predicted-no-effect concentration (PNEC) ratios. For propranolol, the total frond area was the most sensitive endpoint (EC50 = 77.3 mg L(-1)), while for losartan there was no statistically significant difference between the endpoints. Losartan is only slightly more toxic than propranolol. Both concentration addition and independent action models overestimated the mixture toxicity of the pharmaceuticals at all the effect concentration levels evaluated. The joint action of both pharmaceuticals showed an antagonistic interaction to L. minor. Derived WQC assumed lower values for propranolol than for losartan. The MEC/PNEC ratios showed that propranolol may pose a risk for the most sensitive aquatic species, while acceptable risks posed by losartan were estimated for most of aquatic matrices. To the authors knowledge these are the first data about losartan toxicity for L. minor.

Are luminescent bacteria suitable for online detection and monitoring of toxic compounds in drinking water and its sources?

PubMed

Woutersen, Marjolijn; Belkin, Shimshon; Brouwer, Bram; van Wezel, Annemarie P; Heringa, Minne B

2011-05-01

Biosensors based on luminescent bacteria may be valuable tools to monitor the chemical quality and safety of surface and drinking water. In this review, an overview is presented of the recombinant strains available that harbour the bacterial luciferase genes luxCDABE, and which may be used in an online biosensor for water quality monitoring. Many bacterial strains have been described for the detection of a broad range of toxicity parameters, including DNA damage, protein damage, membrane damage, oxidative stress, organic pollutants, and heavy metals. Most lux strains have sensitivities with detection limits ranging from milligrams per litre to micrograms per litre, usually with higher sensitivities in compound-specific strains. Although the sensitivity of lux strains can be enhanced by various molecular manipulations, most reported detection thresholds are still too high to detect levels of individual contaminants as they occur nowadays in European drinking waters. However, lux strains sensing specific toxic effects have the advantage of being able to respond to mixtures of contaminants inducing the same effect, and thus could be used as a sensor for the sum effect, including the effect of compounds that are as yet not identified by chemical analysis. An evaluation of the suitability of lux strains for monitoring surface and drinking water is therefore provided.

Integrating copper toxicity and climate change to understand extinction risk to two species of pond-breeding anurans.

PubMed

Weir, Scott M; Scott, David E; Salice, Christopher J; Lance, Stacey L

2016-09-01

Chemical contamination is often suggested as an important contributing factor to amphibian population declines, but direct links are rarely reported. Population modeling provides a quantitative method to integrate toxicity data with demographic data to understand the long-term effects of contaminants on population persistence. In this study we use laboratory-derived embryo and larval toxicity data for two anuran species to investigate the potential for toxicity to contribute to population declines. We use the southern toad (Anaxyrus terrestris) and the southern leopard frog (Lithobates sphenocephalus) as model species to investigate copper (Cu) toxicity. We use matrix models to project populations through time and quantify extinction risk (the probability of quasi-extinction in 35 yr). Life-history parameters for toads and frogs were obtained from previously published literature or unpublished data from a long-term (>35 yr) data set. In addition to Cu toxicity, we investigate the role of climate change on amphibian populations by including the probability of early pond drying that results in catastrophic reproductive failure (CRF, i.e., complete mortality of all larval individuals). Our models indicate that CRF is an important parameter for both species as both were unable to persist when CRF probability was >50% for toads or 40% for frogs. Copper toxicity alone did not result in significant effects on extinction risk unless toxicity was very high (>50% reduction in survival parameters). For toads, Cu toxicity and high probability of CRF both resulted in high extinction risk but no synergistic (or greater than additive) effects between the two stressors occurred. For leopard frogs, in the absence of CRF survival was high even under Cu toxicity, but with CRF Cu toxicity increased extinction risk. Our analyses highlight the importance of considering multiple stressors as well as species differences in response to those stressors. Our models were consistently most sensitive to juvenile and adult survival, further suggesting the importance of terrestrial stages to population persistence. Future models will incorporate multiple wetlands with different combinations of stressors to understand if our results for a single wetland result in a population sink within the landscape. © 2016 by the Ecological Society of America.

The Role of Mediators in the Indirect Effects of Religiosity on Therapeutic Compliance in African Migrant HIV-Positive Patients.

PubMed

Mambet Doue, Constance; Roussiau, Nicolas

2016-12-01

This research investigates the indirect effects of religiosity (practice and belief) on therapeutic compliance in 81 HIV-positive patients who are migrants from sub-Saharan Africa (23 men and 58 women). Using analyses of mediation and standard multiple regression, including a resampling procedure by bootstrapping, the role of these mediators (magical-religious beliefs and nonuse of toxic substances) was tested. The results show that, through magical-religious beliefs, religiosity has a negative indirect effect, while with the nonuse of toxic substances, religious practice has a positive indirect effect. Beyond religiosity, the role of mediators is highlighted in the interaction with therapeutic compliance.

Toxico-Cheminformatics: New and Expanding Public ...

EPA Pesticide Factsheets

High-throughput screening (HTS) technologies, along with efforts to improve public access to chemical toxicity information resources and to systematize older toxicity studies, have the potential to significantly improve information gathering efforts for chemical assessments and predictive capabilities in toxicology. Important developments include: 1) large and growing public resources that link chemical structures to biological activity and toxicity data in searchable format, and that offer more nuanced and varied representations of activity; 2) standardized relational data models that capture relevant details of chemical treatment and effects of published in vivo experiments; and 3) the generation of large amounts of new data from public efforts that are employing HTS technologies to probe a wide range of bioactivity and cellular processes across large swaths of chemical space. By annotating toxicity data with associated chemical structure information, these efforts link data across diverse study domains (e.g., ‘omics’, HTS, traditional toxicity studies), toxicity domains (carcinogenicity, developmental toxicity, neurotoxicity, immunotoxicity, etc) and database sources (EPA, FDA, NCI, DSSTox, PubChem, GEO, ArrayExpress, etc.). Public initiatives are developing systematized data models of toxicity study areas and introducing standardized templates, controlled vocabularies, hierarchical organization, and powerful relational searching capability across capt

Reduction of mutant huntingtin accumulation and toxicity by lysosomal cathepsins D and B in neurons

PubMed Central

2011-01-01

Background Huntington's disease is caused by aggregation of mutant huntingtin (mHtt) protein containing more than a 36 polyQ repeat. Upregulation of macroautophagy was suggested as a neuroprotective strategy to degrade mutant huntingtin. However, macroautophagy initiation has been shown to be highly efficient in neurons whereas lysosomal activities are rate limiting. The role of the lysosomal and other proteases in Huntington is not clear. Some studies suggest that certain protease activities may contribute to toxicity whereas others are consistent with protection. These discrepancies may be due to a number of mechanisms including distinct effects of the specific intermediate digestion products of mutant huntingtin generated by different proteases. These observations suggested a critical need to investigate the consequence of upregulation of individual lysosomal enzyme in mutant huntingtin accumulation and toxicity. Results In this study, we used molecular approaches to enhance lysosomal protease activities and examined their effects on mutant huntingtin level and toxicity. We found that enhanced expression of lysosomal cathepsins D and B resulted in their increased enzymatic activities and reduced both full-length and fragmented huntingtin in transfected HEK cells. Furthermore, enhanced expression of cathepsin D or B protected against mutant huntingtin toxicity in primary neurons, and their neuroprotection is dependent on macroautophagy. Conclusions These observations demonstrate a neuroprotective effect of enhancing lysosomal cathepsins in reducing mutant huntingtin level and toxicity in transfected cells. They highlight the potential importance of neuroprotection mediated by cathepsin D or B through macroautophagy. PMID:21631942

Soil bioretention protects juvenile salmon and their prey from the toxic impacts of urban stormwater runoff.

PubMed

McIntyre, J K; Davis, J W; Hinman, C; Macneale, K H; Anulacion, B F; Scholz, N L; Stark, J D

2015-08-01

Green stormwater infrastructure (GSI), or low impact development, encompasses a diverse and expanding portfolio of strategies to reduce the impacts of stormwater runoff on natural systems. Benchmarks for GSI success are usually framed in terms of hydrology and water chemistry, with reduced flow and loadings of toxic chemical contaminants as primary metrics. Despite the central goal of protecting aquatic species abundance and diversity, the effectiveness of GSI treatments in maintaining diverse assemblages of sensitive aquatic taxa has not been widely evaluated. In the present study we characterized the baseline toxicity of untreated urban runoff from a highway in Seattle, WA, across six storm events. For all storms, first flush runoff was toxic to the daphniid Ceriodaphnia dubia, causing up to 100% mortality or impairing reproduction among survivors. We then evaluated whether soil media used in bioretention, a conventional GSI method, could reduce or eliminate toxicity to juvenile coho salmon (Oncorhynchus kisutch) as well as their macroinvertebrate prey, including cultured C. dubia and wild-collected mayfly nymphs (Baetis spp.). Untreated highway runoff was generally lethal to salmon and invertebrates, and this acute mortality was eliminated when the runoff was filtered through soil media in bioretention columns. Soil treatment also protected against sublethal reproductive toxicity in C. dubia. Thus, a relatively inexpensive GSI technology can be highly effective at reversing the acutely lethal and sublethal effects of urban runoff on multiple aquatic species. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Codeine and its alternates for pain and cough relief*

PubMed Central

Eddy, Nathan B.; Friebel, Hans; Hahn, Klaus-Jürgen; Halbach, Hans

1968-01-01

This report—the first of a series on codeine and its alternates for pain and cough relief—presents a detailed evaluation of experimental and clinical data concerning the analgesic action of codeine (the antitussive action will be assessed separately). The authors discuss the pharmacology of the drug, including side-effects and toxicity; effects on the respiratory, circulatory, digestive and urinary systems; tolerance, dependence and liability to abuse; metabolic effects; and mechanism of action. Though codeine is generally more toxic than morphine to animals on account of its convulsant action, it is less toxic to man, possibly because it produces less respiratory depression. Again, tolerance to its analgesic effects has been demonstrated in several animal species, but dependence in man is observed far less frequently than it is with morphine, and the abstinence syndrome is less intense. From their extensive review of the evidence available, the authors conclude that codeine is a good analgesic and that little risk to public health is likely to arise from its clinical use to relieve pain. PMID:4972938

Toxicity of formulants and heavy metals in glyphosate-based herbicides and other pesticides.

PubMed

Defarge, N; Spiroux de Vendômois, J; Séralini, G E

2018-01-01

The major pesticides of the world are glyphosate-based herbicides (GBH), and their toxicity is highly debated. To understand their mode of action, the comparative herbicidal and toxicological effects of glyphosate (G) alone and 14 of its formulations were studied in this work, as a model for pesticides. GBH are mixtures of water, with commonly 36-48% G claimed as the active principle. As with other pesticides, 10-20% of GBH consist of chemical formulants. We previously identified these by mass spectrometry and found them to be mainly families of petroleum-based oxidized molecules, such as POEA, and other contaminants. We exposed plants and human cells to the components of formulations, both mixed and separately, and measured toxicity and human cellular endocrine disruption below the direct toxicity experimentally measured threshold. G was only slightly toxic on plants at the recommended dilutions in agriculture, in contrast with the general belief. In the short term, the strong herbicidal and toxic properties of its formulations were exerted by the POEA formulant family alone. The toxic effects and endocrine disrupting properties of the formulations were mostly due to the formulants and not to G. In this work, we also identified by mass spectrometry the heavy metals arsenic, chromium, cobalt, lead and nickel, which are known to be toxic and endocrine disruptors, as contaminants in 22 pesticides, including 11 G-based ones. This could also explain some of the adverse effects of the pesticides. In in vivo chronic regulatory experiments that are used to establish the acceptable daily intakes of pesticides, G or other declared active ingredients in pesticides are assessed alone, without the formulants. Considering these new data, this assessment method appears insufficient to ensure safety. These results, taken together, shed a new light on the toxicity of these major herbicides and of pesticides in general.

Acute toxicity of anionic and non-ionic surfactants to aquatic organisms.

PubMed

Lechuga, M; Fernández-Serrano, M; Jurado, E; Núñez-Olea, J; Ríos, F

2016-03-01

The environmental risk of surfactants requires toxicity measurements. As different test organisms have different sensitivity to the toxics, it is necessary to establish the most appropriate organism to classify the surfactant as very toxic, toxic, harmful or safe, in order to establish the maximum permissible concentrations in aquatic ecosystems. We have determined the toxicity values of various anionic surfactants ether carboxylic derivatives using four test organisms: the freshwater crustacean Daphnia magna, the luminescent bacterium Vibrio fischeri, the microalgae Selenastrum capricornutum (freshwater algae) and Phaeodactylum tricornutum (seawater algae). In addition, in order to compare and classify the different families of surfactants, we have included a compilation of toxicity data of surfactants collected from literature. The results indicated that V. fischeri was more sensitive to the toxic effects of the surfactants than was D. magna or the microalgae, which was the least sensitive. This result shows that the most suitable toxicity assay for surfactants may be the one using V. fischeri. The toxicity data revealed considerable variation in toxicity responses with the structure of the surfactants regardless of the species tested. The toxicity data have been related to the structure of the surfactants, giving a mathematical relationship that helps to predict the toxic potential of a surfactant from its structure. Model-predicted toxicity agreed well with toxicity values reported in the literature for several surfactants previously studied. Predictive models of toxicity is a handy tool for providing a risk assessment that can be useful to establish the toxicity range for each surfactant and the different test organisms in order to select efficient surfactants with a lower impact on the aquatic environment. Copyright © 2015 Elsevier Inc. All rights reserved.

Prospective Environmental Risk Assessment for Sediment-Bound Organic Chemicals: A Proposal for Tiered Effect Assessment.

PubMed

Diepens, Noël J; Koelmans, Albert A; Baveco, Hans; van den Brink, Paul J; van den Heuvel-Greve, Martine J; Brock, Theo C M

A broadly accepted framework for prospective environmental risk assessment (ERA) of sediment-bound organic chemicals is currently lacking. Such a framework requires clear protection goals, evidence-based concepts that link exposure to effects and a transparent tiered-effect assessment. In this paper, we provide a tiered prospective sediment ERA procedure for organic chemicals in sediment, with a focus on the applicable European regulations and the underlying data requirements. Using the ecosystem services concept, we derived specific protection goals for ecosystem service providing units: microorganisms, benthic algae, sediment-rooted macrophytes, benthic invertebrates and benthic vertebrates. Triggers for sediment toxicity testing are discussed.We recommend a tiered approach (Tier 0 through Tier 3). Tier-0 is a cost-effective screening based on chronic water-exposure toxicity data for pelagic species and equilibrium partitioning. Tier-1 is based on spiked sediment laboratory toxicity tests with standard benthic test species and standardised test methods. If comparable chronic toxicity data for both standard and additional benthic test species are available, the Species Sensitivity Distribution (SSD) approach is a more viable Tier-2 option than the geometric mean approach. This paper includes criteria for accepting results of sediment-spiked single species toxicity tests in prospective ERA, and for the application of the SSD approach. We propose micro/mesocosm experiments with spiked sediment, to study colonisation success by benthic organisms, as a Tier-3 option. Ecological effect models can be used to supplement the experimental tiers. A strategy for unifying information from various tiers by experimental work and exposure-and effect modelling is provided.

Toxicology, structure-function relationship, and human and environmental health impacts of polychlorinated biphenyls: progress and problems.

PubMed Central

Safe, S

1993-01-01

Polychlorinated biphenyls (PCBs) are industrial compounds that have been detected as contaminants in almost every component of the global ecosystem including the air, water, sediments, fish, and wildlife and human adipose tissue, milk, and serum. PCBs in commercial products and environmental extracts are complex mixtures of isomers and congeners that can now be analyzed on a congener-specific basis using high-resolution gas chromatographic analysis. PCBs are metabolized primarily via mixed-function oxidases into a broad spectrum of metabolites. The results indicate that metabolic activation is not required for PCB toxicity, and the parent hydrocarbons are responsible for most of the biochemical and toxic responses elicited by these compounds. Some of these responses include developmental and reproductive toxicity, dermal toxicity, endocrine effects, hepatotoxicity, carcinogenesis, and the induction of diverse phase I and phase II drug-metabolizing enzymes. Many of the effects observed for the commercial PCBs are similar to those reported for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related compounds. Structure-function relationships for PCB congeners have identified two major structural classes of PCBs that elicit "TCDD-like" responses, namely, the coplanar PCBs (e.g., 3,3',4,4'-tetraCB, 3,3'4,4',5-pentaCB and 3,3',4,4',5,5'-hexaCB) and their mono-ortho coplanar derivatives. These compounds competitively bind to the TCDD or aryl hydrocarbon (Ah) receptor and exhibit Ah receptor agonist activity. In addition, other structural classes of PCBs elicit biochemical and toxic responses that are not mediated through the Ah receptor. The shor-term effects of PCBs on occupationally exposed humans appear to be reversible, and no consistent changes in overall mortality and cancer mortality have been reported. Recent studies have demonstrated that some developmental deficits in infants and children correlated with in utero exposure to PCBs; however, the etiologic agent(s) or structural class of PCBs responsible for these effects have not been delineated. In contrast, based on a toxic equivalency factor approach, the reproductive and developmental problems in certain wildlife populations appear to be related to the TCDD-like PCB congeners. PMID:8354174

Efficacy of different monotherapies in second-line treatment for small cell lung cancer: a meta-analysis of randomized controlled trials

PubMed Central

Luo, Qiuping; Wang, Ziwei; Li, Shengjie; Zhou, Jianying

2015-01-01

Second-line chemotherapy has been proved to be effective on patients with relapsed or refractory small cell lung cancer (SCLC). Although topotecan has been approved by many countries for the monotherapy with an acknowledged efficacy, its efficacy of low response rate and short median survival time is disappointing. Considering the optimal regimen of second-line therapy is yet uncertain, we conducted this meta-analysis to provide theoretical basis for making clinical decisions. A comprehensive electronic search was performed to identify eligible studies. The ending points included response, overall survival (OS), and adverse events. Odds ratios and 95% confidence interval were calculated to compare the effects. Six trials with 1369 patients were included. With regard to response rate, only amrubicin showed a significant improvement compared with topotecan. Irinotecan and etoposide did not show any advantages. When targeted on OS, neither of these monotherapy regimens exhibited any advantage when compared to topotecan. When aimed at toxicity, amrubicin showed a better effect on reducing hematologic toxicity, but a worse outcome on increasing the nonhematologic toxicity, whereas others showed equal efficacy. There is no strong evidence that any advantage for second-line treatment of SCLC when compared with topotecan, except amrubicin. And amrubicin seems to be superior to topotecan in terms of response rates, with a lower toxicity than topotecan, which is of high value in clinical application, and may be the direction of second-line monotherapy in the future. PMID:26770633

Toxicity, sublethal effects, and potential modes of action of select fungicides on freshwater fish and invertebrates

USGS Publications Warehouse

Elskus, Adria A.

2012-01-01

Despite decades of agricultural and urban use of fungicides and widespread detection of these pesticides in surface waters, relatively few data are available on the effects of fungicides on fish and invertebrates in the aquatic environment. Nine fungicides are reviewed in this report: azoxystrobin, boscalid, chlorothalonil, fludioxonil, myclobutanil, fenarimol, pyraclostrobin, pyrimethanil, and zoxamide. These fungicides were identified as emerging chemicals of concern because of their high or increasing global use rates, detection frequency in surface waters, or likely persistence in the environment. A review of the literature revealed significant sublethal effects of fungicides on fish, aquatic invertebrates, and ecosystems, including zooplankton and fish reproduction, fish immune function, zooplankton community composition, metabolic enzymes, and ecosystem processes, such as leaf decomposition in streams, among other biological effects. Some of these effects can occur at fungicide concentrations well below single-species acute lethality values (48- or 96-hour concentration that effects a response in 50 percent of the organisms, that is, effective concentration killing 50 percent of the organisms in 48 or 96 hours) and chronic sublethal values (for example, 21-day no observed adverse effects concentration), indicating that single-species toxicity values may dramatically underestimate the toxic potency of some fungicides. Fungicide modes of toxic action in fungi can sometimes reflect the biochemical and (or) physiological effects of fungicides observed in vertebrates and invertebrates; however, far more studies are needed to explore the potential to predict effects in nontarget organisms based on specific fungicide modes of toxic action. Fungicides can also have additive and (or) synergistic effects when used with other fungicides and insecticides, highlighting the need to study pesticide mixtures that occur in surface waters. For fungicides that partition to organic matter in sediment and soils, it is particularly important to determine their effects on freshwater mussels and other freshwater benthic invertebrates in contact with sediments, as available toxicity studies with pelagic species, mainly Daphnia magna, may not be representative of these benthic organisms. Finally, there is a critical need for studies of the chronic effects of fungicides on reproduction, immunocompetence, and ecosystem function; sublethal endpoints with population and community-level relevance.

The effects of PCBs and dioxins on child health.

PubMed

Lundqvist, Christofer; Zuurbier, Moniek; Leijs, Marike; Johansson, Carolina; Ceccatelli, Sandra; Saunders, Margaret; Schoeters, Greet; ten Tusscher, Gavin; Koppe, Janna G

2006-10-01

BACKGROUND/EXPOSURE: Dioxins and PCBs are highly persistent and highly toxic environmental pollutants which at present are derived mainly from waste incineration and food contamination. They are widespread in nature and pollute human food, including breast milk so that basically all children in Europe are exposed to measurable levels. RESULTS/TOXICITY IN CHILDREN: The toxicity of dioxins and PCBs are well described both from animal studies and from a number of human epidemiological studies including several large cohort studies. Especially developmental exposure has been shown to affect endocrine and cognitive systems negatively. Measurable outcomes include reduced IQ and changed behaviour. Foetotoxic effects with reduced birth weight and increased congenital anomalies such as cleft lip have also been described. Exposure to PCBs and dioxins must be considered also in the context of multiple exposure to several toxins simultaneously or sequentially. CONCLUSION/SUGGESTED ACTION: Some measures aimed at reducing exposure to dioxins have been partly successful in that the dioxin content of breast milk is going down. However, further steps to reduce exposure must be taken. We suggest legislative measures for reducing the re-entry of especially PCBs from waste into the environment. Individual pre-conception counselling is recommended in order to reduce developmental exposure and its consequences. Biomonitoring of the substances themselves in breast milk and foods is recommended as well as monitoring possible endocrine effects.

Development of spacecraft toxic gas removal agents

NASA Technical Reports Server (NTRS)

Moore, R. S.

1974-01-01

The development of agents suitable for removal of CO, NH3, NO2 SO2, and other spacecraft contaminants was approached. An extensive technology review was conducted, yielding a large number of potentially useful materials and/or concepts. Because the two toxic gases of greatest interest, CO and NH3, suggested the use of catalysis principles emphasis was placed on the intestigation of transition metals on various supports. Forty-three materials were prepared or obtained and 25 were tested. Gas chromatographic techniques were used to find seven candidates that effectively managed various combinations of the four toxic gases: none managed all. These candidates included six transition metal-containing preparations and a supported LiOH material. Three commercial charcoals showed some efficiency for the toxic gases and may constitute candidates for enhancement by doping with transition metals.

Local Control and Toxicity in a Large Cohort of Central Lung Tumors Treated With Stereotactic Body Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Modh, Ankit; Rimner, Andreas; Williams, Eric

2014-12-01

Purpose: Stereotactic body radiation therapy (SBRT) in central lung tumors has been associated with higher rates of severe toxicity. We sought to evaluate toxicity and local control in a large cohort and to identify predictive dosimetric parameters. Methods and Materials: We identified patients who received SBRT for central tumors according to either of 2 definitions. Local failure (LF) was estimated using a competing risks model, and multivariate analysis (MVA) was used to assess factors associated with LF. We reviewed patient toxicity and applied Cox proportional hazard analysis and log-rank tests to assess whether dose-volume metrics of normal structures correlated with pulmonarymore » toxicity. Results: One hundred twenty-five patients received SBRT for non-small cell lung cancer (n=103) or metastatic lesions (n=22), using intensity modulated radiation therapy. The most common dose was 45 Gy in 5 fractions. Median follow-up was 17.4 months. Incidence of toxicity ≥ grade 3 was 8.0%, including 5.6% pulmonary toxicity. Sixteen patients (12.8%) experienced esophageal toxicity ≥ grade 2, including 50% of patients in whom PTV overlapped the esophagus. There were 2 treatment-related deaths. Among patients receiving biologically effective dose (BED) ≥80 Gy (n=108), 2-year LF was 21%. On MVA, gross tumor volume (GTV) was significantly associated with LF. None of the studied dose-volume metrics of the lungs, heart, proximal bronchial tree (PBT), or 2 cm expansion of the PBT (“no-fly-zone” [NFZ]) correlated with pulmonary toxicity ≥grade 2. There were no differences in pulmonary toxicity between central tumors located inside the NFZ and those outside the NFZ but with planning target volume (PTV) intersecting the mediastinum. Conclusions: Using moderate doses, SBRT for central lung tumors achieves acceptable local control with low rates of severe toxicity. Dosimetric analysis showed no significant correlation between dose to the lungs, heart, or NFZ and severe pulmonary toxicity. Esophageal toxicity may be an underappreciated risk, particularly when PTV overlaps the esophagus.« less

Marijuana Revisited.

ERIC Educational Resources Information Center

Archer, James, Jr.; Lopata, Ann

1979-01-01

This review examines recent research on psychological effects of marijuana. The article contains material on potency, research problems, use patterns in the United States, and expectancy, as well as a review of research on acute effects, including psychosis, toxic delirium, acute anxiety, and brain damage. (Author)

Concentrated ambient ultrafine particle exposure induces cardiac change in young healthy volunteers

EPA Science Inventory

Exposure to ambient ultrafine particles has been associated with cardiopulmonary toxicity and mortality. Adverse effects specifically linked to ultrafine particles include loss of sympathovagal balance and altered hemostasis. To characterize the effects of ultrafine particles in ...

Toxics Use Reduction in the Home: Lessons Learned from Household Exposure Studies

PubMed Central

Dunagan, Sarah C.; Dodson, Robin E.; Rudel, Ruthann A.; Brody, Julia G.

2010-01-01

Workers and fence-line communities have been the first to benefit from the substantial reductions in toxic chemical use and byproducts in industrial production resulting from the Massachusetts Toxics Use Reduction Act (TURA). As TURA motivates reformulation of products as well as retooling of production processes, benefits could extend more broadly to large-scale reductions in everyday exposures for the general population. Household exposure studies, including those conducted by Silent Spring Institute, show that people are exposed to complex mixtures of indoor toxics from building materials and a myriad of consumer products. Pollutants in homes are likely to have multiple health effects because many are classified as endocrine disrupting compounds (EDCs), with the ability to interfere with the body's hormone system. Product-related EDCs measured in homes include phthalates, halogenated flame retardants, and alkylphenols. Silent Spring Institute's chemical analysis of personal care and cleaning products confirms many are potential sources of EDCs, highlighting the need for a more comprehensive toxics use reduction (TUR) approach to reduce those exposures. Toxics use reduction targeted at EDCs in consumer products has the potential to substantially reduce occupational and residential exposures. The lessons that have emerged from household exposure research can inform improved chemicals management policies at the state and national levels, leading to safer products and widespread health and environmental benefits. PMID:21516227

Acute toxicity and histopathological effects of naproxen in zebrafish (Danio rerio) early life stages.

PubMed

Li, Qian; Wang, Peipei; Chen, Ling; Gao, Hongwen; Wu, Lingling

2016-09-01

Zebrafish (Danio rerio) embryos and larvae were selected to investigate the potential risk and aquatic toxicity of a widely used pharmaceutical, naproxen. The acute toxicity of naproxen to embryos and larvae was measured, respectively. The histopathology was investigated in the liver of zebrafish larvae after 8-day embryo-larvae exposure to naproxen. The values of 96-h LC50 were 115.2 mg/L for embryos and 147.6 mg/L for larvae, indicating that zebrafish embryos were more sensitive than larvae to naproxen exposure. Large suites of symptoms were induced in zebrafish (D. rerio) early life stages by different dosages of naproxen, including hatching inhibition, lower heart rate, and morphological abnormalities. The most sensitive sub-lethal effect caused by naproxen was pericardial edema, the 72-h EC50 values of which for embryos and larvae were 98.3 and 149.0 mg/L, respectively. In addition, naproxen-treated zebrafish larvae exhibited histopathological liver damage, including swollen hepatocytes, vacuolar degeneration, and nuclei pycnosis. The results indicated that naproxen is a potential threat to aquatic organisms.

Protective effects of Sesamum indicum extract against oxidative stress induced by vanadium on isolated rat hepatocytes.

PubMed

Hosseini, Mir-Jamal; Shahraki, Jafar; Tafreshian, Saman; Salimi, Ahmad; Kamalinejad, Mohammad; Pourahmad, Jalal

2016-08-01

Vanadium toxicity is a challenging problem to human and animal health with no entirely understanding cytotoxic mechanisms. Previous studies in vanadium toxicity showed involvement of oxidative stress in isolated liver hepatocytes and mitochondria via increasing of ROS formation, release of cytochrome c and ATP depletion after incubation with different concentrations (25-200 µM). Therefore, we aimed to investigate the protective effects of Sesamum indicum seed extract (100-300 μg/mL) against oxidative stress induced by vanadium on isolated rat hepatocytes. Our results showed that quite similar to Alpha-tocopherol (100 µM), different concentrations of extract (100-300 μg/mL) protected the isolated hepatocyte against all oxidative stress/cytotoxicity markers induced by vanadium in including cell lysis, ROS generation, mitochondrial membrane potential decrease and lysosomal membrane damage. Besides, vanadium induced mitochondrial/lysosomal toxic interaction and vanadium reductive activation mediated by glutathione in vanadium toxicity was significantly (P < 0.05) ameliorated by Sesamum indicum extracts. These findings suggested a hepato-protective role for extracts against liver injury resulted from vanadium toxicity. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 979-985, 2016. © 2015 Wiley Periodicals, Inc.

Unraveling the molecular mechanism of photosynthetic toxicity of highly fluorescent silver nanoclusters to Scenedesmus obliquus.

PubMed

Zhang, Li; Goswami, Nirmal; Xie, Jianping; Zhang, Bo; He, Yiliang

2017-11-27

While the discovery of numerous attractive properties of silver at the nanoscale has increased their demand in many sectors including medicine, optics, sensing, painting and cosmetics, it has also raised wide public concerns about their effect on living organisms in aquatic environment. Despite the continuous effort to understand the various aspects of the toxicity of silver nanomaterials, the molecular level understanding on their cytotoxicity mechanism to biological organisms has remained unclear. Herein, we demonstrated the underlying mechanism of the photosynthetic toxicity against green algae namely, Scenedesmus obliquus by using an emerging silver nanomaterial, called silver nanoclusters (defined as r-Ag NCs). By exploiting the unique fluorescence properties of r-Ag NCs along with various other analytical/biological tools, we proposed that the photosynthetic toxicity of r-Ag NCs was largely attributed to the "joint-toxicity" effect of particulate form of r-Ag NCs and its released Ag + , which resulted in the disruption of the electron transport chain of light reaction and affected the content of key enzymes (RuBP carboxylase/ oxygenase) of Calvin cycle of algae cells. We believe that the present study can also be applied to the assessment of the ecological risk derived from other metal nanoparticles.

Conference summary & recent advances: The 8th Conference on Metal Toxicity and Carcinogenesis

PubMed Central

Zhou, Xixi; Burchiel, Scott W.; Hudson, Laurie G.; Liu, Ke Jian

2015-01-01

Diseases caused by occupational and environmental exposure to metals are a public health concern. The underlying molecular mechanisms of metal toxicity and carcinogenicity remain largely unknown. Over 130 scientists attended the 8th Conference on Metal Toxicity and Carcinogenesis, presenting their various research concerns and recent findings to stimulate interactions and collaborations among scientists in the field. Several major areas were emphasized, including human & population studies, molecular & cellular mechanisms, biological targets, epigenetic effects, metabolism, and metal mixtures. Here we summarize presentations at the conference sessions and highlight the attendees’ latest work published in this special issue of Biological Trace Element Research. PMID:25975949

Cytotoxicity and the induction of the stress protein Hsp 70 in Chang liver cells in response to zearalenone-induced oxidative stress.

PubMed

Lee, Hyungkyoung; Kang, Changgeun; Yoo, Yong-San; Hah, Do-Yun; Kim, Chung Hui; Kim, Euikyung; Kim, Jong Shu

2013-09-01

Zearalenone (ZEN) has been implicated in several cases of mycotoxicosis in farm animals and humans. The toxic effects of ZEN have been well characterized, but little is known regarding the mechanisms of ZEN toxicity, including the involvement of the oxidative stress pathway. Using Chang liver cells as a model, the aim of this study was to determine if ZEN could elevate the expression of the heat shock protein Hsp 70, induce cytotoxicity and modulate the levels of glutathione (GSH) and thiobarbituric acid reactive substance (TBARS). In addition, the cytoprotective effects of N-acetylcysteine amide (NACA) pre-treatment were assessed. Finally, the involvement of oxidative stress in ZEN-induced toxicity was confirmed. The results of this study demonstrated that ZEN-induced Hsp 70 expression in a dose- and time-dependent manners. This effect occurred at low-ZEN concentrations, and could therefore be considered a biomarker of ZEN-induced toxicity. The cytotoxicity was reduced when Chang liver cells were exposed to sub-lethal heat shock prior to ZEN treatment, demonstrating a cytoprotective effect of Hsp 70. This cytoprotective effect suggested that Hsp 70 might play a key role in the cellular defense mechanism. When cells were pre-treated with NACA prior to ZEN treatment, the cells were also protected from toxicity. This NACA cytoprotective effect suggested the involvement of oxidative stress in ZEN-induced toxicity, and this mechanism was supported by reduced Hsp 70 expression, inhibited cytolethality, increased GSH levels and decreased TBARS formation when cells were pre-treated with NACA prior to ZEN exposure. Our data clearly demonstrated that ZEN induced cytotoxicity in Chang liver cells by inhibiting cell proliferation, decreasing GSH levels and increasing TBARS formation in a dose-dependent manner. ZEN also, induced Hsp 70 expression, and the side effects of ZEN were significantly alleviated by pre-treatment with NACA. Oxidative stress is likely to be one of the primary pathways of ZEN toxicity. This oxidative stress may contribute, at least in part, to the mechanism of ZEN-induced cytotoxicity. Copyright © 2013 Elsevier B.V. All rights reserved.

Environmental transformations and ecological effects of iron-based nanoparticles.

PubMed

Lei, Cheng; Sun, Yuqing; Tsang, Daniel C W; Lin, Daohui

2018-01-01

The increasing application of iron-based nanoparticles (NPs), especially high concentrations of zero-valent iron nanoparticles (nZVI), has raised concerns regarding their environmental behavior and potential ecological effects. In the environment, iron-based NPs undergo physical, chemical, and/or biological transformations as influenced by environmental factors such as pH, ions, dissolved oxygen, natural organic matter (NOM), and biotas. This review presents recent research advances on environmental transformations of iron-based NPs, and articulates their relationships with the observed toxicities. The type and extent of physical, chemical, and biological transformations, including aggregation, oxidation, and bio-reduction, depend on the properties of NPs and the receiving environment. Toxicities of iron-based NPs to bacteria, algae, fish, and plants are increasingly observed, which are evaluated with a particular focus on the underlying mechanisms. The toxicity of iron-based NPs is a function of their properties, tolerance of test organisms, and environmental conditions. Oxidative stress induced by reactive oxygen species is considered as the primary toxic mechanism of iron-based NPs. Factors influencing the toxicity of iron-based NPs are addressed and environmental transformations play a significant role, for example, surface oxidation or coating by NOM generally lowers the toxicity of nZVI. Research gaps and future directions are suggested with an aim to boost concerted research efforts on environmental transformations and toxicity of iron-based NPs, e.g., toxicity studies of transformed NPs in field, expansion of toxicity endpoints, and roles of laden contaminants and surface coating. This review will enhance our understanding of potential risks of iron-based NPs and proper uses of environmentally benign NPs. Copyright © 2017 Elsevier Ltd. All rights reserved.

Acute toxicity of ingested fluoride.

PubMed

Whitford, Gary Milton

2011-01-01

This chapter discusses the characteristics and treatment of acute fluoride toxicity as well as the most common sources of overexposure, the doses that cause acute toxicity, and factors that can influence the clinical outcome. Cases of serious systemic toxicity and fatalities due to acute exposures are now rare, but overexposures causing toxic signs and symptoms are not. The clinical course of systemic toxicity from ingested fluoride begins with gastric signs and symptoms, and can develop with alarming rapidity. Treatment involves minimizing absorption by administering a solution containing calcium, monitoring and managing plasma calcium and potassium concentrations, acid-base status, and supporting vital functions. Approximately 30,000 calls to US poison control centers concerning acute exposures in children are made each year, most of which involve temporary gastrointestinal effects, but others require medical treatment. The most common sources of acute overexposures today are dental products - particularly dentifrices because of their relatively high fluoride concentrations, pleasant flavors, and their presence in non-secure locations in most homes. For example, ingestion of only 1.8 ounces of a standard fluoridated dentifrice (900-1,100 mg/kg) by a 10-kg child delivers enough fluoride to reach the 'probably toxic dose' (5 mg/kg body weight). Factors that may influence the clinical course of an overexposure include the chemical compound (e.g. NaF, MFP, etc.), the age and acid-base status of the individual, and the elapsed time between exposure and the initiation of treatment. While fluoride has well-established beneficial dental effects and cases of serious toxicity are now rare, the potential for toxicity requires that fluoride-containing materials be handled and stored with the respect they deserve. Copyright © 2011 S. Karger AG, Basel.

Reproductive and developmental toxicity of hydrofluorocarbons used as refrigerants.

PubMed

Ema, Makoto; Naya, Masato; Yoshida, Kikuo; Nagaosa, Ryuichi

2010-04-01

The present paper summarizes data on the reproductive and developmental toxicity of hydrofluorocarbons (HFCs), including pentafluoroethane (HFC-125), 1,1,1,2-tetrafluoroethane (HFC-134a), 1,1,1-trifluoroethane (HFC-143a), 1,1-difluoroethane (HFC-152a), difluoromethane (HFC-32) and 1,1,1,3,3-pentafluoropropane (HFC-245fa), used as refrigerants, published in openly available scientific literature. No developmental toxicity of HFC-125 was found even at 50,000 ppm in rats or rabbits. Although HFC-134a exhibited no dominant lethal effect or reproductive toxicity in rats, it caused low body weight in pre- and postnatal offspring and slightly retarded skeletal ossification in fetuses at 50,000 ppm in rats. No maternal or developmental toxicity was noted after exposure to HFC-143a even at 40,000 ppm in rats or rabbits or HFC-152a even at 50,000 ppm in rats. HFC-32 is slightly maternally and developmentally toxic at 50,000 ppm in rats, but not in rabbits. HFC-245fa caused decreases in maternal body weight and food consumption at 10,000 and 50,000 ppm and fetal weight at 50 000ppm. No evidence of teratogenicity for these HFCs was noted in rats or rabbits. There is limited information about the reproductive toxicity of these HFCs. Animal studies remain necessary for risk assessments of chemicals because it is difficult to find alternative methods to determine the toxic effects of chemicals. It is required to reduce emissions of organic vapors containing HFCs to reduce the risk of exposure. Copyright 2009 Elsevier Inc. All rights reserved.

B cell receptor inhibition as a target for CLL therapy.

PubMed

Jeyakumar, Deepa; O'Brien, Susan

2016-03-01

Inhibitors of the B cell receptor (BCR) represent an attractive therapeutic option for patients with chronic lymphocytic leukemia. Recently approved inhibitors of Bruton's tyrosine kinase (ibrutinib) and phosphatidylinositol 3-kinase (idelalisib), are promising agents because they are generally well tolerated and highly effective. These agents may be particularly important in the treatment of older patients who are less able to tolerate the myelosuppression (and infections) associated with chemoimmunotherapy. As a class of medications, BCR inhibitors have some unique side effects including redistribution lymphocytosis. Ibrutinib has specific toxicities including increased risk for bleeding and atrial fibrillation. Idelalisib also has some unique toxicities consisting of transaminitis, diarrhea and pneumonitis. Ongoing clinical trials are evaluating these agents in combination with antibodies, chemotherapy and other small molecules. Copyright © 2016 Elsevier Ltd. All rights reserved.

α-Synuclein in Parkinson's Disease

PubMed Central

Stefanis, Leonidas

2012-01-01

α-Synuclein is a presynaptic neuronal protein that is linked genetically and neuropathologically to Parkinson's disease (PD). α-Synuclein may contribute to PD pathogenesis in a number of ways, but it is generally thought that its aberrant soluble oligomeric conformations, termed protofibrils, are the toxic species that mediate disruption of cellular homeostasis and neuronal death, through effects on various intracellular targets, including synaptic function. Furthermore, secreted α-synuclein may exert deleterious effects on neighboring cells, including seeding of aggregation, thus possibly contributing to disease propagation. Although the extent to which α-synuclein is involved in all cases of PD is not clear, targeting the toxic functions conferred by this protein when it is dysregulated may lead to novel therapeutic strategies not only in PD, but also in other neurodegenerative conditions, termed synucleinopathies. PMID:22355802

DOE Office of Scientific and Technical Information (OSTI.GOV)

Belinsky, S. A.; Hoover, M. D.; Bradley, P. L.

This document from the Inhalation Toxicology Research Institute includes annual reports in the following general areas: (I) Aerosol Technology and Characterization of Airborne Materials; (II) Deposition, transport, and clearance of inhaled Toxicants; (III) Metabolism and Markers of Inhaled Toxicants; (IV) Carcinogenic Responses to Toxicants; (V) Mechanisms of carcinogenic response to Toxicants; (VI) Non carcinogenic responses to inhaled toxicants; (VII) Mechanisms of noncarcinogenic Responses to Inhaled Toxicants; (VIII) The application of Mathematical Modeling to Risk Estimates. 9 appendices are also included. Selected papers are indexed separately for inclusion in the Energy Science and Technology Database.

Effects of manufactured nanomaterials on fishes: a target organ and body systems physiology approach.

PubMed

Handy, R D; Al-Bairuty, G; Al-Jubory, A; Ramsden, C S; Boyle, D; Shaw, B J; Henry, T B

2011-10-01

Manufactured nanomaterials (NM) are already used in consumer products and exposure modelling predicts releases of ng to low µg l(-1) levels of NMs into surface waters. The exposure of aquatic ecosystems, and therefore fishes, to manufactured NMs is inevitable. This review uses a physiological approach to describe the known effects of NMs on the body systems of fishes and to identify the internal target organs, as well as outline aspects of colloid chemistry relevant to fish biology. The acute toxicity data, suggest that the lethal concentration for many NMs is in the mg l(-1) range, and a number of sublethal effects have been reported at concentrations from c. 100 µg to 1 mg l(-1). Exposure to NMs in the water column can cause respiratory toxicity involving altered ventilation, mucus secretion and gill pathology. This may not lead, however, to overt haematological disturbances in the short term. The internal target organs include the liver, spleen and haematopoietic system, kidney, gut and brain; with toxic effects involving oxidative stress, ionoregulatory disturbances and organ pathologies. Some pathology appears to be novel for NMs, such as vascular injury in the brain of rainbow trout Oncorhynchus mykiss with carbon nanotubes. A lack of analytical methods, however, has prevented the reporting of NM concentrations in fish tissues, and the precise uptake mechanisms across the gill or gut are yet to be elucidated. The few dietary exposure studies conducted show no effects on growth or food intake at 10-100 mg kg(-1) inclusions of NMs in the diet of O. mykiss, but there are biochemical disturbances. Early life stages are sensitive to NMs with reports of lethal toxicity and developmental defects. There are many data gaps, however, including how water quality alters physiological responses, effects on immunity and chronic exposure data at environmentally relevant concentrations. Overall, the data so far suggest that the manufactured NMs are not as toxic as some traditional chemicals (e.g. some dissolved metals) and the innovative, responsible, development of nanotechnology should continue, with potential benefits for aquaculture, fisheries and fish health diagnostics. © 2011 The Authors. Journal of Fish Biology © 2011 The Fisheries Society of the British Isles.

Ecotoxicology of organic contaminants to amphibians

USGS Publications Warehouse

Sparling, D.W.; Sparling, Donald W.; Linder, Greg L.; Bishop, Christine A.

2000-01-01

The effects of organic contaminants on amphibians are poorly known but of considerable interest. These contaminants include the highly toxic dioxins and furans as well as PCBs, PAHs and organochlorine pesticides. Although these compounds may have lower acute toxicity than dioxins and furans, they have been implicated in several problems associated with genotoxicity, endocrine disruption, malformations and reduced growth. There is evidence that amphibian tadpoles bioaccumulate these organic compounds and may have biological concentrating factors ranging in the hundreds. This chapter reviews what is known about the effects and concentrations of organic contaminants in amphibians and provides recommendations for further research

Pharmaceuticals and personal care products (PPCPs) are ecological disrupting compounds (EcoDC)

USGS Publications Warehouse

Richmond, Erinn; Grace, Michael; Kelly, John R.; Reisinger, Andrew; Rosi, Emma J.; Walters, David M.

2017-01-01

Pharmaceuticals and personal care products (PPCPs) are ubiquitous in freshwater ecosystems worldwide and are recognized as contaminants of concern. Currently, contaminants of concern are classified for their persistence, bioaccumulation, and toxicity (PBT criteria). PPCPs are not classified as persistent organic pollutants (POPs), although some PPCPs share characteristics similar to POPs. For example, PPCPs are known to be pseudopersistent due to constant discharge into the environment, often at low concentrations. At commonly reported environmental concentrations, PPCPs are rarely toxic, but the ability of these compounds to disrupt ecological processes and functions in freshwater ecosystems is often overlooked. Herein we briefly summarize recent studies highlighting the potential ecological effects of PPCPs, including effects on key ecological processes (e.g. primary productivity and community respiration), and we propose that appropriate screening for harmful effects of PPCPs in surface waters should be expanded to include Ecologically Disrupting Compounds (EcoDC) in addition to the established PBT criteria.

Comparison of IMRT versus 3D-CRT in the treatment of esophagus cancer

PubMed Central

Xu, Dandan; Li, Guowen; Li, Hongfei; Jia, Fei

2017-01-01

Abstract Background: Esophageal cancer (EC) is a common cancer with high mortality because of its rapid progression and poor prognosis. Radiotherapy is one of the most effective treatments for EC. Three-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT) are 2 recently developed radiotherapy techniques. IMRT is believed to be more effective than 3D-CRT in target coverage, dose homogeneity, and reducing toxicity to normal organs. However, these advantages have not been demonstrated in the treatment of EC. This meta-analysis was performed to compare IMRT and 3D-CRT in the treatment of EC in terms of dose–volume histograms and outcomes including survival and toxicity. Methods: A literature search was performed in PubMed, Embase, and the Cochrane library databases from their inceptions to Dec 30, 2016. Two authors independently assessed the included studies and extracted data. The average percent irradiated volumes of adjacent noncancerous organs were calculated and compared between IMRT and 3D-CRT. The odds ratio of overall survival (OS), and radiation pneumonitis and radiation esophagitis was also evaluated. Results: Totally 7 studies were included. Of them, 5 studies (80 patients) were included in the dosimetric comparison, 3 studies (871 patients) were included in the OS analysis, and 2 studies (205 patients) were included in the irradiation toxicity analysis. For lung in patients receiving doses ≥20 Gy and heart in patients receiving dose = 50 Gy, the average irradiated volumes of IMRT were less than those from 3D-CRT. IMRT resulted in a higher OS than 3D-CRT. However, no significant difference was observed in the incidence of radiation pneumonitis and radiation esophagitis between 2 radiotherapy techniques. Conclusion: Our data suggest that IMRT-delivered high radiation dose produces significantly less average percent volumes of irradiated lung and heart than 3D-CRT. IMRT is superior to 3D-CRT in the OS of EC while shows no benefit on radiation toxicity. PMID:28767597

Comparison of IMRT versus 3D-CRT in the treatment of esophagus cancer: A systematic review and meta-analysis.

PubMed

Xu, Dandan; Li, Guowen; Li, Hongfei; Jia, Fei

2017-08-01

Esophageal cancer (EC) is a common cancer with high mortality because of its rapid progression and poor prognosis. Radiotherapy is one of the most effective treatments for EC. Three-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT) are 2 recently developed radiotherapy techniques. IMRT is believed to be more effective than 3D-CRT in target coverage, dose homogeneity, and reducing toxicity to normal organs. However, these advantages have not been demonstrated in the treatment of EC. This meta-analysis was performed to compare IMRT and 3D-CRT in the treatment of EC in terms of dose-volume histograms and outcomes including survival and toxicity. A literature search was performed in PubMed, Embase, and the Cochrane library databases from their inceptions to Dec 30, 2016. Two authors independently assessed the included studies and extracted data. The average percent irradiated volumes of adjacent noncancerous organs were calculated and compared between IMRT and 3D-CRT. The odds ratio of overall survival (OS), and radiation pneumonitis and radiation esophagitis was also evaluated. Totally 7 studies were included. Of them, 5 studies (80 patients) were included in the dosimetric comparison, 3 studies (871 patients) were included in the OS analysis, and 2 studies (205 patients) were included in the irradiation toxicity analysis. For lung in patients receiving doses ≥20 Gy and heart in patients receiving dose = 50 Gy, the average irradiated volumes of IMRT were less than those from 3D-CRT. IMRT resulted in a higher OS than 3D-CRT. However, no significant difference was observed in the incidence of radiation pneumonitis and radiation esophagitis between 2 radiotherapy techniques. Our data suggest that IMRT-delivered high radiation dose produces significantly less average percent volumes of irradiated lung and heart than 3D-CRT. IMRT is superior to 3D-CRT in the OS of EC while shows no benefit on radiation toxicity.

Quinone-induced protein handling changes: Implications for major protein handling systems in quinone-mediated toxicity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xiong, Rui; Siegel, David; Ross, David, E-mail: david.ross@ucdenver.edu

2014-10-15

Para-quinones such as 1,4-Benzoquinone (BQ) and menadione (MD) and ortho-quinones including the oxidation products of catecholamines, are derived from xenobiotics as well as endogenous molecules. The effects of quinones on major protein handling systems in cells; the 20/26S proteasome, the ER stress response, autophagy, chaperone proteins and aggresome formation, have not been investigated in a systematic manner. Both BQ and aminochrome (AC) inhibited proteasomal activity and activated the ER stress response and autophagy in rat dopaminergic N27 cells. AC also induced aggresome formation while MD had little effect on any protein handling systems in N27 cells. The effect of NQO1more » on quinone induced protein handling changes and toxicity was examined using N27 cells stably transfected with NQO1 to generate an isogenic NQO1-overexpressing line. NQO1 protected against BQ–induced apoptosis but led to a potentiation of AC- and MD-induced apoptosis. Modulation of quinone-induced apoptosis in N27 and NQO1-overexpressing cells correlated only with changes in the ER stress response and not with changes in other protein handling systems. These data suggested that NQO1 modulated the ER stress response to potentiate toxicity of AC and MD, but protected against BQ toxicity. We further demonstrated that NQO1 mediated reduction to unstable hydroquinones and subsequent redox cycling was important for the activation of the ER stress response and toxicity for both AC and MD. In summary, our data demonstrate that quinone-specific changes in protein handling are evident in N27 cells and the induction of the ER stress response is associated with quinone-mediated toxicity. - Highlights: • Unstable hydroquinones contributed to quinone-induced ER stress and toxicity.« less

Comparative Analysis of the Relationship between Trichloroethylene Metabolism and Tissue-Specific Toxicity among Inbred Mouse Strains: Kidney Effects

PubMed Central

Yoo, Hong Sik; Bradford, Blair U.; Kosyk, Oksana; Uehara, Takeki; Shymonyak, Svitlana; Collins, Leonard B.; Bodnar, Wanda M.; Ball, Louise M.; Gold, Avram; Rusyn, Ivan

2014-01-01

Trichloroethylene (TCE) is a well-known environmental and occupational toxicant that is classified as carcinogenic to humans based on the epidemiological evidence of an association with higher risk of renal cell carcinoma. A number of scientific issues critical for assessing human health risks from TCE remain unresolved, such as the amount of kidney-toxic glutathione conjugation metabolites formed, inter-species and -individual differences, and the mode of action for kidney carcinogenicity. We hypothesized that TCE metabolite levels in the kidney are associated with kidney-specific toxicity. Oral dosing with TCE was conducted in sub-acute (600 mg/kg/d; 5 days; 7 inbred mouse strains) and sub-chronic (100 or 400 mg/kg/d; 1, 2, or 4 weeks; 2 inbred mouse strains) designs. We evaluated the quantitative relationship between strain-, dose-, and time-dependent formation of TCE metabolites from cytochrome P450-mediated oxidation [trichloroacetic acid (TCA), dichloroacetic acid (DCA), and trichloroethanol] and glutathione conjugation [S-(1,2-dichlorovinyl)-L-cysteine and S-(1,2-dichlorovinyl)glutathione], and various kidney toxicity phenotypes. In sub-acute study, we observed inter-strain differences in TCE metabolite levels in the kidney. In addition, we found that in several strains kidney-specific effects of TCE included induction of peroxisome proliferator-marker genes Cyp4a10 and Acox1, increased cell proliferation, and expression of KIM-1, a marker of tubular damage and regeneration. In sub-chronic study, peroxisome proliferator-marker gene induction and kidney toxicity diminished while cell proliferative response was elevated in a dose-dependent manner in NZW/LacJ, but not C57BL/6J mice. Overall, we show that TCE metabolite levels in the kidney are associated with kidney-specific toxicity and that these effects are strain-dependent. PMID:25424545

Air quality

Treesearch

Andrzej Bytnerowicz; Mark Fenn; Jonathan W. Long

2014-01-01

The major pollutants causing ecological harm in the Sierra Nevada are ozone, which can be toxic to plants, and nitrogen deposition, which can induce undesirable effects on terrestrial and aquatic ecosystems. Other airborne pollutants of concern include black carbon, particulate matter (PM), pesticides, and heavy metals, including mercury. Atmospheric pollutants that...

Effect of toxicity of Ag nanoparticles on SERS spectral variance of bacteria

NASA Astrophysics Data System (ADS)

Cui, Li; Chen, Shaode; Zhang, Kaisong

2015-02-01

Ag nanoparticles (NPs) have been extensively utilized in surface-enhanced Raman scattering (SERS) spectroscopy for bacterial identification. However, Ag NPs are toxic to bacteria. Whether such toxicity can affect SERS features of bacteria and interfere with bacterial identification is still unknown and needed to explore. Here, by carrying out a comparative study on non-toxic Au NPs with that on toxic Ag NPs, we investigated the influence of nanoparticle concentration and incubation time on bacterial SERS spectral variance, both of which were demonstrated to be closely related to the toxicity of Ag NPs. Sensitive spectral alterations were observed on Ag NPs with increase of NPs concentration or incubation time, accompanied with an obvious decrease in number of viable bacteria. In contrast, SERS spectra and viable bacterial number on Au NPs were rather constant under the same conditions. A further analysis on spectral changes demonstrated that it was cell response (i.e. metabolic activity or death) to the toxicity of Ag NPs causing spectral variance. However, biochemical responses to the toxicity of Ag were very different in different bacteria, indicating the complex toxic mechanism of Ag NPs. Ag NPs are toxic to a great variety of organisms, including bacteria, fungi, algae, protozoa etc., therefore, this work will be helpful in guiding the future application of SERS technique in various complex biological systems.

Effect of Shodhana Treatment on Chronic Toxicity and Recovery of Aconite

PubMed Central

Sarkar, P.K.; Prajapati, P.K.; Shukla, V.J.; Ravishankar, B.

2012-01-01

Aconite is one of the poisonous plants used therapeutically in practice of Ayurveda after proper treatment called as ‘Shodhana’. To determine the effect of Shodhana treatment on chronic toxicity and to assess the effect of recovery period after chronic toxicity of aconite. Raw aconite (RV), urine treated aconite (SM), and milk treated aconite (SD) were administered in 6.25 mg/kg dose in Charles Foster strain albino rats for 90 days for chronic toxicity. Six rats from each were kept for another 30 days without test drugs treatment to observe recovery from chronic toxicity. RV was found to be highly toxic in chronic exposure, SM had no apparent toxicity, but SD had mild toxicity in kidney. The toxicities of RV and SD were reversible, but sudden withdrawal of SM caused adverse effects, suggestive of tapering withdrawal. Shodhana treatments remove toxic effects from raw aconite. Chronic toxicity of aconite is reversible. Confirmed the arrangement of abstract PMID:22736901

Fatal serotonin toxicity caused by moclobemide and fluoxetine overdose.

PubMed

Wu, Ming-Ling; Deng, Jou-Fang

2011-01-01

Both moclobemide and fluoxetine are used in the treatment of depression, and have been shown to produce fewer side effects than conventional tricyclic antidepressants. A combination of moclobemide and fluoxetine has been used in refractory depression, however there is potential for severe serotonin toxicity. We describe a lethal case of serotonin toxicity in a 36 year-old woman after she ingested multiple drugs, including moclobemide 4500 mg, fluoxetine 200 mg, propranolol 300 mg and several benzodiazepines. The clinical features included coma, mydriasis, hyperthermia, tremor, hyperreflexia, rhabdomyolysis, renal failure and respiratory insufficiency. Eventually, the patient died of disseminated intravascular coagulation and circulatory collapse at 22.5 h postingestion. Toxicological analysis of the patient's blood confirmed high levels of moclobemide 150 μg/mL (therapeutic 1-3 μg/mL), fluoxetine 3750 ng/mL (therapeutic 47-469 ng/mL) and several benzodiazepines. In conclusion, a combination of moclobemide and fluoxetine should be avoided in depressed patients with high suicidal tendencies. Moreover, early recognition and aggressive intervention are the mainstays in the management of potentially life-threatening serotonin toxicity.

Assessing the toxic effects of DMSO on cord blood to determine exposure time limits and the optimum concentration for cryopreservation.

PubMed

Fry, L J; Querol, S; Gomez, S G; McArdle, S; Rees, R; Madrigal, J A

2015-08-01

Advantages of using cord blood (CB) over other sources of haematopoietic progenitor cells, such as bone marrow, include the ability to cryopreserve and bank the samples until requested for a transplant. Cryopreservation requires the addition of a cryoprotectant to prevent the formation of intracellular ice during freezing. Dimethyl sulphoxide (DMSO) is commonly used at a concentration of 10% (v/v); however, there is evidence to suggest this chemical is toxic to cells as well as to patients after infusion. The toxic effects of DMSO were assessed through cell viability and in vitro functional assays in fresh and post-thaw CB samples before determining the maximum exposure time and optimal concentration for cryopreservation. A dose-dependent toxicity of DMSO was observed in fresh samples with 40% removing all viable and functional haematopoietic progenitor cells (HPC). In fresh and post-thaw analysis, minimal toxic effect was observed when cryopreservation was delayed for up to 1 h after 10% DMSO addition. After thawing, DMSO washout was superior to dilution or unmanipulated when maintained for long periods (advantage observed 1 h after thawing). Finally, the optimum concentration for cryopreserving CB was found to be 7.5 to 10% with detrimental effects observed outside of this range. These results support the use of 7.5-10% as the optimal DMSO concentration and the maximum exposure time should be limited to <1 h prior to freezing and 30 min post-thaw. © 2015 International Society of Blood Transfusion.

Proactive aquatic ecotoxicological assessment of room-temperature ionic liquids

USGS Publications Warehouse

Kulacki, K.J.; Chaloner, D.T.; Larson, J.H.; Costello, D.M.; Evans-White, M. A.; Docherty, K.M.; Bernot, R.J.; Brueseke, M.A.; Kulpa, C.F.; Lamberti, G.A.

2011-01-01

Aquatic environments are being contaminated with a myriad of anthropogenic chemicals, a problem likely to continue due to both unintentional and intentional releases. To protect valuable natural resources, novel chemicals should be shown to be environmentally safe prior to use and potential release into the environment. Such proactive assessment is currently being applied to room-temperature ionic liquids (ILs). Because most ILs are water-soluble, their effects are likely to manifest in aquatic ecosystems. Information on the impacts of ILs on numerous aquatic organisms, focused primarily on acute LC50 and EC50 endpoints, is now available, and trends in toxicity are emerging. Cation structure tends to influence IL toxicity more so than anion structure, and within a cation class, the length of alkyl chain substituents is positively correlated with toxicity. While the effects of ILs on several aquatic organisms have been studied, the challenge for aquatic toxicology is now to predict the effects of ILs in complex natural environments that often include diverse mixtures of organisms, abiotic conditions, and additional stressors. To make robust predictions about ILs will require coupling of ecologically realistic laboratory and field experiments with standard toxicity bioassays and models. Such assessments would likely discourage the development of especially toxic ILs while shifting focus to those that are more environmentally benign. Understanding the broader ecological effects of emerging chemicals, incorporating that information into predictive models, and conveying the conclusions to those who develop, regulate, and use those chemicals, should help avoid future environmental degradation. ?? 2011 Bentham Science Publishers Ltd.

Atorvastatin and Fluoxetine Prevent Oxidative Stress and Mitochondrial Dysfunction Evoked by Glutamate Toxicity in Hippocampal Slices.

PubMed

Ludka, Fabiana K; Dal-Cim, Tharine; Binder, Luisa Bandeira; Constantino, Leandra Celso; Massari, Caio; Tasca, Carla I

2017-07-01

Atorvastatin has been shown to exert a neuroprotective action by counteracting glutamatergic toxicity. Recently, we have shown atorvastatin also exerts an antidepressant-like effect that depends on both glutamatergic and serotonergic systems modulation. Excitotoxicity is involved in several brain disorders including depression; thus, it is suggested that antidepressants may target glutamatergic system as a final common pathway. In this study, a comparison of the mechanisms involved in the putative neuroprotective effect of a repetitive atorvastatin or fluoxetine treatment against glutamate toxicity in hippocampal slices was performed. Adult Swiss mice were treated with atorvastatin (10 mg/kg, p.o.) or fluoxetine (10 mg/kg, p.o.), once a day during seven consecutive days. On the eighth day, animals were killed and hippocampal slices were obtained and subjected to an in vitro protocol of glutamate toxicity. An acute treatment of atorvastatin or fluoxetine was not neuroprotective; however, the repeated atorvastatin or fluoxetine treatment prevented the decrease in cellular viability induced by glutamate in hippocampal slices. The loss of cellular viability induced by glutamate was accompanied by increased D-aspartate release, increased reactive oxygen species (ROS) and nitric oxide (NO) production, and impaired mitochondrial membrane potential. Atorvastatin or fluoxetine repeated treatment also presented an antidepressant-like effect in the tail suspension test. Atorvastatin or fluoxetine treatment was effective in protecting mice hippocampal slices from glutamate toxicity by preventing the oxidative stress and mitochondrial dysfunction.

The U.S. Environmental Protection Agency strategic plan for evaluating the toxicity of chemicals.

PubMed

Firestone, Michael; Kavlock, Robert; Zenick, Hal; Kramer, Melissa

2010-02-01

In the 2007 report Toxicity Testing in the 21st Century: A Vision and a Strategy, the U.S. National Academy of Sciences envisioned a major transition in toxicity testing from cumbersome, expensive, and lengthy in vivo testing with qualitative endpoints, to in vitro robotic high-throughput screening with mechanistic quantitative parameters. Recognizing the need for agencies to partner and collaborate to ensure global harmonization, standardization, quality control and information sharing, the U.S. Environmental Protection Agency is leading by example and has established an intra-agency Future of Toxicity Testing Workgroup (FTTW). This workgroup has produced an ambitious blueprint for incorporating this new scientific paradigm to change the way chemicals are screened and evaluated for toxicity. Four main components of this strategy are discussed, as follows: (1) the impact and benefits of various types of regulatory activities, (2) chemical screening and prioritization, (3) toxicity pathway-based risk assessment, and (4) institutional transition. The new paradigm is predicated on the discovery of molecular perturbation pathways at the in vitro level that predict adverse health effects from xenobiotics exposure, and then extrapolating those events to the tissue, organ, or whole organisms by computational models. Research on these pathways will be integrated and compiled using the latest technology with the cooperation of global agencies, industry, and other stakeholders. The net result will be that chemical toxicity screening will become more efficient and cost-effective, include real-world exposure assessments, and eliminate currently used uncertainty factors.

Identification of compounds in heavy fuel oil that are chronically toxic to rainbow trout embryos by effects-driven chemical fractionation.

PubMed

Adams, Julie; Bornstein, Jason M; Munno, Keenan; Hollebone, Bruce; King, Thomas; Brown, R Stephen; Hodson, Peter V

2014-04-01

The present study isolated and identified compounds in heavy fuel oil 7102 (HFO 7102) that are bioavailable and chronically toxic to rainbow trout embryos (Oncorhynchus mykiss). An effects-driven chemical fractionation combined the chemical separation of oil with toxicity testing and chemical analyses of each fraction to identify the major classes of compounds associated with embryo toxicity. Toxicity was assessed with 2 exposure methods, a high-energy chemical dispersion of oil in water, which included oil droplets in test solutions, and water accommodated fractions which were produced by oiled gravel desorption columns, and which did not contain visible oil droplets. Fractions of HFO with high concentrations of naphthalenes, alkanes, asphaltenes, and resins were nontoxic to embryos over the range of concentrations tested. In contrast, fractions enriched with 3- to 4-ringed alkyl polycyclic aromatic hydrocarbons (PAHs) were embryotoxic, consistent with published studies of crude oils and individual alkyl PAHs. The rank order of fraction toxicity did not vary between the exposure methods and was consistent with their PAH content; fractions with higher-molecular weight alkyl PAHs were the most toxic. Exposure of juvenile trout to most fractions of HFO induced higher activities of cytochrome P450 enzymes, with a rank order of potency that varied with exposure method and differed somewhat from that of embryotoxicity. Induction reflected the bioavailability of PAHs but did not accurately predict embryotoxicity. © 2013 SETAC.

Developmental toxicity of PAH mixtures in fish early life stages. Part II: adverse effects in Japanese medaka.

PubMed

Le Bihanic, Florane; Clérandeau, Christelle; Le Menach, Karyn; Morin, Bénédicte; Budzinski, Hélène; Cousin, Xavier; Cachot, Jérôme

2014-12-01

In aquatic environments, polycyclic aromatic hydrocarbons (PAHs) mostly occur as complex mixtures, for which risk assessment remains problematic. To better understand the effects of PAH mixture toxicity on fish early life stages, this study compared the developmental toxicity of three PAH complex mixtures. These mixtures were extracted from a PAH-contaminated sediment (Seine estuary, France) and two oils (Arabian Light and Erika). For each fraction, artificial sediment was spiked at three different environmental concentrations roughly equivalent to 0.5, 4, and 10 μg total PAH g(-1) dw. Japanese medaka embryos were incubated on these PAH-spiked sediments throughout their development, right up until hatching. Several endpoints were recorded at different developmental stages, including acute endpoints, morphological abnormalities, larvae locomotion, and genotoxicity (comet and micronucleus assays). The three PAH fractions delayed hatching, induced developmental abnormalities, disrupted larvae swimming activity, and damaged DNA at environmental concentrations. Differences in toxicity levels, likely related to differences in PAH proportions, were highlighted between fractions. The Arabian Light and Erika petrogenic fractions, containing a high proportion of alkylated PAHs and low molecular weight PAHs, were more toxic to Japanese medaka early life stages than the pyrolytic fraction. This was not supported by the toxic equivalency approach, which appeared unsuitable for assessing the toxicity of the three PAH fractions to fish early life stages. This study highlights the potential risks posed by environmental mixtures of alkylated and low molecular weight PAHs to early stages of fish development.

Laboratory toxicity and benthic invertebrate field colonization of Upper Columbia River sediments: finding adverse effects using multiple lines of evidence.

PubMed

Fairchild, J F; Kemble, N E; Allert, A L; Brumbaugh, W G; Ingersoll, C G; Dowling, B; Gruenenfelder, C; Roland, J L

2012-07-01

From 1930 to 1995, the Upper Columbia River (UCR) of northeast Washington State received approximately 12 million metric tons of smelter slag and associated effluents from a large smelter facility located in Trail, British Columbia, approximately 10 km north of the United States-Canadian border. Studies conducted during the past two decades have demonstrated the presence of toxic concentrations of heavy metals in slag-based sandy sediments, including cadmium, copper, zinc, and lead in the UCR area as well as the downstream reservoir portion of Lake Roosevelt. We conducted standardized whole-sediment toxicity tests with the amphipod Hyalella azteca (28-day) and the midge Chironomus dilutus (10-day) on 11 samples, including both UCR and study-specific reference sediments. Metal concentrations in sediments were modeled for potential toxicity using three approaches: (1) probable effects quotients (PEQs) based on total recoverable metals (TRMs) and simultaneously extracted metals (SEMs); (2) SEMs corrected for acid-volatile sulfides (AVS; i.e., ∑SEM - AVS); and (3) ∑SEM - AVS normalized to the fractional organic carbon (f(oc)) (i.e., ∑SEM - AVS/f(oc)). The most highly metal-contaminated sample (∑PEQ(TRM) = 132; ∑PEQ(SEM) = 54; ∑SEM - AVS = 323; and ∑SEM - AVS/(foc) = 64,600 umol/g) from the UCR was dominated by weathered slag sediment particles and resulted in 80% mortality and 94% decrease in biomass of amphipods; in addition, this sample significantly decreased growth of midge by 10%. The traditional ∑AVS - SEM, uncorrected for organic carbon, was the most accurate approach for estimating the effects of metals in the UCR. Treatment of the toxic slag sediment with 20% Resinex SIR-300 metal-chelating resin significantly decreased the toxicity of the sample. Samples ∑SEM - AVS > 244 was not toxic to amphipods or midge in laboratory testing, indicating that this value may be an approximate threshold for effects in the UCR. In situ benthic invertebrate colonization studies in an experimental pond (8-week duration) indicated that two of the most metal-contaminated UCR sediments (dominated by high levels of sand-sized slag particles) exhibited decreased invertebrate colonization compared with sand-based reference sediments. Field-exposed SIR-300 resin samples also exhibited decreased invertebrate colonization numbers compared with reference materials, which may indicate behavioral avoidance of this material under field conditions. Multiple lines of evidence (analytical chemistry, laboratory toxicity, and field colonization results), along with findings from previous studies, indicate that high metal concentrations associated with slag-enriched sediments in the UCR are likely to adversely impact the growth and survival of native benthic invertebrate communities. Additional laboratory toxicity testing, refinement of the applications of sediment benchmarks for metal toxicity, and in situ benthic invertebrate studies will assist in better defining the spatial extent, temporal variations, and ecological impacts of metal-contaminated sediments in the UCR system.

Development and application of the adverse outcome pathway framework for understanding and predicting chronic toxicity: I. Challenges and research needs in ecotoxicology.

PubMed

Groh, Ksenia J; Carvalho, Raquel N; Chipman, James K; Denslow, Nancy D; Halder, Marlies; Murphy, Cheryl A; Roelofs, Dick; Rolaki, Alexandra; Schirmer, Kristin; Watanabe, Karen H

2015-02-01

To elucidate the effects of chemicals on populations of different species in the environment, efficient testing and modeling approaches are needed that consider multiple stressors and allow reliable extrapolation of responses across species. An adverse outcome pathway (AOP) is a concept that provides a framework for organizing knowledge about the progression of toxicity events across scales of biological organization that lead to adverse outcomes relevant for risk assessment. In this paper, we focus on exploring how the AOP concept can be used to guide research aimed at improving both our understanding of chronic toxicity, including delayed toxicity as well as epigenetic and transgenerational effects of chemicals, and our ability to predict adverse outcomes. A better understanding of the influence of subtle toxicity on individual and population fitness would support a broader integration of sublethal endpoints into risk assessment frameworks. Detailed mechanistic knowledge would facilitate the development of alternative testing methods as well as help prioritize higher tier toxicity testing. We argue that targeted development of AOPs supports both of these aspects by promoting the elucidation of molecular mechanisms and their contribution to relevant toxicity outcomes across biological scales. We further discuss information requirements and challenges in application of AOPs for chemical- and site-specific risk assessment and for extrapolation across species. We provide recommendations for potential extension of the AOP framework to incorporate information on exposure, toxicokinetics and situation-specific ecological contexts, and discuss common interfaces that can be employed to couple AOPs with computational modeling approaches and with evolutionary life history theory. The extended AOP framework can serve as a venue for integration of knowledge derived from various sources, including empirical data as well as molecular, quantitative and evolutionary-based models describing species responses to toxicants. This will allow a more efficient application of AOP knowledge for quantitative chemical- and site-specific risk assessment as well as for extrapolation across species in the future. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

76 FR 77703 - Hexythiazox; Pesticide Tolerances

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-14

... the relationship of the results of the studies to human risk. EPA has also considered available... effects including potential carcinogenicity of hexythiazox. Specific information on the studies received...-level (NOAEL) and the lowest-observed-adverse-effect- level (LOAEL) from the toxicity studies can be...

78 FR 13252 - Pyroxasulfone; Pesticide Tolerances

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-27

... one of the following methods: Federal eRulemaking Portal: http://www.regulations.gov . Follow the... relationship of the results of the studies to human risk. EPA has also considered available information... adverse effects in several target organs. Effects seen in animal studies included cardiac toxicity...

An analysis of the use of dogs in predicting human toxicology and drug safety.

PubMed

Bailey, Jarrod; Thew, Michelle; Balls, Michael

2013-11-01

Dogs remain the main non-rodent species in preclinical drug development. Despite the current dearth of new drug approvals and meagre pipelines, this continues, with little supportive evidence of its value or necessity. To estimate the evidential weight provided by canine data to the probability that a new drug may be toxic to humans, we have calculated Likelihood Ratios (LRs) for an extensive dataset of 2,366 drugs with both animal and human data, including tissue-level effects and Medical Dictionary for Regulatory Activities (MedDRA) Level 1-4 biomedical observations. The resulting LRs show that the absence of toxicity in dogs provides virtually no evidence that adverse drug reactions (ADRs) will also be absent in humans. While the LRs suggest that the presence of toxic effects in dogs can provide considerable evidential weight for a risk of potential ADRs in humans, this is highly inconsistent, varying by over two orders of magnitude for different classes of compounds and their effects. Our results therefore have important implications for the value of the dog in predicting human toxicity, and suggest that alternative methods are urgently required. 2013 FRAME.

Boron-containing acids: preliminary evaluation of acute toxicity and access to the brain determined by Raman scattering spectroscopy.

PubMed

Soriano-Ursúa, Marvin A; Farfán-García, Eunice D; López-Cabrera, Yessica; Querejeta, Enrique; Trujillo-Ferrara, José G

2014-01-01

Boron-containing compounds (BCCs), particularly boron containing acids (BCAs), have become attractive moieties or molecules in drug development. It has been suggested that when functional groups with boron atoms are added to well-known drugs, the latter are conferred with greater potency and efficacy in relation to their target receptors. However, the use of BCAs in drug development is limited due to the lack of a toxicological profile. Consequently, the aim of the present study was to evaluate the acute toxicity of boric and boronic acids. Thus, a determination was made of the lethal dose (LD50) of test compounds in male CD1 mice, as well as the effective dose required to negatively affect spontaneous motor activity and to produce notable behavioral abnormalities. After treatment of animals at different doses, macroscopic observations were made from a necropsy, and Raman scattering spectroscopic studies were carried out on brain tissue samples. In general, the results show that most of the tested BCAs have very low toxicity, evidenced by the high doses required to induce notable toxic effects (greater than 100 mg/kg of body weight for all compounds, except for 3-thyenilboronic acid). Such toxic effects, presumably mediated by action on the CNS, include eye damage, gastrointestinal effects (e.g., gastric-gut dilatation and fecal retention), sedation, hypnosis and/or trembling. This preliminary toxicological profile suggests that BCAs can be considered potential therapeutic agents or moieties to be added to other compounds in the development of new drugs. Future studies are required to explore possible chronic toxicity of BCCs. Copyright © 2013 Elsevier Inc. All rights reserved.

Hydroxylated polychlorinated biphenyls in the environment: sources, fate, and toxicities.

PubMed

Tehrani, Rouzbeh; Van Aken, Benoit

2014-05-01

Hydroxylated polychlorinated biphenyls (OH-PCBs) are produced in the environment by the oxidation of PCBs through a variety of mechanisms, including metabolic transformation in living organisms and abiotic reactions with hydroxyl radicals. As a consequence, OH-PCBs have been detected in a wide range of environmental samples, including animal tissues, water, and sediments. OH-PCBs have recently raised serious environmental concerns because they exert a variety of toxic effects at lower doses than the parent PCBs and they are disruptors of the endocrine system. Although evidence about the widespread dispersion of OH-PCBs in various compartments of the ecosystem has accumulated, little is currently known about their biodegradation and behavior in the environment. OH-PCBs are, today, increasingly considered as a new class of environmental contaminants that possess specific chemical, physical, and biological properties not shared with the parent PCBs. This article reviews recent findings regarding the sources, fate, and toxicities of OH-PCBs in the environment.

Radiotherapy Does Not Influence the Severe Pulmonary Toxicity Observed With the Administration of Gemcitabine and Bleomycin in Patients With Advanced-Stage Hodgkin's Lymphoma Treated With the BAGCOPP Regimen: A Report by the German Hodgkin's Lymphoma Study Group

DOE Office of Scientific and Technical Information (OSTI.GOV)

Macann, Andrew; Bredenfeld, Henning; Mueller, Rolf-Peter

2008-01-01

Purpose: To evaluate the effect of radiotherapy on the severe pulmonary toxicity observed in the pilot study of BAGCOPP (bleomycin, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone, and gemcitabine) for advanced-stage Hodgkin's lymphoma. Methods and Materials: Patients with Stage III or IV Hodgkin's lymphoma or Stage IIB with risk factors participated in this single-arm, multicenter pilot study. Results: Twenty-seven patients were enrolled on the study before its premature closure as a result of the development of serious pulmonary toxicity in 8 patients. The pulmonary toxicity occurred either during or immediately after the BAGCOPP chemotherapy course. Pulmonary toxicity contributed to one early fatalitymore » but resolved in the other 7 patients after cessation of gemcitabine and bleomycin, allowing continuation of therapy. Fifteen patients received consolidative radiotherapy, including 4 who previously had pulmonary toxicity. There were no reported cases of radiation pneumonitis and no exacerbation of pulmonary symptoms in the 4 patients who had had previous pulmonary toxicity. Conclusions: The severe pulmonary toxicity observed in this study has been attributed to an interaction between gemcitabine and bleomycin. Gemcitabine (when administered without bleomycin) remains of interest in Hodgkin's lymphoma and is being incorporated into a new German Hodgkin's Lymphoma Study Group protocol that also includes consolidative radiotherapy. This study supports the concept of the integration of radiotherapy in gemcitabine-containing regimens in Hodgkin's lymphoma if there is an interval of at least 4 weeks between the two modalities and with a schedule whereby radiotherapy follows the chemotherapy.« less

Contaminants in stream sediments from seven U.S. metropolitan areas: Data summary of a National Pilot Study

USGS Publications Warehouse

Moran, Patrick W.; Calhoun, Dan L.; Nowell, Lisa H.; Kemble, Nile E.; Ingersoll, Chris G.; Hladik, Michelle; Kuivila, Kathryn; Falcone, James A.; Gilliom, Robert J.

2012-01-01

This report presents data collected as a part of a synoptic survey of stream sediment contaminants, associated watershed characteristics and invertebrate responses in laboratory sediment toxicity tests from 98 streams (sites) in seven metropolitan study areas across the continental United States. The report presents methods, data, and sediment-quality guidelines, including the derivation of a new sediment pyrethroid probable effects concentration, for the purposes of relating measured contaminants to land use and toxicity evaluation. The study evaluated sites that ranged in their degree of relative urbanization within the study areas of Atlanta, Boston, Dallas-Fort Worth, Denver, Milwaukee-Green Bay, Salt Lake City, and Seattle-Tacoma. In all, 108 chemical analytes quantified in the study are presented, by class and number of individual compounds, as follows: polyaromatic hydrocarbons (PAHs) (28), organochlorine pesticides (OCs) (18), polychlorinated biphenyls (Aroclors) (3), pyrethroid insecticides (14), fipronil compounds (4), priority trace and other major elements (41). The potential of these sediments to cause toxicity to sediment-dwelling invertebrates was evaluated using two standard sediment toxicity tests: a 28-day growth and survival toxicity test with the amphipod Hyalella azteca, and a 10-day growth and survival toxicity test with the midge Chironomus dilutus. Further, approximately 95 relevant watershed and reach-level characteristics were generated and are presented to aid in interpretation and explanation of contaminant and toxicity patterns. Interpretation of the findings of this study, including the relationships with urbanization and other factors, the relationship between sediment toxicity and sediment chemistry in the seven study areas, and the sources and occurrence of pyrethroid insecticides, are discussed in detail in a forthcoming series of journal articles.

Cinnamon (Cinnamomum zeylanicum) as an antidote or a protective agent against natural or chemical toxicities: a review.

PubMed

Dorri, Mahyar; Hashemitabar, Shirin; Hosseinzadeh, Hossein

2018-01-10

Cinnamon (Cinnamomum zeylanicum, Lauraceae) is a food additive greatly used for its taste. However, recently this medicinal plant has been brought to attention due to its medical effects. Cinnamon has constituents such as cinnamaldehyde and cinnamic acid that offers some health benefits including antioxidant and free-radical scavenging properties, lowering of blood glucose, anti-cholesterolemic, analgesic, antimicrobial, anti-inflammatory, anti-yeast, anti-secretagogue, and anti-gastric ulcer effects. This review summarizes various in vitro and animal studies on the protective effects of cinnamon against natural and chemical toxins. These studies consider the antidotal and/or protective effects of cinnamon and its major constituents against natural toxins and chemical-induced toxicities. It has been mentioned that cinnamon and its main constituents can ameliorate the toxicity of chemical toxins in liver, kidney, blood, brain, embryo, reproductive system, heart, spleen in part through antioxidant effect, radical scavenging, reducing lipid peroxidation, anti-inflammatory, fungistatic and fungicidal activities, modulation of CK-MB, LDH, TNF-α, IL-6, mitogen-activated protein kinase (MAPK), and nuclear factor-ĸB (NF-ĸB) signaling pathways.

Suppression of calpain expression by NSAIDs is associated with inhibition of cell migration in rat duodenum.

PubMed

Silver, Kristopher; Littlejohn, A; Thomas, Laurel; Bawa, Bhupinder; Lillich, James D

2017-05-15

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for the alleviation of pain and inflammation, but these drugs are also associated with a suite of negative side effects. Gastrointestinal (GI) toxicity is particularly concerning since it affects an estimated 70% of individuals taking NSAIDs routinely, and evidence suggests the majority of toxicity is occurring in the small intestine. Traditionally, NSAID-induced GI toxicity has been associated with indiscriminate inhibition of cyclooxygenase isoforms, but other mechanisms, including inhibition of cell migration, intestinal restitution, and wound healing, are likely to contribute to toxicity. Previous efforts demonstrated that treatment of cultured intestinal epithelial cells (IEC) with NSAIDs inhibits expression and activity of calpain proteases, but the effects of specific inhibition of calpain expression in vitro or the effects of NSAIDs on intestinal cell migration in vivo remain to be determined. Accordingly, we examined the effect of suppression of calpain protease expression with siRNA on cell migration in cultured IECs and evaluated the effects of NSAID treatment on epithelial cell migration and calpain protease expression in rat duodenum. Our results show that calpain siRNA inhibits protease expression and slows migration in cultured IECs. Additionally, NSAID treatment of rats slowed migration up the villus axis and suppressed calpain expression in duodenal epithelial cells. Our results are supportive of the hypothesis that suppression of calpain expression leading to slowing of cell migration is a potential mechanism through which NSAIDs cause GI toxicity. Copyright © 2017 Elsevier B.V. All rights reserved.

Antioxidants as a Potential Preventive and Therapeutic Strategy for Cadmium.

PubMed

Brzóska, Malgorzata M; Borowska, Sylwia; Tomczyk, Michal

2016-01-01

Epidemiological studies provide a growing number of evidences that chronic exposure to relatively low levels of cadmium (Cd), nowadays taking place in industrialized countries, may cause health hazard. Thus, growing interest has been focused on effective ways of protection from adverse effects of exposure to this heavy metal. Because numerous effects to Cd's toxic action result from its prooxidative properties, it seems reasonable that special attention should be directed to agents that can prevent or reduce this metal-induced oxidative stress and its consequences in tissues, organs and systems at risk of toxicity, including liver, kidneys, testes, ears, eyes, cardiovascular system and nervous system as well as bone tissue. This review discusses a wide range of natural (plant and animal origin) and synthetic antioxidants together with many plant extracts (e.g. black and green tea, Aronia melanocarpa, Allium sativum, Allium cepa, Ocimum sanctum, Phoenix dactylifera, Physalis peruviana, Zingiber officinale) that have been shown to prevent from Cd toxicity. Moreover, some attention has been focused on the fact that substances not possessing antioxidative potential may also prevent Cd-induced oxidative stress and its consequences. So far, most of the data on the protective effects of the natural and synthetic antioxidants and plant extracts come from studies in animals' models; however, numerous of them seem to be promising preventive/therapeutic strategies for Cd toxicity in humans. Further investigation of prophylactic and therapeutic use of antioxidants in populations exposed to Cd environmentally and occupationally is warranted, given that therapeutically effective chelation therapy for this toxic metal is currently lacking.

Microcystin-LR toxicity on dominant copepods Eurytemora affinis and Pseudodiaptomus forbesi of the upper San Francisco Estuary.

PubMed

Ger, Kemal A; Teh, Swee J; Goldman, Charles R

2009-08-15

This study investigates the toxicity and post-exposure effects of dissolved microcystin (MC-LR) on the dominant copepods of the upper San Francisco Estuary (SFE), where blooms of the toxic cyanobacteria Microcystis aeruginosa coincide with record low levels in the abundance of pelagic organisms including phytoplankton, zooplankton, and fish. The potential negative impact of Microcystis on the copepods Eurytemora affinis and Pseudodiaptomus forbesi has raised concern for further depletion of high quality fish food. Response of copepods to MC-LR (MC) was determined using a 48-h standard static renewal method for acute toxicity testing. Following exposure, a life table test was performed to quantify any post-exposure impacts on survival and reproduction. The 48-h LC-50 and LC-10 values for MC were 1.55 and 0.14 mg/L for E. affinis; and 0.52 and 0.21 mg/L for P. forbesi. Copepod populations recovered once dissolved MC was removed and cultures returned to optimal conditions, suggesting no post-exposure effects of MC on copepod populations. Dissolved microcystin above 0.14 mg/L proved likely to have chronic effects on the survival of copepods in the SFE. Since such high concentrations are unlikely, toxicity from dissolved microcystin is not a direct threat to zooplankton of the SFE, and other mechanisms such as dietary exposure to Microcystis constitute a more severe risk.

Is There a Role for Oral or Intravenous Ascorbate (Vitamin C) in Treating Patients With Cancer? A Systematic Review

PubMed Central

Hutton, Brian; Ng, Terry; Shorr, Risa; Clemons, Mark

2015-01-01

Background. Many cancer patients receive supplemental ascorbate (vitamin C) in the belief that it synergizes the anticancer effects of chemotherapy and reduces its toxicity. Methods. A systematic review was performed to evaluate the antitumor effects and toxicity of ascorbate treatment. Medline (1946 to March 2014), EMBASE (1947 to March 2014), and the Cochrane central register (1993 to March 2014) were searched for randomized and observational studies. Results. Of 696 identified records, 61 full-text articles were screened and 34 were included. In total, 5 randomized controlled trials (RCTs) (n = 322), 12 phase I/II trials (n = 287), 6 observational studies (n = 7,599), and 11 case reports (n = 267) were identified. Because of study heterogeneity, no meta-analyses were performed. No RCTs reported any statistically significant improvements in overall or progression-free survival or reduced toxicity with ascorbate relative to control arm. Evidence for ascorbate’s antitumor effects was limited to case reports and observational and uncontrolled studies. Conclusion. There is no high-quality evidence to suggest that ascorbate supplementation in cancer patients either enhances the antitumor effects of chemotherapy or reduces its toxicity. Given the high financial and time costs to patients of this treatment, high-quality placebo-controlled trials are needed. PMID:25601965

Toxicity Effects of Functionalized Quantum Dots, Gold and Polystyrene Nanoparticles on Target Aquatic Biological Models: A Review.

PubMed

Libralato, Giovanni; Galdiero, Emilia; Falanga, Annarita; Carotenuto, Rosa; de Alteriis, Elisabetta; Guida, Marco

2017-08-31

Nano-based products are widespread in several sectors, including textiles, medical-products, cosmetics, paints and plastics. Nanosafety and safe-by-design are driving nanoparticle (NP) production and applications through NP functionalization (@NPs). Indeed, @NPs frequently present biological effects that differ from the parent material. This paper reviews the impact of quantum dots (QDs), gold nanoparticles (AuNPs), and polystyrene-cored NPs (PSNPs), evidencing the role of NP functionalization in toxicity definition. Key biological models were taken into consideration for NP evaluation: Saccharomyces cerevisiae , fresh- (F) and saltwater (S) microalgae ( Raphidocelis subcapitata (F), Scenedesmus obliquus (F) and Chlorella spp. (F), and Phaeodactylum tricornutum (S)), Daphnia magna , and Xenopus laevis . QDs are quite widespread in technological devices, and they are known to induce genotoxicity and oxidative stress that can drastically change according to the coating employed. For example, AuNPs are frequently functionalized with antimicrobial peptides, which is shown to both increase their activity and decrease the relative environmental toxicity. P-NPs are frequently coated with NH₂ - for cationic and COOH - for anionic surfaces, but when positively charged toxicity effects can be observed. Careful assessment of functionalized and non-functionalized NPs is compulsory to also understand their potential direct and indirect effects when the coating is removed or degraded.

Atomic charges of individual reactive chemicals in binary mixtures determine their joint effects: an example of cyanogenic toxicants and aldehydes.

PubMed

Tian, Dayong; Lin, Zhifen; Yin, Daqiang; Zhang, Yalei; Kong, Deyang

2012-02-01

Environmental contaminants are usually encountered as mixtures, and many of these mixtures yield synergistic or antagonistic effects attributable to an intracellular chemical reaction that pose a potential threat on ecological systems. However, how atomic charges of individual chemicals determine their intracellular chemical reactions, and then determine the joint effects for mixtures containing reactive toxicants, is not well understood. To address this issue, the joint effects between cyanogenic toxicants and aldehydes on Photobacterium phosphoreum were observed in the present study. Their toxicological joint effects differed from one another. This difference is inherently related to the two atomic charges of the individual chemicals: the oxygen charge of -CHO (O(aldehyde toxicant)) in aldehyde toxicants and the carbon-atom charge of a carbon chain in the cyanogenic toxicant (C(cyanogenic toxicant)). Based on these two atomic charges, the following QSAR (quantitative structure-activity relationship) model was proposed: When (O(aldehyde toxicant) -C(cyanogenic toxicant) )> -0.125, the joint effect of equitoxic binary mixtures at median inhibition (TU, the sum of toxic units) can be calculated as TU = 1.00 ± 0.20; when (O(aldehyde toxicant) -C(cyanogenic toxicant) ) ≤ -0.125, the joint effect can be calculated using TU = - 27.6 x O (aldehyde toxicant) - 5.22 x C (cyanogenic toxicant) - 6.97 (n = 40, r = 0.887, SE = 0.195, F = 140, p < 0.001, q(2) (Loo) = 0.748; SE is the standard error of the regression, F is the F test statistic). The result provides insight into the relationship between the atomic charges and the joint effects for mixtures containing cyanogenic toxicants and aldehydes. This demonstrates that the essence of the joint effects resulting from intracellular chemical reactions depends on the atomic charges of individual chemicals. The present study provides a possible approach for the development of a QSAR model for mixtures containing reactive toxicants based on the atomic charges. Copyright © 2011 SETAC.

The toxicity of picaridin containing insect repellent reported to the National Poison Data System.

PubMed

Charlton, Nathan P; Murphy, Lauren T; Parker Cote, Jennifer L; Vakkalanka, J Priyanka

2016-09-01

While low toxicity is reported, there are sparse data on the safety of acute picaridin (icaridin) exposures in humans. The purpose of this study was to review National Poison Data System (NPDS) data regarding ingestion of insect repellents containing picaridin and compare those to insect repellents containing DEET and other insect repellents not containing DEET. NPDS was queried for single agent human insect repellent ingestions reported between 1 January 2000 and 31 May 2015 using the American Association of Poison Control Center generic categories 201048 (Insect Repellents with DEET) and 201049 (Insect Repellents without DEET). Picaridin-containing product exposures were assessed using Poisindex(®) product ID 6744589. Insect repellents of unknown type were not included. 68,429 exposures occurred; 24% were non-DEET-containing products, of which 2% were picaridin-containing products. Among picaridin exposures, 92.9% were managed outside of a health-care facility; there were no reported cases of major effect or death, and only one case of moderate effect. Primary symptoms across all insect repellent exposures included ocular irritation/pain, vomiting, red eye/conjunctivitis, and oral irritation. Treatment primarily included dilution/irrigation/wash. Unintentional ingestion of picaridin-containing and other insect repellents was associated only with minor toxicity and was generally managed outside of a health-care facility.

ToxCast Phase I

EPA Pesticide Factsheets

Background: Chemical toxicity testing is being transformed by advances in biology and computer modeling, concerns over animal use and the thousands of environmental chemicals lacking toxicity data. EPA's ToxCast program aims to address these concerns by screening and prioritizing chemicals for potential human toxicity using in vitro assays and in silico approaches. Objectives: This project aims to evaluate the use of in vitro assays for understanding the types of molecular and pathway perturbations caused by environmental chemicals and to build initial prioritization models of in vivo toxicity. Methods: We tested 309 mostly pesticide active chemicals in 467 assays across 9 technologies, including high-throughput cell-free assays and cell-based assays in multiple human primary cells and cell lines, plus rat primary hepatocytes. Both individual and composite scores for effects on genes and pathways were analyzed. Results: Chemicals display a broad spectrum of activity at the molecular and pathway levels. Many expected interactions are seen, including endocrine and xenobiotic metabolism enzyme activity. Chemicals range in promiscuity across pathways, from no activity to affecting dozens of pathways. We find a statistically significant inverse association between the number of pathways perturbed by a chemical at low in vitro concentrations and the lowest in vivo dose at which a chemical causes toxicity. We also find associations between a small set in vitro ass

Effect of diet quality on chronic toxicity of aqueous lead to the amphipod Hyalella azteca

USGS Publications Warehouse

Besser, John M.; Ivey, Chris D.; Brumbaugh, William G.; Ingersoll, Christopher G.

2016-01-01

The authors investigated the chronic toxicity of aqueous Pb to the amphipod Hyalella azteca (Hyalella) in 42-d tests using 2 different diets: 1) the yeastþcereal leafþtrout pellet (YCT) diet, fed at the uniform low ration used in standard methods for sediment toxicity tests; and 2) a new diet of diatomsþTetraMin flakes (DT), fed at increasing rations over time, that has been optimized for use in Hyalella water-only tests. Test endpoints included survival, weight, biomass, fecundity, and total young. Lethal effects of Pb were similar for the DT and YCT tests (20% lethal concentration [LC20]¼13 mg/L and 15mg/L, respectively, as filterable Pb). In contrast, weight and fecundity endpoints were not significantly affected in the DT test at Pb concentrations up to 63 mg/L, but these endpoints were significantly reduced by Pb in the YCT test—and in a 2005 test in the same laboratory with a diet of conditioned Rabbit Chow (RC-2005). The fecundity and total young endpoints from the YCT and RC-2005 tests were considered unreliable because fecundity in controls did not meet test acceptability criteria, but both of these tests still produced lower Pb effect concentrations (for weight or biomass) than the test with the DT diet. The lowest biotic ligand model–normalized effect concentrations for the 3 tests ranged from 3.7mg/L (weight 20% effect concentration [EC20] for the RC-2005 test) to 8.2 mg/L (total young EC20 for the DT test), values that would rank Hyalella as the second or third most sensitive of 13 genera in a species sensitivity distribution for chronic Pb toxicity. These results demonstrate that toxicity tests with Hyalella fed optimal diets can meet more stringent test acceptability criteria for control performance, but suggest that results of these tests may underestimate sublethal toxic effects of Pb to Hyalella under suboptimal feeding regimes.

Evaluation and comparison of bisphenol A analog activity ...

EPA Pesticide Factsheets

Bisphenol A (BPA) is used in consumer products and industrial applications, primarily in plastics, and has been detected in the environment, human urine, blood, and breast milk. Mainly studied as an endocrine disruptor, other toxicities, including obesity, metabolic conditions such as diabetes, and neurodevelopmental effects have also been associated with exposure to BPA, indicating that its effects may not be limited to estrogenicity. In addition, a number of BPA analogs are in use and may exhibit other additional toxicities. To address these unknowns, we examined the bioactivity of 21 BPA analogs across a selection of ToxCast/Tox21 assays grouped by 7 gene sets including estrogen receptor (ER), androgen receptor (AR), thyroid receptor (TR), peroxisome proliferator-activated receptor (PPAR), pregnane x receptor (PXR), aromatase (AROM), and aryl hydrocarbon receptor (AHR). The most active compounds were bisphenol AF (BPAF) (ER, AR, AROM, AHR), bisphenol A glycidyl methacrylate (TR), 3,3’,5,5’-tetrabromobisphenol A (PPAR) and bisphenol B (BPB) (PXR). We used these data to produce toxicological prioritization index (ToxPi) scores and images to integrate and visually compare the toxicity profiles across all gene sets. The compounds with highest ToxPi scores were BPAF, BPA and BPB. We also mapped the intended gene targets for all ToxCast assays to their associated KEGG BRITE protein families in order to characterize their toxicity profiles on a broader spectr

Cypermethrin induced toxicities in fish and adverse health outcomes: Its prevention and control measure adaptation.

PubMed

Ullah, Sana; Zuberi, Amina; Alagawany, Mahmoud; Farag, Mayada Ragab; Dadar, Maryam; Karthik, Kumaragurubaran; Tiwari, Ruchi; Dhama, Kuldeep; Iqbal, Hafiz M N

2018-01-15

Pesticides are being widely employed in the modern agriculture, though in different quantities, across the globe. Although it is useful for crops yield enhancement, however, there are the serious environment, health and safety related concerns for aquatic and terrestrial living biomes that include humans, animals, and plants. Various in practice and emerging pesticides adversely affect the survival, development and biological systems stability. Several research efforts have been made to highlight the bio-safety and toxicological features of toxicants through risk assessment studies using different animal models, e.g., different fish species. Among several pesticides, cypermethrin is extensively used in agriculture and households, and the reported concentrations of this pesticide in different water bodies including rivers and streams, soil and even in rainwater are threatening. Consequently, cypermethrin is considered for risk assessment studies to know about its deep and different level of toxicological effects subject to its dose, exposure time and route. The cypermethrin existence/persistence in the environment is posing a severe threat to humans as well as another non-target terrestrial and aquatic organism. Herein, the toxic effects of pesticides, with special reference to cypermethrin, on fish, the mode of toxicity, concerns regarding public health and harmful impacts on human beings are comprehensively reviewed. The information is also given on their appropriate control and prevention strategies. Copyright © 2017 Elsevier Ltd. All rights reserved.

General aspects of metal toxicity.

PubMed

Kozlowski, H; Kolkowska, P; Watly, J; Krzywoszynska, K; Potocki, S

2014-01-01

This review is focused on the general mechanisms of metal toxicity in humans. The possible and mainly confirmed mechanisms of their action are discussed. The metals are divided into four groups due to their toxic effects. First group comprises of metal ions acting as Fenton reaction catalyst mainly iron and copper. These types of metal ions participate in generation of the reactive oxygen species. Metals such as nickel, cadmium and chromium are considered as carcinogenic agents. Aluminum, lead and tin are involved in neurotoxicity. The representative of the last group is mercury, which may be considered as a generally toxic metal. Fenton reaction is a naturally occurring process producing most active oxygen species, hydroxyl radical: Fe(2+) + He2O2 ↔ Fe(3+) + OH(-) + OH(•) It is able to oxidize most of the biomolecules including DNA, proteins, lipids etc. The effect of toxicity depends on the damage of molecules i.e. production site of the hydroxyl radical. Chromium toxicity depends critically on its oxidation state. The most hazardous seems to be Cr(6+) (chromates) which are one of the strongest inorganic carcinogenic agents. Cr(6+) species act also as oxidative agents damaging among other nucleic acids. Redox inactive Al(3+), Cd(2+) or Hg(2+) may interfere with biology of other metal ions e.g. by occupying metal binding sites in biomolecules. All these aspects will be discussed in the review.

DOPA Decarboxylase Modulates Tau Toxicity.

PubMed

Kow, Rebecca L; Sikkema, Carl; Wheeler, Jeanna M; Wilkinson, Charles W; Kraemer, Brian C

2018-03-01

The microtubule-associated protein tau accumulates into toxic aggregates in multiple neurodegenerative diseases. We found previously that loss of D 2 -family dopamine receptors ameliorated tauopathy in multiple models including a Caenorhabditis elegans model of tauopathy. To better understand how loss of D 2 -family dopamine receptors can ameliorate tau toxicity, we screened a collection of C. elegans mutations in dopamine-related genes (n = 45) for changes in tau transgene-induced behavioral defects. These included many genes responsible for dopamine synthesis, metabolism, and signaling downstream of the D 2 receptors. We identified one dopamine synthesis gene, DOPA decarboxylase (DDC), as a suppressor of tau toxicity in tau transgenic worms. Loss of the C. elegans DDC gene, bas-1, ameliorated the behavioral deficits of tau transgenic worms, reduced phosphorylated and detergent-insoluble tau accumulation, and reduced tau-mediated neuron loss. Loss of function in other genes in the dopamine and serotonin synthesis pathways did not alter tau-induced toxicity; however, their function is required for the suppression of tau toxicity by bas-1. Additional loss of D 2 -family dopamine receptors did not synergize with bas-1 suppression of tauopathy phenotypes. Loss of the DDC bas-1 reduced tau-induced toxicity in a C. elegans model of tauopathy, while loss of no other dopamine or serotonin synthesis genes tested had this effect. Because loss of activity upstream of DDC could reduce suppression of tau by DDC, this suggests the possibility that loss of DDC suppresses tau via the combined accumulation of dopamine precursor levodopa and serotonin precursor 5-hydroxytryptophan. Published by Elsevier Inc.

A Microfluidic Device for Continuous Sensing of Systemic Acute Toxicants in Drinking Water

PubMed Central

Zhao, Xinyan; Dong, Tao

2013-01-01

A bioluminescent-cell-based microfluidic device for sensing toxicants in drinking water was designed and fabricated. The system employed Vibrio fischeri cells as broad-spectrum sensors to monitor potential systemic cell toxicants in water, such as heavy metal ions and phenol. Specifically, the chip was designed for continuous detection. The chip design included two counter-flow micromixers, a T-junction droplet generator and six spiral microchannels. The cell suspension and water sample were introduced into the micromixers and dispersed into droplets in the air flow. This guaranteed sufficient oxygen supply for the cell sensors. Copper (Cu2+), zinc (Zn2+), potassium dichromate and 3,5-dichlorophenol were selected as typical toxicants to validate the sensing system. Preliminary tests verified that the system was an effective screening tool for acute toxicants although it could not recognize or quantify specific toxicants. A distinct non-linear relationship was observed between the zinc ion concentration and the Relative Luminescence Units (RLU) obtained during testing. Thus, the concentration of simple toxic chemicals in water can be roughly estimated by this system. The proposed device shows great promise for an early warning system for water safety. PMID:24300075

Applicability of ambient toxicity testing to national or regional water-quality assessment

USGS Publications Warehouse

Elder, John F.

1990-01-01

Comprehensive assessment of the quality of natural waters requires a multifaceted approach. Descriptions of existing conditions may be achieved by various kinds of chemical and hydrologic analyses, whereas information about the effects of such conditions on living organisms depends on biological monitoring. Toxicity testing is one type of biological monitoring that can be used to identify possible effects of toxic contaminants. Based on experimentation designed to monitor responses of organisms to environmental stresses, toxicity testing may have diverse purposes in water-quality assessments. These purposes may include identification of areas that warrant further study because of poor water quality or unusual ecological features, verification of other types of monitoring, or assessment of contaminant effects on aquatic communities. Toxicity-test results are most effective when used as a complement to chemical analyses, hydrologic measurements, and other biological monitoring. However, all toxicity-testing procedures have certain limitations that must be considered in developing the methodology and applications of toxicity testing in any large-scale water-quality-assessment program. A wide variety of toxicity-test methods have been developed to fulfill the needs of diverse applications. The methods differ primarily in the selections made relative to four characteristics: (1) test species, (2) endpoint (acute or chronic), (3) test-enclosure type, and (4) test substance (toxicant) that functions as the environmental stress. Toxicity-test approaches vary in their capacity to meet the needs of large-scale assessments of existing water quality. Ambient testing, whereby the test organism is exposed to naturally occurring substances that contain toxicant mixtures in an organic or inorganic matrix, is more likely to meet these needs than are procedures that call for exposure of the test organisms to known concentrations of a single toxicant. However, meaningful interpretation of ambient test results depends on the existence of accompanying chemical analysis of the ambient media. The ambient test substance may be water or sediments. Sediment tests have had limited application, but they are useful because most toxicants tend to accumulate in sediments and many test species either inhabit the sediments or are in frequent contact with them. Biochemical testing methods, which have been developing rapidly in recent years, are likely to be among the most useful procedures for large-scale water-quality assessments. They are relatively rapid and simple, and more. importantly, they focus on biochemical changes that are the initial responses of virtually all organisms to environmental stimuli. Most species are sensitive to relatively few toxicants, and their sensitivities vary as conditions change. Therefore, each test method has particular uses and limitations, and no single test has universal applicability. One of the most informative approaches to toxicity testing is to combine biochemical tests with other test methods in a 'battery of tests' that is diversified enough to characterize different types of toxicants and different trophic levels. However, such an approach can be costly, and if not carefully designed, it may not yield enough additional information to warrant the additional cost. The application of toxicity tests to large-scale water-quality assessments is hampered by a number of difficulties. Toxicity tests often are not sensitive enough to enable detection of most contaminant problems in the natural environment. Furthermore, because sensitivities among different species and test conditions can be highly variable, conclusions about the toxicant problems of an ecosystem are strongly dependent on the test procedure used. In addition, the experimental systems used in toxicity tests cannot replicate the complexity or variability of natural conditions, and positive test results cannot identify the source or nature of

Ashwagandha leaf derived withanone protects normal human cells against the toxicity of methoxyacetic acid, a major industrial metabolite.

PubMed

Priyandoko, Didik; Ishii, Tetsuro; Kaul, Sunil C; Wadhwa, Renu

2011-05-04

The present day lifestyle heavily depends on industrial chemicals in the form of agriculture, cosmetics, textiles and medical products. Since the toxicity of the industrial chemicals has been a concern to human health, the need for alternative non-toxic natural products or adjuvants that serve as antidotes are in high demand. We have investigated the effects of Ayurvedic herb Ashwagandha (Withania somnifera) leaf extract on methoxyacetic acid (MAA) induced toxicity. MAA is a major metabolite of ester phthalates that are commonly used in industry as gelling, viscosity and stabilizer reagents. We report that the MAA cause premature senescence of normal human cells by mechanisms that involve ROS generation, DNA and mitochondrial damage. Withanone protects cells from MAA-induced toxicity by suppressing the ROS levels, DNA and mitochondrial damage, and induction of cell defense signaling pathways including Nrf2 and proteasomal degradation. These findings warrant further basic and clinical studies that may promote the use of withanone as a health adjuvant in a variety of consumer products where the toxicity has been a concern because of the use of ester phthalates.

Thymidine analogue-sparing highly active antiretroviral therapy (HAART).

PubMed

Nolan, David; Mallal, Simon

2003-02-01

The use of alternative nucleoside reverse transcriptase inhibitors (NRTIs) to the thymidine analogues stavudine (d4T) and zidovudine(ZDV) has been advocated as a means of limiting long-term NRTI-associated toxicity, particularly the development of lipoatrophy or fat wasting. This approach reflects an increasing knowledge of the distinct toxicity profiles of NRTI drugs. However, recent clinical trials have demonstrated that the use of thymidine analogue NRTIs and newer alternative backbone NRTIs, such as tenofovir (TNF) and abacavir (ABC), is associated with comparable short-term efficacy and tolerability. Given the importance of toxicity profile differences in determining clinical management, it is important to recognise that d4T and ZDV cary significantly different risks for long-term NRTI toxicity. Recognising that all NRTIs, including thymidine analogues, have individual toxicity profiles provides a more appropriate basis for selecting optimal antiretroviral therapy. The safety and efficacy of TNF and ABC are also reviewed here, although the available data provide only limited knowledge of the long-term effects of these drugs in terms of toxicity and antiviral durability.

Cannabinoid receptor antagonist-induced striated muscle toxicity and ethylmalonic-adipic aciduria in beagle dogs.

PubMed

Tomlinson, Lindsay; Tirmenstein, Mark A; Janovitz, Evan B; Aranibar, Nelly; Ott, Karl-Heinz; Kozlosky, John C; Patrone, Laura M; Achanzar, William E; Augustine, Karen A; Brannen, Kimberly C; Carlson, Kenneth E; Charlap, Jeffrey H; Dubrow, Katherine M; Kang, Liya; Rosini, Laura T; Panzica-Kelly, Julieta M; Flint, Oliver P; Moulin, Frederic J; Megill, John R; Zhang, Haiying; Bennett, Michael J; Horvath, Joseph J

2012-10-01

Ibipinabant (IBI), a potent cannabinoid-1 receptor (CB1R) antagonist, previously in development for the treatment of obesity, causes skeletal and cardiac myopathy in beagle dogs. This toxicity was characterized by increases in muscle-derived enzyme activity in serum and microscopic striated muscle degeneration and accumulation of lipid droplets in myofibers. Additional changes in serum chemistry included decreases in glucose and increases in non-esterified fatty acids and cholesterol, and metabolic acidosis, consistent with disturbances in lipid and carbohydrate metabolism. No evidence of CB1R expression was detected in dog striated muscle as assessed by polymerase chain reaction, immunohistochemistry, Western blot analysis, and competitive radioligand binding. Investigative studies utilized metabonomic technology and demonstrated changes in several intermediates and metabolites of fatty acid metabolism including plasma acylcarnitines and urinary ethylmalonate, methylsuccinate, adipate, suberate, hexanoylglycine, sarcosine, dimethylglycine, isovalerylglycine, and 2-hydroxyglutarate. These results indicated that the toxic effect of IBI on striated muscle in beagle dogs is consistent with an inhibition of the mitochondrial flavin-containing enzymes including dimethyl glycine, sarcosine, isovaleryl-CoA, 2-hydroxyglutarate, and multiple acyl-CoA (short, medium, long, and very long chain) dehydrogenases. All of these enzymes converge at the level of electron transfer flavoprotein (ETF) and ETF oxidoreductase. Urinary ethylmalonate was shown to be a biomarker of IBI-induced striated muscle toxicity in dogs and could provide the ability to monitor potential IBI-induced toxic myopathy in humans. We propose that IBI-induced toxic myopathy in beagle dogs is not caused by direct antagonism of CB1R and could represent a model of ethylmalonic-adipic aciduria in humans.

Effect-directed analysis supporting monitoring of aquatic environments--An in-depth overview.

PubMed

Brack, Werner; Ait-Aissa, Selim; Burgess, Robert M; Busch, Wibke; Creusot, Nicolas; Di Paolo, Carolina; Escher, Beate I; Mark Hewitt, L; Hilscherova, Klara; Hollender, Juliane; Hollert, Henner; Jonker, Willem; Kool, Jeroen; Lamoree, Marja; Muschket, Matthias; Neumann, Steffen; Rostkowski, Pawel; Ruttkies, Christoph; Schollee, Jennifer; Schymanski, Emma L; Schulze, Tobias; Seiler, Thomas-Benjamin; Tindall, Andrew J; De Aragão Umbuzeiro, Gisela; Vrana, Branislav; Krauss, Martin

2016-02-15

Aquatic environments are often contaminated with complex mixtures of chemicals that may pose a risk to ecosystems and human health. This contamination cannot be addressed with target analysis alone but tools are required to reduce this complexity and identify those chemicals that might cause adverse effects. Effect-directed analysis (EDA) is designed to meet this challenge and faces increasing interest in water and sediment quality monitoring. Thus, the present paper summarizes current experience with the EDA approach and the tools required, and provides practical advice on their application. The paper highlights the need for proper problem formulation and gives general advice for study design. As the EDA approach is directed by toxicity, basic principles for the selection of bioassays are given as well as a comprehensive compilation of appropriate assays, including their strengths and weaknesses. A specific focus is given to strategies for sampling, extraction and bioassay dosing since they strongly impact prioritization of toxicants in EDA. Reduction of sample complexity mainly relies on fractionation procedures, which are discussed in this paper, including quality assurance and quality control. Automated combinations of fractionation, biotesting and chemical analysis using so-called hyphenated tools can enhance the throughput and might reduce the risk of artifacts in laboratory work. The key to determining the chemical structures causing effects is analytical toxicant identification. The latest approaches, tools, software and databases for target-, suspect and non-target screening as well as unknown identification are discussed together with analytical and toxicological confirmation approaches. A better understanding of optimal use and combination of EDA tools will help to design efficient and successful toxicant identification studies in the context of quality monitoring in multiply stressed environments. Copyright © 2015 Elsevier B.V. All rights reserved.

Ecotoxicological assessment of flocculant modified soil for lake restoration using an integrated biotic toxicity index.

PubMed

Wang, Zhibin; Zhang, Honggang; Pan, Gang

2016-06-15

Flocculant modified soils/clays are being increasingly studied as geo-engineering materials for lake restoration and harmful algal bloom control. However, the potential impacts of adding these materials in aquatic ecological systems remain unclear. This study investigated the potential effects of chitosan, cationic starch, chitosan modified soils (MS-C) and cationic starch modified soils (MS-S) on the aquatic organisms by using a bioassay battery. The toxicity potential of these four flocculants was quantitatively assessed using an integrated biotic toxicity index (BTI). The test system includes four aquatic species, namely Chlorella vulgaris, Daphnia magna, Cyprinus carpio and Limnodrilus hoffmeisteri, which represent four trophic levels in the freshwater ecosystem. Results showed that median effect concentrations (EC50) of the MS-C and MS-S were 31-124 times higher than chitosan and cationic starch, respectively. D. magna was the most sensitive species to the four flocculants. Histological examination of C. carpio showed that significant pathological changes were found in gills. Different from chitosan and cationic starch, MS-C and MS-S significantly alleviated the acute toxicities of chitosan and cationic starch. The toxicity order of the four flocculants based on BTI were cationic starch > chitosan > MS-S > MS-C. The results suggested that BTI can be used as a quantitative and comparable indicator to assess biotic toxicity for aquatic geo-engineering materials. Chitosan or cationic starch modified soil/clay materials can be used at their optimal dosage without causing substantial adverse effects to the bioassay battery in aquatic ecosystem. Copyright © 2015 Elsevier Ltd. All rights reserved.

Probing the toxicity of nanoparticles: a unified in silico machine learning model based on perturbation theory.

PubMed

Concu, Riccardo; Kleandrova, Valeria V; Speck-Planche, Alejandro; Cordeiro, M Natália D S

2017-09-01

Nanoparticles (NPs) are part of our daily life, having a wide range of applications in engineering, physics, chemistry, and biomedicine. However, there are serious concerns regarding the harmful effects that NPs can cause to the different biological systems and their ecosystems. Toxicity testing is an essential step for assessing the potential risks of the NPs, but the experimental assays are often very expensive and usually too slow to flag the number of NPs that may cause adverse effects. In silico models centered on quantitative structure-activity/toxicity relationships (QSAR/QSTR) are alternative tools that have become valuable supports to risk assessment, rationalizing the search for safer NPs. In this work, we develop a unified QSTR-perturbation model based on artificial neural networks, aimed at simultaneously predicting general toxicity profiles of NPs under diverse experimental conditions. The model is derived from 54,371 NP-NP pair cases generated by applying the perturbation theory to a set of 260 unique NPs, and showed an accuracy higher than 97% in both training and validation sets. Physicochemical interpretation of the different descriptors in the model are additionally provided. The QSTR-perturbation model is then employed to predict the toxic effects of several NPs not included in the original dataset. The theoretical results obtained for this independent set are strongly consistent with the experimental evidence found in the literature, suggesting that the present QSTR-perturbation model can be viewed as a promising and reliable computational tool for probing the toxicity of NPs.

Cutaneous Side Effects of Antiosteoporosis Treatments

PubMed Central

Musette, Philippe; Kaufman, Jean-Marc; Rizzoli, René; Cacoub, Patrice; Brandi, Maria Louisa; Reginster, Jean-Yves

2011-01-01

Cutaneous adverse reactions are reported for many therapeutic agents and, in general, are observed in between 0% and 8% of treated patients depending on the drug. Antiosteoporotic agents are considered to be safe in terms of cutaneous effects, however there have been a number of case reports of cutaneous adverse reactions which warrant consideration. This was the subject of a working group meeting of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis in April 2009, which focused on the impact of cutaneous adverse reactions and drug-induced hypersensitivity in the management of postmenopausal osteoporosis. This position paper was drafted following these discussions and includes a flowchart for their recognition. Cutaneous adverse reactions observed with antiosteoporotic agents were reviewed and included information from case reports, regulatory documents and pharmacovigilance. These reactions ranged from benign effects including exanthematous or maculopapular eruption (drug rash), photosensitivity and urticaria, to the severe and potentially life-threatening reactions of angioedema, drug rash with eosinophilia and systemic symptoms (DRESS), Stevens Johnson syndrome and toxic epidermal necrolysis. A review of the available evidence demonstrates that cutaneous adverse reactions occur with all commonly used antiosteoporotic treatments. Notably, there are reports of Stevens Johnson syndrome and toxic epidermal necrolysis for bisphosphonates, and of DRESS and toxic epidermal necrolysis for strontium ranelate. These severe reactions remain very rare (<1 in 10,000 cases). In general, with proper management and early recognition, including immediate and permanent withdrawal of the culprit agent, accompanied by hospitalization, rehydration and systemic corticosteroids if necessary, the prognosis is positive. PMID:22870464

Locomotor activity and tissue levels following acute administration of lambda- and gamma-cyhalothrin in rats

EPA Science Inventory

Pyrethroids produce neurotoxicity that depends, in part, on the chemical structure. Common behavioral effects include locomotor activity changes and specific toxic syndromes (types I and II). In general these neurobehavioral effects correlate well with peak internal dose metric...

Toxic effects of selenium and copper on the planarian, Dugesia dorotocephala

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rauscher, J.D.

1988-01-01

Aquatic toxicologists have become increasingly concerned with the effects of sublethal concentrations of toxicants on aquatic organisms. Sublethal effects of toxicants on freshwater invertebrates were reviewed. Selenium (Se) and copper (Cu) are both essential trace elements and toxicants. Se has been reported to alter the toxicity of heavy metals. Planarians, Dugesia dorotocephala, were used as test animals. The objectives of this study were to determine: (1) acute toxicity of Se on planarians and the effect of the number of planarians per test chamber, (2) interaction of the acute toxicity of Se and Cu on planarians, and (3) sublethal effects ofmore » Se and Cu on planarians.« less

Critical dose and toxicity index of organs at risk in radiotherapy: Analyzing the calculated effects of modified dose fractionation in non–small cell lung cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pedicini, Piernicola, E-mail: ppiern@libero.it; Strigari, Lidia; Benassi, Marcello

2014-04-01

To increase the efficacy of radiotherapy for non–small cell lung cancer (NSCLC), many schemes of dose fractionation were assessed by a new “toxicity index” (I), which allows one to choose the fractionation schedules that produce less toxic treatments. Thirty-two patients affected by non resectable NSCLC were treated by standard 3-dimensional conformal radiotherapy (3DCRT) with a strategy of limited treated volume. Computed tomography datasets were employed to re plan by simultaneous integrated boost intensity-modulated radiotherapy (IMRT). The dose distributions from plans were used to test various schemes of dose fractionation, in 3DCRT as well as in IMRT, by transforming the dose-volumemore » histogram (DVH) into a biological equivalent DVH (BDVH) and by varying the overall treatment time. The BDVHs were obtained through the toxicity index, which was defined for each of the organs at risk (OAR) by a linear quadratic model keeping an equivalent radiobiological effect on the target volume. The less toxic fractionation consisted in a severe/moderate hyper fractionation for the volume including the primary tumor and lymph nodes, followed by a hypofractionation for the reduced volume of the primary tumor. The 3DCRT and IMRT resulted, respectively, in 4.7% and 4.3% of dose sparing for the spinal cord, without significant changes for the combined-lungs toxicity (p < 0.001). Schedules with reduced overall treatment time (accelerated fractionations) led to a 12.5% dose sparing for the spinal cord (7.5% in IMRT), 8.3% dose sparing for V{sub 20} in the combined lungs (5.5% in IMRT), and also significant dose sparing for all the other OARs (p < 0.001). The toxicity index allows to choose fractionation schedules with reduced toxicity for all the OARs and equivalent radiobiological effect for the tumor in 3DCRT, as well as in IMRT, treatments of NSCLC.« less

Size effect of SnO2 nanoparticles on bacteria toxicity and their membrane damage.

PubMed

Chávez-Calderón, Adriana; Paraguay-Delgado, Francisco; Orrantia-Borunda, Erasmo; Luna-Velasco, Antonia

2016-12-01

Semiconductor SnO 2 nanoparticles (NPs) are being exploited for various applications, including those in the environmental context. However, toxicity studies of SnO 2 NPs are very limited. This study evaluated the toxic effect of two sizes of spherical SnO 2 NPs (2 and 40 nm) and one size of flower-like SnO 2 NPs (800 nm) towards the environmental bacteria E. coli and B. subtilis. SnO 2 NPs were synthesized using a hydrothermal or calcination method and they were well characterized prior to toxicity assessment. To evaluate toxicity, cell viability and membrane damage were determined in cells (1 × 10 9  CFU mL -1 ) exposed to up to 1000 mg L -1 of NPs, using the plate counting method and confocal laser scanning microscopy. Spherical NPs of smaller primary size (E2) had the lowest hydrodynamic size (226 ± 96 nm) and highest negative charge (-30.3 ± 10.1 mV). Smaller spherical NPs also showed greatest effect on viability (IC 50  > 500 mg L -1 ) and membrane damage of B. subtilis, whereas E. coli was unaffected. Scanning electron microscopy confirmed the membrane damage of exposed B. subtilis and also exhibited the attachment of E2 NPs to the cell surface, as well as the elongation of cells. It was also apparent that toxicity was caused solely by NPs, as released Sn 4+ was not toxic to B. subtilis. Thus, surface charge interaction between negatively charged SnO 2 NPs and positively charged molecules on the membrane of the Gram positive B. subtilis was indicated as the key mechanism related to toxicity of NPs. Copyright © 2016 Elsevier Ltd. All rights reserved.

Chloramphenicol Toxicity Revisited: A 12-Year-Old Patient With a Brain Abscess

PubMed Central

Wiest, Donald B.; Cochran, Joel B.; Tecklenburg, Fred W.

2012-01-01

Chloramphenicol, a broad-spectrum antibiotic, is rarely used in the United States due to its well-described adverse effects. Because of its limited use, many clinicians are unfamiliar with its indications, spectrum of activity, and potential adverse drug effects. We describe a 12-year-old patient who presented after two craniotomies for a persistent brain abscess complicated by long-term chloramphenicol administration. Findings for this patient were consistent with many of the adverse drug effects associated with chloramphenicol, including elevated chloramphenicol serum concentrations, anemia, thrombocytopenia, reticulocytopenia, and severe metabolic acidosis. Rare manifestations of chloramphenicol toxicity that developed in this patient included neutropenia, visual field changes, and peripheral neuropathy. Chloramphenicol administration was discontinued, and hemodialysis was initiated for severe metabolic acidosis. The patient recovered with severe visual field deficits. Although chloramphenicol is rarely indicated, it remains an effective antibiotic. Healthcare providers should become familiar with the pharmacology, toxicology, and monitoring parameters for appropriate use of this antibiotic. PMID:23118672

The acute toxicity of the death camas (Zigadenus species) alkaloid zygacine in mice, including the effect of methyllycaconitine coadministration on zygacine toxicity.

PubMed

Welch, K D; Panter, K E; Gardner, D R; Stegelmeier, B L; Green, B T; Pfister, J A; Cook, D

2011-05-01

Death camas (Zigadenus spp.) is a common poisonous plant on foothill rangelands in western North America. The steroidal alkaloid zygacine is believed to be the primary toxic component in death camas. Poisonings on rangelands generally occur in the spring when death camas is abundant, whereas other more desirable forage species are limited in availability. In most cases where livestock are poisoned by plants in a range setting, there is more than one potential poisonous plant in that area. One common poisonous plant that is often found growing simultaneously in the same area as death camas is low larkspur (Delphinium nuttallianum). Consequently, the objectives of this study were to conduct acute toxicity studies in mice and to determine if coadministration of low larkspur will exacerbate the toxicity of death camas. We first characterized the acute toxicity of zygacine in mice. The LD(50) of zygacine administered intravenously (i.v.) and orally was 2.0 ± 0.2 and 132 ± 21 mg/kg, respectively. The rate of elimination of zygacine from whole blood was determined to be 0.06 ± 0.01/min, which corresponds to an elimination half-life of 13.0 ± 2.7 min. The i.v. LD(50) of total alkaloid extracts from a Utah and a Nevada collection were 2.8 ± 0.8 and 2.2 ± 0.3 mg/kg, respectively. The i.v. LD(50) of methyllycaconitine (MLA), a major toxic alkaloid in low larkspur, was 4.6 ± 0.5 mg/kg, whereas the i.v. LD(50) of a 1:1 mixture of MLA and zygacine was 2.9 ± 0.7 mg/kg. The clinical signs in mice treated with this mixture were very similar to those of mice treated with zygacine alone, including the time of onset and death. These results suggest that there is an additive effect of coadministering these 2 alkaloids i.v. in mice. The results from this study increase knowledge and understanding regarding the acute toxicity of death camas. As combined intoxications are most likely common, this information will be useful in further developing management recommendations for ranchers and in designing additional experiments to study the toxicity of death camas to livestock.

Prostate cancer and toxicity from critical use exemptions of methyl bromide: Environmental protection helps protect against human health risks

PubMed Central

2012-01-01

Background Although ozone-depleting methyl bromide was destined for phase-out by 2005, it is still widely applied as a consequence of various critical-use-exemptions and mandatory international regulations aiming to restrict the spread of pests and alien species (e.g. in globalized transport and storage). The withdrawal of methyl bromide because of its environmental risk could fortuitously help in the containment of its human toxicity. Methods We performed a systematic review of the literature, including in vitro toxicological and epidemiological studies of occupational and community exposure to the halogenated hydrocarbon pesticide methyl bromide. We focused on toxic (especially chronic) or carcinogenic effects from the use of methyl bromide, on biomonitoring data and reference values. Eligible epidemiological studies were subjected to meta-analysis. Results Out of the 542 peer reviewed publications between 1990-2011, we found only 91 referring to toxicity of methyl bromide and 29 using the term "carcinogenic", "neoplastic" or "mutagenic". Several studies provide new additional data pertaining to the mechanistic aspects of methyl bromide toxicity. Few studies have performed a detailed exposure assessment including biomonitoring. Three evaluated epidemiological studies assessed a possible association between cancer and methyl bromide. Overall, exposure to methyl bromide is associated with an increased risk of prostate cancer OR, 1.21; 95% CI (0,98-1.49), P = 0.076. Two epidemiological studies have analyzed environmental, non-occupational exposure to methyl bromide providing evidence for its health risk to the general public. None of the epidemiological studies addressed its use as a fumigant in freight containers, although recent field and case reports do refer to its toxic effects associated with its use in shipping and storage. Conclusions Both the epidemiological evidence and toxicological data suggest a possible link between methyl bromide exposure and serious health problems, including prostate cancer risk from occupational and community exposure. The environmental risks of methyl bromide are not in doubt, but also its health risks, especially for genetically predisposed subjects, should not be underestimated. PMID:22284215

Aroclor1254 interferes with estrogen receptor-mediated neuroprotection against beta-amyloid toxicity in cholinergic SN56 cells.

PubMed

Bang, Yeojin; Lim, Juhee; Kim, Sa Suk; Jeong, Hyung Min; Jung, Ki-Kyung; Kang, Il-Hyun; Lee, Kwang-Youl; Choi, Hyun Jin

2011-10-01

Because estrogen plays important neurotrophic and neuroprotective roles in the brain by activating estrogen receptors (ERs), disruption of normal estrogen signaling can leave neurons vulnerable to a variety of insults, including β-amyloid peptide (Aβ). Aroclor1254 (A1254) belongs to the endocrine-disrupting chemical (EDC) polychlorinated biphenyls and has anti-estrogenic properties. In the present study, we evaluated the effect of A1254 on the protective activity of estrogen against Aβ toxicity in differentiated cholinergic SN56 cells. Aged Aβ25-35 causes apoptotic cell death in differentiated SN56 cells, and the cytotoxic evidences are effectively rescued by estrogen. We found that A1254 abolishes the neuroprotective activity of estrogen against Aβ toxicity, and attenuates the suppressive effect of estrogen on Aβ-induced tau phosphorylation and JNK activation. The effects of A1254 on the neuroprotective effects of estrogen in Aβ toxicity are very similar to the effects of the estrogen receptor antagonist ICI182,780. Thus, exposure to EDCs that have anti-estrogenic activity might interfere with normal estrogen-activated neuroprotective signaling events and leave neurons more vulnerable to dangerous stimuli. Our present results provide new understanding of the mechanisms contributing to the harmful effects of EDCs on the function and viability of neurons, and the possible relevance of EDCs in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease. Copyright © 2011 Elsevier B.V. All rights reserved.

Estimation of Potential Population Level Effects of Contaminants on Wildlife

DOE Office of Scientific and Technical Information (OSTI.GOV)

Loar, J.M.

2001-06-11

The objective of this project is to provide DOE with improved methods to assess risks from contaminants to wildlife populations. The current approach for wildlife risk assessment consists of comparison of contaminant exposure estimates for individual animals to literature-derived toxicity test endpoints. These test endpoints are assumed to estimate thresholds for population-level effects. Moreover, species sensitivities to contaminants is one of several criteria to be considered when selecting assessment endpoints (EPA 1997 and 1998), yet data on the sensitivities of many birds and mammals are lacking. The uncertainties associated with this approach are considerable. First, because toxicity data are notmore » available for most potential wildlife endpoint species, extrapolation of toxicity data from test species to the species of interest is required. There is no consensus on the most appropriate extrapolation method. Second, toxicity data are represented as statistical measures (e.g., NOAEL s or LOAELs) that provide no information on the nature or magnitude of effects. The level of effect is an artifact of the replication and dosing regime employed, and does not indicate how effects might increase with increasing exposure. Consequently, slight exceedance of a LOAEL is not distinguished from greatly exceeding it. Third, the relationship of toxic effects on individuals to effects on populations is poorly estimated by existing methods. It is assumed that if the exposure of individuals exceeds levels associated with impaired reproduction, then population level effects are likely. Uncertainty associated with this assumption is large because depending on the reproductive strategy of a given species, comparable levels of reproductive impairment may result in dramatically different population-level responses. This project included several tasks to address these problems: (1) investigation of the validity of the current allometric scaling approach for interspecies extrapolation an d development of new scaling models; (2) development of dose-response models for toxicity data presented in the literature; and (3) development of matrix-based population models that were coupled with dose-response models to provide realistic estimation of population-level effects for individual responses.« less

Metagenomic and metabolomic analysis of the toxic effects of trichloroacetamide-induced gut microbiome and urine metabolome perturbations in mice.

PubMed

Zhang, Yan; Zhao, Fuzheng; Deng, Yongfeng; Zhao, Yanping; Ren, Hongqiang

2015-04-03

Disinfection byproducts (DBPs) in drinking water have been linked to various diseases, including colon, colorectal, rectal, and bladder cancer. Trichloroacetamide (TCAcAm) is an emerging nitrogenous DBP, and our previous study found that TCAcAm could induce some changes associated with host-gut microbiota co-metabolism. In this study, we used an integrated approach combining metagenomics, based on high-throughput sequencing, and metabolomics, based on nuclear magnetic resonance (NMR), to evaluate the toxic effects of TCAcAm exposure on the gut microbiome and urine metabolome. High-throughput sequencing revealed that the gut microbiome's composition and function were significantly altered after TCAcAm exposure for 90 days in Mus musculus mice. In addition, metabolomic analysis showed that a number of gut microbiota-related metabolites were dramatically perturbed in the urine of the mice. These results may provide novel insight into evaluating the health risk of environmental pollutants as well as revealing the potential mechanism of TCAcAm's toxic effects.

In vitro and in vivo toxicity assessment of nanoparticles

NASA Astrophysics Data System (ADS)

Kumar, Vinay; Sharma, Neha; Maitra, S. S.

2017-11-01

Nanotechnology has revolutionized gene therapy, diagnostics and environmental remediation. Their bulk production, uses and disposal have posed threat to the environment. With the appearance of these nanoparticles in the environment, their toxicity assessment is an immediate concern. This review is an attempt to summarize the major techniques used in cytotoxity determination. The review also presents a detailed and elaborative discussion on the toxicity imposed by different types of nanoparticles including carbon nanotubes, gold nanoparticles, silver nanoparticles, quantum dots, fullerenes, aluminium nanoparticles, zinc nanoparticles, iron nanoparticles, titanium nanoparticles and silica nanoparticles. It discusses the in vitro and in vivo toxological effects of nanoparticles on bacteria, microalgae, zebrafish, crustacean, fish, rat, mouse, pig, guinea pig, human cell lines and human. It also discusses toxological effects on organs such as liver, kidney, spleen, sperm, neural tissues, liver lysosomes, spleen macrophages, glioblastoma cells, hematoma cells and various mammalian cell lines. It provides information about the effects of nanoparticles on the gene-expression, growth and reproduction of the organisms.

Management of Side Effects of Novel Therapies for Multiple Myeloma: Consensus Statements Developed by the International Myeloma Foundation’s Nurse Leadership Board

PubMed Central

Bertolotti, Page; Bilotti, Elizabeth; Colson, Kathleen; Curran, Kathleen; Doss, Deborah; Faiman, Beth; Gavino, Maria; Jenkins, Bonnie; Lilleby, Kathy; Love, Ginger; Mangan, Patricia A.; McCullagh, Emily; Miceli, Teresa; Miller, Kena; Rogers, Kathryn; Rome, Sandra; Sandifer, Stacey; Smith, Lisa C.; Tariman, Joseph D.; Westphal, Jeanne

2014-01-01

Nurses play an essential role in managing the care of patients with multiple myeloma, who require education and support to receive and adhere to optimal therapy. The International Myeloma Foundation created a Nurse Leadership Board comprised of oncology nurses from leading cancer centers and community practices. An assessment survey identified the need for specific recommendations for managing key side effects of novel antimyeloma agents. Myelosuppression, thromboembolic events, peripheral neuropathy, steroid toxicities, and gastrointestinal side effects were selected for the first consensus statements. The board developed recommendations for healthcare providers in any medical setting, including grading of side-effect toxicity and strategies for managing the side effects in general, with specific recommendations pertaining to the novel agents. PMID:18490252

Black Seed (Nigella Sativa) and its Constituent Thymoquinone as an Antidote or a Protective Agent Against Natural or Chemical Toxicities

PubMed Central

Tavakkoli, Alireza; Ahmadi, Ali; Razavi, Bibi Marjan; Hosseinzadeh, Hossein

2017-01-01

Nigella sativa (N. sativa), which belongs to the botanical family of Ranunculaceae, is a widely used medicinal plant all over the world. N. sativa seeds and oil have been used in the treatment of different diseases. Various studies on N. sativa have been carried out and a broad spectrum of its pharmacological actions have been established which include antioxidant, antidiabetic, anticancer, antitussive, immunomodulator, analgesic, antimicrobial, anti-inflammatory, spasmolytic, and bronchodilator. This is also indicated that the majority of the therapeutic effects of N. sativa are due to the presence of thymoquinone (TQ) that is the main bioactive constituent of the essential oil. According to several lines of evidence, the protective effects of this plant and its main constituent in different tissues including brain, heart, liver, kidney, and lung have been proved against some toxic agents either natural or chemical toxins in animal studies. In this review article, several in-vitro and animal studies in scientific databases which investigate the antidotal and protective effects of N. sativa and its main constituents against natural and chemical induced toxicities are introduced. Because human reports are rare, further studies are required to determine the efficacy of this plant as an antidote or protective agent in human intoxication. PMID:29844772

Acute and additive toxicity of ten photosystem-II herbicides to seagrass

NASA Astrophysics Data System (ADS)

Wilkinson, Adam D.; Collier, Catherine J.; Flores, Florita; Negri, Andrew P.

2015-11-01

Photosystem II herbicides are transported to inshore marine waters, including those of the Great Barrier Reef, and are usually detected in complex mixtures. These herbicides inhibit photosynthesis, which can deplete energy reserves and reduce growth in seagrass, but the toxicity of some of these herbicides to seagrass is unknown and combined effects of multiple herbicides on seagrass has not been tested. Here we assessed the acute phytotoxicity of 10 PSII herbicides to the seagrass Halophila ovalis over 24 and/or 48 h. Individual herbicides exhibited a broad range of toxicities with inhibition of photosynthetic activity (ΔF/Fm‧) by 50% at concentrations ranging from 3.5 μg l-1 (ametryn) to 132 μg l-1 (fluometuron). We assessed potential additivity using the Concentration Addition model of joint action for binary mixtures of diuron and atrazine as well as complex mixtures of all 10 herbicides. The effects of both mixture types were largely additive, validating the application of additive effects models for calculating the risk posed by multiple PSII herbicides to seagrasses. This study extends seagrass ecotoxicological data to ametryn, metribuzin, bromacil, prometryn and fluometuron and demonstrates that low concentrations of PSII herbicide mixtures have the potential to impact ecologically relevant endpoints in seagrass, including ΔF/Fm‧.

Health effects of groundwater fluoride contamination.

PubMed

Nayak, Bishwajit; Roy, Madan Mohan; Das, Bhaskar; Pal, Arup; Sengupta, Mrinal Kumar; De, Shankar Prasad; Chakraborti, Dipankar

2009-04-01

The people in Berhait block, Sahibganj district, Jharkhand state, India, have been exposed chronically to fluoridecontaminated groundwater. Hereby, we report the clinical effects of chronic exposure to fluoride. The study population was a convenience sample of 342 adults and 258 children living in the affected area. All volunteers filled out questionnaires and were examined. Well water from the six affected villages and urine samples were analyzed for fluoride using an ion-sensitive electrode. Twenty nine percent of 89 well water samples had fluoride concentrations above the Indian permissible limit of fluoride in drinking water. Eighty-five children and 72 adults had clinical fluorosis. Urine fluoride concentrations in children were 0.758-2.88 mg/L whereas in adults they were 0.331-10.36 mg/L. Clinical effects of fluoride included abnormal tooth enamel in children; adults had joint pain and deformity of the limbs and spine, along with ligamentous calcifications and exostosis formations in seven patients. Elevated urine fluoride concentrations supported the clinical diagnosis of fluorosis. Owing to insufficient fluoride-safe wells and lack of awareness of the danger of fluoride toxicity, villagers often drink fluoride-contaminated water. Villagers of Berhait block, including children, are at risk from chronic fluoride toxicity. To combat the situation, villagers need fluoride-safe water, education, and awareness of the danger about fluoride toxicity.

Acute and additive toxicity of ten photosystem-II herbicides to seagrass

PubMed Central

Wilkinson, Adam D.; Collier, Catherine J.; Flores, Florita; Negri, Andrew P.

2015-01-01

Photosystem II herbicides are transported to inshore marine waters, including those of the Great Barrier Reef, and are usually detected in complex mixtures. These herbicides inhibit photosynthesis, which can deplete energy reserves and reduce growth in seagrass, but the toxicity of some of these herbicides to seagrass is unknown and combined effects of multiple herbicides on seagrass has not been tested. Here we assessed the acute phytotoxicity of 10 PSII herbicides to the seagrass Halophila ovalis over 24 and/or 48 h. Individual herbicides exhibited a broad range of toxicities with inhibition of photosynthetic activity (∆F/Fm′) by 50% at concentrations ranging from 3.5 μg l−1 (ametryn) to 132 μg l−1 (fluometuron). We assessed potential additivity using the Concentration Addition model of joint action for binary mixtures of diuron and atrazine as well as complex mixtures of all 10 herbicides. The effects of both mixture types were largely additive, validating the application of additive effects models for calculating the risk posed by multiple PSII herbicides to seagrasses. This study extends seagrass ecotoxicological data to ametryn, metribuzin, bromacil, prometryn and fluometuron and demonstrates that low concentrations of PSII herbicide mixtures have the potential to impact ecologically relevant endpoints in seagrass, including ∆F/Fm′. PMID:26616444

Acute and additive toxicity of ten photosystem-II herbicides to seagrass.

PubMed

Wilkinson, Adam D; Collier, Catherine J; Flores, Florita; Negri, Andrew P

2015-11-30

Photosystem II herbicides are transported to inshore marine waters, including those of the Great Barrier Reef, and are usually detected in complex mixtures. These herbicides inhibit photosynthesis, which can deplete energy reserves and reduce growth in seagrass, but the toxicity of some of these herbicides to seagrass is unknown and combined effects of multiple herbicides on seagrass has not been tested. Here we assessed the acute phytotoxicity of 10 PSII herbicides to the seagrass Halophila ovalis over 24 and/or 48 h. Individual herbicides exhibited a broad range of toxicities with inhibition of photosynthetic activity (∆F/F(m)') by 50% at concentrations ranging from 3.5 μg l(-1) (ametryn) to 132 μg l(-1) (fluometuron). We assessed potential additivity using the Concentration Addition model of joint action for binary mixtures of diuron and atrazine as well as complex mixtures of all 10 herbicides. The effects of both mixture types were largely additive, validating the application of additive effects models for calculating the risk posed by multiple PSII herbicides to seagrasses. This study extends seagrass ecotoxicological data to ametryn, metribuzin, bromacil, prometryn and fluometuron and demonstrates that low concentrations of PSII herbicide mixtures have the potential to impact ecologically relevant endpoints in seagrass, including ∆F/F(m)'.

Feeding Behavior of an Aquatic Snail as a Simple Endpoint to Assess the Exposure to Cadmium.

PubMed

Alonso, Álvaro; Valle-Torres, Guillermo

2018-01-01

One of the aims of ecotoxicology is the assessment of the effects of chemicals on the ecosystems. Bioassays assessing lethality are frequently used in ecotoxicology, however they usually employ supra-environmental toxic concentrations. Toxicity tests employing behavioral endpoints may present a balance between simplicity (i.e., laboratory bioassays) and complexity (i.e., relevant ecological effects). The aim of this study was to develop a feeding behavioral bioassay with the aquatic snail, Potamopyrgus antipodarum, which included a 2 days exposure to cadmium, followed by a 9 days post-exposure observational period. Several behavioral feeding endpoints were monitored, including percentage of actively feeding animals, percentage of animals in food quadrants and a mobility index. The percentage of actively feeding animals was reduced by the four cadmium treatments (0.009, 0.026, 0.091 and 0.230 mg Cd/L) with the stronger effect in the highest concentration. The two highest cadmium concentrations significantly reduced the percentage of animals in food quadrants and the mobility index. Therefore, the percentage of actively feeding animals was the most sensitive endpoint to cadmium toxicity as the four cadmium concentrations caused a significant decrease in this endpoint. It is concluded that feeding behavior is a useful endpoint to detect the exposure of aquatic snails to cadmium.

Antibacterial properties and toxicity from metallic nanomaterials

PubMed Central

Vimbela, Gina V; Ngo, Sang M; Fraze, Carolyn; Yang, Lei; Stout, David A

2017-01-01

The era of antibiotic resistance is a cause of increasing concern as bacteria continue to develop adaptive countermeasures against current antibiotics at an alarming rate. In recent years, studies have reported nanoparticles as a promising alternative to antibacterial reagents because of their exhibited antibacterial activity in several biomedical applications, including drug and gene delivery, tissue engineering, and imaging. Moreover, nanomaterial research has led to reports of a possible relationship between the morphological characteristics of a nanomaterial and the magnitude of its delivered toxicity. However, conventional synthesis of nanoparticles requires harsh chemicals and costly energy consumption. Additionally, the exact relationship between toxicity and morphology of nanomaterials has not been well established. Here, we review the recent advancements in synthesis techniques for silver, gold, copper, titanium, zinc oxide, and magnesium oxide nanomaterials and composites, with a focus on the toxicity exhibited by nanomaterials of multidimensions. This article highlights the benefits of selecting each material or metal-based composite for certain applications while also addressing possible setbacks and the toxic effects of the nanomaterials on the environment. PMID:28579779

Progression-Free Survival Among Patients With Well-Differentiated or Dedifferentiated Liposarcoma Treated With CDK4 Inhibitor Palbociclib: A Phase 2 Clinical Trial.

PubMed

Dickson, Mark A; Schwartz, Gary K; Keohan, Mary Louise; D'Angelo, Sandra P; Gounder, Mrinal M; Chi, Ping; Antonescu, Cristina R; Landa, Jonathan; Qin, Li-Xuan; Crago, Aimee M; Singer, Samuel; Koff, Andrew; Tap, William D

2016-07-01

More than 90% of well-differentiated or dedifferentiated liposarcomas (WD/DDLS) have CDK4 amplification. The selective CDK4 and CDK6 inhibitor palbociclib inhibits growth and induces senescence in liposarcoma cell lines and xenografts. Our prior phase 2 study demonstrated that treatment with palbociclib (200 mg daily for 14 days every 21 days) resulted in clinical benefit in WD/DDLS but moderate hematologic toxic effects. It is important to understand whether palbociclib at a new dose and schedule-125 mg daily for 21 days every 28 days-results in clinical benefit and manageable toxic effects. To determine the progression-free survival (PFS) at 12 weeks of patients with WD/DDLS treated with palbociclib (PD0332991). In this phase 2, nonrandomized, open-label clinical trial conducted at the Memorial Sloan Kettering Cancer Center, 60 patients 18 years and older with advanced WD/DDLS and measurable disease by RECIST 1.1 were enrolled from December 2011 to January 2014 and followed to March 2015. Patients received oral palbociclib at 125 mg daily for 21 days in 28-day cycles. Primary end point was PFS. Secondary end points included response rate and toxic effects. Overall, 30 patients were enrolled in the initial cohort and 30 more in an expansion cohort. Median (range) age was 61.5 (35-87) years; 31 patients (52%) were male; median (range) Eastern Cooperative Oncology Group score was 0 (0-1). Progression-free survival at 12 weeks was 57.2% (2-sided 95% CI, 42.4%-68.8%), and the median PFS was 17.9 weeks (2-sided 95% CI, 11.9-24.0 weeks). There was 1 complete response. Toxic effects were primarily hematologic and included neutropenia (grade 3, n = 20 [33%]; grade 4, n = 2 [3%]) but no neutropenic fever. In patients with advanced WD/DDLS, treatment with palbociclib was associated with a favorable PFS and occasional tumor response. This dose and schedule appears active and may have less toxic effects than 200 mg for 14 days. clinicaltrials.gov Identifier: NCT01209598.

Bivalve embryo bioassay to assess the potential toxicity of dredged material before dumping

DOE Office of Scientific and Technical Information (OSTI.GOV)

Quiniou, F.

1995-12-31

Dredged harbor sediments frequently contain a wide spectrum of contaminants in addition to a significant percentage of organic matter. Also, dredging and dumping activities into sea water, of these highly contaminated soil may induce a harmful effect on the environment. In France, in accordance with Oslo convention guidelines, a working group on dredging activities and environment (GEODE) created since 1991 decided to set up a pilot research program to assess the intrinsic toxicity of four harbor sludges. Intrinsic toxicity of harbor muds were tested by solid phase (whole sediment) and aqueous extract bioassays (sea water elutriates) using the sublethal toxicitymore » test bivalve embryo bioassay (Crassostrea gigas). Elutriates enable them to detect the toxicity of contaminants which may be released in the soluble form into the water column during dredging operations. While, whole sediment integrate the synergistic effects of all the contaminants (hydrophilic and hydrophobic) including pore water. Bioassays results, correlated to chemical analysis, are compared to contaminant levels determined by French working group GEODE and Canadian sediment quality criteria.« less

Recommendations: Will the Tobacco and Vaping Products Act go far enough?

PubMed

Tulsieram, Kurt L; Rinaldi, Sylvia; Shelley, Jacob J

2017-09-14

E-cigarette use among adolescents and young adults in Canada is increasing. Potvin's (2016) editorial outlined the need for more evidence on e-cigarettes as a gateway to combustible cigarettes and their toxicity. Since then, new evidence has emerged supporting the gateway effect and establishing toxicity. Health Canada has reviewed the evidence and recently opted to regulate e-cigarettes, including prohibiting brick-and-mortar retail access for youth under 18 years of age. However, many online e-cigarette retailers exist, which increases adolescents' access to e-cigarettes and currently unregulated nicotine-containing refills. Recent evidence on the toxicity of particular compounds in e-cigarette refills has demonstrated how these compounds may be amplified by certain types of e-cigarette devices. The toxicity of e-cigarettes is not only of concern to the user but potentially a concern to the public as well. The message that e-cigarettes have a benign effect on users and the public needs to change and should be reflected in Health Canada's future regulations concerning the Tobacco and Vaping Products Act.

Curcumin Modulates α-Synuclein Aggregation and Toxicity

PubMed Central

2012-01-01

In human beings, Parkinson’s disease (PD) is associated with the oligomerization and amyloid formation of α-synuclein (α-Syn). The polyphenolic Asian food ingredient curcumin has proven to be effective against a wide range of human diseases including cancers and neurological disorders. While curcumin has been shown to significantly reduce cell toxicity of α-Syn aggregates, its mechanism of action remains unexplored. Here, using a series of biophysical techniques, we demonstrate that curcumin reduces toxicity by binding to preformed oligomers and fibrils and altering their hydrophobic surface exposure. Further, our fluorescence and two-dimensional nuclear magnetic resonance (2D-NMR) data indicate that curcumin does not bind to monomeric α-Syn but binds specifically to oligomeric intermediates. The degree of curcumin binding correlates with the extent of α-Syn oligomerization, suggesting that the ordered structure of protein is required for effective curcumin binding. The acceleration of aggregation by curcumin may decrease the population of toxic oligomeric intermediates of α-Syn. Collectively; our results suggest that curcumin and related polyphenolic compounds can be pursued as candidate drug targets for treatment of PD and other neurological diseases. PMID:23509976

An assessment of the potential toxicity of runoff from an urban roadscape during rain events.

PubMed

Waara, Sylvia; Färm, Carina

2008-05-01

The potential negative impact of urban storm water on aquatic freshwater ecosystems has been demonstrated in various studies with different types of biological methods. There are a number of factors that influence the amount and bioavailability of contaminants in storm water even if it is derived from an area with a fairly homogenous land use such as a roadscape where a variation in toxicity during rain events might be expected. There are only a few previous investigations on the toxicity of highway runoff and they have not explored these issues extensively. The main objective of this study is therefore to characterize the potential toxicity of highway runoff during several rain events before it enters a detention pond in Västerås, Sweden, using laboratory bioassays with test organisms representing various functional groups in an aquatic ecosystem. The results are to be used for developing a monitoring program, including biological methods. The storm water was sampled before the entrance to a detention pond, which receives run-off from a highway with approximately 20,000 vehicles a day. The drainage area, including the roadscape and vegetated areas, is 4.3 ha in size. Samples for toxicity tests were taken with an automatic sampler or manually during storm events. In total, the potential toxicity of 65 samples representing 15 different storm events was determined. The toxicity was assessed with 4 different test organisms; Vibrio fischeri using the Microtox comparison test, Daphnia magna using Daphtoxkit-F agna, Thamnocephalus platyurus using the ThamnotoxkitF and Lemna minor, duckweed using SS 028313. Of the 65 samples, 58 samples were tested with DaphniatoxkitF agna, 57 samples with the Microtox comparison test, 48 samples with ThamnotoxkitF and 20 samples with Lemna minor, duckweed. None of the storm water samples were toxic. No toxicity was detected with the Lemna minor test, but in 5 of the 23 samples tested in comparison to the control a growth stimulation of 22-46% was observed. This is in accordance with the chemical analysis of the storm water, which indicated rather large concentrations of tot-N and tot-P. In addition to the growth stimulation, morphological changes were observed in all the 5 samples from the winter event that was sampled. The lack of toxicity observed in our study might be due to a lower traffic intensity (20,000 vehicles/day) at the site and the trapping of pollutants in the vegetated areas of the roadscape, resulting in much smaller loads of pollutants in the storm water than in some previous studies. Ecotoxicological evaluations of storm water including run off from rain events from urban roadscape studies clearly reveal that toxicity may or may not be detected depending upon site, storm condition and the test organism chosen. However, storm water might not be as polluted as previously reported nor may the first flush be such a widespread phenomenon as we originally expected. In this study, there was also a good correlation between pollutant load measured and the lack of toxicity. The test organisms chosen in this study are commonly used in effluent control programs in Sweden and other countries, which makes it possible to compare the results with those from other effluents. In this study, only acute toxicity tests were used and further studies using chronic toxicity tests, assays for genotoxic compounds or in situ bioassays might reveal biological effects at this site. Furthermore, most of the samples were taken in spring, summer or fall and it is possible that winter conditions might alter the constituents in the storm water and, thus, the toxicity of the samples. Considering the complex nature of run off from urban roadscapes, it will be virtually impossible to evaluate properly the potential hazard of particular storm water and the efficiency of a particular treatment strategy from only physical and chemical characterizations of the effluent. Therefore, despite the lack of toxicity detected in this study, it is recommended that toxicity tests or other biological methods should be included in evaluations of the effects of runoff from roadscapes.

Guidance on the selection of cohorts for the extended one-generation reproduction toxicity study (OECD test guideline 443).

PubMed

Moore, Nigel P; Beekhuijzen, Manon; Boogaard, Peter J; Foreman, Jennifer E; North, Colin M; Palermo, Christine; Schneider, Steffen; Strauss, Volker; van Ravenzwaay, Bennard; Poole, Alan

2016-10-01

The extended one-generation reproduction toxicity study (EOGRTS; OECD test guideline 433) is a new and technically complex design to evaluate the putative effects of chemicals on fertility and development, including effects upon the developing nervous and immune systems. In addition to offering a more comprehensive assessment of developmental toxicity, the EOGRTS offers important improvements in animal welfare through reduction and refinement in a modular study design. The challenge to the practitioner is to know how the modular aspects of the study should be triggered on the basis of prior knowledge of a particular chemical, or on earlier findings in the EOGRTS itself, requirements of specific regulatory frameworks notwithstanding. The purpose of this document is to offer guidance on science-based triggers for these extended evaluations. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Nrf2-dependent protection against acute sodium arsenite toxicity in zebrafish

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fuse, Yuji; Nguyen, Vu Thanh; Kobayashi, Makoto, E

Transcription factor Nrf2 induces a number of detoxifying enzymes and antioxidant proteins to confer protection against the toxic effects of a diverse range of chemicals including inorganic arsenicals. Although a number of studies using cultured cells have demonstrated that Nrf2 has a cell-protective function against acute and high-dose arsenic toxicity, there is no clear in vivo evidence of this effect. In the present study, we genetically investigated the protective role of Nrf2 against acute sodium arsenite toxicity using the zebrafish Nrf2 mutant, nrf2a{sup fh318}. After treatment with 1 mM sodium arsenite, the survival of nrf2a{sup fh318} larvae was significantly shortermore » than that of wild-type siblings, suggesting that Nrf2 protected the zebrafish larvae against high-dose arsenite exposure. To understand the molecular basis of the Nrf2-dependent protection, we analyzed the gene expression profiles after arsenite exposure, and found that the genes involved in the antioxidative function (prdx1 and gclc), arsenic metabolism (gstp1) and xenobiotic elimination (abcc2) were induced in an Nrf2-dependent manner. Furthermore, pre-treatment with sulforaphane, a well-known Nrf2 activator improved the survival of zebrafish larvae after arsenic exposure. Based on these results, we concluded that Nrf2 plays a fundamental and conserved role in protection against acute sodium arsenite toxicity. - Highlights: • The role of Nrf2 under arsenite exposure was valuated using zebrafish. • Nrf2 mutant zebrafish was highly sensitive to acute arsenic toxicity. • Nrf2 induced anti-arsenic genes in response to arsenite. • Sulforaphane attenuated arsenic toxicity through Nrf2 activation. • Nrf2 system plays an important role in the defense against acute arsenic toxicity.« less

Petroleum Hydrocarbon Mixture Toxicity and a Trait Based Approach to Soil Invertebrate Species for Site Specific Risk Assessments.

PubMed

Gainer, Amy; Cousins, Mark; Hogan, Natacha; Siciliano, Steven D

2018-05-05

Although petroleum hydrocarbons (PHCs) released to the environment typically occur as mixtures, PHC remediation guidelines often reflect individual substance toxicity. It is well documented that groups of aliphatic PHCs act via the same mechanism of action, nonpolar narcosis and, theoretically, concentration addition mixture toxicity principles apply. To assess this theory, ten standardized acute and chronic soil invertebrate toxicity tests on a range of organisms (Eisenia fetida, Lumbricus terrestris, Enchytraeus crypticus, Folsomia candida, Oppia nitens and Hypoaspis aculeifer) were conducted with a refined PHC binary mixture. Reference models for concentration addition and independent action were applied to the mixture toxicity data with consideration of synergism, antagonism and dose level toxicity. Both concentration addition and independent action, without further interactions, provided the best fit with observed response to the mixture. Individual fraction effective concentration values were predicted from optimized, fitted reference models. Concentration addition provided a better estimate than independent action of individual fraction effective concentrations based on comparison with available literature and species trends observed in toxic responses to the mixture. Interspecies differences in standardized laboratory soil invertebrate species responses to PHC contaminated soil was reflected in unique traits. Diets that included soil, large body size, permeable cuticle, low lipid content, lack of ability to molt and no maternal transfer were traits linked to a sensitive survival response to PHC contaminated soil in laboratory tests. Traits linked to sensitive reproduction response in organisms tested were long life spans with small clutch sizes. By deriving single fraction toxicity endpoints considerate of mixtures, we reduce resources and time required in conducting site specific risk assessments for the protection of soil organism's exposure pathway. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

UGT1A1*6 and UGT1A1*28 polymorphisms are correlated with irinotecan-induced toxicity: A meta-analysis.

PubMed

Yang, Yuwei; Zhou, MengMeng; Hu, Mingjun; Cui, Yanjie; Zhong, Qi; Liang, Ling; Huang, Fen

2018-06-22

Previous articles explored the role of UGT1A1 polymorphism on predicting irinotecan-induced toxicity, but the conclusions were still inconsistent and not comprehensive. We performed this meta-analysis to investigate the association between UGT1A1 polymorphism and irinotecan-induced toxicity. PubMed and Web of Science were searched for articles before July 2017. Inclusion and exclusion criteria were set to select eligible articles, and corresponding data were extracted from those articles. Subgroup analyses based on different cancer categories, doses and races were carried out to achieve comprehensive results. Statistical analyses were conducted using STATA 11.0. A total of 38 studies with 6742 cases were included after reading full text. Both UGT1A1*6 and UGT1A1*28 polymorphism are significantly associated with severe irinotecan-induced toxicity. Both Asian and Caucasian cancer patients with UGT1A1*28 variant had an increased risk. Compared with heterozygous variant, patients with homozygous variant suffered from a higher risk of toxicity. The effect of UGT1A1*28 polymorphism on diarrhea was less than on neutropenia. Subgroup analysis exhibited that for UGT1A1*6 polymorphism, patients treated with low-dose irinotecan were at a notable risk of toxicity. Moreover, the association between UGT1A1*6 polymorphism and irinotecan-induced toxicity was found in patients suffering from respiratory system cancers. Both UGT1A1*6 and UGT1A1*28 polymorphisms can be considered as predictors of irinotecan-induced toxicity, with effect varying by race, cancer type and irinotecan dose. © 2018 John Wiley & Sons Australia, Ltd.

Structure-activity relationship analysis of mitochondrial toxicity caused by antiviral ribonucleoside analogs.

PubMed

Jin, Zhinan; Kinkade, April; Behera, Ishani; Chaudhuri, Shuvam; Tucker, Kathryn; Dyatkina, Natalia; Rajwanshi, Vivek K; Wang, Guangyi; Jekle, Andreas; Smith, David B; Beigelman, Leo; Symons, Julian A; Deval, Jerome

2017-07-01

Recent cases of severe toxicity during clinical trials have been associated with antiviral ribonucleoside analogs (e.g. INX-08189 and balapiravir). Some have hypothesized that the active metabolites of toxic ribonucleoside analogs, the triphosphate forms, inadvertently target human mitochondrial RNA polymerase (POLRMT), thus inhibiting mitochondrial RNA transcription and protein synthesis. Others have proposed that the prodrug moiety released from the ribonucleoside analogs might instead cause toxicity. Here, we report the mitochondrial effects of several clinically relevant and structurally diverse ribonucleoside analogs including NITD-008, T-705 (favipiravir), R1479 (parent nucleoside of balapiravir), PSI-7851 (sofosbuvir), and INX-08189 (BMS-986094). We found that efficient substrates and chain terminators of POLRMT, such as the nucleoside triphosphate forms of R1479, NITD-008, and INX-08189, are likely to cause mitochondrial toxicity in cells, while weaker chain terminators and inhibitors of POLRMT such as T-705 ribonucleoside triphosphate do not elicit strong in vitro mitochondrial effects. Within a fixed 3'-deoxy or 2'-C-methyl ribose scaffold, changing the base moiety of nucleotides did not strongly affect their inhibition constant (K i ) against POLRMT. By swapping the nucleoside and prodrug moieties of PSI-7851 and INX-08189, we demonstrated that the cell-based toxicity of INX-08189 is mainly caused by the nucleoside component of the molecule. Taken together, these results show that diverse 2' or 4' mono-substituted ribonucleoside scaffolds cause mitochondrial toxicity. Given the unpredictable structure-activity relationship of this ribonucleoside liability, we propose a rapid and systematic in vitro screen combining cell-based and biochemical assays to identify the early potential for mitochondrial toxicity. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Balancing risk and benefit for first-line treatment of metastatic colorectal cancer: a graphic communication tool for patients and physicians.

PubMed

Sanatani, Michael S; Vincent, Mark D

2007-01-01

Advances in the treatment of metastatic colorectal cancer have improved overall survival (OS); however, this might come at the cost of increased toxicity. Health-related quality of life, a significant concern closely related to toxicity and important when discussing palliative therapy, is infrequently assessed and reported in older clinical trials. As the number of tested regimens increases, the question arises on how to best present palliative treatment options. We present a simple way to compare treatment options in terms of potential risks and benefits. The literature was surveyed for reports of first-line systemic chemotherapies for metastatic colorectal cancer. The largest recent reports with detailed toxicity data were selected as representative for a regimen. Toxicity sum of a regimen was calculated as percent occurrences in the study cohort of severe adverse effects: diarrhea, mucositis, neurocutaneous conditions (excluding alopecia), vomiting, and febrile neutropenia. Limitations of toxicity reporting precluded inclusion of other or milder adverse events. Benefits (OS and progression-free survival [PFS]) were plotted graphically as benefit versus toxicity sum. Thirty-four regimens were found. Overall survival, PFS, and toxicity sum ranged from 8.9-24.7 months, 4.9-9.2 months, and 12-70 months, respectively. Weaknesses of our study include omission of some specific toxicities and of symptom control benefit, as well as heterogeneity of trial design and study populations. Furthermore, more recent OS data might reflect the availability of more lines of therapy rather than the effect of the first-line regimen, as comparison with PFS outcomes show. Our comparative tool helps physicians discuss the large number of available options with a patient in order to arrive at the treatment plan most appropriate to the individual and improve informed consent and disclosure, while highlighting limitations in available evidence.

In Vitro Comparison of Cytotoxic and Antibacterial Effects of 16 Commercial Toothpastes

PubMed Central

Ghapanchi, Jannan; Kamali, Fereshteh; Moattari, Afagh; Poorshahidi, Sara; Shahin, Esmaiel; Rezazadeh, Fahimeh; Khorshidi, Hooman; Jamshidi, Samira

2015-01-01

Background: Toothpastes are considered as one of the most common and usable cosmetic and hygienic materials. Such materials contain chemicals which may have an adverse effect on oral tissue in humans. The present study aimed to compare the toxic effect of current commercial toothpastes including Iranian products and imported types which are consumed globally on oral epithelial- and HeLa cells as well as to evaluate their antibacterial effect on Streptococcus mutans in Shiraz, Iran. Materials and Methods: In this experimental study, 16 types of commercial toothpastes were prepared, and their effect was determined on primer epithelial cells of the oral cavity and HeLa cells. Toothpastes anti streptococcal property and toxicity were examined in vitro in different intervals of 1, 2, and 5 min. Data collection and analysis were done using one-way analysis of variance. Results: All experimented toothpastes revealed variable toxic effects on cultured cells. Through an increase in the time of exposure with toothpastes, the toxicity of these materials substantially increased (P = 0.005). On the other hand, all tested toothpastes showed varying degrees of anti-streptococcal effect in the laboratory (P = 0.005). Conclusions: The most cytotoxic effect on primer epithelial cells of oral mucosa and HeLa cells, respectively, belongs to Bath, Daroogar2, Latifeh2, Crend, Sehat, Nasim and Aqua fresh toothpastes; however, the least cytotoxic effect on primer epithelial cells of oral mucosa and HeLa cells, respectively, belongs to Pronamel followed by Crest (sensitive), Close-up, Oral-B, Signal, Colgate, Paradent, and AME. PMID:25878477

Scientific and regulatory policy committee (SRPC) paper: Assessment of Circulating Hormones in Nonclinical Toxicity Studies. III Female Reproductive Hormones

EPA Science Inventory

Hormonally mediated effects on the female reproductive system may manifest in pathologic changes of endocrine-responsive organs and altered reproductive function. Identification of these effects requires proper assessment, which may include investigative studies of female reprod...

Mechanism of Action of Lung Damage Caused by a Nanofilm Spray Product

PubMed Central

Larsen, Søren T.; Dallot, Constantin; Larsen, Susan W.; Rose, Fabrice; Poulsen, Steen S.; Nørgaard, Asger W.; Hansen, Jitka S.; Sørli, Jorid B.; Nielsen, Gunnar D.; Foged, Camilla

2014-01-01

Inhalation of waterproofing spray products has on several occasions caused lung damage, which in some cases was fatal. The present study aims to elucidate the mechanism of action of a nanofilm spray product, which has been shown to possess unusual toxic effects, including an extremely steep concentration-effect curve. The nanofilm product is intended for application on non-absorbing flooring materials and contains perfluorosiloxane as the active film-forming component. The toxicological effects and their underlying mechanisms of this product were studied using a mouse inhalation model, by in vitro techniques and by identification of the binding interaction. Inhalation of the aerosolized product gave rise to increased airway resistance in the mice, as evident from the decreased expiratory flow rate. The toxic effect of the waterproofing spray product included interaction with the pulmonary surfactants. More specifically, the active film-forming components in the spray product, perfluorinated siloxanes, inhibited the function of the lung surfactant due to non-covalent interaction with surfactant protein B, a component which is crucial for the stability and persistence of the lung surfactant film during respiration. The active film-forming component used in the present spray product is also found in several other products on the market. Hence, it may be expected that these products may have a toxicity similar to the waterproofing product studied here. Elucidation of the toxicological mechanism and identification of toxicological targets are important to perform rational and cost-effective toxicological studies. Thus, because the pulmonary surfactant system appears to be an important toxicological target for waterproofing spray products, study of surfactant inhibition could be included in toxicological assessment of this group of consumer products. PMID:24863969

Reproductive and Developmental Toxicity of Formaldehyde: A Systematic Review

PubMed Central

Duong, Anh; Steinmaus, Craig; McHale, Cliona M.; Vaughan, Charles P.; Zhang, Luoping

2011-01-01

Formaldehyde, the recently classified carcinogen and ubiquitous environmental contaminant, has long been suspected of causing adverse reproductive and developmental effects, but previous reviews were inconclusive, due in part, to limitations in the design of many of the human population studies. In the current review, we systematically evaluated evidence of an association between formaldehyde exposure and adverse reproductive and developmental effects, in human populations and in vivo animal studies, in the peer-reviewed literature. The mostly retrospective human studies provided evidence of an association of maternal exposure with adverse reproductive and developmental effects. Further assessment of this association by meta-analysis revealed an increased risk of spontaneous abortion (1.76, 95% CI 1.20–2.59, p=0.002) and of all adverse pregnancy outcomes combined (1.54, 95% CI 1.27–1.88, p<0.001), in formaldehyde-exposed women, although differential recall, selection bias, or confounding cannot be ruled out. Evaluation of the animal studies including all routes of exposure, doses and dosing regimens studied, suggested positive associations between formaldehyde exposure and reproductive toxicity, mostly in males. Potential mechanisms underlying formaldehyde-induced reproductive and developmental toxicities, including chromosome and DNA damage (genotoxicity), oxidative stress, altered level and/or function of enzymes, hormones and proteins, apoptosis, toxicogenomic and epigenomic effects (such as DNA methylation), were identified. To clarify these associations, well-designed molecular epidemiologic studies, that include quantitative exposure assessment and diminish confounding factors, should examine both reproductive and developmental outcomes associated with exposure in males and females. Together with mechanistic and animal studies, this will allow us to better understand the systemic effect of formaldehyde exposure. PMID:21787879

Environmental Quality Research-Fate of Toxic Jet Fuel Components in Aquatic Systems

DTIC Science & Technology

1981-12-01

literature suggests that the maximum growt rate of Chlorella vulgaris is almost certainly between 1.5 and 2.5 days at water temperatures near 25°C...the results of an investigation of the potential toxic effects of the jet fuel JP-4 (petroleum-based and shale-based) on the aqueous environ- ment... investigated included fuel/ H 2 0 ratios and mixing times. Hydrocarbon composition of the WSF of JP-4, both petroleum e.nd shale-derived, appears to be

User’s Guide for T.E.S.T. (version 4.2) (Toxicity Estimation Software Tool) A Program to Estimate Toxicity from Molecular Structure

EPA Science Inventory

The user's guide describes the methods used by TEST to predict toxicity and physical properties (including the new mode of action based method used to predict acute aquatic toxicity). It describes all of the experimental data sets included in the tool. It gives the prediction res...

Research on Hygiene Based on Fieldwork and Experimental Studies.

PubMed

Yajima, Ichiro

2017-01-01

Several experimental studies on hygiene have recently been performed and fieldwork studies are also important and essential tools. However, the implementation of experimental studies is insufficient compared with that of fieldwork studies on hygiene. Here, we show our well-balanced implementation of both fieldwork and experimental studies of toxic-element-mediated diseases including skin cancer and hearing loss. Since the pollution of drinking well water by toxic elements induces various diseases including skin cancer, we performed both fieldwork and experimental studies to determine the levels of toxic elements and the mechanisms behind the development of toxic-element-related diseases and to develop a novel remediation system. Our fieldwork studies in several countries including Bangladesh, Vietnam and Malaysia demonstrated that drinking well water was polluted with high concentrations of several toxic elements including arsenic, barium, iron and manganese. Our experimental studies using the data from our fieldwork studies demonstrated that these toxic elements caused skin cancer and hearing loss. Further experimental studies resulted in the development of a novel remediation system that adsorbs toxic elements from polluted drinking water. A well-balanced implementation of both fieldwork and experimental studies is important for the prediction, prevention and therapy of toxic-element-mediated diseases.

Integrated survey on toxic effects of lindane on neotropical fish: Corydoras paleatus and Jenynsia multidentata.

PubMed

Pesce, Silvia F; Cazenave, Jimena; Monferrán, Magdalena V; Frede, Silvia; Wunderlin, Daniel A

2008-12-01

We report the effect of lindane on fish experimentally exposed to lindane. Sublethal toxicity was assessed through (a) changes in histopathology; (b) the activity of GST in different organs; and (c) bioaccumulation in exposed fish. We present a survey on toxic effects of lindane at these three levels, proposing a sequence of dose-dependent effects. Physiological damage was reversible at lowest doses, but severe at the highest, including damage consistent with fibrosis in liver and karyolitic nucleus in brain of both studied species. Exposure of Jenynsia multidentata above 6 microg L(-1) caused activation a GST in liver and gills, followed by inhibition at 75 microg L(-1). Interestingly, the bioaccumulation rate was suddenly increased when GST was inhibited. Corydoras paleatus exposed to 6.0 microg L(-1) lindane did not present significant changes in GST activity; however, enzymatic inhibition was observed above 25 microg L(-1). The bioaccumulation rate in C. paleatus remained constant throughout the experiments. All in all, these results evidence that C. paleatus is more sensitive to lindane than J. multidentata.

Selenium and Human Health: Witnessing a Copernican Revolution?

PubMed

Jablonska, Ewa; Vinceti, Marco

2015-01-01

In humans, selenium was hypothesized to lower the risk of several chronic diseases, mainly due to the antioxidant activity of selenium-containing proteins. Recent epidemiologic and laboratory studies, however, are changing our perception of the biological effects of this nutritionally essential trace element. We reviewed the most recent epidemiologic and biochemical literature on selenium, synthesizing the findings from these studies into a unifying view. Randomized trials have shown that selenium did not protect against cancer and other chronic diseases, but even increased the risk of specific neoplasms such as advanced prostate cancer and skin cancer, in addition to type 2 diabetes. Biochemical studies indicate that selenium may exert a broad pattern of toxic effects at unexpectedly low concentrations. Furthermore, its upregulation of antioxidant proteins (selenium-dependent and selenium-independent) may be a manifestation of self-induced oxidative stress. In conclusion, toxic effects of selenium species occur at lower concentrations than previously believed. Those effects may include a large range of proteomic changes and adverse health effects in humans. Since the effects of environmental exposure to this element on human health still remain partially unknown, but are potentially serious, the toxicity of selenium exposure should be further investigated and considered as a public health priority.

Development of a biopolymer nanoparticle-based method of oral toxicity testing in aquatic invertebrates.

PubMed

Gott, Ryan C; Luo, Yangchao; Wang, Qin; Lamp, William O

2014-06-01

Aquatic toxicity testing generally focuses on the water absorption/dermal route of exposure to potential toxic chemicals, while much less work has been done on the oral route of exposure. This is due in part to the difficulties of applying traditional oral toxicity testing to aquatic environments, including the tendency for test chemicals to dissolve into water. The use of biopolymer nanoparticles to encapsulate test chemicals onto food to prevent dissolution is one solution presented herein. The biopolymers zein and chitosan were explored for their previously known nanoparticle-forming abilities. Nanoparticles containing the test chemical rhodamine B were formed, applied as films to coat food, and then fed to the test organism, the freshwater amphipod Hyalella azteca. In feeding trials both zein and chitosan nanoparticles showed a significantly lower release rate of rhodamine B into water than food dyed with rhodamine B without biopolymer nanoparticles. Zein nanoparticles also showed better retention ability than chitosan nanoparticles. Both kinds of nanoparticles showed no significant effect on the survival, growth, or feeding behavior of H. azteca. Thus these biopolymers may be an effective system to encapsulate and deliver chemicals to aquatic invertebrates without interfering with common toxicity assessment endpoints like survival and growth. Copyright © 2014 Elsevier Inc. All rights reserved.

Toxicity evaluation of prodigiosin from Serratia marcescens in a Caenorhabditis elegans model

NASA Astrophysics Data System (ADS)

Seah, Siew-Wei; Nathan, Sheila; Wan, Kiew-Lian

2016-11-01

Serratia marcescens produces several secondary metabolites, including a red antimicrobial pigment, prodigiosin. There is considerable interest in prodigiosin and its derivatives due to their anticancer and immunosuppressive properties. Prodigiosin has also become the main choice of red dye in textiles. As prodigiosin has potentially high commercial value, there is a demand to develop high-throughput and cost-effective bioprocesses for prodigiosin production. However little is still known about its toxicity. This study was carried out to investigate the toxicity effect of prodigiosin. To determine if prodigiosin was potentially toxic to eukaryotic systems, the S. marcescens ATCC 274 wild type (Sma 274) and the non-prodigiosin producer S. marcescens Bizio WF mutant ATCC 29635 (WF mutant) were grown under the optimised conditions for prodigiosin production and fed to the nematode Caenorhabditis elegans. The mean time to death (TDmean) for Sma 274-infected worms assayed on agar was 112.6 hours while the WF mutant culture had a TDmean of 104.4 hours. However, the nematode killing kinetics were not significantly different between the prodigiosin-producing and non-producing S. marcescens strains (p>0.05). In lieu of its non-toxic property, prodigiosin has the potential to be developed for safe therapeutic applications and as a safe environmental friendly bio-dye.

The toxicity and invasive effects of QDs on mung bean development

NASA Astrophysics Data System (ADS)

Zhai, Peng; Wang, Xiaomei; Wang, Ruhua; Huang, Xuan; Feng, Gang; Lin, Guimiao; Chen, Qiang; Xu, Gaixia; Chen, Danni

2014-09-01

Objective: Nowadays, the nanomaterials have been applied in every aspects of our life, including cosmetics, fresh-keeping, antisepsis and medicines. However, we know little about the toxic effects of nanoparticles towards plants. In this thesis, we synthesized quantum dots (QDs), and then toxicity and invasive effects of QDs for mung beans were investigated. Methods: We synthesised red CdTe QDs in water sphase with L-Cystein stabilizers, then prepared different concentration of QDs solution to cultivate mung bean plant, the radical length of mung beans was measured after four days every day, after 7 days, the distribution of QDs in mung bean plant was recorded under the microscopic. Results: The result showed the QDs inhibited the growth of mung beans, the higher the concentration of QDs was, the greater the inhibition effect was. After 7 days, the radicle average lengths of mung beans in different concentrations of QDs solution - blank 0.1μmol/L 0.2μmol/L 0.5 μmol/L 1 μmol/L - were 19.350+/- 0.427, 14.050+/- 0.879, 10.525+/- 0.554, 7.250+/- 0.522, 7.650+/- 0.229. The QDs mostly adhered onto the root surface and hairs. Conclusion: In conclusion, the QDs synthesized with L-cystein have effects on the growth of mung beans. However, it is necessary to do more experiments to confirm the mechanism of the toxicity effect of QDs on plants.

Radiotherapy for malignancy in patients with scleroderma: The Mayo Clinic experience

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gold, Douglas G.; Miller, Robert C.; Petersen, Ivy A.

2007-02-01

Purpose: To determine the frequency of acute and chronic adverse effects in patients with scleroderma who receive radiotherapy for treatment of cancer. Methods and Materials: Records were reviewed of 20 patients with scleroderma who received radiotherapy. Acute and chronic toxic effects attributable to radiotherapy were analyzed, and freedom from radiation-related toxicity was calculated. Results: Of the 20 patients, 15 had acute toxic effects, with Grade 3 or higher toxicity for 3 patients. Seven patients had self-limited Grade 1 or 2 radiation dermatitis, and no patient had Grade 3 or higher radiation dermatitis. Thirteen patients had chronic toxic effects, with Grademore » 3 or higher chronic toxicity for 3 patients. The median estimated time to any grade chronic toxicity was 0.4 years, and the median estimated time to Grade 3 or higher chronic toxicity has not been reached. Conclusions: The results suggest that although some patients with scleroderma treated with radiation experience considerable toxic effects, the occurrence of Grade 3 or higher toxicity may be less than previously anticipated.« less

Air toxics and asthma: impacts and end points.

PubMed Central

Eschenbacher, W L; Holian, A; Campion, R J

1995-01-01

The National Urban Air Toxics Research Center (NUATRC) hosted a medical/scientific workshop focused on possible asthma/air toxics relationships, with the results of the NUATRC's first research contract with the University of Cincinnati as the point of discussion. The workshop was held at the Texas Medical Center on 4 February 1994 and featured presentations by distinguished academic, government, and industry scientists. This one-day session explored the impact of various environmental factors, including air toxics, on asthma incidence and exacerbation; an emphasis was placed on future research directions to be pursued in the asthma/air toxics area. A key research presentation on the association of air toxics and asthma, based on the study sponsored by NUATRC, was given by Dr. George Leikauf of the University of Cincinnati Medical Center. Additional presentations were made by H. A. Boushey, Jr., Cardiovascular Research Institute/University of California at San Francisco, who spoke on of the Basic Mechanisms of Asthma; K. Sexton, U.S. Environmental Protection Agency, who spoke on hazardous air pollutants: science/policy interface; and D. V. Bates, Department of Health Care and Epidemiology at the University of British Columbia, who spoke on asthma epidemiology. H. Koren, U.S. Environmental Protection Agency, and M. Yeung, of the Respiratory Division/University of British Columbia, Vancouver General Hospital, discussed occupational health impacts on asthma. Doyle Pendleton, Texas Natural Resource Conservation Commission, reviewed air quality measurements in Texas. The information presented at the workshop suggested a possible association of asthma exacerbations with ozone and particulate matter (PM10); however, direct relationships between worsening asthma and air toxic ambient levels were not established. Possible respiratory health effects associated with air toxics will require considerably more investigation, especially in the area of human exposure assessment. Two major recommendations for future research resulted from this workshop and an accompanying NUATRC Scientific Advisory Panel meeting: a need for more complete individual personal exposure assessments so that accurate determinations of actual personal exposures to various pollutants can be made; and a need for field experiments utilizing biomarkers of exposure and effect to more accurately assess the extent and variability of the biological effects, if any, of individual air toxics. PMID:8549475

Inhalational mold toxicity: fact or fiction? A clinical review of 50 cases.

PubMed

Khalili, Barzin; Montanaro, Marc T; Bardana, Emil J

2005-09-01

Three well-accepted mechanisms of mold-induced disease exist: allergy, infection, and oral toxicosis. Epidemiologic studies suggest a fourth category described as a transient aeroirritation effect. Toxic mold syndrome or inhalational toxicity continues to cause public concern despite a lack of scientific evidence that supports its existence. To conduct a retrospective review of 50 cases of purported mold-induced toxic effects and identify unrecognized conditions that could explain presenting symptoms; to characterize a subgroup with a symptom complex suggestive of an aeroirritation-mediated mechanism and compare this group to other diagnostic categories, such as sick building syndrome and idiopathic chemical intolerance; and to discuss the evolution of toxic mold syndrome from a clinical perspective. Eighty-two consecutive medical evaluations were analyzed of which 50 met inclusion criteria. These cases were critically reviewed and underwent data extraction of 23 variables, including demographic data, patient symptoms, laboratory, imaging, and pulmonary function test results, and an evaluation of medical diagnoses supported by medical record review, examination, and/or test results. Upper respiratory tract, lower respiratory tract, systemic, and neurocognitive symptoms were reported in 80%, 94%, 74%, and 84% of patients, respectively. Thirty patients had evidence of non-mold-related conditions that explained their presenting complaints. Two patients had evidence of allergy to mold allergens, whereas 1 patient exhibited mold-induced psychosis best described as toxic agoraphobia. Seventeen patients displayed a symptom complex that could be postulated to be caused by a transient mold-induced aeroirritation. The clinical presentation of patients with perceived mold-induced toxic effects is characterized by a disparate constellation of symptoms. Close scrutiny revealed a number of preexisting diagnoses that could plausibly explain presenting symptoms. The pathogenesis of aeroirritation implies completely transient symptoms linked to exposures at the incriminated site. Toxic mold syndrome represents the furtive evolution of aeroirritation from a transient to permanent symptom complex in patients with a psychogenic predisposition. In this respect, the core symptoms of toxic mold syndrome and their gradual transition to chronic symptoms related to nonspecific environmental fragrances and irritants appear to mimic what has been observed with other pseudodiagnostic categories, such as sick building syndrome and idiopathic chemical intolerance.

Multi-Toxic Endpoints of the Foodborne Mycotoxins in Nematode Caenorhabditis elegans

PubMed Central

Yang, Zhendong; Xue, Kathy S.; Sun, Xiulan; Tang, Lili; Wang, Jia-Sheng

2015-01-01

Aflatoxins B1 (AFB1), deoxynivalenol (DON), fumonisin B1 (FB1), T-2 toxin (T-2), and zearalenone (ZEA) are the major foodborne mycotoxins of public health concerns. In the present study, the multiple toxic endpoints of these naturally-occurring mycotoxins were evaluated in Caenorhabditis elegans model for their lethality, toxic effects on growth and reproduction, as well as influence on lifespan. We found that the lethality endpoint was more sensitive for T-2 toxicity with the EC50 at 1.38 mg/L, the growth endpoint was relatively sensitive for AFB1 toxic effects, and the reproduction endpoint was more sensitive for toxicities of AFB1, FB1, and ZEA. Moreover, the lifespan endpoint was sensitive to toxic effects of all five tested mycotoxins. Data obtained from this study may serve as an important contribution to knowledge on assessment of mycotoxin toxic effects, especially for assessing developmental and reproductive toxic effects, using the C. elegans model. PMID:26633509

Comparative In Vitro Toxicity Evaluation of Heavy Metals (Lead, Cadmium, Arsenic, and Methylmercury) on HT-22 Hippocampal Cell Line.

PubMed

Karri, Venkatanaidu; Kumar, Vikas; Ramos, David; Oliveira, Eliandre; Schuhmacher, Marta

2018-07-01

Heavy metals are considered some of the most toxic environmental pollutants. Exposure to heavy metals including lead (Pb), cadmium (Cd), arsenic (As), and methyl mercury (MeHg) has long been known to cause damage to human health. Many recent studies have supported the hippocampus as the major target for these four metals for inflicting cognitive dysfunction. In the present study, we proposed hippocampal relevant in vitro toxicity of Pb, Cd, As, and MeHg in HT-22 cell line. This study reports, initially, cytotoxic effects in acute, subchronic, chronic exposures. We further investigated the mechanistic potency of DNA damage and apoptosis damage with the observed cytotoxicity. The genotoxicity and apoptosis were measured by using the comet assay, annexin-V FTIC / propidium iodide (PI) assay, respectively. The results of cytotoxicity assay clearly demonstrated significant concentration and time-dependent effects on HT-22 cell line. The genotoxic and apoptosis effects also concentration-dependent fashion with respect to their potency in the range of IC 10 -IC 30, maximal level of damage observed in MeHg. In conclusion, the obtained result suggests concentration and potency-dependent response; the maximal level of toxicity was observed in MeHg. These novel findings support that Pb, Cd, As, and MeHg induce cytotoxic, genotoxic, and apoptotic effects on HT-22 cells in potency-dependent manner; MeHg> As> Cd> Pb. Therefore, the toxicity of Pb, Cd, As, and MeHg could be useful for knowing the common underlying molecular mechanism, and also for estimating the mixture impacts on HT-22 cell line.

[Efectiveness of topical therapies in patients with breast cancer that experience radiodermatitis. A systematic review].

PubMed

Fernández-Castro, Mercedes; Martín-Gil, Belén

2015-01-01

After radiation therapy most patients experience acute skin toxicity to some degree. The purpose of this systematic review is to assess the available evidence concerning the effectivity of topical therapies on patients with breast cancer that experience radiodermatitis after radiotherapy. The review included clinical trials aimed to evaluate topical therapies for prevention or treatment of acute radiodermatitis in women with breast cancer, which were published between 2009 and 2014. The bibliographic search was carried out in the following databases: PubMed, Cinahl, Cochrane Plus, IBECS and LILACS. The studies were selected independently by peer reviewers using the Critical Appraisal Skills Programme in its Spanish version. 86 bibliographical references were identified. Twenty full-text articles of clinical trials were assessed and two were excluded because they were not completed; 12 of clinical trials evaluated topical treatment with creams and ointments, three with corticosteroid creams and other three with dressings. The effectivity of human epidermal growth factor cream, linoleic acid emulsion, topical silver sulfadiazine, corticosteroids creams and polyurethane dressings has been shown in these clinical trials. Given that radiodermatitis is a dynamic process, these topical agents were effective in different stages of skin toxicity. Some of them delayed the onset, others decreased the development and severity of acute skin toxicity degree and others improved the subjective symptoms (itching, pain, burning). Only polyurethane dressings suggest effectiveness in all stages of skin toxicity, in prevention, management of the different skin toxicity degrees and improvement of wellbeing. Copyright © 2015. Published by Elsevier España, S.L.U.

Protective effects of chlorogenic acid in 3-nitropropionic acid induced toxicity and genotoxicity.

PubMed

Alarcón-Herrera, Norberto; Flores-Maya, Saúl; Bellido, Belén; García-Bores, Ana M; Mendoza, Ernesto; Ávila-Acevedo, Guillermo; Hernández-Echeagaray, Elizabeth

2017-11-01

Mitochondrial inhibition with the toxin 3-Nitropropionic acid (3-NP) has been used to study the underlying mechanisms in striatal neurodegeneration, but few experiments have evaluated its toxicity and genotoxicity of in vivo administration. Furthermore, different antioxidant molecules may prevent degeneration induced by the toxic effects of 3-NP. Therefore, the purpose of this study was to evaluate the toxicity and genotoxicity induced by 3-NP (15 mg/kg) in the micronuclei assay method; also, we assessed chlorogenic acid (CGA, 100 mg/kg) for its anti-toxic and anti-genotoxic effect in damage produced by in vivo treatment with 3-NP. 3-NP induced toxicity and genotoxicity. CGA administered as a co-treatment with 3-NP (3-NP + CA) reduced toxicity by 32.76%, as a pre-treatment for 5 days only, followed by 3-NP treatment (P/CA, 3-NP) inhibiting toxicity by 24.04%, or as a pre-treatment, plus a co-treatment with 3-NP (P/CA, 3-NP + CA) avoided any toxic effect. CGA alone did not exhibit any toxic effect. Only P/CGA, 3-NP + CGA group, avoided toxicity and genotoxicity, suggesting that CGA could be suitable to prevent, reduce or delay toxicity and cell death. Copyright © 2017 Elsevier Ltd. All rights reserved.

Metabolomics reveals the mechanisms for the cardiotoxicity of Pinelliae Rhizoma and the toxicity-reducing effect of processing

NASA Astrophysics Data System (ADS)

Su, Tao; Tan, Yong; Tsui, Man-Shan; Yi, Hua; Fu, Xiu-Qiong; Li, Ting; Chan, Chi Leung; Guo, Hui; Li, Ya-Xi; Zhu, Pei-Li; Tse, Anfernee Kai Wing; Cao, Hui; Lu, Ai-Ping; Yu, Zhi-Ling

2016-10-01

Pinelliae Rhizoma (PR) is a commonly used Chinese medicinal herb, but it has been frequently reported about its toxicity. According to the traditional Chinese medicine theory, processing can reduce the toxicity of the herbs. Here, we aim to determine if processing reduces the toxicity of raw PR, and to explore the underlying mechanisms of raw PR-induced toxicities and the toxicity-reducing effect of processing. Biochemical and histopathological approaches were used to evaluate the toxicities of raw and processed PR. Rat serum metabolites were analyzed by LC-TOF-MS. Ingenuity pathway analysis of the metabolomics data highlighted the biological pathways and network functions involved in raw PR-induced toxicities and the toxicity-reducing effect of processing, which were verified by molecular approaches. Results showed that raw PR caused cardiotoxicity, and processing reduced the toxicity. Inhibition of mTOR signaling and activation of the TGF-β pathway contributed to raw PR-induced cardiotoxicity, and free radical scavenging might be responsible for the toxicity-reducing effect of processing. Our data shed new light on the mechanisms of raw PR-induced cardiotoxicity and the toxicity-reducing effect of processing. This study provides scientific justifications for the traditional processing theory of PR, and should help in optimizing the processing protocol and clinical combinational application of PR.

Potential fluoride toxicity from oral medicaments: A review.

PubMed

Ullah, Rizwan; Zafar, Muhammad Sohail; Shahani, Nazish

2017-08-01

The beneficial effects of fluoride on human oral health are well studied. There are numerous studies demonstrating that a small amount of fluoride delivered to the oral cavity decreases the prevalence of dental decay and results in stronger teeth and bones. However, ingestion of fluoride more than the recommended limit leads to toxicity and adverse effects. In order to update our understanding of fluoride and its potential toxicity, we have described the mechanisms of fluoride metabolism, toxic effects, and management of fluoride toxicity. The main aim of this review is to highlight the potential adverse effects of fluoride overdose and poorly understood toxicity. In addition, the related clinical significance of fluoride overdose and toxicity has been discussed.

Implications of the Differential Toxicological Effects of III-V Ionic and Particulate Materials for Hazard Assessment of Semiconductor Slurries.

PubMed

Jiang, Wen; Lin, Sijie; Chang, Chong Hyun; Ji, Zhaoxia; Sun, Bingbing; Wang, Xiang; Li, Ruibin; Pon, Nanetta; Xia, Tian; Nel, André E

2015-12-22

Because of tunable band gaps, high carrier mobility, and low-energy consumption rates, III-V materials are attractive for use in semiconductor wafers. However, these wafers require chemical mechanical planarization (CMP) for polishing, which leads to the generation of large quantities of hazardous waste including particulate and ionic III-V debris. Although the toxic effects of micron-sized III-V materials have been studied in vivo, no comprehensive assessment has been undertaken to elucidate the hazardous effects of submicron particulates and released III-V ionic components. Since III-V materials may contribute disproportionately to the hazard of CMP slurries, we obtained GaP, InP, GaAs, and InAs as micron- (0.2-3 μm) and nanoscale (<100 nm) particles for comparative studies of their cytotoxic potential in macrophage (THP-1) and lung epithelial (BEAS-2B) cell lines. We found that nanosized III-V arsenides, including GaAs and InAs, could induce significantly more cytotoxicity over a 24-72 h observation period. In contrast, GaP and InP particulates of all sizes as well as ionic GaCl3 and InCl3 were substantially less hazardous. The principal mechanism of III-V arsenide nanoparticle toxicity is dissolution and shedding of toxic As(III) and, to a lesser extent, As(V) ions. GaAs dissolves in the cell culture medium as well as in acidifying intracellular compartments, while InAs dissolves (more slowly) inside cells. Chelation of released As by 2,3-dimercapto-1-propanesulfonic acid interfered in GaAs toxicity. Collectively, these results demonstrate that III-V arsenides, GaAs and InAs nanoparticles, contribute in a major way to the toxicity of III-V materials that could appear in slurries. This finding is of importance for considering how to deal with the hazard potential of CMP slurries.

Behavioral toxicology in the 21st century: challenges and opportunities for behavioral scientists. Summary of a symposium presented at the annual meeting of the neurobehavioral teratology society, June, 2009.

PubMed

Bushnell, Philip J; Kavlock, Robert J; Crofton, Kevin M; Weiss, Bernard; Rice, Deborah C

2010-01-01

The National Research Council (NRC) of the National Academies of Science recently published a report of its vision of toxicity testing in the 21st century. The report proposes that the current toxicity testing paradigm that depends upon whole-animal tests be replaced with a strategy based upon in vitro tests, in silico models and evaluations of toxicity at the human population level. These goals are intended to set in motion changes that will transform risk assessment into a process in which adverse effects on public health are predicted by quantitative structure-activity relationship (QSAR) models and data from suites of high-throughput in vitro tests. The potential roles for whole-animal testing in this futuristic vision are both various and undefined. A symposium was convened at the annual meeting of the Neurobehavioral Teratology Society in Rio Grande, Puerto Rico in June, 2009 to discuss the potential challenges and opportunities for behavioral scientists in developing and/or altering this strategy toward the ultimate goal of protecting public health from hazardous chemicals. R. Kavlock described the NRC vision, introduced the concept of the 'toxicity pathway' (a central guiding principle of the NRC vision), and described the current status of an initial implementation this approach with the EPA's ToxCast(R) program. K. Crofton described a pathway based upon disruption of thyroid hormone metabolism during development, including agents, targets, and outcomes linked by this mode of action. P. Bushnell proposed a pathway linking the neural targets and cellular to behavioral effects of acute exposure to organic solvents, whose predictive power is limited by our incomplete understanding of the complex CNS circuitry that mediates the behavioral responses to solvents. B. Weiss cautioned the audience regarding a pathway approach to toxicity testing, using the example of the developmental toxicity of phthalates, whose effects on mammalian sexual differentiation would be difficult to identify based on screening tests in vitro. Finally, D. Rice raised concerns regarding the use of data derived from toxicity screening tests to human health risk assessments. Discussion centered around opportunities and challenges for behavioral toxicologists regarding this impending paradigm shift. Opportunities include: identifying and characterizing toxicity pathways; informing the conditions and limits of extrapolation; addressing issues of susceptibility and variability; providing reality-checks on selected positives and negatives from screens; and performing targeted testing and dose-response assessments of chemicals flagged during screening. Challenges include: predicting behavior using models of complex neurobiological pathways; standardizing study designs and dependent variables to facilitate creation of databases; and managing the cost and efficiency of behavioral assessments. Thus, while progress is being made in approaching the vision of 21st century toxicology, we remain a long way from replacing whole-animal tests; indeed, some animal testing will be essential for the foreseeable future at least. Initial advances will likely provide better prioritization tools so that animal resources are used more efficiently and effectively.

Assessing potential dietary toxicity of heavy metals in selected vegetables and food crops*

PubMed Central

Islam, Ejaz ul; Yang, Xiao-e; He, Zhen-li; Mahmood, Qaisar

2007-01-01

Heavy metals, such as cadmium, copper, lead, chromium and mercury, are important environmental pollutants, particularly in areas with high anthropogenic pressure. Their presence in the atmosphere, soil and water, even in traces can cause serious problems to all organisms, and heavy metal bioaccumulation in the food chain especially can be highly dangerous to human health. Heavy metals enter the human body mainly through two routes namely: inhalation and ingestion, ingestion being the main route of exposure to these elements in human population. Heavy metals intake by human populations through food chain has been reported in many countries. Soil threshold for heavy metal toxicity is an important factor affecting soil environmental capacity of heavy metal and determines heavy metal cumulative loading limits. For soil-plant system, heavy metal toxicity threshold is the highest permissible content in the soil (total or bioavailable concentration) that does not pose any phytotoxic effects or heavy metals in the edible parts of the crops does not exceed food hygiene standards. Factors affecting the thresholds of dietary toxicity of heavy metal in soil-crop system include: soil type which includes soil pH, organic matter content, clay mineral and other soil chemical and biochemical properties; and crop species or cultivars regulated by genetic basis for heavy metal transport and accumulation in plants. In addition, the interactions of soil-plant root-microbes play important roles in regulating heavy metal movement from soil to the edible parts of crops. Agronomic practices such as fertilizer and water managements as well as crop rotation system can affect bioavailability and crop accumulation of heavy metals, thus influencing the thresholds for assessing dietary toxicity of heavy metals in the food chain. This paper reviews the phytotoxic effects and bioaccumulation of heavy metals in vegetables and food crops and assesses soil heavy metal thresholds for potential dietary toxicity. PMID:17173356

Assessing potential dietary toxicity of heavy metals in selected vegetables and food crops.

PubMed

Islam, Ejaz ul; Yang, Xiao-e; He, Zhen-li; Mahmood, Qaisar

2007-01-01

Heavy metals, such as cadmium, copper, lead, chromium and mercury, are important environmental pollutants, particularly in areas with high anthropogenic pressure. Their presence in the atmosphere, soil and water, even in traces can cause serious problems to all organisms, and heavy metal bioaccumulation in the food chain especially can be highly dangerous to human health. Heavy metals enter the human body mainly through two routes namely: inhalation and ingestion, ingestion being the main route of exposure to these elements in human population. Heavy metals intake by human populations through food chain has been reported in many countries. Soil threshold for heavy metal toxicity is an important factor affecting soil environmental capacity of heavy metal and determines heavy metal cumulative loading limits. For soil-plant system, heavy metal toxicity threshold is the highest permissible content in the soil (total or bioavailable concentration) that does not pose any phytotoxic effects or heavy metals in the edible parts of the crops does not exceed food hygiene standards. Factors affecting the thresholds of dietary toxicity of heavy metal in soil-crop system include: soil type which includes soil pH, organic matter content, clay mineral and other soil chemical and biochemical properties; and crop species or cultivars regulated by genetic basis for heavy metal transport and accumulation in plants. In addition, the interactions of soil-plant root-microbes play important roles in regulating heavy metal movement from soil to the edible parts of crops. Agronomic practices such as fertilizer and water managements as well as crop rotation system can affect bioavailability and crop accumulation of heavy metals, thus influencing the thresholds for assessing dietary toxicity of heavy metals in the food chain. This paper reviews the phytotoxic effects and bioaccumulation of heavy metals in vegetables and food crops and assesses soil heavy metal thresholds for potential dietary toxicity.

The Effects of Temperature and Hydrostatic Pressure on Metal Toxicity: Insights into Toxicity in the Deep Sea.

PubMed

Brown, Alastair; Thatje, Sven; Hauton, Chris

2017-09-05

Mineral prospecting in the deep sea is increasing, promoting concern regarding potential ecotoxicological impacts on deep-sea fauna. Technological difficulties in assessing toxicity in deep-sea species has promoted interest in developing shallow-water ecotoxicological proxy species. However, it is unclear how the low temperature and high hydrostatic pressure prevalent in the deep sea affect toxicity, and whether adaptation to deep-sea environmental conditions moderates any effects of these factors. To address these uncertainties we assessed the effects of temperature and hydrostatic pressure on lethal and sublethal (respiration rate, antioxidant enzyme activity) toxicity in acute (96 h) copper and cadmium exposures, using the shallow-water ecophysiological model organism Palaemon varians. Low temperature reduced toxicity in both metals, but reduced cadmium toxicity significantly more. In contrast, elevated hydrostatic pressure increased copper toxicity, but did not affect cadmium toxicity. The synergistic interaction between copper and cadmium was not affected by low temperature, but high hydrostatic pressure significantly enhanced the synergism. Differential environmental effects on toxicity suggest different mechanisms of action for copper and cadmium, and highlight that mechanistic understanding of toxicity is fundamental to predicting environmental effects on toxicity. Although results infer that sensitivity to toxicants differs across biogeographic ranges, shallow-water species may be suitable ecotoxicological proxies for deep-sea species, dependent on adaptation to habitats with similar environmental variability.