40 CFR 797.1600 - Fish early life stage toxicity test.
Code of Federal Regulations, 2014 CFR
2014-07-01
... the test solution concentrations. The test terminates following 60 days of post-hatch exposure (for an... 40 Protection of Environment 32 2014-07-01 2014-07-01 false Fish early life stage toxicity test... Fish early life stage toxicity test. (a) Purpose. This guideline is intended to be used for assessing...
40 CFR 797.1600 - Fish early life stage toxicity test.
Code of Federal Regulations, 2011 CFR
2011-07-01
... the test solution concentrations. The test terminates following 60 days of post-hatch exposure (for an... 40 Protection of Environment 32 2011-07-01 2011-07-01 false Fish early life stage toxicity test... Fish early life stage toxicity test. (a) Purpose. This guideline is intended to be used for assessing...
TOXICITY OF AHR AGONISTS TO FISH EARLY LIFE STAGES
Fish early life stages are exceptionally sensitive to the lethal toxicity of chemicals that act as arylhydrocarbon receptor (AhR) agonists. Toxicity characterizations based on 2,3,7,8-tetrachlorodibenzo-p-dioxin, generally the most potent AhR agonist, support the toxicity equiva...
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.
To better understand the mechanisms by which persistent bioaccumulative toxicants (PBTs) produce toxicity during fish early life stages (ELS), dose response relationships need to be determined in relation to the dynamic distribution of chemicals in sensitive tissues. In this stud...
The toxicity of TCDD to early life stages of F1 generation brook trout (Salvelinus fontinalis) was determined when dosed by maternal transfer. Effects were compared across six treatments including a control. The experimental groups based on TCDD concentrations in freshly spawned ...
Fish early life stages (ELS) are more sensitive than juveniles or adults to many persistent bioaccumulative toxicants (PBTs). To better understand the mechanisms by which these chemicals produce toxicity during ELS, dose-response relationships need to be determined in relation t...
Fish early life stages (ELS) are more sensitive than juveniles or adults to many persistent bioaccumulative toxicants (PBTs). To better understand the mechanisms by which these chemicals produce toxicity during fish ELS, dose-response relationships need to be determined in relat...
DOE Office of Scientific and Technical Information (OSTI.GOV)
Patton, Gregory W; Dauble, Dennis D; Chamness, Mickie A
The objective of this study was to evaluate site-specific effects for early life-stage (eyed eggs to free swimming juveniles) fall chinook salmon that might be exposed to hexavalent chromium from Hanford groundwater sources. Our exposure conditions included hexavalent chromium obtained from Hanford groundwater wells near the Columbia River, Columbia River water as the diluent, and locally adapted populations of fall chinook salmon. This report describes both a 96-hr pretest using rainbow trout eggs and an early life-stage test beginning with chinook salmon eggs.
The toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) to the early life stages of F1 generation brook trout (Salvelinus fontinalis) was determined, when dosed by maternal transfer.Effects were compared across six treatments, including a control.The experimental groups, based...
Lasier, P.; Winger, P.; Bogenrieder, K.; Shelton, J.
2000-01-01
The robust redhorse is a ?Species-at-Risk? in the lower Oconee River, GA. The population is composed of aging adults with little natural recruitment. Factors contributing to the loss of early-life stages are unknown, but contaminants associated with fine sediments may play a role. The objectives of this study were to determine toxicities of sediments and pore waters from the Oconee River to early-life stages of robust redhorse and to establish toxic thresholds of metals (Cd, Cu, Mn, Zn) and ammonia, elements potentially threatening this species. Depositional sediments were collected from the only known spawning site and three sites downstream of major tributaries. Sediment pore waters were extracted in the laboratory from all sites and in situ at two sites. Toxicity tests with sediments, pore waters and metal solutions were initiated with eggs, yolk-sac fry and swim-up fry to determine effects on the life stage initially exposed as well as effects manifested in later developmental stages. Survival and growth were test endpoints, and toxicity was observed in both sediments and pore waters. Although the yolk- sac stage was the most sensitive across all tests, sediment toxicity was elicited only in tests initiated with eggs that developed through the yolk-sac stage. Toxicity appeared to be due to Mn in sediment and pore water exposures, but was more prevalent in pore waters. Sediment handling and the associated effects on redox potential contributed to the elevated concentrations of Mn in pore waters. Pore waters extracted in situ had significantly less Mn and were less toxic than laboratory-extracted pore waters. These data suggest that sediment-associated Mn may impact early-life stages of robust redhorse in the Oconee River.
Walker, Mary K.; Zabel, Erik W.; Akerman, Gun; Balk, Lennart; Wright, Peggy J.; Tillitt, Donald E.
1996-01-01
In the environment, lipophilic contaminants such as halogenated aromatic hydrocarbons (HAHs, e.g., polychlorinated biphenyls, PCBs) and polycyclic aromatic hydrocarbons (PAHs, e.g., benzo[a]pyrene) readily bioaccumulate in fish, and the bioaccumulation of these lipophilic chemicals by adult fish may have significant consequences on the development and survival of their offspring. Halogenated and polycyclic aromatic hydrocarbons translocate from adult female body stores into eggs during oocyte maturation, and early life stages of fish are often more sensitive than adults to the toxicity of these chemicals. Thus, the presence of persistent, bioaccumulative contaminants in the environment may pose a risk to fish early life stage survival and ultimately reduce recruitment into the adult population.Typically, standard early life stage toxicity studies exposed embryos, larvae, and juveniles to graded concentrations of waterborne toxicants, and dose-response relationships are based on the concentrations of chemicals in the water. However, use of waterborne exposure to assess the toxicity of persistent, bioaccumulative contaminants, such as HAHs and PAHs, has two significant drawbacks. First, uptake of hydrophobic chemicals, such as HAHs and PAHs, into the developing embryo from water is not a significant route of exposure in the environment since concentrations of these chemicals freely dissolved in water are extremely low. Rather, maternal deposition into developing oocytes is the most significant source of these chemicals to the embryo. Second, the dose received by the target tissue, in this case the developing embryo, is the most accurate predictor of the toxic response, and since extrapolation from water concentrations of the chemical to egg concentrations is required, the exact dose received by the embryo can only be estimated, often with large uncertainty. Due to these drawbacks, it is important to develop an alternative exposure method that will directly expose the developing embryo without the need to chronically expose adult fish with subsequent natural deposition of hydrophobic chemicals into the oocytes. Fish egg injection provides this exposure route. Embryos are exposed directly after fertilization with known doses of contaminants, the dose is delivered prior to critical developmental events, and extrapolation of the dose received by the embryo is not needed.We have developed two unique fish egg injection methods as alternative routes of exposure for fish early life stage toxicity studies of lipophilic environmental contaminants. With either method, individual fish eggs are injected with a known dose of chemical. The first approach, a microinjection method, originally developed to assess the developmental toxicity of HAH congeners to early life stages of salmonids, utilizes micro-syringes, 30- gauge stainless steel injection needles, and micro- to nanoliter injection volume. The second approach, a nano-injection method, utilizes glass capillary micropipettes with 2 to 10 µm tips as injection needles, and nano- to picoliter injection volume, allowing injection of nearly any size of fish egg.Both of these egg injection methods allow an investigator to assess the toxicity of lipophilic environmental contaminants to early life stages of fish in a manner that realistically reflects environmental exposure and allows accurate quantitation of the dose to the developing embryo. These injection techniques, however, are not limited to use with only lipophilic chemicals. Since the developmental toxicity of many environmental contaminants ultimately depends on the dose received by the embryo, these egg injection methods could serve as a realistic exposure route in many fish early life stage toxicity studies.
Chronic fish toxicity is a key parameter for hazard classification and environmental risk assessment of chemicals, and the OECD 210 fish early life-stage (FELS) test is the primary guideline test used for various international regulatory programs. There exists a need to develop ...
Toxicity of naproxen sodium and its mixture with tramadol hydrochloride on fish early life stages.
Sehonova, Pavla; Plhalova, Lucie; Blahova, Jana; Doubkova, Veronika; Prokes, Miroslav; Tichy, Frantisek; Fiorino, Emma; Faggio, Caterina; Svobodova, Zdenka
2017-12-01
Pharmaceuticals occur in water bodies as a consequence of their incomplete removal during waste water treatment processes. The occurence of pharmaceuticals in surface waters as well as their possible impact on aquatic vertebrates have received considerable attention in recent years. However, there is still a lack of informations on the chronic effects of widely used drugs as well as their possible mixture toxicity on non-target aquatic vertebrates as well as their possible mixture toxicity. The aim of this study was to assess the effects of naproxen sodium on early life stages of fish and evaluate its mixture toxicity with tramadol hydrochloride, which was assessed in our earlier study as a single substance. Two embryo-larval toxicity tests with common carp (Cyprinus carpio) were performed according to the OECD guideline 210 (Fish, Early-life Stage Toxicity Test) in order to assess the subchronic toxicity of naproxen sodium and tramadol hydrochlorid-naproxen sodium mixture at the concentrations of 10; 50; 100 and 200 μg/L. These experiments were conducted for 32 days. The subchronic exposure to naproxen sodium and naproxen sodium and tramadol hydrochloride mixture had a strong effect on the early life stages of common carp. Hatching, developmental rate, morphology, histopathology and, in the case of the naproxen sodium and tramadol hydrochloride mixture, mortality were influenced. The bioindicators of oxidative stress were also influenced. The LOEC was determined at 10 μg/L for both naproxen sodium and naproxen sodium and tramadol hydrochloride mixture. Copyright © 2017 Elsevier Ltd. All rights reserved.
Fish early life stage: Developing AOPs to support targeted reduction and replacement
There is an interest in developing alternatives to the fish early-life stage (FELS) test (OECD test guideline 210), for predicting adverse chronic toxicity outcomes (e.g., impacts on growth and survival). Development and characterization of adverse outcome pathways (AOPs) related...
The fish early life-stage (FELS) test (OECD Test Guideline 210) is the primary test used internationally to estimate chronic fish toxicity in support of ecological risk assessments and chemical management programs. As part of an on-going effort to develop efficient and cost-effec...
There is an interest in developing alternatives to the fish early-life stage (FELS) test (OECD test guideline 210), for predicting adverse outcomes (e.g., impacts on growth and survival) using less resource-intensive methods. Development and characterization of adverse outcome pa...
There is an interest in developing alternatives to the fish early-life stage (FELS) test (OECD test guideline 210), for predicting adverse outcomes (e.g., impacts on growth and survival) using less resource-intensive methods. Development and characterization of adverse outcome pa...
Chemical defense of early life stages of benthic marine invertebrates.
Lindquist, Niels
2002-10-01
Accurate knowledge of factors affecting the survival of early life stages of marine invertebrates is critically important for understanding their population dynamics and the evolution of their diverse reproductive and life-history characteristics. Chemical defense is an important determinant of survival for adult stages of many sessile benthic invertebrates, yet relatively little consideration has been given to chemical defenses at the early life stages. This review examines the taxonomic breadth of early life-stage chemical defense in relation to various life-history and reproductive characteristics, as well as possible constraints on the expression of chemical defense at certain life stages. Data on the localization of defensive secondary metabolites in larvae and the fitness-related consequences of consuming even a small amount of toxic secondary metabolites underpin proposals regarding the potential for Müllerian and Batesian mimicry to occur among marine larvae. The involvement of microbial symbionts in the chemical defense of early life stages illustrates its complexity for some species. As our knowledge of chemical defenses in early life stages grows, we will be able to more rigorously examine connections among phylogeny, chemical defenses, and the evolution of reproductive and life-history characteristics among marine invertebrates.
This presentation discusses methods used to extrapolate from in vitro high-throughput screening (HTS) toxicity data for an endocrine pathway to in vivo for early life stages in humans, and the use of a life stage PBPK model to address rapidly changing physiological parameters. A...
Acute toxicity of firefighting chemical formulations to four life stages of fathead minnow
Gaikowski, Mark P.; Hamilton, Steve J.; Buhl, Kevin J.; McDonald, Susan F.; Summers, Cliff H.
1996-01-01
Laboratory studies were conducted with four early life stages of fathead minnow,Pimephales promelas,to determine the acute toxicity of five firefighting chemical formulations in standardized soft and hard water. Egg, fry, 30-day posthatch, and 60-day posthatch life stages were tested with three fire retardants (Fire-Trol GTS-R, Fire-Trol LCG-R, and Phos-Chek D75-F) and two fire-suppressant foams (Phos-Chek WD-881 and Ansul Silv-Ex). Fry were generally the most sensitive life stage tested, whereas the eggs were the least sensitive life stage. Formulation toxicity was greater in hard water than in soft water for all life stages tested. Fire-suppressant foams were more toxic than the fire retardants. The 96-hr LC50s derived for fathead minnows were rank ordered from the most toxic to the least toxic formulation as follows: Phos-Chek WD-881 (13a??32 mg/liter) > Silv-Ex (19a??32 mg/liter) > Fire-Trol GTS-R (135a??787 mg/liter) > Phos-Chek D75-F (168a??2250 mg/liter) > Fire-Trol LCG-R (519a??6705 mg/liter) (ranges are the lowest and highest 96-hr LC50for each formulation). (C) 1996 Academic Press, Inc.
Currently, the fish early life-stage (FELS) test (OECD 210) is the primary guideline used to estimate chronic toxicity of regulated chemicals. Although already more cost-efficient than adult fish tests, the FELS test has some important drawbacks. Both industry and regulatory inst...
Buhl, Kevin J.; Hamilton, Steven J.
1998-01-01
Laboratorys studies were conducted to determine the acute toxicity of three fire retardants (Fire-Trol GTS-R, Fire-Trol LCG-R, and Phos-Chek D75-F), and two fire-suppressant foams (Phos-Chek WD-881 and Ansul Silv-Ex) to early life stages of chinook salmon, Oncorhynchus tshawytscha, in hard and soft water. Regardless of water type, swim-up fry and juveniles (60 and 90 d posthatch) exhibited similar sensitivities to each chemical and these life stages were more sensitive than eyed eggs. Foam suppressants were more toxic to each life stage than the fire retardants in both water types. The descending rank order of toxicity for these chemicals tested with swim-up fry and juveniles (range of 96-h median lethal concentrations [LC50s]) was Phos-Chek WD-881 (7–13 mg/L) > Ansul Silv-Ex (11–22 mg/L) > Phos-Chek D75-F (218–305 mg/L) > Fire-Trol GTS-R (218–412 mg/L) > Fire-Trol LCG-R (685–1,195 mg/L). Water type had a minor effect on the toxicity of these chemicals. Comparison of acute toxicity values with recommended application concentrations indicates that accidental inputs of these chemicals into stream environments would require substantial dilution (237- to 1,429-fold) to reach concentrations equivalent to their 96-h LC50s.
Lethal effect of dehydroleucodine (DhL) on amphibian Bufo arenarum embryos.
Moreno, Liliana Elizabeth; Juárez, Américo Osvaldo; Pelzer, Lilian Eugenia
2012-03-01
The dehydroleucodine is a sesquiterpene lactone isolated from Artemisia douglasiana Besser which is used in popular medicine. Toxicity tests using embryos of amphibian have been widely used in order to predict toxic effects of different compounds. However, to our knowledge, there are not studies focussed on the toxic effects of dehydroleucodine on Bufo arenarum, which is an anuran widely distributed in South America. The effect of dehydroleucodine on the survival of embryos was evaluated in an acute test during the early life stage of B. arenarum embryos. Lethality and the degree of adverse effects were dehydroleucodine dose-dependent. Overall, amphibian early life stages appeared to be more susceptible to the embryotoxicity associated with exposure to dehydroleucodine, especially at concentration greater that 3mM. This increased susceptibility may result from the relatively high rate of cellular differentiation and morphogenesis that occurs at this early stage of development. Copyright © 2012 Elsevier Ltd. All rights reserved.
Cross-taxa distinctions in aquatic toxicity between representative species for risk assessment
Standard ecological risk assessment practices often rely on larval and juvenile fish toxicity data as representative of the amphibian aquatic stage. Although empirical evidence suggests fish early life stage tests frequently are sufficiently sensitive to protect larval amphibian...
40 CFR 797.1600 - Fish early life stage toxicity test.
Code of Federal Regulations, 2013 CFR
2013-07-01
... dilution water or the test solution. (4) “Control” an exposure of test organisms to dilution water only or... (treatment) concentrations of a test substance and one control are required to conduct an early life stage... trays or cups for each test concentration and control (i.e., 30 per embryo cup with 2 replicates); (C...
40 CFR 797.1600 - Fish early life stage toxicity test.
Code of Federal Regulations, 2010 CFR
2010-07-01
... dilution water or the test solution. (4) “Control” an exposure of test organisms to dilution water only or... (treatment) concentrations of a test substance and one control are required to conduct an early life stage... trays or cups for each test concentration and control (i.e., 30 per embryo cup with 2 replicates); (C...
40 CFR 797.1600 - Fish early life stage toxicity test.
Code of Federal Regulations, 2012 CFR
2012-07-01
... dilution water or the test solution. (4) “Control” an exposure of test organisms to dilution water only or... (treatment) concentrations of a test substance and one control are required to conduct an early life stage... trays or cups for each test concentration and control (i.e., 30 per embryo cup with 2 replicates); (C...
García-Alonso, Javier; Rodriguez-Sanchez, Neus; Misra, Superb K.; Valsami-Jones, Eugenia; Croteau, Marie-Noële; Luoma, Samuel N.; Rainbow, Philip S.
2014-01-01
Pollutants affecting species at the population level generate ecological instability in natural systems. The success of early life stages, such as those of aquatic invertebrates, is highly affected by adverse environmental conditions. Silver released into the environment from emerging nanotechnology represents such a threat. Sediments are sinks for numerous pollutants, which aggregate and/or associate with depositing suspended particles. Deposit feeder such as the annelid Platynereis dumerilii, which has a large associated literature on its development, is an excellent model organism for exposure studies in coastal environments. We exposed eggs, larvae, juveniles and adults of P. dumerilii to various concentrations of citrate (cit-Ag NPs) or humic acid (HA-Ag NPs) capped silver nanoparticles (Ag NPs) as well to dissolved Ag (added as AgNO3). We showed that mortality and abnormal development rate increased with younger life stages. While adults and juvenile were the most tolerant life stages, fertilized eggs were highly sensitive to AgNO3, cit-Ag NPs and HA-Ag NPs. Exposures to HA-Ag NPs triggered the highest cute toxicity responses in P. dumerilii and in most cases both Ag NPs were more toxic than AgNO3. Uptake rate of HA-Ag NPs in adult worms was also higher than from other Ag forms, consistent with toxicity to other life stages. The early stages of the life cycle of marine coastal organisms are more affected by Ag NPs than the juvenile or adult life stages, indicating that exposure experiments at the larval level contribute to realistic eco-toxicological studies in aquatic environments.
Lee, Changkeun; Kwon, Bong-Oh; Hong, Seongjin; Noh, Junsung; Lee, Junghyun; Ryu, Jongseong; Kang, Seong-Gil; Khim, Jong Seong
2018-06-06
The potential leakage from marine CO 2 storage sites is of increasing concern, but few studies have evaluated the probable adverse effects on marine organisms. Fish, one of the top predators in marine environments, should be an essential representative species used for water column toxicity testing in response to waterborne CO 2 exposure. In the present study, we conducted fish life cycle toxicity tests to fully elucidate CO 2 toxicity mechanism effects. We tested sub-lethal and lethal toxicities of elevated CO 2 concentrations on marine medaka (Oryzias melastigma) at different developmental stages. At each developmental stage, the test species was exposed to varying concentrations of gaseous CO 2 (control air, 5%, 10%, 20%, and 30%), with 96 h of exposure at 0-4 d (early stage), 4-8 d (middle stage), and 8-12 d (late stage). Sub-lethal and lethal effects, including early developmental delays, cardiac edema, tail abnormalities, abnormal pigmentation, and mortality were monitored daily during the 14 d exposure period. At the embryonic stage, significant sub-lethal and lethal effects were observed at pH < 6.30. Hypercapnia can cause long-term and/or delayed developmental embryonic problems, even after transfer back to clean seawater. At fish juvenile and adult stages, significant mortality was observed at pH < 5.70, indicating elevated CO 2 exposure might cause various adverse effects, even during short-term exposure periods. It should be noted the early embryonic stage was found more sensitive to CO 2 exposure than other developmental stages of the fish life cycle. Overall, the present study provided baseline information for potential adverse effects of high CO 2 concentration exposure on fish developmental processes at different life cycle stages in marine ecosystems. Copyright © 2018 Elsevier Ltd. All rights reserved.
The OECD 210 fish early life]stage (FELS) test is the primary guideline test used to estimate chronic fish toxicity, as well as support ecological risk assessments and chemical management programs around the world. As a step toward developing alternatives to the FELS test, a HES...
Gaikowski, Mark P.; Hamilton, Steven J.; Buhl, Kevin J.; McDonald, Susan F.; Summers, Cliff H.; Linder, G.; Krest, S.; Sparling, D.; Little, E.
1996-01-01
Laboratory studies were conducted with five early life stages of rainbow trout, Oncorhynchus mykiss, to determine the acute toxicities of five fire-fighting chemical formulations in standardized soft and hard water. Eyed egg, embryo–larvae, swim-up fry, and 60- and 90-d posthatch juveniles were exposed to three fire retardants (Fire-Trol LCG-R, Fire-Trol GTS-R, and Phos-Chek D75-F) and two fire-suppressant foams (Phos-Chek WD-881 and Silv-Ex). Swim-up fry were generally the most sensitive life stage, whereas the eyed-egg was the least sensitive. Toxicity of fire-fighting formulations was greater in hard water than in soft water for all life stages tested with Fire-Trol GTS-R and Silv-Ex and for 90-d-old juveniles tested with Fire-Trol LCG-R. The fire-suppressant foams were more toxic than the fire retardants. The 96-h median lethal concentrations (LC50s) were ranked from the most toxic to the least toxic formulation as follows (ranges are the lowest and highest 96-h LC50 calculated for each formulation): Phos-Chek WD-881 (11–44 mg/L), Silv-Ex (11–78 mg/L), Phos-Chek D75-F (218–>3,600 mg/L), Fire-Trol GTS-R (207–>6,000 mg/L), and Fire-Trol LCG-R (872–>10,000 mg/L). Toxicity values suggest that accidental entry of fire-fighting chemicals into aquatic environments could adversely affect fish populations.
Prosser, R S; Rochfort, Q; McInnis, R; Exall, K; Gillis, P L
2017-11-01
In temperate urbanized areas where road salting is used for winter road maintenance, the level of chloride in surface waters has been increasing. While a number of studies have shown that the early-life stages of freshwater mussels are particularly sensitive to salt; few studies have examined the toxicity of salt-impacted winter road runoff to the early-life stages of freshwater mussels to confirm that chloride is the driver of toxicity in this mixture. This study examines the acute toxicity of field-collected winter road runoff to the glochidia of wavy-rayed lampmussels (Lampsilis fasciola) (48 h exposure) and newly released juvenile fatmucket mussels (Lampsilis siliquoidea) (<1 week old; 96 h exposure) under different water hardness. The chronic toxicity (28 d) to older juvenile L. siliquoidea (7-12 months old) was also investigated. The 48-h EC50 and 96-h LC50 for L. fasciola glochidia and L. siliquoidea juveniles exposed to different dilutions of road run-off created with moderately hard synthetic water (∼80 mg CaCO 3 /L) were 1177 (95% confidence interval (CI): 1011-1344 mg Cl - /L) and 2276 mg Cl - /L (95% CI: 1698-2854 mg Cl - /L), respectively. These effect concentrations correspond with the toxicity of chloride reported in other studies, indicating that chloride is likely the driver of toxicity in salt-impacted road-runoff, with other contaminants (e.g., metals, polycyclic aromatic hydrocarbons) playing a de minimis role. Toxicity data from the current study and literature and concentrations of chloride in the surface waters of Ontario were used to conduct a probabilistic risk assessment of chloride to early-life stage freshwater mussels. The assessment indicated that chronic exposure to elevated chloride levels could pose a risk to freshwater mussels; further investigation is warranted to ensure that the most sensitive organisms are protected. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.
The effect of tramadol hydrochloride on early life stages of fish.
Sehonova, Pavla; Plhalova, Lucie; Blahova, Jana; Berankova, Petra; Doubkova, Veronika; Prokes, Miroslav; Tichy, Frantisek; Vecerek, Vladimir; Svobodova, Zdenka
2016-06-01
The aim of this study was to perform the fish embryo acute toxicity test (FET) on zebrafish (Danio rerio) and the early-life stage toxicity test on common carp (Cyprinus carpio) with tramadol hydrochloride. The FET was performed using the method inspired by the OECD guideline 236. Newly fertilized zebrafish eggs were exposed to tramadol hydrochloride at concentrations of 10; 50; 100 and 200μg/l for a period of 144h. An embryo-larval toxicity test on C. carpio was performed according to OECD guideline 210 also with tramadol hydrochloride at concentrations 10; 50; 100 and 200μg/l for a period of 32 days. Hatching was significantly influenced in both acute and subchronic toxicity assays. Subchronic exposure also influenced early ontogeny, both morphometric and condition characteristics and caused changes in antioxidant enzyme activity. The LOEC value was found to be 10μg/l tramadol hydrochloride. Copyright © 2016 Elsevier B.V. All rights reserved.
Fish early life stages are highly sensitive to exposure to persistent bioaccumulative toxicants (PBTs). The factors that contribute to this are unknown, but may include the distribution of PBTs to sensitive tissues during critical stages of development. Multiphoton laser scannin...
Banan, Ashkan; Kalbassi Masjed Shahi, Mohammad Reza; Bahmani, Mahmoud; Yazdani Sadati, Mohammad Ali
2016-05-01
Silver nanoparticles (AgNPs) are widely used in consumer products mainly due to their antimicrobial action. The rapidly increasing use of nanoparticles (NPs) has driven more attention to their possible ecotoxicological effects. In this study, the acute toxicity of colloidal AgNPs was evaluated during the embryonic stage of Persian sturgeon (Acipenser persicus) and starry sturgeon (Acipenser stellatus) at concentrations of 0, 0.25, 0.5, 1, 2, 4, and 8 mg/L. Fertilized eggs (75 eggs per replicate) were exposed to aforementioned concentrations for 96 h in triplicate. 96-h LC50 values in Persian sturgeon and starry sturgeon were calculated as 0.163 and 0.158 mg/L, respectively. Furthermore, in starry sturgeon, the short-term effects of AgNPs on the hatching rate, survival rate, and Ag accumulation during early life stages (before active feeding commences) were also analyzed at concentrations of 0, 0.025, 0.05, and 0.1 mg/L of colloidal AgNPs. The highest silver accumulation occurred in larvae exposed to 0.1 mg/L AgNPs; however, the body burden of silver did not alter survival rate, and there were no significant differences among treatments. Based on the obtained results from the acute toxicity exposures, AgNPs induced a concentration-dependent toxicity in both species during early life stages, while complementary studies are suggested for investigating their short-term effects in detail.
Scholz, Stefan; Schreiber, Rene; Armitage, James; Mayer, Philipp; Escher, Beate I; Lidzba, Annegret; Léonard, Marc; Altenburger, Rolf
2018-04-01
Fish early life stage (ELS) tests (Organisation for Economic Co-operation and Development test guideline 210) are widely conducted to estimate chronic fish toxicity. In these tests, fish are exposed from the embryonic to the juvenile life stages. To analyze whether certain modes of action are related to high toxic ratios (i.e., ratios between baseline toxicity and experimental effect) and/or acute-to-chronic ratios (ACRs) in the fish ELS test, effect concentrations (ECs) for 183 compounds were extracted from the US Environmental Protection Agency's ecotoxicity database. Analysis of ECs of narcotic compounds indicated that baseline toxicity could be observed in the fish ELS test at similar concentrations as in the acute fish toxicity test. All nonnarcotic modes of action were associated with higher toxic ratios, with median values ranging from 4 to 9.3 × 10 4 (uncoupling < reactivity < neuromuscular toxicity < methemoglobin formation < endocrine disruption < extracellular matrix formation inhibition). Four modes of action were also found to be associated with high ACRs: 1) lysyl oxidase inhibition leading to notochord distortion, 2) putative methemoglobin formation or hemolytic anemia, 3) endocrine disruption, and 4) compounds with neuromuscular toxicity. For the prediction of ECs in the fish ELS test with alternative test systems, endpoints targeted to the modes of action of compounds with enhanced toxic ratios or ACRs could be used to trigger fish ELS tests or even replace these tests. Environ Toxicol Chem 2018;37:955-969. © 2018 SETAC. © 2018 SETAC.
Life-Stage Physiologically-Based Pharmacokinetic (PBPK) ...
This presentation discusses methods used to extrapolate from in vitro high-throughput screening (HTS) toxicity data for an endocrine pathway to in vivo for early life stages in humans, and the use of a life stage PBPK model to address rapidly changing physiological parameters. Adverse outcome pathways (AOPs), in this case endocrine disruption during development, provide a biologically-based framework for linking molecular initiating events triggered by chemical exposures to key events leading to adverse outcomes. The application of AOPs to human health risk assessment requires extrapolation of in vitro HTS toxicity data to in vivo exposures (IVIVE) in humans, which can be achieved through the use of a PBPK/PD model. Exposure scenarios for chemicals in the PBPK/PD model will consider both placental and lactational transfer of chemicals, with a focus on age dependent dosimetry during fetal development and after birth for a nursing infant. This talk proposes a universal life-stage computational model that incorporates changing physiological parameters to link environmental exposures to in vitro levels of HTS assays related to a developmental toxicological AOP for vascular disruption. In vitro toxicity endpoints discussed are based on two mechanisms: 1) Fetal vascular disruption, and 2) Neurodevelopmental toxicity induced by altering thyroid hormone levels in neonates via inhibition of thyroperoxidase in the thyroid gland. Application of our Life-stage computati
Sexual Maturity and Life Stage Influences Toxic Metal Accumulation in Croatian Brown Bears.
Lazarus, Maja; Sekovanić, Ankica; Orct, Tatjana; Reljić, Slaven; Jurasović, Jasna; Huber, Đuro
2018-02-01
The influence of reproductive and (early) life stages on toxic metal levels was investigated in the brown bear (Ursus arctos), the largest mammalian predator species in Croatia. The purpose was to examine critical clusters in a population that might be at a higher risk of adverse health effects caused by metals as environmental contaminants. Levels of cadmium, mercury and lead in muscle, liver and kidney cortex of 325 male and 139 female bears, quantified by inductively coupled plasma mass spectrometry, were analysed according to distinct bear life stages (young: cub, yearling, subadult; mature: adult). Metal levels did not differ among sexes in young animals (< 4 years), except for mercury in muscles (higher in females), and adult females had higher cadmium and mercury. A trend of renal cadmium accumulation with age in immature male animals disappeared once they reached maturity, whereas for females this trend has only slowly declined in mature compared to immature bears. In early life stage (< 1 year), bear cubs had lower cadmium, comparable mercury, and higher lead in the kidneys than the bears of the following age category (yearlings). Due to a higher proportion of renal lead transfer from the mother to the cub compared with cadmium, it may be that the high burden of cadmium found in kidneys of older females has lower toxicological concern for their cubs than the lead content. Sex, reproductive, and life stages of bears were confirmed as important in assessing toxic metal burden.
Balangoda, Anusha; Deepananda, K H M Ashoka; Wegiriya, H C E
2018-02-01
This study investigated the potential toxic effects of environmentally relevant nitrate concentrations on development, growth, and mortality of early life stages of common hour-glass tree frog, Polypedates cruciger. Tadpoles from hatchlings through pre-adult were exposed to environmentally relevant nitrate concentrations detected in Mirissa, Sri Lanka. Newly hatched, external gill stage, and internal gill stage tadpoles were exposed to potassium nitrate for bioassay tests. No behavioral changes or abnormalities were observed in control and nitrate-induced group. However, detected environmental nitrate concentration significantly increased (p < 0.05) the growth of the tadpoles up to 25 days old. Results revealed that newly hatched and external gill stage was more susceptible to the nitrate pollution than internal gill stage. The results suggest that environmentally relevant nitrate can cause mortality on the amphibian population in ecosystems associated with agro-pastoral activities through altering the growth and direct toxicological effects on the survivorship.
Draft Test Guideline: Fish Early-Life Stage Toxicity Test
The following draft test guideline is part of a series of test guidelines that have been developed by EPA for use in the testing of pesticides and toxic substances, and the development of test data for submission to the Agency for review.
Buhl, Kevin J.; Hamilton, Steven J.
1990-01-01
The acute toxicities of four trace inorganics associated with placer mining were determined, individually and in environmentally relevant mixtures, to early life stages of Arctic grayling (Thymallus arcticus) from Alaska and Montana, coho salmon (Oncorhynchus kitsutch) from Alaska and Washington, and rainbow trout (Oncorhynchus mykiss) from Montana. The descending rank order of toxicity to all species and life stages was copper > zinc > lead > arsenic. For each of the three species, sensitivity to the inorganics was greater in juveniles than in alvenins or in swim-up fry. Arctic grayling from Alaska were more sensitive than the other species tested, including Arctic grayling from Montana. For Arctic grayling, sensitivity to all four inorganics was significantly greater in swim-up fry from Alaska than in alevins from Montana, and sensitivity to arsenic and copper was significantly greater in juveniles from Alaska than in juveniles from Montana. In tests with environmentally relevant mixtures (based on ratios of concentrations measured in streams with placer mining) of these four inorganics, copper was identified as the major toxic component because it accounted for ⩾97% of the summed toxic units of the mixture, and an equitoxic mixture of these inorganics showed less-than-additive toxicity. Total and total recoverable copper concentrations reported in five Alaskan streams with active placer mines were higher than the acutely toxic concentrations, either individually or in mixtures, that the authors found to be acutely toxic to Arctic grayling and coho salmon from Alaska. However, caution should be used when comparing our results obtained in “clear” water to field situations, because speciation and toxicity of these inorganics may be altered in the presence of sediments suspended by placer mining activities.
Comparative toxicity of two oil dispersants to the early life stages of two marine species
DOE Office of Scientific and Technical Information (OSTI.GOV)
Singer, M.M.; George, S.; Benner, D.
1993-10-01
Acute, flow-through, spiked-exposure toxicity tests were performed on the early life stages of two marine species using two oil dispersants. The species represent two common near-shore marine taxa: molluscs (red abalone, Haliotis rufescens) and crustaceans (kelp forest mysid, Holmesimysis costata). The dispersants were composed of complex mixtures of anionic and nonionic surfactants and solvents. The toxicity data showed that one dispersant, Slik-A-Way, was more toxic than the other, Nokomis[reg sign] 3, to both species. Median-effect concentration estimates for the two dispersants were significantly different between species. Slik-A-Way median-effect concentrations ranged from 16.8 to 23.9 initial ppm for Haliotis and 25.9more » to 34.6 initial ppm for Holmesimysis, whereas Nokomis[reg sign] 3 median-effect concentrations ranged from 21.0 to 24.0 initial ppm for Haliotis and from 118.0 to 123.2 initial ppm for Holmesimysis. Differences in toxicity seen in the two dispersants may be due to differences in surfactant formulations.« less
Early life-stage toxicity tests with copper and pentachlorophenol (PCP) were conducted with two species listed under the U.S. Endangered Species Act (fountain darter, Etheostoma fonticola, and spotfin chub, Cyprinella monacha) and two surrogate species (fathead minnow, Pimephales...
The presence of MWCNTs reduces developmental toxicity of PFOS in early life stage of zebrafish.
Wang, Shutao; Zhuang, Changlu; Du, Jia; Wu, Chuan; You, Hong
2017-03-01
Both carbon nanotubes (CNTs) and perfluorooctane sulfonate (PFOS) are used widely. There is considerable concern regarding their ecotoxicity. CNTs might interact with PFOS in water and result in different impacts compared with those after single exposures. To our knowledge, the developmental toxicity of PFOS in the presence of multi-walled carbon nanotubes (MWCNTs) in the early life stage of zebrafish (from 3 h post fertilization (hpf) to 96 hpf) was investigated for the first time in this study. The embryos and larvae were exposed to PFOS (0.2, 0.4, 0.8, and 1.6 mg/L), MWCNTs (50 mg/L), and a mixture of both. Compared with PFOS exposure, the adverse effects induced by PFOS on the hatching rate of zebrafish embryos and the heart rate and body length of zebrafish larvae were reduced in the presence of MWCNTs, and mortality and malformation were also alleviated. In addition, zebrafish larvae exposed to PFOS showed decreased activities of superoxide dismutase, catalase, and glutathione peroxidase, as well as decreased levels of reactive oxygen species and malondialdehyde, in the presence of MWCNTs, indicating that oxidative stress and lipid peroxidation was relieved. Thus, the presence of MWCNTs reduces the developmental toxicity of PFOS in the early life stage of zebrafish. Copyright © 2016 Elsevier Ltd. All rights reserved.
Embryotoxicity of nitrophenols to the early life stages of zebrafish (Danio rerio).
Ceylan, Zeynep; Şişman, Turgay; Yazıcı, Zehra; Altıkat, Aysun Özen
2016-08-01
The nitrophenols (NPs) are water-soluble compounds. These compounds pose a significant health threat since they are priority environmental pollutants. In this study, 2-Nitrophenol (2NP) and 2,4-dinitrophenol (DNP) were examined for embryo and early life stage toxicity in zebrafish (Danio rerio). Acute toxicity and teratogenicity of 2NP and DNP were tested for 4 days using zebrafish embryos. The typical lesions observed were no somite formation, incomplete eye and head development, tail curvature, weak pigmentation (≤48 hours postfertilization (hpf)), kyphosis, scoliosis, yolk sac deformity, and nonpigmentation (72 hpf). Also, embryo and larval mortality increased and hatching success decreased. The severity of abnormalities and mortalities were concentration- and compound-dependent. Of the compounds tested, 2,4-DNP was found to be highly toxic to the fish embryos following exposure. The median lethal concentrations and median effective concentrations for 2NP are 18.7 mg/L and 7.9 mg/L, respectively; the corresponding values for DNP are 9.65 mg/L and 3.05 mg/L for 48 h. The chorda deformity was the most sensitive endpoint measured. It is suggested that the embryotoxicity may be mediated by an oxidative phosphorylation uncoupling mechanism. This article is the first to describe the teratogenicity and embryotoxicity of two NPs to the early life stages of zebrafish. © The Author(s) 2014.
Lethal toxicity of industrial chemicals to early life stages of Tilapia guineensis.
Ezemonye, L I N; Ogeleka, D F; Okieimen, F E
2008-08-30
The toxic effects of industrial chemicals on three early life stages of an economically important fish, Tilapia guineensis were investigated using the Organisation for Economic Cooperation and Development (OECD) # 203 recommended semi-static renewal bioassay. The assessment was necessary for the uncontrollable disposal of Neatex (liquid detergent) and Norust CR 486 (corrosion inhibitor) into the Niger Delta environment of Nigeria. The estimated 96-h LC(50) for 7-, 14- and 28-day-old fish in Norust CR 486 exposure was considered "more toxic" than Neatex in all life stages and was dependent on species age, exposure duration and environment. In the fresh water test, for Neatex and Norust CR 486 exposures for day 7, 14 and 28, the 96-h LC50 were 8.79, 17.10 and 82.42 mg/l and 5.55, 13.58 and 20.21 mg/l, respectively. In the brackish test, 15.42 and 46.52 mg/l, not determined (ND) and 7.35, 13.95 and 24.50mg/l were obtained. Differential toxicity was observed in the fresh and brackish water fish for the two chemicals and controls at p<0.05. The high sensitivity of the 7-day-old test organisms to both chemicals provides a rationale for regulatory surveillance and monitoring of both chemicals in the fragile Niger Delta environment.
Chen, Pei-Jen; Wu, Wan-Lin; Wu, Kevin Chia-Wen
2013-08-01
Nanoscale zerovalent iron (nZVI)-mediated oxidation reaction is increasingly being used for enhanced treatment of water or wastewater processes; however, the fate and eco-toxicological effects of nZVI in the surface aquifer remain unclear. We investigated bioaccumulation and lethal-to-sublethal toxic effects on early life development of Japanese medaka (Oryzias latipes) with 7-day exposure to 25-200 mg/L of well-characterized solutions containing carboxymethyl cellulose (CMC)-stabilized nZVI (CMC-nZVI), nanoscale iron oxide (nFe3O4) or ferrous ion [Fe(II)aq]. The CMC-nZVI solution had the greatest acute mortality and developmental toxic effects in embryos, with lesser and the least effects with Fe(II)aq and nFe3O4. The toxicity of CMC-nZVI was ascribed to its high reactivity in the oxygenic solution, which led to a combination of hypoxia and production of reactive oxygen species (ROS) and Fe(II)aq. nFe3O4 (50-100 mg/L) was more bioavailable to embryos and bioaccmulative in hatchlings than suspended CMC-nZVI. The antioxidant balance was differentially altered by induced intracellular ROS in hatchlings with all 3 iron species. We revealed causal toxic effects of nZVI and its oxidized products in early life stages of medaka fish using different organizational levels of biomarker assays. The toxicity results implicate a potential eco-toxicological impact of nZVI on the aquatic environment. Copyright © 2013 Elsevier Ltd. All rights reserved.
Little, E.E.; Calfee, R.D.; Linder, G.
2012-01-01
White sturgeon (Acipenser transmontanus) populations throughout western North America are in decline, likely as a result of overharvest, operation of dams, and agricultural and mineral extraction activities in their watersheds. Recruitment failure may reflect the loss of early-life stage fish in spawning areas of the upper Columbia River, which are contaminated with metals from effluents associated with mineral-extraction activities. Early-life stage white sturgeon (A. transmontanus) from the Columbia River and Kootenai River populations were exposed to copper during 96-h flow-through toxicity tests to determine their sensitivity to the metal. Similar tests were conducted with rainbow trout (RBT [Oncorhynchus mykiss]) to assess the comparative sensitivity of this species as a surrogate for white sturgeon. Exposures were conducted with a water quality pH 8.1-8.3, hardness 81-119 mg/L as CaCO2, and dissolved organic carbon 0.2-0.4 mg/L. At approximately 30 days posthatch (dph), sturgeon were highly sensitive to copper with median lethal concentration (LC50) values ranging from 4.1 to 6.8 μg/L compared with 36.5 μg/L for 30 dph RBT. White sturgeon at 123-167 dph were less sensitive to copper with LC50 values ranging from 103.7 to 268.9 μg/L. RBT trout, however, remained more sensitive to copper at 160 dph with an LC50 value of 30.9 μg/L. The results indicate that high sensitivity to copper in early-life stage white sturgeon may be a factor in recruitment failure occurring in the upper Columbia and Kootenai rivers. When site-specific water-quality criteria were estimated using the biotic ligand model (BLM), derived values were not protective of early-life stage fish, nor were estimates derived by water-hardness adjustment.
2016-09-01
Standardization (ISO). 2015. Water quality - calanoid copepod early- life stage test with Acartia tonsa. ISO 16778:2015. International Organization for...Toxicity Test Methods for Marine Water Quality Evaluations by Alan J Kennedy, Guilherme Lotufo, Jennifer G. Laird, and J. Daniel Farrar PURPOSE: The...MPRSA evaluations in some regions. The organisms used in these test methods are not planktonic for most of their life cycles (juveniles and adults
EARLY LIFE STAGE TOXICITY OF COPPER TO ENDANGERED AND SURROGATE FISH SPECIES
Water quality criteria (WQC) for the protection of aquatic life have not explicitly considered the degree of protection afforded to aquatic species listed as endangered or threatened under the U.S. Endangered Species Act (listed species) . Most WQCs are based primarily on respon...
A SHORT-TERM REPRODUCTIVE TEST WITH THE FATHEAD MINNOW (PIMEPHALES PROMELAS)
Due to the time and expense associated with full life-cycle testing, most current toxicity tests with fish do not explicity consider reproductive output as an endpoint but, rather, focus on early life-stage survival and development. However, there are classes of chemicals that co...
A SHORT-TERM REPRODUCTION TEST WITH THE FATHEAD MINNOW (PIMEPHALES PROMELAS): L METHODS DESCRIPTION
Due to the time and expense associated with full life-cycle testing, most current toxicity tests with fish do not explicity consider reproductive output as an endpoint but, rather, focus on early life-stage survival and development. However, there are classes of chemicals that co...
Little, E.E.; Calfee, R.D.; Linder, G.
2014-01-01
The toxicity of five smelter slag-contaminated sediments from the upper Columbia River and metals associated with those slags (cadmium, copper, zinc) was evaluated in 96-h exposures of White Sturgeon (Acipenser transmontanus Richardson, 1836) at 8 and 30 days post-hatch. Leachates prepared from slag-contaminated sediments were evaluated for toxicity. Leachates yielded a maximum aqueous copper concentration of 11.8 μg L−1 observed in sediment collected at Dead Man's Eddy (DME), the sampling site nearest the smelter. All leachates were nonlethal to sturgeon that were 8 day post-hatch (dph), but leachates from three of the five sediments were toxic to fish that were 30 dph, suggesting that the latter life stage is highly vulnerable to metals exposure. Fish maintained consistent and prolonged contact with sediments and did not avoid contaminated sediments when provided a choice between contaminated and uncontaminated sediments. White Sturgeon also failed to avoid aqueous copper (1.5–20 μg L−1). In water-only 96-h exposures of 35 dph sturgeon with the three metals, similar toxicity was observed during exposure to water spiked with copper alone and in combination with cadmium and zinc. Cadmium ranging from 3.2 to 41 μg L−1 or zinc ranging from 21 to 275 μg L−1 was not lethal, but induced adverse behavioral changes including a loss of equilibrium. These results suggest that metals associated with smelter slags may pose an increased exposure risk to early life stage sturgeon if fish occupy areas contaminated by slags.
Ecotoxicity in the Reconquista River, province of Buenos Aires, Argentina: a preliminary study.
Herkovits, J; Perez-Coll, C S; Herkovits, F D
1996-02-01
The Reconquista River in Argentina is considered a "supercritical" river basin due to environmental degradation. Within its valley of 1.547 km2, there are more than 3 million inhabitants and 12,000 industries. Using early-life-stage toxicity tests with Bufo arenarum embryos (the most sensitive of three native species), we determined the water quality at six sampling stations of the river valley and expressed the results as acute and chronic toxicity units. Along most of the river, the toxicity was higher than the allowable level of whole industrial effluent toxicity recommended by U.S. EPA. In a tributary stream, Arroyo Moron, the water was about 10 times more toxic than the criteria maximum concentration (CMC) recommended by U.S. EPA for industrial effluents. Similar degradation of the water quality was found taking as a reference value an upstream sampling station. In all places where the water quality was worse than the CMC, no macroorganisms were found, and in one of these places, a large number of dead fishes was observed. Our study points out that amphibian early-life-stage toxicity tests could be appropriate for assessing water contamination and water quality, which is essential for diagnosis, protection of environmental services, monitoring, and restoration purposes.
Lake trout embryos and sac fry are very sensitive to toxicity associated with maternal exposures to 2,3,7,8-tetrachlorodibenza-p-dioxin (TCDD) and structurally related chemicals that act through a common aryl hydrocarbon receptor (AHR)- mediated mechanism of action. The presence ...
In June 2010, the ILSI Health and Environmental Sciences Institute (HESI) with support from sanofi-aventis, NC3Rs, the Humane Society, L’Oreal, and ECVAM, held a workshop aimed at examining critical science needs related to the development of alternatives to chronic fish toxicity...
Fuel oil and dispersant toxicity to the Antarctic sea urchin (Sterechinus neumayeri).
Alexander, Frances J; King, Catherine K; Reichelt-Brushett, Amanda J; Harrison, Peter L
2017-06-01
The risk of a major marine fuel spill in Antarctic waters is increasing, yet there are currently no standard or suitable response methods under extreme Antarctic conditions. Fuel dispersants may present a possible solution; however, little data exist on the toxicity of dispersants or fuels to Antarctic species, thereby preventing informed management decisions. Larval development toxicity tests using 3 life history stages of the Antarctic sea urchin (Sterechinus neumayeri) were completed to assess the toxicity of physically dispersed, chemically dispersed, and dispersant-only water-accommodated fractions (WAFs) of an intermediate fuel oil (IFO 180, BP) and the chemical dispersant Slickgone NS (Dasic International). Despite much lower total petroleum hydrocarbon concentrations, physically dispersed fuels contained higher proportions of low-to-intermediate weight carbon compounds and were generally at least an order of magnitude more toxic than chemically dispersed fuels. Based on concentrations that caused 50% abnormality (EC50) values, the embryonic unhatched blastula life stage was the least affected by fuels and dispersants, whereas the larval 4-armed pluteus stage was the most sensitive. The present study is the first to investigate the possible implications of the use of fuel dispersants for fuel spill response in Antarctica. The results indicate that the use of a fuel dispersant did not increase the hydrocarbon toxicity of IFO 180 to the early life stages of Antarctic sea urchins, relative to physical dispersal. Environ Toxicol Chem 2017;36:1563-1571. © 2016 SETAC. © 2016 SETAC.
Early life stage (ELS) toxicity of sucralose to fathead minnows, Pimephales promelas.
Stoddard, K I; Huggett, D B
2014-10-01
Sucralose, an intense artificial sweetener, has been detected in wastewater and surface waters at concentrations ranging from ng/L to low µg/L. Although over a hundred studies have been conducted to evaluate the safety of sucralose for human consumption, few studies have focused on the chronic ecotoxicological effects of this compound in fish. As a remedy to this data gap, an early-life stage toxicity test was conducted to assess the effects of sucralose on hatching, survival, and growth of fathead minnows (Pimephales promelas). Hatching, survival, and growth were unaffected by 98 mg/L of sucralose. The Lowest-Observed-Effect Concentration (LOEC) and the No-Observed-Effect Concentration (NOEC) for fathead minnows determined by this study are >98 and 98 mg/L, respectively. The results from this study suggest that the concentrations of sucralose detected in the environment are well below those required to cause adverse effects to developing aquatic organisms.
Butler, Josh D; Parkerton, Thomas F; Redman, Aaron D; Letinski, Daniel J; Cooper, Keith R
2016-08-02
Aromatic hydrocarbons (AH) are known to impair fish early life stages (ELS). However, poorly defined exposures often confound ELS-test interpretation. Passive dosing (PD) overcomes these challenges by delivering consistent, controlled exposures. The objectives of this study were to apply PD to obtain 5 d acute embryo lethality and developmental data and 30 d chronic embryo-larval survival and growth-effects data using zebrafish with different AHs; to analyze study and literature toxicity data using target-lipid (TLM) and chemical-activity (CA) models; and to extend PD to a mixture and test the assumption of AH additivity. PD maintained targeted exposures over a concentration range of 6 orders of magnitude. AH toxicity increased with log Kow up to pyrene (5.2). Pericardial edema was the most sensitive sublethal effect that often preceded embryo mortality, although some AHs did not produce developmental effects at concentrations causing mortality. Cumulative embryo-larval mortality was more sensitive than larval growth, with acute-to-chronic ratios of <10. More-hydrophobic AHs did not exhibit toxicity at aqueous saturation. The relationship and utility of the TLM-CA models for characterizing fish ELS toxicity is discussed. Application of these models indicated that concentration addition provided a conservative basis for predicting ELS effects for the mixture investigated.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Villalobos, S.A.; Papoulias, D.M.; Meadows, J.
2000-02-01
Polychlorinated naphthalenes (PCNs) are organic compounds with some chemical properties and uses similar to polychlorinated biphenyls. Polychlorinated naphthalenes have been detected in biota from certain aquatic environments. The toxicities of several PCN technical mixtures (Halowax) to medaka (Oryzias latipes) were determined by use of an embryo nanoinjection method. Medaka eggs (early gastrula) were injected with 0.5 nl of triolein (vehicle control) or 0.5 nl of four to five graded doses (0.3--30 ng/egg) of Halowax 1014, Halowax 1013, or Halowax 1051 in triolein. Following exposure, embryos developed, and fry were reared to sexual maturity (4 months), at which time they weremore » euthanized. Responses were evaluated as early life stage (ELS) and early adult life stage (EALS) assessments. For ELS, lethality and sublethal alterations in embryos and larvae (<16 d old), such as craniofacial, cardiovascular, and myoskeletal deformities and abnormal or delayed hatch, were monitored for the first 9 d, and a dose severity index was computed. The EALS assessment examined the survival of 16-d-old larvae until early adulthood (123 {+-} 3 d old), including gonadosomatic index (GSI) and morphometry. Halowax 1014 was found to be the most toxic mixture (LD50 4.2 ng/egg), whereas Halowax 1013 and 1051 were significantly less toxic (LD50s could not be determined). The gonadosomatic index of females was significantly less in fish dosed with Halowax 1014 or 1051. The LD50 for medaka embryos nanoinjected with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is about 0.75 pg/egg. Thus, Halowax 1014 was 5,585-fold less potent than TCDD. For Halowax 1014, ELS assessments accurately predicted the results of EALS assessments.« less
Villalobos, Sergio A.; Papoulias, Diana M.; Meadows, John C.; Blankenship, Alan L.; Pastva, Stephanie D.; Kannan, Kurunthachalam; Hinton, D.E.; Tillitt, Donald E.; Giesy, John P.
2000-01-01
Polychlorinated naphthalenes (PCNs) are organic compounds with some chemical properties and uses similar to polychlorinated biphenyls. Polychlorinated naphthalenes have been detected in biota from certain aquatic environments. The toxicities of several PCN technical mixtures (Halowax) to medaka (Oryzias latipes) were determined by use of an embryo nanoinjection method. Medaka eggs (early gastrula) were injected with 0.5 nl of triolein (vehicle control) or 0.5 nl of four to five graded doses (0.3-30 ng/egg) of Halowax 1014, Halowax 1013, or Halowax 1051 in triolein. Following exposure, embryos developed, and fry were reared to sexual maturity (4 months), at which time they were euthanized. Responses were evaluated as early life stage (ELS) and early adult life stage (EALS) assessments. For ELS, lethality and sublethal alterations in embryos and larvae ( < 16 d old), such as craniofacial, cardiovascular, and myoskeletal deformities and abnormal or delayed hatch, were monitored for the first 9 d, and a dose severity index was computed. The EALS assessment examined the survival of 16-d-old larvae until early adulthood (123 ?? 3 d old), including gonadosomatic index (GSI) and morphometry. Halowax 1014 was found to be the most toxic mixture (LD50 4.2 ng/egg), whereas Halowax 1013 and 1051 were significantly less toxic (LD50s could not be determined). The gonadosomatic index of females was significantly less in fish dosed with Halowax 1014 or 1051. The LD50 for medaka embryos nanoinjected with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is about 0.75 pg/egg. Thus, Halowax 1014 was 5,585-fold less potent than TCDD. For Halowax 1014, ELS assessments accurately predicted the results of EALS assessments.
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.
Ecotoxicity in the Reconquista River, province of Buenos Aires, Argentina: a preliminary study.
Herkovits, J; Perez-Coll, C S; Herkovits, F D
1996-01-01
The Reconquista River in Argentina is considered a "supercritical" river basin due to environmental degradation. Within its valley of 1.547 km2, there are more than 3 million inhabitants and 12,000 industries. Using early-life-stage toxicity tests with Bufo arenarum embryos (the most sensitive of three native species), we determined the water quality at six sampling stations of the river valley and expressed the results as acute and chronic toxicity units. Along most of the river, the toxicity was higher than the allowable level of whole industrial effluent toxicity recommended by U.S. EPA. In a tributary stream, Arroyo Moron, the water was about 10 times more toxic than the criteria maximum concentration (CMC) recommended by U.S. EPA for industrial effluents. Similar degradation of the water quality was found taking as a reference value an upstream sampling station. In all places where the water quality was worse than the CMC, no macroorganisms were found, and in one of these places, a large number of dead fishes was observed. Our study points out that amphibian early-life-stage toxicity tests could be appropriate for assessing water contamination and water quality, which is essential for diagnosis, protection of environmental services, monitoring, and restoration purposes. Images Figure 1. Figure 2. Figure 3. Figure 4. Figure 5. Figure 6. PMID:8820587
Damare, Leigh M; Bridges, Kristin N; Alloy, Matthew M; Curran, Thomas E; Soulen, Brianne K; Forth, Heather P; Lay, Claire R; Morris, Jeffrey M; Stoeckel, James A; Roberts, Aaron P
2018-05-01
The 2010 explosion of the Deepwater Horizon (DWH) oil rig led to the release of millions of barrels of oil in the Gulf of Mexico. Oil in aquatic ecosystems exerts toxicity through multiple mechanisms, including photo-induced toxicity following co-exposure with UV radiation. The timing and location of the spill coincided with both fiddler crab reproduction and peak yearly UV intensities, putting early life stage fiddler crabs at risk of injury due to photo-induced toxicity. The present study assessed sensitivity of fiddler crab larvae to photo-induced toxicity during co-exposure to a range of environmentally relevant dilutions of high-energy water accommodated fractions of DWH oil, and either <10, 50, or 100% ambient sunlight, achieved with filters that allowed for variable UV penetration. Solar exposures (duration: 7-h per day) were conducted for two consecutive days, with a dark recovery period (duration: 17-h) in between. Survival was significantly decreased in treatments the presence of >10% UV and relatively low concentrations of oil. Results of the present study indicate fiddler crab larvae are sensitive to photo-induced toxicity in the presence of DWH oil. These results are of concern, as fiddler crabs play an important role as ecosystem engineers, modulating sediment biogeochemical processes via burrowing action. Furthermore, they occupy an important place in the food web in the Gulf of Mexico.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Liu, Xin; Fang, Hui; Tian, Yuan
Purpose: To evaluate the dosimetric superiority, efficacy, toxicity, and quality of life (QOL) data of intensity modulated radiation therapy (IMRT) in patients with primary gastric diffuse large B-cell lymphoma (PG-DLBCL). Methods and Materials: Forty-six consecutive patients with early-stage PG-DLBCL underwent IMRT after chemotherapy. The majority of patients (61.5%) were subclassified as the non-germinal center B cell–like subtype. Dosimetric parameters of the planning target volume (PTV) and organs at risk were assessed. Survival rates were depicted with the Kaplan-Meier method and compared with the log-rank test. Quality of life was evaluated using the QLQ-C30-STO22 questionnaires at the last follow-up contact. Results: Themore » median PTV mean dose was 41.6 Gy. Only 0.73% of the PTV received <95% of the prescribed dose, indicating excellent target coverage. The median kidney V20 and liver V30 were 14.1% and 16.1%, respectively. The 5-year overall survival (OS), progression-free survival, and locoregional control rates for all patients were 80.4%, 75.0%, and 93.2%, respectively. Stage, lactate dehydrogenase level, and immunophenotype were significant prognostic factors for OS, and only stage was a significant factor for locoregional control. Consolidation IMRT in patients with complete response after chemotherapy resulted in significantly better OS and progression-free survival than salvage IMRT in patients with non-complete response. Two of 8 patients who had chronic liver disease experienced grade 4 or grade 5 acute hepatic failure after 4 to 5 cycles of rituximab-based chemotherapy and IMRT (40 Gy). No other serious acute or late toxicity was observed. The long-term global and functional QOL scales were excellent, with negligible symptom scales. Conclusions: Intensity modulated radiation therapy yielded excellent target coverage and critical tissue sparing and achieved favorable outcomes with acceptable toxicity and good long-term QOL in early-stage PG-DLBCL.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Fort, D.J.; Stover, E.L.
1996-12-31
An evaluation of the effects of low-level copper and pentachlorophenol exposure on various early life stages of the South African clawed frog, Xenopus laevis, was performed using stage-specific and long-term continuous exposures. Stage-specific exposure experiments were conducted such that separate subsets of embryos and larvae from the same clutch were exposed to two toxicants, copper and pentachlorphenol, from 0 d to 4 d (standard Frog Embryo Teratogenesis Assay--Xenopus [FETAX]), 4 d to 8 d, 8 d to 12 d, and 12 d to 16 d. Results from two separate concentration-response experiments indicated that sensitivity to either toxicant increased in eachmore » successive time period. Longer-term exposure studies conducted for 60 to 75 days indicated that copper, but not pentachlorophenol induced reduction deficiency malformations of the hind limb at concentrations as low as 0.05 mg/L. Pentachlorophenol concentrations as low as 0.5 {micro}g/L inhibited tail resorption. However, copper did not adversely affect the process of tail resorption. These results indicated that studies evaluating longer-term developmental processes are important in ecological hazard evaluation.« less
Effect of chronic copper and pentachlorophenol exposure to early life stages of Xenopus laevis
DOE Office of Scientific and Technical Information (OSTI.GOV)
Fort, D.J.; Stover, E.L.
1995-12-31
An evaluation of the effects of low-level copper and pentachlorophenol exposure on various early life stages of the South African clawed frog, Xenopus laevis was performed using stage-specific and long-term continuous exposures. Stage-specific exposure experiments were conducted such that separate subsets of embryos and larvae from the same clutch were exposed to two toxicants, copper and pentachlorophenol, from 0 d to 4 d (standard Frog Embryo Teratagenesis Assay Xenopus [FETAX]), 4 d to 8 d, 8 d to 12 d, and 12 d to 16 d. Results from two separate concentration-response experiments indicated that sensitivity to either toxicant increased inmore » each successive time period. Continuous exposure studies conducted for 60 to 75 days indicated that copper, but not pentachlorophenol induced reduction deficiency malformations of the hind limb at concentrations as low as 0.05 mg/L. Pentachlorophenol concentrations as low as 0.5/{micro}g/L inhibited tail resorption. However, copper did not adversely affect the process of tail resorption. These results indicated that studies evaluating longer-term developmental processes are important in ecological hazard evaluation.« less
Naddy, Rami B; Rehner, Anita B; McNerney, Gina R; Gorsuch, Joseph W; Kramer, James R; Wood, Chris M; Paquin, Paul R; Stubblefield, William A
2007-09-01
The chronic (early life stage [ELS]) and short-term chronic (STC) toxicity of silver (as silver nitrate) to fathead minnows (FHM) was determined concurrently in flow-through exposures (33 volume additions/d). Paired ELS (approximately 30 d) and STC (7 d) studies were conducted with and without the addition of 60 mg/L Cl (as NaCl). The paired studies in unamended water were later repeated using standard flow conditions (9 volume additions/d). The purpose of the paired studies was to determine if short-term chronic endpoints can be used to predict effects in ELS studies. For each experiment, a "split-chamber" design (organisms were held in a common exposure chamber) allowed the direct comparison between short-term and chronic exposures. It appeared that the chronic toxicity of silver was mitigated to some extent by NaCl addition. The maximum acceptable toxicant concentration for growth in the ELS study was 0.53 microg dissolved Ag/L under standard flow conditions. Early life stage and STC endpoints in all three studies typically agreed within a factor of two. Whole-body sodium and silver concentrations measured in individual fathead minnows during these studies showed an increase in silver body burdens and a decrease in sodium concentration. These results indicate that the STC study could be used as a surrogate test to estimate chronic toxicity and that the mechanism of chronic silver toxicity may be the same as for acute toxicity.
Kovrižnych, Jevgenij A.; Zeljenková, Dagmar; Rollerová, Eva; Szabová, Elena; Wimmerová, Soňa
2013-01-01
At present, nanoparticles are beginning to influence our lives in many ways and understanding the environmental health and safety aspect of nanomaterials has become a crucial issue. The aim of the work was to assess and compare the acute toxicity of 31 different nanomaterials to fish mature individuals Danio rerio with that to fish early life stages on using evaluation of the 48- and 96- hour LC50 values. A further aim was to evaluate teratogenicity of the nanoparticles tested to fish eggs. The nanoparticles tested were: 8 pure metals, 10 metal oxides, 5 other metal compounds and their mixtures, 2 silicon compounds, 3 calcium compounds, and 3 carbon compounds. Using 48-h and 96-h tests of acute toxicity (according to OECD 203), we evaluated mortality data, LC50 values, occurrence of malformations, as well as hatching time. In our study, 6 kinds of nanoparticles – calcium oxide, copper, copper in the form of oxide and CuZnFe4O4, magnesium oxide, and nickel – caused cumulative mortality. Two kinds of nanoparticles – copper and silver – were toxic for fish with LC50 values of approximately 3 mg/L. We did not observe marked differences between the 48-hour and 96-hour acute toxicity LC50 values, yet the possibility to evaluate hatching time in the 96-h acute fish toxicity test seems to be an advantage against that of the 48-hour toxicity. PMID:24179431
Genetic architecture of evolved tolerance to PCBs in the estuarine fish Fundulus heteroclitus
Populations of Atlantic killifish (F. heteroclitus) resident to coastal estuarine habitats contaminated with halogenated aromatic hydrocarbons (HAHs) exhibit heritable resistance to the early life-stage toxicity associated with these compounds. Beyond our knowledge of the aryl hy...
Mhadhbi, Lazhar; Fumega, José; Boumaiza, Moncef; Beiras, Ricardo
2012-03-01
The environmental presence of polybrominated diphenyl ethers (PBDEs), among which BDE-47 and BDE-99 are particularly abundant, makes toxicity data necessary to assess the hazard risk posed by PBDE to aquatic organisms. This study examines the effects of BDE-47 and BDE-99 on embryo-larval stages of the marine flatfish turbot. The turbot embryos were exposed at nominal concentrations of BDE-47 and BDE-99 for 6 days. Selected dose levels were relevant for investigating sublethal and lethal effects. Both tested compounds caused lethal toxicity as well as non-lethal malformations during embryo development. We found a high toxic potency of BDE-47 compared to BDE-99 (LC₅₀ values for embryos and larvae, respectively, BDE-47: 27.35 and 14.13 μg L⁻¹; BDE-99: 38.28 and 29.64 μg L⁻¹). The present study shows high sensitivity of fish early life stages (ELS) to PBDE compounds. Based on environmental concentrations of dissolved PBDEs from various aquatic ecosystems, waterborne BDE-47 and BDE-99 pose little risk of acute toxicity to marine fish at relevant environmental concentrations. Turbot fish ELS proved to be an excellent model for the study of ecotoxicity of contaminants in seawater. The results demonstrate harmful effects of PBDE on turbot ELS at concentrations in the range of parts per billion units. In the perspective of risk assessment, ELS endpoints provide rapid, cost-effective and ecologically relevant information, and links should be sought between these short-term tests and effects of long-term exposures in more realistic scenarios.
Pollino, Carmel A; Holdway, Douglas A
2002-07-01
The toxicity of petroleum hydrocarbons to marine aquatic organisms has been widely investigated; however, the effects on freshwater environments have largely been ignored. In the Australian freshwater environment, the potential impacts of petroleum hydrocarbons are virtually unknown. The toxicity of crude oil and related compounds were measured in the sensitive early life stages of the crimson-spotted rainbowfish (Melanotaenia fluviatilis). Waterborne petroleum hydrocarbons crossed the chorion of embryonic rainbowfish, reducing survival and hatchability. Acute exposures resulted in developmental abnormalities at and above 0.5 mg/L total petroleum hydrocarbons (TPH). Deformities included pericardial edema, disturbed axis formation, and abnormal jaw development. When assessing the acute toxicities of the water-accommodated fraction (WAF) of crude oil, dispersants, dispersant-oil mixtures, and naphthalene to larval rainbowfish, the lowest to highest 96-h median lethal concentrations for day of hatch larvae were naphthalene (0.51 mg/L), dispersed crude oil WAF (DCWAF)-9527 (0.74 mg/L TPH), WAF (1.28 mg/L TPH), DCWAF-9500 (1.37 mg/L TPH), Corexit 9500 (14.5 mg/L TPH), and Corexit 9527 (20.1 mg/L). Using naphthalene as a reference toxicant, no differences were found between the sensitivities of larval rainbowfish collected from adults exposed to petroleum hydrocarbons during embryonic development and those collected from unexposed adults.
A 3R compliant testing strategy to predict chronic fish toxicity
To ensure an ecologically relevant basis for environmental quality standards, whole-organism vertebrate tests are considered most suitable. Currently, the fish early life-stage (FELS) test (OECD 210), which involves an exposure up to one - two months, is used to estimate chronic ...
BEHAVIOR OF PERSISTENT BIOACCUMULATIVE TOXICANTS IN FISH EARLY LIFE STAGES
Whether through environmental criteria or site-specific risk assessments, many EPA programs rely on linking environmental exposures to levels of adverse effect (or no effect) in fish and wildlife. While empirical relationships of exposure to effect can be used for such assessmen...
TOXICITY OF PENTACHLOROPHENOL TO ENDANGERED AND SURROGATE FISH SPECIES
Water quality criteria (WQC) generally are based on the responses of easily cultured and tested surrogate species. Little is known about the relative sensitivity of surrogate and endangered species. The objective of this study was to compare acute and chronic (early life-stage) ...
Fish endpoints measured in early life stage toxicity tests are often used as representative of larval amphibian sensitivity in Ecological Risk Assessment (ERA). This application potentially overlooks the impact of developmental delays on amphibian metamorphosis, and thereby red...
Campbell, Brittany E; Miller, Dini M
2017-03-15
Standard toxicity evaluations of insecticides against insect pests are primarily conducted on adult insects. Evaluations are based on a dose-response or concentration-response curve, where mortality increases as the dose or concentration of an insecticide is increased. Standard lethal concentration (LC50) and lethal dose (LD50) tests that result in 50% mortality of a test population can be challenging for evaluating toxicity of insecticides against non-adult insect life stages, such as eggs and early instar or nymphal stages. However, this information is essential for understanding insecticide efficacy in all bed bug life stages, which affects control and treatment efforts. This protocol uses a standard dipping bioassay modified for bed bug eggs and a contact insecticidal assay for treating nymphal first instars. These assays produce a concentration-response curve to further quantify LC50 values for insecticide evaluations.
Felter, Susan P; Daston, George P; Euling, Susan Y; Piersma, Aldert H; Tassinari, Melissa S
2015-03-01
Abstract Over the last couple of decades, the awareness of the potential health impacts associated with early-life exposures has increased. Global regulatory approaches to chemical risk assessment are intended to be protective for the diverse human population including all life stages. However, questions persist as to whether the current testing approaches and risk assessment methodologies are adequately protective for infants and children. Here, we review physiological and developmental differences that may result in differential sensitivity associated with early-life exposures. It is clear that sensitivity to chemical exposures during early-life can be similar, higher, or lower than that of adults, and can change quickly within a short developmental timeframe. Moreover, age-related exposure differences provide an important consideration for overall susceptibility. Differential sensitivity associated with a life stage can reflect the toxicokinetic handling of a xenobiotic exposure, the toxicodynamic response, or both. Each of these is illustrated with chemical-specific examples. The adequacy of current testing protocols, proposed new tools, and risk assessment methods for systemic noncancer endpoints are reviewed in light of the potential for differential risk to infants and young children.
Mu, Jingli; Jin, Fei; Ma, Xindong; Lin, Zhongsheng; Wang, Juying
2014-11-01
The authors assessed the bioavailability and chronic toxicity of water-accommodated fractions of crude oil (WAFs) and 2 dispersants plus dispersed crude oil (chemical dispersant + crude oil [CE-WAF] and biological dispersant + crude oil [BE-WAF]) on the early life stages of marine medaka, Oryzias melastigma. The results showed that the addition of the 2 dispersants caused a 3- and 4-fold increase in concentrations of summed priority polycyclic aromatic hydrocarbons (PAHs) and high-molecular-weight PAHs with 3 or more benzene rings. The chemical and biological dispersants increased the bioavailability (as measured by ethoxyresorufin-O-dethylase activity) of crude oil 6-fold and 3-fold, respectively. Based on nominal concentrations, chronic toxicity (as measured by deformity) in WAFs exhibited a 10-fold increase in CE-WAF and a 3-fold increase in BE-WAF, respectively. When total petroleum hydrocarbon was measured, the differences between WAF and CE-WAF treatments disappeared, and CE-WAF was approximately 10 times more toxic than BE-WAF. Compared with the chemical dispersant, the biological dispersant possibly modified the toxicity of oil hydrocarbons because of the increase in the proportion of 2- and 3-ringed PAHs in water. The chemical and biological dispersants enhanced short-term bioaccumulation and toxicity, through different mechanisms. These properties should be considered in addition to their efficacy in degrading oil when oil spill management strategies are selected. © 2014 SETAC.
To characterize intra-specific variation in sensitivity to highly toxic pollutants in the non-migratory estuarine Atlantic killifish (Fundulus heteroclitus), we compared early life stage responses to the prototypical dioxin-like compound, 3,3’4,4’,5 hexachlorobiphenyl (PCB126). ...
Ecotoxicological assessment of glyphosate-based herbicides: Effects on different organisms.
de Brito Rodrigues, Laís; de Oliveira, Rhaul; Abe, Flávia Renata; Brito, Lara Barroso; Moura, Diego Sousa; Valadares, Marize Campos; Grisolia, Cesar Koppe; de Oliveira, Danielle Palma; de Oliveira, Gisele Augusto Rodrigues
2017-07-01
Glyphosate-based herbicides are the most commonly used worldwide because they are effective and relatively nontoxic to nontarget species. Unlimited and uncontrolled use of such pesticides can have serious consequences for human health and ecological balance. The present study evaluated the acute toxicity and genotoxicity of 2 glyphosate-based formulations, Roundup Original (Roundup) and Glyphosate AKB 480 (AKB), on different organisms: cucumber (Cucumis sativus), lettuce (Lactuca sativa), and tomato (Lycopersicon esculentum) seeds, and microcrustacean Artemia salina and zebrafish (Danio rerio) early life stages. For the germination endpoint, only L. esculentum presented significant sensitivity to AKB and L. sativa to Roundup, whereas both formulations significantly inhibited the root growth of all species tested. Both AKB and Roundup induced significant toxicity to A. salina; both are classified as category 3, which indicates a hazard for the aquatic environment, according to criteria of the Globally Harmonized Classification System. However, Roundup was more toxic than AKB, with 48-h median lethal concentration (LC50) values of 14.19 mg/L and 37.53 mg/L, respectively. For the embryo-larval toxicity test, Roundup proved more toxic than AKB for the mortality endpoint (96-h LC50 values of 10.17 mg/L and 27.13 mg/L, respectively), whereas for the hatching parameter, AKB was more toxic than Roundup. No significant genotoxicity to zebrafish larvae was found. We concluded that AKB and Roundup glyphosate-based formulations are phytotoxic and induce toxic effects in nontarget organisms such as A. salina and zebrafish early life stages. Environ Toxicol Chem 2017;36:1755-1763. © 2016 SETAC. © 2016 SETAC.
Waller, Diane L.; Luoma, James A.
2016-01-01
The biopesticide, Zequanox®, is registered for dreissenid mussel control in open water systems. Previous toxicity trials with nontarget organisms, including young-of-the year of several fish species and invertebrates, demonstrated selectivity of Zequanox for dreissenids. However, data are lacking on its safety to reproductive and early life stages of fish. The present study evaluated the effects of Zequanox on spawning and early life stages of the fathead minnow, Pimephales promelas, at the maximum approved concentration (100 mg Zequanox active ingredient /L) and exposure duration (8 h) for open water application. The results showed no significant effect of Zequanox on survival, condition, or cumulative egg deposition (21 d) in adult fathead minnow. Eggs (<24-h old) exposed to Zequanox developed to the eyed-stage at a similar rate to that of unexposed eggs. Additionally, Zequanox did not have a significant effect on survival and growth (90 d) of newly hatched fry (<24-h old). The results indicate that Zequanox treatment will not affect survival, spawning, and early life development of fathead minnows when applied at the recommended treatment regime.
Balancing risk and benefit in early-stage classical Hodgkin lymphoma.
Bröckelmann, Paul J; Sasse, Stephanie; Engert, Andreas
2018-04-12
With defined chemotherapy and radiotherapy (RT) and risk-adapted treatment, early-stage classical Hodgkin lymphoma (HL) has become curable in a majority of patients. Hence, a major current goal is to reduce treatment-related toxicity while maintaining long-term disease control. Patients with early-stage favorable disease (ie, limited stage without risk factors [RFs]) are frequently treated with 2 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (2×ABVD) followed by 20-Gy involved-field or involved-site RT (IF/ISRT). In patients with early-stage unfavorable disease (ie, limited stage with RFs), 4 cycles of chemotherapy are usually consolidated with 30-Gy IF/ISRT. Compared with 4×ABVD, 2 cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (2×BEACOPP escalated ) followed by 2×ABVD improved 5-year progression-free survival (PFS), with similar 5-year overall survival. Recently, treatment strategies based on [ 18 F]fluorodeoxyglucose positron emission tomography (PET) response were evaluated. In early-stage unfavorable HL, a majority of patients achieved a negative interim PET after 2×ABVD and an excellent outcome after 4×ABVD, whereas in those with a positive interim PET, 2×BEACOPP escalated improved 5-year PFS. Furthermore, a PET-guided RT approach was evaluated to decrease long-term toxicity. Although both the RAPID and H10 trials reported poorer disease control without RT, PET-guided omission of RT can constitute a valid therapeutic option in patients with an increased risk of RT-associated toxicity (eg, because of sex, age, or disease localization). Implementation of drugs such as the anti-CD30 antibody-drug conjugate brentuximab vedotin or the anti-programmed death 1 antibodies nivolumab or pembrolizumab might allow further reduction of overall mortality and improve quality of life in affected patients. © 2018 by The American Society of Hematology.
Photoenhanced toxicity of a carbamate insecticide to early life stage anuran amphibians
Zaga, A.; Little, E.E.; Rabeni, C.F.; Ellersieck, Mark R.
1998-01-01
Aican clawed frog (Xenopus laevis) and gray tree frog (Hyla versicolor) embryos and tadpoles were exposed to sublethal levels of carbaryl, a broad-spectrum insecticide, and ultraviolet radiation to determine interactive and sublethal effects. Ultraviolet intensity (UV-B [285–320 nm] plus UV-A [321–400 nm]) was controlled with various types of plastic filters and quantified with a scanning spectroradiometer. Significant differences in swimming activity and mortality of both species were evident during the 96-h experiments. Ultraviolet-B radiation alone and carbaryl in the presence of UV-B significantly decreased swimming activity of both species. As little as 1.5% intensity of ambient solar UV-B radiation photoactivated carbaryl. Toxicity of 7.5 mg/L carbaryl increased by 10-fold in the presence of UV-B in all species and life stages tested. Our results indicate that photoenhancement by solar UV-B radiation should be considered when evaluating the toxicity of contaminants to amphibians and other organisms.
Crane, Mark; Finnegan, Meaghean; Weltje, Lennart; Kosmala-Grzechnik, Sylwia; Gross, Melanie; Wheeler, James R
2016-10-01
Amphibians are currently the most threatened and rapidly declining group of vertebrates and this has raised concerns about their potential sensitivity and exposure to plant protection products and other chemicals. Current environmental risk assessment procedures rely on surrogate species (e.g. fish and birds) to cover the risk to aquatic and terrestrial life stages of amphibians, respectively. Whilst a recent meta-analysis has shown that in most cases amphibian aquatic life stages are less sensitive to chemicals than fish, little research has been conducted on the comparative sensitivity of terrestrial amphibian life stages. Therefore, in this paper we address the questions "What is the relative sensitivity of terrestrial amphibian life stages to acute chemical oral exposure when compared with mammals and birds?" and "Are there correlations between oral toxicity data for amphibians and data for mammals or birds?" Identifying a relationship between these data may help to avoid additional vertebrate testing. Acute oral amphibian toxicity data collected from the scientific literature and ecotoxicological databases were compared with toxicity data for mammals and birds. Toxicity data for terrestrial amphibian life stages are generally sparse, as noted in previous reviews. Single-dose oral toxicity data for terrestrial amphibian life stages were available for 26 chemicals and these were positively correlated with LD50 values for mammals, while no correlation was found for birds. Further, the data suggest that oral toxicity to terrestrial amphibian life stages is similar to or lower than that for mammals and birds, with a few exceptions. Thus, mammals or birds are considered adequate toxicity surrogates for use in the assessment of the oral exposure route in amphibians. However, there is a need for further data on a wider range of chemicals to explore the wider applicability of the current analyses and recommendations. Copyright © 2016 Elsevier Inc. All rights reserved.
Lau, Winnie Lik Sing; Law, Ing Kuo; Liow, Guat Ru; Hii, Kieng Soon; Usup, Gires; Lim, Po Teen; Leaw, Chui Pin
2017-12-01
In 2015, a remarkably high density bloom of Alexandrium minutum occurred in Sungai Geting, a semi-enclosed lagoon situated in the northeast of Peninsular Malaysia, causing severe discoloration and contaminated the benthic clams (Polymesoda). Plankton and water samples were collected to investigate the mechanisms of bloom development of this toxic species. Analysis of bloom samples using flow cytometry indicated that the bloom was initiated by the process of active excystment, as planomycetes (>4C cells) were observed in the early stage of the bloom. Increase in planozygotes (2C cells) was evident during the middle stage of the bloom, coinciding with an abrupt decrease in salinity and increase of temperature. The bloom was sustained through the combination of binary division of vegetative cells, division of planozygotes, and cyst germination through continuous excystment. Nutrient depletion followed by precipitation subsequently caused the bloom to terminate. This study provides the first continuous record of in situ life-cycle stages of a natural bloom population of A. minutum through a complete bloom cycle. The event has provided a fundamental understanding of the pelagic life-cycle stages of this tropical dinoflagellate, and demonstrated a unique bloom development characteristic shared among toxic Alexandrium species in coastal embayments. Copyright © 2017 Elsevier B.V. All rights reserved.
Wang, Yanhua; Lv, Lu; Yu, Yijun; Yang, Guiling; Xu, Zhenlan; Wang, Qiang; Cai, Leiming
2017-03-01
Instead of individual ones, pesticides are usually detected in water environment as mixtures of contaminants. Laboratory tests were conducted in order to investigate the effects of individual and joint pesticides (phoxim, atrazine, chlorpyrifos, butachlor and λ-cyhalothrin) on zebrafish (Denio rerio). Results from 96-h semi-static toxicity test indicated that λ-cyhalothrin had the greatest toxicity to the three life stages (embryonic, larval and juvenile stages) of D. rerio with LC 50 values ranging from 0.0031 (0.0017-0.0042) to 0.38 (0.21-0.53) mg a.i. L -1 , followed by butachlor and chlorpyrifos with LC 50 values ranging from 0.45 (0.31-0.59) to 1.93 (1.37-3.55) and from 0.28 (0.13-0.38) to 13.03 (7.54-19.71) mg a.i. L -1 , respectively. In contrast, atrazine showed the least toxicity with LC 50 values ranging from 6.09 (3.34-8.35) to 34.19 (24.42-51.9) mg a.i. L -1 . The larval stage of D. rerio was a vulnerable period to most of the selected pesticides in the multiple life stages tested. Pesticide mixtures containing phoxim and λ-cyhalothrin exerted synergistic effects on the larvae of D. rerio. Moreover, the binary mixture of phoxim-atrazine also displayed synergistic response to zebrafish. It has been assumed that most chemicals are additive in toxicity. Therefore, it is crucial to clarify the synergistic interaction for pesticide regulators and environment managers. In the present study, our data provided a clear picture on ecological risk of these pesticide mixtures to aquatic organisms. Moreover, joint effects play a more important role than individual ones, which require more attention when defining standard for water environment quality and risk assessment protocols. Copyright © 2016 Elsevier Ltd. All rights reserved.
Wheeler, James R; Maynard, Samuel K; Crane, Mark
2014-08-01
The chronic toxicity of chemicals to fish is routinely assessed by using fish early life stage (ELS) test results. Fish full life cycle (FLC) tests are generally required only when toxicity, bioaccumulation, and persistence triggers are met or when there is a suspicion of potential endocrine-disrupting properties. This regulatory approach is based on a relationship between the results of fish ELS and FLC studies first established more than 35 yrs ago. Recently, this relationship has been challenged by some regulatory authorities, and it has been recommended that more substances should undergo FLC testing. In addition, a project proposal has been submitted to the Organisation for Economic Cooperation and Development (OECD) to develop a fish partial life cycle (PLC) test including a reproductive assessment. Both FLC and PLC tests are animal- and resource-intensive and technically challenging and should therefore be undertaken only if there is clear evidence that they are necessary for coming to a regulatory decision. The present study reports on an analysis of a database of paired fish ELS and FLC endpoints for plant protection product active substances from European Union draft assessment reports and the US Environmental Protection Agency Office of Pesticide Programs Pesticide Ecotoxicity Database. Analysis of this database shows a clear relationship between ELS and FLC responses, with similar median sensitivity across substances when no-observed-effect concentrations (NOECs) are compared. There was also no indication that classification of a substance as a mammalian reproductive toxicant leads to more sensitive effects in fish FLC tests than in ELS tests. Indeed, the response of the ELS tests was generally more sensitive than the most sensitive reproduction NOEC from a FLC test. This analysis indicates that current testing strategies and guidelines are fit for purpose and that there is no need for fish full or partial life cycle tests for most plant protection product active substances. © 2014 SETAC.
Page, David S.; Chapman, Peter M.; Landrum, Peter F.; Neff, Jerry; Elston, Ralph
2012-01-01
This article presents a critical review of two groups of studies that reported adverse effects to salmon and herring eggs and fry from exposure to 1 μg/L or less of aqueous total polycyclic aromatic hydrocarbons (TPAH), as weathered oil, and a more toxic aqueous extract of “very weathered oil.” Exposure media were prepared by continuously flowing water up through vertical columns containing gravel oiled at different concentrations of Prudhoe Bay crude oil. Uncontrolled variables associated with the use of the oiled gravel columns included time- and treatment-dependent variations in the PAH concentration and composition in the exposure water, unexplored toxicity from other oil constituents/degradation products, potential toxicity from bacterial and fungal activity, oil droplets as a potential contaminant source, inherent differences between control and exposed embryo populations, and water flow rate differences. Based on a review of the evidence from published project reports, peer-reviewed publications, chemistry data in a public database, and unpublished reports and laboratory records, the reviewed studies did not establish consistent dose (concentration) response or causality and thus do not demonstrate that dissolved PAH alone from the weathered oil resulted in the claimed effects on fish embryos at low μg/L TPAH concentrations. Accordingly, these studies should not be relied on for management decision-making, when assessing the risk of very low–level PAH exposures to early life stages of fish. PMID:22754275
Hutler Wolkowicz, Ianina R; Aronzon, Carolina M; Pérez Coll, Cristina S
2013-12-15
Lethal and sublethal toxicity of the major chemical used in epoxide compounds, epichlorohydrin (ECH) was evaluated on the early life cycle of the common South American toad, Rhinella arenarum (Anura, Bufonidae). The stages evaluated were (according to Del Conte and Sirlin): early blastula (S.3-S.4), gastrula (S.10-S.12), rotation (S.15), tail bud (S.17), muscular response (S.18), gill circulation (S.20), open mouth (S.21), opercular folds (S.23) and complete operculum (S.25). The LC50 and EC50 values for lethal and sublethal effects were calculated. The early blastula was the most sensitive stage to ECH both for continuously and pulse-exposures (LC50-24h=50.9 mg L(-1)), while S.20 was the most resistant (LC50-24h=104.9 mg L(-1)). Among sublethal effects, early blastula was also the most sensitive stage (LOEC-48 h=20 mg L(-1)) and it has a Teratogenic Index of 2.5, which indicates the teratogenic potential of the substance. The main abnormalities were persistent yolk plugs, cell dissociation, tumors, hydropsy, oral malformations, axial/tail flexures, delayed development and reduced body size. ECH also caused neurotoxicity including scarce response to stimuli, reduction in the food intake, general weakness, spasms and shortening, erratic or circular swimming. Industrial contamination is considered an important factor on the decline of amphibian populations. Considering the available information about ECH's toxicity and its potential hazard to the environment, this work shows the first results of its developmental toxicity on a native amphibian species, Rhinella arenarum. Copyright © 2013 Elsevier B.V. All rights reserved.
Arnberg, Maj; Moodley, Leon; Dunaevskaya, Evgenia; Ramanand, Sreerekha; Ingvarsdóttir, Anna; Nilsen, Marianne; Ravagnan, Elisa; Westerlund, Stig; Sanni, Steinar; Tarling, Geraint A; Bechmann, Renée K
2017-01-01
Rising oil and gas activities in northern high latitudes have led to an increased risk of petroleum pollution in these ecosystems. Further, seasonal high UV radiation at high latitudes may elevate photo-enhanced toxicity of petroleum pollution to marine organisms. Zooplanktons are a key ecological component of northern ecosystems; therefore, it is important to assess their sensitivity to potential pollutants of oil and gas activity. As ontogenetic development may be particularly sensitive, the aim of this study was to examine the impact of chronic exposure to oil water dispersion (OWD) on development and feeding of early life stages of the Northern krill, Meganyctiphanes norvegica. In a range of experiments, embryonic, nonfeeding, and feeding larval stages were exposed to concentrations of between 0.01 and 0.1 mg/L of oil or photo-modified oil for 19 and 21 d. No significant effects on egg respiration, hatching success, development, length and larval survival were observed from these treatments. Similarly, evolution of fatty acid composition patterns during ontogenetic development was unaffected. The results indicates a high degree of resilience of these early developmental stages to such types and concentrations of pollutants. However, feeding and motility in later calyptopis-stage larvae were significantly impaired at exposure of 0.1 mg/L oil. Data indicate that feeding larval stage of krill was more sensitive to OWD than early nonfeeding life stages. This might be attributed to the narcotic effects of oil pollutants, their direct ingestion, or accumulated adverse effects over early development.
Abe, Flavia R; Mendonça, Jacqueline N; Moraes, Luiz A B; Oliveira, Gisele A R de; Gravato, Carlos; Soares, Amadeu M V M; Oliveira, Danielle P de
2017-07-01
Organic dyes extracted from natural sources have been widely used to develop safety and eco-friendly dyes as an alternative to synthetic ones, since the latter are usually precursors of mutagenic compounds. Thereby, toxicity tests to non-target organisms are critical step to develop harmless dyes to environment and in this context, zebrafish early life stages are becoming an important alternative model. We aimed to assess the toxic effects of the synthetic dye Basic Red 51 (BR51, used in cosmetic industry), the natural dye erythrostominone (ERY, a potential commercial dye extracted from fungi) and its photodegradation product (DERY), using zebrafish early life assays. Developmental malformations on embryos and behavioral impairment on larvae were explored. Our results showed that embryos exposed to BR51 and ERY exhibited a large yolk sac (LOEC = 7.5 mg L -1 ), possibly due to a deformity or delayed resorption. ERY also induced pericardial and yolk sac edemas at high concentrations (LOEC = 15 and 30 mg L -1 , respectively). Moreover, larvae swan less distance and time when exposed to ERY (LOEC = 7.5 mg L -1 ) and BR51 (LOEC = 1.875 mg L -1 ). The lowest larvae locomotion have been associated with impairment of the yolk sac, important tissue of the energy source. Interestingly, DERY did not affect neither development nor behavior of zebrafish, showing that ERY photodegradation is sufficient to prevent its toxic effects. In conclusion, both natural and synthetic dyes impaired development and behavior of zebrafish early life, therefore, a simple treatment of the natural dye can prevent the aquatic life impact. Copyright © 2017 Elsevier Ltd. All rights reserved.
The authors developed a toxicity database for unionid mussels to examine the extent of intra- and interlaboratory variability in acute toxicity tests with mussel larvae (glochidia) and juveniles; the extent of differential sensitivity of the 2 life stages; and the variation in se...
Di Paolo, Carolina; Groh, Ksenia J; Zennegg, Markus; Vermeirssen, Etiënne L M; Murk, Albertinka J; Eggen, Rik I L; Hollert, Henner; Werner, Inge; Schirmer, Kristin
2015-12-01
The occurrence of chronic or delayed toxicity resulting from the exposure to sublethal chemical concentrations is an increasing concern in environmental risk assessment. The Fish Embryo Toxicity (FET) test with zebrafish provides a reliable prediction of acute toxicity in adult fish, but it cannot yet be applied to predict the occurrence of chronic or delayed toxicity. Identification of sublethal FET endpoints that can assist in predicting the occurrence of chronic or delayed toxicity would be advantageous. The present study characterized the occurrence of delayed toxicity in zebrafish larvae following early exposure to PCB126, previously described to cause delayed effects in the common sole. The first aim was to investigate the occurrence and temporal profiles of delayed toxicity during zebrafish larval development and compare them to those previously described for sole to evaluate the suitability of zebrafish as a model fish species for delayed toxicity assessment. The second aim was to examine the correlation between the sublethal endpoints assessed during embryonal and early larval development and the delayed effects observed during later larval development. After exposure to PCB126 (3-3000ng/L) until 5 days post fertilization (dpf), larvae were reared in clean water until 14 or 28 dpf. Mortality and sublethal morphological and behavioural endpoints were recorded daily, and growth was assessed at 28 dpf. Early life exposure to PCB126 caused delayed mortality (300 ng/L and 3000 ng/L) as well as growth impairment and delayed development (100 ng/L) during the clean water period. Effects on swim bladder inflation and cartilaginous tissues within 5 dpf were the most promising for predicting delayed mortality and sublethal effects, such as decreased standard length, delayed metamorphosis, reduced inflation of swim bladder and column malformations. The EC50 value for swim bladder inflation at 5 dpf (169 ng/L) was similar to the LC50 value at 8 dpf (188 and 202 ng/L in two experiments). Interestingly, the patterns of delayed mortality and delayed effects on growth and development were similar between sole and zebrafish. This indicates the comparability of critical developmental stages across divergent fish species such as a cold water marine flatfish and a tropical freshwater cyprinid. Additionally, sublethal effects in early embryo-larval stages were found promising for predicting delayed lethal and sublethal effects of PCB126. Therefore, the proposed method with zebrafish is expected to provide valuable information on delayed mortality and delayed sublethal effects of chemicals and environmental samples that may be extrapolated to other species. Copyright © 2015 Elsevier B.V. All rights reserved.
Horie, Yoshifumi; Yamagishi, Takahiro; Shintaku, Yoko; Iguchi, Taisen; Tatarazako, Norihisa
2018-07-01
Tributyltin, an organotin compound, was used worldwide as an antifouling agent in aquatic environments and there has been much concern about the toxicological and ecotoxicological properties of organotin compounds. Even though it has been prohibited worldwide, tributyltin is still detected at low concentrations in aquatic environments. Here we investigated the effects of tributyltin on the early life-stage, reproduction, and gonadal sex differentiation in Japanese medaka (Oryzias latipes). In adults, exposure to tributyltin at 3.82 μg/L suppressed fecundity and fertility and increased mortality. At 10.48 μg/L all medaka died by the sixth day of exposure. Exposure to tributyltin during early life-stages induced no significant differences in mortality or embryonic development, but growth was suppressed in groups exposed to 0.13 and 0.68 μg/L. Furthermore, there was no abnormal gonadal development in Japanese medaka exposed to tributyltin. These results provide evidence of the negative effects of tributyltin on reproduction in a teleost fish. Tributyltin did not affect gonadal sex differentiation in Japanese medaka, but fecundity and fertility were suppressed, although it is not clear whether this suppression resulted from the endocrine-disrupting action of tributyltin or its toxicity. Copyright © 2018 Elsevier Ltd. All rights reserved.
Tartaglione, Anna Maria; Venerosi, Aldina; Calamandrei, Gemma
2016-01-01
The developmental origin of health and disease hypothesis states that adverse fetal and early childhood exposures can predispose to obesity, cardiovascular, and neurodegenerative diseases (NDDs) in adult life. Early exposure to environmental chemicals interferes with developmental programming and induces subclinical alterations that may hesitate in pathophysiology and behavioral deficits at a later life stage. The mechanisms by which perinatal insults lead to altered programming and to disease later in life are still undefined. The long latency between exposure and onset of disease, the difficulty of reconstructing early exposures, and the wealth of factors which the individual is exposed to during the life course make extremely difficult to prove the developmental origin of NDDs in clinical and epidemiological studies. An overview of animal studies assessing the long-term effects of perinatal exposure to different chemicals (heavy metals and pesticides) supports the link between exposure and hallmarks of neurodegeneration at the adult stage. Furthermore, models of maternal immune activation show that brain inflammation in early life may enhance adult vulnerability to environmental toxins, thus supporting the multiple hit hypothesis for NDDs' etiology. The study of prospective animal cohorts may help to unraveling the complex pathophysiology of sporadic NDDs. In vivo models could be a powerful tool to clarify the mechanisms through which different kinds of insults predispose to cell loss in the adult age, to establish a cause-effect relationship between "omic" signatures and disease/dysfunction later in life, and to identify peripheral biomarkers of exposure, effects, and susceptibility, for translation to prospective epidemiological studies.
We developed a toxicity database for unionid mussels to examine the extent of intra- and inter-laboratory variability in acute toxicity tests with mussel larvae (glochidia) and juveniles; the extent of differential sensitivity of the two life stages; and the variation in sensitiv...
He, Yuhe; Sun, Chenxing; Zhang, Yifeng; Folkerts, Erik J; Martin, Jonathan W; Goss, Greg G
2018-03-20
Hydraulic fracturing (HF) has emerged as a major recovery method of unconventional oil and gas reservoirs and concerns have been raised regarding the environmental impact of releases of Flowback and Produced Water (FPW) to aquatic ecosystems. To investigate potential effects of HF-FPW on fish embryo development, HF-FPW samples were collected from two different wells and the organic fractions were isolated from both aqueous and particle phases to eliminate the confounding effects of high salinity. Each organic extract was characterized by non-target analysis with HPLC-Orbitrap-MS, with targeted analysis for polycyclic aromatic hydrocarbons provided as markers of petroleum-affected water. The organic profiles differed between samples, including PAHs and alkyl PAHs, and major substances identified by non-target analysis included polyethylene glycols, alkyl ethoxylates, octylphenol ethoxylates, and other high molecular weight (C 49-79 ) ethylene oxide polymeric material. Zebrafish embryos were exposed to various concentrations of FPW organic extracts to investigate acute (7-day) and developmental toxicity in early life stages. The acute toxicity (LD 50 ) of the extracted FPW fractions ranged from 2.8× to 26× the original organic content. Each extracted FPW fraction significantly increased spinal malformation, pericardial edema, and delayed hatch in exposed embryos and altered the expression of a suite of target genes related to biotransformation, oxidative stress, and endocrine-mediation in developing zebrafish embryos. These results provide novel information on the variation of organic profiles and developmental toxicity among different sources and fractions of HF-FPWs.
Blewett, Tamzin A; Dow, Elissa M; Wood, Chris M; McGeer, James C; Smith, D Scott
2018-05-24
Nickel (Ni) emissions resulting from production and transportation raise concerns about the impact of Ni exposure to marine ecosystems. Ni bioavailability models are established for FW systems, but the influence of chemical parameters (e.g. dissolved organic carbon (DOC)) on Ni toxicity within marine systems is less well understood. To examine the effects of DOC concentration and composition on Ni toxicity, acute toxicity tests were conducted on early life-stages of blue mussels (Mytilus edulis) and sea urchin embryos (Strongylocentrotus purpuratus) in full strength sea water (32 ppt). Nine different field collected samples of water with varying concentration (up to 4.5 mg C/L) and composition of DOC were collected from the east coast of the United States. Organic matter compositional analysis included molecular fluorescence and absorbance spectroscopy. The different DOC sources had different protective effects against embryo toxicity. The control (no DOC) Ni 48 h-EC 50 for Mytilus embryos was 133 µg/L (95% confidence interval (C.I.) of 123-144 µg/L), while Strongylocentrotus embryos displayed control 96-h EC 50 values of 207 µg/L (167-247 µg/L). The most significantly protective sample had high humic acid concentrations (as determined from fluorescence spectroscopy), which yielded an EC 50 of 195 µg/L (169-222 µg/L) for Mytilus, and an EC 50 of 394 µg/L (369-419 µg/L) for S. purpuratus. Among all samples, protection was related to both DOC quantity and quality, with fluorescence-resolved humic and fulvic acid concentrations showing the strongest correlations with protection for both species. These data suggest that DOC is protective against Ni toxicity in M. edulis and S. purpuratus, and that accounting for a DOC quality factor will improve predictive toxicity models such as the biotic ligand model. Copyright © 2018 Elsevier Inc. All rights reserved.
Picone, Marco; Bergamin, Martina; Delaney, Eugenia; Ghirardini, Annamaria Volpi; Kusk, Kresten Ole
2018-01-01
The early-life stages of development of the calanoid copepod Acartia tonsa from egg to copepodite I is proposed as an endpoint for assessing sediment toxicity by exposing newly released eggs directly onto the sediment-water interface. A preliminary study of 5 sediment samples collected in the lagoon of Venice highlighted that the larval development rate (LDR) and the early-life stages (ELS) mortality endpoints with A. tonsa are more sensitive than the standard amphipod mortality test; moreover LDR resulted in a more reliable endpoint than ELS mortality, due to the interference of the sediment with the recovery of unhatched eggs and dead larvae. The LDR data collected in a definitive study of 48 sediment samples from the Venice Lagoon has been analysed together with the preliminary data to evaluate the statistical performances of the bioassay (among replicate variance and minimum significant difference between samples and control) and to investigate the possible correlation with sediment chemistry and physical properties. The results showed that statistical performances of the LDR test with A. tonsa correspond with the outcomes of other tests applied to the sediment-water interface (Strongylocentrotus purpuratus embryotoxicity test), sediments (Neanthes arenaceodentata survival and growth test) and porewater (S. purpuratus); the LDR endpoint did, however, show a slightly higher variance as compared with other tests used in the Lagoon of Venice, such as 10-d amphipod lethality test and larval development with sea urchin and bivalves embryos. Sediment toxicity data highlighted the high sensitivity and the clear ability of the larval development to discriminate among sediments characterized by different levels of contamination. The data of the definitive study evidenced that inhibition of the larval development was not affected by grain-size and the organic carbon content of the sediment; in contrast, a strong correlation between inhibition of the larval development and the sediment concentrations of some metals (Cu, Hg, Pb, Zn), acid-volatile sulphides (AVS), polychlorinated biphenyls (PCBs) and polynuclear aromatic hydrocarbons (PAHs) was found. No correlation was found with DDTs, hexachlorobenzene and organotin compounds. Copyright © 2017 Elsevier Inc. All rights reserved.
Waller, Diane L.; Luoma, James A.
2017-01-01
The biopesticide, Zequanox®, is registered for dreissenid mussel control in open water systems in the United States. Previous toxicity trials with nontarget organisms, including several young-of-the-year fish species and invertebrates, demonstrated selectivity of Zequanox for dreissenid mussels, but data are lacking on the treatment-related effects on reproduction and early life stage development of fish. The present study evaluated the effects of Zequanox on spawning and early life stages of the fathead minnow, Pimephales promelas, after exposure to the maximum approved concentration [100 mg active ingredient (AI)/L] and exposure duration (8h) for open water application. The results showed no significant treatment-related effect of Zequanox on survival, condition, or cumulative egg production (21 d) in adult fathead minnow. Eggs (≤24 h old) exposed to Zequanox developed to the eyed-stage at a similar rate to that of untreated eggs. Additionally, Zequanox did not have a significant effect on survival and growth (90 d) of newly hatched larvae (≤24-h old). Zequanox may be an option for control of dreissenid mussels in localized open water habitats where concerns exist regarding reproduction and recruitment of cyprinids and related species.
Saraf, Spencer R; Frenkel, Amy; Harke, Matthew J; Jankowiak, Jennifer G; Gobler, Christopher J; McElroy, Anne E
2018-01-01
Freshwater cyanobacterial harmful algal blooms (CyanoHABs) caused by algae in the genus Microcystis have been increasing in frequency and severity in recent decades. Microcystis blooms threaten aquatic organisms through effects associated with the rapid increase of biomass and the production of the hepatotoxin microcystin (MC) by toxic strains. Among fish, effects of blooms are likely to be more severe for early life stages, and physiological impacts on this life stage could significantly impact recruitment and fish populations. This study explores the effects of Microcystis blooms on the development of fish using the model organism, the Japanese medaka (Oryzias latipes), under realistic exposure conditions. Medaka embryos were exposed to natural blooms collected from New York City (USA) lakes, lab cultures of Microcystis, and MC-LR solutions. Field collected samples were more toxic than lab cultures (even when compared at the same algal density or MC concentration), causing decreased survival, premature time to hatch, reduced body length, yolk sac edema, and decreased heart rate, while lab culture exposures only resulted in bradycardia. Heart rate was the most sensitive endpoint measured, being depressed in embryos exposed to both lab cultures and field collected blooms. Generalized linear model analysis indicated bradycardia was statistically associated with both cell densities of blooms and MC concentrations, while single factor analysis indicated that MC concentrations had a stronger correlation compared to cell densities. However, MC exposure could not fully explain the effects observed, as exposures to MC-LR solutions alone were not able to reduce heart rate as severely as algal exposures. Collectively, these experiments indicate that factors beyond exposure to MC or even isolated Microcystis strains influence heart rate of fish exposed to Microcystis blooms. Enhanced mortality, depressed heart rate, and abnormal development observed in response to environmentally realistic exposures of Microcystis blooms could affect success of fish at both individual or population levels. Copyright © 2017 Elsevier B.V. All rights reserved.
Phototoxicity of TiO2 nanoparticles to zebrafish (Danio rerio) is dependent on life stage
The zebrafish (Danio rerio) embryo has been increasingly used as a model to evaluate toxicity of manufactured nanomaterials. Many studies indicate that the embryo chorion may protect animals from toxic effects of nanomaterials, suggesting that post-hatch life stages may be more s...
Laboratory sediment tests were conducted to evaluate the bioaccumulation and photoinduced toxicity of fluoranthene in larval and adult life-stages of Chironomus tentans. In the first of two experiments, fourth-instar and adult C. tentans exposed to spiked sediments were collected...
Olsvik, Pål A; Berntssen, Marc H G; Hylland, Ketil; Eriksen, Dag Ø; Holen, Elisabeth
2012-07-01
The aim of this study was to investigate whether (226)Ra, a radionuclide present in produced water from oil platforms in the North Sea and other offshore drilling areas, could affect vulnerable early life stages of Atlantic cod (Gadus morhua). Blastula-stage embryonic cells (EC) from fertilized eggs of Atlantic cod were isolated and exposed to environmental relevant concentrations of (226)Ra and transcription of selected genes quantified. The results showed a weak, but significant up-regulation of GPx3 and HSP70 transcripts after 48 h of exposure to 2.11 Bq/L. In EC exposed to three (226)Ra concentrations (2.11, 23 and 117 Bq/L) for 12 h, metallothionein, HSP90AA, thioredoxin and caspase 8 were significantly up-regulated in cells exposed to 117 Bq/L, whereas thioredoxin was also significantly up-regulated in EC exposed to 23 Bq/L. When EC were exposed to the same (226)Ra concentrations for 48 h, only heme oxygenase was significantly up-regulated in the 23 Bq/L exposure group. The results suggest that environmentally relevant activities of (226)Ra may induce oxidative stress and apoptosis in fish ECs. Exposure of Atlantic cod EC to Cd, selected as a model toxicant, supported the ability of EC around blastula stage to respond to toxicants by altered transcription. Due to dilution, environmentally relevant concentrations of radionuclides present in produced water would be expected to pose a minor threat to early life stages of fish. Copyright © 2012 Elsevier Ltd. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Pagano, Giovanni, E-mail: gbpagano@tin.it; Guida, Marco; Siciliano, Antonietta
Background: Broad-ranging adverse effects are known for rare earth elements (REE), yet only a few studies tested the toxicity of several REE, prompting studies focusing on multi-parameter REE toxicity. Methods: Trichloride salts of Y, La, Ce, Nd, Sm, Eu and Gd were tested in Paracentrotus lividus sea urchin embryos and sperm for: (1) developmental defects in either REE-exposed larvae or in the offspring of REE-exposed sperm; (2) fertilization success; (3) mitotic anomalies in REE-exposed embryos and in the offspring of REE-exposed sperm, and (4) reactive oxygen species (ROS) formation, and malondialdehyde (MDA) and nitric oxide (NO) levels. Results: REEs affectedmore » P. lividus larvae with concentration-related increase in developmental defects, 10{sup −6} to 10{sup −4} M, ranking as: Gd(III)>Y(III)>La(III)>Nd(III)≅Eu(III)>Ce(III)≅Sm(III). Nominal concentrations of REE salts were confirmed by inductively coupled plasma mass spectrometry (ICP-MS). Significant increases in MDA levels, ROS formation, and NO levels were found in REE-exposed embryos. Sperm exposure to REEs (10{sup −5} to 10{sup −4} M) resulted in concentration-related decrease in fertilization success along with increase in offspring damage. Decreased mitotic activity and increased aberration rates were detected in REE-exposed embryos and in the offspring of REE-exposed sperm. Conclusion: REE-associated toxicity affecting embryogenesis, fertilization, cytogenetic and redox endpoints showed different activities of tested REEs. Damage to early life stages, along with redox and cytogenetic anomalies should be the focus of future REE toxicity studies. - Highlights: • Seven rare earth elements exerted different effects on sea urchin early life stages. • Embryo-, spermio- and mitotoxicity, and oxidative/ nitrosative stress were found. • Nominal vs. analytical REE concentrations were checked. • Comparative toxicities were evaluated for the different REE.« less
Walker, M.K.; Hufnagle, L.C.; Clayton, M.K.; Peterson, R.E.
1992-01-01
To characterize the risk that polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), and biphenyls (PCBs) pose to salmonid early life stage survival, we developed a method to expose rainbow trout (Oncorhynchus mykiss) eggs to graded doses of PCDD, PCDF, and PCB congeners, using 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as a prototype. Rainbow trout eggs were injected 24–50 h post-fertilization with 0.2 μl of 50 mM phosphatidylcholine (PC) liposomes (control) or 0.2 μl of 5–7 graded doses of TCDD incorporated into 50 mM PC liposomes. Injection volume never exceeded 0.6% egg volume. Immediately following injection, the injection site was sealed with Super glue®, resulting in 92–97% of TCDD dose retained by the egg. Following both egg injection and waterborne egg exposure. TCDD toxicity in rainbow trout was manifested by half-hatching mortality but predominantly by sac fry mortality associated with hemorrhages, pericardial edema, and yolk sac edema. TCDD LD50s, following injection and waterborne exposure of rainbow trout eggs, were 421 (331–489) and 439 (346–519) pg TCDD/g egg (LD50, 95% fiducial limits), respectively. As in rainbow trout, TCDD toxicity in lake trout (Salvelinus namaycush) following the same two routes of exposure was manifested by half-hatching mortality but predominantly by sac fry mortality preceded by hemorrhages and yolk sac edema. LD50s, based on the dose of TCDD in lake trout eggs, were 47 (21–65) and 65 (60–71) pg/g following injection and waterborne exposure, respectively. The egg injection method is ideal for assessing the relationship between early life stage mortality in rainbow trout and graded egg doses of individual PCDD, PCDF, or PCB congeners.
Comparative effects of pH and Vision herbicide on two life stages of four anuran amphibian species.
Edginton, Andrea N; Sheridan, Patrick M; Stephenson, Gerald R; Thompson, Dean G; Boermans, Herman J
2004-04-01
Vision, a glyphosate-based herbicide containing a 15% (weight:weight) polyethoxylated tallow amine surfactant blend, and the concurrent factor of pH were tested to determine their interactive effects on early life-stage anurans. Ninety-six-hour laboratory static renewal studies, using the embryonic and larval life stages (Gosner 25) of Rana clamitans, R. pipiens, Bufo americanus, and Xenopus laevis, were performed under a central composite rotatable design. Mortality and the prevalence of malformations were modeled using generalized linear models with a profile deviance approach for obtaining confidence intervals. There was a significant (p < 0.05) interaction of pH with Vision concentration in all eight models, such that the toxicity of Vision was amplified by elevated pH. The surfactant is the major toxic component of Vision and is hypothesized, in this study, to be the source of the pH interaction. Larvae of B. americanus and R. clamitans were 1.5 to 3.8 times more sensitive than their corresponding embryos, whereas X. laevis and R. pipiens larvae were 6.8 to 8.9 times more sensitive. At pH values above 7.5, the Vision concentrations expected to kill 50% of the test larvae in 96-h (96-h lethal concentration [LC50]) were predicted to be below the expected environmental concentration (EEC) as calculated by Canadian regulatory authorities. The EEC value represents a worst-case scenario for aerial Vision application and is calculated assuming an application of the maximum label rate (2.1 kg acid equivalents [a.e.]/ha) into a pond 15 cm in depth. The EEC of 1.4 mg a.e./L (4.5 mg/L Vision) was not exceeded by 96-h LC50 values for the embryo test. The larvae of the four species were comparable in sensitivity. Field studies should be completed using the more sensitive larval life stage to test for Vision toxicity at actual environmental concentrations.
Toxicity of formalin, malachite green, and the mixture to four life stages of rainbow trout
Bills, Terry D.; Advised by: Hosler, Charles F.; Cumming, Kenneth B.; Nord, Richard P.; Senff, Robert E.
1974-01-01
Formalin, malachite green, or a mixture of them are utilized in fish culture for control of external parasites of fish and control of fungus on fish and fish eggs. Very little information is available concerning the toxicity of these compounds to fish under laboratory test conditions or the differences in sensitivity to these chemicals at various life stages. This study was designed to 1) determine the toxicity of formalin, malachite green and the mixture to four life stages of rainbow trout (Salmo gairdneri) under various laboratory test conditions, 2) determine the degradation of formalin and malachite green in water, 3) determine the effect of additive toxicity, and 4) determine the differences in sensitivity of two different lots of eggs to the chemicals. The 96-hour LC50 (lethal concentration required to produce 50% mortality) for formalin against rainbow trout in soft water ranged from 580 micrograms/liter for the eyed egg stage to 134 micrograms/liter for the fingerling stage. The 96-hour LC50 for malachite green against rainbow trout in soft water ranged from 2.00 mg/L for the eyed egg stage to 0.0224 mg/L for the fingerling stage. The additive indices for formalin and malachite green when applied in combination show strictly additive toxicity as the ranges overlap zero in all tests. Deactivation indices for formalin and malachite green show essentially no change in toxicity of the solutions to rainbow trout when aged for periods of 1, 2, and 3 weeks.
Hazard assessment of inorganics to three endangered fish in the Green River, Utah
Hamilton, S.J.
1995-01-01
Acute toxicity tests were conducted with three life stages of Colorado squawfish (Ptychocheilus lucius), razorback sucker (Xyrauchen texanus), and bonytail (Gila elegans) in a reconstituted water quality simulating the middle part of the Green River of Utah. Tests were conducted with boron, lithium, selenate, selenite, uranium, vanadium, and zinc. The overall rank order of toxicity to all species and life stages combined from most to least toxic was vanadium = zinc > selenite > lithium = uranium > selenate > boron. There was no difference between the three species in their sensitivity to the seven inorganics based on a rank-order evaluation at the species level. Colorado squawfish were 2-5 times more sensitive to selenate and selenite at the swimup life stage than older stages, whereas razorback suckers displayed equal sensitivity among life stages. Bonytail exhibited equal sensitivity to selenite, but were five times more sensitive to selenate at the swimup life stage than the older stages. Comparison of 96-hr LC50 values with a limited number of environmental water concentrations in Ashley Creek, Utah, which receives irrigation drainwater, revealed moderate hazard ratios for boron, selenate, selenite, and zinc, low hazard ratios for uranium and vanadium, but unknown ratios for lithium. These inorganic contaminants in drainwaters may adversely affect endangered fish in the Green River.
Gravina, Maria; Pagano, Giovanni; Oral, Rahime; Guida, Marco; Toscanesi, Maria; Siciliano, Antonietta; Di Nunzio, Aldo; Burić, Petra; Lyons, Daniel M; Thomas, Philippe J; Trifuoggi, Marco
2018-05-01
Heavy rare earth elements (HREEs) were tested for adverse effects to early life stages of the sea urchin Sphaerechinus granularis. Embryos were exposed to analytically measured HREE concentrations ranging from 10 -7 to 10 -5 M. No significant developmental defect (DD) increases were observed in embryos exposed to 10 -7 M HREEs, whereas 10 -5 M HREEs resulted in significant DD increase up to 96% for HoCl 3 versus 14% in controls. Embryos exposed to 10 -6 M HREEs showed the highest DD frequency in embryos exposed to 10 -6 M DyCl 3 and HoCl 3 . Cytogenetic analysis of HREE-exposed embryos revealed a significant decrease in mitotic activity, with increased mitotic aberrations. When S. granularis sperm were exposed to HREEs, the offspring of sperm exposed to 10 -5 M GdCl 3 and LuCl 3 showed significant DD increases. The results warrant investigations on HREEs in other test systems, and on REE-containing complex mixtures.
Tang, Monica; Horsley, Patrick; Lewis, Craig R
2018-05-01
(Neo)adjuvant chemotherapy for early stage breast cancer is associated with side-effects, resulting in increased emergency department (ED) presentations. Treatment-related toxicity can affect quality of life, compromise chemotherapy delivery and treatment outcomes, and increase healthcare use. We performed a retrospective study of ED presentations in patients receiving curative chemotherapy for early breast cancer to identify factors contributing to ED presentations. Of 102 patients, 39 (38%) presented to ED within 30 days of chemotherapy, resulting in 63 ED presentations in total. Most common reasons were non-neutropenic fever (17 presentations/27%), neutropenic fever (15/24%), pain (9/14%), drug reaction (6/10%) and infection (4/6%). Factors significantly associated with ED presentation were adjuvant chemotherapy timing compared to neoadjuvant timing (P = 0.031), prophylactic antibiotics (P = 0.045) and docetaxel-containing regimen (P = 0.018). © 2018 Royal Australasian College of Physicians.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Xu, Yong-Gang; Qi, Shu-Nan; Wang, Shu-Lian
Purpose: To assess the dosimetric benefit, prognosis, and toxicity of intensity modulated radiation therapy (IMRT) for early-stage, diffuse large B-cell lymphoma of Waldeyer ring (WR-DLBCL). Methods and Materials: Sixty-one patients with early-stage WR-DLBCL who received chemotherapy followed by IMRT were retrospectively reviewed. Dosimetric parameters for the target volume and critical normal structures were evaluated, and survival was calculated. Linear regression analysis was used to assess the effect of the mean dose (D{sub mean}) to the parotid glands on xerostomia. Results: The median conformity index and homogeneity index of the planning target volume (PTV) were 0.83 and 0.90, respectively, demonstrating verymore » good coverage of the target volume. The mean dose to the parotid glands was 24.9 Gy. The 5-year overall survival (OS), progression-free survival (PFS), and locoregional control (LRC) were 94.7%, 93.1%, and 98.3%, respectively. Early and late toxicities were mild, and no patient experienced late grade ≥3 toxicities. The D{sub mean} to the parotid glands had a linear correlation with late grade ≥2 xerostomia. Conclusions: IMRT after chemotherapy can provide excellent dose conformity and achieve favorable survival and LRC with mild toxicities in patients with early-stage WR-DLBCL. Dose constraints for the parotid glands should be limited to <24 Gy for early-stage WR-DLBCL.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Herkovits, J.; Perez-Coll, C.S.; Herkovits, F.D.
1995-12-31
Test of early life stages are very sensitive to toxic effects and moreover a good predictive correlation between embryo-larval survival and independent ecological parameters such as species richness and diversity have been established. The main purpose of this preliminary study is to report that Bufo arenarum embryos are very sensitive to contaminants from a variety of sources such as leachates, industrial effluents, surface and ground water. The toxicity of 30 samples (five from each category plus controls of surface and ground water from reference places) was evaluated during a 14 day renewal toxicity test at 20 C, conducted with 10more » embryos (by triplicate) from stage 23--25 onwards using six concentrations (V/V) of each sample of Holtfreter`s solution. For industrial effluents and leachates the results range from a concentration of 0.6% resulting in 24hs LC100 up to a sample which exert 20% of lethality after 14 days of treatment. The survival of controls and in samples from reference places was over 90% for 7 days and over 80% for 14 days. The results with Bufo arenarum embryos confirm that a 7 day Short-term Chronic Toxicity Test is appropriate for toxicity screening of industrial effluents (as it was established by EPA for whole effluent toxicity test for aquatic life protection performed with other species) as well as for leachates. On the other hand, for freshwater (surface and ground), it is convenient to extend the exposure period until 14 days in order to record situations of low, but significant levels of toxicity, which could be of particular value for surface as well as ground water quality criteria.« less
Acute and early life stage toxicity of industrial effluent on Japanese medaka (Oryzias latipes).
Zha, Jinmiao; Wang, Zijian
2006-03-15
To develop the whole effluent toxicity testing methods (WET), embryo larval stage toxicity test using Japanese medaka (Oryzias latipes) was conducted to evaluate an effluent from a banknote printing plant (BPP). The method is based on acute toxicity using endpoint of 96-h larval morality and on chronic toxicity using endpoints such as the time to hatch, hatching success, deformity, growth rate, swim-up failure, accumulative mortality and sexual ratio. In test for 96-h larval mortality, LC50 (the concentration was lethal to 50% of newly hatching medaka larvae) was 72.9%. In chronic toxicity test, newly fertilized embryos (<5-h old) were exposed to 1%, 6.25%, 12.5%, 25%, 50% effluent concentrations and to 200 mug/l BPA in a 24-h static renewal system at 25+/-1 degrees C until 15 day post-hatch. The results showed that all chronic endpoints were significantly different from the control at 50% dilution (p < 0.01). Embryos began to show lesions on 4th day at higher concentrations (12.5%, 25%, 50% BPP effluent concentrations). Treatment group of 25% dilution showed delayed time to hatch. A reduction in body weight was observed at 25% dilutions for males and females, respectively. Deformities were observed in newly hatched larvae at 25% and 50% BPP effluent concentrations. At 25% dilution, sex ratio of larvae was alternated and there was feminization phenomenon. We conclude that embryo larval stage test using medaka is feasible to evaluate both acute and chronic toxicities and potential endocrine disrupting activity of industrial effluents.
Wagner, Norman; Veith, Michael; Lötters, Stefan; Viertel, Bruno
2017-01-01
Environmental contamination is suggested to contribute to amphibian population declines. However, the effects of a contaminant on a particular amphibian species can differ among populations. The authors investigated the toxic effects of 2 herbicide formulations on different populations and on representative developmental stages of the European common frog (Rana temporaria). Larvae from forest populations were more sensitive to a commonly used glyphosate-based herbicide compared with individuals from agrarian land. Median lethal concentrations correlated with measured glyphosate levels in the breeding ponds, which may be a sign of evolved tolerances. The reverse result was observed for a less commonly used cycloxydim-based herbicide. Effects of the glyphosate-based herbicide were stronger for earlier larval stages compared with later larval stages. Hence, applications in early spring (when early larvae are present in breeding ponds) pose greater risk concerning acute toxic effects on R. temporaria. With regard to late larval stages, short exposure (96 h) of prometamorphic larvae prolonged time to metamorphosis, but only at the highest test concentration that did not significantly induce mortality. This could be due to impairment of the thyroid axis. Notably, nearly all test concentrations of the 2 herbicides provoked growth retardation. Further research on how evolved or induced tolerances are acquired, actual contamination levels of amphibian habitats, and potential endocrine effects of glyphosate-based herbicides is necessary. Environ Toxicol Chem 2017;36:190-200. © 2016 SETAC. © 2016 SETAC.
Shaw, Benjamin J; Liddle, Corin C; Windeatt, Kirsten M; Handy, Richard D
2016-09-01
There are concerns that regulatory toxicity tests are not fit for purpose for engineered nanomaterials (ENMs) or need modifications. The aim of the current study was to evaluate the OECD 210 fish, early-life stage toxicity test for use with TiO2 ENMs, Ag ENMs, and MWCNT. Both TiO2 ENMS (≤160 mg l(-1)) and MWCNT (≤10 mg l(-1)) showed limited acute toxicity, whilst Ag ENMs were acutely toxic to zebrafish, though less so than AgNO3 (6-day LC50 values of 58.6 and 5.0 µg l(-1), respectively). Evidence of delayed hatching, decreased body length and increased muscle width in the tail was seen in fish exposed to Ag ENMs. Oedema (swollen yolk sacs) was also seen in fish from both Ag treatments with, for example, mean yolk sac volumes of 17, 35 and 39 µm(3) for the control, 100 µg l(-1) Ag ENMs and 5 µg l(-1) AgNO3 treatments, respectively. Among the problems with the standard test guidelines was the inability to maintain the test solutions within ±20 % of nominal concentrations. Pronounced settling of the ENMs in some beakers also made it clear the fish were not being exposed to nominal concentrations. To overcome this, the exposure apparatus was modified with the addition of an exposure chamber that ensured mixing without damaging the delicate embryos/larvae. This allowed more homogeneous ENM exposures, signified by improved measured concentrations in the beakers (up to 85.7 and 88.1 % of the nominal concentrations from 10 mg l(-1) TiO2 and 50 µg l(-1) Ag ENM exposures, respectively) and reduced variance between measurements compared to the original method. The recommendations include: that the test is conducted using exposure chambers, the use of quantitative measurements for assessing hatching and morphometrics, and where there is increased sensitivity of larvae over embryos to conduct a shorter, larvae-only toxicity test with the ENMs.
Early-life stage fish can be more sensitive to chemical exposure than mature, adult fish. Therefore, defining adverse outcome pathways (AOPs) relevant to early-life stages is critical for linking perturbations of key events during fish development to potential adverse outcomes of...
Study design and early result of a phase I study of SABR for early-stage glottic cancer.
Yu, Tosol; Wee, Chan Woo; Choi, Noorie; Wu, Hong-Gyun; Kang, Hyun-Cheol; Park, Jong Min; Kim, Jung-In; Kim, Jin Ho; Kwon, Tack-Kyun; Chung, Eun-Jae
2018-05-14
Avoidance of organs at risk has become possible with advances in image-guided volumetric-modulated arc therapy (VMAT) techniques. This study was designed to evaluate the safety and feasibility of stereotactic ablative radiotherapy (SABR) for early stage glottic cancer. This report presents the preliminary result of the first and second dose level. Fraction size was increased from 3.5 gray (Gy) (total dose 59.5 Gy) to 9 Gy (total dose 45 Gy). Dose-limiting toxicities were defined as grade 3 or higher treatment-related toxicities. Voice outcome was assessed with electroglottography, and quality of life (QoL) was measured with the Head and Neck Cancer Inventory (HNCI). Seven patients received 59.5 Gy at 3.5 Gy per fraction as the first dose level, and five patients received 55 Gy at 5 Gy per fraction as the second dose level. None of the patients developed grade 3+ toxicity throughout a median follow-up of 17.5 months (range, 1.7-30.6 months). One patient in the second dose level recurred in the primary site at 4 months after radiotherapy (RT) and received total laryngectomy. The rest of participants were disease-free at locoregional and distant sites. Jitter, shimmer, mean phonation time, and noise-to-harmony ratio did not change significantly at 6 months after RT. HNCI scores between pretreatment and posttreatment were not significantly different (P = 0.221). This study revealed acceptable toxicity, voice outcome, and QoL in patients treated with hypofractionated VMAT of 3.5 Gy and 5 Gy per fraction. This phase I study is currently ongoing with a dose of 55 Gy in 11 fractions and 45 Gy in five fractions. 2b. Laryngoscope, 2018. © 2018 The American Laryngological, Rhinological and Otological Society, Inc.
2007-08-01
ERDC/TN ANSRP-07-2 August 2007 Detection of Apoptosis in Early Life Stages as a Tool to Evaluate Chemical Control of Invasive Species by J...4. TITLE AND SUBTITLE Detection of Apoptosis in Early Life Stages as a Tool to Evaluate Chemical Control of Invasive Species 5a. CONTRACT NUMBER 5b...heralding apoptosis . Data analysis. An apoptotic index (API) was established by calculating the percentage of embryos in each life stage with
Partial Life-Cycle and Acute Toxicity of Perfluoroalkyl Acids to Freshwater Mussels
Freshwater mussels are among the most sensitive aquatic organisms to many contaminants and have complex life-cycles that include several distinct life stages with unique contaminant exposure pathways. Standard acute (24–96 h) and chronic (28 d) toxicity tests with free larva (glo...
To investigate the contribution of different life stages on response to toxicants, we utilized a custom designed RT-PCR array to examine the effects of acute exposure by oral gavage of the volatile organic solvent toluene (0.00, 0.65 or 1.0 glkg) in the brains of ma1e Brown Norwa...
Villeneuve, Daniel; Volz, David C; Embry, Michelle R; Ankley, Gerald T; Belanger, Scott E; Léonard, Marc; Schirmer, Kristin; Tanguay, Robert; Truong, Lisa; Wehmas, Leah
2014-01-01
The fish early-life stage (FELS) test (Organisation for Economic Co-operation and Development [OECD] test guideline 210) is the primary test used internationally to estimate chronic fish toxicity in support of ecological risk assessments and chemical management programs. As part of an ongoing effort to develop efficient and cost-effective alternatives to the FELS test, there is a need to identify and describe potential adverse outcome pathways (AOPs) relevant to FELS toxicity. To support this endeavor, the authors outline and illustrate an overall strategy for the discovery and annotation of FELS AOPs. Key events represented by major developmental landmarks were organized into a preliminary conceptual model of fish development. Using swim bladder inflation as an example, a weight-of-evidence–based approach was used to support linkage of key molecular initiating events to adverse phenotypic outcomes and reduced young-of-year survival. Based on an iterative approach, the feasibility of using key events as the foundation for expanding a network of plausible linkages and AOP knowledge was explored and, in the process, important knowledge gaps were identified. Given the scope and scale of the task, prioritization of AOP development was recommended and key research objectives were defined relative to factors such as current animal-use restrictions in the European Union and increased demands for fish toxicity data in chemical management programs globally. The example and strategy described are intended to guide collective efforts to define FELS-related AOPs and develop resource-efficient predictive assays that address the toxicological domain of the OECD 210 test. Environ Toxicol Chem 2014;33:158–169. © 2013 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited. PMID:24115264
Good daily habits during the early stages of life determine success throughout life.
Kohyama, Jun
2016-01-01
This paper assesses hypothesis that sufficient sleep duration and proper circadian rhythms during the early stages of life are indispensable to a successful life. Successful life was defined according to the famous cohort studies of Mischel's and Dunedin. To assess the hypothesis, neuronal elements presumably affecting early daily habits and successful life are reviewed. The effect of sufficient sleep duration and proper circadian rhythms during early stages of life on the development of the prefrontal cortex has been found to be the key issue to verify the hypothesis. Socioeconomic status is found to be another issue to be studied.
Early-life stage fish can be more sensitive to chemical exposure than mature, adult fish. Therefore, defining adverse outcome pathways (AOPs) relevant to early-life stages is critical for linking perturbations of key events during fish development to potential adverse outcomes of...
Early-life stage fish can be more sensitive to chemical exposure than adult fish. Therefore, determining possible adverse outcome pathways (AOPs) for early-life stages is crucial. To determine chemical effects and/or mechanisms of action in exposed fish embryos and larvae, whole-...
Toxicity of TFM lampricide to early life stages of walleye
Seelye, J.G.; Marking, L.L.; King, E.L.; Hanson, L.H.; Bills, T.D.
1987-01-01
The authors studied the effects of the lampricide 3-trifluoromethyl-4-nitrophenol (TFM) on gametes, newly fertilized eggs, eyed eggs, larvae, and swim-up fry of the walleye Stizostedion vitreum . When gametes from sexually mature walleyes were stripped into solutions of TFM, no effects were observed during the fertilization process at concentrations up to 3.0 mg/L - three times the concentration lethal to 99.9% of larval sea lampreys Petromyzon marinus held 12 h (LC99.9) under the same test conditions. Newly fertilized eggs likewise were unaffected during water hardening by concentrations of TFM that were lethal to sea lamprey ammocoetes. Eyed eggs, sac fry, and swim-up fry yielded LC25 values that were 2.5 to 5 times greater than the 12-h LC99.9 for sea lamprey ammocoetes. The data thus indicated that all of the early life stages of walleyes tested were considerably more resistant than sea lamprey ammocoetes to TFM, and that it is unlikely they would be adversely affected by standard stream treatments to kill sea lamprey ammocoetes.
Effect of thiacloprid on early life stages of common carp (Cyprinus carpio).
Velisek, Josef; Stara, Alzbeta
2018-03-01
Toxicity of the neonicotinoid pesticide thiacloprid to embryos and larvae of common carp Cyprinus carpio was assessed under laboratory conditions. Carp embryos and larvae were exposed to thiacloprid at four concentrations: 4.5 (environmental concentration), 45, 225, and 450 μg/L for 35 days and compared to a non-treated control group. The effects on lipid peroxidation, antioxidant enzyme levels (superoxide dismutase, glutathione reductase, catalase, glutathione S-transferase, and reduced glutathione), mortality, growth, development, and histopathogenesis were assessed. Thiacloprid at tested concentrations were not associated with negative effects on hatching, behaviour, embryo viability, or Fulton's condition factor. Carp exposed to 45 μg/L thiacloprid showed lower weight and length compared to controls. Thiacloprid at 225 and 450 μg/L delayed development and led to lower weight and length of carp. Significantly lower superoxide dismutase and glutathione reductase activity was observed at all tested concentrations of thiacloprid compared with the control group. Chronic thiacloprid exposure of early-life stages of carp affected ontogeny and growth rate, and inhibited antioxidant capacity. Copyright © 2017 Elsevier Ltd. All rights reserved.
Faria, Melissa; Navarro, Ana; Luckenbach, Till; Piña, Benjamin; Barata, Carlos
2011-01-17
The study of the cellular mechanisms of tolerance of organisms to pollution is a key issue in aquatic environmental risk assessment. Recent evidence indicates that multixenobiotic resistance (MXR) mechanisms represent a general biological defense of many marine and freshwater organisms against environmental toxicants. In this work, toxicologically relevant xenobiotic efflux transporters were studied in early life stages of zebra mussels (Dreissena polymorpha). Expression of a P-gp1 (ABCB1) transporter gene and its associated efflux activities during development were studied, using qRT-PCR and the fluorescent transporter substrates rhodamine B and calcein-AM combined with specific transporter inhibitors (chemosensitizers). Toxicity bioassays with the model P-gp1 chemotherapeutic drug vinblastine applied singly and in combination with different chemosensitizers were performed to elucidate the tolerance role of the P-gp1 efflux transporter. Results evidenced that the gene expression and associated efflux activities of ABC transporters were low or absent in eggs and increased significantly in 1-3d old trochophora and veliger larvae. Specific inhibitors of Pgp1 and/or MRP transport activities including cyclosporine A, MK571, verapamil and reversin 205 and the musk celestolide resulted in a concentration dependent inhibition of related transport activities in zebra mussel veliger larvae, with IC50 values in the lower micromolar range and similar to those reported for mammals, fish and mussels. Binary mixtures of the tested transporter inhibitors except celestolide with the anticancer drug and P-gp1 substrate vinblastine increased the toxicity of the former compound more than additively. These results indicate that MXR transporter activity is high in early life-stages of the zebra mussel and that may play an important role in the tolerance to environmental contaminants. Copyright © 2010 Elsevier B.V. All rights reserved.
Tillitt, Donald E.; Buckler, Justin A.; Nicks, Diane; Candrl, James; Claunch, Rachel; Gale, Robert W.; Puglis, Holly J.; Little, Edward E.; Linbo, Tiffany L.; Baker, Mary
2017-01-01
The aquatic food web of the Great Lakes has been contaminated with polychlorinated biphenyls (PCBs) since the mid-20th century. Threats of PCB exposures to long-lived species of fish, such as lake sturgeon (Acipenser fulvescens), have been uncertain because of a lack of information on the relative sensitivity of the species. The objective of the present study was to evaluate the sensitivity of early–life stage lake sturgeon to 3,3′,4,4′,5-pentachlorobiphenyl (PCB-126) or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure. Mortality, growth, morphological and tissue pathologies, swimming performance, and activity levels were used as assessment endpoints. Pericardial and yolk sac edema, tubular heart, yolk sac hemorrhaging, and small size were the most commonly observed pathologies in both TCDD and PCB-126 exposures, beginning as early as 4 d postfertilization, with many of these pathologies occurring in a dose-dependent manner. Median lethal doses for PCB-126 and TCDD in lake sturgeon were 5.4 ng/g egg (95% confidence interval, 3.9–7.4 ng/g egg) and 0.61 ng/g egg (0.47–0.82 ng/g egg), respectively. The resulting relative potency factor for PCB-126 (0.11) was greater than the World Health Organization estimate for fish (toxic equivalency factor = 0.005), suggesting that current risk assessments may underestimate PCB toxicity toward lake sturgeon. Swimming activity and endurance were reduced in lake sturgeon survivors from the median lethal doses at 60 d postfertilization. Threshold and median toxicity values indicate that lake sturgeon, like other Acipenser species, are more sensitive to PCB and TCDD than the other genus of sturgeon, Scaphirhynchus, found in North America. Indeed, lake sturgeon populations in the Great Lakes and elsewhere are susceptible to PCB/TCDD-induced developmental toxicity in embryos and reductions in swimming performance.
Donovan, Elysia K; Swaminath, Anand
2018-01-01
Stereotactic body radiation therapy (SBRT) has emerged as a new technology in radiotherapy delivery, allowing for potentially curative treatment in many patients previously felt not to be candidates for radical surgical resection of stage I non-small-cell lung cancer (NSCLC). Several studies have demonstrated very high local control rates using SBRT, and more recent data have suggested overall survival may approach that of surgery in operable patients. However, SBRT is not without unique toxicities, and the balance of toxicity, and effect on patient-reported quality of life need to be considered with respect to oncologic outcomes. We therefore aim to review SBRT in the context of important patient-related factors, including quality of life in several domains (and in comparison to other therapies such as conventional radiation, surgery, or no treatment). We will also describe scenarios in which SBRT may be reasonably offered (i.e. elderly patients and those with severe COPD), and where it may need to be approached with some caution due to increased risks of toxicity (i.e. tumor location, patients with interstitial lung disease). In total, we hope to characterize the physical, emotional, and functional consequences of SBRT, in relation to other management strategies, in order to aid the clinician in deciding whether SBRT is the optimal treatment choice for each patient with early stage NSCLC.
Effect of species, life stage, and water temperature on the toxicity of hydrogen peroxide to fish
Rach, J.J.; Schreier, Theresa M.; Howe, G.E.; Redman, S.D.
1997-01-01
Hydrogen peroxide is a drug of low regulatory priority status that is effective in treating fish and fish eggs infected by fungi. However, only limited information is available to guide fish culturists in administering hydrogen peroxide to diseased fish. Laboratory tests were conducted to determine (1) the sensitivity of brown trout Salmo trutta, lake trout Salvelinus namaycush, fathead minnow Pimephales promelas, walleye Stizostedion vitreum, channel catfish Ictalurus punctatus, and bluegill Lepomis, machrochirus to hydrogen peroxide treatments; (2) the sensitivity of various life stages of rainbow trout Oncorhynchus mykiss to hydrogen peroxide treatments; and (3) the effect of water temperature on the acute toxicity of hydrogen peroxide to three fish species. Fish were exposed to hydrogen peroxide concentrations ranging from 100 to 5,000 mu L/L (ppm) for 15-min or 45-min treatments every other day for four consecutive treatments to determine the sensitivity of various species and life stages of fish. Except for walleye, most species of fish tested (less than or equal to 2 g) tolerated hydrogen peroxide of 1,000 mu L/L or greater. Walleyes were sensitive to hydrogen peroxide concentrations as low as 100 mu L/L. A correlation was found between the toxicity of hydrogen peroxide and the life stages of rainbow trout; larger fish were more sensitive. Generally, the toxicity of hydrogen peroxide increased for all species as water temperature increased. The results of these experiments demonstrate that it is important to consider the effects of species, life stage, and water temperature when conducting hydrogen peroxide treatments.
Lakoski, Susan; Mackey, John R.; Douglas, Pamela S.; Haykowsky, Mark J.; Jones, Lee W.
2013-01-01
Molecularly targeted therapeutics (MTT) are the future of cancer systemic therapy. They have already moved from palliative therapy for advanced solid malignancies into the setting of curative-intent treatment for early-stage disease. Cardiotoxicity is a frequent and potentially serious adverse complication of some targeted therapies, leading to a broad range of potentially life-threatening complications, therapy discontinuation, and poor quality of life. Low-cost pleiotropic interventions are therefore urgently required to effectively prevent and/or treat MTT-induced cardiotoxicity. Aerobic exercise therapy has the unique capacity to modulate, without toxicity, multiple gene expression pathways in several organ systems, including a plethora of cardiac-specific molecular and cell-signaling pathways implicated in MTT-induced cardiac toxicity. In this review, we examine the molecular signaling of antiangiogenic and HER2-directed therapies that may underpin cardiac toxicity and the hypothesized molecular mechanisms underlying the cardioprotective properties of aerobic exercise. It is hoped that this knowledge can be used to maximize the benefits of small molecule inhibitors, while minimizing cardiac damage in patients with solid malignancies. PMID:23335619
Early Life Origins of Metabolic Syndrome: The Role of Environmental Toxicants
Wang, Guoying; Chen, Zhu; Bartell, Tami; Wang, Xiaobin
2014-01-01
Metabolic syndrome (MetS) affects more than 47 million people in the U.S. Even more alarming, MetS, once regarded as an “adult problem”, has become increasingly common in children. To date, most related research and intervention efforts have occurred in the adult medicine arena, with limited understanding of the root causes and lengthy latency of MetS. This review highlights new science on the early life origins of MetS, with a particular focus on exposure to two groups of environmental toxicants: endocrine disrupting chemicals (EDCs) and metals during the prenatal and early postnatal periods, and their specific effects and important differences in the development of MetS. It also summarizes available data on epigenetic effects, including the role of EDCs in the androgen/estrogen pathways. Emerging evidence supports the link between exposures to environmental toxicants during early life and the development of MetS later in life. Additional research is needed to address important research gaps in this area, including prospective birth cohort studies to delineate temporal and dose-response relationships, important differences in the effects of various environmental toxicants and their joint effects on MetS, as well as epigenetic mechanisms underlying the effects of specific toxicants such as EDCs and metals. PMID:24883264
Weltje, Lennart; Janz, Philipp; Sowig, Peter
2017-12-01
This paper presents a model to predict acute dermal toxicity of plant protection products (PPPs) to terrestrial amphibian life stages from (regulatory) fish data. By combining existing concepts, including interspecies correlation estimation (ICE), allometric relations, lethal body burden (LBB) and bioconcentration modelling, an equation was derived that predicts the amphibian median lethal dermal dose (LD 50 ) from standard acute toxicity values (96-h LC 50 ) for fish and bioconcentration factors (BCF) in fish. Where possible, fish BCF values were corrected to 5% lipid, and to parent compound. Then, BCF values were adjusted to an exposure duration of 96 h, in case steady state took longer to be achieved. The derived correlation equation is based on 32 LD 50 values from acute dermal toxicity experiments with 15 different species of anuran amphibians, comprising 15 different PPPs. The developed ICE model can be used in a screening approach to estimate the acute risk to amphibian terrestrial life stages from dermal exposures to PPPs with organic active substances. This has the potential to reduce unnecessary testing of vertebrates. Copyright © 2017 Elsevier Ltd. All rights reserved.
Cunha, Isabel; Torres, Tiago; Oliveira, Helena; Martins, Rosário; McGowan, Thomas; Sheahan, David; Santos, Miguel Machado
2017-04-01
This study provides toxicity values for early life stages (ELS) of two phylogenetically distinct marine animal taxa, the sea urchin (Paracentrotus lividus), a deuterostome invertebrate, and the turbot (Scophthalmus maximus), a vertebrate (teleost), when challenged by six hazardous and noxious substances (HNS): aniline, butyl acrylate, m-cresol, cyclohexylbenzene, hexane and trichloroethylene. The aim of the study was to provide preliminary information on toxic effects of representative and relevant priority HNS to assess the risk posed by spills to marine habitats and therefore improve preparedness and the response at the operational level. Selection criteria to include each compound in the study were (1) inclusion in the HASREP (2005) list; (2) presence on the priority list established by Neuparth et al. (2011); (3) paucity of toxicological data (TOXnet and ECOTOX) for marine organisms; (4) behaviour in the water according to the categories defined by the European Behaviour classification system (GESAMP 2002), by selecting compounds with different behaviours in water; and (5) physicochemical and toxicological properties, where available, in order to anticipate the most toxic compounds. Aniline and m-cresol were the most toxic compounds with no observed apical effect concentration (NOAEC) values for sea urchin ranging between 0.01 and 0.1 mg/L, followed by butyl acrylate and cyclohexylbenzene with NOAECs ranging between 0.1 and 1.0 mg/L and trichloroethylene with NOAEC values that were in the range between 1 and 10 mg/L, reflecting their behaviour in water, mostly vapour pressure, but also solubility and log Kow. Hexane was toxic only for turbot embryos, due to its neurotoxic effects, and not for sea urchin larvae, at concentrations in the range between 1 and 10 mg/L. The concentrations tested were of the same order of magnitude for both species, and it was observed that sea urchin embryos (length of the longest arm) are more sensitive than turbot eggs larvae (hatching and cumulative mortality rates) to the HNS tested (except hexane). For this specific compound, concentrations up to 70 mg/L were tested in sea urchin larvae and no effects were observed on the length of the larvae. Both tests were found to be complementary depending on behaviour in water and toxicity target of the compounds analysed.
Amphibians at risk? Susceptibility of terrestrial amphibian life stages to pesticides.
Brühl, Carsten A; Pieper, Silvia; Weber, Brigitte
2011-11-01
Current pesticide risk assessment does not specifically consider amphibians. Amphibians in the aquatic environment (aquatic life stages or postmetamorphic aquatic amphibians) and terrestrial living juvenile or adult amphibians are assumed to be covered by the risk assessment for aquatic invertebrates and fish, or mammals and birds, respectively. This procedure has been evaluated as being sufficiently protective regarding the acute risk posed by a number of pesticides to aquatic amphibian life stages (eggs, larvae). However, it is unknown whether the exposure and sensitivity of terrestrial living amphibians are comparable to mammalian and avian exposure and sensitivity. We reviewed the literature on dermal pesticide absorption and toxicity studies for terrestrial life stages of amphibians, focusing on the dermal exposure pathway, that is, through treated soil or direct overspray. In vitro studies demonstrated that cutaneous absorption of chemicals is significant and that chemical percutaneous passage, P (cm/h), is higher in amphibians than in mammals. In vivo, the rapid and substantial uptake of the herbicide atrazine from treated soil by toads (Bufo americanus) has been described. Severe toxic effects on various amphibian species have been reported for field-relevant application rates of different pesticides. In general, exposure and toxicity studies for terrestrial amphibian life stages are scarce, and the reported data indicate the need for further research, especially in light of the global amphibian decline. Copyright © 2011 SETAC.
Lethal and teratogenic effects of phenol on Bufo arenarum embryos.
Paisio, Cintia Elizabeth; Agostini, Elizabeth; González, Paola Solange; Bertuzzi, Mabel Lucía
2009-08-15
Phenol and their derivatives are used in several industries and they have a high potential toxicity for animal and plant species. They were found in variable concentrations, as high as 1000 mg/L, in industrial wastewater and, they are often discharged into the environment. Amphibian embryos are useful indicators of environmental pollution. However, to our knowledge, there are not studies focussed on the toxic effects of phenol on Bufo arenarum, which is an anuran widely distributed in South America. Therefore, the effect of phenol on the survival and morphogenesis of these amphibian embryos was evaluated by means of AMPHITOX test. Embryos at 25 stage of development (acute test) and embryos at 2-4 blastomers stage (early life stage test), were exposed to phenol solutions in concentrations ranging from 25 to 250 mg/L, which were frequently found in the environment. Mortality and malformations were registered each 24h. LC(50), LC(99), NOEC, TC(50) and TI(50) values were 183.70, 250, 60, 113 mg/L and 1.62, respectively, at 96 h of treatment. Mortality and the percentage of malformations increased with increasing phenol concentrations. Teratogenic effects more frequently produced by phenol were: axial flexure, persistent yolk plug and different abnormalities which caused death of blastulae. Moreover, other malformations were registered, such as irregular form, acephalism, edema, axial shortening and underdevelopment of gills, among others. Larvae of B. arenarum, at early embryonic stages (blastulae), showed higher sensitivity to phenol than tadpoles at stage 25. Results confirm high susceptibility of amphibians to phenol and that environmental concentrations of this pollutant might be harmful to these populations.
Life-stage dependent response in zebrafish (Danio rerio) to phototoxicity of TiO2 nanoparticles
The Zebrafish, and especially its embryo stage, has been increasingly used as a model to evaluate toxicity of manufactured nanomaterials. However, many studies have indicated that the chorion may protect developing embroys from the toxic effects of nanomaterials, suggesting that ...
DOE Office of Scientific and Technical Information (OSTI.GOV)
Oral, Rahime
Background: Heavy rare earth elements (HREEs) have been scarcely studied for their toxicity, in spite of their applications in several technologies. Thus HREEs require timely investigations for their adverse health effects. Methods: Paracentrotus lividus and Arbacia lixula embryos and sperm were exposed to trichloride salts of five HREEs (Dy, Ho, Er, Yb and Lu) and to Ce(III) as a light REE (LREE) reference to evaluate: 1) developmental defects (% DD) in HREE-exposed larvae or in the offspring of HREE-exposed sperm; 2) mitotic anomalies; 3) fertilization success; and 4) reactive oxygen species (ROS) formation, and nitric oxide (NO) and malondialdehyde (MDA)more » levels. Nominal HREE concentrations were confirmed by inductively coupled plasma mass spectrometry (ICP-MS). Results: HREEs induced concentration-related DD increases in P. lividus and A. lixula larvae, ranging from no significant DD increase at 10{sup −7} M HREEs up to ≅100% DD at 10{sup −5} M HREE. Larvae exposed to 10{sup −5} M Ce(III) resulted in less severe DD rates compared to HREEs. Decreased mitotic activity and increased aberration rates were found in HREE-exposed P. lividus embryos. Significant increases in ROS formation and NO levels were found both in HREE-exposed and in Ce(III) embryos, whereas only Ce(III), but not HREEs resulted in significant increase in MDA levels. Sperm exposure to HREEs (10{sup −5}–10{sup −4} M) resulted in a concentration-related decrease in fertilization success along with increase in offspring damage. These effects were significantly enhanced for Dy(III), Ho(III), Er(III) and Yb(III), compared to Lu(III) and to Ce(III). Conclusion: HREE-associated toxicity affected embryogenesis, fertilization, cytogenetic and redox endpoints showing different toxicities of tested HREEs. - Highlights: • Different toxicities were exerted by five tested HREEs on sea urchin early life stages. • Sea urchin embryos and sperm were sensitive to HREE levels ranging from 1 to 100 μM, according to different exposures. • The findings support investigations on comparative toxicity studies of HREEs in other test systems.« less
Wang, N.; Ingersoll, C.G.; Ivey, C.D.; Hardesty, D.K.; May, T.W.; Augspurger, T.; Roberts, A.D.; Van Genderen, E.; Barnhart, M.C.
2010-01-01
Toxicity of lead, cadmium, or zinc to early life stages of freshwater mussels (fatmucket, Lampsilis siliquoidea; Neosho mucket, L. rafinesqueana) was evaluated in 48-h exposures with mussel larvae (glochidia), in 96-h exposures with newly transformed (5-d-old) and two- or six-month-old juvenile mussels, or in 28-d exposures with two- or four-month-old mussels in reconstituted soft water. The 24-h median effect concentrations (EC50s) for fatmucket glochidia (>299??g Pb/L, >227??g Cd/L, 2,685??g Zn/L) and 96-h EC50s for two- or six-month-old fatmucket (>426??g Pb/L, 199??g Cd/L, 1,700??g Zn/L) were much higher than 96-h EC50s for newly transformed fatmucket (142 and 298??g Pb/L, 16??g Cd/L, 151 and 175??g Zn/L) and Neosho mucket (188??g Pb/L, 20??g Cd/L, 145??g Zn/L). Chronic values for fatmucket were 10??g Pb/L, 6.0??g Cd/L, and 63 and 68??g Zn/L. When mussel data from the present study and the literature were included in updated databases for deriving U.S. Environmental Protection Agency water quality criteria, mussel genus mean acute values were in the lower percentiles of the sensitivity distribution of all freshwater species for Pb (the 26th percentile), Cd (the 15th to 29th percentile), or Zn (the 12th to 21st percentile). The mussel (Lampsilis) genus mean chronic value was the lowest value ever reported for Pb (the 9th percentile) but was near the middle of the sensitivity distribution for Cd (the 61st percentile) or Zn (the 44th percentile). These results indicate that mussels were relatively sensitive to the acute toxicity of these three metals and to the chronic toxicity of Pb, but were moderately sensitive to the chronic toxicity of Cd or Zn compared to other freshwater species. ?? 2010 SETAC.
Wang, Ning; Ingersoll, Christopher G; Ivey, Christopher D; Hardesty, Douglas K; May, Thomas W; Augspurger, Tom; Roberts, Andy D; van Genderen, Eric; Barnhart, M Chris
2010-09-01
Toxicity of lead, cadmium, or zinc to early life stages of freshwater mussels (fatmucket, Lampsilis siliquoidea; Neosho mucket, L. rafinesqueana) was evaluated in 48-h exposures with mussel larvae (glochidia), in 96-h exposures with newly transformed (5-d-old) and two- or six-month-old juvenile mussels, or in 28-d exposures with two- or four-month-old mussels in reconstituted soft water. The 24-h median effect concentrations (EC50s) for fatmucket glochidia (>299 microg Pb/L, >227 microg Cd/L, 2,685 microg Zn/L) and 96-h EC50s for two- or six-month-old fatmucket (>426 microg Pb/L, 199 microg Cd/L, 1,700 microg Zn/L) were much higher than 96-h EC50s for newly transformed fatmucket (142 and 298 microg Pb/L, 16 microg Cd/L, 151 and 175 microg Zn/L) and Neosho mucket (188 microg Pb/L, 20 microg Cd/L, 145 microg Zn/L). Chronic values for fatmucket were 10 microg Pb/L, 6.0 microg Cd/L, and 63 and 68 microg Zn/L. When mussel data from the present study and the literature were included in updated databases for deriving U.S. Environmental Protection Agency water quality criteria, mussel genus mean acute values were in the lower percentiles of the sensitivity distribution of all freshwater species for Pb (the 26th percentile), Cd (the 15th to 29th percentile), or Zn (the 12th to 21st percentile). The mussel (Lampsilis) genus mean chronic value was the lowest value ever reported for Pb (the 9th percentile) but was near the middle of the sensitivity distribution for Cd (the 61st percentile) or Zn (the 44th percentile). These results indicate that mussels were relatively sensitive to the acute toxicity of these three metals and to the chronic toxicity of Pb, but were moderately sensitive to the chronic toxicity of Cd or Zn compared to other freshwater species. Copyright 2010 SETAC.
Güngördü, Abbas
2013-09-15
The assessments of pesticide toxicity on nontarget organisms have largely been focused on the determination of median lethal concentration (LC50) values using single/laboratory species. Although useful, these studies cannot describe the biochemical mechanisms of toxicity and also cannot explain the effects of pesticides on natural species. In this study, the toxic effects of glyphosate and methidathion were evaluated comparatively on early developmental stages of 3 anurans-2 natural (Pelophylax ridibundus, Pseudepidalea viridis) and 1 laboratory species (Xenopus laevis). The 96-h LC50 values for methidathion and glyphosate were determined as 25.7-19.6 mg active ingredient (AI)/L for P. viridis, 27.4-22.7 mg AI/L for P. ridibundus, and 15.3-5.05 mg AI/L for X. laevis tadpoles. Furthermore, as early signs of intoxication, glutathione S-transferase (GST), acetylcholinesterase (AChE), carboxylesterase (CaE), glutathione reductase, lactate dehydrogenase, and aspartate aminotrasferase were assayed in 4-day-old tadpoles after 96-h pesticide exposure. The GST induction after 3.2mg AI/L methidathion exposure was determined to be 173%, 83%, and 38% of control, and the AChE inhibition for the same dose was determined to be 86%, 96%, and 30% of control for P. ridibundus, P. viridis, and X. laevis, respectively. Unlike the application of methidathion, all enzyme activities showed statistically significant increases on glyphosate exposure compared to controls. However, these increases in enzyme activities were not shown to be parallel with the increase of concentration. The levels of increases of GST and AChE were determined to be 111% and 31% for P. ridibundus, 13% and 51% for P. viridis, and 15% and 36% for X. laevis after 3.2mg AI/L glyphosate exposure, respectively. The findings of the study suggest that the most sensitive species to pesticide exposure is X. laevis. The selected biomarker enzymes AChE, CaE, and GST are useful in understanding the toxic mechanisms of these pesticides in anuran tadpoles as early warning indicators. Copyright © 2013 Elsevier B.V. All rights reserved.
Ducharme, Nicole A; Reif, David M; Gustafsson, Jan-Ake; Bondesson, Maria
2015-08-01
With the high cost and slow pace of toxicity testing in mammals, the vertebrate zebrafish has become a tractable model organism for high throughput toxicity testing. We present here a meta-analysis of 600 chemicals tested for toxicity in zebrafish embryos and larvae. Nineteen aggregated and 57 individual toxicity endpoints were recorded from published studies yielding 2695 unique data points. These data points were compared to lethality and reproductive toxicology endpoints analyzed in rodents and rabbits and to exposure values for humans. We show that although many zebrafish endpoints did not correlate to rodent or rabbit acute toxicity data, zebrafish could be used to accurately predict relative acute toxicity through the rat inhalation, rabbit dermal, and rat oral exposure routes. Ranking of the chemicals based on toxicity and teratogenicity in zebrafish, as well as human exposure levels, revealed that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), benzo(a)pyrene, and chlorpyrifos ranked in the top nine of all chemicals for these three categories, and as such should be considered high priority chemicals for testing in higher vertebrates. Copyright © 2014 Elsevier Inc. All rights reserved.
Elucidating the Links Between Endocrine Disruptors and Neurodevelopment
Blawas, Ashley M.; Gray, Kimberly; Heindel, Jerrold J.; Lawler, Cindy P.
2015-01-01
Recent data indicate that approximately 12% of children in the United States are affected by neurodevelopmental disorders, including attention deficit hyperactivity disorder, learning disorders, intellectual disabilities, and autism spectrum disorders. Accumulating evidence indicates a multifactorial etiology for these disorders, with social, physical, genetic susceptibility, nutritional factors, and chemical toxicants acting together to influence risk. Exposure to endocrine-disrupting chemicals during the early stages of life can disrupt normal patterns of development and thus alter brain function and disease susceptibility later in life. This article highlights research efforts and pinpoints approaches that could shed light on the possible associations between environmental chemicals that act on the endocrine system and compromised neurodevelopmental outcomes. PMID:25714811
Hedouin, Laetitia; Wolf, Ruth E.; Phillips, Jeff; Gates, Ruth D.
2016-01-01
Our data support the paradigm that upward excursions in temperature influence physiological processes in corals that play key roles in regulating metal toxicity. These influences are more pronounced in larva versus adult corals. These findings are important when contextualized climate change-driven warming in the oceans and highlight that predictions of ecological outcomes to metal pollutants will be improved by considering environmental context and the life stages of organism under study.
Existing sediment toxicity test methods are limited to acute and chronic exposure of invertebrates and acute exposure of vertebrates, with limited guidance on the chronic exposure of vertebrates, specifically fishes. A series of life stage-specific studies were conducted to dete...
2017-04-11
Musculoskeletal Complication; Recurrent Breast Carcinoma; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Therapy-Related Toxicity
Dietrich, Joseph P; Van Gaest, Ahna L; Strickland, Stacy A; Hutchinson, Greg P; Krupkin, Alex B; Arkoosh, Mary R
2014-08-15
Long-term fire retardants are used to prevent the spread of wildland fire, but have inadvertently entered aquatic habitats and resulted in fish kills. We examined the toxicity of two fire retardant products; PHOS-CHEK 259F and LC-95A, on Chinook salmon with two different life histories, ocean-type and stream-type, at different stages of their development. Ocean-type Chinook outmigrate to the ocean as subyearlings; while, stream-type salmon overwinter in freshwater and outmigrate as yearlings. Ocean-type and stream-type salmon were exposed to the fire retardants prior to their parr to smolt transition (presmolts) as subyearlings (stream-type and ocean-type) and yearlings (stream-type only), as well as during their transition (smolts). The salmon were exposed to eight concentrations of each retardant and a control for 96h to determine acute toxicity. Lethal concentration curves were modeled by logistic regression for each life history and life stage exposed to the two fire retardants. Among all life histories and life stages tested, PHOS-CHEK 259F was most toxic to stream-type salmon at smolt stage and PHOS-CHEK LC-95A was most toxic to ocean-type salmon at smolt stage. To determine the delayed effects of product exposures on fish health as well as for the potential of recovery, 24-hour seawater challenges were performed immediately after fire retardant exposure, as well as after a recovery period. Previous PHOS-CHEK exposure reduced survival during seawater challenge among salmon from both life histories undergoing the parr-smolt transition and was more pronounced after PHOS-CHEK LC-95A exposure. However, this delayed effect was not observed 34 or more days after either PHOS-CHEK exposure. We conclude that accidental PHOS-CHEK LC-95A or 259F drops during salmon outmigration would have adverse impacts that extend beyond the acute mortality that occurs within the immediate drop and dilution areas. Published by Elsevier B.V.
Triazole-induced toxicity in developing rare minnow (Gobiocypris rarus) embryos.
Zhu, Bin; Liu, Lei; Gong, Yu-Xin; Ling, Fei; Wang, Gao-Xue
2014-12-01
Using rare minnow (Gobiocypris rarus) at early-life stages as experimental models, the developmental toxicity of five widely used triazole fungicides (myclobutanil, fluconazole, flusilazole, triflumizole, and epoxiconazole) were investigated following exposure to 1-15 mg/L for 72 h. Meanwhile, morphological parameters (body length, body weight, and heart rate), enzyme activities (superoxide dismutase (SOD), glutathione S-transferase (GST), adenosine triphosphatase (ATPase), and acetyl cholinesterase (AChE)), and mRNA levels (hsp70, mstn, mt, apaf1, vezf1, and cyp1a) were also recorded following exposure to 0.2, 1.0, and 5.0 mg/L for 72 h. Results indicated that increased malformation and mortality, decreased body length, body weight, and heart rate provide a concentration-dependent pattern; values of 72 h LC50 (median lethal concentration) and EC50 (median effective concentration) ranged from 3 to 12 mg/L. Most importantly, the results of the present study suggest that even at the lowest concentration, 0.2 mg/L, five triazole fungicides also caused notable changes in enzyme activities and mRNA levels. Overall, the present study points out that those five triazole fungicides are highly toxic to the early development of G. rarus embryos. The information presented in this study will be helpful in better understanding the toxicity induced by triazole fungicides in fish embryos.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Bar Ad, Voichita; Paltiel, Ora; Glatstein, Eli
2008-12-01
The treatment of Hodgkin's lymphoma has improved dramatically over the past decades. Over the last half century, Hodgkin's lymphoma has become one of the most curable cancers of adulthood. More than 90% of the patients with localized stages of the disease can be cured with modern treatment strategies. Long-term toxicities are now the major concern for survivors of early-stage disease. Contemporary therapeutic approaches for Hodgkin's lymphoma attempt to preserve the high cure rate achieved, while reducing treatment-related acute and late toxicities. The aim of this review is to re-examine the historical and the current role of radiotherapy for early-stage Hodgkin'smore » lymphoma, given the latest evidence of an increasing role of chemotherapy for the treatment of this malignancy. The literature search was performed in PubMed Plus. Studies on children were excluded.« less
Ingersoll, Christopher G.; Contributions by Wang, Ning; Calfee, Robin D.; Beahan, Erinn; Brumbaugh, William G.; Dorman, Rebecca A.; Hardesty, Doug K.; Kunz, James L.; Little, Edward E.; Mebane, Christopher A.; Puglis, Holly J.
2014-01-01
White sturgeon (Acipenser transmontanus) are experiencing poor recruitment in the trans boundary reach of the upper Columbia River in eastern Washington State. Limited toxicity data indicated that early life stages of white sturgeon are sensitive to metals. In acute 4-day (d) exposures with larval white sturgeon, previous studies have reported that the 4-day median lethal concentrations (LC50) based on biotic ligand model (BLM) normalization for copper were below the U.S. Environmental Protection Agency national recommended acute water-quality criterion. In previously published chronic 66-d exposures starting with newly fertilized eggs of white sturgeon, 20-percent lethal effect concentrations (LC20s) for copper, cadmium, or zinc generally were within a factor of two of the chronic values of the most sensitive fish species in the databases of the U.S. Environmental Protection Agency water-quality criteria (WQC) for the three metals. However, there were some uncertainties in the chronic exposures previously performed with white sturgeon, including (1) low control survival (37 percent), (2) more control fish tested in each replicate compared to other treatments, (3) limited replication of treatments (n=2), (4) lack of reported growth data (such as dry weight), and (5) wide dilution factors for exposure concentrations (6- to 8-fold dilutions). The U.S. Environmental Protection Agency concluded that additional studies are needed to generate more toxicity data to better define lethal and sublethal toxicity thresholds for metals for white sturgeon. The objective of the study was to further evaluate the acute and chronic toxicity of cadmium, copper, lead, or zinc to early life stages of white sturgeon in water-only exposures. Toxicity tests also were performed with commonly tested rainbow trout (Oncorhynchus mykiss) under similar test conditions to determine the relative sensitivity between white sturgeon and rainbow trout to these metals. Toxicity data generated from this study were used to evaluate the sensitivity of early life stages of white sturgeon and rainbow trout relative to data published for other test organisms. Toxicity data generated from this study also were used to evaluate the level of protection of U.S. Environmental Protection Agency WQC or Washington State water-quality standards (WQS) for copper, zinc, cadmium, or lead to white sturgeon inhabiting the upper Columbia River. Chapter A of this report summarizes the results of acute toxicity tests performed for 4 d with white sturgeon and rainbow trout exposed to copper, cadmium, or zinc. Chapter B of this report summarizes the results of chronic toxicity tests performed for as many as 53 days with white sturgeon or rainbow trout exposed to copper, cadmium, zinc, or lead. Appendixes to the report are available at http://pubs.usgs.gov/sir/2013/5204. Supporting documentation for chapter A toxicity testing is provided in appendix 1. Supporting documentation for chapter B toxicity testing is provided in Appendix 2. Supporting documentation on analysis of water chemistry for chapter A and chapter B is provided in appendix 3 and 4. The rationale for applying corrections to measured copper and zinc values in water samples from some of the toxicity tests performed in chapter A is provided in appendix 5. A summary of dissolved organic carbon measurement variability and implications for biotic ligand model normalization for toxicity data summarized in chapter A and chapter B are provided in appendix 6. An evaluation of an interlaboratory comparison of analyses for dissolved organic carbon in water from the U.S. Geological Survey Columbia Environmental Research Center and University of Saskatchewan is provided in appendix 7. Finally, appendix 8 provides a summary of retesting of white sturgeon in 2012 to determine if improved survival of sturgeon would affect copper effect concentrations in 24-d copper exposures started with newly hatched larvae, and to evaluate the effect of light intensity or temperature on the response of newly hatched larvae during a 25-d study.
Tillitt, Donald E; Buckler, Justin A; Nicks, Diane K; Candrl, James S; Claunch, Rachel A; Gale, Robert W; Puglis, Holly J; Little, Edward E; Linbo, Tiffany L; Baker, Mary
2017-04-01
The aquatic food web of the Great Lakes has been contaminated with polychlorinated biphenyls (PCBs) since the mid-20th century. Threats of PCB exposures to long-lived species of fish, such as lake sturgeon (Acipenser fulvescens), have been uncertain because of a lack of information on the relative sensitivity of the species. The objective of the present study was to evaluate the sensitivity of early-life stage lake sturgeon to 3,3',4,4',5-pentachlorobiphenyl (PCB-126) or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure. Mortality, growth, morphological and tissue pathologies, swimming performance, and activity levels were used as assessment endpoints. Pericardial and yolk sac edema, tubular heart, yolk sac hemorrhaging, and small size were the most commonly observed pathologies in both TCDD and PCB-126 exposures, beginning as early as 4 d postfertilization, with many of these pathologies occurring in a dose-dependent manner. Median lethal doses for PCB-126 and TCDD in lake sturgeon were 5.4 ng/g egg (95% confidence interval, 3.9-7.4 ng/g egg) and 0.61 ng/g egg (0.47-0.82 ng/g egg), respectively. The resulting relative potency factor for PCB-126 (0.11) was greater than the World Health Organization estimate for fish (toxic equivalency factor = 0.005), suggesting that current risk assessments may underestimate PCB toxicity toward lake sturgeon. Swimming activity and endurance were reduced in lake sturgeon survivors from the median lethal doses at 60 d postfertilization. Threshold and median toxicity values indicate that lake sturgeon, like other Acipenser species, are more sensitive to PCB and TCDD than the other genus of sturgeon, Scaphirhynchus, found in North America. Indeed, lake sturgeon populations in the Great Lakes and elsewhere are susceptible to PCB/TCDD-induced developmental toxicity in embryos and reductions in swimming performance. Environ Toxicol Chem 2017;36:988-998. Published 2016 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America. Published 2016 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America.
Toxicity of synthetic musks to early life stages of the freshwater mussel Lampsilis cardium
Gooding, M.P.; Newton, T.J.; Bartsch, M.R.; Hornbuckle, K.C.
2006-01-01
Polycyclic musk fragrances are common additives to many consumer products. As a result of their widespread use and slow degradation rates, they are widely found in aquatic environments. This study reports on the lethal and sublethal toxicity of the polycyclic musks AHTN (Tonalide??) and HHCB (Galaxolide??) to glochidial (larval) and juvenile life stages of the freshwater mussel Lampsilis cardium (Rafinesque, 1820). In glochidia, 24-h median lethal concentrations (LC50s) ranged from 454 to 850 ??g AHTN/L and from 1000 to >1750 ??g HHCB/L (water solubility). Results for 48-h tests were similar to the 24-h tests. In 96-h tests with juveniles, we did not observe a dose-response relation between mortality and either musk. However, the growth rate was reduced by musk exposure. The median effective concentrations (EC50s, based on growth) were highly variable and ranged from 108 to 1034 ??g AHTN/L and 153 to 831 ??g HHCB/L. While all adverse effects occurred at concentrations that are much greater than those reported in natural waters (low ??g/L to ng/L), these results indicate the potential for adverse effects on these long-lived organisms from exposure to synthetic musk fragrances. ?? 2006 Springer Science+Business Media, Inc.
Toxicity of Synthetic Musks to Early Life Stages of the Freshwater Mussel Lampsilis cardium
Gooding, M.P.; Newton, T.J.; Bartsch, M.R.; Hornbuckle, K.C.
2009-01-01
Polycyclic musk fragrances are common additives to many consumer products. As a result of their widespread use and slow degradation rates, they are widely found in aquatic environments. This study reports on the lethal and sublethal toxicity of the polycyclic musks AHTN (Tonalide®) and HHCB (Galaxolide®) to glochidial (larval) and juvenile life stages of the freshwater mussel Lampsilis cardium (Rafinesque, 1820). In glochidia, 24-h median lethal concentrations (LC50s) ranged from 454 to 850 μg AHTN/L and from 1000 to >1750 μg HHCB/L (water solubility). Results for 48-h tests were similar to the 24-h tests. In 96-h tests with juveniles, we did not observe a dose-response relation between mortality and either musk. However, growth rate was reduced by musk exposure. The median effective concentrations (EC50s, based on growth) were highly variable and ranged from 108 to 1034 μg AHTN/L and 153 to 831 μg HHCB/L. While all adverse effects occurred at concentrations that are much greater than those reported in natural waters (low μg/L to ng/L), these results indicate the potential for adverse effects on these long-lived organisms from exposure to synthetic musk fragrances. PMID:16944041
Technical Committee on Aricultural Chemical Safety (ACSA) Life Stages Task Force
This document takes a life stages approach to the assessment of risk attributable to crop protection products, and well-known experts in the field are contributing authors. The paper presents an in-depth justification for proposed changes in current protocols for toxicity testing...
Preventing Obesity Across Generations: Evidence for Early Life Intervention.
Haire-Joshu, Debra; Tabak, Rachel
2016-01-01
To prevent the intergenerational transfer of obesity and end the current epidemic, interventions are needed across the early life stages, from preconception to prenatal to infancy through the age of 2 years. The foundation for obesity is laid in early life by actions and interactions passed from parent to child that have long-lasting biologic and behavioral consequences. The purpose of this paper is to examine the best evidence about (a) factors in parents and offspring that promote obesity during the early life stages, (b) the social determinants and dimensions of obesity in early life, (c) promising and effective interventions for preventing obesity in early life, and (d) opportunities for future research into strategies to disrupt the intergenerational cycle of obesity that begins early in life. The pathway for halting the intergenerational obesity epidemic requires the discovery and development of evidence-based interventions that can act across multiple dimensions of influence on early life.
Preventing Obesity Across Generations: Evidence for Early Life Intervention
Haire-Joshu, Debra; Tabak, Rachel
2017-01-01
To prevent the intergenerational transfer of obesity and end the current epidemic, interventions are needed across the early life stages, from preconception to prenatal to infancy through the age of 2 years. The foundation for obesity is laid in early life by actions and interactions passed from parent to child that have long-lasting biologic and behavioral consequences. The purpose of this paper is to examine the best evidence about (a) factors in parents and offspring that promote obesity during the early life stages, (b) the social determinants and dimensions of obesity in early life, (c) promising and effective interventions for preventing obesity in early life, and (d) opportunities for future research into strategies to disrupt the intergenerational cycle of obesity that begins early in life. The pathway for halting the intergenerational obesity epidemic requires the discovery and development of evidence-based interventions that can act across multiple dimensions of influence on early life. PMID:26989828
Phototoxicity of TiO2 nanoparticles to zebrafish (Danio rerio) is dependent on life stage.
Ma, Hongbo; Diamond, Stephen A
2013-09-01
Zebrafish embryos have been used increasingly to evaluate nanomaterial toxicity. The present study compared phototoxicity of TiO2 nanoparticles with zebrafish at 4 life stages (embryos, yolk-sac larvae, free-swimming larvae, and juvenile) under simulated sunlight using the 96-h standard toxicity assay. Yolk-sac larvae were found to be the most sensitive to TiO2 phototoxicity, suggesting that the widely used zebrafish embryo test may not fully or accurately predict hazard and risk of these nanoparticles to small fish. Copyright © 2013 SETAC.
Impacts of triclosan exposure on zebrafish early-life stage: Toxicity and acclimation mechanisms.
Falisse, Elodie; Voisin, Anne-Sophie; Silvestre, Frédéric
2017-08-01
Triclosan (TCS) is a broad spectrum antibacterial agent widely used in personal care products and present in most aquatic ecosystems. This study investigated the occurrence of triclosan acclimation and the biological mechanisms underlying the stress response triggered in early-life stage of zebrafish. Zebrafish eggs were first exposed to four different sublethal concentrations of TCS (2, 20, 50 and 100μg/L) for 7days following fertilization and subsequently exposed to a lethal concentration of TCS (1000μg/L). During the time-to-death exposure (TTD), mortality was continuously recorded to evaluate if increased resistance occurred. Overall, larvae exposed to 50μg/L of TCS demonstrated higher sensitivity, with delayed hatching and increased mortality during the sub-lethal exposure and significant lower mean time-to-death (TTD) value compared to the other groups. Interestingly, fish exposed to the highest concentration of TCS (100μg/L) presented a similar mean TTD value as controls and a significantly better survival in comparison with embryos exposed to 50μg/L, suggesting that acclimation process has been triggered at this concentration. Proteomic and enzymatic analyses were conducted on 7days post fertilization (dpf) larvae exposed to 50μg/L and 100μg/L of TCS giving insights into the functional changes triggered at those specific concentrations. TCS seemed to affect proteins involved in cytoskeleton, stress response, eyes and neuronal development. This was endorsed by the enzymatic results, which suggest impairment in glutathione metabolism and acute neurotoxicity. A significant 2.5-fold and 3-fold increase of AChE activity was observed following TCS exposure. Moreover, GPx activity was significantly increased whereas a significant inhibition of GR activity was observed, suggesting that de novo synthesis of reduced GSH might occur in order to maintain the ratio between reduced and oxidized GSH. Proteomic results revealed possible candidate protein involved in the acclimation process of larvae exposed to 100μg/L of TCS. Our integrative analysis revealed complex non-monotonic concentration-related effects on zebrafish early-life stages with increased resistance between 50 and 100μg/L exposures. This research highlighted oxidative stress and neurotoxicity as major toxicity mechanisms of TCS during development. Copyright © 2017 Elsevier B.V. All rights reserved.
2014-01-01
Background Pollen donor compositions differ during the early stages of reproduction due to various selection mechanisms. In addition, ovules linearly ordered within a fruit have different probabilities of reaching maturity. Few attempts, however, have been made to directly examine the magnitude and timing of selection, as well as the mechanisms during early life stages and within fruit. Robinia pseudoacacia, which contains linear fruit and non-random ovule maturation and abortion patterns, has been used to study the viability of selection within fruit and during the early stages of reproduction. To examine changes in the pollen donor composition during the early stages of reproduction and of progeny originating from different positions within fruit, paternity analyses were performed for three early life stages (aborted seeds, mature seeds and seedlings) in the insect-pollinated tree R. pseudoacacia. Results Selection resulted in an overall decrease in the level of surviving selfed progeny at each life stage. The greatest change was observed between the aborted seed stage and mature seed stage, indicative of inbreeding depression (the reduced fitness of a given population that occurs when related individual breeding was responsible for early selection). A selective advantage was detected among paternal trees. Within fruits, the distal ends showed higher outcrossing rates than the basal ends, indicative of selection based on the order of seeds within the fruit. Conclusions Our results suggest that selection exists both within linear fruit and during the early stages of reproduction, and that this selection can affect male reproductive success during the early life stages. This indicates that tree species with mixed-mating systems may have evolved pollen selection mechanisms to increase the fitness of progeny and adjust the population genetic composition. The early selection that we detected suggests that inbreeding depression caused the high abortion rate and low seed set in R. pseudoacacia. PMID:24655746
Yuan, Cun-Quan; Sun, Yu-Han; Li, Yun-Fei; Zhao, Ke-Qi; Hu, Rui-Yang; Li, Yun
2014-03-21
Pollen donor compositions differ during the early stages of reproduction due to various selection mechanisms. In addition, ovules linearly ordered within a fruit have different probabilities of reaching maturity. Few attempts, however, have been made to directly examine the magnitude and timing of selection, as well as the mechanisms during early life stages and within fruit. Robinia pseudoacacia, which contains linear fruit and non-random ovule maturation and abortion patterns, has been used to study the viability of selection within fruit and during the early stages of reproduction. To examine changes in the pollen donor composition during the early stages of reproduction and of progeny originating from different positions within fruit, paternity analyses were performed for three early life stages (aborted seeds, mature seeds and seedlings) in the insect-pollinated tree R. pseudoacacia. Selection resulted in an overall decrease in the level of surviving selfed progeny at each life stage. The greatest change was observed between the aborted seed stage and mature seed stage, indicative of inbreeding depression (the reduced fitness of a given population that occurs when related individual breeding was responsible for early selection). A selective advantage was detected among paternal trees. Within fruits, the distal ends showed higher outcrossing rates than the basal ends, indicative of selection based on the order of seeds within the fruit. Our results suggest that selection exists both within linear fruit and during the early stages of reproduction, and that this selection can affect male reproductive success during the early life stages. This indicates that tree species with mixed-mating systems may have evolved pollen selection mechanisms to increase the fitness of progeny and adjust the population genetic composition. The early selection that we detected suggests that inbreeding depression caused the high abortion rate and low seed set in R. pseudoacacia.
Dong, Wu; Macaulay, Laura J; Kwok, Kevin W H; Hinton, David E; Stapleton, Heather M
2013-05-15
Polybrominated diphenyl ethers (PBDEs) and their oxidative metabolites (hydroxylated PBDEs; OH-BDEs) are known endocrine disrupting contaminants that have been shown to disrupt thyroid hormone regulation both in mammals and in fish. The purpose of this study was to determine the precise organ and tissue locations that express genes critical to thyroid hormone regulation in developing zebrafish (Danio rerio), and to determine the effects of an OH-BDE on their expression. While RT-PCR can provide quantitative data on gene expression, it lacks spatial sensitivity to examine localized gene expression; and, isolation of organs from zebrafish embryos is technically difficult, if not impossible. For this reason, the present study used whole mount in situ hybridization to simultaneously localize and quantify gene expression in vivo. While PBDEs and OH-BDEs have been shown to inhibit the activity and expression of deiodionases, a family of enzymes that regulate thyroid hormone concentrations intracellularly, it is unclear whether or not they can affect regional expression of the different isoforms during early development. In this study we investigated deiodinase 1 (Dio1), deiodinase 2 (Dio2), and deiodinase 3 (Dio3) mRNA expression at the following life stages (2, 8, and 1k-cells; 50%-epiboly, 6 and 18-somites, 22, 24, 48, 72 hpf and/or 10 dpf) in zebrafish and found life stage specific expression of these genes that were highly localized. To demonstrate the use of this technique for investigating potential endocrine disrupting effects, zebrafish embryos were exposed to 1, 10 and 100nM 6-OH-BDE-47. Significant increases in mean intensity of Dio1 and Dio3 expression in the periventricular zone of brain and pronephric duct, respectively (quantified by measuring intensity of coloration using ImageJ analysis software) were observed, suggesting localized response at the HPT axis with the possibility of impacting neurodevelopment. Our results demonstrate effects of OH-BDEs on thyroid regulating gene expression and provide more insight into potential sites of injury during early life stages. Copyright © 2013 Elsevier B.V. All rights reserved.
Dong, Wu; Macaulay, Laura; Kwok, Kevin WH; Hinton, David E; Stapleton, Heather M.
2013-01-01
Polybrominated diphenyl ethers (PBDEs) and their oxidative metabolites (hydroxylated PBDEs; OH-BDEs) are known endocrine disrupting contaminants that have been shown to disrupt thyroid hormone regulation both in mammals and in fish. The purpose of this study was to determine the precise organ and tissue locations that express genes critical to thyroid hormone regulation in developing zebrafish (Danio rerio), and to determine the effects of an OH-BDE on their expression. While RT-PCR can provide quantitative data on gene expression, it lacks spatial sensitivity to examine localized gene expression; and, isolation of organs from zebrafish embryos is technically difficult, if not impossible. For this reason, the present study used whole mount in situ hybridization to simultaneously localize and quantify gene expression in vivo. While PBDEs and OH-BDEs have been shown to inhibit the activity and expression of deiodionases, a family of enzymes that regulate thyroid hormone concentrations intracellularly, it is unclear whether or not they can affect regional expression of the different isoforms during early development. In this study we investigated deiodinase 1 (Dio1), deiodinase 2 (Dio2), and deiodinase 3 (Dio3) mRNA expression at the following life stages (2, 8, and 1k-cells; 50%-epiboly, 6 and 18-somites, 22, 24, 48, 72 hpf and/or 10 dpf) in zebrafish and found life stage specific expression of these genes that were highly localized. To demonstrate the use of this technique for investigating potential endocrine disrupting effects, zebrafish embryos were exposed to 1, 10 and 100 nM 6-OH-BDE-47. Significant increases in mean intensity of Dio1 and Dio3 expression in the periventricular zone of brain and pronephric duct, respectively (quantified by measuring intensity of coloration using ImageJ analysis software) were observed, suggesting localized response at the HPT axis with the possibility of impacting neurodevelopment. Our results demonstrate effects of OH-BDEs on thyroid regulating gene expression and provide more insight into potential sites of injury during early life stages. PMID:23531416
Macagnan, Natani; Rutkoski, Camila F; Kolcenti, Cassiane; Vanzetto, Guilherme V; Macagnan, Luan P; Sturza, Paola F; Hartmann, Paulo A; Hartmann, Marilia T
2017-09-01
It is important to establish the toxicity pesticides against non-target species, especially those pesticides used in commercial formulations. Pyrethroid insecticides are widely used in agriculture despite their toxicity to aquatic animals. In this study, we determine the toxicity of commercial formulation of two pyrethroid insecticides, cypermethrin and deltamethrin, in two life stages of Physalaemus gracilis, a frog that breeds in agricultural ecosystems and has potential contact with pyrethroid pesticides. The acute toxicity test (96 h) was carried out with embryos of stage 17:18 and larvae of stages 24:25. Embryos were more resistant to both pesticides than larvae. In embryo mobility assays, we found that both pesticides caused spasmodic contractions, suggestive of neurological effects. In acute toxicity assays, we found that P. gracilis is more resistant to these insecticides than other studied species.
Nye, Monica D; Fry, Rebecca C; Hoyo, Cathrine; Murphy, Susan K
2014-01-01
Increasing evidence suggest that epigenetic alterations can greatly impact human health, and that epigenetic mechanisms (DNA methylation, histone modifications, and microRNAs) may be particularly relevant in responding to environmental toxicant exposure early in life. The epigenome plays a vital role in embryonic development, tissue differentiation and disease development by controlling gene expression. In this review we discuss what is currently known about epigenetic alterations in response to prenatal exposure to inorganic arsenic (iAs) and lead (Pb), focusing specifically on their effects on DNA methylation. We then describe how epigenetic alterations are being studied in newborns as potential biomarkers of in utero environmental toxicant exposure, and the benefits and challenges of this approach. In summary, the studies highlighted herein indicate how epigenetic mechanisms are impacted by early life exposure to iAs and Pb, and the research that is being done to move towards understanding the relationships between toxicant-induced epigenetic alterations and disease development. Although much remains unknown, several groups are working to understand the correlative and causal effects of early life toxic metal exposure on epigenetic changes and how these changes may result in later development of disease.
de Sisternes, Luis; Hu, Julia; Rubin, Daniel L; Marmor, Michael F
2015-05-01
To evaluate the relative involvement of inner and outer retina in hydroxychloroquine (HCQ) retinopathy while on the drug, and after drug cessation, using data from spectral-domain optical coherence tomography (SD-OCT). A total of 102 SD-OCT scans were obtained from 11 patients (classified as having early, moderate, or severe stages of toxicity) over a period of 4 years after cessation of HCQ. The inner and outer retina boundaries were identified automatically to measure thickness and characterize progression topographically. The segmentation of retinal layers was verified in SD-OCT cross-sections for all eyes and scans included in this study (a total of 102 scans). Topographic analysis showed that inner retina was not involved in HCQ toxicity to any meaningful degree, either between stages of retinopathy or after the drug is stopped. The characteristic bull's eye pattern of outer macula thinning appears when comparing moderate retinopathy (before any RPE damage) to the early stage. Later damage, as toxicity evolved to a severe stage, was diffuse across most of the macula. If the drug was stopped at an early or moderate stage, progression was limited to the first year and occurred diffusely without parafoveal localization. Hydroxychloroquine retinopathy primarily involves outer retina (photoreceptors). Outer retinal thinning while using HCQ initially involves the parafovea, but becomes diffuse across the macula as damage progresses or after drug cessation. When HCQ is stopped at an early or moderate stage (before RPE damage), progression seems to be limited to the first year.
Federal Register 2010, 2011, 2012, 2013, 2014
2012-03-27
... Survey, Ages and Stages Questionnaire (ASQ-I), Mullen Stages of Early Development (MSEL), Postpartum...% of all US mothers. Early and regular prenatal care is a major predicator of positive birth outcomes... endpoints. Biological sample analysis, surveys, and developmental screenings will be performed during this...
Impact of Life-Cycle Stage and Gender on the Ability to Balance Work and Family Responsibilities.
ERIC Educational Resources Information Center
Higgins, Christopher; And Others
1994-01-01
Examined impact of gender and life-cycle stage on three components of work-family conflict using sample of 3,616 respondents. For men, levels of work-family conflict were moderately lower in each successive life-cycle stage. For women, levels were similar in two early life-cycle stages but were significantly lower in later life-cycle stage.…
Edvardsen, Bente; Dittami, Simon M; Groben, René; Brubak, Sissel; Escalera, Laura; Rodríguez, Francisco; Reguera, Beatriz; Chen, Jixin; Medlin, Linda K
2013-10-01
Dinophysis and Phalacroma species containing diarrheic shellfish toxins and pectenotoxins occur in coastal temperate waters all year round and prevent the harvesting of mussels during several months each year in regions in Europe, Chile, Japan, and New Zealand. Toxicity varies among morphologically similar species, and a precise identification is needed for early warning systems. Molecular techniques using ribosomal DNA sequences offer a means to identify and detect precisely the potentially toxic species. We designed molecular probes targeting the 18S rDNA at the family and genus levels for Dinophysis and Phalacroma and at the species level for Dinophysis acuminata, Dinophysis acuta, and Dinophysis norvegica, the most commonly occurring, potentially toxic species of these genera in Western European waters. Dot blot hybridizations with polymerase chain reaction (PCR)-amplified rDNA from 17 microalgae were used to demonstrate probe specificity. The probes were modified along with other published fluorescence in situ hybridization and PCR probes and tested for a microarray platform within the MIDTAL project ( http://www.midtal.com ). The microarray was applied to field samples from Norway and Spain and compared to microscopic cell counts. These probes may be useful for early warning systems and monitoring and can also be used in population dynamic studies to distinguish species and life cycle stages, such as cysts, and their distribution in time and space.
Wang, Yanhua; Wu, Shenggan; Chen, Jine; Zhang, Changpeng; Xu, Zhenlan; Li, Gang; Cai, Leiming; Shen, Weifeng; Wang, Qiang
2018-02-01
Pesticides usually present in mixtures in surface waters, although they are traditionally regulated on an individual basis in aquatic ecosystems. In this study, we aimed to investigate the lethal and transcriptional responses of individual and combined pesticides (iprodione, pyrimethanil, pyraclostrobin and acetamiprid) on zebrafish (Danio rerio). Semi-static toxicity test indicated that the greatest toxicity to the four life stages (embryonic, larval, juvenile and adult stages) of D. rerio was detected from pyraclostrobin, followed by iprodione and pyrimethanil. In contrast, the lowest toxicity to the organisms was found from acetamiprid. Most of the selected pesticides exerted greater toxicities to D. rerio of embryonic stage compared with other life stages. Synergistic responses were observed from all binary mixtures of iprodione in combination with pyrimethanil or acetamiprid and ternary mixtures of iprodione+pyraclostrobin in combination with pyrimethanil or acetamiprid. The expressions of 16 genes related to cell apoptosis pathway, oxidative stress response, innate immunity and endocrine disruption at the mRNA level showed that zebrafish embryos were affected by the individual or combined pesticides. The expressions of P53, Tnf, TRβ, Tsh and Cyp19a exhibited greater changes upon exposure to combined pesticides compared with individual pesticides. Taken together, increased toxicity might be triggered by the simultaneous presence of several pesticides in the aquatic environment, which seriously damaged the non-target organisms. Copyright © 2017 Elsevier Ltd. All rights reserved.
Developmental rate and behavior of early life stages of bighead carp and silver carp
Chapman, Duane C.; George, Amy E.
2011-01-01
The early life stages of Asian carp are well described by Yi and others (1988), but since these descriptions are represented by line drawings based only on live individuals and lacked temperature controls, further information on developmental time and stages is of use to expand understanding of early life stages of these species. Bighead carp and silver carp were cultured under two different temperature treatments to the one-chamber gas bladder stage, and a photographic guide is provided for bighead carp and silver carp embryonic and larval development, including notes about egg morphology and larval swimming behavior. Preliminary information on developmental time and hourly thermal units for each stage is also provided. Both carp species developed faster under warmer conditions. Developmental stages and behaviors are generally consistent with earlier works with the exception that strong vertical swimming immediately after hatching was documented in this report.
Electrochemical remediation of amoxicillin: Detoxification and reduction of antimicrobial activity.
Brito, Lara Barroso; Garcia, Luane Ferreira; Caetano, Marcos Pereira; Lobón, Germán Sanz; Teles de Oliveira, Mayk; de Oliveira, Rhaul; Sapateiro Torres, Ieda Maria; Yepez, Alfonso; Vaz, Boniek Gontijo; Luque, Rafael; Grisolia, Cesar Koppe; Valadares, Marize Campos; de Souza Gil, Eric; Rodrigues de Oliveira, Gisele Augusto
2018-06-16
Amoxicillin (AMX) is one of the most commonly prescribed antibiotics around the world to treat and prevent several diseases in both human and veterinary medicine. Incomplete removal of AMX during wastewater treatment contributes to its presence in water bodies and drinking water. AMX is an emerging contaminant since its impact on the environment and human health remains uncertain. This contribution was aimed to evaluate the electrochemical oxidation (EO) of AMX using different anodes in tap water, NaCl or Na 2 SO 4 solutions and to evaluate the potential toxicity of remaining AMX and its by-products on zebrafish early-life stages. Chemical intermediates generated after EO were determined by mass spectrometry and their resulting antimicrobial activity was evaluated. AMX did not induce significant mortality in zebrafish during extended exposure but affected zebrafish development (increased body length) from 6.25 mg/L to 25 mg/L and inhibited enzymatic biomarkers. Carbon modified with titanium oxide (TiO 2 @C) anode achieved complete AMX removal in just a few minutes and efficiency of the supported electrolytes occurred in the following order: 0.1 M NaCl > 0.1 M Na 2 SO 4 > 0.01 M NaCl > tap water. The order of potential toxicity to zebrafish early life-stages related to lethal and sublethal effects was as follows: 0.1 M Na 2 SO 4 > 0.1 M NaCl >0.01 M NaCl = tap water. Additionally, the EO of AMX using TiO 2 @C electrode with 0.01 M NaCl was able to inhibit the antimicrobial activity of AMX, reducing the possibility of developing bacterial resistance. Copyright © 2018. Published by Elsevier B.V.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Stiles-Jewell, S.
1994-01-01
Fertilized eggs were exposed to 0.1, 10 and 100 mg/l of benzene, naphthalene and Aroclor 1254 individually and in combination in seawater at temperatures and salinities of 20 and 25. Toxicity was measured as frequencies of: (1) meiotic and mitotic abnormalities in 3-hour embryos; (2) total development to the 48-hour straight-hinge larval stage; (3) mortality and abnormality at the 48-hour larval stage; (4) mean size of larvae at 48 hours; and (5) cytogenetic and cytological abnormalities in 48-hour larvae. Dose-dependent responses were observed. Overall, naphthalene and aroclor at 100 mg/l had few embryos that survived to the stage where theymore » could be examined and scored for cytogenetic and cytological abnormality even by 3-hours post-fertilization. Abnormality of the few embryos available for examination was somewhat higher for aroclor but was significantly higher for naphthalene than for control embryos and those exposed to 0.1 mg/l. At the highest concentration of 100 mg/l, mortality was 100% by the larval stage for naphthalene and aroclor. Though total development and survival of embryos to the larval stage at the 10 mg/l dose were high, many of the larvae were dead or abnormal in the aroclor-exposed cultures. This mean incidence was significantly higher than for all other groups. Larvae developing in these cultures with 10 mg/l were also significantly smaller and cytological condition of the larvae was significantly worse. Higher temperature appeared to increase the frequency of deleterious effects, particularly for naphthalene and aroclor. Results with salinity were more variable. Overall, results showed that petroleum aromatic hydrocarbons and PCBs can have toxic effects on the development and survival of early life stages of oysters, as well as sublethal effects on growth and cytological condition, depending on dose and interactions with other compound and with environmental variables.« less
Duffy, Tara A.; Iwanowicz, Luke R.; McCormick, Stephen D.
2014-01-01
Atlantic salmon (Salmo salar) are endangered anadromous fish that may be exposed to feminizing endocrine disrupting compounds (EDCs) during early development, potentially altering physiological capacities, survival and fitness. To assess differential life stage sensitivity to common EDCs, we carried out short-term (four day) exposures using three doses each of 17α-ethinylestradiol (EE2), 17β-estradiol (E2), and nonylphenol (NP) on four early life stages; embryos, yolk-sac larvae, feeding fry and one year old smolts. Differential response was compared using vitellogenin (Vtg, a precursor egg protein) gene transcription. Smolts were also examined for impacts on plasma Vtg, cortisol, thyroid hormones (T4/T3) and hepatosomatic index (HSI). Compound-related mortality was not observed in any life stage, but Vtg mRNA was elevated in a dose-dependent manner in yolk-sac larvae, fry and smolts but not in embyos. The estrogens EE2 and E2 were consistently stronger inducers of Vtg than NP. Embryos responded significantly to the highest concentration of EE2 only, while older life stages responded to the highest doses of all three compounds, as well as intermediate doses of EE2 and E2. Maximal transcription was greater for fry among the three earliest life stages, suggesting fry may be the most responsive life stage in early development. Smolt plasma Vtg was also significantly increased, and this response was observed at lower doses of each compound than was detected by gene transcription suggesting this is a more sensitive indicator at this life stage. HSI was increased at the highest doses of EE2 and E2 and plasma T3 decreased at the highest dose of EE2. Our results indicate that all life stages after hatching are potentially sensitive to endocrine disruption by estrogenic compounds and that physiological responses were altered over a short window of exposure, indicating the potential for these compounds to impact fish in the wild.
NASA Astrophysics Data System (ADS)
Mensah, P. K.; Muller, W. J.; Palmer, C. G.
Glyphosate based herbicides, including Roundup®, are frequently used in the chemical control of weeds and invading alien plant species in South Africa. These herbicides ultimately get into water courses directly or indirectly through processes such as drifting, leaching, surface runoff and foliar spray of aquatic nuisance plants. Despite their widespread use, no water quality guideline exists to protect indigenous South African freshwater organisms from the toxic effects of these herbicides. The toxicity of the herbicide Roundup® was assessed using three different life stages of the freshwater shrimp Caridina nilotica, a prevalent species in South African freshwater ecosystems. Neonate (<7 days post hatching (dph)), juvenile (>7 dph and <20 dph) and adult (>40 dph) shrimps were exposed to varying concentrations (1.5-50 mg/L acid equivalence (a.e.)) of the herbicide in 48 and 96 h acute toxicity tests in order to determine the most sensitive life-stage. The results showed neonates to be more sensitive to Roundup® than both juveniles and adults with mean 96 h LC 50 values of 2.5, 7.0 and 25.3 mg/L a.e. respectively. The estimated 96 h LC 50 of neonates is much lower than the application rate (20-30 mg/L a.e.), although the application’s impact will depend on the dilution rate of the applied concentration in the environment. All three life-stages of unexposed animals exhibited active and coordinated movement but exposed shrimps were erratic and slow in their movements, with neonates showing most of these behavioral irregularities. This study shows that low levels of the herbicide Roundup® may adversely affect C. nilotica health and survival. Thus, the herbicide should be carefully managed to minimize any negative impact on non-target freshwater organisms.
Gilbert, Kathleen M.; Woodruff, William; Blossom, Sarah J.
2014-01-01
Developmental exposure to environmental toxicants may induce immune system alterations that contribute to adult stage autoimmune disease. We have shown that continuous exposure of MRL+/+ mice to trichloroethylene (TCE) from gestational day (GD) 0 to postnatal day (PND) 49 alters several aspects of CD4+ T cell function. This window of exposure corresponds to conception-adolescence/young adulthood in humans. More narrowly defining the window of TCE developmental exposure causes immunotoxicity that would establish the stage at which avoidance and/or intervention would be most effective. The current study divided continuous TCE exposure into two separate windows, namely, gestation only (GD0 to birth (PND0)) and early-life only (PND0-PND49). The mice were examined for specific alterations in CD4+ T cell function at PND49. One potentially long-lasting effect of developmental exposure, alterations in retrotransposon expression indicative of epigenetic alterations, was found in peripheral CD4+ T cells from both sets of developmentally exposed mice. Interestingly, certain other effects, such as alterations in thymus cellularity, were only found in mice exposed to TCE during gestation. In contrast, expansion of memory/activation cell subset of peripheral CD4+ T cells were only found in mice exposed to TCE during early life. Different windows of developmental TCE exposure can have different functional consequences. PMID:24696780
He, Yuhe; Patterson, Sarah; Wang, Nan; Hecker, Markus; Martin, Jonathan W; El-Din, Mohamed Gamal; Giesy, John P; Wiseman, Steve B
2012-12-01
Due to a policy of no release, oil sands process-affected water (OSPW), produced by the surface-mining oil sands industry in North Eastern Alberta, Canada, is stored on-site in tailings ponds. Currently, ozonation is considered one possible method for remediation of OSPW by reducing the concentrations of dissolved organic compounds, including naphthenic acids (NAs), which are considered the primary toxic constituents. However, further work was needed to evaluate the effectiveness of ozonation in reducing the toxicity of OSPW and to ensure that ozonation does not increase the toxicity of OSPW. This study examined effects of untreated, ozone-treated, and activated charcoal-treated OSPW (OSPW, O3-OSPW, and AC-OSPW) on the early life stage (ELS) of fathead minnow (Pimephales promelas). Success of hatching of eggs, spontaneous movement, and incidences of hemorrhage, pericardial edema, and malformation of the spine of embryos were examined. To elucidate the mechanism of toxicity, concentrations of reactive oxygen species (ROS) were measured, and the abundances of transcripts of genes involved in biotransformation of xenobiotics, response to oxidative stress, and apoptosis were quantified by real-time PCR. Compared to the control group, which had an embryo survival rate of 97.9 ± 2.08%, survival was significantly less when exposed to OSPW (43.8 ± 7.12%). Eggs exposed to untreated OSPW exhibited a significantly greater rate of premature hatching, and embryos exhibited greater spontaneous movement. Incidences of hemorrhage (50.0 ± 3.40%), pericardial edema (56.3 ± 7.12%), and malformation of the spine (37.5 ± 5.38%) were significantly greater in embryos exposed to OSPW compared to controls. These effects are typical of exposure to dioxin-like compounds, however, abundance of transcripts of cyp1a was not significantly greater in embryos exposed to OSPW. Significantly greater concentrations of ROS, and greater abundances of transcripts cyp3a, gst, sod, casp9, and apopen compared to controls, indicated that exposure to OSPW caused oxidative stress, which can result in damage to mitochondria and promote activation of caspase enzymes and apoptotic cell death. Removal of dissolved organic constituents by ozone treatment, or by activated charcoal, significantly attenuated all of the adverse effects associated with untreated OSPW. The results suggest that the organic fraction of OSPW can negatively impact the development of fathead minnow embryos through oxidative stress and apoptosis, and that ozonation attenuates this developmental toxicity. Copyright © 2012 Elsevier Ltd. All rights reserved.
Luo, Si; Wu, Benli; Xiong, Xiaoqin; Wang, Jianwei
2016-01-01
The ionic composition of water is important for all fish. In the present study, the effects of total hardness and Ca(2+):Mg(2+) ratio on early life stages of rare minnows (Gobiocypris rarus), a promising laboratory fish in China, were evaluated. Paired parent fish were transferred to spawning aquaria (16 L) containing water at different total hardness and Ca:Mg ratios, and their offspring were further cultured at 25 ± 1 °C and 12:12-h light:dark photoperiod. Fertilization rates were not affected by total hardness to 480 mg L(-1) CaCO3, but egg size decreased with increasing total hardness. Ca:Mg ratios less than 1:20 or greater than 8:1 had adverse influences on hatching, feeding, development, larval growth, and survival. Embryos and larvae incubated in Mg(2+)- and Ca(2+)-deficient waters exhibited high malformation rates and high mortality. Our results demonstrate that rare minnows can adapt to a wide range of total hardness and Ca:Mg ratios, although an imbalance between Ca(2+) and Mg(2+) in water is toxic to this species. To increase the comparability and usefulness of test results, we recommend the use of reconstituted or drinking water of defined total hardness and Ca:Mg ratio for the culture and toxicity testing of rare minnows.
Noonan, Sam H. C.; Willis, Bette L.; Fabricius, Katharina E.; Negri, Andrew P.
2016-01-01
Inshore coral reefs are experiencing the combined pressures of excess nutrient availability associated with coastal activities and warming seawater temperatures. Both pressures are known to have detrimental effects on the early life history stages of hard corals, but studies of their combined effects on early demographic stages are lacking. We conducted a series of experiments to test the combined effects of nutrient enrichment (three levels) and elevated seawater temperature (up to five levels) on early life history stages of the inshore coral Acropora tenuis, a common species in the Indo-Pacific and Red Sea. Gamete fertilization, larval survivorship and larval settlement were all significantly reduced as temperature increased, but only fertilization was further affected by simultaneous nutrient enrichment. Combined high temperatures and nutrient enrichment affected fertilization in an additive manner, whereas embryo abnormalities increased synergistically. Higher than normal temperatures (32°C) increased coral juvenile growth rates 1.6-fold, but mortality also increased by 50%. The co-occurrence of nutrient enrichment with high temperatures reduced juvenile mortality to 36%, ameliorating temperature stress (antagonistic interaction). Overall, the types of effect (additive vs synergistic or antagonistic) and their magnitude varied among life stages. Gamete and embryo stages were more affected by temperature stress and, in some cases, also by nutrient enrichment than juveniles. The data suggest that coastal runoff events might exacerbate the impacts of warming temperatures on fertilization if these events co-occur during corals spawning. The cumulative impacts of simultaneous exposure to nutrient enrichment and elevated temperatures over all early life history stages increases the likelihood for failure of larval supply and recruitment for this coral species. Our results suggest that improving the water quality of river discharges into coastal areas might help to enhance the thermal tolerances of early life history stages in this common coral species. PMID:27575699
Acute toxic effects of endosulfan sulfate on three life stages of grass shrimp, Palaemonetes pugio.
Key, Peter B; Chung, Katy W; Venturella, John J; Shaddrick, Brian; Fulton, Michael H
2010-01-01
In this study, the toxicity of endosulfan sulfate, the primary degradation product of the insecticide endosulfan, was determined in three life stages of the grass shrimp (Palaemonetes pugio). After 96 h exposure to endosulfan sulfate, the grass shrimp adult LC50 was 0.86 microg/L (95% CI 0.56-1.31), the grass shrimp larvae LC50 was 1.64 microg/L (95% CI 1.09-2.47) and the grass shrimp embryo LC50 was 45.85 microg/L (95% CI 23.72-88.61 microg/L). This was compared to the previously published grass shrimp 96-h LC50s for endosulfan. The toxicity of the two compounds was similar for the grass shrimp life stages with adults more sensitive than larvae and embryos. The presence of sediment in 24h endosulfan sulfate-exposures raised LC50s for both adult and larval grass shrimp but not significantly. The USEPA expected environmental concentrations (EEC) for total endosulfan and endosulfan sulfate and the calculations of risk quotients (RQ) based on the more sensitive adult grass shrimp 96-h LC50 clearly show that environmental concentrations equal to acute EECs would prove detrimental to grass shrimp or other similarly sensitive aquatic organisms. These results indicate that given the persistence and toxicity of endosulfan sulfate, future risk assessments should consider the toxicity potential of the parent compound as well as this degradation product.
Silver nanoparticles induce developmental stage-specific embryonic phenotypes in zebrafish
NASA Astrophysics Data System (ADS)
Lee, Kerry J.; Browning, Lauren M.; Nallathamby, Prakash D.; Osgood, Christopher J.; Xu, Xiao-Hong Nancy
2013-11-01
Much is anticipated from the development and deployment of nanomaterials in biological organisms, but concerns remain regarding their biocompatibility and target specificity. Here we report our study of the transport, biocompatibility and toxicity of purified and stable silver nanoparticles (Ag NPs, 13.1 +/- 2.5 nm in diameter) upon the specific developmental stages of zebrafish embryos using single NP plasmonic spectroscopy. We find that single Ag NPs passively diffuse into five different developmental stages of embryos (cleavage, early-gastrula, early-segmentation, late-segmentation, and hatching stages), showing stage-independent diffusion modes and diffusion coefficients. Notably, the Ag NPs induce distinctive stage and dose-dependent phenotypes and nanotoxicity, upon their acute exposure to the Ag NPs (0-0.7 nM) for only 2 h. The late-segmentation embryos are most sensitive to the NPs with the lowest critical concentration (CNP,c << 0.02 nM) and highest percentages of cardiac abnormalities, followed by early-segmentation embryos (CNP,c < 0.02 nM), suggesting that disruption of cell differentiation by the NPs causes the most toxic effects on embryonic development. The cleavage-stage embryos treated with the NPs develop into a wide variety of phenotypes (abnormal finfold, tail/spinal cord flexure, cardiac malformation/edema, yolk sac edema, and acephaly). These organ structures are not yet developed in cleavage-stage embryos, suggesting that the earliest determinative events to create these structures are ongoing, and disrupted by NPs, which leads to the downstream effects. In contrast, the hatching embryos are most resistant to the Ag NPs, and majority of embryos (94%) develop normally, and none of them develop abnormally. Interestingly, early-gastrula embryos are less sensitive to the NPs than cleavage and segmentation stage embryos, and do not develop abnormally. These important findings suggest that the Ag NPs are not simple poisons, and they can target specific pathways in development, and potentially enable target specific study and therapy for early embryonic development.Much is anticipated from the development and deployment of nanomaterials in biological organisms, but concerns remain regarding their biocompatibility and target specificity. Here we report our study of the transport, biocompatibility and toxicity of purified and stable silver nanoparticles (Ag NPs, 13.1 +/- 2.5 nm in diameter) upon the specific developmental stages of zebrafish embryos using single NP plasmonic spectroscopy. We find that single Ag NPs passively diffuse into five different developmental stages of embryos (cleavage, early-gastrula, early-segmentation, late-segmentation, and hatching stages), showing stage-independent diffusion modes and diffusion coefficients. Notably, the Ag NPs induce distinctive stage and dose-dependent phenotypes and nanotoxicity, upon their acute exposure to the Ag NPs (0-0.7 nM) for only 2 h. The late-segmentation embryos are most sensitive to the NPs with the lowest critical concentration (CNP,c << 0.02 nM) and highest percentages of cardiac abnormalities, followed by early-segmentation embryos (CNP,c < 0.02 nM), suggesting that disruption of cell differentiation by the NPs causes the most toxic effects on embryonic development. The cleavage-stage embryos treated with the NPs develop into a wide variety of phenotypes (abnormal finfold, tail/spinal cord flexure, cardiac malformation/edema, yolk sac edema, and acephaly). These organ structures are not yet developed in cleavage-stage embryos, suggesting that the earliest determinative events to create these structures are ongoing, and disrupted by NPs, which leads to the downstream effects. In contrast, the hatching embryos are most resistant to the Ag NPs, and majority of embryos (94%) develop normally, and none of them develop abnormally. Interestingly, early-gastrula embryos are less sensitive to the NPs than cleavage and segmentation stage embryos, and do not develop abnormally. These important findings suggest that the Ag NPs are not simple poisons, and they can target specific pathways in development, and potentially enable target specific study and therapy for early embryonic development. Electronic supplementary information (ESI) available. See DOI: 10.1039/c3nr03210h
Besser, John M.; Mebane, Christopher A.; Mount, David R.; Ivey, Chris D.; Kunz, James L.; Greer, I. Eugene; May, Thomas W.; Ingersoll, Christopher G.
2007-01-01
Studies of fish communities of streams draining mining areas suggest that sculpins (Cottus spp.) may be more sensitive than salmonids to adverse effects of metals. We compared the toxicity of zinc, copper, and cadmium to mottled sculpin (C. bairdi) and rainbow trout (Onchorhynchus mykiss) in laboratory toxicity tests. Acute (96-h) and early life-stage chronic (21- or 28-d) toxicity tests were conducted with rainbow trout and with mottled sculpins from populations in Minnesota and Missouri, USA, in diluted well water (hardness = 100 mg/L as CaCO3). Acute and chronic toxicity of metals to newly hatched and swim-up stages of mottled sculpins differed between the two source populations. Differences between populations were greatest for copper, with chronic toxicity values (ChV = geometric mean of lowest-observed-effect concentration and no-observed-effect concentration) of 4.4 μg/L for Missouri sculpins and 37 μg/L for Minnesota sculpins. Cadmium toxicity followed a similar trend, but differences between sculpin populations were less marked, with ChVs of 1.1 μg/L (Missouri) and 1.9 μg/L (Minnesota). Conversely, zinc was more toxic to Minnesota sculpins (ChV = 75 μg/L) than Missouri sculpins (chronic ChV = 219 μg/L). Species-average acute and chronic toxicity values for mottled sculpins were similar to or lower than those for rainbow trout and indicated that mottled sculpins were among the most sensitive aquatic species to toxicity of all three metals. Our results indicate that current acute and chronic water quality criteria for cadmium, copper, and zinc adequately protect rainbow trout but may not adequately protect some populations of mottled sculpins. Proposed water quality criteria for copper based on the biotic ligand model would be protective of both sculpin populations tested.
Besser, J.M.; Mebane, C.A.; Mount, D.R.; Ivey, C.D.; Kunz, J.L.; Greer, I.E.; May, T.W.; Ingersoll, C.G.
2007-01-01
Studies of fish communities of streams draining mining areas suggest that sculpins (Cottus spp.) may be more sensitive than salmonids to adverse effects of metals. We compared the toxicity of zinc, copper, and cadmium to mottled sculpin (C. bairdi) and rainbow trout (Onchorhynchus mykiss) in laboratory toxicity tests. Acute (96-h) and early life-stage chronic (21- or 28-d) toxicity tests were conducted with rainbow trout and with mottled sculpins from populations in Minnesota and Missouri, USA, in diluted well water (hardness = 100 mg/L as CaCO3). Acute and chronic toxicity of metals to newly hatched and swim-up stages of mottled sculpins differed between the two source populations. Differences between populations were greatest for copper, with chronic toxicity values (ChV = geometric mean of lowest-observed-effect concentration and no-observed-effect concentration) of 4.4 ??g/L for Missouri sculpins and 37 ??g/L for Minnesota sculpins. Cadmium toxicity followed a similar trend, but differences between sculpin populations were less marked, with ChVs of 1.1 ??g/L (Missouri) and 1.9 ??g/L (Minnesota). Conversely, zinc was more toxic to Minnesota sculpins (ChV = 75 ??g/L) than Missouri sculpins (chronic ChV = 219 ??g/L). Species-average acute and chronic toxicity values for mottled sculpins were similar to or lower than those for rainbow trout and indicated that mottled sculpins were among the most sensitive aquatic species to toxicity of all three metals. Our results indicate that current acute and chronic water quality criteria for cadmium, copper, and zinc adequately protect rainbow trout but may not adequately protect some populations of mottled sculpins. Proposed water quality criteria for copper based on the biotic ligand model would be protective of both sculpin populations tested. ?? 2007 SETAC.
Casas-Mulet, Roser; Saltveit, Svein Jakob; Alfredsen, Knut Tore
2016-12-15
Alterations in hydrological and thermal regimes can potentially affect salmonid early life stages development and survival. The dewatering of salmon spawning redds due to hydropeaking can lead to mortality in early life stages, with higher impact on the alevins as they have lower tolerance to dewatering than the eggs. Flow-related mitigation measures can reduce early life stage mortality. We present a set of modelling tools to assess impacts and mitigation options to minimise the risk of mortality in early life stages in hydropeaking rivers. We successfully modelled long-term hydrological and thermal alterations and consequences for development rates. We estimated the risk of early life stages mortality and assessed the cost-effectiveness of implementing three release-related mitigation options (A,B,C). The economic cost of mitigation was low and ranged between 0.7% and 2.6% of the annual hydropower production. Options reducing the flow during spawning (B and C) in addition to only release minimum flows during development (A) were considered more effective for egg and alevin survival. Options B and C were however constraint by water availability in the system for certain years, and therefore only option A was always feasible. The set of modelling tools used in this study were satisfactory and their applications can be useful especially in systems where little field data is available. Targeted measures built on well-informed modelling tools can be tested on their effectiveness to mitigate dewatering effects vs. the hydropower system capacity to release or conserve water for power production. Environmental flow releases targeting specific ecological objectives can provide better cost-effective options than conventional operational rules complying with general legislation. Copyright © 2016 Elsevier B.V. All rights reserved.
Chlorine toxicity to early life stages of freshwater mussels (Bivalvia: Unionidae)
Valenti, T.W.; Cherry, D.S.; Currie, R.J.; Neves, R.J.; Jones, J.W.; Mair, R.; Kane, C.M.
2006-01-01
Chlorine (Cl) is a highly toxic, widely used halogen disinfectant that is present in point-source pollution discharges from wastewater treatment plants and industrial facilities. The U.S. Environmental Protection Agency freshwater criteria for Cl are 19 ??g total residual Cl (TRC)/L as a maximum 1-h average concentration and 11 ??g TRC/L as a maximum 4-d average; however, toxicological data for unionids were not used in these calculations. To address this void in the data, we conducted acute tests with glochidia from several species and 21-d bioassays with three-month-old Epioblasma capsaeformis and three-, six-, and 12-month-old Villosa iris juveniles. The 24-h lethal concentration 50 values for glochidia were between 70 and 220 ??g TRC/L, which are 2.5 to 37 times higher than those reported in other studies for cladocerans. Significant declines in growth and survivorship were observed in the 21-d test with E. capsaeformis at 20 ??g TRC/L. Lowest-observed-adverse- effects concentrations in bioassays with juvenile V. iris were higher (30-60 ??g TRC/L) but showed a significant trend of declining toxicity with increased age. Although endpoints were above water quality criteria, the long life spans of unionids and potential implications of chronic exposure to endangered juvenile mussels still warrant concern. ?? 2006 SETAC.
Xiong, Xiaoqin; Luo, Si; Wu, Benli; Wang, Jianwei
2017-02-01
Dimethyl sulfoxide (DMSO), a widely used carrier solvent, can be toxic to test organisms and has species-specific sensitivity. In this study, the developmental toxicity and stress protein responses of DMSO to rare minnow (Gobiocypris rarus) and zebrafish (Danio rerio) with two tests were compared in the early life stage. In the first test, fertilized eggs were exposed to 0%, 0.0001%, 0.001%, 0.01%, 0.1%, 1.0%, 1.5%, and 2.0% v/v of DMSO until 3 days post hatching. In the second test, larvae from 0 to 8 d were exposed to 2% DMSO until 4 days. Our results showed that DMSO was toxic to rare minnow and zebrafish on multiple indexes, and the no-observed-effect concentrations of DMSO in both species were 1.0% and 0.001% for developmental toxicity analysis and stress protein analysis, respectively. Furthermore, rare minnow larvae were more sensitive than zebrafish to DMSO for spinal malformation. The sensitive period for induction of spinal malformation by DMSO was 0-7 d after hatch (dah) for rare minnow and 0-4 dah for zebrafish. Together, these results will provide support to the use of DMSO in ecotoxicological studies using rare minnow and will contribute to a better understanding of the toxicity of DMSO.
Early Stages of the Evolution of Life: a Cybernetic Approach
NASA Astrophysics Data System (ADS)
Melkikh, Alexey V.; Seleznev, Vladimir D.
2008-08-01
Early stages of the evolution of life are considered in terms of control theory. A model is proposed for the transport of substances in a protocell possessing the property of robustness with regard to changes in the environmental concentration of a substance.
Early stages of the evolution of life: a cybernetic approach.
Melkikh, Alexey V; Seleznev, Vladimir D
2008-08-01
Early stages of the evolution of life are considered in terms of control theory. A model is proposed for the transport of substances in a protocell possessing the property of robustness with regard to changes in the environmental concentration of a substance.
Effects of the herbicides linuron and S-metolachlor on Perez's frog embryos.
Quintaneiro, Carla; Soares, Amadeu M V M; Monteiro, Marta S
2018-03-01
Presence of pesticides in the environment and their possible effects on aquatic organisms are of great concern worldwide. The extensive use of herbicides in agricultural areas are one of the factors contributing to the known decline of amphibian populations. Thus, as non-target species, amphibians can be exposed in early life stages to herbicides in aquatic systems. In this context, this study aims to evaluate effects of increasing concentrations of two maize herbicides, linuron and S-metolachlor on embryos of the Perez' frog (Pelophylax perezi) during 192 h. Apical endpoints were determined for each herbicide: mortality, hatching rate, malformations and length. Frog embryos presented a LC 50 of 21 mg/l linuron and 37.5 mg/l S-metolachlor. Furthermore, sub-lethal concentrations of both herbicides affected normal embryonic development, delaying hatching, decreasing larvae length and causing several malformations. Length of larvae decreased with increasing concentrations of each herbicide, even at the lower concentrations tested. Malformations observed in larvae exposed to both herbicides were oedemas, spinal curvature and deformation, blistering and microphtalmia. Overall, these results highlight the need to assess adverse effects of xenobiotics to early life stages of amphibians regarding beside mortality the embryonic development, which could result in impairments at later stages. However, to unravel mechanisms involved in toxicity of these herbicides further studies regarding lower levels of biological organisation such as biochemical and genomic level should be performed. Copyright © 2017 Elsevier Ltd. All rights reserved.
Raimondo, Sandy; Lilavois, Crystal R.; Lee, Larisa; Augspurger, Tom; Wang, Ning; Ingersoll, Christopher G.; Bauer, Candice R.; Hammer, Edward J.; Barron, Mace G.
2016-01-01
We developed a toxicity database for unionid mussels to examine the extent of intra- and inter-laboratory variability in acute toxicity tests with mussel larvae (glochidia) and juveniles; the extent of differential sensitivity of the two life stages; and the variation in sensitivity among commonly tested mussels (Lampsilis siliquoidea, Utterbackia imbecillis, Villosa iris), commonly tested cladocerans (Daphnia magna, Ceriodaphnia dubia) and fish (Oncorhynchus mykiss, Pimephales promelas, Lepomis macrochirus). The results of these analyses indicate intra-laboratory variability for median effect concentrations (EC50) averaged about 2 fold for both life stages, while inter-laboratory variability averaged 3.6 fold for juvenile mussels and 6.3 fold for glochidia. The EC50s for juveniles and glochidia were within a factor of 2 of each other for 50% of paired records across chemicals, with juveniles more sensitive than glochidia by more than 2 fold for 33% of the comparisons made between life stages. There was a high concurrence of the sensitivity of commonly tested L. siliquoidea, U. imbecillis, and V. iris to that of other mussels. However, this concurrence decreases as the taxonomic distance of the commonly tested cladocerans and fish to mussels increases. The compiled mussel database and determination of data variability will advance risk assessments by including more robust species sensitivity distributions, interspecies correlation estimates, and availability of taxon-specific empirically derived application factors for risk assessment.
The die is cast: arsenic exposure in early life and disease susceptibility.
Thomas, David J
2013-12-16
Early life exposure to arsenic in humans and mice produces similar patterns of disease in later life. Given the long interval between exposure and effect, epigenetic effects of early life exposure to arsenic may account for the development and progression of disease in both species. Mode of action and dosimetric studies in the mouse may help assess the role of age at exposure as a factor in susceptibility to the toxic and carcinogenic effects of arsenic in humans.
Small, William; James, Jennifer L; Moore, Timothy D; Fintel, Dan J; Lutz, Stephen T; Movsas, Benjamin; Suntharalingam, Mohan; Garces, Yolanda I; Ivker, Robert; Moulder, John; Pugh, Stephanie; Berk, Lawrence B
2018-04-01
The primary objective of NRG Oncology Radiation Therapy Oncology Group 0123 was to test the ability of the angiotensin-converting enzyme inhibitor captopril to alter the incidence of pulmonary damage after radiation therapy for lung cancer; secondary objectives included analyzing pulmonary cytokine expression, quality of life, and the long-term effects of captopril. Eligible patients included stage II-IIIB non-small cell lung cancer, stage I central non-small cell lung cancer, or limited-stage small cell. Patients who met eligibility for randomization at the end of radiotherapy received either captopril or standard care for 1 year. The captopril was to be escalated to 50 mg three times a day. Primary endpoint was incidence of grade 2+ radiation-induced pulmonary toxicity in the first year. Eighty-one patients were accrued between June 2003 and August 2007. Given the low accrual rate, the study was closed early. No significant safety issues were encountered. Eight patients were ineligible for registration or withdrew consent before randomization and 40 patients were not randomized postradiation. Major reasons for nonrandomization included patients' refusal and physician preference. Of the 33 randomized patients, 20 were analyzable (13 observation, 7 captopril). The incidence of grade 2+ pulmonary toxicity attributable to radiation therapy was 23% (3/13) in the observation arm and 14% (1/7) in the captopril arm. Despite significant resources and multiple amendments, NRG Oncology Radiation Therapy Oncology Group 0123 was unable to test the hypothesis that captopril mitigates radiation-induced pulmonary toxicity. It did show the safety of such an approach and the use of newer angiotensin-converting enzyme inhibitors started during radiotherapy may solve the accrual problems.
The interaction between stress and exercise, and its impact on brain function.
Russell, Vivienne A; Zigmond, Michael J; Dimatelis, Jacqueline J; Daniels, William M U; Mabandla, Musa V
2014-06-01
In response to acute adversity, emotional signals shift the body into a state that permits rapid detection, identification, and appropriate response to a potential threat. The stress response involves the release of a variety of substances, including neurotransmitters, neurotrophic factors, hormones, and cytokines, that enable the body to deal with the challenges of daily life. The subsequent activation of various physiological systems can be both protective and damaging to the individual, depending on timing, intensity, and duration of the stressor. Successful recovery from stressful challenges during early life leads to strengthening of synaptic connections in health-promoting neural networks and reduced vulnerability to subsequent stressors that can be protective in later life. In contrast, chronic intense uncontrollable stress can be pathogenic and lead to disorders such as depression, anxiety, hypertension, Alzheimer's disease, Parkinson's disease, and an increased toxic response to additional stressors such as traumatic brain injury and stroke. This review briefly explores the interaction between stress experienced at different stages of development and exercise later in life.
Kuivila, K.M.; Moon, G.E.
2004-01-01
The San Francisco Estuary is critical habitat for delta smelt Hypomesus transpacificus, a fish whose abundance has declined greatly since 1983 and is now listed as threatened. In addition, the estuary receives drainage from the Central Valley, an urban and agricultural region with intense and diverse pesticide usage. One possible factor of the delta smelt population decline is pesticide toxicity during vulnerable larval and juvenile stages, but pesticide concentrations are not well characterized in delta smelt spawning and nursery habitat. The objective of this study was to estimate the potential exposure of delta smelt during their early life stages to dissolved pesticides. For 3 years (1998-2000), water samples from the Sacramento-San Joaquin Delta were collected during April-June in coordination with the California Department of Fish and Game's delta smelt early life stage monitoring program. Samples were analyzed for pesticides using solid-phase extraction and gas chromatography/mass spectrometry. Water samples contained multiple pesticides, ranging from 2 to 14 pesticides in each sample. In both 1999 and 2000, elevated concentrations of pesticides overlapped in time and space with peak densities of larval and juvenile delta smelt. In contrast, high spring outflows in 1998 transported delta smelt away from the pesticide sampling sites so that exposure could not be estimated. During 2 years, larval and juvenile delta smelt were potentially exposed to a complex mixture of pesticides for a minimum of 2-3 weeks. Although the measured concentrations were well below short-term (96-h) LC50 values for individual pesticides, the combination of multiple pesticides and lengthy exposure duration could potentially have lethal or sublethal effects on delta smelt, especially during early larval development.
Guo, Dongmei; Wang, Yanhua; Qian, Yongzhong; Chen, Chen; Jiao, Bining; Cai, Leiming; Wang, Qiang
2017-01-01
It remains a daunting challenge to determine ecotoxicological risks of exposure to mixtures of endocrine disrupting chemicals (EDCs) in environmental toxicology. In the present study, we investigated acute and endocrine disruptive toxicities of cypermethrin (CPM), malathion (MAL), prochloraz (PRO) and their binary mixtures of MAL + CPM and MAL + PRO to the early life stages of zebrafish. In the acute lethal toxicity test, three pesticides exhibited different levels of toxicity to zebrafish larvae, and the order of toxicity was as follows: CPM > PRO > MAL. The binary mixture of MAL + CPM displayed a synergistic effect on zebrafish larvae after exposure for 24, 48, 72 and 96 h. However, binary mixture of MAL + PRO showed an antagonistic effect. To evaluate the estrogenic effect, the expression of genes in the hypothalamic-pituitary-gonadal axis was assessed after zebrafish embryos were exposed to CPM, MAL, PRO and their binary mixtures from blastula stage (1 h post-fertilization, 1 hpf) to 14 dpf (14 d post-fertilization). Our data indicated that the transcription patterns of many key genes (vtg1, vtg2, era, erβ1, erβ2, cyp19a1a and cyp19a1b) were affected in hatched zebrafish after exposure to CPM, MAL and PRO. Moreover, following exposure to binary mixtures of 1000 μg/L MAL +4 μg/L CPM and 1000 μg/L MAL +900 μg/L PRO, the gene expressions were significantly changed compared with the individual pesticides. Our data provided a better understanding of bidirectional interactions of toxic response induced by these pesticides. Copyright © 2016 Elsevier Ltd. All rights reserved.
Chen, Ze; Zhao, Zhe; Li, Yunzepeng; Zhang, Xingyu; Li, Bin; Chen, Liaobin; Wang, Hui
2018-04-01
Dexamethasone, a synthetic long-acting glucocorticoid, is routinely used for treating mothers at risk for preterm delivery. However, intrauterine overexposure to glucocorticoids induces low birth weight and cartilage dysplasia in offspring. Also, the "critical window" and safe dose of this treatment are largely unknown. This study investigated the course-, dose-, and stage-dependent toxic effects and the possible mechanisms of prenatal dexamethasone exposure (PDE) on fetal development and articular cartilage development. Pregnant mice (C57BL/6) received subcutaneous injection of dexamethasone (0.8 mg/kg d) once on gestational day (GD) 15 or once a day from GD 15 to 17, or received various doses of dexamethasone (0, 0.2, 0.8, and 1.2 mg/kg d) on GD 15-17, or received dexamethasone (0.8 mg/kg d) at early stage (GD 12-14) or late stage of pregnancy (GD 15-17). Offspring's knee joints were harvested at birth for morphological analyses and detection of gene expression. Repeated PDE significantly suppressed fetal and articular cartilage development, which were characterized by decreased body weight and body length, coarse articular cartilage surfaces, and reduced gene and protein expression of Col2a1 and aggrecan. For those newborns treated with repeated PDE at different doses, the toxic effects on fetal and articular cartilage development were observed at doses of 0.8 and 1.2 mg/kg d, whereas no obvious toxic effects were observed at the dose of 0.2 mg/kg d. Moreover, PDE at 0.8 mg/kg d during the early embryonic stage induced stronger toxic effects on fetal and articular cartilage development, compared with PDE during the late embryonic stage. Detection of gene expression showed that the TGFβ signaling pathway in the articular cartilage was down-regulated after PDE. Taken together, PDE induces fetal developmental toxicity and articular cartilage developmental toxicity in a course-, dose-, and stage-dependent manner. Copyright © 2018 Elsevier B.V. All rights reserved.
Exposure of juvenile Danio rerio to aged TiO₂ nanomaterial from sunscreen.
Fouqueray, Manuela; Noury, Patrice; Dherret, Lysiane; Chaurand, Perrine; Abbaci, Khedidja; Labille, Jerome; Rose, Jerome; Garric, Jeanne
2013-05-01
The toxicity of dietary exposure to artificially aged TiO₂ nanomaterial (T-Lite) used in sunscreen cream was studied on Danio rerio. Embryolarval assays were conducted to assess the effects of TiO₂ residues of nanomaterial (RNM) on fish early life stages. Juvenile fishes were exposed by the trophic route in two experiments. During the first experiment, juvenile fishes were exposed to TiO₂ RNM for 14 days by adding RNM to commercial fish food. The second one consisted in producing a trophic food chain. Pseudokirchneriella subcapitata algae, previously contaminated with TiO₂ RNM in growth medium, was used to feed Daphnia magna neonates over a 48-h period. Daphnia were used next to feed juvenile fishes for 7 days. Accumulation of Ti, life traits (survival and growth) and biochemical parameters such as energy reserves, digestive (trypsin, esterase, cellulose and amylase) and antioxidant (superoxide dismutase and catalase) enzyme activity were measured at the end of exposures. As expected in the receiving aquatic system, TiO2 RNM at low concentrations caused a low impact on juvenile zebrafish. A slight impact on the early life stage of zebrafish with premature hatching was observed, and this effect appeared mainly indirect, due to possible embryo hypoxia. When juvenile fish are exposed to contaminated food, digestive enzyme activity indicated a negative effect of TiO₂ RNM. Digestive physiology was altered after 14 days of exposure and seemed to be an indirect target of TiO₂ RNM when provided by food.
In May 2012, a HESI-sponsored expert workshop yielded a proposed research strategy for systematically discovering, characterizing, and annotating fish early life-stage (FELS) adverse outcome pathways (AOPs) as well as prioritizing AOP development in light of current restrictions ...
There is evidence that exposure to endocrine disrupting chemicals (EDCs) during early life stages can alter sex differentiation in fishes. Fathead minnows (Pimephales promelas) are commonly used as a model fish species in endocrine disruption studies. However, limited knowledge...
DOE Office of Scientific and Technical Information (OSTI.GOV)
Mayyas, E; Brown, S; Liu, J
Purpose: Stereotactic body radiotherapy (SBRT) is commonly used to treat early stage lung tumors. This study was designed to evaluate associations between dose, volume and clinical outcomes including analysis of both clinical toxicity scores and quality of life (QOL) data for non-small cell lung cancer patients treated with SBRT. Preliminary results are presented. Methods: Sixty-seven NSCLC patients, 46 primarily with early stage, and 21 with recurrent disease were treated with dose regimens consisting mainly of 12 Gy x 4 fractions, and 3 or 5 fractions at lower dose, for patients with recurrent disease (Table 1). Follow-up data is being collectedmore » at baseline, after treatment and at 3, 6, 12, 18 and 24 months post-treatment. Clinical follow-up data acquired to date was assessed using the Charlson Comorbidity Clinical and Toxicity Scoring forms. QOL data was evaluated using the EQ-5D, and FACT-TOI validated surveys. All outcomes surveys are collected within an “in-house” developed outcomes database. Results: The median follow-up was 3.5±0.8 months. Mean lung doses (MLD) were converted to BED-2 Gy using the linear-quadratic model with an alpha/beta=3.0. Average MLD was 3.7+3.1 Gy (range: 0.4–20.9 Gy). The percentages of patients with > grade 2 cough, dyspnea and fatigue were 13.3, 17.0, 6.3%, respectively. Preliminary analyses (at 3 months after SBRT) show a mild correlation between MLD > 2 Gy and > grade 2 cough (borderline significant) and dyspnea (significant, p<0.05). One patient was observed with a grade 3 cough. Given the short follow-up, tumor control is not yet assessable. Conclusion: The SBRT dose fractionation regimen of 12 Gy x 4 was well tolerated at early time points. Additional follow-up is required to assess the long-term clinical outcome efficacy and toxicity profiles of the dose regimen.« less
Studies have shown correlations between in utero and early life environments and diseases later in life, including hypertension, coronary heart disease, diabetes, obesity, schizophrenia, early onset chronic renal failure, cancer and compromised repro-duction. Current development...
Acute toxicity of polyacrylamide flocculants to early life stages of freshwater mussels
Buczek, Sean B.; Cope, W. Gregory; McLaughlin, Richard A.; Kwak, Thomas J.
2017-01-01
Polyacrylamide has become an effective tool for reducing construction-related suspended sediment and turbidity, which are considered to have significant adverse impacts on aquatic ecosystems and are a leading cause of the degradation of North American streams and rivers. However, little is known about the effects of polyacrylamide on many freshwater organisms, and prior to the present study, no information existed on the toxicity of polyacrylamide compounds to native freshwater mussels (family Unionidae), one of the most imperiled faunal groups globally. Following standard test guidelines, we exposed juvenile mussels (test duration 96 h) and glochidia larvae (test duration 24 h) to 5 different anionic polyacrylamide compounds and 1 non-ionic compound. Species tested included the yellow lampmussel (Lampsilis cariosa), an Atlantic Slope species that is listed as endangered in North Carolina; the Appalachian elktoe (Alasmidonta raveneliana), a federally endangered Interior Basin species; and the washboard (Megalonaias nervosa), a common Interior Basin species. We found that median lethal concentrations (LC50s) of polyacrylamide ranged from 411.7 to >1000 mg/L for glochidia and from 126.8 to >1000 mg/L for juveniles. All LC50s were orders of magnitude greater (2–3) than concentrations typically recommended for turbidity control (1–5 mg/L), regardless of their molecular weight or charge density. The results demonstrate that the polyacrylamide compounds tested were not acutely toxic to the mussel species and life stages tested, indicating minimal risk of short-term exposure from polyacrylamide applications in the environment. However, other potential uses of polyacrylamide in the environment (e.g., wastewater treatment, paper processing, mining, algae removal) and their chronic or sublethal effects remain uncertain and warrant additional investigation.
Living with early-stage dementia: a review of qualitative studies.
Steeman, Els; de Casterlé, Bernadette Dierckx; Godderis, Jan; Grypdonck, Mieke
2006-06-01
This paper presents a literature review whose aim was to provide better understanding of living with early-stage dementia. Even in the early stages, dementia may challenge quality of life. Research on early-stage dementia is mainly in the domain of biomedical aetiology and pathology, providing little understanding of what it means to live with dementia. Knowledge of the lived experience of having dementia is important in order to focus pro-active care towards enhancing quality of life. Qualitative research is fundamentally well suited to obtaining an insider's view of living with early-stage dementia. We performed a meta-synthesis of qualitative research findings. We searched MEDLINE, CINAHL, and PsycINFO and reviewed the papers cited in the references of pertinent articles, the references cited in a recently published book on the subjective experience of dementia, one thesis, and the journal Dementia. Thirty-three pertinent articles were identified, representing 28 separate studies and 21 different research samples. Findings were coded, grouped, compared and integrated. Living with dementia is described from the stage a person discovers the memory impairment, through the stage of being diagnosed with dementia, to that of the person's attempts to integrate the impairment into everyday life. Memory loss often threatens perceptions of security, autonomy and being a meaningful member of society. At early stages of memory loss, individuals use self-protecting and self-adjusting strategies to deal with perceived changes and threats. However, the memory impairment itself may make it difficult for an individual to deal with these changes, thereby causing frustration, uncertainty and fear. Our analysis supports the integration of proactive care into the diagnostic process, because even early-stage dementia may challenge quality of life. Moreover, this care should actively involve both the individual with dementia and their family so that both parties can adjust positively to living with dementia.
Robles-Mendoza, C; García-Basilio, C; Cram-Heydrich, S; Hernández-Quiroz, M; Vanegas-Pérez, C
2009-02-01
Ambystoma mexicanum is an endemic salamander of Xochimilco, a wetland of the basin of Mexico valley. Nowadays, axolotl populations are decreasing due environmental stressors. Particularly, studies about organophosphorus pesticides (OPPs; i.e. chlorpyrifos and malathion) toxicity are of great importance due to their intensive use in agricultural activities in Xochimilco. Thus, the aim of this study was to evaluate under controlled conditions the toxicity of chlorpyrifos (CPF) and malathion (MLT) on embryos and larvae (stage 44 and 54) of A. mexicanum. Embryos and larvae were exposure 96h from 0.5 to 3mg CPFL(-1) and from 10 to 30mg MLTL(-1) in independent tests. Embryos at the end of this period were maintained 9d without pesticide in order to identify possible recuperation. Differences obtained in mortality, hatching success, development, morphological abnormalities, behaviour and activity, suggest that toxicity of CPF and MLT differs in embryos and larval stages. Embryos were less sensitive to OPPs acute exposure than axolotl larvae; additionally, toxicity of CPF in larval stages was greater than MLT. On the other hand, data obtained in axolotl embryos during the period of recuperation to CPF in particular as delay and inhibition of development, malformations and success of hatching, indicated that these responses turned out more sensitive than mortality. This study allowed to identify the toxicological potential of OPPs on early developmental stages of A. mexicanum and it is a valuable contribution for the future management of the axolotl wild population.
Liu, Lei; Jiang, Chao; Wu, Zhuo-Qi; Gong, Yu-Xin; Wang, Gao-Xue
2013-12-01
The strobilurins are used widely in the world as effective fungicidal agents to control Asian soybean rust. In this study, the early life stage of grass carp (Ctenopharyngodon idella), which is one of the most important aquaculture species in China, was chosen to measure the acute toxicity of three common strobilurin-derived fungicides (trifloxystrobin (TFS), azoxystrobin (AZ) and kresoxim-methyl (KM)). As endpoints, normal developmental parameters (lethal concentration (LC₅₀) and average heart rate), expression of relative genes, and three antioxidant enzyme activities in the developing juveniles were recorded during a 48 h exposure. The results revealed that values of LC₅₀ were TFS 0.051 (0.046-0.058) mg L⁻¹, AZ 0.549 (0.419-0.771) mg L⁻¹ and KM 0.338 (0.284-0.407) mg L⁻¹ for juveniles. For the potential toxicity mechanisms, these three fungicides increased catalase (CAT) and peroxidase (POD) activity and decreased superoxide dismutase (SOD) activity, significantly inhibited expressions of three growth-related genes (IGF-1, IGF-2 and GHR) and two energy-related-genes (CCK and PYY), and caused pronounced up-regulation a stress-gene (HSP70). The present study demonstrated potential toxic effects of TFS, AZ and KM on the early development of C. idella. Overall, three strobilurins (TFS, AZ and KM) might cause serious damages to the aquatic species; therefore, their pollution supervision in water ecological environment should be strengthened.
Durán, I; Beiras, R
2013-10-01
Acute water quality criteria (WQC) for the protection of coastal ecosystems are developed on the basis of short-term ecotoxicological data using the most sensitive life stages of representative species from the main taxa of marine water column organisms. A probabilistic approach based on species sensitivity distribution (SSD) curves has been chosen and compared to the WQC obtained applying an assessment factor to the critical toxicity values, i.e. the 'deterministic' approach. The criteria obtained from HC5 values (5th percentile of the SSD) were 1.01 μg/l for Hg, 1.39 μg/l for Cu, 3.83 μg/l for Cd, 25.3 μg/l for Pb and 8.24 μg/l for Zn. Using sensitive early life stages and very sensitive endpoints allowed calculation of WQC for marine coastal ecosystems. These probabilistic WQC, intended to protect 95% of the species in 95% of the cases, were calculated on the basis of a limited ecotoxicological dataset, avoiding the use of large and uncertain assessment factors. Copyright © 2013 Elsevier B.V. All rights reserved.
Duffy, T A; Iwanowicz, L R; McCormick, S D
2014-07-01
Atlantic salmon (Salmo salar) are endangered anadromous fish that may be exposed to feminizing endocrine disrupting compounds (EDCs) during early development, potentially altering physiological capacities, survival and fitness. To assess differential life stage sensitivity to common EDCs, we carried out short-term (4 day) exposures using three doses each of 17 α-ethinylestradiol (EE2), 17 β-estradiol (E2), and nonylphenol (NP) on four early life stages; embryos, yolk-sac larvae, feeding fry and 1 year old smolts. Differential response was compared using vitellogenin (Vtg, a precursor egg protein) gene transcription. Smolts were also examined for impacts on plasma Vtg, cortisol, thyroid hormones (T4/T3) and hepatosomatic index (HSI). Compound-related mortality was not observed in any life stage, but Vtg mRNA was elevated in a dose-dependent manner in yolk-sac larvae, fry and smolts but not in embryos. The estrogens EE2 and E2 were consistently stronger inducers of Vtg than NP. Embryos responded significantly to the highest concentration of EE2 only, while older life stages responded to the highest doses of all three compounds, as well as intermediate doses of EE2 and E2. Maximal transcription was greater for fry among the three earliest life stages, suggesting fry may be the most responsive life stage in early development. Smolt plasma Vtg was also significantly increased, and this response was observed at lower doses of each compound than was detected by gene transcription suggesting plasma Vtg is a more sensitive indicator at this life stage. HSI was increased at the highest doses of EE2 and E2, and plasma T3 was decreased at the highest dose of EE2. Our results indicate that all life stages are potentially sensitive to endocrine disruption by estrogenic compounds and that physiological responses were altered over a short window of exposure, indicating the potential for these compounds to impact fish in the wild. Copyright © 2014 Elsevier B.V. All rights reserved.
Acute and sub-chronic toxicity of four cytostatic drugs in zebrafish.
Kovács, Róbert; Bakos, Katalin; Urbányi, Béla; Kövesi, Judit; Gazsi, Gyöngyi; Csepeli, Andrea; Appl, Ádám János; Bencsik, Dóra; Csenki, Zsolt; Horváth, Ákos
2016-08-01
The acute and sub-chronic effects of four cytostatic drugs-5-fluorouracil (5-FU), cisplatin (CisPt), etoposide (ET) and imatinib mesylate (IM)-on zebrafish (Danio rerio) were investigated. Acute tests were carried out in a static system in accordance with the OECD guideline 203 for adult fish and the draft guideline for fish embryos (FET test) in order to find the LC50 values of the four cytostatic drugs. Early-life stage toxicity test on zebrafish was conducted according the OECD guideline 210 using the cytostatic drugs 5-FU and IM in a semistatic system with the objective of investigating the sub-chronic effects of the cytostatic drugs on fish. In adult fish, the cytostatic drugs 5-FU and ET did not pass the limit test, thus, are considered non-toxic. In case of cisplatin, LC50 was calculated at 64.5 mg L(-1), whereas in case of IM, LC50 was at 70.8 mg L(-1). In the FET test, LC50 of 5-FU at 72-h post fertilization (hpf) was 2441.6 mg L(-1). In case of CisPt, LC50 was 349.9 mg L(-1) at 48 hpf and it progressively decreased to 81.3 mg L(-1) at 120 hpf. In addition, CisPt caused a significant delay in the hatch of larvae. In case of ET, LC50 values were not calculable as they were higher than 300 mg L(-1) at which concentration the substance crystallized in the solution. LC50 values of IM were 48 hpf; 158.3 mg L(-1) , 72 hpf; 141.6 mg L(-1), 96 hpf; 118.0 mg L(-1), and 120 hpf; 65.9 mg L(-1). In the Early-life Stage Test with 5-FU, embryonic deformities were not detected during the tests. Regarding mortalities, the 10 mg L(-1) concentration can be considered as LOEC, as statistically significant difference in mortalities was detected in this group alone. Concerning dry body weight and standard length, 1 mg L(-1) is the LOEC. In case of IM, the highest tested concentration (10 mg L(-1)) can be considered LOEC for mortalities, however, the treatment did not have an effect on the other investigated parameters (dry and wet weight, standard length). All four cytostatic drugs were characterized by low toxicity in zebrafish in acute and sub-chronic tests.
Effects of the insecticide permethrin on three life stages of the grass shrimp, Palaemonetes pugio.
DeLorenzo, M E; Serrano, L; Chung, K W; Hoguet, J; Key, P B
2006-06-01
Toxicity of the pyrethroid insecticide permethrin was assessed using three life stages of the estuarine grass shrimp, Palaemonetes pugio. Adult and larval shrimp were tested with and without sediment. An aqueous embryo test was also conducted. Cellular stress biomarkers, glutathione, and lipid peroxidation, were assessed. Larval shrimp were the most sensitive life stage with a 96-h lethal concentration (LC(50)) value of 0.05 microg/L, compared to 0.25 microg/L for adults, and 6.4 microg/L for embryos. The presence of sediment significantly decreased toxicity of permethrin to both adult and larval shrimp. Permethrin exposure increased time to hatch in embryos and decreased swimming behavior of larvae. Lipid peroxidation levels were significantly decreased in the adult shrimp, but increased in larval shrimp exposed to permethrin. Low levels of permethrin may negatively affect grass shrimp health and survival. Permethrin use in the coastal zone should be carefully managed to avoid adverse impacts on nontarget estuarine organisms.
Current Development in Reproductive Toxicity Testing of Pesticides
A protocol to evaluate the potential developmental and reproductive effects of test chemicals has been developed by the Life Stages Task Force of the International Life Sciences Institute (ILSI)/Health and Environmental Sciences Institute (HESI) Agricultural Chemical Safety Asses...
Reproductive Toxicity of T Cells in Early Life: Abnormal Immune Development and Postnatal Diseases.
Liu, Han-Xiao; Jiang, Aifang; Chen, Ting; Qu, Wen; Yan, Hui-Yi; Ping, Jie
2017-01-01
Immunity is a balanced status with adequate biological defenses to recognize and fight "non-self", as well as adequate tolerance to recognize "self". To maintain this immune homeostasis, a well-organized T cell immune network is required, which in part depends on the well-controlled development of alternative effector T cells, with different cytokine repertoires. Recent researches have pointed that developing fetal T cells network is a remarkably sensitive toxicological target for adverse factors in early life. Epidemiological and experimental studies showed an inseparable relationship between T cell developmental toxicity and immune diseases in adults. Considering that the inflammatory and immune disorders have become a growing health problem worldwide, increasing attention is now being paid to the T cell developmental toxicity. We propose that adverse factors may have programming effects on the crucial functions of immune system during early life which is critical for fetal T cell development and the establishment of the distinct T cell repertoires balance. The permanently disturbed intrathymic or peripheral T cell development may in turn lead to the immune disorders in later life. In this manuscript, we reviewed how adverse factors affected T cell development in early-life with the consequence of the immune dysfunction and immune diseases, and further elucidate the mechanisms. These mechanisms will be helpful in prevention and treatment of the increased prevalence of immune diseases by interfering those pathways. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
Multiphoton laser scanning micrsocopy holds promise as a tool to study the tissue distribution of environmental chemical contaminants during fish early life stage development. One such chemical for which this is possible is benzo[a]pyrene (BaP), a polyaromatic hydrocarbon that a...
USDA-ARS?s Scientific Manuscript database
Climate change effects on plants are expected to be primarily mediated through early life stage transitions. Snowfall variability, in particular, may have profound impacts on seedling recruitment; structuring plant populations and communities, especially in mid-latitude systems. These water-limi...
Sims, Ian; Crane, Mark; Johnson, Ian; Credland, Peter
2009-10-01
This paper examines the impact of an industrial point-source atmospheric emission on the feeding of early life stages of a terrestrial invertebrate. Larvae of a bagworm moth, Luffia ferchaultella [Stephens], were fed terrestrial epiphytic algae (Desmococcus viridis [Menegh]) collected from five sites located along a 16 km transect around the Avonmouth zinc smelter. After 10 days of exposure symptoms of lethal and sublethal toxicity (mortality and paralysis) were observed. Reductions in the amount of faecal material (frass) produced were also identified, and these correlated with distance downwind of the smelter. The elevated concentrations of lead, mercury, arsenic, antimony, copper, cadmium, lead and nickel present in the algae could account for these symptoms of toxicity. Similar symptoms were observed when larvae were fed algae spiked with inorganic mercury. These results are consistent with other studies of soil toxicity conducted around the Avonmouth smelter. However, the current study suggests that the impacted area exceeds this 16 km transect and demonstrates the value of bagmoth larvae as sensitive biomonitors of metallic atmospheric pollutants above the rhizosphere.
Lucas, Brett T; Quinteros, Claudio; Burnett-Seidel, Charlene; Elphick, James R
2017-06-01
Limited data are available describing the aquatic toxicity of molybdenum in freshwater environments, making it difficult to assess the aquatic risk to freshwater organisms. In order to increase available information on the aquatic toxicity of molybdenum, a 96-h LC50 test with the oligochaete Tubifex tubifex and an 85-day development test using brown trout, Salmo trutta, were conducted. The T. tubifex test resulted in an LC50 value of 2782 mg/L. No adverse effects were observed on brown trout survival or length in the concentrations tested, however an IC10 value for growth (wet weight) was determined to be 202 mg/L. Whole body fish tissue concentrations for molybdenum increased in all treatment concentrations tested, although bioconcentration factors decreased at greater exposure concentrations, and ranged from 0.13 at an exposure concentration of 20 mg/L to 0.04 at an exposure of 1247 mg/L. A body burden of 26.0 mg/kg was associated with reduced wet weight.
Cope, W.G.; Bringolf, R.B.; Buchwalter, D.B.; Newton, T.J.; Ingersoll, C.G.; Wang, N.; Augspurger, T.; Dwyer, F.J.; Barnhart, M.C.; Neves, R.J.; Hammer, E.
2008-01-01
Freshwater mussels (superfamily Unionoidea) are in serious global decline and in urgent need of protection and conservation. The declines have been attributed to a wide array of human activities resulting in pollution and water-quality degradation, and habitat destruction and alteration. Linkages among poor water quality, pollutant sources, and mussel decline in rivers and streams have been associated with results of laboratory-based tests of specific pollutants. However, uncertainties remain about the relationship of laboratory data to actual contaminant exposure routes for various mussel species, life stages, and in the habitats occupied during these exposures. We evaluated the pathways of exposure to environmental pollutants for all 4 life stages (free glochidia, encysted glochidia, juveniles, adults) of unionoidean mussels and found that each life stage has both common and unique characteristics that contribute to observed differences in exposure and sensitivity. Free glochidia typically are exposed only briefly (e.g., seconds to days) through surface water, whereas adults sustain exposure over years to decades through surface water, pore water, sediment, and diet. Juveniles live largely burrowed in the sediment for the first 0 to 4 y of life. Thus, sediment, pore water, and diet are the predominant exposure routes for this life stage, but surface water also might contribute to exposure during certain periods and environmental conditions. The obligate parasitic stage (encysted glochidia stage) on a host fish might be exposed from surface water while partially encysted or from toxicants in host-fish tissue while fully encysted. Laboratory methods for testing for acute and chronic exposures in water have advanced, and toxicant-specific information has increased in recent years. However, additional research is needed to understand interactions of life history, habitat, and long-term exposure to contaminants through water, pore water, sediment, and diet so that the risks of environmental exposures can be properly assessed and managed. ?? 2008 by The North American Benthological Society.
TOXICITY PATHWAY ANALYSIS IN AGING BROWN NORWAY RAT BRAIN FOLLOWING ACUTE TOLUENE EXPOSURE
The influence of aging on susceptibility to environmental stressors is poorly understood. To investigate the contribution of different life stages on response to toxicants, we examined the effects of acute exposure by oral gavage of the volatile organic solvent toluene (0.00, 0.3...
Cook, R.; Jones, D. L.; Nehra, R.; Kumar, A. M.; Prabhakar, S.; Waldrop-Valverde, D.; Sharma, S.; Kumar, M.
2017-01-01
HIV disease progression is associated with declining quality of life and overall health status, although most research in this domain has been conducted among Western populations where B is the infecting clade. This study sought to determine the effects of early-stage clade-C HIV infection (CD4 count ≥400 cells/mm3) on neurocognitive functioning, cognitive depression, and fatigue by comparing a matched sample of HIV-positive and HIV-negative Northern Indians. This study also examined the impact of these factors on quality of life within the HIV-positive individuals. HIV-positive participants demonstrated reduced cognitive functioning, increased fatigue, and lower quality of life. Fatigue and cognitive impairment interacted to negatively impact quality of life. Results suggest that early-stage HIV clade-C-infected individuals may experience subclinical symptoms, and further research is needed to explore the benefit of therapeutic interventions to ensure optimal clinical outcomes and maintain quality of life in this vulnerable population. PMID:23722088
Cook, R; Jones, D L; Nehra, R; Kumar, A M; Prabhakar, S; Waldrop-Valverde, D; Sharma, S; Kumar, M
2016-07-01
HIV disease progression is associated with declining quality of life and overall health status, although most research in this domain has been conducted among Western populations where B is the infecting clade. This study sought to determine the effects of early-stage clade-C HIV infection (CD4 count ≥400 cells/mm(3)) on neurocognitive functioning, cognitive depression, and fatigue by comparing a matched sample of HIV-positive and HIV-negative Northern Indians. This study also examined the impact of these factors on quality of life within the HIV-positive individuals. HIV-positive participants demonstrated reduced cognitive functioning, increased fatigue, and lower quality of life. Fatigue and cognitive impairment interacted to negatively impact quality of life. Results suggest that early-stage HIV clade-C-infected individuals may experience subclinical symptoms, and further research is needed to explore the benefit of therapeutic interventions to ensure optimal clinical outcomes and maintain quality of life in this vulnerable population. © The Author(s) 2013.
Advances in understanding the response of fish to linear alcohols in the environment.
Belanger, Scott E; Rawlings, Jane M; Stackhouse, Ricky
2018-09-01
Short to long chain alcohols have a range of ecotoxicity to aquatic life driven by hydrophobic interactions with biological membranes. Carbon chain length and octanol:water partitioning coefficients are surrogates for hydrophobicity and strongly relate to aquatic toxicity. In these investigations, the toxicity of ethanol to 1-n-dodecanol to juvenile fish in standard acute toxicity tests is reviewed. Toxicity tests employing fish embryos (zebrafish Danio rerio and fathead minnow Pimephales promelas) in the Fish Embryo Test (OECD 236) format were conducted from C2 to C10 to compare against standard juvenile fish toxicity. Quantitative structure activity relationships for FET and fish individually and combined demonstrate that embryos are not different in sensitivity to juvenile fish. A combined QSAR was developed of the form Log 96 h LC50 (mM/L) = -0.925*log Kow + 2.060 (R2 10 = 0.954). Alcohols of 11-12 carbons show a deflection in the QSAR as toxicity approaches the solubility limit. Alcohols with longer chain lengths may only be tested at lower exposures relevant for chronic toxicity. Decanol was evaluated in a 33-d fish early life stage test (OECD 210) and survival was the most sensitive endpoint (EC10 = 0.43 mg/L, 0.0027 mM/L). This study suggests a reasonable acute to chronic ratio of 6.5 in line with historical literature for non-polar narcotic compounds. Fish are not uniquely more sensitive than Daphnia magna which suggests estimations of environmental hazard can be confidently made with either taxon. The overall environmental risk assessments for the longer chain alcohols included in this research remain largely unchanged primarily due to previous research demonstrating a very minimal environmental exposure even for highly toxic members of the category. Copyright © 2018 Elsevier Ltd. All rights reserved.
Seven fractions to deliver partial breast irradiation: the toxicity is Low.
Trovo, Marco; Avanzo, Michele; Vinante, Lorenzo; Furlan, Carlo; Fiorica, Francesco; Perin, Tiziana; Militello, Loredana; Spazzapan, Simon; Berretta, Massimiliano; Jena, Rajesh; Stancanello, Joseph; Piccoli, Erica; Mileto, Mario; Micheli, Elvia; Roncadin, Mario; Massarut, Samuele
2017-05-23
To assess toxicity and clinical outcome, in breast cancer patients treated with external beam partial breast irradiation (PBI) consisting of 35 Gy in 7 daily fractions (5 Gy/fraction). Patients affected by early-stage breast cancer were enrolled in this phase II trial. Patients had to be 60 years old or over and treated with breast conservative surgery for early stage invasive carcinoma. Seventy-three patients were analyzed. Median follow-up was 40 months. The proposed schedule was well tolerated. No Grade 3 toxicity was documented. Late toxicity was assessable for all the treated patients. Two patients (2.7%) developed Grade 2 pain 6 months after PBI. Four patients (5%) developed asymptomatic fat necrosis. Grade 2 fibrosis was observed in 5 patients (6.7%). No correlation was found between early and late toxicity and the type of adjuvant systemic therapy (no therapy vs. hormonal therapy vs. chemotherapy). No statistical correlation between dosimetric parameters and toxicity was found. Patients who developed Grade 2 radiation fibrosis had not higher radiation volumes to the untreated normal breast than those without fibrosis. Cosmesis was judged good/excellent in the majority of the cases (93%). One patient relapsed locally, and one developed distant metastases, corresponding to a 5-year local control and distant metastases-free survival of 98% and 96.7%, respectively. 35 Gy in 7 daily fractions is an effective and well-tolerated regimen to deliver PBI.
Leite, Maria Bernadete Neiva Lemos; de Araújo, Milena Maria Sampaio; Nascimento, Iracema Andrade; da Cruz, Andrea Cristina Santos; Pereira, Solange Andrade; do Nascimento, Núbia Costa
2011-04-01
Concerns over the sustained availability of fossil fuels and their impact on global warming and pollution have led to the search for fuels from renewable sources to address worldwide rising energy demands. Biodiesel is emerging as one of the possible solutions for the transport sector. It shows comparable engine performance to that of conventional diesel fuel, while reducing greenhouse gas emissions. However, the toxicity of products and effluents from the biodiesel industry has not yet been sufficiently investigated. Brazil has a very high potential as a biodiesel producer, in view of its climatic conditions and vast areas for cropland, with consequent environmental risks because of possible accidental biodiesel spillages into water bodies and runoff to coastal areas. This research determined the toxicity to two marine organisms of the water-soluble fractions (WSF) of three different biodiesel fuels obtained by methanol transesterification of castor oil (CO), palm oil (PO), and waste cooking oil (WCO). Microalgae and sea urchins were used as the test organisms, respectively, for culture-growth-inhibition and early-life-stage-toxicity tests. The toxicity levels of the analyzed biodiesel WSF showed the highest toxicity for the CO, followed by WCO and the PO. Methanol was the most prominent contaminant; concentrations increased over time in WSF samples stored up to 120 d. Copyright © 2010 SETAC.
Morgana, Silvia; Gambardella, Chiara; Falugi, Carla; Pronzato, Roberto; Garaventa, Francesca; Faimali, Marco
2016-04-01
Behavioral endpoints have been used for decades to assess chemical impacts at concentrations unlikely to cause mortality. With recently developed techniques, it is possible to investigate the swimming behavior of several organisms under laboratory conditions. The aims of this study were: i) assessing for the first time the feasibility of swimming speed analysis of the early developmental stage sea urchin Paracentrotus lividus by an automatic recording system ii) investigating any Swimming Speed Alteration (SSA) on P. lividus early stages exposed to a chemical reference; iii) identifying the most suitable stage for SSA test. Results show that the swimming speed of all the developmental stages was easily recorded. The swimming speed was inhibited as a function of toxicant concentration. Pluteus were the most appropriate stage for evaluating SSA in P. lividus as ecotoxicological endpoint. Finally, swimming of sea urchin early stages represents a sensitive endpoint to be considered in ecotoxicological investigations. Copyright © 2016 Elsevier Ltd. All rights reserved.
Dose-Escalated Robotic SBRT for Stage I–II Prostate Cancer
Meier, Robert
2015-01-01
Stereotactic body radiotherapy (SBRT) is the precise external delivery of very high-dose radiotherapy to targets in the body, with treatment completed in one to five fractions. SBRT should be an ideal approach for organ-confined prostate cancer because (I) dose-escalation should yield improved rates of cancer control; (II) the unique radiobiology of prostate cancer favors hypofractionation; and (III) the conformal nature of SBRT minimizes high-dose radiation delivery to immediately adjacent organs, potentially reducing complications. This approach is also more convenient for patients, and is cheaper than intensity-modulated radiotherapy (IMRT). Several external beam platforms are capable of delivering SBRT for early-stage prostate cancer, although most of the mature reported series have employed a robotic non-coplanar platform (i.e., CyberKnife). Several large studies report 5-year biochemical relapse rates which compare favorably to IMRT. Rates of late GU toxicity are similar to those seen with IMRT, and rates of late rectal toxicity may be less than with IMRT and low-dose rate brachytherapy. Patient-reported quality of life (QOL) outcomes appear similar to IMRT in the urinary domain. Bowel QOL may be less adversely affected by SBRT than with other radiation modalities. After 5 years of follow-up, SBRT delivered on a robotic platform is yielding outcomes at least as favorable as IMRT, and may be considered appropriate therapy for stage I–II prostate cancer. PMID:25905037
Bi, Xi-Wen; Li, Ye-Xiong; Fang, Hui; Jin, Jing; Wang, Wei-Hu; Wang, Shu-Lian; Liu, Yue-Ping; Song, Yong-Wen; Ren, Hua; Dai, Jian-Rong
2013-12-01
To assess the dosimetric benefit, treatment outcome, and toxicity of high-dose and extended-field intensity modulated radiation therapy (IMRT) in patients with early-stage NK/T-cell lymphoma of Waldeyer's ring (WR-NKTCL). Thirty patients with early-stage WR-NKTCL who received extended-field IMRT were retrospectively reviewed. The prescribed dose was 50 Gy to the primary involved regions and positive cervical lymph nodes (planning target volume requiring radical irradiation [PTV50]) and 40 Gy to the negative cervical nodes (PTV40). Dosimetric parameters for the target volume and critical normal structures were evaluated. Locoregional control (LRC), overall survival (OS), and progression-free survival (PFS) were calculated using the Kaplan-Meier method. The median mean doses to the PTV50 and PTV40 were 53.2 Gy and 43.0 Gy, respectively. Only 1.4% of the PTV50 and 0.9% of the PTV40 received less than 95% of the prescribed dose, indicating excellent target coverage. The average mean doses to the left and right parotid glands were 27.7 and 28.4 Gy, respectively. The 2-year OS, PFS, and LRC rates were 71.2%, 57.4%, and 87.8%. Most acute toxicities were grade 1 to 2, except for grade ≥3 dysphagia and mucositis. The most common late toxicity was grade 1-2 xerostomia, and no patient developed any ≥grade 3 late toxicities. A correlation between the mean dose to the parotid glands and the degree of late xerostomia was observed. IMRT achieves excellent target coverage and dose conformity, as well as favorable survival and locoregional control rates with acceptable toxicities in patients with WR-NKTCL. Copyright © 2013 Elsevier Inc. All rights reserved.
Modelling interactions of toxicants and density dependence in wildlife populations
Schipper, Aafke M.; Hendriks, Harrie W.M.; Kauffman, Matthew J.; Hendriks, A. Jan; Huijbregts, Mark A.J.
2013-01-01
1. A major challenge in the conservation of threatened and endangered species is to predict population decline and design appropriate recovery measures. However, anthropogenic impacts on wildlife populations are notoriously difficult to predict due to potentially nonlinear responses and interactions with natural ecological processes like density dependence. 2. Here, we incorporated both density dependence and anthropogenic stressors in a stage-based matrix population model and parameterized it for a density-dependent population of peregrine falcons Falco peregrinus exposed to two anthropogenic toxicants [dichlorodiphenyldichloroethylene (DDE) and polybrominated diphenyl ethers (PBDEs)]. Log-logistic exposure–response relationships were used to translate toxicant concentrations in peregrine falcon eggs to effects on fecundity. Density dependence was modelled as the probability of a nonbreeding bird acquiring a breeding territory as a function of the current number of breeders. 3. The equilibrium size of the population, as represented by the number of breeders, responded nonlinearly to increasing toxicant concentrations, showing a gradual decrease followed by a relatively steep decline. Initially, toxicant-induced reductions in population size were mitigated by an alleviation of the density limitation, that is, an increasing probability of territory acquisition. Once population density was no longer limiting, the toxicant impacts were no longer buffered by an increasing proportion of nonbreeders shifting to the breeding stage, resulting in a strong decrease in the equilibrium number of breeders. 4. Median critical exposure concentrations, that is, median toxicant concentrations in eggs corresponding with an equilibrium population size of zero, were 33 and 46 μg g−1 fresh weight for DDE and PBDEs, respectively. 5. Synthesis and applications. Our modelling results showed that particular life stages of a density-limited population may be relatively insensitive to toxicant impacts until a critical threshold is crossed. In our study population, toxicant-induced changes were observed in the equilibrium number of nonbreeding rather than breeding birds, suggesting that monitoring efforts including both life stages are needed to timely detect population declines. Further, by combining quantitative exposure–response relationships with a wildlife demographic model, we provided a method to quantify critical toxicant thresholds for wildlife population persistence.
Kaneto, Hideaki; Matsuoka, Taka-Aki; Kimura, Tomohiko; Obata, Atsushi; Shimoda, Masashi; Kamei, Shinji; Mune, Tomoatsu; Kaku, Kohei
2016-03-01
Pancreatic β-cells secrete insulin when blood glucose levels become high; however, when β-cells are chronically exposed to hyperglycemia, β-cell function gradually deteriorates, which is known as β-cell glucose toxicity. In the diabetic state, nuclear expression of the pancreatic transcription factors pancreatic and duodenal homeobox 1 (PDX-1) and v-Maf musculoaponeurotic fibrosarcoma oncogene family, protein A (MafA) is decreased. In addition, incretin receptor expression in β-cells is decreased, which is likely involved in the impairment of incretin effects in diabetes. Clinically, it is important to select appropriate therapy for type 2 diabetes mellitus (T2DM) so that β-cell function can be preserved. In addition, when appropriate pharmacological interventions against β-cell glucose toxicity are started at the early stages of diabetes, β-cell function is substantially restored, which is not observed if treatment is started at advanced stages. These observations indicate that it is likely that downregulation of pancreatic transcription factors and/or incretin receptors is involved in β-cell dysfunction observed in T2DM and it is very important to start appropriate pharmacological intervention against β-cell glucose toxicity in the early stages of diabetes. © 2015 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.
Hutler Wolkowicz, Ianina; Svartz, Gabriela V; Aronzon, Carolina M; Pérez Coll, Christina
2016-12-01
Bisphenol A diglycidyl ether (BADGE) is used in packaging materials, in epoxy adhesives, and as an additive for plastics, but it is also a potential industrial wastewater contaminant. The aim of the present study was to evaluate the adverse effects of BADGE on Rhinella arenarum by means of standardized bioassays at embryo-larval development. The results showed that BADGE was more toxic to embryos than to larvae at all exposure times. At acute exposure, lethality rates of embryos exposed to concentrations of 0.0005 mg/L BADGE and greater were significantly higher than rates in the vehicle control, whereas lethality rates of larvae were significantly higher in concentrations of 10 mg/L BADGE and greater. The toxicity then increased significantly, with 96-h median lethal concentrations (LC50s) of 0.13 mg/L and 6.9 mg/L BADGE for embryos and larvae, respectively. By the end of the chronic period, the 336-h LC50s were 0.04 mg/L and 2.2 mg/L BADGE for embryos and larvae, respectively. This differential sensitivity was also ascertained by the 24-h pulse exposure experiments, in which embryos showed a stage-dependent toxicity, with blastula being the most sensitive stage and S.23 the most resistant. The most important sublethal effects in embryos were cell dissociation and delayed development, whereas the main abnormalities observed in larvae related to neurotoxicity, as scare response to stimuli and narcotic effect. Environ Toxicol Chem 2016;35:3031-3038. © 2016 SETAC. © 2016 SETAC.
Prabhaker, Nilima; Gispert, Carmen; Castle, Steven J
2012-08-01
Between 2006 and 2008, 20 populations of Planococcus ficus (Signoret), from Coachella and San Joaquin Valleys of California were measured in the laboratory for susceptibility to buprofezin, chlorpyrifos, dimethoate, methomyl, and imidacloprid. Toxicity was assessed using a petri dish bioassay technique for contact insecticides and by a systemic uptake technique for imidacloprid. Mixed life stages were tested for susceptibility to all insecticides except for buprofezin, which was measured against early and late instars (first, second, and third). Dose-response regression lines from the mortality data established LC50 and LC99 values by both techniques. Responses of populations from the two geographical locations to all five insecticides varied, in some cases significantly. Variations in susceptibility to each insecticide among sample sites showed a sevenfold difference for buprofezin, 11-fold to chlorpyrifos, ninefold to dimethoate, 24-fold to methomyl, and 8.5-fold to imidacloprid. In spite of susceptibility differences between populations, baseline toxicity data revealed that all five insecticides were quite effective based on low LC50s. Chlorpyrifos was the most toxic compound to Planococcus ficus populations as shown by lowest LC50s. Buprofezin was toxic to all immature stages but was more potent to first instars. The highest LC99 estimated by probit analysis of the bioassay data of all 20 populations for each compound was selected as a candidate discriminating dose for use in future resistance monitoring efforts. Establishment of baseline data and development of resistance monitoring tools such as bioassay methods and discriminating doses are essential elements of a sustainable management program for Planococcus ficus.
Phom, Limamanen; Achumi, Bovito; Alone, Debasmita P.; Muralidhara
2014-01-01
Abstract Selective degeneration of dopaminergic neurons in the substantia nigra underlies the basic motor impairments of Parkinson's disease (PD). Curcumin has been used for centuries in traditional medicines in India. Our aim is to understand the efficacy of genotropic drug curcumin as a neuroprotective agent in PD. Analysis of different developmental stages in model organisms revealed that they are characterized by different patterns of gene expression which is similar to that of developmental stages of human. Genotropic drugs would be effective only during those life cycle stages for which their target molecules are available. Hence there exists a possibility that targets of genotropic compounds such as curcumin may not be present in all life stages. However, no reports are available in PD models illustrating the efficacy of curcumin in later phases of adult life. This is important because this is the period during which late-onset disorders such as idiopathic PD set in. To understand this paradigm, we tested the protective efficacy of curcumin in different growth stages (early, late health stage, and transition phase) in adult Drosophila flies. Results showed that it can rescue the motor defects during early stages of life but is ineffective at later phases. This observation was substantiated with the finding that curcumin treatment could replenish depleted brain dopamine levels in the PD model only during early stages of life cycle, clearly suggesting its limitation as a therapeutic agent in late-onset neurodegenerative disorders such as PD. PMID:25238331
To Stay or to Go? Narratives of Early-Stage Sociologists about Persisting in Academia
ERIC Educational Resources Information Center
Wöhrer, Veronika
2014-01-01
Based on analyses of life course questionnaires, semi-structured qualitative interviews and focus group interviews carried out with early-stage sociologists over a period of 8 years, this paper presents analyzes of continuity and change in the decisions made by early-stage researchers in regard to their work and careers. The longitudinal approach…
Chang, Joe Y; Zhang, Wencheng; Komaki, Ritsuko; Choi, Noah C; Chan, Shen; Gomez, Daniel; O'Reilly, Michael; Jeter, Melenda; Gillin, Michael; Zhu, Xiaorong; Zhang, Xiaodong; Mohan, Radhe; Swisher, Stephen; Hahn, Stephen; Cox, James D
2017-02-01
The aim of this phase I/II study was to assess the long-term clinical benefits and toxicities of proton beam therapy for medically inoperable early-stage non-small cell lung cancer (NSCLC). From June 2006 to September 2011, 35 patients with medically inoperable T1N0M0 (central or superior location, 12 patients) or T2-3N0M0 (any location, 23 patients) NSCLC were treated with 87.5Gy at 2.5Gy/fraction of proton therapy. Toxicities were scored according to the Common Terminology Criteria for Adverse Events, version 4.0. The median follow-up time was 83.1months (95% CI: 69.2-97.1months). For all 35 patients, the 1, 3, and 5-year overall survival rates were 85.7%, 42.9%, and 28.1%, respectively. The 5-year local recurrence-free, regional recurrence-free, and distant metastasis-free survival rates were 85.0%, 89.2%, and 54.4%, respectively. Different T stages had no effect on local and regional recurrence (p=0.499, p=1.00). However, with the increase in T stages, the distant metastasis rate increased significantly (p=0.006). The most common adverse effects were dermatitis (grade 2, 51.4%; grade 3, 2.9%) and radiation pneumonitis (grade 2, 11.4%; grade 3, 2.9%). Other grade 2 toxicities included esophagitis (2.9%), rib fracture (2.9%), heart toxicities (5.7%), and chest wall pain (2.9%). According to our long-term follow-up data, proton therapy with ablative doses is well tolerated and effective in medically inoperable early-stage NSCLC. Systemic therapy should be considered to reduce the rate of distant metastasis in cases of T2 and T3 lesions. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Pineda, M. Carmen; McQuaid, Christopher D.; Turon, Xavier; López-Legentil, Susanna; Ordóñez, Víctor; Rius, Marc
2012-01-01
All ontogenetic stages of a life cycle are exposed to environmental conditions so that population persistence depends on the performance of both adults and offspring. Most studies analysing the influence of abiotic conditions on species performance have focussed on adults, while studies covering early life-history stages remain rare. We investigated the responses of early stages of two widely introduced ascidians, Styela plicata and Microcosmus squamiger, to different abiotic conditions. Stressors mimicked conditions in the habitats where both species can be found in their distributional ranges and responses were related to the selection potential of their populations by analysing their genetic diversity. Four developmental stages (egg fertilisation, larval development, settlement, metamorphosis) were studied after exposure to high temperature (30°C), low salinities (26 and 22‰) and high copper concentrations (25, 50 and 100 µg/L). Although most stressors effectively led to failure of complete development (fertilisation through metamorphosis), fertilisation and larval development were the most sensitive stages. All the studied stressors affected the development of both species, though responses differed with stage and stressor. S. plicata was overall more resistant to copper, and some stages of M. squamiger to low salinities. No relationship was found between parental genetic composition and responses to stressors. We conclude that successful development can be prevented at several life-history stages, and therefore, it is essential to consider multiple stages when assessing species' abilities to tolerate stress. Moreover, we found that early development of these species cannot be completed under conditions prevailing where adults live. These populations must therefore recruit from elsewhere or reproduce during temporal windows of more benign conditions. Alternatively, novel strategies or behaviours that increase overall reproductive success might be responsible for ensuring population survival. PMID:23077518
Silver nanoparticles induce developmental stage-specific embryonic phenotypes in zebrafish.
Lee, Kerry J; Browning, Lauren M; Nallathamby, Prakash D; Osgood, Christopher J; Xu, Xiao-Hong Nancy
2013-12-07
Much is anticipated from the development and deployment of nanomaterials in biological organisms, but concerns remain regarding their biocompatibility and target specificity. Here we report our study of the transport, biocompatibility and toxicity of purified and stable silver nanoparticles (Ag NPs, 13.1 ± 2.5 nm in diameter) upon the specific developmental stages of zebrafish embryos using single NP plasmonic spectroscopy. We find that single Ag NPs passively diffuse into five different developmental stages of embryos (cleavage, early-gastrula, early-segmentation, late-segmentation, and hatching stages), showing stage-independent diffusion modes and diffusion coefficients. Notably, the Ag NPs induce distinctive stage and dose-dependent phenotypes and nanotoxicity, upon their acute exposure to the Ag NPs (0-0.7 nM) for only 2 h. The late-segmentation embryos are most sensitive to the NPs with the lowest critical concentration (CNP,c < 0.02 nM) and highest percentages of cardiac abnormalities, followed by early-segmentation embryos (CNP,c < 0.02 nM), suggesting that disruption of cell differentiation by the NPs causes the most toxic effects on embryonic development. The cleavage-stage embryos treated with the NPs develop into a wide variety of phenotypes (abnormal finfold, tail/spinal cord flexure, cardiac malformation/edema, yolk sac edema, and acephaly). These organ structures are not yet developed in cleavage-stage embryos, suggesting that the earliest determinative events to create these structures are ongoing, and disrupted by NPs, which leads to the downstream effects. In contrast, the hatching embryos are most resistant to the Ag NPs, and majority of embryos (94%) develop normally, and none of them develop abnormally. Interestingly, early-gastrula embryos are less sensitive to the NPs than cleavage and segmentation stage embryos, and do not develop abnormally. These important findings suggest that the Ag NPs are not simple poisons, and they can target specific pathways in development, and potentially enable target specific study and therapy for early embryonic development.
Stereotactic radiotherapy for early lung cancer: Evidence-based approach and future directions
Chehade, Samer; Palma, David A.
2015-01-01
Aim To review key studies evaluating stereotactic radiotherapy in the setting of early-stage non-small cell lung cancer (NSCLC) for inoperable or high-risk patients, and discuss areas of ongoing research and clinical trials. Background The use of stereotactic radiotherapy for the treatment of early stage non-small cell lung cancer (NSCLC) has increased rapidly over the past decade. Numerous studies have reported outcomes for patients treated with SBRT who are unfit for surgical resection, or at high risk of surgical complications. Materials and methods A narrative review. Results The preponderance of evidence suggests that SBRT is associated with excellent local control (∼90% at 3 years) and a favorable toxicity profile. In patients with higher operative risks, such as the elderly and patients with severe COPD, SBRT may provide a less-toxic treatment than surgery with similar oncologic outcomes. Ongoing studies are evaluating the use of SBRT for locally advanced or oligometastatic NSCLC. Conclusions A large body of evidence now exists to support the use of SBRT for early-stage NSCLC. Decisions regarding the optimal choice of treatment should be individualized, and made in the context of a multidisciplinary team. PMID:26696779
Bioaccumulation of lipophilic substances in fish early life stages
DOE Office of Scientific and Technical Information (OSTI.GOV)
Petersen, G.I.; Kristensen, P.
1998-07-01
Accumulation of {sup 14}C-labeled polycyclic aromatic hydrocarbons, naphthalene, phenanthrene, pyrene, and benzo(a)pyrene and polychlorinated biphenyl (PCB) congeners PCB 31 and PCB 105 with a log octanol/water partition coefficient (K{sub ow}) range from 3.37 to 6.5 was investigated in eggs and larvae of zebra fish (Brachydanio rerio), and in larvae of cod (Gadus morhua), herring (Clupea harengus), and turbot (Scophthalmus maximus). Significant differences in the uptake and elimination rate constants between eggs and larvae of zebra fish were seen. The low rate of uptake and the lower elimination rate of eggs did, however, lead to bioconcentration factors (BCFs) comparable to thosemore » for larvae. As biotransformation of xenobiotics in embryonic and larval stages was indicated to be insignificant compared to juvenile/adult stages, body burdens of readily biotransformed chemicals may be higher in fish early life stages. Because weight and lipid content did not differ much between the investigated species, the main reason for the variability in BCFs between marine species and freshwater species was considered to be caused by differences in exposure temperatures that affect the degree of biotransformation. Due to the smaller size of larvae and thus an increased total surface of the membranes per unit fish weight, steady-state conditions were reached at a faster r/ate in early life stages than in juvenile/adult life stages. The lipid-normalized bioconcentration factors (BCF{sub L}) were linearly related to K{sub ow} but BCF{sub L} was, in general, higher than K{sub ow}, indicating that octanol is not a suitable surrogate for fish lipids. Differences in bioconcentration kinetics between larvae and juvenile/adult life stages are considered to be the main reason for the higher sensitivity, with respect to external effect concentrations, generally obtained for early life stages of fish.« less
Underlying Motivations of Volunteering Across Life Stages.
Yamashita, Takashi; Keene, Jennifer R; Lu, Chi-Jung; Carr, Dawn C
2017-03-01
Volunteering is beneficial not only for individuals' well-being but also for society's well-being; yet only a fraction of U.S. citizens regularly engage in volunteer activities. This study examined how underlying motivations are associated with interest in volunteering for individuals in three major life phases: early, middle, and later adulthood. Data were collected from 1,046 adults who volunteered through nonprofit organizations in Nevada (USA). Exploratory factor analysis revealed that community service, career advancement, and well-being were common underlying motivations for individuals across life stages. However, generativity among the later adulthood group, and social networking among the early and middle adulthood groups were unique motivations for volunteering. Regression analysis showed that the community service motivation was significantly associated with individuals' interest in volunteering among all life stages. Simultaneously, generativity for the later adulthood group, and career advancement for the early adulthood group were unique motivations linked to their actual interest in volunteering.
Gonzales, Emily K; Arcese, Peter
2008-12-01
The dominance of nonnative plants coupled with declines of native plants suggests that competitive displacement drives extinctions, yet empirical examples are rare. Herbivores, however, can alter vegetation structure and reduce diversity when abundant. Herbivores may act on mature, reproductive life stages whereas some of the strongest competitive effects might occur at early life stages that are difficult to observe. For example, competition by perennial nonnative grasses can interfere with the establishment of native seeds. We contrasted the effects of ungulate herbivory and competition by neighboring plants on the performance of native plant species at early and established life stages in invaded oak meadows. We recorded growth, survival, and flowering in two native species transplanted as established plants, six native species grown from seed, and five extant lily species as part of two 2 x 2 factorial experiments that manipulated herbivory and competition. Herbivory reduced the performance of nearly all focal native species at early and established life stages, whereas competition had few measurable effects. Our results suggest that herbivory has a greater local influence on native plant species than competition and that reducing herbivore impacts will be required to successfully restore endangered oak meadows where ungulates are now abundant.
2017-05-03
Stage I Ovarian Cancer; Stage IA Fallopian Tube Cancer; Stage IB Fallopian Tube Cancer; Stage IC Fallopian Tube Cancer; Stage II Ovarian Cancer; Stage IIA Fallopian Tube Cancer; Stage IIB Fallopian Tube Cancer; Stage IIC Fallopian Tube Cancer; Stage III Ovarian Cancer; Stage III Primary Peritoneal Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIC Fallopian Tube Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer
AGE-RELATED TOXICITY PATHWAY ANALYSIS IN BROWN NORWAY RAT BRAIN FOLLOWING ACUTE TOLUENE EXPOSURE
The influence of aging on susceptibility to environmental exposures is poorly understood. To investigate-the contribution of different life stages on response to toxicants, we examined the effects of an acute exposure to the volatile organic compound, toluene (0.0 or 1.0 g/kg), i...
Calfee, Robin D.; Little, Edward E.; Puglis, Holly J.; Scott, Erinn L.; Brumbaugh, William G.; Mebane, Christopher A.
2014-01-01
The acute toxicity of cadmium, copper, and zinc to white sturgeon (Acipenser transmontanus) and rainbow trout (Oncorhynchus mykiss) were determined for 7 developmental life stages in flow-through water-only exposures. Metal toxicity varied by species and by life stage. Rainbow trout were more sensitive to cadmium than white sturgeon across all life stages, with median effect concentrations (hardness-normalized EC50s) ranging from 1.47 µg Cd/L to 2.62 µg Cd/L with sensitivity remaining consistent during later stages of development. Rainbow trout at 46 d posthatch (dph) ranked at the 2nd percentile of a compiled database for Cd species sensitivity distribution with an EC50 of 1.46 µg Cd/L and 72 dph sturgeon ranked at the 19th percentile (EC50 of 3.02 µg Cd/L). White sturgeon were more sensitive to copper than rainbow trout in 5 of the 7 life stages tested with biotic ligand model (BLM)-normalized EC50s ranging from 1.51 µg Cu/L to 21.9 µg Cu/L. In turn, rainbow trout at 74 dph and 95 dph were more sensitive to copper than white sturgeon at 72 dph and 89 dph, indicating sturgeon become more tolerant in older life stages, whereas older trout become more sensitive to copper exposure. White sturgeon at 2 dph, 16 dph, and 30 dph ranked in the lower percentiles of a compiled database for copper species sensitivity distribution, ranking at the 3rd (2 dph), 5th (16 dph), and 10th (30 dph) percentiles. White sturgeon were more sensitive to zinc than rainbow trout for 1 out of 7 life stages tested (2 dph with an biotic ligand model–normalized EC50 of 209 µg Zn/L) and ranked in the 1st percentile of a compiled database for zinc species sensitivity distribution.
NASA Astrophysics Data System (ADS)
Zhang, Yunlong; Wu, Qiaowan; Hu, Weihua; Wang, Fan; Shao, Weihan; Zhang, Chengming; Zhao, Zhongbo; He, Hui; Fan, Qixue; Gu, Zemao
2016-07-01
The length-weight relationship and allometric growth patterns of hatchery-reared Chinese loach, Paramisgurnus dabryanus (Dabry de Thiersant, 1872), were determined from hatching to 60 days after hatching. A best power model was estimated for the length-weight relationship during the early life stages. Positive allometric growth for the head segment, trunk length, tail length and eye diameter was also found in the early life stages, while body depth, tail depth, tail fin length, pectoral fin length and barbel length displayed a negative coefficient. During the subsequent early developmental stage, the growth coefficients showed a clear and common tendency towards isometry for all measured body ratios. The allometric growth changes in Chinese loach during the early stage are possibly the result of selective organogenesis directed towards survival priorities.
Mamalyga, M L
2013-01-01
The disbalance of autonomic heart regulation (AHR) develops already in the presymptomatic stage of Parkinson's disease. The early symptomatic stage is accompanied by the aggravation of heart dysfunction due to the shift of the autonomic balance towards the increase of sympathetic and decrease of parasympathic effect on the heart. Coronary disorders concomitant to Parkinson's disease increase a risk of life threatening arrhythmia and sudden death syndrome not only in the early symptomatic stage but also in the presymptomatic stage. L-DOPA effectively restores the structure of AHR and prevents the risk of life threatening arrhythmia only in the presymptomatic stage of Parkinson's disease.
Gunther, Jillian R; Fanale, Michelle A; Reddy, Jay P; Akhtari, Mani; Smith, Grace L; Pinnix, Chelsea C; Milgrom, Sarah A; Yehia, Zeinab Abou; Allen, Pamela K; Osborne, Eleanor M; Mawlawi, Osama; Dabaja, Bouthaina S
2016-09-01
The German Hodgkin Study Group HD11 trial validated 4 cycles of doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) chemotherapy followed by involved field radiation therapy (IFRT) for early unfavorable Hodgkin lymphoma (HL) patients. However, practitioners often recommend 6 cycles followed by RT, especially for bulky disease. We compared patient outcomes after treatment with 4 or 6 cycles of ABVD followed by RT (IFRT and involved site RT [ISRT]). We identified 128 patients treated for early unfavorable HL (GHSG criteria) between 2000 and 2013. Clinical outcomes (overall survival [OS] and freedom from relapse [FFR]) were estimated using Kaplan-Meier analysis. Toxicities were evaluated. The median follow-up time was 5.0 years. Patients received 4 (70 patients, 55%) or 6 (58 patients, 45%) cycles of chemotherapy. Bulky disease was present in 22 patients (31%; 0 stage IA, 3 stage IB, 19 stage IIA) of the 4-cycle group and 42 patients (72%; 5 stage IA, 3 stage IB, 34 stage IIA) of the 6-cycle group. For patients receiving 4 and 6 cycles, the 6-year OS was 100% and 97% (P=.35), respectively, and the 6 year FFR was 100% and 98% (P=.28), respectively. More patients received 6 cycles if they were treated before 2010 (HD11 report) (P=.01) and if they had bulky disease (P<.01). Sixty-eight percent of patients received ISRT. The 6-year FFR was 99% and 100% for patients receiving ISRT and IFRT, respectively (P=.58). More patients experienced bleomycin pulmonary toxicity in the 6-cycle group (20% vs 31%, P=.16). For patients with bulky disease, the 4-year FFR was similar with receipt of 4 (100%) or 6 (98%) cycles (P=.48) and IFRT (100%) or ISRT (98%) (P=.52). There were no deaths among patients with bulky disease. Patients with early unfavorable HL have excellent outcomes with 4 cycles of ABVD chemotherapy followed by ISRT. Six cycles of chemotherapy does not appear superior for disease control, even for bulky disease. Copyright © 2016 Elsevier Inc. All rights reserved.
Weil, Mirco; Scholz, Stefan; Zimmer, Michaela; Sacher, Frank; Duis, Karen
2009-09-01
Based on the hypothesis that analysis of gene expression could be used to predict chronic fish toxicity, the zebrafish (Danio rerio) embryo test (DarT), developed as a replacement method for the acute fish test, was expanded to a gene expression D. rerio embryo test (Gene-DarT). The effects of 14 substances on lethal and sublethal endpoints of the DarT and on expression of potential marker genes were investigated: the aryl hydrocarbon receptor 2, cytochrome P450 1A (cypla), heat shock protein 70, fizzy-related protein 1, the transcription factors v-maf musculoaponeurotic fibrosarcoma oncogene family protein g (avian) 1 and NF-E2-p45-related factor, and heme oxygenase 1 (hmox1). After exposure of zebrafish embryos for 48 h, differential gene expression was evaluated using reverse transcriptase-polymerase chain reaction, gel electrophoresis, and densitometric analysis of the gels. All tested compounds significantly affected the expression of at least one potential marker gene, with cyp1a and hmox1 being most sensitive. Lowest-observed-effect concentrations (LOECs) for gene expression were below concentrations resulting in 10% lethal effects in the DarT. For 10 (3,4- and 3,5-dichloroaniline, 1,4-dichlorobenzene, 2,4-dinitrophenol, atrazine, parathion-ethyl, chlorotoluron, genistein, 4-nitroquinoline-1-oxide, and cadmium) out of the 14 tested substances, LOEC values derived with the Gene-DarT differ by a factor of less than 10 from LOEC values of fish early life stage tests with zebrafish. For pentachloroaniline and pentachlorobenzene, the Gene-DarT showed a 23- and 153-fold higher sensitivity, respectively, while for lindane, it showed a 13-fold lower sensitivity. For ivermectin, the Gene-DarT was by a factor of more than 1,000 less sensitive than the acute fish test. The results of the present study indicate that gene expression analysis in zebrafish embryos could principally be used to predict effect concentrations in the fish early life stage test.
Yusof, Shahrizad; Ismail, Ahmad; Alias, Mohamad Shafiq
2014-08-30
Glyphosate is globally a widely used herbicide, yet there is little information on their toxicity to marine fishes. Java medaka, a small tropical fish native to coastal areas in several Southeast Asian countries, is viewed as a suitable candidate for toxicity test and thus was used for this study. Java medaka adults were cultured in the laboratory and the fertilized eggs of the F2 generation were exposed to different concentrations of glyphosate-based herbicide (100, 200, 300, 400 and 500 ppm) until they hatched. The survival and hatching rates of the embryos, changes in the heart rate and morphological impairments were recorded. Generally, survival and hatching percentage decreased as glyphosate concentration increased. Absence of pectoral fin(s) and cornea, permanently bent tail, irregular shaped abdomen, and cell disruption in the fin, head and abdomen are among the common teratogenic effects observed. Furthermore, risk factor also increased with the increased in glyphosate concentrations. Copyright © 2014 Elsevier Ltd. All rights reserved.
Toxic effects of brominated indoles and phenols on zebrafish embryos.
Kammann, U; Vobach, M; Wosniok, W
2006-07-01
Organobromine compounds in the marine environment have been the focus of growing attention in past years. In contrast to anthropogenic brominated flame retardants, other brominated compounds are produced naturally, e.g., by common polychaete worms and algae. Brominated phenols and indoles assumed to be of biogenic origin have been detected in water and sediment extracts from the German Bight. These substances as well as some of their isomers have been tested with the zebrafish embryo test and were found to cause lethal as well as nonlethal malformations. The zebrafish test was able to detect a log K(OW)-related toxicity for bromophenols, suggesting nonpolar narcosis as a major mode of action. Different effect patterns could be observed for brominated indoles and bromophenols. The comparison of effective concentrations in the zebrafish embryo test with the concentrations determined in water samples suggests the possibility that brominated indoles may affect early life stages of marine fish species in the North Sea.
Toxicity of tributyltin in the marine mollusc Mytilus edulis.
Hagger, Josephine A; Depledge, Michael H; Galloway, Tamara S
2005-01-01
Our previous studies have demonstrated that tributyltin (TBT) is genotoxic to the early life stages of marine mussels and worms. Here, the toxicity of TBT to adult organisms was determined using a suite of biomarkers designed to detect cytotoxic, immunotoxic and genotoxic effects. Exposure of adult mussels, Mytilus edulis, to environmentally realistic concentrations of TBTO for 7 days resulted in a statistically significant decrease in cell viability at concentrations of 0.5 microg/l and above. TBT had no effect on phagocytic activity or antioxidant capacity (FRAP assay). There was a statistically significant increase in DNA damage detected using the comet and micronucleus assays between the controls and 0.5, 1 and 5 microg/l of TBTO (P > 0.0005). Furthermore there was a strong correlation between DNA strand breaks (comet assay) and formation of micronuclei (P = 0.0005; R2 = 61.5%). Possible mechanisms by which TBT could damage DNA either directly or indirectly are discussed including the possibility that TBT is genotoxic due to its ability to disrupt calcium homeostasis.
Code of Federal Regulations, 2012 CFR
2012-01-01
... early life stages 2 SMALL, MODERATE, OR LARGE. The impacts of entrainment are small at many plants but... fish and shellfish in early life stages 1 SMALL. Entrainment of fish has not been found to be a problem... questionable. In particular, science cannot rule out the possibility that there will be no cancer fatalities...
DOE Office of Scientific and Technical Information (OSTI.GOV)
Preez-Coll, C.S.; Herkovits, J.
Over the last several years, environmental contamination with cadmium has significantly increased because of its extensive use In anthropogenic activities. This heavy metal is a very toxic xenobiotic producing reproductive and developmental impairments in a wide spectrum of organisms. Within the life cycle of organisms, the embryo is the most sensitive period to adverse conditions. Moreover, stage-dependent susceptibilities to toxic agents in amphibian embryos treated with lead, cadmium and aluminium were described. In the case of cadmium, this differential sensitivity could be related to changes in the metal accumulation through development or in the induction of defense mechanisms against cadmiummore » toxicity, such as metallothionein (Mt) synthesis, which seems to be developmentally regulated. In the case of the toad Bufo arenarum, susceptibility to cadmium seems to follow a biphasic pattern during embryonic development. From the two-cell stage to the neurula stage an increase in susceptibility occurs, whereas from the last stage onwards a gradual increase in the resistance against this heavy metal seems to be achieved. This stage reports the uptake profile of cadmium at different post-hatching stages. 20 refs., 3 figs.« less
Mechanisms of biotic resistance across complex life cycles.
Rius, Marc; Potter, Elaine E; Aguirre, J David; Stachowicz, John J
2014-01-01
Biotic resistance is the ability of communities to inhibit the establishment, spread or impact of novel species. However, the interactions that underlie biotic resistance depend heavily on the contexts in which species interact. Consequently, studies of biotic resistance that consider single processes, patches, species or life-history stages may provide an incomplete picture of the capacity for communities to resist invasion. Many organisms have multiphasic life cycles, where individuals can occupy distinct niches at different stages of the life history. Generally, studies of biotic resistance focus on interactions within a single life-history stage, and interactions at other life-history stages are overlooked. Here, we demonstrate that different mechanisms of biotic resistance occur across the life history and together limit the invasion success of an introduced marine invertebrate (Ciona intestinalis) in Northern California. We tested the role of interactions (competition and predation) with the resident community in limiting the abundance of Ciona through experiments conducted on fertilization, larval survival, settlement, early postsettlement survival, and the survival of juveniles and adults. Under some circumstances, Ciona became abundant in mid-successional stages and showed more rapid growth rates than a morphologically similar native species, Ascidia ceratodes. However, predators reduced Ciona abundance much more than that of Ascidia at several life stages. Furthermore, Ciona appeared to be a weaker competitor at the adult stage. Early life-history interactions with other sessile species at the fertilization, larval and recruit stages had modest to no effects on Ciona abundance. The presence of biotic resistance mechanisms acting at multiple life stages, and potentially under different conditions, suggests that different components of biotic resistance interact to enhance the resident community's resistance to invasion. © 2013 The Authors. Journal of Animal Ecology © 2013 British Ecological Society.
Childhood should be viewed as a sequence of lifestages, from birth through infancy and adolescence. When assessing early life risks, consideration is given to risks resulting from fetal exposure via the pregnant mother, as well as postnatal exposures.
Sonnack, Laura; Klawonn, Thorsten; Kriehuber, Ralf; Hollert, Henner; Schäfers, Christoph; Fenske, Martina
2018-03-01
Metal toxicity is a global environmental challenge. Fish are particularly prone to metal exposure, which can be lethal or cause sublethal physiological impairments. The objective of this study was to investigate how adverse effects of chronic exposure to non-toxic levels of essential and non-essential metals in early life stage zebrafish may be explained by changes in the transcriptome. We therefore studied the effects of three different metals at low concentrations in zebrafish embryos by transcriptomics analysis. The study design compared exposure effects caused by different metals at different developmental stages (pre-hatch and post-hatch). Wild-type embryos were exposed to solutions of low concentrations of copper (CuSO 4 ), cadmium (CdCl 2 ) and cobalt (CoSO 4 ) until 96h post-fertilization (hpf) and microarray experiments were carried out to determine transcriptome profiles at 48 and 96hpf. We found that the toxic metal cadmium affected the expression of more genes at 96hpf than 48hpf. The opposite effect was observed for the essential metals cobalt and copper, which also showed enrichment of different GO terms. Genes involved in neuromast and motor neuron development were significantly enriched, agreeing with our previous results showing motor neuron and neuromast damage in the embryos. Our data provide evidence that the response of the transcriptome of fish embryos to metal exposure differs for essential and non-essential metals. Copyright © 2017 Elsevier Inc. All rights reserved.
Yang, Yang Claire; Gerken, Karen; Schorpp, Kristen; Boen, Courtney; Harris, Kathleen Mullan
2017-01-01
A growing literature has demonstrated a link between early-life socioeconomic conditions and adult health at a singular point in life. No research exists, however, that specifies the life course patterns of socioeconomic status (SES) in relation to the underlying biological processes that determine health. Using an innovative life course research design consisting of four nationally representative longitudinal datasets that collectively cover the human life span from early adolescence to old age (Add Health, MIDUS, NSHAP, and HRS), we address this scientific gap and assess how SES pathways from childhood into adulthood are associated with biophysiological outcomes in different adult life stages. For each dataset, we constructed standardized composite measures of early-life SES and adult SES and harmonized biophysiological measurements of immune and metabolic functioning. We found that the relative importance of early-life SES and adult SES varied across young, mid, and late adulthood, such that early-life SES sets a life course trajectory of socioeconomic well-being and operates through adult SES to influence health as adults age. We also documented evidence of the detrimental health effects of downward mobility and persistent socioeconomic disadvantage. These findings are the first to specify the life course patterns of SES that matter for underlying biophysiological functioning in different stages of adulthood. The study thus contributes new knowledge critical for improving population health by identifying the particular points in the life course at which interventions might be most effective in preventing disease and premature mortality.
Garner, Andrew S; Shonkoff, Jack P
2012-01-01
Advances in a wide range of biological, behavioral, and social sciences are expanding our understanding of how early environmental influences (the ecology) and genetic predispositions (the biologic program) affect learning capacities, adaptive behaviors, lifelong physical and mental health, and adult productivity. A supporting technical report from the American Academy of Pediatrics (AAP) presents an integrated ecobiodevelopmental framework to assist in translating these dramatic advances in developmental science into improved health across the life span. Pediatricians are now armed with new information about the adverse effects of toxic stress on brain development, as well as a deeper understanding of the early life origins of many adult diseases. As trusted authorities in child health and development, pediatric providers must now complement the early identification of developmental concerns with a greater focus on those interventions and community investments that reduce external threats to healthy brain growth. To this end, AAP endorses a developing leadership role for the entire pediatric community-one that mobilizes the scientific expertise of both basic and clinical researchers, the family-centered care of the pediatric medical home, and the public influence of AAP and its state chapters-to catalyze fundamental change in early childhood policy and services. AAP is committed to leveraging science to inform the development of innovative strategies to reduce the precipitants of toxic stress in young children and to mitigate their negative effects on the course of development and health across the life span.
Finch, Bryson E; Stubblefield, William A
2016-05-01
Significant increases in toxicity have been observed as a result of polycyclic aromatic hydrocarbon (PAH) absorption of ultraviolet (UV) radiation in aquatic organisms. Early life stage aquatic organisms are predicted to be more susceptible to PAH photo-enhanced toxicity as a result of their translucence and tendency to inhabit shallow littoral or surface waters. The objective of the present study was to evaluate the sensitivity of varying ages of larval mysid shrimp (Americamysis bahia), inland silverside (Menidia beryllina), sheepshead minnow (Cyprinodon variegatus), and Gulf killifish (Fundulus grandis) to photo-enhanced toxicity and to examine the correlation between photo-enhanced toxicity and organism pigmentation. Organisms were exposed to fluoranthene and artificial UV light at different larval ages and results were compared using median lethal concentrations (LC50s) and the lethal time-to-death (LT50s). In addition, a high UV light intensity, short-duration (4-h) experiment was conducted at approximately 24 W/m(2) of ultraviolet radiation A (UV-A) and compared with a low-intensity, long-duration (12-h) experiment at approximately 8 W/m(2) of UV-A. The results indicated decreased toxicity with increasing age for all larval organisms. The amount of organism pigmentation was correlated with observed LC50 and LT50 values. High-intensity short-duration exposure resulted in greater toxicity than low-intensity long-duration UV treatments for mysid shrimp, inland silverside, and sheepshead minnow. Data from these experiments suggest that toxicity is dependent on age, pigmentation, UV light intensity, and fluoranthene concentration. © 2015 SETAC.
Basti, Leila; Nagai, Kiyohito; Go, Jiyoji; Okano, Sho; Oda, Tatsuya; Tanaka, Yuji; Nagai, Satoshi
2016-11-01
The inimical effects of the ichthyotoxic harmful algal bloom (HAB)-forming raphidophytes Heterosigma akashiwo, Chattonella marina, and Chattonella antiqua on the early-life stages of the Japanese pearl oyster Pinctada fucata martensii were studied. Fertilized eggs and developing embryos were not affected following exposure to the harmful raphidophytes; however, all three algal species severely affected trochophores and D-larvae, early-stage D-larvae, and late-stage pre-settling larvae. Exposure to C. marina (5×10 2 cellsml -1 ), C. antiqua (10 3 cellsml -1 ), and H. akashiwo (5×10 3 cellsml -1 ) resulted in decreased success of metamorphosis to the trochophore stage. A complete inhibition of trochophore metamorphosis was observed following exposure to C. antiqua at 5×10 3 cellsml -1 and C. marina at 8×10 3 cellsml -1 . In all experiments, more than 80% of newly formed trochophores were anomalous, and in the case of exposure to H. akashiwo at 10 5 cellsml -1 more than 70% of D-larvae were anomalous. The activity rates of D-larvae (1-day-old) were significantly reduced following exposure to C. antiqua (8×10 3 cellsml -1 , 24h), C. marina (8×10 3 cellsml -1 , 24h), and H. akashiwo (10 4 cellsml -1 , 24h). The activity rates of pre-settling larvae (21-day-old) were also significantly reduced following exposure to C. antiqua (10 3 cellsml -1 , 24h),C. marina (8×10 3 cellsml -1 , 24h), and H. akashiwo (5×10 4 cellsml -1 , 24h). Significant mortalities of both larval stages were induced by all three raphidophytes, with higher mortality rates registered for pre-settling larvae than D-larvae, especially following exposure to C. marina (5×10 2 -8×10 3 cellsml -1 , 48-86h) and C. antiqua (10 3 -8×10 3 cellsml -1 , 72-86h). Contact between raphidophyte cells and newly metamorphosed trochophores and D-larvae, 1-day-old D-larvae, and 21-day-old larvae resulted in microscopic changes in the raphidophytes, and then, in the motile early-life stages of pearl oysters. Upon contact and physical disturbance of their cells by larval cilia, H. akashiwo, C. marina and C. antiqua became immotile and shed their glycocalyx. The trochophores and larvae were observed trapped in a conglomerate of glycocalyx and mucus, most probably a mixture of larval mucous and raphidophyte tricosyts and mucocytes. All motile stages of pearl oyster larvae showed a typical escape behavior translating into increased swimming in an effort to release themselves from the sticky mucous traps. The larvae subsequently became exhausted, entrapped in more heavy mucous, lost their larval cilia, sank, become immotile, and died. Although other toxic mediators could have been involved, the results of the present study indicate that all three raphidophytes were harmful only for motile stages of pearl oysters, and that the physical disturbance of their cells upon contact with the ciliary structures of pearl oyster larvae initiated the harmful mechanism. The present study is the first report of lethal effects of harmful Chattonella spp. towards larvae of a bivalve mollusc. Blooms of H. akashiwo, C. antiqua and C. marina occur in all major cultivation areas of P. fucata martensii during the developmental period of their larvae. Therefore, exposure of the motile early-life stages of Japanese pearl oysters could adversely affect their population recruitment. In addition, the present study shows that further research with early-life development of pearl oysters and other bivalves could contribute to improving the understanding of the controversial harmful mechanisms of raphidophytes in marine organisms. Copyright © 2016 Elsevier B.V. All rights reserved.
Current developments in the treatment of early-stage classical Hodgkin lymphoma.
Borchmann, Sven; von Tresckow, Bastian; Engert, Andreas
2016-09-01
After presenting the current treatment recommendations for early-stage Hodgkin lymphoma, we give an overview on recently published clinical trials in this setting. Furthermore, the potential influence of current trials on the treatment of early-stage Hodgkin lymphoma and integration of newly emerging drugs into treatment protocols will be discussed. Trials attempting treatment de-escalation and omission of radiotherapy on the basis of early interim PET-scans have been disappointing so far, but results of some large trials employing this strategy are still awaited. In contrast, a more defensive strategy of starting treatment with less aggressive doxorubicine, bleomycin, vinblastine, dacarbazine (ABVD) chemotherapy and intensifying treatment in early interim PET-positive patients has shown encouraging results. New drugs such as brentuximab vedotin and immune checkpoint inhibitors have shown promising results in relapsed and refractory Hodgkin lymphoma. Clinical trials of brentuximab vedotin in early-stage Hodgkin lymphoma have been initiated. Additionally, biomarker-based treatment de-escalation might be a possible route for future improvements. The challenge for future clinical research in early-stage Hodgkin lymphoma is to continue to cure the majority of patients with first-line treatment while reducing long-term toxicity. New strategies to achieve that goal are currently being developed and will further refine treatment of early-stage Hodgkin lymphoma.
[Blood and urine lead levels in children with attention deficit hyperactivity disorder].
Sánchez-Villegas, M del Carmen S; Cortés-Vargas, Astrid; Hidalgo-Luna, Ricardo Gerardo; Alam-Escamilla, David Abraham; Vargas-García, Víctor Manuel; Loría-Castellanos, Jorge
2014-01-01
Attention deficit hyperactivity disorder is the most common neuropsychiatric disorder in children; symptoms can persist into adult life by 60 %. Our objective was to quantify the levels of lead in blood and urine in pediatric patients with attention deficit hyperactivity disorder. We did an observational study which included a captive population of children diagnosed with attention deficit hyperactivity disorder in the mental health service of Hospital General, from Centro Médico Nacional La Raza. Lead levels were determined in blood and urine by atomic absorption technique. We included 39 patients, 932 % male, with a mean age of 9.2 ± 2.16 years. The deficit and hyperactivity disorder combined type was the most frequent (69.2 %); 49 % of patients were found with toxic lead levels in blood (above 10 mg/dL); 17.9 % with stage III and 5.12 % with stage IV, according to the Mexican Official Standard (NOM-199-SSA-2000). Significant association was found between blood lead levels and the clinical expression of attention deficit hyperactivity disorder. Levels of lead exposure during early childhood have been shown to be inversely proportional to neurological development in the first seven years of life. Data results are insufficient to relate them with causality.
Toxic release consequence analysis tool (TORCAT) for inherently safer design plant.
Shariff, Azmi Mohd; Zaini, Dzulkarnain
2010-10-15
Many major accidents due to toxic release in the past have caused many fatalities such as the tragedy of MIC release in Bhopal, India (1984). One of the approaches is to use inherently safer design technique that utilizes inherent safety principle to eliminate or minimize accidents rather than to control the hazard. This technique is best implemented in preliminary design stage where the consequence of toxic release can be evaluated and necessary design improvements can be implemented to eliminate or minimize the accidents to as low as reasonably practicable (ALARP) without resorting to costly protective system. However, currently there is no commercial tool available that has such capability. This paper reports on the preliminary findings on the development of a prototype tool for consequence analysis and design improvement via inherent safety principle by utilizing an integrated process design simulator with toxic release consequence analysis model. The consequence analysis based on the worst-case scenarios during process flowsheeting stage were conducted as case studies. The preliminary finding shows that toxic release consequences analysis tool (TORCAT) has capability to eliminate or minimize the potential toxic release accidents by adopting the inherent safety principle early in preliminary design stage. 2010 Elsevier B.V. All rights reserved.
Watson, Linda C; Gies, Donna; Thompson, Emmanuel; Thomas, Bejoy
2012-05-01
Standard skin care instructions regarding the use of antiperspirants during radiotherapy to the breast varies across North America. Women have articulated that when instructed to not use antiperspirant, the potential for body odor is distressing. Historical practices and individual opinions have often guided practice in this field. The present study had 2 purposes. To evaluate whether the use of aluminum-based antiperspirant while receiving external beam radiotherapy for stage 0, I, or II breast cancer will increase axilla skin toxicity and to evaluate whether the use of antiperspirant during external beam radiotherapy improves quality of life. A total of 198 participants were randomized to either the experimental group (antiperspirant) or control group (standard care-wash only). The skin reactions in both groups were measured weekly and 2 weeks after treatment using the National Cancer Institute Common Toxicity Criteria Adverse Events, version 3, toxicity grading criteria. Both groups completed the Functional Assessment for Chronic Illness Therapy's questionnaire for the breast population quality of life assessment tool, with additional questions evaluating the effect of underarm antiperspirant use on quality of life before treatment, immediately after treatment, and 2 weeks after treatment during the study. The skin reaction data were analyzed using the generalized estimating equation. No statistically significant difference was seen in the skin reaction between the 2 groups over time. The quality of life data also revealed no statistically significant difference between the 2 groups over time. Data analysis indicates that using antiperspirant routinely during external beam radiotherapy for Stage 0, I, or II breast cancer does not affect the intensity of the skin reaction or the self-reported quality of life. This evidence supports that in this particular population, there is no purpose to restrict these women from using antiperspirants during their treatment, and the decision to use an antiperspirant or not in this setting should be left to the discretion of the patient. Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.
Rodin, Danielle; Caulley, Lisa; Burger, Emily; Kim, Jane; Johnson-Obaseki, Stephanie; Palma, David; Louie, Alexander V; Hansen, Aaron; O'Sullivan, Brian
2017-03-15
The objective of this study was to compare the cost-effectiveness of transoral robotic surgery (TORS) versus the standard treatment modality for oropharyngeal squamous cell carcinoma (OPSCC), radiation therapy (RT), in a subset of patients with early-stage OPSCC. We developed a microsimulation state-transition model associated with RT and TORS for patients with clinically staged T1N0M0 to T2N1M0 OPSCC. Transition probabilities, utilities, and costs for each health state were estimated from recently published data and discounted by 3% annually over a lifetime time horizon. Model outcomes included lifetime costs (in 2014 US dollars), health benefits (quality-adjusted life-years [QALYs]), and cost-effectiveness ratios from a societal perspective. Under base-case assumptions, TORS was associated with modest gains in QALYs. RT yielded 10.43 QALYs at a cost of $123,410 per patient, whereas TORS yielded 11.10 QALYs at a cost of $178,480. This resulted in an incremental cost-effectiveness ratio of $82,190/QALY gained. The incremental cost-effectiveness ratio was most sensitive to the need for adjuvant therapy, cost of late toxicity, age at diagnosis, disease state utilities, and discount rate. Accounting for joint parameter uncertainty, RT had a higher probability of demonstrating a cost-effective profile compared with TORS, at 54% compared with 46%. By use of standard benchmarks for cost-effectiveness in the United States, TORS may be a cost-effective alternative for the subset of patients with early-stage OPSCC but demonstrates considerable sensitivity to assumptions around quality of life. Copyright © 2016. Published by Elsevier Inc.
Van Leeuwen, C H A; Dokk, T; Haugen, T O; Kiffney, P M; Museth, J
2017-06-01
Behaviour of early life stages of the salmonid European grayling Thymallus thymallus was investigated by assessing the timing of larval downstream movement from spawning areas, the depth at which larvae moved and the distribution of juvenile fish during summer in two large connected river systems in Norway. Trapping of larvae moving downstream and electrofishing surveys revealed that T. thymallus larvae emerging from the spawning gravel moved downstream predominantly during the night, despite light levels sufficient for orientation in the high-latitude study area. Larvae moved in the water mostly at the bottom layer close to the substratum, while drifting debris was caught in all layers of the water column. Few young-of-the-year still resided close to the spawning areas in autumn, suggesting large-scale movement (several km). Together, these observations show that there may be a deliberate, active component to downstream movement of T. thymallus during early life stages. This research signifies the importance of longitudinal connectivity for T. thymallus in Nordic large river systems. Human alterations of flow regimes and the construction of reservoirs for hydropower may not only affect the movement of adult fish, but may already interfere with active movement behaviour of fish during early life stages. © 2017 The Fisheries Society of the British Isles.
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.
Fish embryo toxicity of carbamazepine, diclofenac and metoprolol.
van den Brandhof, Evert-Jan; Montforts, Mark
2010-11-01
Frequently measured pharmaceuticals in environmental samples were tested in fish embryo toxicity (FET) tests with Danio rerio, based on the draft OECD test protocol. In this FET test 2-h-old zebrafish embryos were exposed for 72 h to carbamazepine, diclofenac and metoprolol to observe effects on embryo mortality, gastrulation, somite formation, tail movement and detachment, pigmentation, heartbeat, malformation of head, otoliths and heart, scoliosis, deformity of yolk, and hatching success at 24, 48 and 72 h. We found specific effects on growth retardation above 30.6 mg/l for carbamazepine, on hatching, yolk sac and tail deformation above 1.5mg/l for diclofenac, and on scoliosis and growth retardation above 12.6 mg/l for metoprolol. Scoring all effect parameters, the 72-h-EC(50) values were: for carbamazepine 86.5mg/l, for diclofenac 5.3mg/l and for metoprolol 31.0mg/l (mean measured concentrations). In conclusion, our results for carbamazepine and metoprolol are in agreement with other findings for aquatic toxicity, and also fish embryos responded in much the same way as rat embryos did. For diclofenac, the FET test performs comparably to Early Life Stage testing. Copyright © 2010 Elsevier Inc. All rights reserved.
Stage-dependent toxicity of bisphenol a on Rhinella arenarum (anura, bufonidae) embryos and larvae.
Wolkowicz, Ianina R Hutler; Herkovits, Jorge; Pérez Coll, Cristina S
2014-02-01
The acute and chronic toxicity of bisphenol A (BPA) was evaluated on the common South American toad Rhinella arenarum embryos and larvae by means of continuous and pulse exposure treatments. Embryos were treated continuously from early blastula (S.4) up to complete operculum (S.25), during early larval stages and by means of 24 h pulse exposures of BPA in concentrations ranging between 1.25 and 40 mg L(-1) , in order to evaluate the susceptibility to this compound in different developmental stages. For lethal effects, S.25 was the most sensitive and gastrula was the most resistant to BPA. The Teratogenic Index for neurula, the most sensitive embryonic stage for sublethal effects was 4.7. The main morphological alterations during early stages were: delayed or arrested development, reduced body size, persistent yolk plug, microcephaly, axial/tail flexures, edemas, blisters, waving fin, underdeveloped gills, mouth malformations, and cellular dissociation. BPA caused a remarkable narcotic effect from gill circulation stage (S.20) onwards in all the organisms exposed after 3 h of treatment with 10 mg L(-1) BPA. After recovering, the embryos exhibited scarce response to stimuli, erratic or circular swimming, and spasmodic contractions from 5 mg L(-1) onwards. Our results highlight the lethal and sublethal effectsof BPA on R. arenarum embryos and larvae, in the last case both at structural and functional levels. Copyright © 2011 Wiley Periodicals, Inc., A Wiley Company.
Persistent carry-over effects of planktonic exposure to ocean acidification in the Olympia oyster.
Hettinger, Annaliese; Sanford, Eric; Hill, Tessa M; Russell, Ann D; Sato, Kirk N S; Hoey, Jennifer; Forsch, Margaux; Page, Heather N; Gaylord, Brian
2012-12-01
Predicting impacts of global environmental change is challenging due to the complex life cycles that characterize many terrestrial and aquatic taxa. Different life stages often interact with the physical environment in distinct ways, and a growing body of work suggests that stresses experienced during one life stage can "carry over" to influence subsequent stages. Assessments of population responses to environmental perturbation must therefore consider how effects might propagate across life-history transitions. We investigated consequences of ocean acidification (decreased pH and carbonate saturation) for early life stages of the Olympia oyster (Ostrea lurida), a foundation species in estuaries along the Pacific coast of North America. We reared oysters at three levels of seawater pH, including a control (8.0) and two additional levels (7.9 and 7.8). Oysters were cultured through their planktonic larval period to metamorphosis and into early juvenile life. Larvae reared under pH 7.8 exhibited a 15% decrease in larval shell growth rate, and a 7% decrease in shell area at settlement, compared to larvae reared under control conditions. Impacts were even more pronounced a week after settlement, with juveniles that had been reared as larvae under reduced pH exhibiting a 41% decrease in shell growth rate. Importantly, the latter effect arose regardless of the pH level the oysters experienced as juveniles, indicating a strong carry-over effect from the larval phase. Adverse impacts of early exposure to low pH persisted for at least 1.5 months after juveniles were transferred to a common environment. Overall, our results suggest that a stringent focus on a single phase of the life cycle (e.g., one perceived as the "weakest link") may neglect critical impacts that can be transferred across life stages in taxa with complex life histories.
Stages of Mycosis Fungoides and the Sezary Syndrome
... usually palliative , to relieve symptoms and improve the quality of life . Patients with early stage disease may live many ... as palliative therapy to relieve symptoms and improve quality of life . Sometimes, total skin electron beam (TSEB) radiation therapy ...
George, D R; Sparagano, O A E; Port, G; Okello, E; Shiel, R S; Guy, J H
2010-03-01
Seven essential oils with potential as acaricides for use against the poultry red mite, Dermanyssus gallinae (De Geer) (Acari: Dermanyssidae), were selected for study. These products (essential oils of manuka, cade, pennyroyal, thyme, garlic, clove bud and cinnamon bark) were deployed against different life stages of D. gallinae in laboratory tests at the (lethal concentration) LC(50) level for adult mites. For all essential oils tested, toxicity to D. gallinae juveniles was as high as toxicity to adults, if not higher. However, at the LC(50) level determined for adults, some oils were ineffective in preventing hatching of D. gallinae eggs. The essential oils were also tested under laboratory conditions at their LC(90) levels for D. gallinae adults on two model non-target species, the brine shrimp, Artemia salina (L.), and the mealworm beetle, Tenebrio molitor (L.). Results showed that not all essential oils were as toxic to A. salina and T. molitor as they were to D. gallinae, suggesting that it may be possible to select certain oils for development as acaricides against D. gallinae that would have minimal impact on non-target organisms. However, the level of toxicity to A. salina and T. molitor was not consistent across the selected essential oils.
Reproductive and early life stages pathology - Histopathology workshop report
Bruno, D.W.; Nowak, B.; Elliott, Diane G.
2006-01-01
Pathology occurring during reproduction and larval development represents an important part of the life cycle of fish, and the diseases that affect eggs and larvae often result in significant losses. However, mortality during this period is frequently ignored or poorly researched as the temptation is to replace the losses rather than investigate the causes. A histopathology workshop organised at the newly refurnished laboratory within the Danish Veterinary School was an opportunity to discuss the pathology of selected diseases associated with Reproductive and Early Life Stages Pathology. Several people also kindly provided reference slides.
Thompson, Jamie N.; Beauchamp, David A.
2014-01-01
We evaluated freshwater growth and survival from juvenile (ages 0–3) to smolt (ages 1–5) and adult stages in wild steelhead Oncorhynchus mykiss sampled in different precipitation zones of the Skagit River basin, Washington. Our objectives were to determine whether significant size-selective mortality (SSM) in steelhead could be detected between early and later freshwater stages and between each of these freshwater stages and returning adults and, if so, how SSM varied between these life stages and mixed and snow precipitation zones. Scale-based size-at-annulus comparisons indicated that steelhead in the snow zone were significantly larger at annulus 1 than those in the mixed rain–snow zone. Size at annuli 2 and 3 did not differ between precipitation zones, and we found no precipitation zone × life stage interaction effect on size at annulus. Significant freshwater and marine SSM was evident between the juvenile and adult samples at annulus 1 and between each life stage at annuli 2 and 3. Rapid growth between the final freshwater annulus and the smolt migration did not improve survival to adulthood; rather, it appears that survival in the marine environment may be driven by an overall higher growth rate set earlier in life, which results in a larger size at smolt migration. Efforts for recovery of threatened Puget Sound steelhead could benefit by considering that SSM between freshwater and marine life stages can be partially attributed to growth attained in freshwater habitats and by identifying those factors that limit growth during early life stages.
PPTOX III: environmental stressors in the developmental origins of disease--evidence and mechanisms.
Schug, Thaddeus T; Barouki, Robert; Gluckman, Peter D; Grandjean, Philippe; Hanson, Mark; Heindel, Jerold J
2013-02-01
Fetal and early postnatal development constitutes the most vulnerable time period of human life in regard to adverse effects of environmental hazards. Subtle effects during development can lead to functional deficits and increased disease risk later in life. The hypothesis stating that environmental exposures leads to altered programming and, thereby, to increased susceptibility to disease or dysfunction later in life has garnered much support from both experimental and epidemiological studies. Similar observations have been made on the long-term impact of nutritional unbalance during early development. In an effort to bridge the fields of nutritional and environmental developmental toxicity, the Society of Toxicology sponsored this work. This report summarizes novel findings in developmental toxicity as reported by select invited experts and meeting attendees. Recommendations for the application and improvement of current and future research efforts are also presented.
Baker, Bridget B; Yee, Jeremiah S; Meyer, Danielle N; Yang, Doris; Baker, Tracie R
2016-10-01
We have shown that zebrafish (Danio rerio) are an excellent model for evaluating the link between early life stage exposure to environmental chemicals and disease in adulthood and subsequent unexposed generations. Previously, we used this model to identify transgenerational effects of dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin [TCDD]) on skeletal development, sex ratio, and reproductive capacity. Transgenerational inheritance of TCDD toxicity, notably decreased reproductive capacity, appears to be mediated through the male germ line. Thus, we examine testicular tissue for structural and gene expression changes using histology, microarray, and quantitative reverse transcription polymerase chain reaction (qRT-PCR). Histological analysis revealed decreased spermatozoa with concurrent increase in spermatogonia, and decreased germinal epithelium thickness in TCDD-exposed males compared with controls. We also identified altered expression of genes associated with testis development, steroidogenesis, spermatogenesis, hormone metabolism, and xenobiotic response. Altered genes are in pathways involving lipid metabolism, molecular transport, small molecule biochemistry, cell morphology, and metabolism of vitamins and minerals. These data will inform future investigations to elucidate the mechanism of adult-onset and transgenerational infertility due to TCDD exposure in zebrafish.
Suga, Hirotaka; Shiraishi, Tomohiro; Takushima, Akihiko; Harii, Kiyonori
2016-01-01
Toxic shock syndrome is a rare but life-threatening complication after plastic surgery procedures. We experienced 2 cases of toxic shock syndrome after expander-based breast reconstruction caused by methicillin-resistant Staphylococcus aureus. The first patient took a severe clinical course due to the delayed diagnosis and treatment, and the second patient recovered rapidly after the early diagnosis and treatment based on our experience of the first case. Fever, rash, and gastrointestinal symptoms (diarrhea and/or vomiting) were characteristic and important for the early diagnosis of toxic shock syndrome. Considering the increased prevalence of methicillin-resistant Staphylococcus aureus, we should suspect methicillin-resistant Staphylococcus aureus in cases of toxic shock syndrome that occur postoperatively, and the empiric administration of vancomycin should be initiated in such cases.
Rodriguez-Saona, Cesar; Wanumen, Andrea Carolina; Salamanca, Jordano; Holdcraft, Robert; Kyryczenko-Roth, Vera
2016-04-15
Laboratory and extended laboratory bioassays were conducted to determine the residual toxicities of various insecticides against two key pests of cranberries, Sparganothis sulfureana and Choristoneura parallela (Lepidoptera: Tortricidae), and their non-target effects on the predatory Orius insidiosus (Hemiptera: Anthocoridae). The effects of nine insecticides with different modes of action on S. sulfureana and Ch. parallela eggs, larvae, and adults were tested in the laboratory, while the efficacy of a post-bloom application on larval mortality and mass of these pests and on adult O. insidiosus was evaluated in extended laboratory experiments. The organophosphate chlorpyrifos and the spinosyn spinetoram provided long-lasting (seven-day) control against all stages of both pests. The growth regulator methoxyfenozide and the diamides chlorantraniliprole and cyantraniliprole had strong (1-7 days) larvicidal, particularly on young larvae, and growth inhibitory activity, but only the diamides were adulticidal. Among neonicotinoids, acetamiprid had stronger ovicidal and adulticidal activity than thiamethoxam, showing within-insecticide class differences in toxicities; however, both were weak on larvae. Lethality of novaluron and indoxacarb was inconsistent, varying depending on species and stage. Chlorpyrifos was most toxic to O. insidiosus. These results show species- and stage-specific toxicities, and greater compatibility with biological control, of the newer reduced-risk classes of insecticides than older chemistries.
Barjhoux, Iris; Clérandeau, Christelle; Menach, Karyn Le; Anschutz, Pierre; Gonzalez, Patrice; Budzinski, Hélène; Morin, Bénédicte; Baudrimont, Magalie; Cachot, Jérôme
2017-08-01
Sediment compartment is a long term sink for pollutants and a secondary source of contamination for aquatic species. The abiotic factors controlling the bioavailability and thus the toxicity of complex mixtures of pollutants accumulated in sediments are poorly documented. To highlight the different factors influencing sediment toxicity, we identified and analyzed the physico-chemical properties, micro-pollutant contents, and toxicity level of six contrasted sediments in the Lot-Garonne continuum. Sediment toxicity was evaluated using the recently described Japanese medaka (Oryzias latipes) embryo-larval assay with direct exposure to whole sediment (MELAc). Multiple toxicity endpoints including embryotoxicity, developmental defects and DNA damage were analyzed in exposed embryos. Chemical analyses revealed significant variations in the nature and contamination profile of sediments, mainly impacted by metallic trace elements and, unexpectedly, polycyclic aromatic hydrocarbons. Exposure to sediments induced different toxic impacts on medaka early life stages when compared with the reference site. Principal component analysis showed that the toxic responses following exposure to sediments from the Lot River and its tributary were associated with micro-pollutant contamination: biometric measurements, hatching success, genotoxicity, craniofacial deformities and yolk sac malabsorption were specifically correlated to metallic and organic contaminants. Conversely, the main biological responses following exposure to the Garonne River sediments were more likely related to their physico-chemical properties than to their contamination level. Time to hatch, cardiovascular injuries and spinal deformities were correlated to organic matter content, fine particles and dissolved oxygen levels. These results emphasize the necessity of combining physico-chemical analysis of sediment with toxicity assessment to accurately evaluate the environmental risks associated with sediment contamination. Copyright © 2017 Elsevier Inc. All rights reserved.
NASA Astrophysics Data System (ADS)
Losso, C.; Arizzi Novelli, A.; Picone, M.; Marchetto, D.; Pessa, G.; Molinaroli, E.; Ghetti, P. F.; Volpi Ghirardini, A.
2004-11-01
Toxic hazard in sites with varying types and levels of contamination in the Lagoon of Venice was estimated by means of toxicity bioassays based on the early life-stages of the autochthonous sea urchin Paracentrotus lividus. Elutriate was chosen as the test matrix, due to its ability to highlight potential toxic effects towards sensitive biological components of the water column caused by sediment resuspension phenomena affecting the Lagoon. Surficial sediments (core-top 5 cm deep), directly influenced by resuspension/redeposition processes, and core sediments (core 20 cm deep), recording time-mediated contamination, were sampled in some sites located in the lagoonal area most greatly influenced by anthropogenic activities. Particle size, organic matter and water content were also analysed. In two sites, the results of physical parameters showed that the core-top sediments were coarser than the 20-cm core sediments. Sperm cell toxicity test results showed the negligible acute toxicity of elutriates from all investigated sites. The embryo toxicity test demonstrated a short-term chronic toxicity gradient for elutriates from the 20-cm core sediments, in general agreement both with the expected contamination gradient and with results of the Microtox® solid-phase test. Elutriates of the core-top 5-cm sediments revealed a totally inverted gradient, in comparison with that for the 20-cm core sediments, and the presence of a "hot spot" of contamination in the site chosen as a possible reference. Investigations on ammonia and sulphides as possible confounding factors excluded their contribution to this "hot spot". Integrated physico-chemical and toxicity results on sediments at various depths demonstrated the presence of disturbed sediments in the central basin of the Lagoon of Venice.
Carreon-Martinez, Lucia B.; Walter, Ryan P.; Johnson, Timothy B.; Ludsin, Stuart A.; Heath, Daniel D.
2015-01-01
Nutrient-rich, turbid river plumes that are common to large lakes and coastal marine ecosystems have been hypothesized to benefit survival of fish during early life stages by increasing food availability and (or) reducing vulnerability to visual predators. However, evidence that river plumes truly benefit the recruitment process remains meager for both freshwater and marine fishes. Here, we use genotype assignment between juvenile and larval yellow perch (Perca flavescens) from western Lake Erie to estimate and compare recruitment to the age-0 juvenile stage for larvae residing inside the highly turbid, south-shore Maumee River plume versus those occupying the less turbid, more northerly Detroit River plume. Bayesian genotype assignment of a mixed assemblage of juvenile (age-0) yellow perch to putative larval source populations established that recruitment of larvae was higher from the turbid Maumee River plume than for the less turbid Detroit River plume during 2006 and 2007, but not in 2008. Our findings add to the growing evidence that turbid river plumes can indeed enhance survival of fish larvae to recruited life stages, and also demonstrate how novel population genetic analyses of early life stages can contribute to determining critical early life stage processes in the fish recruitment process. PMID:25954968
Buhl, Kevin J.; Hamilton, S.J.
1996-01-01
Two life stages of three federally-listed endangered fishes, Colorado squawfish (Ptychocheilus lucius), bonytail (Gila elegans), and razorback sucker (Xyrauchen texanus) were exposed to copper, selenate, selenite, and zinc individually, and to mixtures of nine inorganics in a reconstituted water that simulated the water quality of the middle Green River, Utah. The mixtures simulated environmental ratios of arsenate, boron, copper, molybdenum, selenate, selenite, uranium, vanadium, and zinc in two tributaries, Ashley Creek and Stewart Lake outlet, of the middle Green River. The rank order of toxicity of the individual inorganics, from most to least toxic, was: copper > zinc > selenite > selenate. Colorado squawfish larvae were more sensitive to all four inorganics and the two mixtures than the juveniles, whereas there was no consistent response between the two life stages for the other two species. There was no consistent difference in sensitivity to the inorganics among the three endangered fishes. Both mixtures exhibited either additive or greater than additive toxicity to these fishes. The primary toxic components in the mixtures, based on toxic units, were copper and zinc. Acute toxicity values were compared to measured environmental concentrations in the two tributaries to derive margins of uncertainty. Margins of uncertainty were low for both mixtures (9–22 for the Stewart Lake outlet mixture, and 12–32 for the Ashley Creek mixture), indicating that mixtures of inorganics derived from irrigation activities may pose a hazard to endangered fishes in the Green River.
Treatment Options by Stage (Mycosis Fungoides and the Sezary Syndrome)
... usually palliative , to relieve symptoms and improve the quality of life . Patients with early stage disease may live many ... as palliative therapy to relieve symptoms and improve quality of life . Sometimes, total skin electron beam (TSEB) radiation therapy ...
Metcalfe, Tracy L; Dillon, Peter J; Metcalfe, Chris D
2008-04-01
Golf courses impact the environment through alterations to habitat and through the release of nutrients and pesticides. The Precambrian Shield region of central Ontario, Canada, which is a major recreational area, is especially susceptible to the impacts of golf courses as a result of the geology and hydrology of the region. In a monitoring program at two golf courses in the Muskoka region conducted during the spring, summer, and fall of 2002, semipermeable membrane devices (SPMDs) were deployed into streams that drain the golf courses. The extracts from the SPMDs were tested for toxicity using bioassays with early life stages of an aquarium fish, the Japanese medaka (Oryzias latipes). Toxicity was assessed using a scoring system developed for the present study. The bioassays with medaka indicated that toxicity was highest in extracts from SPMDs deployed during the spring and the fall. The peaks in toxicity for the SPMDs deployed at the two golf courses corresponded with the presence in the SPMD extracts of pentachloronitrobenzene (PCNB) at concentrations up to 334 ng/SPMD. Quintozene is the turfgrass fungicide in which PCNB is the active ingredient. Pentachlorothioanisole, an anaerobic degradation product of PCNB, also was detected in the SPMDs deployed during the spring. Extracts prepared from SPMDs with high toxicity contained residues of a surfactant used in pesticide formulations, nonylphenol, at concentrations up to approximately 20 microg/SPMD. Overall, these data indicate that some pesticides applied to golf courses in the Precambrian Shield of central Ontario may have the potential to cause toxic impacts to aquatic organisms in adjacent watersheds.
Morgan, T P; Guadagnolo, C M; Grosell, M; Wood, C M
2005-09-30
Early life stages of rainbow trout were exposed to 0, 0.1 and 1 microg/L Ag (as AgNO(3)) in very soft water (2mg/L CaCO(3)), moderately hard water (150 mg/L CaCO(3)) and hard water (400mg/L CaCO(3)) of low dissolved organic carbon concentration (0.5mg C/L) from fertilization to swim-up (64 days) under flow-through conditions, and monitored for whole embryo/larval silver accumulation, Na(+) and Cl(-) concentrations, Na(+) uptake and Na(+)K(+)-ATPase activity. The objective of the study was to investigate potential protective effects of water hardness on the physiological responses to chronic silver exposure. In the absence of silver, there was little effect of hardness on the ionoregulatory parameters studied, though higher hardness did improve survival post-hatch. At all three water hardness levels, whole embryo/larval Na(+) uptake was low and relatively constant prior to 50% hatch, but dramatically increased following 50% hatch, whereas Na(+)K(+)-ATPase activity steadily increased over development. Whole embryo/larval Na(+) and Cl(-) concentrations were low and constant prior to 50% hatch, but following 50% hatch Na(+) concentration increased, while Cl(-) concentration decreased. Following 50% hatch, exposure to 0.1 and 1 microg/L Ag resulted in a decrease in whole embryo/larval Na(+) concentration, Cl(-) concentration, Na(+) uptake and Na(+)K(+)-ATPase activity, indicating that the mechanism of chronic silver toxicity involves an ionoregulatory disturbance, and is similar to the mechanism of acute silver toxicity. An increase in water hardness reduced or eliminated the effect of silver on these parameters while enhancing survival, suggesting that the nature of the protective effect of hardness involves effects on the ionoregulatory disturbance associated with silver exposure. An increase in water hardness did not fully protect against the accumulation of silver associated with silver exposure. These results suggest that it may be possible to model chronic silver toxicity using a biotic ligand type model, and that a physiologically based model may be more appropriate because Na(+)K(+)-ATPase activity or Na(+) uptake is an endpoint for prediction rather than whole embryo or larval silver accumulation.
Tharwat, Alaa; Moemen, Yasmine S; Hassanien, Aboul Ella
2017-04-01
Measuring toxicity is an important step in drug development. Nevertheless, the current experimental methods used to estimate the drug toxicity are expensive and time-consuming, indicating that they are not suitable for large-scale evaluation of drug toxicity in the early stage of drug development. Hence, there is a high demand to develop computational models that can predict the drug toxicity risks. In this study, we used a dataset that consists of 553 drugs that biotransformed in liver. The toxic effects were calculated for the current data, namely, mutagenic, tumorigenic, irritant and reproductive effect. Each drug is represented by 31 chemical descriptors (features). The proposed model consists of three phases. In the first phase, the most discriminative subset of features is selected using rough set-based methods to reduce the classification time while improving the classification performance. In the second phase, different sampling methods such as Random Under-Sampling, Random Over-Sampling and Synthetic Minority Oversampling Technique (SMOTE), BorderLine SMOTE and Safe Level SMOTE are used to solve the problem of imbalanced dataset. In the third phase, the Support Vector Machines (SVM) classifier is used to classify an unknown drug into toxic or non-toxic. SVM parameters such as the penalty parameter and kernel parameter have a great impact on the classification accuracy of the model. In this paper, Whale Optimization Algorithm (WOA) has been proposed to optimize the parameters of SVM, so that the classification error can be reduced. The experimental results proved that the proposed model achieved high sensitivity to all toxic effects. Overall, the high sensitivity of the WOA+SVM model indicates that it could be used for the prediction of drug toxicity in the early stage of drug development. Copyright © 2017 Elsevier Inc. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Stanic, Sinisa, E-mail: sinisa.stanic@carle.com; Paulus, Rebecca; Timmerman, Robert D.
2014-04-01
Purpose: To investigate pulmonary function test (PFT) results and arterial blood gas changes (complete PFT) following stereotactic body radiation therapy (SBRT) and to see whether baseline PFT correlates with lung toxicity and overall survival in medically inoperable patients receiving SBRT for early stage, peripheral, non-small cell lung cancer (NSCLC). Methods and Materials: During the 2-year follow-up, PFT data were collected for patients with T1-T2N0M0 peripheral NSCLC who received effectively 18 Gy × 3 in a phase 2 North American multicenter study (Radiation Therapy Oncology Group [RTOG] protocol 0236). Pulmonary toxicity was graded by using the RTOG SBRT pulmonary toxicity scale. Paired Wilcoxon signedmore » rank test, logistic regression model, and Kaplan-Meier method were used for statistical analysis. Results: At 2 years, mean percentage predicted forced expiratory volume in the first second and diffusing capacity for carbon monoxide declines were 5.8% and 6.3%, respectively, with minimal changes in arterial blood gases and no significant decline in oxygen saturation. Baseline PFT was not predictive of any pulmonary toxicity following SBRT. Whole-lung V5 (the percentage of normal lung tissue receiving 5 Gy), V10, V20, and mean dose to the whole lung were almost identical between patients who developed pneumonitis and patients who were pneumonitis-free. Poor baseline PFT did not predict decreased overall survival. Patients with poor baseline PFT as the reason for medical inoperability had higher median and overall survival rates than patients with normal baseline PFT values but with cardiac morbidity. Conclusions: Poor baseline PFT did not appear to predict pulmonary toxicity or decreased overall survival after SBRT in this medically inoperable population. Poor baseline PFT alone should not be used to exclude patients with early stage lung cancer from treatment with SBRT.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Bi, Xi-Wen; Li, Ye-Xiong, E-mail: yexiong@yahoo.com; Fang, Hui
2013-12-01
Purpose: To assess the dosimetric benefit, treatment outcome, and toxicity of high-dose and extended-field intensity modulated radiation therapy (IMRT) in patients with early-stage NK/T-cell lymphoma of Waldeyer's ring (WR-NKTCL). Methods and Materials: Thirty patients with early-stage WR-NKTCL who received extended-field IMRT were retrospectively reviewed. The prescribed dose was 50 Gy to the primary involved regions and positive cervical lymph nodes (planning target volume requiring radical irradiation [PTV{sub 50}]) and 40 Gy to the negative cervical nodes (PTV{sub 40}). Dosimetric parameters for the target volume and critical normal structures were evaluated. Locoregional control (LRC), overall survival (OS), and progression-free survival (PFS)more » were calculated using the Kaplan-Meier method. Results: The median mean doses to the PTV{sub 50} and PTV{sub 40} were 53.2 Gy and 43.0 Gy, respectively. Only 1.4% of the PTV{sub 50} and 0.9% of the PTV{sub 40} received less than 95% of the prescribed dose, indicating excellent target coverage. The average mean doses to the left and right parotid glands were 27.7 and 28.4 Gy, respectively. The 2-year OS, PFS, and LRC rates were 71.2%, 57.4%, and 87.8%. Most acute toxicities were grade 1 to 2, except for grade ≥3 dysphagia and mucositis. The most common late toxicity was grade 1-2 xerostomia, and no patient developed any ≥grade 3 late toxicities. A correlation between the mean dose to the parotid glands and the degree of late xerostomia was observed. Conclusions: IMRT achieves excellent target coverage and dose conformity, as well as favorable survival and locoregional control rates with acceptable toxicities in patients with WR-NKTCL.« less
Effects of Chemotherapy on the Brain in Women With Newly Diagnosed Early-Stage Breast Cancer
2017-11-21
Breast Cancer; Chemotherapeutic Agent Toxicity; Cognitive/Functional Effects; Fatigue; Long-term Effects Secondary to Cancer Therapy in Adults; Neurotoxicity; Psychosocial Effects of Cancer and Its Treatment
Distribution of early life history stages of fishes in selected pools of the upper Mississippi River
Holland, L.E.
1986-01-01
Effective management of the fishery resources of the Upper Mississippi River and successful mitigation of the loss of critical habitat depend in part on an understanding of the reproductive and early life history requirements of the affected fishes. However, little is known about the use of nursery areas by fishes in the river. Of the nearly 130 species identified in the adult ichthyofauna, only a few are represented proportionally in the available data on early life stages because study designs have not included consideration of the early stages, collection gears have not adequately sampled the young, and eggs and larvae of some species are difficult to sample by conventional approaches. For the species collected, information is available on seasonal variations in total densities, composition, and catch among different habitat types. However, the data are most accurate for species with buoyant early life stages, such as freshwater drum (Aplodinotus grunniens) and gizzard shad (Dorosoma cepedianum). Eggs and larvae of freshwater drum dominate collections made in the main channel, whereas other larval fishes are usually most abundant in backwater habitats. The species found there usually deposit eggs on the substrate or on vegetation. Habitat preferences (as indicated by relative abundance) often shift as development proceeds and physical and behavioral changes occur in the larvae. Only limited information is available on the distribution of larvae within habitats, but it is clear that variations within habitats are significant.
COMPARATIVE SENSITIVITY OF DIFFERENT LIFE-STAGES OF MEDAKA AND SALMONID FISHES TO 2,3,7,8-TCDD
The early life stages of fish are known to be more sensitive than the adults to the toxicological effects of 2,3,7,8-tetrachlorodibenzo(p)dioxin (TCDD). Embryo larval stages of medake, for example, experience 50% lethality when TCDD residues in the eggs are 1396 pg/g. By contrast...
Buchwalter, D.B.; Sandahl, J.F.; Jenkins, J.J.; Curtis, L.R.
2004-01-01
Early life stages of aquatic organisms tend to be more sensitive to various chemical contaminants than later life stages. This research attempted to identify the key biological factors that determined sensitivity differences among life stages of the aquatic insect Chironomous riparius. Specifically, second to fourth instar larvae were exposed in vivo to both low and high waterborne concentrations of chlorpyrifos to examine differences in accumulation rates, chlorpyrifos biotransformation, and overall sensitivity among instars. In vitro acetylcholinesterase (AChE) assays were performed with chlorpyrifos and the metabolite, chlorpyrifos-oxon, to investigate potential target site sensitivity differences among instars. Earlier instars accumulated chlorpyrifos more rapidly than later instars. There were no major differences among instars in the biotransformation rates of chlorpyrifos to the more polar metabolites, chlorpyrifos-oxon, and chlorpyridinol (TCP). Homogenate AChE activities from second to fourth instar larvae were refractory to chlorpyrifos, even at high concentrations. In contrast, homogenate AChE activities were responsive in a dose-dependent manner to chlorpyrifos-oxon. In general, it appeared that chlorpyrifos sensitivity differences among second to fourth instar C. riparius were largely determined by differences in uptake rates. In terms of AChE depression, fourth instar homogenates were more sensitive to chlorpyrifos and chlorpyrifos-oxon than earlier instars. However, basal AChE activity in fourth instar larvae was significantly higher than basal AChE activity in second to third instar larvae, which could potentially offset the apparent increased sensitivity to the oxon. ?? 2003 Elsevier B.V. All rights reserved.
2000-06-30
Center for Environmental Health Research (USACEHR), the United States Environmental Protection Agency (USEPA), Johns Hopkins University Applied Physics...Joanne M. Burkholder and fellow North Carolina State researchers in 1988, has the ability to assume a toxic life cycle stage under appropriate...P. piscicida form. If the toxic form ofP. piscicida is present in the optimal quantity, the fish \\vill usually die within an hour. Dr. Burkholder
Toward Understanding How Early-Life Stress Reprograms Cognitive and Emotional Brain Networks.
Chen, Yuncai; Baram, Tallie Z
2016-01-01
Vulnerability to emotional disorders including depression derives from interactions between genes and environment, especially during sensitive developmental periods. Adverse early-life experiences provoke the release and modify the expression of several stress mediators and neurotransmitters within specific brain regions. The interaction of these mediators with developing neurons and neuronal networks may lead to long-lasting structural and functional alterations associated with cognitive and emotional consequences. Although a vast body of work has linked quantitative and qualitative aspects of stress to adolescent and adult outcomes, a number of questions are unclear. What distinguishes 'normal' from pathologic or toxic stress? How are the effects of stress transformed into structural and functional changes in individual neurons and neuronal networks? Which ones are affected? We review these questions in the context of established and emerging studies. We introduce a novel concept regarding the origin of toxic early-life stress, stating that it may derive from specific patterns of environmental signals, especially those derived from the mother or caretaker. Fragmented and unpredictable patterns of maternal care behaviors induce a profound chronic stress. The aberrant patterns and rhythms of early-life sensory input might also directly and adversely influence the maturation of cognitive and emotional brain circuits, in analogy to visual and auditory brain systems. Thus, unpredictable, stress-provoking early-life experiences may influence adolescent cognitive and emotional outcomes by disrupting the maturation of the underlying brain networks. Comprehensive approaches and multiple levels of analysis are required to probe the protean consequences of early-life adversity on the developing brain. These involve integrated human and animal-model studies, and approaches ranging from in vivo imaging to novel neuroanatomical, molecular, epigenomic, and computational methodologies. Because early-life adversity is a powerful determinant of subsequent vulnerabilities to emotional and cognitive pathologies, understanding the underlying processes will have profound implications for the world's current and future children.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Brannon, E.L.; Moulton, L.L.; Gilbertson, L.G.
1995-12-31
This paper discusses results of field programs initiated within a few days of the spill and designed to assess spill effects on critical early life stages of pink salmon in postspill years. Samples of water and stream sediments from throughout the spill area were used to define the exposure of pink salmon to residual hydrocarbons from the spill. Mean sediment concentrations of polycyclic aromatic hydrocarbons (PAH) up to 300 ppb were measured in oiled streams in 1989 and generally followed a downward trend toward background in 1990 and 1991. These PAH concentrations were then used in regression analyses of potentialmore » effects on key early life stages of pink salmon. Water samples taken from both nearshore feeding and rearing areas and offshore migratory areas show that hydrocarbon concentrations were from one to four orders of magnitude lower than concentrations reported in the literature to cause acute or chronic effects on fish species. The postspill field and laboratory studies of pink salmon early life stages included examination of potential effects on 1989, 1990, and 1991 eggs, fry, and juveniles. 28 refs., 8 figs., 8 tabs.« less
Micro-topography mediates interactions between corals, algae, and herbivorous fishes on coral reefs
NASA Astrophysics Data System (ADS)
Brandl, S. J.; Hoey, A. S.; Bellwood, D. R.
2014-06-01
Processes occurring during the early life stages of corals are important for the replenishment of coral assemblages and the resilience of coral reefs. However, the factors influencing early life stages of corals are not well understood, and the role of micro-topographic complexity for habitat associations of juvenile corals is largely unexplored. This study investigated the microhabitat distribution patterns of early life stages of corals and a potential macroalgal competitor ( Turbinaria ornata) across two reef zones (reef crest and outer reef flat) on Lizard Island, Great Barrier Reef. In both reef zones, both corals and T. ornata were significantly more abundant in concealed microhabitats than in semi-concealed or open microhabitats (GLMM: P < 0.001). The prevalence of juvenile corals and T. ornata within concealed environments suggests that they might be effective refuges from grazing by herbivorous fishes. The density of juvenile corals was positively related, and density of T. ornata negatively related to the abundance of two groups of herbivorous fishes, pairing rabbitfishes, and surgeonfishes in the genus Zebrasoma (BEST ENV-BIO: r s = 0.72, P < 0.01), which feed in concealed microhabitats. This correlative evidence suggests that crevices may be important for early life stages of both coral and macroalgae, and that a specific suite of crevice-feeding fishes may influence benthic community dynamics in these microhabitats.
Oribe, Madalen; Lertxundi, Aitana; Basterrechea, Mikel; Begiristain, Haizea; Santa Marina, Loreto; Villar, María; Dorronsoro, Miren; Amiano, Pilar; Ibarluzea, Jesús
2015-01-01
To estimate the prevalence of exclusive breastfeeding (EB) during the first 6 months of life in the Gipuzkoa birth cohort, identify the reasons for abandonment of EB, and establish the associated factors. The study population consisted of 638 pregnant women from the INMA-Gipuzkoa (Infancia y Medio Ambiente, www.proyectoinma.org) birth cohort, who were followed up from the third trimester of pregnancy until the child was aged 14 months. To determine the factors related to abandonment of EB, logistic regression models were used in two different stages (4 months or early stage and 6 months or late stage). The prevalence of EB within the Gipuzkoa cohort was 84.8% after hospital discharge, 53.7% at 4 months of life and 15.4% at 6 months of life. The reasons given by the mothers for early EB cessation were: breastfeeding problems, low weight gain and hypogalactia. Other factors influencing the early phase were the intention to provide EB, parity, area of residence and social class. Abandonment in the late stage was influenced by the length of maternity leave. From a public health perspective, the results of this study could help health professionals to develop strategies to support breastfeeding mothers, taking into account the main reasons for early and late abandonment. Copyright © 2014 SESPAS. Published by Elsevier Espana. All rights reserved.
Erikson's Psychosocial Theories Help Explain Early Adolescence.
ERIC Educational Resources Information Center
Manning, M. Lee
1988-01-01
Middle school educators can design a learning environment for early adolescents based on Erik Erikson's social development theories, which divide human life into eight psychological stages. The identity versus role confusion stage characterizing adolescence will significantly determine the developing person's future. Schools can help learners…
Deneka, Alexander Y; Haber, Leora; Kopp, Meghan C; Gaponova, Anna V; Nikonova, Anna S; Golemis, Erica A
2017-01-01
Non-small cell lung cancer (NSCLC) is the leading cause of cancer death worldwide, with a 5-year survival of only ~16%. Potential strategies to address NSCLC mortality include improvements in early detection and prevention, and development of new therapies suitable for use in patients with early and late stage diagnoses. Controlling the growth of early stage tumors could yield significant clinical benefits for patients with comorbidities that make them poor candidates for surgery: however, many drugs that limit cancer growth are not useful in the setting of long-term use or in comorbid patients, because of associated toxicities. In this study, we explored the use of a recently described small molecule agent, STA-8666, as a potential agent for controlling early stage tumor growth. STA-8666 uses a cleavable linker to merge a tumor-targeting moiety that binds heat shock protein 90 (HSP90) with the cytotoxic chemical SN38, and has been shown to have high efficacy and low toxicity, associated with efficient tumor targeting, in preclinical studies using patient-derived and other xenograft models for pancreatic, bladder, and small cell lung cancer. Using a genetically engineered model of NSCLC arising from induced mutation of KRas and knockout of Trp53, we continuously dosed mice with STA-8666 from immediately after tumor induction for 15 weeks. STA-8666 significantly slowed the rate of tumor growth, and was well tolerated over this extended dosing period. STA-8666 induced DNA damage and apoptosis, and reduced proliferation and phosphorylation of the proliferation-associated protein ERK1/2, selectively in tumor tissue. In contrast, STA-8666 did not affect tumor features, such as degree of vimentin staining, associated with epithelial-mesenchymal transition (EMT), or downregulate tumor expression of HSP90. These data suggest STA-8666 and other similar targeted compounds may be useful additions to control the growth of early stage NSCLC in patient populations.
ADMET in silico modelling: towards prediction paradise?
van de Waterbeemd, Han; Gifford, Eric
2003-03-01
Following studies in the late 1990s that indicated that poor pharmacokinetics and toxicity were important causes of costly late-stage failures in drug development, it has become widely appreciated that these areas should be considered as early as possible in the drug discovery process. However, in recent years, combinatorial chemistry and high-throughput screening have significantly increased the number of compounds for which early data on absorption, distribution, metabolism, excretion (ADME) and toxicity (T) are needed, which has in turn driven the development of a variety of medium and high-throughput in vitro ADMET screens. Here, we describe how in silico approaches will further increase our ability to predict and model the most relevant pharmacokinetic, metabolic and toxicity endpoints, thereby accelerating the drug discovery process.
Developmental origins of non-communicable disease: Implications for research and public health
2012-01-01
This White Paper highlights the developmental period as a plastic phase, which allows the organism to adapt to changes in the environment to maintain or improve reproductive capability in part through sustained health. Plasticity is more prominent prenatally and during early postnatal life, i.e., during the time of cell differentiation and specific tissue formation. These developmental periods are highly sensitive to environmental factors, such as nutrients, environmental chemicals, drugs, infections and other stressors. Nutrient and toxicant effects share many of the same characteristics and reflect two sides of the same coin. In both cases, alterations in physiological functions can be induced and may lead to the development of non-communicable conditions. Many of the major diseases – and dysfunctions – that have increased substantially in prevalence over the last 40 years seem to be related in part to developmental factors associated with either nutritional imbalance or exposures to environmental chemicals. The Developmental Origins of Health and Disease (DOHaD) concept provides significant insight into new strategies for research and disease prevention and is sufficiently robust and repeatable across species, including humans, to require a policy and public health response. This White Paper therefore concludes that, as early development (in utero and during the first years of postnatal life) is particularly sensitive to developmental disruption by nutritional factors or environmental chemical exposures, with potentially adverse consequences for health later in life, both research and disease prevention strategies should focus more on these vulnerable life stages. PMID:22715989
Recovery of lotic macroinvertebrate communities from disturbance
NASA Astrophysics Data System (ADS)
Wallace, J. Bruce
1990-09-01
Ecosystem disturbances produce changes in macrobenthic community structure (abundances, biomass, and production) that persist for a few weeks to many decades. Examples of disturbances with extremely long-term effects on benthic communities include contamination by persistent toxic agents, physical changes in habitats, and altered energy inputs. Stream size, retention, and local geomorphology may ameliorate the influence of disturbances on invertebrates. Disturbances can alter food webs and may select for favorable genotypes (e.g., insecticidal resistance). Introductions of pesticides into lotic ecosystems, which do not result in major physical changes within habitats, illustrate several factors that influence invertebrate recovery time from disturbance. These include: (1) magnitude of original contamination, toxicity, and extent of continued use; (2) spatial scale of the disturbance; (3) persistence of the pesticide; (4) timing of the contamination in relation to the life history stages of the organisms; (5) vagility of populations influenced by pesticides; and (6) position within the drainage network. The ability of macroinvertebrates to recolonize denuded stream habitats may vary greatly depending on regional life histories, dispersal abilities, and position within the stream network (e.g., headwaters vs larger rivers). Although downstream drift is the most frequently cited mechanism of invertebrate recolonization following disturbance in middle- and larger-order streams, evidence is presented that shows aerial recolonization to be potentially important in headwater streams. There is an apparent stochastic element operating for aerial recolonization, depending on the timing of disturbance and flight periods of various taxa. Available evidence indicates that recolonization of invertebrate taxa without an aerial adult stage requires longer periods of time than for those that possess winged, terrestrial adult stages (i.e., most insects). Innovative, manipulative experiments are needed in order to address recolonization mechanisms of animals inhabiting streams that differ in size, latitude, disturbance frequency and magnitude, as well as the potential influence of early colonists on successional sequences of species following disturbance.
DOE Office of Scientific and Technical Information (OSTI.GOV)
van Kessel, W.H.; Brocades Zaalberg, R.W.; Seinen, W.
1989-10-01
Juvenile stages of Caenorhabditis elegans (nematoda) were isolated and grown in an axenic medium containing various concentrations of CdCl2. Growth of the organisms was significantly reduced from a level of 1 microM CdCl2. Reproduction of the nematodes was also reduced from that 1 microM exposure level. At levels of 160 and 320 microM, growth was retarded at the early juvenile stages and the organisms did not reach the adult stage and could therefore not reproduce. The test system turned out to be simple and reproducible and is therefore suitable for the investigation of the toxicity of compounds to soil nematodes.
Fleming, Jonathan J
2015-02-01
A key element required for translating new knowledge into effective therapies is early-stage venture capital that finances the work needed to identify a lead molecule or medical device prototype and to develop it to the proof-of-concept stage. This early investment is distinguished by great uncertainty over whether the molecule or prototype is safe and effective, the stability of the regulatory standards to which clinical trials are designed, and the likelihood that large follow-on investments for commercial development can be secured. Regulatory and reimbursement policies have a profound impact on the amount of capital and the types of life science projects that investors pursue. In this article I analyze several recent trends in early-stage venture capital funding, describe how these trends are influenced by regulatory and reimbursement policies, and discuss the role of policy makers in bringing new treatments to market. Policy makers can foster renewed private investment into critically needed early-stage products by increasing Small Business Innovation Research (SBIR) funding and public support for clinical trials in targeted areas of interest; creating regulatory pathways to enable early testing of experimental compounds in limited populations; and offering economic incentives for investors and developers in designated therapeutic areas. Project HOPE—The People-to-People Health Foundation, Inc.
Rius, Marc; Turon, Xavier; Marshall, Dustin J
2009-04-01
Studies examining the effects of invasive species have focussed traditionally on the direct/lethal effects of the invasive on the native community but there is a growing recognition that invasive species may also have non-lethal effects. In terrestrial systems, non-lethal effects of invasive species can disrupt early life-history phases (such as fertilisation, dispersal and subsequent establishment) of native species, but in the marine environment most studies focus on adult rather than early life-history stages. Here, we examine the potential for an introduced sessile marine invertebrate (Styela plicata) to exert both lethal and non-lethal effects on a native species (Microcosmus squamiger) across multiple early life-history stages. We determined whether sperm from the invasive species interfered with the fertilisation of eggs from the native species and found no effect. However, we did find strong effects of the invasive species on the post-fertilisation performance of the native species. The invasive species inhibited the settlement of native larvae and, in the field, the presence of the invasive species was associated with a ten-fold increase in the post-settlement mortality of the native species, as well as an initial reduction of growth in the native. Our results suggest that larvae of the native species avoid settling near the invasive species due to reduced post-settlement survival in its presence. Overall, we found that invasive species can have complex and pervasive effects (both lethal and non-lethal) across the early life-history stages of the native species, which are likely to result in its displacement and to facilitate further invasion.
Lema, Kimberley A; Bourne, David G; Willis, Bette L
2014-10-01
Early establishment of coral-microbial symbioses is fundamental to the fitness of corals, but comparatively little is known about the onset and succession of bacterial communities in their early life history stages. In this study, bacterial associates of the coral Acropora millepora were characterized throughout the first year of life, from larvae and 1-week-old juveniles reared in laboratory conditions in the absence of the dinoflagellate endosymbiont Symbiodinium to field-outplanted juveniles with established Symbiodinium symbioses, and sampled at 2 weeks and at 3, 6 and 12 months. Using an amplicon pyrosequencing approach, the diversity of both nitrogen-fixing bacteria and of bacterial communities overall was assessed through analysis of nifH and 16S rRNA genes, respectively. The consistent presence of sequences affiliated with diazotrophs of the order Rhizobiales (23-58% of retrieved nifH sequences; 2-12% of 16S rRNA sequences), across all samples from larvae to 12-month-old coral juveniles, highlights the likely functional importance of this nitrogen-fixing order to the coral holobiont. Dominance of Roseobacter-affiliated sequences (>55% of retrieved 16S rRNA sequences) in larvae and 1-week-old juveniles, and the consistent presence of sequences related to Oceanospirillales and Altermonadales throughout all early life history stages, signifies their potential importance as coral associates. Increased diversity of bacterial communities once juveniles were transferred to the field, particularly of Cyanobacteria and Deltaproteobacteria, demonstrates horizontal (environmental) uptake of coral-associated bacterial communities. Although overall bacterial communities were dynamic, bacteria with likely important functional roles remain stable throughout early life stages of Acropora millepora. © 2014 John Wiley & Sons Ltd.
Dementia Care at End of Life: Current Approaches.
Bartley, Mairead M; Suarez, Laura; Shafi, Reem M A; Baruth, Joshua M; Benarroch, Amanda J M; Lapid, Maria I
2018-06-23
Dementia is a progressive and life-limiting condition that can be described in three stages: early, middle, and late. This article reviews current literature on late-stage dementia. Survival times may vary across dementia subtypes. Yet, the overall trajectory is characterized by progressive decline until death. Ideally, as people with dementia approach the end of life, care should focus on comfort, dignity, and quality of life. However, barriers prevent optimal end-of-life care in the final stages of dementia. Improved and earlier advanced care planning for persons with dementia and their caregivers can help delineate goals of care and prepare for the inevitable complications of end-stage dementia. This allows for timely access to palliative and hospice care, which ultimately improves dementia end-of-life care.
Ambient and household air pollution: complex triggers of disease
Farmer, Stephen A.; Nelin, Timothy D.; Falvo, Michael J.
2014-01-01
Concentrations of outdoor air pollution are on the rise, particularly due to rapid urbanization worldwide. Alternatively, poor ventilation, cigarette smoke, and other toxic chemicals contribute to rising concentrations of indoor air pollution. The World Health Organization recently reported that deaths attributable to indoor and outdoor air pollutant exposure are more than double what was originally documented. Epidemiological, clinical, and animal data have demonstrated a clear connection between rising concentrations of air pollution (both indoor and outdoor) and a host of adverse health effects. During the past five years, animal, clinical, and epidemiological studies have explored the adverse health effects associated with exposure to both indoor and outdoor air pollutants throughout the various stages of life. This review provides a summary of the detrimental effects of air pollution through examination of current animal, clinical, and epidemiological studies and exposure during three different periods: maternal (in utero), early life, and adulthood. Additionally, we recommend future lines of research while suggesting conceivable strategies to curb exposure to indoor and outdoor air pollutants. PMID:24929855
Brooks, Steven J; Bolam, Thi; Tolhurst, Laura; Bassett, Janice; La Roche, Jay; Waldock, Mike; Barry, Jon; Thomas, Kevin V
2007-08-01
The effects of humic acid (HA) on copper speciation and its subsequent toxicity to the sensitive early life stages of the Pacific oyster (Crassostrea gigas) are presented. Differential pulse anodic stripping voltammetry with a hanging mercury drop electrode was used to measure the copper species as labile copper (LCu; free ion and inorganic copper complexes) and total copper (TCu) with respect to increasing HA concentration. The TCu and LCu 50% effect concentrations (EC50s) in the absence of HA were 20.77 microg/L (95% confidence interval [CI], 24.02-19.97 microg/L) and 8.05 microg/L (95% CI, 9.6-5.92 microg/L) respectively. A corrected dissolved organic carbon (DOC) concentration (HA only) of 1.02 mg/L was required to significantly increase the TCu EC50 to approximately 41.09 microg/L (95% CI, 44.27-37.52 microg/L; p < 0.05), almost doubling that recorded when DOC (as HA) was absent from the test media. In contrast, the LCu EC50 was unaffected by changes in DOC concentration and was stable throughout the corrected DOC concentration range. The absence of change in the LCu EC50, despite increased HA concentration, suggests that the LCu fraction, not TCu, was responsible for the observed toxicity to the oyster embryo. This corresponds with the current understanding of copper toxicity and supports the free-ion activity model for copper toxicity.
Glyphosate induces cardiovascular toxicity in Danio rerio.
Roy, Nicole M; Ochs, Jeremy; Zambrzycka, Ewelina; Anderson, Ariann
2016-09-01
Glyphosate is a broad spectrum herbicide used aggressively in agricultural practices as well as home garden care. Although labeled "safe" by the chemical industry, doses tested by industry do not mimic chronic exposures to sublethal doses that organisms in the environment are exposed to over long periods of time. Given the widespread uses of and exposure to glyphosate, studies on developmental toxicity are needed. Here we utilize the zebrafish vertebrate model system to study early effects of glyphosate on the developing heart. Treatment by embryo soaking with 50μg/ml glyphosate starting at gastrulation results in structural abnormalities in the atrium and ventricle, irregular heart looping, situs inversus as well as decreased heartbeats by 48h as determined by live imaging and immunohistochemistry. Vasculature in the body was also affected as determined using fli-1 transgenic embryos. To determine if the effects noted at 48h post fertilization are due to early stage alterations in myocardial precursors, we also investigate cardiomyocyte development with a Mef2 antibody and by mef2ca in situ hybridization and find alterations in the Mef2/mef2ca staining patterns during early cardiac patterning stages. We conclude that glyphosate is developmentally toxic to the zebrafish heart. Copyright © 2016 Elsevier B.V. All rights reserved.
NASA Astrophysics Data System (ADS)
Bellas, Juan; Nieto, Óscar; Beiras, Ricardo
2011-04-01
Elutriate embryo-larval bioassays with sea-urchins ( Paracentrotus lividus) were conducted concurrently with chemical analyses of sediments and biota as part of an integrative assessment of pollution in highly productive coastal regions. High metal contents and organic compounds in sediments and mussels were found in localised areas from the inner part of the estuaries indicating a clear anthropogenic influence. In particular, average maximum concentrations of 2803 mg Cu/kg dw, 776 mg Pb/kg dw, 2.5 mg Hg/kg dw and 5803 μg ∑ 7PAHs/kg dw were measured in sediments from the most polluted sites. Significant correlations were observed between sediment chemistry and toxicity bioassays. Moreover, the Mantel test revealed a significant correlation ( rM=0.80; p<0.01) between sediment pollutant concentrations and toxicity data profiles. In addition, sediment quality criteria were used to help in the ecological interpretation of sediment chemistry data and to identify pollutants of concern. The toxicity bioassays identified polluted sites and quantified the level of toxicity, providing a cost-effective tool to complement the routine chemical monitoring currently conducted in European coastal waters with ecologically relevant information. This is in line with the recent European legislation that advocates the use of biological tools with the ultimate aim of protecting marine resources from anthropogenic substances that will affect their sensitive early life stages.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Eaton, J.G.; Swenson, W.A.; McCormick, J.H.
1992-01-01
One-half of Little Rock Lake, a small seepage lake in north-central Wisconsin, was gradually acidified by additions of sulfuric acid between August 1983 and November 1990. The ambient pH (6.1) of the lake was reduced at successive 2-year intervals to pH 5.6, 5.1, and 4.7. Responses of largemouth bass Micropterus salmoides, rock bass Ambloplites rupestris, black crappie Pomoxis nigromaculatus, and yellow perch Perca flavescens populations to the pH reductions were recorded and compared to the responses of these species during in situ bioassays and laboratory toxicity tests on embryos and larvae. Laboratory results obtained for largemouth bass and rock bassmore » underestimated, black crappie results overestimated, and yellow perch results were similar to effects observed in field studies. In situ bioassays predicted field responses better than did laboratory toxicity tests. Laboratory results showed that monomeric Al concentrations of approximately 50 microgram/l, which were comparable to Al concentrations in the acidified half of the lake, altered low-pH toxicity. Reduced recruitment was observed in field populations at higher pH than that at which adult mortality was observed. The results indicate that laboratory toxicity tests with early life stages may not accurately predict field population responses and that results from laboratory tests should be field-validated whenever possible.« less
Ba, Qian; Li, Mian; Chen, Peizhan; Huang, Chao; Duan, Xiaohua; Lu, Lijun; Li, Jingquan; Chu, Ruiai; Xie, Dong; Song, Haiyun; Wu, Yongning; Ying, Hao; Jia, Xudong; Wang, Hui
2017-03-01
Environmental cadmium, with a high average dietary intake, is a severe public health risk. However, the long-term health implications of environmental exposure to cadmium in different life stages remain unclear. We investigated the effects of early exposure to cadmium, at an environmentally relevant dosage, on adult metabolism and the mechanism of action. We established mouse models with low-dose cadmium (LDC) exposure in early life to examine the long-term metabolic consequences. Intestinal flora measurement by 16S rDNA sequencing, microbial ecological analyses, and fecal microbiota transplant was conducted to explore the potential underlying mechanisms. Early LDC exposure (100 nM) led to fat accumulation in adult male mice. Hepatic genes profiling revealed that fatty acid and lipid metabolic processes were elevated. Gut microbiota were perturbed by LDC to cause diversity reduction and compositional alteration. Time-series studies indicated that the gut flora at early-life stages, especially at 8 weeks, were vulnerable to LDC and that an alteration during this period could contribute to the adult adiposity, even if the microbiota recovered later. The importance of intestinal bacteria in LDC-induced fat accumulation was further confirmed through microbiota transplantation and removal experiments. Moreover, the metabolic effects of LDC were observed only in male, but not female, mice. An environmental dose of cadmium at early stages of life causes gut microbiota alterations, accelerates hepatic lipid metabolism, and leads to life-long metabolic consequences in a sex-dependent manner. These findings provide a better understanding of the health risk of cadmium in the environment. Citation: Ba Q, Li M, Chen P, Huang C, Duan X, Lu L, Li J, Chu R, Xie D, Song H, Wu Y, Ying H, Jia X, Wang H. 2017. Sex-dependent effects of cadmium exposure in early life on gut microbiota and fat accumulation in mice. Environ Health Perspect 125:437-446; http://dx.doi.org/10.1289/EHP360.
Ba, Qian; Li, Mian; Chen, Peizhan; Huang, Chao; Duan, Xiaohua; Lu, Lijun; Li, Jingquan; Chu, Ruiai; Xie, Dong; Song, Haiyun; Wu, Yongning; Ying, Hao; Jia, Xudong; Wang, Hui
2016-01-01
Background: Environmental cadmium, with a high average dietary intake, is a severe public health risk. However, the long-term health implications of environmental exposure to cadmium in different life stages remain unclear. Objectives: We investigated the effects of early exposure to cadmium, at an environmentally relevant dosage, on adult metabolism and the mechanism of action. Methods: We established mouse models with low-dose cadmium (LDC) exposure in early life to examine the long-term metabolic consequences. Intestinal flora measurement by 16S rDNA sequencing, microbial ecological analyses, and fecal microbiota transplant was conducted to explore the potential underlying mechanisms. Results: Early LDC exposure (100 nM) led to fat accumulation in adult male mice. Hepatic genes profiling revealed that fatty acid and lipid metabolic processes were elevated. Gut microbiota were perturbed by LDC to cause diversity reduction and compositional alteration. Time-series studies indicated that the gut flora at early-life stages, especially at 8 weeks, were vulnerable to LDC and that an alteration during this period could contribute to the adult adiposity, even if the microbiota recovered later. The importance of intestinal bacteria in LDC-induced fat accumulation was further confirmed through microbiota transplantation and removal experiments. Moreover, the metabolic effects of LDC were observed only in male, but not female, mice. Conclusions: An environmental dose of cadmium at early stages of life causes gut microbiota alterations, accelerates hepatic lipid metabolism, and leads to life-long metabolic consequences in a sex-dependent manner. These findings provide a better understanding of the health risk of cadmium in the environment. Citation: Ba Q, Li M, Chen P, Huang C, Duan X, Lu L, Li J, Chu R, Xie D, Song H, Wu Y, Ying H, Jia X, Wang H. 2017. Sex-dependent effects of cadmium exposure in early life on gut microbiota and fat accumulation in mice. Environ Health Perspect 125:437–446; http://dx.doi.org/10.1289/EHP360 PMID:27634282
2013-01-01
Background Preliminary evidence suggests that goal-oriented cognitive rehabilitation (CR) may be a clinically effective intervention for people with early-stage Alzheimer’s disease, vascular or mixed dementia and their carers. This study aims to establish whether CR is a clinically effective and cost-effective intervention for people with early-stage dementia and their carers. Methods/design In this multi-centre, single-blind randomised controlled trial, 480 people with early-stage dementia, each with a carer, will be randomised to receive either treatment as usual or cognitive rehabilitation (10 therapy sessions over 3 months, followed by 4 maintenance sessions over 6 months). We will compare the effectiveness of cognitive rehabilitation with that of treatment as usual with regard to improving self-reported and carer-rated goal performance in areas identified as causing concern by people with early-stage dementia; improving quality of life, self-efficacy, mood and cognition of people with early-stage dementia; and reducing stress levels and ameliorating quality of life for carers of participants with early-stage dementia. The incremental cost-effectiveness of goal-oriented cognitive rehabilitation compared to treatment as usual will also be examined. Discussion If the study confirms the benefits and cost-effectiveness of cognitive rehabilitation, it will be important to examine how the goal-oriented cognitive rehabilitation approach can most effectively be integrated into routine health-care provision. Our aim is to provide training and develop materials to support the implementation of this approach following trial completion. Trial registration Current Controlled Trials ISRCTN21027481 PMID:23710796
Schumacher, V L; Martel, A; Pasmans, F; Van Immerseel, F; Posthaus, H
2013-07-01
Beta toxin (CPB) is known to be an essential virulence factor in the development of lesions of Clostridium perfringens type C enteritis in different animal species. Its target cells and exact mechanism of toxicity have not yet been clearly defined. Here, we evaluate the suitability of a neonatal piglet jejunal loop model to investigate early lesions of C. perfringens type C enteritis. Immunohistochemically, CPB was detected at microvascular endothelial cells in intestinal villi during early and advanced stages of lesions induced by C. perfringens type C. This was first associated with capillary dilatation and subsequently with widespread hemorrhage in affected intestinal segments. CPB was, however, not demonstrated on intestinal epithelial cells. This indicates a tropism of CPB toward endothelial cells and suggests that CPB-induced endothelial damage plays an important role in the early stages of C. perfringens type C enteritis in pigs.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Geist, David R.; Linley, Timothy J.; Cullinan, Valerie I.
2013-02-01
Chum salmon Oncorhynchus keta alevin developing in gravel habitats downstream of Bonneville Dam on the Columbia River are exposed to elevated levels of total dissolved gas (TDG) when water is spilled at the dam to move migrating salmon smolts downstream to the Pacific Ocean. Current water quality criteria for the management of dissolved gas in dam tailwaters were developed primarily to protect salmonid smolts and are assumed to be protective of alevin if adequate depth compensation is provided. We studied whether chum salmon alevin exposed to six levels of dissolved gas ranging from 100% to 130% TDG at three developmentmore » periods between hatch and emergence (hereafter early, middle, and late stage) suffered differential mortality, growth, gas bubble disease, or seawater tolerance. Each life stage was exposed for 50 d (early stage), 29 d (middle stage), or 16 d (late stage) beginning at 13, 34, and 37 d post-hatch, respectively, through 50% emergence. The mortality for all stages from exposure to emergence was estimated to be 8% (95% confidence interval (CI) of 4% to 12%) when dissolved gas levels were between 100% and 117% TDG. Mortality significantly increased as dissolved gas levels rose above 117% TDG,; with the lethal concentration that produced 50% mortality (LC50 ) was estimated to be 128.7% TDG (95% CI of 127.2% to 130.2% TDG) in the early and middle stages. By contrast, there was no evidence that dissolved gas level significantly affected growth in any life stage except that the mean wet weight at emergence of early stage fish exposed to 130% TDG was significantly less than the modeled growth of unexposed fish. The proportion of fish afflicted with gas bubble disease increased with increasing gas concentrations and occurred most commonly in the nares and gastrointestinal tract. Early stage fish exhibited higher ratios of filament to lamellar gill chloride cells than late stage fish, and these ratios increased and decreased for early and late stage fish, respectively, as gas levels increased; however, there were no significant differences in mortality between life stages after 96 h in seawater. The study results suggest that current water quality guidelines for the management of dissolved gas appear to offer a conservative level of protection to chum salmon alevin incubating in gravel habitat downstream of Bonneville Dam.« less
Gobler, Christopher J; DePasquale, Elizabeth L; Griffith, Andrew W; Baumann, Hannes
2014-01-01
Low oxygen zones in coastal and open ocean ecosystems have expanded in recent decades, a trend that will accelerate with climatic warming. There is growing recognition that low oxygen regions of the ocean are also acidified, a condition that will intensify with rising levels of atmospheric CO2. Presently, however, the concurrent effects of low oxygen and acidification on marine organisms are largely unknown, as most prior studies of marine hypoxia have not considered pH levels. We experimentally assessed the consequences of hypoxic and acidified water for early life stage bivalves (bay scallops, Argopecten irradians, and hard clams, Mercenaria mercenaria), marine organisms of significant economic and ecological value and sensitive to climate change. In larval scallops, experimental and naturally-occurring acidification (pH, total scale = 7.4-7.6) reduced survivorship (by >50%), low oxygen (30-50 µM) inhibited growth and metamorphosis (by >50%), and the two stressors combined produced additively negative outcomes. In early life stage clams, however, hypoxic waters led to 30% higher mortality, while acidified waters significantly reduced growth (by 60%). Later stage clams were resistant to hypoxia or acidification separately but experienced significantly (40%) reduced growth rates when exposed to both conditions simultaneously. Collectively, these findings demonstrate that the consequences of low oxygen and acidification for early life stage bivalves, and likely other marine organisms, are more severe than would be predicted by either individual stressor and thus must be considered together when assessing how ocean animals respond to these conditions both today and under future climate change scenarios.
Svartz, Gabriela; Acquaroni, Mercedes; Pérez Coll, Cristina
2018-06-07
Agricultural fungicide application in Argentina has increased twice since 2008, with Maxim® XL (2.5% fludioxonil +1% metalaxyl-M) as one of the most used fungicide formulation. The toxicity of this pesticide on Rhinella arenarum was assessed by means of continuous (from embryo and larval development) and 24-h pulse exposure standardized bioassays. Lethality was concentration- and exposure time-dependent. Maxim® XL caused a progressive lethal effect along the bioassays with higher toxicity on embryos than larvae, obtaining 50% lethal concentrations at 96, 336, and 504 h of 10.85, 2.89, and 1.71 mg/L for embryos, and 43.94, 11.79, and 5.76 mg/L for larvae respectively. Lethal 504-h no observed effect concentration values for embryos and larvae were 1 and 2.5 mg/L respectively. A stage-dependent toxicity of Maxim® XL was also demonstrated within the embryo development, with early stages more sensitive than the later ones, and blastula as the most sensitive developmental stage. The risk quotients obtained for chronic risk assessment determined a potential threat for the survival and continuity of R. arenarum populations under these conditions. The results indicate that the levels of the fungicide reaching amphibian habitats could be risky for the early development of this amphibian species. This study also emphasizes the necessity to evaluate the chronic effects of fungicides in pesticide risk assessment.
Ghobadian, Mehdi; Nabiuni, Mohammad; Parivar, Kazem; Fathi, Mojtaba; Pazooki, Jamileh
2015-12-01
Magnesium oxide nanoparticles (MgONPs) are used in medicine, manufacturing and food industries. Because of their extensive application in our daily lives, environmental exposure to these nanoparticles is inevitable. The present study examined the effects of MgONPs on zebrafish (Danio rerio) early developmental stages. The results showed that, at different concentrations, MgONPs induced cellular apoptosis and intracellular reactive oxygen species. The hatching rate and survival of embryos decreased in a dose dependent manner. The 96-h LC50 value of MgONPs on zebrafish survival was 428 mg/l and the 48-h EC50 value of MgONPs on zebrafish embryo hatching rate was 175 mg/l. Moreover different types of malformation were observed in exposed embryos. The results demonstrate the toxic effects of MgONPs on zebrafish embryos and emphasize the need for further studies. Copyright © 2015 Elsevier Inc. All rights reserved.
Hawkins, C; Miaskowski, C
1996-09-01
To describe the pathophysiologic mechanisms, histologic and clinical staging, diagnosis, and medical and nursing management of testicular cancer. Published studies, review articles, and Physician Data Query database. Testicular cancer is a complex disease resulting from transformation of gonadal tissues. The pathophysiologic mechanisms involve damage to tissue in utero and after birth. Orchiectomy is the treatment of choice for early-stage disease. Orchiectomy can have profound physiologic and psychological consequences for young males. Subsequent chemotherapy and radiation therapy also may have severe side effects including azoospermia, bone marrow suppression, nephrotoxicity, and pulmonary toxicity. Early detection of this disease results in improved patient outcomes. Patients treated with radical inguinal orchiectomy and radiation therapy have fewer long-term side effects and toxicities than patients who require more extensive surgery and chemotherapy. Nursing care must focus not only on relieving the patient's physical symptoms but on helping him deal with the psychosexual issues associated with the disease and its treatment.
Copper and thermal perturbations on the early life processes of the hard coral Platygyra acuta
NASA Astrophysics Data System (ADS)
Kwok, C. K.; Lam, K. Y.; Leung, S. M.; Chui, A. P. Y.; Ang, P. O.
2016-09-01
Anthropogenic pollutants and climate change are major threats to coral reefs today. Yet interactions between chemical and thermal perturbations have not been fully explored in reef studies. Here, we present the single and combined effects of copper (Cu) with thermal stress on five early life-history stages/processes (fertilization, larval mortality, swimming ability, metamorphosis and growth of juvenile recruits) of the massive coral Platygyra acuta in Hong Kong. In the first four experiments, coral gametes and larvae were exposed to different Cu doses (0-200 μg L-1, apart from the fertilization assay in which 0-1000 μg L-1 was used) and temperature treatments (ambient and ambient +2 or +3 °C as a thermal stress treatment) following a factorial experimental design. Exposure time was 5 h for the fertilization assay and 48 h for the other experiments. The last experiment on growth of coral recruits was conducted over 56 d with 0-80 μg L-1 Cu used. Cu significantly reduced percent fertilization success, percentage of active swimming larvae and larval survivorship (EC50s, the half maximal effective concentrations, for percent fertilization success and percentage of active swimming larvae were 92-145 and 45-47 μg L-1 respectively. While LC50, the lethal concentration that kills 50% of the population, was 101-110 μg L-1), while growth of coral recruits was not affected at 80 μg L-1 Cu for 56 d. No settling cues were used in the settlement experiment. In their absence, percent metamorphosis increased with Cu doses, in sharp contrast to earlier findings. Settlement and metamorphosis may thus be strategies for coral larvae to escape from Cu toxicity. Thermal treatment did not significantly affect any experimental end points. This is likely because the thermal regimes used in the experiments were within the range experienced by local corals. The high variability in Cu toxicities indicates differential susceptibilities of the various life-history stages/processes of P. acuta. The level of Cu tolerance was also markedly higher than that reported in the literature for other coral species. This provides evidence to suggest possible adaptation of this species to survive in a highly polluted marine environment like that in Hong Kong.
Rodriguez-Saona, Cesar; Wanumen, Andrea Carolina; Salamanca, Jordano; Holdcraft, Robert; Kyryczenko-Roth, Vera
2016-01-01
Laboratory and extended laboratory bioassays were conducted to determine the residual toxicities of various insecticides against two key pests of cranberries, Sparganothis sulfureana and Choristoneura parallela (Lepidoptera: Tortricidae), and their non-target effects on the predatory Orius insidiosus (Hemiptera: Anthocoridae). The effects of nine insecticides with different modes of action on S. sulfureana and Ch. parallela eggs, larvae, and adults were tested in the laboratory, while the efficacy of a post-bloom application on larval mortality and mass of these pests and on adult O. insidiosus was evaluated in extended laboratory experiments. The organophosphate chlorpyrifos and the spinosyn spinetoram provided long-lasting (seven-day) control against all stages of both pests. The growth regulator methoxyfenozide and the diamides chlorantraniliprole and cyantraniliprole had strong (1–7 days) larvicidal, particularly on young larvae, and growth inhibitory activity, but only the diamides were adulticidal. Among neonicotinoids, acetamiprid had stronger ovicidal and adulticidal activity than thiamethoxam, showing within-insecticide class differences in toxicities; however, both were weak on larvae. Lethality of novaluron and indoxacarb was inconsistent, varying depending on species and stage. Chlorpyrifos was most toxic to O. insidiosus. These results show species- and stage-specific toxicities, and greater compatibility with biological control, of the newer reduced-risk classes of insecticides than older chemistries. PMID:27092527
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
Aschenbrenner, Alexandre; Hackradt, Carlos Werner; Ferreira, Beatrice Padovani
2016-02-01
The early life history of Lutjanus alexandrei and Lutjanus jocu in Southwestern Atlantic is still largely unknown. Habitat use of different life stages (i.e. size categories and densities) of the Brazilian snapper (L. alexandrei) and dog snapper (L. jocu) was examined in a tropical portion of NE coast of Brazil. Visual surveys were conducted in different shallow habitats (mangroves and reefs). Both snapper species showed higher densities in early life stages in mangrove habitat, with a clear increase in fish size from mangrove to adjacent reefs. Post-settler individuals were exclusively found in mangroves for both species. Juveniles of L. alexandrei were also registered only in mangroves, while sub-adult individuals were associated with both mangrove and reef habitats. Mature individuals of L. alexandrei were only observed in reef habitats. Juvenile and sub-adult individuals of the dog snapper were both associated with mangrove and reef habitats, with high densities registered in mangroves. Mature individuals of L. jocu were not registered in the study area. This pattern suggests preference for mangrove habitat in early life stages for both species. Ontogenetic movement between habitats was also recorded. This pattern denotes habitat selection across different life cycle of both species. Such information highlights the importance of directing management and conservation efforts to these habitats to secure the continuity of contribution to adult populations. Copyright © 2015 Elsevier Ltd. All rights reserved.
NASA Astrophysics Data System (ADS)
Song, Hyun-Pa; Kim, Dong-Ho; Yook, Hong-Sun; Kim, Kyung-Soo; Kwon, Joong-Ho; Byun, Myung-Woo
2004-09-01
This study was carried out to evaluate the application of food irradiation as a method for extending shelf life of Kimchi. Gamma irradiation up to 10 kGy in the early stage of Kimchi fermentation had a dose-dependent effect on the inactivation of fermentative microbes, lowering the lactate dehydrogenase (LDH) activity and delaying acidification. Although gamma irradiation on the mid-fermentation stage of Kimchi inactivated the fermentative microbes effectively, LDH activity remained high and acidification continued. Kimchi irradiated at 10 kGy had lower scores in acceptability than those of control, 2.5 and 5 kGy irradiated. Therefore, gamma irradiation upto 5 kGy in the early fermentation stage is recommended for aging control and the improvement of shelf life of Kimchi.
Åstrøm, Anne N; Ekback, Gunnar; Ordell, Sven; Unell, Lennart
2011-08-01
Using a prospective cohort design, this study assessed loss of natural teeth between ages 50 and 65. Guided by a conceptual framework grouping variables according to the life-course stage at which they would be expected to operate, this study assessed the impacts of socio-behavioral and disease-related factors on tooth loss between ages 50 and 65. In 1992, all 50-year-olds in two counties of Sweden were invited to participate in a longitudinal questionnaire survey. Of the total population of 8,888 subjects, 6,346 responded (71.4%). Of the 6346 subjects who completed the 1992 questionnaire, 4,143 (65%) completed postal follow-ups at ages 55, 60 and 65. For the total sample, the prevalence of having lost at least some teeth increased from 76% at age 50-85.5% at age 65. A total of 14% women and 13% men changed from having all teeth in 1992 to having tooth loss in 2007. Stepwise logistic regression analyses focused on predictors of tooth loss between 1992 and 2007. The following life-stage predictors achieved or approached statistical significance with respect to overall tooth loss; country of birth and education (early life and young adult life stage), marital status, dental care avoidance because of high cost, smoking and reporting consistent pain (middle-age and early-old-age life stage). Fewer substantial proportions of the 1942 cohort experienced tooth loss between ages 50 and 65. Tooth loss was highly prevalent from age 50 and increased moderately with increasing age. Oral disease-related factors and socio-behavioral characteristics such as refraining from dental care because of financial limitations, acting at earlier and later life-course stages were major risk factors for having tooth loss. Early primary prevention of smoking and increased equitable access to dental care might improve tooth retention throughout the transition from middle age to early-older age. © 2010 John Wiley & Sons A/S.
Impacts of treatments on the quality of life among esophageal squamous cell carcinoma patients.
Chen, C-Y; Hsieh, V C-R; Chang, C-H; Chen, P-R; Liang, W-M; Pan, S-C; Shieh, S-H
2017-10-01
This study aims to investigate the effects of treatments on the quality of life for patients with esophageal squamous cell carcinoma patients diagnosed at early and late stages. From a medical center in central Taiwan, patients who had been diagnosed with esophageal squamous cell carcinoma from February 2007 and March 2011 were recruited. Using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and the Quality of Life Questionnaire Oesophageal 18 (QLQ-OES18), quality of life scores for 105 esophageal squamous cell carcinoma patients were obtained and assessed. Multivariate analysis was performed on the quality of life scores after stratification by cancer stage. Among early-stage esophageal squamous cell carcinoma patients, those received only surgery (S-only) performed better in physical and social functioning compared with patients who underwent surgery and concurrent chemoradiotherapy (S+CCRT) (β = 9.0, P = 0.03; β = 12.1, P = 0.04, respectively). For those that received only concurrent chemoradiotherapy (CCRT-only), they performed worse in role and emotional functioning relative to S+CCRT patients (β = -17.2, P = 0.02; β = -15.7, P = 0.05, respectively). Among late-stage patients, CCRT-only treatment gave insignificantly better global health status and functional scale scores and less severe symptoms compared to the S+CCRT option. Better functional scores and less aggravated symptoms are observed in early-stage esophageal squamous cell carcinoma patients who received surgery-only treatment relative to those that underwent both surgery and chemoradiotherapy. For late-stage esophageal cancer patients, the measured difference of quality of life is not significant between CCRT-only and S+CCRT treatments. © The Authors 2017. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Detection and monitoring of cardiotoxicity-what does modern cardiology offer?
Jurcut, Ruxandra; Wildiers, Hans; Ganame, Javier; D'hooge, Jan; Paridaens, Robert; Voigt, Jens-Uwe
2008-05-01
With new anticancer therapies, many patients can have a long life expectancy. Treatment-related comorbidities become an issue for cancer survivors. Cardiac toxicity remains an important side effect of anticancer therapies. Myocardial dysfunction can become apparent early or long after end of therapy and may be irreversible. Detection of cardiac injury is crucial since it may facilitate early therapeutic measures. Traditionally, chemotherapy-induced cardiotoxicity has been detected by measuring changes in left ventricular ejection fraction. This parameter is, however, insensitive to subtle changes in myocardial function as they occur in early cardiotoxicity. This review will discuss conventional and modern cardiologic approaches of assessing myocardial function. It will focus on Doppler myocardial imaging, a method which allows to sensitively measure myocardial function parameters like myocardial velocity, deformation (strain), or deformation rate (strain rate) and which has been shown to reliably detect early abnormalities in both regional and global myocardial function in an early stage. Other newer echocardiographic function estimators are based on automated border detection algorithms and ultrasonic integrated backscatter analysis. A further technique to be discussed is dobutamine stress echocardiography. The use of new biomarkers like B-type natriuretic peptide and troponin and less often used imaging techniques like magnetic resonance imaging and computed tomography will also be mentioned.
Safeguarding Our Children at Home: Reducing Exposures to Toxic Chemicals and Heavy Metals
ERIC Educational Resources Information Center
Miller, Elise; Snow, Nancy
2005-01-01
Emerging research suggests that exposure to environmental pollutants, prenatally and in early childhood, may contribute significantly to diseases and disabilities. For example, exposures to mercury or lead early in life can impact the nervous system and brain, potentially contributing to learning, behavioral, and developmental disabilities. The…
Brion, F; Tyler, C R; Palazzi, X; Laillet, B; Porcher, J M; Garric, J; Flammarion, P
2004-06-24
Zebrafish (Danio rerio) were exposed for 3 weeks to low concentrations of estradiol including environmentally relevant concentrations (5, 25 and 100 ng/l), encompassing either their embryo-larvae (from fertilization to 21 day post-fertilization (dpf)), juvenile (from 21 to 42 dpf) or adult life stages (>200 dpf) with a view to investigating the most sensitive life stage of the zebrafish to 17beta-estradiol (E2). At all sampling points, whole-body vitellogenin concentrations and gonadal development were analyzed in order to investigate the effects of estrogen exposure on these endpoint in the zebrafish. In the adult stage, additional endpoints were measured including secondary sexual characteristics (manifestation of the uro-genital papillae (UGP) in males), gonadal growth (the gonado-somatic index (GSI)) and sex ratio. For all the different life stage exposures, reproductive performance of the F0 generation was assessed (egg production) and survival and development of the F1 embryo-larvae. Exposure to low concentrations of E2 resulted in vitellogenin induction whatever the life stage exposed but these effects were reversible after depuration. The effective concentration for vitellogenin induction in zebrafish early life stages was 100 ng E2/l, and in adult male zebrafish the effective concentration for vitellogenin induction (between 5 and 25 ng/l) was lower than for the early life stage fish. Exposure to E2 prior to (from fertilization to 21 dpf) and during the time of sex differentiation (from 21 to 42 dpf) also caused disruptions in the process of sexual differentiation (resulting in formation of a retrogonadal cavity in presumptive male, germ cell development and leading to a significant change of the sex ratio towards the female sex at the dose of 100 ng E2/l for the fish exposure as embryo-larvae) and altered patterns of egg production in the subsequent adults. Exposure of adult fish to E2 resulted in a modification of the secondary sexual characteristic in males at 25 and 100 ng E2/l as well as a dose-dependent inhibition of egg production. The findings from this study show that the nature and intensity of the reproductive effects of E2 are dependent of the time and concentration of exposures of zebrafish to E2, some of these effects being permanent (effect on the sexual differentiation) while others being reversible (effect on the Vtg induction). This study demonstrated that early life stages of zebrafish are sensitive to low concentrations of E2 and provides relevant data that could be used for the adaptation of existing fish early life stage test for the in vivo testing of estrogenic compounds. The data presented raise further concerns about the effects of steroid estrogens in the environment on fish reproductive health.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Wang Hua; Department of Radiation Oncology, Cancer Hospital of Jiangxi Province, Jiangxi Province; Li Yexiong, E-mail: yexiong@yahoo.com
Purpose: The value of intensity-modulated radiotherapy (IMRT) for early-stage nasal NK/T-cell lymphoma has not been previously reported. The aim of the present study was to assess the dosimetric parameters, toxicity, and treatment outcomes of patients with nasal NK/T-cell lymphoma. Methods and Materials: Between 2003 and 2008, 42 patients with early-stage nasal NK/T-cell lymphoma underwent definitive high-dose and extended involved-field IMRT with or without combination chemotherapy. The median radiation dose to the primary tumor was 50 Gy. The dose-volume histograms of the target volume and critical normal structures were evaluated in all patients. The locoregional control, overall survival, and progression-free survivalmore » were calculated using the Kaplan-Meier method. Results: The average mean dose delivered to the planning target volume was 55.5 Gy. Only 1.3% and 2.5% of the planning target volume received <90% and 95% of the prescribed dose, respectively, indicating excellent planning target volume coverage. The mean dose and average dose to the parotid glands was 15 Gy and 14 Gy, respectively. With a median follow-up time of 27 months, the 2-year locoregional control, overall survival, and progression-free survivalrate was 93%, 78%, and 74%, respectively. No Grade 4 or 5 acute or late toxicity was reported. Conclusions: High-dose and extended involved-field IMRT for patients with early-stage nasal NK/T-cell lymphoma showed favorable locoregional control, overall survival, and progression-free survival, with mild toxicity. The dose constraints of IMRT for the parotid glands can be limited to <20 Gy in these patients.« less
NASA Astrophysics Data System (ADS)
Amorim, Eva; Ramos, Sandra; Elliott, Michael; Bordalo, Adriano A.
2016-01-01
Connectivity between coastal spawning grounds and estuarine nurseries is a critical step in the life cycle of many fish species. Larval immigration and transport-associated physical-biological processes are determinants of recruitment success to nursery areas. The recruitment of the European flounder, Platichthys flesus, to estuarine nurseries located at the southern edge of the species distribution range, has been usually investigated during its juvenile stages, while estuarine recruitment during the earlier planktonic life stage remains largely unstudied. The present study investigated the patterns of flounder larval recruitment and the influence of environmental factors on the immigration of the early life stages to the Lima estuary (NW Portugal), integrating data on fish larvae and post-settlement individuals (< 50 mm length), collected over 7 years. Late-stage larvae arrived at the estuary between February and July and peak abundances were observed in April. Post-settlement individuals (< 50 mm) occurred later between April and October, whereas newly-settled ones (< 20 mm) were found only in May and June. Variables associated with the spawning, survival and growth of larvae in the ocean (sea surface temperature, chlorophyll a and inland hydrological variables) were the major drivers of flounder occurrence in the estuarine nursery. Although the adjacent coastal area is characterized by a current system with strong seasonality and mesoscale variability, we did not identify any influence of variables related with physical processes (currents and upwelling) on the occurrence of early life stages in the estuary. A wider knowledge on the influence of the coastal circulation variability and its associated effects upon ocean-estuarine connectivity is required to improve our understanding of the population dynamics of marine spawning fish that use estuarine nurseries.
Comparative Developmental Toxicity of Flavonoids Using an Integrative Zebrafish System
Bugel, Sean M.; Bonventre, Josephine A.; Tanguay, Robert L.
2016-01-01
Flavonoids are a large, structurally diverse class of bioactive naturally occurring chemicals commonly detected in breast milk, soy based infant formulas, amniotic fluid, and fetal cord blood. The potential for pervasive early life stage exposures raises concerns for perturbation of embryogenesis, though developmental toxicity and bioactivity information is limited for many flavonoids. Therefore, we evaluated a suite of 24 flavonoid and flavonoid-like chemicals using a zebrafish embryo-larval toxicity bioassay—an alternative model for investigating developmental toxicity of environmentally relevant chemicals. Embryos were exposed to 1–50 µM of each chemical from 6 to 120 h postfertilization (hpf), and assessed for 26 adverse developmental endpoints at 24, 72, and 120 hpf. Behavioral changes were evaluated in morphologically normal animals at 24 and 72 hpf, at 120 hpf using a larval photomotor response (LPR) assay. Gene expression was comparatively evaluated for all compounds for effects on biomarker transcripts indicative of AHR (cyp1a) and ER (cyp19a1b, esr1, lhb, vtg) pathway bioactivity. Overall, 15 of 24 flavonoids elicited adverse effects on one or more of the developmental or behavioral endpoints. Hierarchical clustering and principle component analyses compared toxicity profiles and identified 3 distinct groups of bioactive flavonoids. Despite robust induction of multiple estrogen-responsive biomarkers, co-exposure with ER and GPER antagonists did not ameliorate toxicity, suggesting ER-independence and alternative modes of action. Taken together, these studies demonstrate that development is sensitive to perturbation by bioactive flavonoids in zebrafish that are not related to traditional estrogen receptor mode of action pathways. This integrative zebrafish platform provides a useful framework for evaluating flavonoid developmental toxicity and hazard prioritization. PMID:27492224
Le Bihanic, Florane; Morin, Bénédicte; Cousin, Xavier; Le Menach, Karyn; Budzinski, Hélène; Cachot, Jérôme
2014-12-01
A new gravel-contact assay using rainbow trout, Oncorhynchus mykiss, embryos was developed to assess the toxicity of polycyclic aromatic hydrocarbons (PAHs) and other hydrophobic compounds. Environmentally realistic exposure conditions were mimicked with a direct exposure of eyed rainbow trout embryos incubated onto chemical-spiked gravels until hatching at 10 °C. Several endpoints were recorded including survival, hatching delay, hatching success, biometry, developmental abnormalities, and DNA damage (comet and micronucleus assays). This bioassay was firstly tested with two model PAHs, fluoranthene and benzo[a]pyrene. Then, the method was applied to compare the toxicity of three PAH complex mixtures characterized by different PAH compositions: a pyrolytic extract from a PAH-contaminated sediment (Seine estuary, France) and two petrogenic extracts from Arabian Light and Erika oils, at two environmental concentrations, 3 and 10 μg g(-1) sum of PAHs. The degree and spectrum of toxicity were different according to the extract considered. Acute effects including embryo mortality and decreased hatching success were observed only for Erika oil extract. Arabian Light and pyrolytic extracts induced mainly sublethal effects including reduced larvae size and hemorrhages. Arabian Light and Erika extracts both induced repairable DNA damage as revealed by the comet assay versus the micronucleus assay. The concentration and proportion of methylphenanthrenes and methylanthracenes appeared to drive the toxicity of the three PAH fractions tested, featuring a toxic gradient as follows: pyrolytic < Arabian Light < Erika. The minimal concentration causing developmental defects was as low as 0.7 μg g(-1) sum of PAHs, indicating the high sensitivity of the assay and validating its use for toxicity assessment of particle-bound pollutants.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Greeley Jr, Mark Stephen; Elmore, Logan R; McCracken, Kitty
2012-05-01
On December 22, 2008, a dike containing fly ash and bottom ash in an 84-acre complex of the Tennessee Valley Authority's (TVA) Kingston Steam Plant in East Tennessee failed and released a large quantity of ash into the adjacent Emory River. Ash deposits extended as far as 4 miles upstream (Emory River mile 6) of the Plant, and some ash was carried as far downstream as Tennessee River mile 564 ({approx}4 miles downstream of the Tennessee River confluence with the Clinch River). A byproduct of coal burning power plants, fly ash contains a variety of metals and other elements which,more » at sufficient concentrations and in specific forms, can be toxic to biological systems. The effects of fly ash contamination on exposed fish populations depend on the magnitude and duration of exposure, with the most significant risk considered to be the effects of specific ash constituents, especially selenium, on fish early life stages. Uptake by adult female fish of fly ash constituents through the food chain and subsequent maternal transfer of contaminants to the developing eggs is thought to be the primary route of selenium exposure to larval fish (Woock and others 1987, Coyle and others 1993, Lemly 1999, Moscatello and others 2006), but direct contact of the fertilized eggs and developing embryos to ash constituents in river water and sediments is also a potential risk factor (Woock and others 1987, Coyle and others 1993, Jezierska and others 2009). To address the risk of fly ash from the Kingston spill to the reproductive health of downstream fish populations, ORNL has undertaken a series of studies in collaboration with TVA including: (1) a field study of the bioaccumulation of fly ash constituents in fish ovaries and the reproductive condition of sentinel fish species in reaches of the Emory and Clinch Rivers affected by the fly ash spill; (2) laboratory tests of the potential toxicity of fly ash from the spill area on fish embryonic and larval development (reported in the current technical manuscript); (3) additional laboratory experimentation focused on the potential effects of long-term exposures to fly ash on fish survival and reproductive competence; and (4) a combined field and laboratory study examining the in vitro developmental success of embryos and larvae obtained from fish exposed in vivo for over two years to fly ash in the Emory and Clinch Rivers. These fish reproduction and early life-stage studies are being conducted in conjunction with a broader biological monitoring program administered by TVA that includes a field study of the condition of larval fish in the Emory and Clinch Rivers along with assessments of water quality, sediment composition, ecotoxicological studies, terrestrial wildlife studies, and human and ecological risk assessment. Information and data generated from these studies will provide direct input into risk assessment efforts and will also complement and help support other phases of the overall biomonitoring program. Fish eggs, in general, are known to be capable of concentrating heavy metals and other environmental contaminants from water-borne exposures during embryonic development (Jezierska and others 2009), and fathead minnow embryos in particular have been shown to concentrate methylmercury (Devlin 2006) as well as other chemical toxicants. This technical report focuses on the responses of fathead minnow embryos to simple contact exposures to fly ash in laboratory toxicity tests adapted from a standard fathead minnow (Pimephales promelas) 7-d embryo-larval survival and teratogenicity test (method 1001.0 in EPA 2002) with mortality, hatching success, and the incidences of developmental abnormalities as measured endpoints.« less
Defining the role of tyrosine kinase inhibitors in early stage non-small cell lung cancer.
Lampaki, Sofia; Lazaridis, George; Zarogoulidis, Konstantinos; Kioumis, Ioannis; Papaiwannou, Antonis; Tsirgogianni, Katerina; Karavergou, Anastasia; Tsiouda, Theodora; Karavasilis, Vasilis; Yarmus, Lonny; Darwiche, Kaid; Freitag, Lutz; Sakkas, Antonios; Kantzeli, Angeliki; Baka, Sofia; Hohenforst-Schmidt, Wolfgang; Zarogoulidis, Paul
2015-01-01
Historical, the non-small cell lung cancer (NSCLC) was as a united disease entity and the chemotherapy to the metastatic cancer had limited results. Recent studies for the metastatic non-small cell lung cancer led to the ascertainment that the NSCLC does not constitute exclusively a disease entity, but different neoplasms guided from different molecular paths, different biological behavior and at extension requires different confrontation. Thus the new direction for the therapeutic approach of NSCLC is henceforth the most individualized approach based on the activated molecular paths of tumor. Distinct subtypes of NSCLC are driven by a specific genetic alteration, like EGFR, ALK, ROS1 or BRAF mutations, and these genetic alterations are sensitized to the inhibition of specific oncogenic pathways. The benefit from the use of tyrosine kinase inhibitors in patients with EGFR mutations it was confirmed by six randomized studies of phase III that investigated the role of gefitinib, erlotinib and afatinib. In these studies the response rates vary in the impressive percentages from 55% to 86% and were connected with a remarkable median progression free survival of approximately 8 to 13 months, and with better quality of life compared to that of chemotherapy. In early stages NSCLC is needed the individualization of systemic treatment in order to reduce toxicity that is observed in the classic chemotherapy and to impact outcome. The role of EGFR TKI's has been evaluated in the adjuvant chemotherapy in early stage resected NSCLC. The data from these studies suggest that adjuvant TKI therapy might not increase the overall survival, but delay the recurrences. Prospective trials restricted to EGFR or ALK driven NSCLC subsets potentially offering the opportunity for a definitive answer in early disease adjuvant setting (ALCHEMIST) or as induction treatment before stage III chemo-radiotherapy (RTOG 1210/Alliance 31101), are ongoing. Ongoing prospective trials may offer the opportunity for a definitive answer of the role of tyrosine kinase inhibitors in induction treatment before chemo-radiotherapy or in early disease adjuvant therapy.
Pessoa, P C; Luchmann, K H; Ribeiro, A B; Veras, M M; Correa, J R M B; Nogueira, A J; Bainy, A C D; Carvalho, P S M
2011-10-01
Nile tilapia Oreochromis niloticus at 9 days post-hatch were exposed in semi-static experiments to the carbamate insecticide carbofuran, which is applied in agricultural systems in Brazil. Although the molecular mechanism of carbofuran toxicity is well known, a detailed understanding of the ecological mechanisms through which carbofuran effects can propagate towards higher levels of biological organization in fish is incomplete. Mortality rates were quantified for larvae exposed for 96 h to 8.3, 40.6, 69.9, 140, 297 and 397 μg/L carbofuran, and the LC(50) 96 h was 214.7 μg/L. In addition, the biochemical biomarker cholinesterase inhibition and behavioral biomarkers related to vision, swimming, prey capture and predator avoidance were quantified in individual larvae, as well as their growth in weight. The behavioral parameters were quantified by analysis of digitally recorded videos of individual larvae within appropriate experimental setups. The activity of the enzyme cholinesterase decreased after exposure to carbofuran with a lowest observed effects concentration (LOEC) of 69.9 μg/L. Visual acuity deficits were detected after carbofuran exposure with a LOEC of 40.6 μg/L. Swimming speed decreased with carbofuran exposure, with a LOEC of 397.6 μg/L. The number of attacks to prey (Daphnia magna nauplii) decreased in larvae exposed to carbofuran, with a LOEC of 397.6 μg/L. Growth in weight was significantly reduced in a dose dependent manner, and all carbofuran groups exhibited a statistically significant decrease in growth when compared to controls (p<0.05). The number of predator attacks necessary to capture larvae decreased after exposure to carbofuran, and the LOEC was 69.9 μg/L. These results show that exposure of sensitive early life stages of tilapia O. niloticus to sublethal concentrations of carbofuran can affect fundamental aspects of fish larval ecology that are relevant to recruitment of fish populations, and that can be better understood by the application of behavioral biomarkers. Copyright © 2011 Elsevier B.V. All rights reserved.
The effects of parasites on the early life stages of a damselfish
NASA Astrophysics Data System (ADS)
Sun, D.; Blomberg, S. P.; Cribb, T. H.; McCormick, M. I.; Grutter, A. S.
2012-12-01
Early life history traits, such as larval growth, influence the success of coral reef fish in the transition from the larval to the juvenile life phase. Few studies, however, have examined the relationship between parasites and growth in the early life history stages of such fishes. This study examined how parasite prevalence (% infected) and load, and the relationship between parasite presence and fish growth, differed among life stages of the damselfish Pomacentrus amboinensis. Parasite prevalence decreased significantly between the larval stage, which was sampled immediately before settlement on the reef (97 %) and recently settled juveniles (60 %); prevalence was also high for 4-month-old juveniles (90 %), 7-month-old juveniles (100 %) and adult fish (100 %). Total numbers of parasites per fish decreased dramatically (fourfold) between larval and recently settled fish, and then increased in the older stages to levels similar to those observed in larvae, but they did so more gradually than did prevalence. One explanation for these patterns is that heavily infected larvae were preferentially removed from the population during or soon after settlement. Daily fish growth, determined from otolith increments, revealed that growth did not differ between parasitised and non-parasitised larval fish, whereas recently settled fish that were parasitised had faster growth; these parasitised recently settled fish also displayed faster growth prior to settlement. These data provide evidence that parasites may explain some of the variation in growth and survival observed among coral reef fishes after settlement and thereby have a greater impact on population dynamics than previously understood.
Rutkoski, Camila F; Macagnan, Natani; Kolcenti, Cassiane; Vanzetto, Guilherme V; Sturza, Paola F; Hartmann, Paulo A; Hartmann, Marilia T
2018-05-01
Water sources used as reproductive sites by crying frog, Physalaemus gracilis, are extensively associated with agroecosystems in which the herbicide atrazine is employed. To evaluate the lethal and sublethal effects of atrazine commercial formulation, acute and chronic toxicity tests were performed in the embryonic phase and the beginning of the larval phase of P. gracilis. Tests were started on stage 19 of Gosner (Herpetologica 16:183-190, 1960) and performed in 24-well cell culture plates. Acute tests had a duration of 96 h with embryo mortality monitoring every 24 h. Chronic assays contemplated the transition from the embryonic to larval stages and lasted 168 h. Every 24 h the embryos/larvae were observed for mortality, mobility, and malformations. The LC50 of atrazine determined for P. gracilis embryos was 229.34 mg L -1 . The sublethal concentrations did not affect the development of the larvae but were observed effects on mobility and malformations, such as spasmodic contractions, reduced mobility, malformations in mouth and intestine, and edema arising. From 1 mg L -1 atrazine, the exposed larvae began to have changes in mobility and malformations. The atrazine commercial formulation has caused early life effects of P. gracilis that may compromise the survival of this species but at higher concentrations than recorded in the environment, so P. gracilis can be considered tolerant to this herbicide at environmentally relevant concentrations.
Managing Money throughout Life. A Four-Part Series.
ERIC Educational Resources Information Center
American Association of Retired Persons, Washington, DC.
This packet of four brochures focuses on money management for four stages of life, from early adulthood to preretirement. The first brochure, for young adults, discusses early financial tasks, such as selecting a financial institution, and checking and savings accounts, credit establishments, and employee benefits. The second brochure, for young…
DOE Office of Scientific and Technical Information (OSTI.GOV)
Rahimi, Asal, E-mail: asal.rahimi@utsouthwestern.edu; Thomas, Kimberly; Spangler, Ann
Purpose: To evaluate the tolerability of a dose-escalated 5-fraction stereotactic body radiation therapy for partial-breast irradiation (S-PBI) in treating early-stage breast cancer after partial mastectomy; the primary objective was to escalate dose utilizing a robotic stereotactic radiation system treating the lumpectomy cavity without exceeding the maximum tolerated dose. Methods and Materials: Eligible patients included those with ductal carcinoma in situ or invasive nonlobular epithelial histologies and stage 0, I, or II, with tumor size <3 cm. Patients and physicians completed baseline and subsequent cosmesis outcome questionnaires. Starting dose was 30 Gy in 5 fractions and was escalated by 2.5 Gy total for each cohortmore » to 40 Gy. Results: In all, 75 patients were enrolled, with a median age of 62 years. Median follow-up for 5 cohorts was 49.9, 42.5, 25.7, 20.3, and 13.5 months, respectively. Only 3 grade 3 toxicities were experienced. There was 1 dose-limiting toxicity in the overall cohort. Ten patients experienced palpable fat necrosis (4 of which were symptomatic). Physicians scored cosmesis as excellent or good in 95.9%, 100%, 96.7%, and 100% at baseline and 6, 12, and 24 months after S-PBI, whereas patients scored the same periods as 86.5%, 97.1%, 95.1%, and 95.3%, respectively. The disagreement rates between MDs and patients during those periods were 9.4%, 2.9%, 1.6%, and 4.7%, respectively. There have been no recurrences or distant metastases. Conclusion: Dose was escalated to the target dose of 40 Gy in 5 fractions, with the occurrence of only 1 dose-limiting toxicity. Patients felt cosmetic results improved within the first year after surgery and stereotactic body radiation therapy. Our results show minimal toxicity with excellent cosmesis; however, further follow-up is warranted in future studies. This study is the first to show the safety, tolerability, feasibility, and cosmesis results of a 5-fraction dose-escalated S-PBI treatment for early-stage breast cancer in the adjuvant setting.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Venkataramiah, A.; Lakshmi, G.J.; Best, C.
1981-06-01
Ammonia and chlorine were chosen for toxicity studies as they pose the greatest potential environmental threat. Acute and chronic bioassays determined the LT/sub 50/, LC/sub 50/ and the behavior of mullet (Mugil cephalus), sargassum shrimp (Latreutes focorum) and filefish (Monocanthus hispidus). The chronic bioassays were carried out mainly in sublethal concentrations of ammonia and chlorine. The findings indicate that high concentrations of ammonia and chlorine from the OTEC plants are toxic to marine animals. Also the level of toxicity is related to the species, their habitats and life stages.
Cavallaro, Michael C; Morrissey, Christy A; Headley, John V; Peru, Kerry M; Liber, Karsten
2017-02-01
Nontarget aquatic insects are susceptible to chronic neonicotinoid insecticide exposure during the early stages of development from repeated runoff events and prolonged persistence of these chemicals. Investigations on the chronic toxicity of neonicotinoids to aquatic invertebrates have been limited to a few species and under different laboratory conditions that often preclude direct comparisons of the relative toxicity of different compounds. In the present study, full life-cycle toxicity tests using Chironomus dilutus were performed to compare the toxicity of 3 commonly used neonicotinoids: imidacloprid, clothianidin, and thiamethoxam. Test conditions followed a static-renewal exposure protocol in which lethal and sublethal endpoints were assessed on days 14 and 40. Reduced emergence success, advanced emergence timing, and male-biased sex ratios were sensitive responses to low-level neonicotinoid exposure. The 14-d median lethal concentrations for imidacloprid, clothianidin, and thiamethoxam were 1.52 μg/L, 2.41 μg/L, and 23.60 μg/L, respectively. The 40-d median effect concentrations (emergence) for imidacloprid, clothianidin, and thiamethoxam were 0.39 μg/L, 0.28 μg/L, and 4.13 μg/L, respectively. Toxic equivalence relative to imidacloprid was estimated through a 3-point response average of equivalencies calculated at 20%, 50%, and 90% lethal and effect concentrations. Relative to imidacloprid (toxic equivalency factor [TEF] = 1.0), chronic (lethality) 14-d TEFs for clothianidin and thiamethoxam were 1.05 and 0.14, respectively, and chronic (emergence inhibition) 40-d TEFs were 1.62 and 0.11, respectively. These population-relevant endpoints and TEFs suggest that imidacloprid and clothianidin exert comparable chronic toxicity to C. dilutus, whereas thiamethoxam induced comparable effects only at concentrations an order of magnitude higher. However, the authors caution that under field conditions, thiamethoxam readily degrades to clothianidin, thereby likely enhancing toxicity. Environ Toxicol Chem 2017;36:372-382. © 2016 SETAC. © 2016 SETAC.
Gobler, Christopher J.; DePasquale, Elizabeth L.; Griffith, Andrew W.; Baumann, Hannes
2014-01-01
Low oxygen zones in coastal and open ocean ecosystems have expanded in recent decades, a trend that will accelerate with climatic warming. There is growing recognition that low oxygen regions of the ocean are also acidified, a condition that will intensify with rising levels of atmospheric CO2. Presently, however, the concurrent effects of low oxygen and acidification on marine organisms are largely unknown, as most prior studies of marine hypoxia have not considered pH levels. We experimentally assessed the consequences of hypoxic and acidified water for early life stage bivalves (bay scallops, Argopecten irradians, and hard clams, Mercenaria mercenaria), marine organisms of significant economic and ecological value and sensitive to climate change. In larval scallops, experimental and naturally-occurring acidification (pH, total scale = 7.4–7.6) reduced survivorship (by >50%), low oxygen (30–50 µM) inhibited growth and metamorphosis (by >50%), and the two stressors combined produced additively negative outcomes. In early life stage clams, however, hypoxic waters led to 30% higher mortality, while acidified waters significantly reduced growth (by 60%). Later stage clams were resistant to hypoxia or acidification separately but experienced significantly (40%) reduced growth rates when exposed to both conditions simultaneously. Collectively, these findings demonstrate that the consequences of low oxygen and acidification for early life stage bivalves, and likely other marine organisms, are more severe than would be predicted by either individual stressor and thus must be considered together when assessing how ocean animals respond to these conditions both today and under future climate change scenarios. PMID:24416169
An example of fisheries oceanography: Walleye pollock in Alaskan waters
NASA Astrophysics Data System (ADS)
Schumacher, Jim; Kendall, Arthur W.
1995-07-01
A major area of research in fisheries oceanography examines relationships between recruitment dynamics of fish populations and the marine environment. A primary goal is to understand the natural causes of variability in year-class strength of commercially valuable species and apply this knowledge to management [Perry, 1994]. The paradigm that the majority of mortality occurs during transport of early life history stages from spawning to nursery grounds [Rothschild, 1986; Houde, 1987] provides an initial temporal focus for most research. The spatial domain includes the region occupied by early life history stages. Since global climate variability impacts regional ecosystem dynamics, however, the spatial domain often must be expanded. The relative importance and manifestation of biological factors [starvation and predation] that limit survival varies each year. Marked interannual and longer period variations in temperature (an influence on metabolic rates and behavior), transport of planktonic stages, and turbulence can exert an influence on both survival of early life history stages, and distribution of juveniles and adults. To understand how these environmental factors influence reproductive success of fish stocks also requires knowledge of the impact of these factors on predators and prey throughout the food web.
Hall, Peter S; McCabe, Christopher; Stein, Robert C; Cameron, David
2012-01-04
Multi-parameter genomic tests identify patients with early-stage breast cancer who are likely to derive little benefit from adjuvant chemotherapy. These tests can potentially spare patients the morbidity from unnecessary chemotherapy and reduce costs. However, the costs of the test must be balanced against the health benefits and cost savings produced. This economic evaluation compared genomic test-directed chemotherapy using the Oncotype DX 21-gene assay with chemotherapy for all eligible patients with lymph node-positive, estrogen receptor-positive early-stage breast cancer. We performed a cost-utility analysis using a state transition model to calculate expected costs and benefits over the lifetime of a cohort of women with estrogen receptor-positive lymph node-positive breast cancer from a UK perspective. Recurrence rates for Oncotype DX-selected risk groups were derived from parametric survival models fitted to data from the Southwest Oncology Group 8814 trial. The primary outcome was the incremental cost-effectiveness ratio, expressed as the cost (in 2011 GBP) per quality-adjusted life-year (QALY). Confidence in the incremental cost-effectiveness ratio was expressed as a probability of cost-effectiveness and was calculated using Monte Carlo simulation. Model parameters were varied deterministically and probabilistically in sensitivity analysis. Value of information analysis was used to rank priorities for further research. The incremental cost-effectiveness ratio for Oncotype DX-directed chemotherapy using a recurrence score cutoff of 18 was £5529 (US $8852) per QALY. The probability that test-directed chemotherapy is cost-effective was 0.61 at a willingness-to-pay threshold of £30 000 per QALY. Results were sensitive to the recurrence rate, long-term anthracycline-related cardiac toxicity, quality of life, test cost, and the time horizon. The highest priority for further research identified by value of information analysis is the recurrence rate in test-selected subgroups. There is substantial uncertainty regarding the cost-effectiveness of Oncotype DX-directed chemotherapy. It is particularly important that future research studies to inform cost-effectiveness-based decisions collect long-term outcome data.
A Qualitative Analysis of Acute Skin Toxicity among Breast Cancer Radiotherapy Patients
Schnur, Julie B.; Ouellette, Suzanne C.; DiLorenzo, Terry A.; Green, Sheryl; Montgomery, Guy H.
2013-01-01
Objectives One of the most common acute side effects of breast cancer radiotherapy is treatment induced skin changes, referred to as skin toxicity. Yet no research to date has focused expressly on skin toxicity-related quality of life in breast cancer radiotherapy patients. Therefore, our aim was to use qualitative approaches to better understand the impact of skin toxicity on quality of life. Methods Semi-structured interviews were conducted with 20 women (Stage 0-III breast cancer), during their last week of external beam radiotherapy. Each interview was transcribed verbatim, and thematic analysis was performed. Results Three themes were identified based on the interview responses: First, skin changes affect multiple dimensions of quality of life. They cause physical discomfort, body image disturbance, emotional distress, and impair both day-to-day functioning and satisfaction with radiation treatment. Second, individual differences affect women’s experiences. Generally African-American women, younger women, women who are not currently in a relationship, women who are being treated during the summer, and women who are more invested in their appearance are more distressed by skin toxicity. Third, women use a variety of symptom management strategies including self-medication, complementary/alternative medicine approaches, and psychological strategies. Conclusions Implications of results are: 1) Skin toxicity affects numerous dimensions of quality of life, and assessment approaches and psychosocial interventions should address this; 2) individual differences may affect the experience of skin toxicity, and should be considered in treatment and education approaches; and 3) participants’ own creativity and problem-solving should be used to improve the treatment experience. PMID:20238306
Early life stages contribute strongly to local adaptation in Arabidopsis thaliana.
Postma, Froukje M; Ågren, Jon
2016-07-05
The magnitude and genetic basis of local adaptation is of fundamental interest in evolutionary biology. However, field experiments usually do not consider early life stages, and therefore may underestimate local adaptation and miss genetically based tradeoffs. We examined the contribution of differences in seedling establishment to adaptive differentiation and the genetic architecture of local adaptation using recombinant inbred lines (RIL) derived from a cross between two locally adapted populations (Italy and Sweden) of the annual plant Arabidopsis thaliana We planted freshly matured, dormant seeds (>180 000) representing >200 RILs at the native field sites of the parental genotypes, estimated the strength of selection during different life stages, mapped quantitative trait loci (QTL) for fitness and its components, and quantified selection on seed dormancy. We found that selection during the seedling establishment phase contributed strongly to the fitness advantage of the local genotype at both sites. With one exception, local alleles of the eight distinct establishment QTL were favored. The major QTL for establishment and total fitness showed evidence of a fitness tradeoff and was located in the same region as the major seed dormancy QTL and the dormancy gene DELAY OF GERMINATION 1 (DOG1). RIL seed dormancy could explain variation in seedling establishment and fitness across the life cycle. Our results demonstrate that genetically based differences in traits affecting performance during early life stages can contribute strongly to adaptive differentiation and genetic tradeoffs, and should be considered for a full understanding of the ecology and genetics of local adaptation.
NASA Astrophysics Data System (ADS)
Chambers, R. C.; Habeck, E. A.; Candelmo, A. C.; Poach, M.; Wieczorek, D.; Phelan, B.; Caldarone, E.; Cooper, K. R.
2012-12-01
The limited available evidence about effects on finfish of high CO2 levels and acidification of our oceans suggests that effects will differ across fish species, be subtle, and interact with other stressors. A carefully planned, experimental framework was developed to cast an extensive yet strategic inferential net. Three key elements of our approach are the use of 1) multiple marine finfish species of relevance to the northeastern USA that differ in their ecologies including spawning season and habitat of early life-stages; 2) a wide yet realistic range of environmental conditions (i.e., concurrent manipulation of CO2 levels and water temperatures), and 3) a diverse set of response variables related to fish sensitivity to elevated CO2 levels, water temperatures, and their interactions. The response variable set reflects fish condition, fitness, and likelihood of recruitment, and includes measures of viability, physiology, histopathology, growth, development, and behavior expressed during fish early life-stages (i.e., gametes, embryos, and larvae). Early life-stages were chosen due to the anticipation of their vulnerability to acid-base challenges in their environment. To date, factorial experiments have been implemented on summer flounder (Paralichthys dentatus) and winter flounder (Pseudopleuronectes americanus). Initial results reveal survival of summer flounder embryos is compromised by pH < 7.7 (CO2 > 790 ppm). These results were similar across offspring groups (i.e., embryos from different parents). Winter flounder are larger at hatching when exposed to high CO2 levels in the coolest environment implemented in our experiments (range 4 to 10 ○C). Further responses of advanced larvae of both flounder species are currently being assessed for evidence of other whole body, component organ, and biochemical impairment. This study will aid researchers and resource managers in identifying species types, life-stages, and biotic responses that are most sensitive to the expected future levels of CO2 and water temperature in our oceans.
Alzheimer's Disease in Down Syndrome: Neurobiology and Risk
ERIC Educational Resources Information Center
Zigman, Warren B.; Lott, Ira T.
2007-01-01
Down syndrome (DS) is characterized by increased mortality rates, both during early and later stages of life, and age-specific mortality risk remains higher in adults with DS compared with the overall population of people with mental retardation and with typically developing populations. Causes of increased mortality rates early in life are…
Liu, Jing; Zhao, Yong; Ge, Wei; Zhang, Pengfei; Liu, Xinqi; Zhang, Weidong; Hao, Yanan; Yu, Shuai; Li, Lan; Chu, Meiqiang; Min, Lingjiang; Zhang, Hongfu; Shen, Wei
2017-06-27
The impacts of zinc oxide nanoparticles on embryonic development following oocyte stage exposure are unknown and the underlying mechanisms are sparsely understood. In the current investigation, intact nanoparticles were detected in ovarian tissue in vivo and cultured cells in vitro under zinc oxide nanoparticles treatment. Zinc oxide nanoparticles exposure during the oocyte stage inhibited embryonic development. Notably, in vitro culture data closely matched in vivo embryonic data, in that the impairments caused by Zinc oxide nanoparticles treatment passed through cell generations; and both gamma-H2AX and NF-kappaB pathways were involved in zinc oxide nanoparticles caused embryo-toxicity. Copper oxide and silicon dioxide nanoparticles have been used to confirm that particles are important for the toxicity of zinc oxide nanoparticles. The toxic effects of zinc oxide nanoparticles emanate from both intact nanoparticles and Zn2+. Our investigation along with others suggests that zinc oxide nanoparticles are toxic to the female reproductive system [ovaries (oocytes)] and subsequently embryo-toxic and that precaution should be taken regarding human exposure to their everyday use.
Liu, Jing; Zhao, Yong; Ge, Wei; Zhang, Pengfei; Liu, Xinqi; Zhang, Weidong; Hao, Yanan; Yu, Shuai; Li, Lan; Chu, Meiqiang; Min, Lingjiang; Zhang, Hongfu; Shen, Wei
2017-01-01
The impacts of zinc oxide nanoparticles on embryonic development following oocyte stage exposure are unknown and the underlying mechanisms are sparsely understood. In the current investigation, intact nanoparticles were detected in ovarian tissue in vivo and cultured cells in vitro under zinc oxide nanoparticles treatment. Zinc oxide nanoparticles exposure during the oocyte stage inhibited embryonic development. Notably, in vitro culture data closely matched in vivo embryonic data, in that the impairments caused by Zinc oxide nanoparticles treatment passed through cell generations; and both gamma-H2AX and NF-kappaB pathways were involved in zinc oxide nanoparticles caused embryo-toxicity. Copper oxide and silicon dioxide nanoparticles have been used to confirm that particles are important for the toxicity of zinc oxide nanoparticles. The toxic effects of zinc oxide nanoparticles emanate from both intact nanoparticles and Zn2+. Our investigation along with others suggests that zinc oxide nanoparticles are toxic to the female reproductive system [ovaries (oocytes)] and subsequently embryo-toxic and that precaution should be taken regarding human exposure to their everyday use. PMID:28487501
Pagano, Giovanni; Guida, Marco; Siciliano, Antonietta; Oral, Rahime; Koçbaş, Fatma; Palumbo, Anna; Castellano, Immacolata; Migliaccio, Oriana; Thomas, Philippe J; Trifuoggi, Marco
2016-05-01
Broad-ranging adverse effects are known for rare earth elements (REE), yet only a few studies tested the toxicity of several REE, prompting studies focusing on multi-parameter REE toxicity. Trichloride salts of Y, La, Ce, Nd, Sm, Eu and Gd were tested in Paracentrotus lividus sea urchin embryos and sperm for: (1) developmental defects in either REE-exposed larvae or in the offspring of REE-exposed sperm; (2) fertilization success; (3) mitotic anomalies in REE-exposed embryos and in the offspring of REE-exposed sperm, and (4) reactive oxygen species (ROS) formation, and malondialdehyde (MDA) and nitric oxide (NO) levels. REEs affected P. lividus larvae with concentration-related increase in developmental defects, 10(-6) to 10(-4)M, ranking as: Gd(III)>Y(III)>La(III)>Nd(III)≅Eu(III)>Ce(III)≅Sm(III). Nominal concentrations of REE salts were confirmed by inductively coupled plasma mass spectrometry (ICP-MS). Significant increases in MDA levels, ROS formation, and NO levels were found in REE-exposed embryos. Sperm exposure to REEs (10(-5) to 10(-4)M) resulted in concentration-related decrease in fertilization success along with increase in offspring damage. Decreased mitotic activity and increased aberration rates were detected in REE-exposed embryos and in the offspring of REE-exposed sperm. REE-associated toxicity affecting embryogenesis, fertilization, cytogenetic and redox endpoints showed different activities of tested REEs. Damage to early life stages, along with redox and cytogenetic anomalies should be the focus of future REE toxicity studies. Copyright © 2016 Elsevier Inc. All rights reserved.
Harnessing Apoptotic Cell Clearance to Treat Autoimmune Arthritis
Saas, Philippe; Bonnefoy, Francis; Toussirot, Eric; Perruche, Sylvain
2017-01-01
Early-stage apoptotic cells possess immunomodulatory properties. Proper apoptotic cell clearance during homeostasis has been shown to limit subsequent immune responses. Based on these observations, early-stage apoptotic cell infusion has been used to prevent unwanted inflammatory responses in different experimental models of autoimmune diseases or transplantation. Moreover, this approach has been shown to be feasible without any toxicity in patients undergoing allogeneic hematopoietic cell transplantation to prevent graft-versus-host disease. However, whether early-stage apoptotic cell infusion can be used to treat ongoing inflammatory disorders has not been reported extensively. Recently, we have provided evidence that early-stage apoptotic cell infusion is able to control, at least transiently, ongoing collagen-induced arthritis. This beneficial therapeutic effect is associated with the modulation of antigen-presenting cell functions mainly of macrophages and plasmacytoid dendritic cells, as well as the induction of collagen-specific regulatory CD4+ T cells (Treg). Furthermore, the efficacy of this approach is not altered by the association with two standard treatments of rheumatoid arthritis (RA), methotrexate and tumor necrosis factor (TNF) inhibition. Here, in the light of these observations and recent data of the literature, we discuss the mechanisms of early-stage apoptotic cell infusion and how this therapeutic approach can be transposed to patients with RA. PMID:29062314
Harnessing Apoptotic Cell Clearance to Treat Autoimmune Arthritis.
Saas, Philippe; Bonnefoy, Francis; Toussirot, Eric; Perruche, Sylvain
2017-01-01
Early-stage apoptotic cells possess immunomodulatory properties. Proper apoptotic cell clearance during homeostasis has been shown to limit subsequent immune responses. Based on these observations, early-stage apoptotic cell infusion has been used to prevent unwanted inflammatory responses in different experimental models of autoimmune diseases or transplantation. Moreover, this approach has been shown to be feasible without any toxicity in patients undergoing allogeneic hematopoietic cell transplantation to prevent graft- versus -host disease. However, whether early-stage apoptotic cell infusion can be used to treat ongoing inflammatory disorders has not been reported extensively. Recently, we have provided evidence that early-stage apoptotic cell infusion is able to control, at least transiently, ongoing collagen-induced arthritis. This beneficial therapeutic effect is associated with the modulation of antigen-presenting cell functions mainly of macrophages and plasmacytoid dendritic cells, as well as the induction of collagen-specific regulatory CD4 + T cells (Treg). Furthermore, the efficacy of this approach is not altered by the association with two standard treatments of rheumatoid arthritis (RA), methotrexate and tumor necrosis factor (TNF) inhibition. Here, in the light of these observations and recent data of the literature, we discuss the mechanisms of early-stage apoptotic cell infusion and how this therapeutic approach can be transposed to patients with RA.
Wang, Zhenghe; Li, Changwei; Yang, Zhongping; Ma, Jun; Zou, Zhiyong
2017-06-14
To explore the associations between the Chinese famine exposure in early life and the dyslipidemia in adulthood. We selected 2752 participants from the baseline survey of China Health and Retirement Longitudinal Study (CHARLS) 2011-2012 to evaluate the associations of early life the Chinese famine exposure with risk of dyslipidemia in adulthood. Dyslipidemia was defined as TC (Total Cholesterol): HDL-C (High-Density Lipoprotein Cholesterol) ratio ≥ 5.0 or use cholesterol lowering drugs. Famine exposure cohorts were categorized by birthdates of participants. Binary logistics regression model was used to examine the associations of early-life famine exposure with the risk of dyslipidemia. The dyslipidemia prevalence of the non-exposed cohort, fetal stage-, infant stage-, and preschool stage-exposed cohorts in adulthood was 15.7%, 23.1%, 22.0%, and 18.6%, respectively. Early-life exposure to the Chinese famine significantly increased LDL cholesterol concentrations in adulthood after adjusted for age. The risks of dyslipidemia in fetal (OR = 1.58; 95% CI: 1.23-2.03; P < 0.001) and infant (OR = 1.52; 95% CI: 1.15-2.00; P = 0.003) stage-exposed cohorts were significantly higher than the non-exposed cohort after adjusted for gender and current family economic status. Following gender stratification, we found that fetal (OR = 1.80; 95% CI: 1.26-2.57; P = 0.001), infant (OR = 1.75; 95% CI: 1.17-2.62; P = 0.006), and preschool (OR = 1.63; 95% CI: 1.10-2.42; P = 0.015) -stage exposure to severe famine aggravated the risk of dyslipidemia in female adults. However, the similar association was not observed for male adults. Early-life exposure to severe Chinese famine could link with the higher dyslipidemia risk in female adulthood, but not in male adulthood. This gender-specific effect might be associated with the hypothesis that parents in China prefer boys to girls traditionally or survivors' bias.
English, Sinead; Bateman, Andrew W; Mares, Rafael; Ozgul, Arpat; Clutton-Brock, Tim H
2014-01-01
Resource availability plays a key role in driving variation in somatic growth and body condition, and the factors determining access to resources vary considerably across life stages. Parents and carers may exert important influences in early life, when individuals are nutritionally dependent, with abiotic environmental effects having stronger influences later in development as individuals forage independently. Most studies have measured specific factors influencing growth across development or have compared relative influences of different factors within specific life stages. Such studies may not capture whether early-life factors continue to have delayed effects at later stages, or whether social factors change when individuals become nutritionally independent and adults become competitors for, rather than providers of, food. Here, we examined variation in the influence of the abiotic, social and maternal environment on growth across life stages in a wild population of cooperatively breeding meerkats. Cooperatively breeding vertebrates are ideal for investigating environmental influences on growth. In addition to experiencing highly variable abiotic conditions, cooperative breeders are typified by heterogeneity both among breeders, with mothers varying in age and social status, and in the number of carers present. Recent rainfall had a consistently marked effect on growth across life stages, yet other seasonal terms only influenced growth during stages when individuals were growing fastest. Group size and maternal dominance status had positive effects on growth during the period of nutritional dependence on carers, but did not influence mass at emergence (at 1 month) or growth at independent stages (>4 months). Pups born to older mothers were lighter at 1 month of age and subsequently grew faster as subadults. Males grew faster than females during the juvenile and subadult stage only. Our findings demonstrate the complex ways in which the external environment influences development in a cooperative mammal. Individuals are most sensitive to social and maternal factors during the period of nutritional dependence on carers, whereas direct environmental effects are relatively more important later in development. Understanding the way in which environmental sensitivity varies across life stages is likely to be an important consideration in predicting trait responses to environmental change. PMID:24102215
Avila-Poveda, Omar Hernando; Abadia-Chanona, Quetzalli Yasú
2013-01-01
This study describes and recognises, using histological and microscopical examinations on a morphometrical basis, several gonad traits through the early life stages of Chiton articulatus and C. albolineatus. Gonadal ontogenesis, gonad development stages, sexual differentiation, onset of the first sexual maturity, and growth sequences or "early life stages" were determined. In addition, allometry between lengths and body weight pooled for both sexes per each chiton were calculated using equation Y = aX(b) . A total of 125 chitons (4≤TL≤40 mm, in total length "TL") were used. All allometric relations showed a strong positive correlation (r), close to 1, with b-values above three, indicating an isometric growth. Gonadal ontogenesis and gonad development stages were categorised into three periods ("Pw" without gonad, "Pe" gonad emergence, and "Pf" gonadal sac formed) and four stages ("S0" gametocytogenesis, "S1" gametogenesis, "S2" mature, and "S3" spawning), respectively. Compound digital images were attained for each process. Periods and stages are overlapped among them and between species, with the following overall confidence intervals in TL: Pw 6.13-14.32 mm, Pe 10.32-16.93 mm, Pf 12.99-25.01 mm, S0 16.08-24.34 mm (females) and 19.51-26.60 mm (males), S1 27.15-35.63 mm (females) and 23.45-32.27 mm (males), S2 24.48-40.24 mm (females) and 25.45-32.87 mm (males). Sexual differentiation (in S0) of both chitons occurs first as a female then as a male; although, males reach the onset of the first sexual maturity earlier than females, thus for C. articulatus males at 17 mm and females at 32 mm, and for C. albolineatus males at 23.5 mm and females at 28 mm, all in TL. Four early life stages (i.e., subjuvenile, juvenile, subadult, and adult) are described and proposed to distinguish growth sequences. Our results may be useful to diverse disciplines, from developmental biology to fisheries management.
ERIC Educational Resources Information Center
Hinchliffe, J. R.
1973-01-01
Outlines the advantages of using the readily available eggs of the nematode Rhabditis in studying the early cleavage stages of animal development. Discusses the identification and life history of Rhabditis, how to culture and examine the organism, the cleavage stages and cell lineage, and sources of visual aids. (JR)
ERIC Educational Resources Information Center
Inman, Marjorie
The existing physical forms of housing are not always compatible with prevalent social patterns. To investigate the relationship between family system characteristics and attitudes about residential space, 64 Indiana families in 4 stages of the family life cycle (early years with no children, crowded years with at least one preschool child, peak…
Marentette, Julie R; Frank, Richard A; Bartlett, Adrienne J; Gillis, Patricia L; Hewitt, L Mark; Peru, Kerry M; Headley, John V; Brunswick, Pamela; Shang, Dayue; Parrott, Joanne L
2015-07-01
Naphthenic acids (NAs) are constituents of oil sands process-affected water (OSPW). These compounds can be both toxic and persistent and thus are a primary concern for the ultimate remediation of tailings ponds in northern Alberta's oil sands regions. Recent research has focused on the toxicity of NAs to the highly vulnerable early life-stages of fish. Here we examined fathead minnow embryonic survival, growth and deformities after exposure to extracted NA fraction components (NAFCs), from fresh and aged oil sands process-affected water (OSPW), as well as commercially available NA mixtures. Commercial NA mixtures were dominated by acyclic O2 species, while NAFCs from OSPW were dominated by bi- and tricyclic O2 species. Fathead minnow embryos less than 24h old were reared in tissue culture plates terminating at hatch. Both NAFC and commercial NA mixtures reduced hatch success, although NAFCs from OSPW were less toxic (EC50=5-12mg/L, nominal concentrations) than commercial NAs (2mg/L, nominal concentrations). The toxicities of NAFCs from aged and fresh OSPW were similar. Embryonic heart rates at 2 days post-fertilization (dpf) declined with increasing NAFC exposure, paralleling patterns of hatch success and rates of cardiovascular abnormalities (e.g., pericardial edemas) at hatch. Finfold deformities increased in exposures to commercial NA mixtures, not NAFCs. Thus, commercial NA mixtures are not appropriate surrogates for NAFC toxicity. Further work clarifying the mechanisms of action of NAFCs in OSPW, as well as comparisons with additional aged sources of OSPW, is merited. Crown Copyright © 2015. Published by Elsevier B.V. All rights reserved.
LeCorgne, Hunter; Tudosie, Andrew M; Lavik, Kari; Su, Robin; Becker, Kathryn N; Moore, Sara; Walia, Yashna; Wisner, Alexander; Koehler, Daniel; Alberts, Arthur S; Williams, Frederick E; Eisenmann, Kathryn M
2018-01-01
The mammalian Diaphanous-related (mDia) formins are cytoskeletal regulators that assemble and, in some cases, bundle filamentous actin (F-actin), as well as stabilize microtubules. The development of small molecule antagonists and agonists that interrogate mDia formin function has allowed us to investigate the roles of formins in disease states. A small molecule inhibitor of FH2 domain (SMIFH2) inhibits mDia-dependent actin dynamics and abrogates tumor cell migration and cell division in vitro and ex vivo tissue explants. mDia formin activation with small molecule intramimics IMM01/02 and mDia2-DAD peptides inhibited glioblastoma motility and invasion in vitro and ex vivo rat brain slices. However, SMIFH2, IMMs, and mDia2 DAD efficacy in vivo remains largely unexplored and potential toxicity across a range of developmental phenotypes has not been thoroughly characterized. In this study, we performed an in vivo screen of early life-stage toxicity in Danio rerio zebrafish embryos 2 days post-fertilization (dpf) in response to SMIFH2, IMM01/02, and mDia2 DAD. SMIFH2 at concentrations ≥5-10 μM induced significant defects in developing zebrafish, including shorter body lengths, tail curvature and defective tail cellularity, craniofacial malformations, pericardial edema, absent and/or compromised vasculature function and flow, depressed heart rates and increased mortality. Conversely, IMM and mDia2 DAD peptides were minimally toxic at concentrations up to 10-20 and 50 μM, respectively. SMIFH2's therapeutic potential may therefore be limited by its substantial in vivo toxicity at functional concentrations. mDia formin agonism with IMMs and mDia2 DADs may therefore be a more effective and less toxic anti-invasive therapeutic approach.
LeCorgne, Hunter; Tudosie, Andrew M.; Lavik, Kari; Su, Robin; Becker, Kathryn N.; Moore, Sara; Walia, Yashna; Wisner, Alexander; Koehler, Daniel; Alberts, Arthur S.; Williams, Frederick E.; Eisenmann, Kathryn M.
2018-01-01
The mammalian Diaphanous-related (mDia) formins are cytoskeletal regulators that assemble and, in some cases, bundle filamentous actin (F-actin), as well as stabilize microtubules. The development of small molecule antagonists and agonists that interrogate mDia formin function has allowed us to investigate the roles of formins in disease states. A small molecule inhibitor of FH2 domain (SMIFH2) inhibits mDia-dependent actin dynamics and abrogates tumor cell migration and cell division in vitro and ex vivo tissue explants. mDia formin activation with small molecule intramimics IMM01/02 and mDia2-DAD peptides inhibited glioblastoma motility and invasion in vitro and ex vivo rat brain slices. However, SMIFH2, IMMs, and mDia2 DAD efficacy in vivo remains largely unexplored and potential toxicity across a range of developmental phenotypes has not been thoroughly characterized. In this study, we performed an in vivo screen of early life-stage toxicity in Danio rerio zebrafish embryos 2 days post-fertilization (dpf) in response to SMIFH2, IMM01/02, and mDia2 DAD. SMIFH2 at concentrations ≥5–10 μM induced significant defects in developing zebrafish, including shorter body lengths, tail curvature and defective tail cellularity, craniofacial malformations, pericardial edema, absent and/or compromised vasculature function and flow, depressed heart rates and increased mortality. Conversely, IMM and mDia2 DAD peptides were minimally toxic at concentrations up to 10–20 and 50 μM, respectively. SMIFH2's therapeutic potential may therefore be limited by its substantial in vivo toxicity at functional concentrations. mDia formin agonism with IMMs and mDia2 DADs may therefore be a more effective and less toxic anti-invasive therapeutic approach. PMID:29692731
Selection is stronger in early-versus-late stages of divergence in a Neotropical livebearing fish.
Ingley, Spencer J; Johnson, Jerald B
2016-03-01
How selection acts to drive trait evolution at different stages of divergence is of fundamental importance in our understanding of the origins of biodiversity. Yet, most studies have focused on a single point along an evolutionary trajectory. Here, we provide a case study evaluating the strength of divergent selection acting on life-history traits at early-versus-late stages of divergence in Brachyrhaphis fishes. We find that the difference in selection is stronger in the early-diverged population than the late-diverged population, and that trait differences acquired early are maintained over time. © 2016 The Author(s).
This study demonstrates the potential of whole-mount in situ hybridization (WISH), in conjunction with quantitative real-time polymerase chain reaction (QPCR) assays, to examine the mechanistic basis of the effects of toxicants on early-lifestage fathead minnows. Specifically, fathead minnow embryos were exposed to the environmentally-relevant estrogen receptor agonist, estrone, and the data show that: (1) the estrogen-responsive gene transcripts esr1, vtg, and cyp19b can be up-regulated in very early-lifestages of the fathead minnow, (2) WISH methods developed for zebrafish can also be applied successfully to fathead minnows, and (3) WISH has potential to be a useful tool for toxicological studies pertaining to early-lifestage development in the fathead minnow. This type of mechanistic information relative to spatial distribution of gene expression is important in determining potential biological pathways that may be impacted by targeted chemicals and the development of associated adverse outcome pathways.This dataset is associated with the following publication:Cavallin, J., A. Schroeder, K. Jensen , D. Villeneuve , B. Blackwell, K. Carlson, M. Kahl , C. LaLone , E. Randolph , and G. Ankley. Evaluation of whole-mount in situ hybridization as a tool for pathway-based toxicological research with early-life stage fathead minnows. AQUATIC TOXICOLOGY. Elsevier Science Ltd, New York, NY, USA, 169: 19-26, (2015).
Rosa, Rui; Pimentel, Marta S.; Boavida-Portugal, Joana; Teixeira, Tatiana; Trübenbach, Katja; Diniz, Mário
2012-01-01
Background The knowledge about the capacity of organisms’ early life stages to adapt to elevated temperatures is very limited but crucial to understand how marine biota will respond to global warming. Here we provide a comprehensive and integrated view of biological responses to future warming during the early ontogeny of a keystone invertebrate, the squid Loligo vulgaris. Methodology/Principal Findings Recently-spawned egg masses were collected and reared until hatching at present day and projected near future (+2°C) temperatures, to investigate the ability of early stages to undergo thermal acclimation, namely phenotypic altering of morphological, behavioural, biochemical and physiological features. Our findings showed that under the projected near-future warming, the abiotic conditions inside the eggs promoted metabolic suppression, which was followed by premature hatching. Concomitantly, the less developed newborns showed greater incidence of malformations. After hatching, the metabolic burst associated with the transition from an encapsulated embryo to a planktonic stage increased linearly with temperature. However, the greater exposure to environmental stress by the hatchlings seemed to be compensated by physiological mechanisms that reduce the negative effects on fitness. Heat shock proteins (HSP70/HSC70) and antioxidant enzymes activities constituted an integrated stress response to ocean warming in hatchlings (but not in embryos). Conclusions/Significance The stressful abiotic conditions inside eggs are expected to be aggravated under the projected near-future ocean warming, with deleterious effects on embryo survival and growth. Greater feeding challenges and the lower thermal tolerance limits of the hatchlings are strictly connected to high metabolic demands associated with the planktonic life strategy. Yet, we found some evidence that, in the future, the early stages might support higher energy demands by adjusting some cellular functional properties to increase their thermal tolerance windows. PMID:22701620
Terry, Claire; Hays, Sean; McCoy, Alene T; McFadden, Lisa G; Aggarwal, Manoj; Rasoulpour, Reza J; Juberg, Daland R
2016-03-01
A strategic and comprehensive program in which toxicokinetic (TK) measurements are made for all agrochemicals undergoing toxicity testing (both new compounds and compounds already registered for use) is described. This approach provides the data to more accurately assess the toxicokinetics of agrochemicals and their metabolites in laboratory animals and humans. Having this knowledge provides the ability to conduct more insightful toxicity studies, refine and interpret exposure assessments and reduce uncertainty in risk assessments. By developing a better understanding of TK across species, including humans via in vitro metabolism studies, any differences across species in TK can be identified early and the most relevant species can be selected for toxicity tests. It also provides the ability to identify any non-linearities in TK as a function of dose, which in turn can be used to identify a kinetically derived maximum dose (KMD) and avoid dosing inappropriately outside of the kinetic linear range. Measuring TK in key life stages also helps to identify changes in ADME parameters from in utero to adults. A robust TK database can also be used to set internal concentration based "Reference Concentrations" and Biomonitoring Equivalents (BE), and support selection of Chemical Specific Adjustment Factors (CSAF). All of these factors support the reduction of uncertainty throughout the entire risk assessment process. This paper outlines how a TK research strategy can be integrated into new agrochemical toxicity testing programs, together with a proposed Framework for future use. Copyright © 2015 Elsevier Inc. All rights reserved.
Influence of potentially confounding factors on sea urchin porewater toxicity tests
Carr, R.S.; Biedenbach, J.M.; Nipper, M.
2006-01-01
The influence of potentially confounding factors has been identified as a concern for interpreting sea urchin porewater toxicity test data. The results from >40 sediment-quality assessment surveys using early-life stages of the sea urchin Arbacia punctulata were compiled and examined to determine acceptable ranges of natural variables such as pH, ammonia, and dissolved organic carbon on the fertilization and embryological development endpoints. In addition, laboratory experiments were also conducted with A. punctulata and compared with information from the literature. Pore water with pH as low as 6.9 is an unlikely contributor to toxicity for the fertilization and embryological development tests with A. punctulata. Other species of sea urchin have narrower pH tolerance ranges. Ammonia is rarely a contributing factor in pore water toxicity tests using the fertilization endpoint, but the embryological development endpoint may be influenced by ammonia concentrations commonly found in porewater samples. Therefore, ammonia needs to be considered when interpreting results for the embryological development test. Humic acid does not affect sea urchin fertilization at saturation concentrations, but it could have an effect on the embryological development endpoint at near-saturation concentrations. There was no correlation between sediment total organic carbon concentrations and porewater dissolved organic carbon concentrations. Because of the potential for many varying substances to activate parthenogenesis in sea urchin eggs, it is recommended that a no-sperm control be included with every fertilization test treatment. ?? 2006 Springer Science+Business Media, Inc.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Eaton, J.G.; McCormick, J.H.; Swenson, W.A.
1992-09-01
One-half of Little Rock Lake, a small seepage lake in north-central Wisconsin, was gradually acidified by additions of sulfuric acid between August 1983 and November 1990. The ambient pH (6.1) of the lake was reduced at successive 2-year intervals to pH 5.6, 5.1, and 4.7. Responses of largemouth bass Micropterus salmoides, rock bass Ambloplites rupestris, black crappie Pomoxis nigromaculatus, and yellow perch Perca flavescens populations to the pH reductions were recorded and compared to the responses of these species during in situ bioassays and laboratory toxicity tests on embryos and larvae. Laboratory results obtained for largemouth bass and rock bassmore » underestimated, black crappie results overestimated, and yellow perch results were similar to effects observed in field studies. In situ bioassays predicted field responses better than did laboratory toxicity tests. Laboratory results showed that monomeric Al concentrations of approximately 50 [mu]g/L, which were comparable to Al concentrations in the acidified half of the lake, altered low-pH toxicity. Reduced recruitment was observed in field populations at higher pH than that at which adult mortality was observed. The results indicate that laboratory toxicity tests with early life stages may not accurately predict field population responses and that results from laboratory tests should be field-validated whenever possible. 42 refs., 2 figs., 7 tabs.« less
Hogan, Natacha S; Duarte, Paula; Wade, Michael G; Lean, David R S; Trudeau, Vance L
2008-05-01
During the transformation from larval tadpole to juvenile frog, there are critical periods of metamorphic development and sex differentiation that may be particularly sensitive to endocrine disruption. The aim of the present study was to identify sensitive developmental periods for estrogenic endocrine disruption in the northern leopard frog (Rana pipiens) using short, targeted exposures to the synthetic estrogen, ethinylestradiol (EE2). Post-hatch tadpoles (Gosner stage 27) were exposed over five distinct periods of metamorphosis: early (stage 27-30), mid (stage 30-36), early and mid (stage 27-36), late (stage 36-42), and the entire metamorphic period (chronic; stage 27-42). For each period, animals were sampled immediately following the EE2 exposure and at metamorphic climax (stage 42). The effects of EE2 on metamorphic development and sex differentiation were assessed through measures of length, weight, developmental stage, days to metamorphosis, sex ratios and incidence of gonadal intersex. Our results show that tadpoles exposed to EE2 during mid-metamorphosis were developmentally delayed immediately following exposure and took 2 weeks longer to reach metamorphic climax. In the unexposed groups, there was low proportion (0.15) of intersex tadpoles at stage 30 and gonads appeared to be morphologically distinct (male and female) in all individuals by stage 36. Tadpoles exposed early in development displayed a strong female-biased sex ratio compared to the controls. Moreover, these effects were also seen at metamorphic climax, approximately 2-3 months after the exposure period, demonstrating that transient early life-stage exposure to estrogen can induce effects on the reproductive organs that persist into the beginning of adult life-stages.
Role of chemotherapy and targeted therapy in early-stage non-small cell lung cancer.
Nagasaka, Misako; Gadgeel, Shirish M
2018-01-01
Adjuvant platinum based chemotherapy is accepted as standard of care in stage II and III non-small cell lung cancer (NSCLC) patients and is often considered in patients with stage IB disease who have tumors ≥ 4 cm. The survival advantage is modest with approximately 5% at 5 years. Areas covered: This review article presents relevant data regarding chemotherapy use in the perioperative setting for early stage NSCLC. A literature search was performed utilizing PubMed as well as clinical trial.gov. Randomized phase III studies in this setting including adjuvant and neoadjuvant use of chemotherapy as well as ongoing trials on targeted therapy and immunotherapy are also discussed. Expert commentary: With increasing utilization of screening computed tomography scans, it is possible that the percentage of early stage NSCLC patients will increase in the coming years. Benefits of adjuvant chemotherapy in early stage NSCLC patients remain modest. There is a need to better define patients most likely to derive survival benefit from adjuvant therapy and spare patients who do not need adjuvant chemotherapy due to the toxicity of such therapy. Trials for adjuvant targeted therapy, including adjuvant EGFR-TKI trials and trials of immunotherapy drugs are ongoing and will define the role of these agents as adjuvant therapy.
FETAX assay for evaluation of developmental toxicity.
Mouche, Isabelle; Malesic, Laure; Gillardeaux, Olivier
2011-01-01
The Frog Embryo Teratogenesis Assay Xenopus (FETAX) test is a development toxicity screening test. Due to the small amount of compound needed and the capability to study organogenesis in a short period of time (96 h), FETAX test constitutes an efficient development toxicity alert test when performed early in drug safety development. The test is conducted on fertilized Xenopus laevis mid-blastula stage eggs over the organogenesis period. Compound teratogenic potential is determined after analysis of the mortality and malformation observations on larva. In parallel, FETAX test provides also information concerning embryotoxic effect based on larva length.
FETAX Assay for Evaluation of Developmental Toxicity.
Mouche, Isabelle; Malésic, Laure; Gillardeaux, Olivier
2017-01-01
The frog embryo teratogenesis assay Xenopus (FETAX) test is a development toxicity screening test. Due to the small amount of compound needed and the capability to study organogenesis in a short period of time (96 h), FETAX test constitutes an efficient development toxicity alert test when performed early in drug safety development. The test is conducted on fertilized Xenopus laevis mid-blastula-stage eggs over the organogenesis period. Compound teratogenic potential is determined after analysis of the mortality and malformation observations on larvae. In parallel, FETAX test provides also information concerning embryotoxic effect based on larva length.
Douglas, Joanne T
2014-06-01
Primary progressive aphasia (PPA) is a young-onset neurodegenerative disorder characterized by declining language ability. The nonfluent/agrammatic variant of PPA (PPA-G) has the core features of agrammatism in language production and effortful, halting speech. As with other frontotemporal spectrum disorders, there is currently no cure for PPA, nor is it possible to slow the course of progression. The primary goal of treatment is therefore palliative in nature. However, there is a paucity of published information about strategies to make meaningful improvements to the quality of life of people with PPA, particularly in the early stages of the disease where any benefit could most be appreciated by the affected person. This report describes a range of strategies and adaptations designed to improve the quality of life of a person with early-stage PPA-G, based on my experience under the care of a multidisciplinary medical team. © The Author(s) 2014.
Doss, J G; Ghani, W M N; Razak, I A; Yang, Y H; Rogers, S N; Zain, R B
2017-06-01
This study aimed to assess changes in oral cancer patients' health-related quality of life (HRQOL) and the impact of disease stage on HRQOL scores. HRQOL data were collected from seven hospital-based centres using the Functional Assessment of Cancer Therapy-Head and Neck (FACT-H&N) version 4.0 instrument. The independent samples t-test, χ 2 test, and paired samples t-test were used to analyse the data. A total of 300 patients were recruited. The most common oral cancer sub-site was tongue and floor of mouth (42.6%). Surgical intervention (41.1%) was the most common treatment modality. Significant differences in ethnicity and treatment modality were observed between early and late stage patients. Pre-treatment HRQOL scores were significantly lower for late than early stage patients. At 1 month post-treatment, the functional and head and neck domains and the FACT-H&N (TOI) summary scores showed significant deterioration in both early and late stage patients. In contrast, the emotional domain showed a significant improvement for early and late stage patients at 1, 3, and 6 months post-treatment. Although HRQOL deterioration was still observed among early and late stage patients at 6 months post-treatment, this was not statistically significant. In conclusion, advanced disease is associated with poorer HRQOL. Although ethnic differences were observed across different disease stages, the influence of ethnicity on patient HRQOL was not evident in this study. Copyright © 2017 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
Social Relationships and Health Behavior Across Life Course
Umberson, Debra; Crosnoe, Robert; Reczek, Corinne
2011-01-01
Sociological theory and research point to the importance of social relationships in affecting health behavior. This work tends to focus on specific stages of the life course, with a division between research on childhood/adolescent and adult populations. Yet recent advances demonstrate that early life course experiences shape health outcomes well into adulthood. We synthesize disparate bodies of research on social ties and health behavior throughout the life course, with attention to explaining how various social ties influence health behaviors at different life stages and how these processes accumulate and reverberate throughout the life course. PMID:21921974
Early Exposure to Toxic Substances Damages Brain Architecture. Working Paper #4
ERIC Educational Resources Information Center
National Scientific Council on the Developing Child, 2006
2006-01-01
New science shows that exposure to toxins prenatally or early in life can have a devastating and lifelong effect on the developing architecture of the brain. Exposures to many chemicals have much more severe consequences for embryos, fetuses, and young children, whose brains are still developing, than for adults. Substances that can have a truly…
Pain Medicines for Pets: Know the Risks
... and must be used cautiously in animals with pre-existing kidney or liver problems. Because most liver-associated toxicities occur during the first three weeks, it’s especially important to closely monitor the results of blood tests during the early stages of long-term NSAID ...
Trovo, Marco; Roncadin, Mario; Polesel, Jerry; Piccoli, Erica; Mileto, Mario; Micheli, Elvia; Perin, Tiziana; Carbone, Antonino; Massarut, Samuele; Trovo, Mauro G
2013-10-01
To assess the toxicity and cosmetic results in breast cancer patients undergoing adjuvant partial breast irradiation (PBI) to a total dose of 40 Gy in 10 daily fractions (4 Gy/fraction). Patients affected by early-stage breast cancer were enrolled in this phase II trial. Patients had to be 60 years old and treated with breast conservative surgery for early stage (pT1-T2 pN0-N1a) invasive ductal carcinoma. 77 patients were enrolled. Median follow-up was 18 months. The proposed schedule was well tolerated. One patient reported Grade 3 pain at the site of irradiation. Four (5%) patients experience Grade 2 erythema. Late Grade 2 and 1 fibrosis was observed in 3 (4%) and 14 (18%) patients, respectively. Cosmesis was judged "good/excellent" and "poor" in 75 (97%) and in 2 (3%) patients, respectively. 40 Gy in 10 daily fractions, 4 Gy/fraction, is a well tolerated regimen to deliver PBI. Copyright © 2013 Elsevier Ltd. All rights reserved.
Method refinements for the midge life-cycle, Chironomus dilutus test
Larval stages of non-biting midges can be found in almost any freshwater ecosystem, and one of the commonly tested midges is Chironomus dilutus (Chironomidae, Diptera) which is used for toxicity testing and ecological risk assessment of freshwater contaminants. USEPA, ASTM, Envir...
Life-Stage PBPK Models for Multiple Routes of Ethanol Exposure in the Rat
Ethanol is commonly blended with gasoline (10% ethanol) in the US, and higher ethanol concentrations are being considered. While the pharmacokinetics and toxicity of orally-ingested ethanol are widely reported, comparable work is limited for inhalation exposure (IE), particularly...
AGE-RELATED SUSCEPTIBILITY: A GENOMICS APPROACH.
By the year 2030 more than 70 million Americans will be over the age of 65. These older adults are a subpopulation that may have special susceptibility to toxic insult due to critical characteristics of their life-stage. Current EPA testing guidelines do not identify the elderl...
LIFE-STAGE DEPENDENT DOSIMETRY AND POTENTIAL IMPACTS ON RISK ASSESSMENT APPROACHES
Increasingly reproductive and developmental toxicity studies are utilized in assessing the potential for adverse affects in pregnant women, nursing infants, and children. These studies largely have been utilized based upon the dose to the mother due to the complexity of describi...
Wang, Huili; Che, Baoguang; Duan, Ailian; Mao, Jingwen; Dahlgren, Randy A; Zhang, Minghua; Zhang, Hongqin; Zeng, Aibing; Wang, Xuedong
2014-10-01
This study evaluated the effects of β-diketone antibiotics (DKAs) on the development of embryo-larval zebrafish (Danio rerio). When exposure to DKAs, developmental malformations, such as hatching delay, curved body axis, pericardial edema, uninflated swim bladder and yolk sac edema, were observed at 120 h postfertilization (hpf). The estimated 120 hpf nominal concentrations of no observed effect concentration and lowest observed effect concentration for DKAs were 18.75 and 37.50 mg/L, respectively, suggesting that DKAs have much lower toxicity than other persistent pollutants. Following DKA exposure, embryonic heart rates were significantly reduced as compared to the controls at 48 and 60 hpf. The peak bending motion frequency appeared 1 h earlier than in control embryos. The 2.34 and 9.38-mg/L treatment groups had a higher basal swim rate than control groups at 120 hpf in both light and light-to-dark photoperiod experiments. The occurrence of high speed swim rates was enhanced approximately threefold to sevenfold in the 2.34 and 9.38 mg/L treatments compared to the control. Glutathione (GSH) concentrations in the 2.34 and 9.38-mg/L treatments were significantly higher than the control at 72 hpf, suggesting that GSH production was induced at the end of the hatching period. When exposed to DKAs, zebrafish superoxide dismutase enzyme (SOD) activities were significantly inhibited in the early embryonic period, demonstrating that the clearing ability in zebrafish was lower than the generation rate of free radicals. In summary, the combined DKAs were developmentally toxic to zebrafish in their early life stages and had the ability to impair individual behaviors that are of great importance in the assessment of their ecological fitness. Copyright © 2013 Wiley Periodicals, Inc., a Wiley company.
Chen, Liang; Wang, Yeke; Giesy, John P; Chen, Feng; Shi, Ting; Chen, Jun; Xie, Ping
2018-05-22
Frequencies and durations of blooms of cyanobacteria are increasing. Some cyanobacteria can produce cyanotoxins including microcystins (MCs). MCs are the most common toxic products of hazardous algal blooms (HABs), with the greatest potential for exposure and to cause toxicity. Recently, MCs have been shown to disrupt endocrine functions. In this study, for the first time, effects of MC-LR on the hypothalamic-pituitary-inter-renal (HPI) axis during early embryonic development (embryos/larvae) of zebrafish (Danio rerio), were investigated. Embryos/larvae of zebrafish were exposed to 1, 10, 100, or 300 μg MC-LR/L during the period of 4-168 h post-fertilization (hpf). Exposure to 300 μg MC-LR/L resulted in significantly greater concentrations of whole-body cortisol than those in controls. Expressions of genes along the HPI axis and mineralocorticoid receptor (MR-) and glucocorticoid receptor (GR-) centered gene networks were evaluated by use of quantitative real-time PCR. Expression of mRNA for crh was significantly down-regulated by exposure to 300 μg MC-LR/L, while expressions of crhbp, crhr1, and crhr2 were significantly up-regulated, relative to controls. MC-LR caused significantly lesser levels of mRNA for steroidogenic genes including hmgra, star, and cyp17, but expression of mRNA for hsd20b was significantly greater than that of controls. Treatment with MC-LR also altered profiles of transcription of MR- and GR-centered gene networks, which might result in multiple responses. Taken together, these results demonstrated that MC-LR affected the corticosteroid-endocrine system of larvae of zebrafish. This study provided valuable insights into molecular mechanisms behind potential toxicity and endocrine disruption of MCs. Copyright © 2018 Elsevier Ltd. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Gunther, Jillian R.; Fanale, Michelle A.; Reddy, Jay P.
Purpose: The German Hodgkin Study Group HD11 trial validated 4 cycles of doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) chemotherapy followed by involved field radiation therapy (IFRT) for early unfavorable Hodgkin lymphoma (HL) patients. However, practitioners often recommend 6 cycles followed by RT, especially for bulky disease. We compared patient outcomes after treatment with 4 or 6 cycles of ABVD followed by RT (IFRT and involved site RT [ISRT]). Methods and Materials: We identified 128 patients treated for early unfavorable HL (GHSG criteria) between 2000 and 2013. Clinical outcomes (overall survival [OS] and freedom from relapse [FFR]) were estimated using Kaplan-Meier analysis. Toxicitiesmore » were evaluated. Results: The median follow-up time was 5.0 years. Patients received 4 (70 patients, 55%) or 6 (58 patients, 45%) cycles of chemotherapy. Bulky disease was present in 22 patients (31%; 0 stage IA, 3 stage IB, 19 stage IIA) of the 4-cycle group and 42 patients (72%; 5 stage IA, 3 stage IB, 34 stage IIA) of the 6-cycle group. For patients receiving 4 and 6 cycles, the 6-year OS was 100% and 97% (P=.35), respectively, and the 6 year FFR was 100% and 98% (P=.28), respectively. More patients received 6 cycles if they were treated before 2010 (HD11 report) (P=.01) and if they had bulky disease (P<.01). Sixty-eight percent of patients received ISRT. The 6-year FFR was 99% and 100% for patients receiving ISRT and IFRT, respectively (P=.58). More patients experienced bleomycin pulmonary toxicity in the 6-cycle group (20% vs 31%, P=.16). For patients with bulky disease, the 4-year FFR was similar with receipt of 4 (100%) or 6 (98%) cycles (P=.48) and IFRT (100%) or ISRT (98%) (P=.52). There were no deaths among patients with bulky disease. Conclusions: Patients with early unfavorable HL have excellent outcomes with 4 cycles of ABVD chemotherapy followed by ISRT. Six cycles of chemotherapy does not appear superior for disease control, even for bulky disease.« less
A Parent-Offspring Trade-Off Limits the Evolution of an Ontogenetic Niche Shift.
Ten Brink, Hanna; de Roos, André M
2017-07-01
Many free-living animal species, including the majority of fish, insects, and amphibians, change their food and habitat during their life. Even though these ontogenetic changes in niche are common, it is not well understood which ecological conditions have favored the evolution of these shifts. Using an adaptive dynamics approach, we show that it is evolutionarily advantageous to switch to an alternative food source in the course of ontogeny when this results in a higher intake rate for the switching consumers. Individuals are, however, not able to specialize on this new food source when this negatively affects the performance early in life on the original food source. Selection on these early life stages is so strong that in species with a complete diet shift, evolution results in large juveniles and adults that are maladapted to the alternative food source while their offspring are specialized on the original food source when young. These outcomes suggest strong selection to decouple the different life stages, such that they can maximize their performance on different food sources independently from each other. Metamorphosis could be a way to decouple the different life stages and therefore evolve in species that feed on multiple food sources during their life.
Stenehjem, David D; Bellows, Brandon K; Yager, Kraig M; Jones, Joshua; Kaldate, Rajesh; Siebert, Uwe; Brixner, Diana I
2016-02-01
A prognostic test was developed to guide adjuvant chemotherapy (ACT) decisions in early-stage non-small cell lung cancer (NSCLC) adenocarcinomas. The objective of this study was to compare the cost-utility of the prognostic test to the current standard of care (SoC) in patients with early-stage NSCLC. Lifetime costs (2014 U.S. dollars) and effectiveness (quality-adjusted life-years [QALYs]) of ACT treatment decisions were examined using a Markov microsimulation model from a U.S. third-party payer perspective. Cancer stage distribution and probability of receiving ACT with the SoC were based on data from an academic cancer center. The probability of receiving ACT with the prognostic test was estimated from a physician survey. Risk classification was based on the 5-year predicted NSCLC-related mortality. Treatment benefit with ACT was based on the prognostic score. Discounting at a 3% annual rate was applied to costs and QALYs. Deterministic one-way and probabilistic sensitivity analyses examined parameter uncertainty. Lifetime costs and effectiveness were $137,403 and 5.45 QALYs with the prognostic test and $127,359 and 5.17 QALYs with the SoC. The resulting incremental cost-effectiveness ratio for the prognostic test versus the SoC was $35,867/QALY gained. One-way sensitivity analyses indicated the model was most sensitive to the utility of patients without recurrence after ACT and the ACT treatment benefit. Probabilistic sensitivity analysis indicated the prognostic test was cost-effective in 65.5% of simulations at a willingness to pay of $50,000/QALY. The study suggests using a prognostic test to guide ACT decisions in early-stage NSCLC is potentially cost-effective compared with using the SoC based on globally accepted willingness-to-pay thresholds. Providing prognostic information to decision makers may help some patients with high-risk early stage non-small cell lung cancer receive appropriate adjuvant chemotherapy while avoiding the associated toxicities and costs in patients with low-risk disease. This study used an economic model to assess the effectiveness and costs associated with using a prognostic test to guide adjuvant chemotherapy decisions compared with the current standard of care in patients with non-small cell lung cancer. When compared with current standard care, the prognostic test was potentially cost effective at commonly accepted thresholds in the U.S. This study can be used to help inform decision makers who are considering using prognostic tests. ©AlphaMed Press.
Brooks, Eric D; Sun, Bing; Zhao, Lina; Komaki, Ritsuko; Liao, Zhonxing; Jeter, Melenda; Welsh, James W; O'Reilly, Michael S; Gomez, Daniel R; Hahn, Stephen M; Heymach, John V; Rice, David C; Chang, Joe Y
2017-07-15
To discern the effectiveness and toxicity of stereotactic ablative radiation therapy (SABR) in the elderly population (aged ≥75 years) and to consider how SABR outcomes compare with surgical outcomes historically reported in the elderly. A total of 772 patients with clinical early-stage I-II non-small cell lung cancer (NSCLC; stage T1-T3N0M0) underwent SABR (50 Gy in 4 fractions or 70 Gy in 10 fractions) from 2004 to 2014 at our center (n=442, aged <75 years; n=330, aged ≥75 years). The primary endpoints included overall survival (OS), time-to-progression, and grade ≥3 toxicity. The median follow-up time was approximately 55 months. Compared with patients aged <75 years, those aged ≥75 years had no difference in the time-to-progression (P=.419), lung cancer-specific survival (P=.275), or toxicity (P=.536). OS was the same between both age groups at 2 years of follow-up but diverged thereafter, with patients aged <75 years when treatment began having greater OS rates at 5 years. The median OS rates for patients aged ≥75 years were 86% at 1 year, 57.5% at 3 years, and 39.5% at 5 years. The median OS rates for patients aged <75 years were 87.3% at 1 year, 67.6% at 3 years, and 51.5% at 5 years. No patient aged ≥75 years experienced any grade 4 or 5 toxicity. The effectiveness of SABR was the same for the elderly as for the average-age population according to lung cancer-specific survival and time-to-progression. It also poses no increased toxicity. Compared with the historical outcomes with surgery in the elderly, SABR outcomes can be considered comparable for stage I-II disease but with less morbidity. Copyright © 2016 Elsevier Inc. All rights reserved.
Involved-Field, Low-Dose Chemoradiotherapy for Early-Stage Anal Carcinoma
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hatfield, Paul; Cooper, Rachel; Sebag-Montefiore, David
2008-02-01
Purpose: To report the results of patients with early-stage anal cancer treated using a low-dose, reduced-volume, involved-field chemoradiotherapy protocol. Methods and Materials: Between June 2000 and June 2006, 21 patients were treated with external beam radiotherapy (30 Gy in 15 fractions within 3 weeks) and concurrent chemotherapy (bolus mitomycin-C 12 mg/m{sup 2} on Day 1 to a maximum of 20 mg followed by infusion 5-fluorouracil 1,000 mg/m{sup 2}/24 h on Days 1-4). Of the 21 patients, 18 underwent small-volume, involved-field radiotherapy and 3 were treated with anteroposterior-posteroanterior parallel-opposed pelvic fields. Of the 21 patients, 17 had had lesions that weremore » excised with close (<1 mm) or involved margins, 1 had had microinvasive disease on biopsy, and 3 had had macroscopic tumor <2 cm in diameter (T1). All were considered to have Stage N0 disease radiologically. Results: After a median follow-up of 42 months, only 1 patient (4.7%) had experienced local recurrence and has remained disease free after local excision. No distant recurrences or deaths occurred. Only 1 patient could not complete treatment (because of Grade 3 gastrointestinal toxicity). Grade 3-4 hematologic toxicity occurred in only 2 patients (9.5%). No significant late toxicity was identified. Conclusion: The results of our study have shown that for patients with anal carcinoma who have residual microscopic or very-small-volume disease, a policy of low-dose, reduced-volume, involved-field chemoradiotherapy produces excellent local control and disease-free survival, with low rates of acute and late toxicity.« less
The early life stages of fish are known to be more sensitive than the adults to the toxicological effects of 2,3,7,8-tetrachlorodibenzo(p)dioxide (TCDD). TCDD concentrations in surface waters are sufficiently low that direct exposure of the developing embryo is unlikely to be o...
Brian V. Smithers; Malcolm P. North; Constance I. Millar; Andrew M. Latimer
2017-01-01
In response to climate warming, subalpine treelines are expected to move up in elevation since treelines are generally controlled by growing season temperature. Where treeline is advancing, dispersal differences and early life stage environmental tolerances are likely to affect how species expand their ranges. Species with an establishment advantage will...
Chen, Eric; Brown, David M; Benz, Matthew S; Fish, Richard H; Wong, Tien P; Kim, Rosa Y; Major, James C
2010-10-21
While the long-term incidence of hydroxychloroquine (HCQ) retinopathy is low, there remains no definitive clinical screening test to recognize HCQ toxicity before ophthalmoscopic fundus changes or visual symptoms. Patients receiving HCQ were evaluated with spectral domain optical coherence tomography (SD OCT) to assess the feasibility of identifying HCQ retinopathy at an early stage. Twenty-five patients referred for the evaluation of hydroxychloroquine toxicity underwent a comprehensive ocular examination, Humphrey visual field (HVF) perimetry, time domain OCT, and SD OCT. Some patients with screening abnormalities also underwent further diagnostic testing at the discretion of the treating providers. Five patients were found to have SD OCT findings corresponding to HCQ toxicity and retinal damage as seen by clinical exam and/or HVF perimetry. Two patients with advanced toxicity were found to have significant outer retina disruption in the macula on SD OCT. Three patients with early HCQ toxicity and HVF 10-2 perifoveal defects were found to have loss of the perifoveal photoreceptor inner segment/outer segment (IS/OS) junction with intact outer retina directly under the fovea, creating the "flying saucer" sign. While two of these three patients had early ophthalmoscopic fundus changes, one had none. Outer retinal abnormalities including perifoveal photoreceptor IS/OS junction disruption can be identified by SD OCT in early HCQ toxicity, sometimes even before ophthalmoscopic fundus changes are apparent. SD OCT may have a potential complementary role in screening for HCQ retinopathy due to its quick acquisition and because it is more objective than automated perimetry.
[Infections and epigenetic changes in cancer].
Corvalán, Alejandro H; Maturana, María José
2016-01-01
The role of epigenetics and infectious diseases at early stages of life influence pre-malignant lesions of cancer, in particular, gastric cancer, one of the most frequent tumours in Chile, Latin America, and worldwide. This article examines the role of H.pylori and epigenetic alterations (i.e. DNA methylation) at early stages of gastric cancer and proposes, from the paediatric point of view, strategies for prevention and early detection. Copyright © 2016. Publicado por Elsevier España, S.L.U.
Cold storage of Acartia tonsa eggs: a practical use in ecotoxicological studies.
Vitiello, V; Zhou, C; Scuderi, A; Pellegrini, D; Buttino, I
2016-07-01
The calanoid copepod Acartia tonsa has been recommended as a marine organism for ecotoxicological tests due to its wide distribution, short life cycle and high productivity. This species is used in acute and chronic toxicity tests to assess water and sediment quality; egg hatching success and the survival of the first larval stages are considered endpoints. Toxicity test protocols require a large number of organisms and an appropriate culture system. Eggs stored under conditions that delay hatching could ensure sufficient quantities of biological materials for ecotoxicological tests. In the current study early-spawned eggs were stored at 3 °C (±1) up to 240 days and their hatching success was evaluated on a monthly basis. Our results showed that the percentage of hatching success for eggs stored for 30 days was >80 % and decreased by about 8 % for every 20 days of storage, up to 120 days. A further increase of time in cold storage brought about a significant reduction, in statistical term, of hatching success compared with the control group (43.69 ± 22.19 %). Almost 50 % of eggs hatched or died during the cold storage period, with more than 80 % lost after periods longer than 150 days. To verify the suitability of stored eggs for toxicity test, 48 h acute tests were performed using nickel chloride as a referent toxicant. Eggs stored for 30, 60, 90 and 120 days gave EC50 values ranging from 0.130 to 0.221 mg L(-1), similar to the value recorded for early-spawned eggs, suggesting that these eggs can be used for ecotoxicological tests. Our results open new possibilities for a wider use of the Mediterranean strain of A. tonsa copepod for ecotoxicological tests.
2017-03-01
complete a specific part of its life cycle due to resuspended sediment. However, there is limited information concerning species-specific biological...and to determine its effects on the early life stages of aquatic organisms. Studies using FLEES use fine-grained sediment particles which are most...the dredge to areas where the critical life stages of the species of concern may be exposed. Target endpoints were project specific, including
Parental dietary seleno-L-methionine exposure and resultant offspring developmental toxicity
Chernick, Melissa; Ware, Megan; Albright, Elizabeth; Kwok, Kevin W.H.; Dong, Wu; Zheng, Na; Hinton, David E.
2015-01-01
Selenium (Se) leaches into water from agricultural soils and from storage sites for coal fly ash. Se toxicity causes population and community level effects in fishes and birds. We used the laboratory aquarium model fish, Japanese medaka (Oryzias latipes), an asynchronous breeder, to determine aspects of uptake in adults and resultant developmental toxicity in their offspring. The superior imaging properties of the model enabled detailed descriptions of phenotypic alterations not commonly reported in the existing Se literature. Adult males and females in treatment groups were exposed, separately and together, to a dry diet spiked with 0, 12.5, 25, or 50 µg/g (dry weight) seleno-L-methionine (SeMet) for 6 days, and their embryo progeny collected for 5 days, maintained under controlled conditions and observed daily for hatchability, mortality and/or developmental toxicity. Sites of alteration included: craniofacial, pericardium and abdomen (Pc/Ab), notochord, gall bladder, spleen, blood, and swim bladder. Next, adult tissue Se concentrations (liver, skeletal muscle, ovary and testis) were determined and compared in treatment groups of bred and unbred individuals. No significant difference was found across treatment groups at the various SeMet concentrations; and, subsequent analysis compared exposed vs. control in each of the treatment groups at 10 dpf. Increased embryo mortality was observed in all treatment groups, compared to controls, and embryos had a decreased hatching rate when both parents were exposed. Exposure resulted in significantly more total altered phenotypes than controls. When altered phenotypes following exposure of both parents were higher than maternal only exposure, a male role was suggested. The comparisons between treatment groups revealed that particular types of phenotypic change may be driven by the sex of the exposed parent. Additionally, breeding reduced Se concentrations in some adult tissues, specifically the liver of exposed females and skeletal muscle of exposed males. Detailed phenotypic analysis of progeny from SeMet exposed parents should inform investigations of later life stages in an effort to determine consequences of early life exposure. PMID:26655662
Managing Breast Cancer in the Older Patient
O’Connor, Tracey; Shinde, Arvind; Doan, Caroline; Katheria, Vani; Hurria, Arti
2013-01-01
Breast cancer is a disease associated with aging, with almost one-half of all new breast cancer cases diagnosed annually in the United States occurring in women age 65 and older. Recent data suggest that although breast cancer outcomes in younger women have shown substantial improvement as a result of advances in treatment and screening, the benefits in older women have been less pronounced. Although older adults have been under-represented on cancer clinical trials there is an emerging body of literature to help guide treatment decisions. For early stage breast cancer, the discussion regarding treatment options involves balancing the reduction in risk of recurrence gained by specific therapies with the potential for increased treatment-related toxicity potentially exacerbated by physiological decline or comorbidities that often co-exist in the older population. A key component of care of the older adult is the recognition that chronologic age alone cannot guide the management of an older individual with breast cancer; rather, treatment decisions must also take into account an individual’s functional status, estimated life expectancy, the risks and benefits of the therapy, potential barriers to treatment, and patient preference. This article reviews the available evidence for therapeutic management of early-stage breast cancer in older adults, and highlights data from geriatric oncology literature that provides a basis on which to facilitate evidence-based treatment. PMID:24472802
Saghir, Shakil A; Bartels, Michael J; Rick, David L; McCoy, Alene T; Rasoulpour, Reza J; Ellis-Hutchings, Robert G; Sue Marty, M; Terry, Claire; Bailey, Jason P; Billington, Richard; Bus, James S
2012-07-01
Integrated toxicokinetics (TK) data provide information on the rate, extent and duration of systemic exposure across doses, species, strains, gender, and life stages within a toxicology program. While routine for pharmaceuticals, TK assessments of non-pharmaceuticals are still relatively rare, and have never before been included in a full range of guideline studies for a new agrochemical. In order to better understand the relationship between diurnal systemic dose (AUC(24h)) and toxicity of agrochemicals, TK analyses in the study animals is now included in all short- (excluding acute), medium- and long-term guideline mammalian toxicity studies including reproduction/developmental tests. This paper describes a detailed procedure for the implementation of TK in short-, medium- and long-term regulatory toxicity studies, without the use of satellite animals, conducted on three agrochemicals (X11422208, 2,4-D and X574175). In these studies, kinetically-derived maximum doses (KMD) from short-term studies instead of, or along with, maximum tolerated doses (MTD) were used for the selection of the high dose in subsequent longer-term studies. In addition to leveraging TK data to guide dose level selection, the integrated program was also used to select the most appropriate method of oral administration (i.e., gavage versus dietary) of test materials for rat and rabbit developmental toxicity studies. The integrated TK data obtained across toxicity studies (without the use of additional/satellite animals) provided data critical to understanding differences in response across doses, species, strains, sexes, and life stages. Such data should also be useful in mode of action studies and to improve human risk assessments. Copyright © 2012 Elsevier Inc. All rights reserved.
Age, stage and senescence in plants
Caswell, Hal; Salguero-Gómez, Roberto
2013-01-01
1. Senescence (an increase in the mortality rate or force of mortality, or a decrease in fertility, with increasing age) is a widespread phenomenon. Theories about the evolution of senescence have long focused on the age trajectories of the selection gradients on mortality and fertility. In purely age-classified models, these selection gradients are non-increasing with age, implying that traits expressed early in life have a greater impact on fitness than traits expressed later in life. This pattern leads inevitably to the evolution of senescence if there are trade-offs between early and late performance. 2. It has long been suspected that the stage- or size-dependent demography typical of plants might change these conclusions. In this paper, we develop a model that includes both stage- and age-dependence and derive the age-dependent, stage-dependent and age×stage-dependent selection gradients on mortality and fertility. 3. We applied this model to stage-classified population projection matrices for 36 species of plants, from a wide variety of growth forms (from mosses to trees) and habitats. 4. We found that the age-specific selection gradients within a life cycle stage can exhibit increases with age (we call these contra-senescent selection gradients). In later stages, often large size classes in plant demography, the duration of these contra-senescent gradients can exceed the life expectancy by several fold. 5. Synthesis. The interaction of age- and stage-dependence in plants leads to selection pressures on senescence fundamentally different from those found in previous, age-classified theories. This result may explain the observation that large plants seem less subject to senescence than most kinds of animals. The methods presented here can lead to improved analysis of both age-dependent and stage-dependent demographic properties of plant populations. PMID:23741075
Ecotoxicological models generally have large data requirements and are frequently based on existing information from diverse sources. Standardizing data for toxicological models may be necessary to reduce extraneous variation and to ensure models reflect intrinsic relationships. ...
2009-09-01
testing may be a preferable or complementary strategy in certain situations utilizing a weight of evidence approach (Baird et al. 2007). One of the most...embryonic development, or post-exposure feeding rate are discussed. It is acknowledged that a plethora of additional endpoints have utility for use in situ...example, may have proven utility , it is generally preferable to evaluate toxicity using ecologically relevant species and life stages (i.e., those
USSR Report, Life Sciences, Biomedical and Behavioral Sciences.
1987-02-06
containing hyphal bodies were innocuous for the aphids. Some toxicity was shown by the 2-day culture marked by initial stages of sporulation. Highest...Medical Institute] [Abstract] Medium MW blood peptides have been previously demonstrated in burn studies to possess toxic effect, a fact that provided a...and 7-12 days after use of 0.6-1.2g doses of the drug three times a day. The effect of mebicar was compared with the effect of piracetam in doses
Textile dyes induce toxicity on zebrafish early life stages.
de Oliveira, Gisele Augusto Rodrigues; de Lapuente, Joaquín; Teixidó, Elisabet; Porredón, Constança; Borràs, Miquel; de Oliveira, Danielle Palma
2016-02-01
Textile manufacturing is one of the most polluting industrial sectors because of the release of potentially toxic compounds, such as synthetic dyes, into the environment. Depending on the class of the dyes, their loss in wastewaters can range from 2% to 50% of the original dye concentration. Consequently, uncontrolled use of such dyes can negatively affect human health and the ecological balance. The present study assessed the toxicity of the textile dyes Direct Black 38 (DB38), Reactive Blue 15 (RB15), Reactive Orange 16 (RO16), and Vat Green 3 (VG3) using zebrafish (Danio rerio) embryos for 144 h postfertilization (hpf). At the tested conditions, none of the dyes caused significant mortality. The highest RO16 dose significantly delayed or inhibited the ability of zebrafish embryos to hatch from the chorion after 96 hpf. From 120 hpf to 144 hpf, all the dyes impaired the gas bladder inflation of zebrafish larvae, DB38 also induced curved tail, and VG3 led to yolk sac edema in zebrafish larvae. Based on these data, DB38, RB15, RO16, and VG3 can induce malformations during embryonic and larval development of zebrafish. Therefore, it is essential to remove these compounds from wastewater or reduce their concentrations to safe levels before discharging textile industry effluents into the aquatic environment. © 2015 SETAC.
Thomas, Jith K; Janz, David M
2015-08-18
The objectives of this study were (1) to establish egg selenium (Se) toxicity thresholds for mortality and deformities in early life stages of zebrafish (Danio rerio) after exposure to excess selenomethionine (SeMet, the dominant chemical species of Se in diets) via in ovo maternal transfer and (2) to investigate the persistent effects of developmental exposure to excess SeMet on swim performance and metabolic capacities in F1-generation adult zebrafish. Adult zebrafish were fed either control food (1.3 μg Se/g, dry mass or d.m.) or food spiked with increasing measured concentrations of Se (3.4, 9.8, or 27.5 μg Se/g, d.m.) in the form of SeMet for 90 d. In ovo exposure to SeMet increased mortality and deformities in larval zebrafish in a concentration-dependent fashion with threshold egg Se concentrations (EC10s) of 7.5 and 7.0 μg Se/g d.m., respectively. Impaired swim performance and greater respiration and metabolic rates were observed in F1-generation zebrafish exposed in ovo to 6.8 and 12.7 μg Se/g d.m and raised to adulthood in clean water. A species sensitivity distribution (SSD) based on egg Se developmental toxicity thresholds suggests that zebrafish are the most sensitive fish species studied to date.
Identification of Chemical Toxicity Using Ontology Information of Chemicals.
Jiang, Zhanpeng; Xu, Rui; Dong, Changchun
2015-01-01
With the advance of the combinatorial chemistry, a large number of synthetic compounds have surged. However, we have limited knowledge about them. On the other hand, the speed of designing new drugs is very slow. One of the key causes is the unacceptable toxicities of chemicals. If one can correctly identify the toxicity of chemicals, the unsuitable chemicals can be discarded in early stage, thereby accelerating the study of new drugs and reducing the R&D costs. In this study, a new prediction method was built for identification of chemical toxicities, which was based on ontology information of chemicals. By comparing to a previous method, our method is quite effective. We hope that the proposed method may give new insights to study chemical toxicity and other attributes of chemicals.
Kearn, James; Lilley, Catherine; Urwin, Peter; O'Connor, Vincent; Holden-Dye, Lindy
2017-10-01
Fluensulfone is a new nematicide with an excellent profile of selective toxicity against plant parasitic nematodes. Here, its effects on the physiology and biochemistry of the potato cyst nematode Globodera pallida have been investigated and comparisons made with its effect on the life-span of the free-living nematode Caenorhabditis elegans to provide insight into its mode of action and its selective toxicity. Fluensulfone exerts acute effects (≤1h; ≥100μM) on stylet thrusting and motility of hatched second stage G. pallida juveniles (J2s). Chronic exposure to lower concentrations of fluensulfone (≥3days; ≤30μM), reveals a slowly developing metabolic insult in which G. pallida J2s sequentially exhibit a reduction in motility, loss of a metabolic marker for cell viability, high lipid content and tissue degeneration prior to death. These effects are absent in adults and dauers of the model genetic nematode Caenorhabditis elegans. The nematicidal action of fluensulfone follows a time-course which progresses from an early impact on motility through to an accumulating metabolic impairment, an inability to access lipid stores and death. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
Arsenic and Immune Response to Infection During Pregnancy and Early Life
Attreed, Sarah E.; Navas-Acien, Ana
2017-01-01
Purpose of Review Arsenic, a known carcinogen and developmental toxicant, is a major threat to global health. While the contribution of arsenic exposure to chronic diseases and adverse pregnancy and birth outcomes is recognized, its ability to impair critical functions of humoral and cell-mediated immunity—including the specific mechanisms in humans—is not well understood. Arsenic has been shown to increase risk of infectious diseases that have significant health implications during pregnancy and early life. Here, we review the latest research on the mechanisms of arsenic-related immune response alterations that could underlie arsenic-associated increased risk of infection during the vulnerable periods of pregnancy and early life. Recent Findings The latest evidence points to alteration of antibody production and transplacental transfer as well as failure of T helper cells to produce IL-2 and proliferate. Summary Critical areas for future research include the effects of arsenic exposure during pregnancy and early life on immune responses to natural infection and the immunogenicity and efficacy of vaccines. PMID:28488132
Arsenic and Immune Response to Infection During Pregnancy and Early Life.
Attreed, Sarah E; Navas-Acien, Ana; Heaney, Christopher D
2017-06-01
Arsenic, a known carcinogen and developmental toxicant, is a major threat to global health. While the contribution of arsenic exposure to chronic diseases and adverse pregnancy and birth outcomes is recognized, its ability to impair critical functions of humoral and cell-mediated immunity-including the specific mechanisms in humans-is not well understood. Arsenic has been shown to increase risk of infectious diseases that have significant health implications during pregnancy and early life. Here, we review the latest research on the mechanisms of arsenic-related immune response alterations that could underlie arsenic-associated increased risk of infection during the vulnerable periods of pregnancy and early life. The latest evidence points to alteration of antibody production and transplacental transfer as well as failure of T helper cells to produce IL-2 and proliferate. Critical areas for future research include the effects of arsenic exposure during pregnancy and early life on immune responses to natural infection and the immunogenicity and efficacy of vaccines.
Effects of Salinity on Oil Spill Dispersant Toxicity in Estuarine Organisms
NASA Astrophysics Data System (ADS)
Eckmann, C. A.
2016-02-01
Chemical dispersants can be a useful tool to mitigate oil spills, but the potential risks to sensitive estuarine species should be carefully considered. To improve the decision making process, more information is needed regarding the effects of oil spill dispersants on the health of coastal ecosystems under variable environmental conditions such as salinity. The two oil dispersants used in this study were Corexit ® 9500 and Finasol ® OSR 52. Corexit ® 9500 was the primary dispersant used during the 2010 Deepwater Horizon oil spill event, while Finasol® OSR 52 is another dispersant approved for oil spill response in the U.S., yet considerably less is known regarding its toxicity to estuarine species. The grass shrimp, Palaemonetes pugio, was used as a model estuarine species. It is a euryhaline species that tolerates salinities from brackish to full strength seawater. Adult and larval life stages were tested with each dispersant at three salinities, 5ppt, 20ppt, and 30ppt. Median acute lethal toxicity thresholds were calculated. Lipid peroxidation assays were conducted on surviving shrimp to investigate sublethal effects. The toxicity of both dispersants was significantly influenced by salinity, with greatest toxicity observed at the lowest salinity tested. Larval shrimp were significantly more sensitive than adult shrimp to both dispersants, and both life stages were significantly more sensitive to Finasol than to Corexit. Furthermore, significant sublethal effects were seen at higher concentrations of both dispersants compared to the control. These data will enable environmental managers to make informed decisions regarding dispersant use in future oil spills.
Effects of Salinity on Oil Spill Dispersant Toxicity in Estuarine Organisms
NASA Astrophysics Data System (ADS)
Eckmann, C. A.
2015-12-01
Chemical dispersants can be a useful tool to mitigate oil spills, but the potential risks to sensitive estuarine species should be carefully considered. To improve the decision making process, more information is needed regarding the effects of oil spill dispersants on the health of coastal ecosystems under variable environmental conditions such as salinity. The two oil dispersants used in this study were Corexit ® 9500 and Finasol ® OSR 52. Corexit ® 9500 was the primary dispersant used during the 2010 Deepwater Horizon oil spill event, while Finasol® OSR 52 is another dispersant approved for oil spill response in the U.S., yet considerably less is known regarding its toxicity to estuarine species. The grass shrimp, Palaemonetes pugio, was used as a model estuarine species. It is a euryhaline species that tolerates salinities from brackish to full strength seawater. Adult and larval life stages were tested with each dispersant at three salinities, 5ppt, 20ppt, and 30ppt. Median acute lethal toxicity thresholds were calculated. Lipid peroxidation assays were conducted on surviving shrimp to investigate sublethal effects. The toxicity of both dispersants was significantly influenced by salinity, with greatest toxicity observed at the lowest salinity tested. Larval shrimp were significantly more sensitive than adult shrimp to both dispersants, and both life stages were significantly more sensitive to Finasol than to Corexit. Furthermore, significant sublethal effects were seen at higher concentrations of both dispersants compared to the control. These data will enable environmental managers to make informed decisions regarding dispersant use in future oil spills.
Stereotactic body radiation therapy of early-stage non-small-cell lung carcinoma: Phase I study
DOE Office of Scientific and Technical Information (OSTI.GOV)
McGarry, Ronald C.; Papiez, Lech; Williams, Mark
Purpose: A Phase I dose escalation study of stereotactic body radiation therapy to assess toxicity and local control rates for patients with medically inoperable Stage I lung cancer. Methods and Materials: All patients had non-small-cell lung carcinoma, Stage T1a or T1b N0, M0. Patients were immobilized in a stereotactic body frame and treated in escalating doses of radiotherapy beginning at 24 Gy total (3 x 8 Gy fractions) using 7-10 beams. Cohorts were dose escalated by 6.0 Gy total with appropriate observation periods. Results: The maximum tolerated dose was not achieved in the T1 stratum (maximum dose = 60 Gy),more » but within the T2 stratum, the maximum tolerated dose was realized at 72 Gy for tumors larger than 5 cm. Dose-limiting toxicity included predominantly bronchitis, pericardial effusion, hypoxia, and pneumonitis. Local failure occurred in 4/19 T1 and 6/28 T2 patients. Nine local failures occurred at doses {<=}16 Gy and only 1 at higher doses. Local failures occurred between 3 and 31 months from treatment. Within the T1 group, 5 patients had distant or regional recurrence as an isolated event, whereas 3 patients had both distant and regional recurrence. Within the T2 group, 2 patients had solitary regional recurrences, and the 4 patients who failed distantly also failed regionally. Conclusions: Stereotactic body radiation therapy seems to be a safe, effective means of treating early-stage lung cancer in medically inoperable patients. Excellent local control was achieved at higher dose cohorts with apparent dose-limiting toxicities in patients with larger tumors.« less
Buckler, Justin; Candrl, James S.; McKee, Michael J.; Papoulias, Diana M.; Tillitt, Donald E.; Galat, David L.
2015-01-01
Concern exists that polychlorinated biphenyls (PCBs) may be contributing to the current decline of shovelnose sturgeon (Scaphirhynchus platorynchus) and the US federally endangered pallid sturgeon (Scaphirhynchus albus). Waterborne exposures with newly fertilized eggs were used to assess developmental and morphological effects of 2 of the most potent aryl hydrocarbon receptor (AhR) agonists, 3,3′,4,4′,5-pentachlorobiphenyl (PCB-126) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), on early life stage shovelnose and pallid sturgeon. No dose-related effects of PCB-126 were observed on percent development or hatch in either species at concentrations as high as 1711 ng/g egg. Effects of TCDD on percent development were not assessed in shovelnose sturgeon. However, percent development was not affected by TCDD in pallid sturgeon, and percent hatch was unaffected by TCDD doses as high as 60 ng/g egg to 81 ng/g egg in either species. Morphological pathologies such as yolk sac edema and craniofacial deformities were typical of AhR agonist exposure and were similar in both species. Calculated PCB-126 50% lethal dose (LD50, 95% fiducial limits) values were 196 ng/g egg (188–203 ng/g) for shovelnose and 159 ng/g egg (122–199 ng/g) for pallid sturgeon. Likewise, calculated TCDD LD50 values were 13 ng/g egg (11–15 ng/g) for shovelnose and 12 ng/g egg (10–14 ng/g) for pallid sturgeon. These LD50 values are among the highest recorded in early life stage fish, suggesting that early life stage Scaphirhynchus sturgeon may be comparatively insensitive to AhR agonists.
Raj, Akanksha; Shah, Prasanna
2017-01-01
Silver nanoparticles (AgNPs) containing consumer products have been proliferating in the market due to its unique antimicrobial property, however, lack of in-depth knowledge about their potential effect on human health in a longer run is of great concern. Therefore, we investigated dose-dependent in vivo effect of AgNPs using Drosophila as a model system. Drosophila, a genetically tractable organism with distinct developmental stages, short life cycle and significant homology with human serves as an ideal organism to study nanomaterial-mediated toxicity. Our studies suggest that ingestion of AgNPs in Drosophila during adult stage for short and long duration significantly affects egg laying capability along with impaired growth of ovary. Additionally, dietary intake of AgNPs from larval stage has more deleterious effects that result in reduced survival, longevity, ovary size and egg laying capability at a further lower dosage. Interestingly, the trans-generational effect of AgNPs was also observed without feeding progeny with AgNPs, thereby suggesting its impact from previous generation. Our results strongly imply that higher doses of AgNPs and its administration early during development is detrimental to the reproductive health and survival of Drosophila that follows in generations to come without feeding them to AgNPs. PMID:28542630
Raj, Akanksha; Shah, Prasanna; Agrawal, Namita
2017-01-01
Silver nanoparticles (AgNPs) containing consumer products have been proliferating in the market due to its unique antimicrobial property, however, lack of in-depth knowledge about their potential effect on human health in a longer run is of great concern. Therefore, we investigated dose-dependent in vivo effect of AgNPs using Drosophila as a model system. Drosophila, a genetically tractable organism with distinct developmental stages, short life cycle and significant homology with human serves as an ideal organism to study nanomaterial-mediated toxicity. Our studies suggest that ingestion of AgNPs in Drosophila during adult stage for short and long duration significantly affects egg laying capability along with impaired growth of ovary. Additionally, dietary intake of AgNPs from larval stage has more deleterious effects that result in reduced survival, longevity, ovary size and egg laying capability at a further lower dosage. Interestingly, the trans-generational effect of AgNPs was also observed without feeding progeny with AgNPs, thereby suggesting its impact from previous generation. Our results strongly imply that higher doses of AgNPs and its administration early during development is detrimental to the reproductive health and survival of Drosophila that follows in generations to come without feeding them to AgNPs.
Vardy, Janette; Dhillon, Haryana M; Clarke, Stephen J; Olesen, Inger; Leslie, Felicity; Warby, Anne; Beith, Jane; Sullivan, Anne; Hamilton, Anne; Beale, Philip; Rittau, Anneliese; McLachlan, Andrew J
2013-12-01
Women receiving treatment for breast cancer commonly ingest herbal medicines. Little is known about the potential for herb-drug interactions in this population. The aim of this study is to investigate the effect of ginkgo biloba co-administration on the pharmacokinetics of tamoxifen, anastrozole and letrozole. This was a prospective open-label cross-over study in 60 women with early stage breast cancer taking either tamoxifen, anastrozole or letrozole (n=20/group). Participants received ginkgo biloba (EGb 761) for 3 weeks (120 mg twice daily). Trough concentrations of drugs were measured before and after ginkgo biloba treatment using LC-MS/MS. Toxicities were graded according to National Cancer Institute Common Terminology Criteria for Adverse Events. Trough concentrations before and after treatment with ginkgo biloba were not significantly different for tamoxifen (93.5 ± 29.0, 86.5 ± 25.3 ng/mL; p=0.16), letrozole (91.1 ± 50.4, 89.6 ± 52.14 ng/mL; p=0.60) or anastrozole (29.1 ± 8.6, 29.1 ± 7.6 ng/mL; p=0.97). Ginkgo biloba was well tolerated, with no difference in toxicity during ginkgo biloba. Co-administration of ginkgo biloba does not significantly affect the pharmacokinetics of tamoxifen, anastrozole or letrozole. There was no difference in the toxicity profile of hormone therapy with ginkgo biloba use in women with early stage breast cancer.
Aguirre-Sierra, Aránzazu; Alonso, Alvaro; Camargo, Julio A
2011-05-01
In contrast to aquatic vertebrates, there is scarce available information on the contrasting tolerance to fluoride of different life stages and/or sizes of aquatic invertebrates. The purpose of this study was to assess the likely differences in sensitivity between juveniles and adults of the aquatic snail Potamopyrgus antipodarum (Hydrobiidae, Mollusca) to short-term (4 days) toxicity of fluoride ion (F(-)). LC50 and EC50 values for juveniles were significantly lower than those for adults at 24, 48, 72 and 96 h. Based on our results, the use of fluoride data of bioassays with juveniles should provide more protective water quality criteria than data from adult stage. © Springer Science+Business Media, LLC 2011
ERIC Educational Resources Information Center
Bozzon, Rossella; Murgia, Annalisa; Poggio, Barbara; Rapetti, Elisa
2017-01-01
This paper addresses the topic of work-life interferences in academic contexts. More specifically, it focuses on early career researchers in the Italian university system. The total availability required from those who work in the research sector is leading to significant transformations of the temporalities of work, especially among the new…
Blohmer, J U; Rezai, M; Kümmel, S; Kühn, T; Warm, M; Friedrichs, K; Benkow, A; Valentine, W J; Eiermann, W
2013-01-01
The 21-gene assay (Oncotype DX Breast Cancer Test (Genomic Health Inc., Redwood City, CA)) is a well validated test that predicts the likelihood of adjuvant chemotherapy benefit and the 10-year risk of distant recurrence in patients with ER+, HER2- early-stage breast cancer. The aim of this analysis was to evaluate the cost-effectiveness of using the assay to inform adjuvant chemotherapy decisions in Germany. A Markov model was developed to make long-term projections of distant recurrence, survival, quality-adjusted life expectancy, and direct costs for patients with ER+, HER2-, node-negative, or up to 3 node-positive early-stage breast cancer. Scenarios using conventional diagnostic procedures or the 21-gene assay to inform treatment recommendations for adjuvant chemotherapy were modeled based on a prospective, multi-center trial in 366 patients. Transition probabilities and risk adjustment were based on published landmark trials. Costs (2011 Euros (€)) were estimated from a sick fund perspective based on resource use in patients receiving chemotherapy. Future costs and clinical benefits were discounted at 3% annually. The 21-gene assay was projected to increase mean life expectancy by 0.06 years and quality-adjusted life expectancy by 0.06 quality-adjusted life years (QALYs) compared with current clinical practice over a 30-year time horizon. Clinical benefits were driven by optimized allocation of adjuvant chemotherapy. Costs from a healthcare payer perspective were lower with the 21-gene assay by ∼€561 vs standard of care. Probabilistic sensitivity analysis indicated that there was an 87% probability that the 21-gene assay would be dominant (cost and life saving) to standard of care. Country-specific data on the risk of distant recurrence and quality-of-life were not available. Guiding decision-making on adjuvant chemotherapy using the 21-gene assay was projected to improve survival, quality-adjusted life expectancy, and be cost saving vs the current standard of care women with ER+, HER2- early-stage breast cancer.
McClusky, Leon M
2006-09-01
Naturally occurring heavy metals and synthetic compounds are potentially harmful for testicular function but evidence linking heavy metal exposure to reduced semen parameters is inconclusive. Elucidation of the exact stage at which the toxicant interferes with spermatogenesis is difficult because the various germ cell stages may have different sensitivities to any given toxicant, germ cell development is influenced by supporting testicular somatic cells and the presence of inter-Sertoli cell tight junctions create a blood-testis barrier, sequestering meiotic and postmeiotic germ cells in a special microenvironment. Sharks such as Squalus acanthias provide a suitable model for studying aspects of vertebrate spermatogenosis because of their unique features: spermatogenesis takes place within spermatocysts and relies mainly on Sertoli cells for somatic cell support; spermatocysts are linearly arranged in a maturational order across the diameter of the elongated testis; spermatocysts containing germ cells at different stages of development are topographically separated, resulting in visible zonation in testicular cross sections. We have used the vital dye acridine orange and a novel fluorescence staining technique to study this model to determine (1) the efficacy of these methods in assays of apoptosis and blood-testis barrier function, (2) the sensitivity of the various spermatogonial generations in Squalus to cadmium (as an illustrative spermatotoxicant) and (3) the way that cadmium might affect more mature spermatogenic stages and other physiological processes in the testis. Our results show that cadmium targets early spermatogenic stages, where it specifically activates a cell death program in susceptible (mature) spermatogonial clones, and negatively affects blood-testis barrier function. Since other parameters are relatively unaffected by cadmium, the effects of this toxicant on apoptosis are presumably process-specific and not attributable to general toxicity.
NASA Technical Reports Server (NTRS)
Phelps, H. L.
1984-01-01
Heavy metals in the estuarine environment can be toxic to fish and shellfish early life history stages and concentrations build up to levels of concern in marketable shellfish. The present survey was begun just before startup in 1974 of the 1900 megawatt Calvert Cliffs Nuclear Power Plant on the Chesapeake Bay in order to assess and understand factors relating to heavy metal accumulation in estuarine biota. Oysters were collected in large numbers at test and reference sites in June 1974 to 77 and individually analyzed for copper and zinc. Oyster copper and zinc concentrations were correlated with salinity read at time of collection. The relationship of oyster age to metal concentration was examined with two sets of oysters of known age and genetic origin (laboratory spawned). Copper sorption by typical mid Bay sediments, and field studies on cadmium concentrations in sediments were examined.
PHOTODYNAMIC THERAPY OF CANCER: AN UPDATE
Agostinis, Patrizia; Berg, Kristian; Cengel, Keith A.; Foster, Thomas H.; Girotti, Albert W.; Gollnick, Sandra O.; Hahn, Stephen M.; Hamblin, Michael R.; Juzeniene, Asta; Kessel, David; Korbelik, Mladen; Moan, Johan; Mroz, Pawel; Nowis, Dominika; Piette, Jacques; Wilson, Brian C.; Golab, Jakub
2011-01-01
Photodynamic therapy (PDT) is a clinically approved, minimally invasive therapeutic procedure that can exert a selective cytotoxic activity toward malignant cells. The procedure involves administration of a photosensitizing agent followed by irradiation at a wavelength corresponding to an absorbance band of the sensitizer. In the presence of oxygen, a series of events lead to direct tumor cell death, damage to the microvasculature and induction of a local inflammatory reaction. Clinical studies revealed that PDT can be curative particularly in early-stage tumors. It can prolong survival in inoperable cancers and significantly improve quality of life. Minimal normal tissue toxicity, negligible systemic effects, greatly reduced long-term morbidity, lack of intrinsic or acquired resistance mechanisms, and excellent cosmetic as well as organ function-sparing effects of this treatment make it a valuable therapeutic option for combination treatments. With a number of recent technological improvements, PDT has the potential to become integrated into the mainstream of cancer treatment. PMID:21617154
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.
Report of the NASA Mammalian Developmental Biology Working Group
NASA Technical Reports Server (NTRS)
Keefe, J. R.
1985-01-01
Development is considered to encompass all aspects of the mammalian life span from initial initial germ cell production through the complete life cycle to death of the organism. Thus, gamete production, fertilization, embryogenesis, implantation, fetogenesis, birth, peri- and postnatal maturation, and aging were all considered as stages of a development continuum relevant to problems of Space Biology. Deliberations thus far have been limited to stages of the development cycle from fertilization to early postnatal life. The deliberations are detailed.
Mahalingaiah, Shruthi; Winter, Michael R.; Aschengrau, Ann
2016-01-01
Background Tetrachloroethylene (PCE) is an organic lipophilic solvent with possible neuroendocrine toxicity. The objective of this study was to determine the association of prenatal and early childhood exposure to PCE-contaminated drinking water and development of adult-onset Polycystic Ovary Syndrome (PCOS), endometriosis, difficulty conceiving and miscarriage. Methods Five-hundred exposed and 331 unexposed female participants born between 1969 and 1983 completed questionnaires on demographic and lifestyle characteristics, and reproductive disorders. Residential locations from the prenatal period through five years of age were used to estimate early life PCE exposure with water modeling software. Results For any early life exposure to PCE, the adjusted risk ratio for PCOS was 0.9 (95% CI: 0.5–1.6). No statistically significant associations were observed for increasing levels of exposure with PCOS or the other reproductive disorders. Conclusion No meaningful associations were found among adult women with early life exposure to PCE-contaminated drinking water and adult-onset reproductive disorders. PMID:27412368
Zambonino-Infante, José L; Claireaux, Guy; Ernande, Bruno; Jolivet, Aurélie; Quazuguel, Patrick; Sévère, Armelle; Huelvan, Christine; Mazurais, David
2013-05-07
An individual's environmental history may have delayed effects on its physiology and life history at later stages in life because of irreversible plastic responses of early ontogenesis to environmental conditions. We chose a marine fish, the common sole, as a model species to study these effects, because it inhabits shallow marine areas highly exposed to environmental changes. We tested whether temperature and trophic conditions experienced during the larval stage had delayed effects on life-history traits and resistance to hypoxia at the juvenile stage. We thus examined the combined effect of global warming and hypoxia in coastal waters, which are potential stressors to many estuarine and coastal marine fishes. Elevated temperature and better trophic conditions had a positive effect on larval growth and developmental rates; warmer larval temperature had a delayed positive effect on body mass and resistance to hypoxia at the juvenile stage. The latter suggests a lower oxygen demand of individuals that had experienced elevated temperatures during larval stages. We hypothesize that an irreversible plastic response to temperature occurred during early ontogeny that allowed adaptive regulation of metabolic rates and/or oxygen demand with long-lasting effects. These results could deeply affect predictions about impacts of global warming and eutrophication on marine organisms.
Early developmental stages of fish are extremely sensitive to a class of toxic and persistent environmental contaminants known as dioxin-like compounds (DLCs). Most of the toxicological actions of DLCs are mediated via the Aryl hydrocarbon Receptor (AhR) that regulates transcript...
Calfee, Robin D; Little, Edward E; Puglis, Holly J; Scott, Erinn; Brumbaugh, William G; Mebane, Christopher A
2014-01-01
The acute toxicity of cadmium, copper, and zinc to white sturgeon (Acipenser transmontanus) and rainbow trout (Oncorhynchus mykiss) were determined for 7 developmental life stages in flow-through water-only exposures. Metal toxicity varied by species and by life stage. Rainbow trout were more sensitive to cadmium than white sturgeon across all life stages, with median effect concentrations (hardness-normalized EC50s) ranging from 1.47 µg Cd/L to 2.62 µg Cd/L with sensitivity remaining consistent during later stages of development. Rainbow trout at 46 d posthatch (dph) ranked at the 2nd percentile of a compiled database for Cd species sensitivity distribution with an EC50 of 1.46 µg Cd/L and 72 dph sturgeon ranked at the 19th percentile (EC50 of 3.02 µg Cd/L). White sturgeon were more sensitive to copper than rainbow trout in 5 of the 7 life stages tested with biotic ligand model (BLM)-normalized EC50s ranging from 1.51 µg Cu/L to 21.9 µg Cu/L. In turn, rainbow trout at 74 dph and 95 dph were more sensitive to copper than white sturgeon at 72 dph and 89 dph, indicating sturgeon become more tolerant in older life stages, whereas older trout become more sensitive to copper exposure. White sturgeon at 2 dph, 16 dph, and 30 dph ranked in the lower percentiles of a compiled database for copper species sensitivity distribution, ranking at the 3rd (2 dph), 5th (16 dph), and 10th (30 dph) percentiles. White sturgeon were more sensitive to zinc than rainbow trout for 1 out of 7 life stages tested (2 dph with an biotic ligand model–normalized EC50 of 209 µg Zn/L) and ranked in the 1st percentile of a compiled database for zinc species sensitivity distribution. Environ Toxicol Chem 2014;33:2259–2272. © 2014. The Authors. This article is a US government work and, as such, is in the public domain in the United States of America. Environmental Toxicology and Chemistry published byWiley Periodicals, Inc. on behalf of SETAC. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. PMID:25043712
Predicting Maternal Rat and Pup Exposures: How Different Are They?
Risk and safety assessments for early life exposures to environmental chemicals or pharmaceuticals based on cross-species extrapolation would greatly benefit from information on chemical dosimetry in the young. Although relevant toxicity studies involve exposures during multiple ...
The influence of aging on susceptibility to environmental contaminants is poorly understood. The objectives of this study were to test whether oxidative stress (OS) is a potential toxicity pathway following toluene exposure and to determine if these effects are age-dependent. We ...
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...
Application of a multi-channel system for continuous monitoring and an early warning system.
Lee, J H; Song, C H; Kim, B C; Gu, M B
2006-01-01
A multi-channel continuous toxicity monitoring system developed in our laboratory, based on two-stage mini-bioreactors, was successfully implemented in the form of computer-based data acquisition. The multi-channel system consists of a series of a two-stage minibioreactor systems connected by a fiber optic probe to a luminometer, and uses genetically engineered bioluminescent bacteria for the detection of the potential toxicity from the soluble chemicals. This system can be stably and continuously operated due to the separation of the culture reactor from the test reactor and accomplish easy and long-term monitoring without system shut down by abrupt inflows of severe polluting chemicals. Four different recombinant bioluminescent bacteria were used in different channels so that the modes of the samples toxicities can be reasonably identified and evaluated based upon the response signature of each channel. The bioluminescent signatures were delivered from four channels by switching one at once, while the data is automatically logged to an IBM compatible computer. We also achieved the enhancement of the system through the manipulation of the dilution rate and the use of thermo-lux fusion strains. Finally, this system is now being implemented to a drinking water reservoir and river for remote sensing as an early warning system.
English, Sinead; Bateman, Andrew W; Mares, Rafael; Ozgul, Arpat; Clutton-Brock, Tim H
2014-03-01
Resource availability plays a key role in driving variation in somatic growth and body condition, and the factors determining access to resources vary considerably across life stages. Parents and carers may exert important influences in early life, when individuals are nutritionally dependent, with abiotic environmental effects having stronger influences later in development as individuals forage independently. Most studies have measured specific factors influencing growth across development or have compared relative influences of different factors within specific life stages. Such studies may not capture whether early-life factors continue to have delayed effects at later stages, or whether social factors change when individuals become nutritionally independent and adults become competitors for, rather than providers of, food. Here, we examined variation in the influence of the abiotic, social and maternal environment on growth across life stages in a wild population of cooperatively breeding meerkats. Cooperatively breeding vertebrates are ideal for investigating environmental influences on growth. In addition to experiencing highly variable abiotic conditions, cooperative breeders are typified by heterogeneity both among breeders, with mothers varying in age and social status, and in the number of carers present. Recent rainfall had a consistently marked effect on growth across life stages, yet other seasonal terms only influenced growth during stages when individuals were growing fastest. Group size and maternal dominance status had positive effects on growth during the period of nutritional dependence on carers, but did not influence mass at emergence (at 1 month) or growth at independent stages (>4 months). Pups born to older mothers were lighter at 1 month of age and subsequently grew faster as subadults. Males grew faster than females during the juvenile and subadult stage only. Our findings demonstrate the complex ways in which the external environment influences development in a cooperative mammal. Individuals are most sensitive to social and maternal factors during the period of nutritional dependence on carers, whereas direct environmental effects are relatively more important later in development. Understanding the way in which environmental sensitivity varies across life stages is likely to be an important consideration in predicting trait responses to environmental change. © 2013 The Authors. Journal of Animal Ecology published by John Wiley & Sons Ltd on behalf of the British Ecological Society.
Gamma radiation tolerance in different life stages of the fruit fly Drosophila melanogaster.
Paithankar, Jagdish Gopal; Deeksha, K; Patil, Rajashekhar K
2017-04-01
Insects are known to have higher levels of radiation tolerance than mammals. The fruit fly Drosophila provides opportunities for genetic analysis of radiation tolerance in insects. A knowledge of stage-specific sensitivity is required to understand the mechanisms and test the existing hypothesis of insect radiation tolerance. Drosophila melanogaster were irradiated using gamma rays at different life stages. Irradiation doses were chosen to start from 100-2200 Gy with increments of 100 Gy, with a dose rate of 12.5 and 25 Gy/min. The threshold of mortality, LD 50 and LD 100 1 h post-irradiation was recorded for larvae and adults and 24 h post-irradiation for eggs and after 2-3 days for early and late pupae. Total antioxidant capacity for all the life stages was measured using the phosphomolybdenum method. Twenty-four hours post-irradiation, 100% mortality was recorded for eggs at 1000 Gy. One hour post irradiation 100% mortality was recorded at 1300 Gy for first instar larvae, 1700 Gy for second instar larvae, 1900 Gy for feeding third instar larvae and 2200 Gy for non-feeding third instar larvae. Post-irradiation complete failure of emergence (100% mortality) was observed at 130 Gy for early pupae and 1500 Gy for late pupae; 100% mortality was observed at 1500 Gy for adults. The values of LD 50 were recorded as 452 Gy for eggs, 1049 Gy for first instar larvae, 1350 Gy for second instar larvae, 1265 Gy for feeding third instar larvae, 1590 Gy for non-feeding third instar larvae, 50 Gy for early pupae, 969 Gy for late pupae, 1228 Gy for adult males and 1250 Gy for adult females. Early pupae were found to be prone to radiation, whereas the non-feeding third instar larvae were most resistant among all stages. The chromosome number being constant and total antioxidant capacity being nearly constant in all stages, we suggest that high rate of cell division during early pupae makes this stage sensitive to radiation.
Milam, C.D.; Farris, J.L.; Dwyer, F.J.; Hardesty, D.K.
2005-01-01
Acute (24-h) toxicity tests were used in this study to compare lethality responses in early life stages (glochidia) of six freshwater mussel species, Leptodea fragilis, U. imbecillis, Lampsilis cardium, Lampsilis siliquoidea, Megalonaias nervosa, and Ligumia subrostrata, and two standard test organisms, Ceriodaphnia dubia and Daphnia magna. Concentrations of carbaryl, copper, 4-nonylphenol, pentachlorophenol, permethrin, and 2,4-D were used in acute exposures to represent different chemical classes and modes of action. The relative sensitivities of species were evaluated by ranking their LC 50 values for each chemical. We used these ranks to determine the extent to which U. imbecillis (one of the most commonly used unionids in toxicity tests) was representative of the tolerances of other mussels. We also calculated geometric mean LC50s for the families Unionidae and Daphnidae. Rankings of these data were used to assess the extent to which Daphnidae can be used as surrogates for freshwater mussels relative to chemical sensitivity. While no single chemical elicited consistently high or low toxicity estimates, carbaryl and 2,4-D were generally the least toxic to all species tested. No species was always the most sensitive, and Daphnidae were generally protective of Unionidae. Utterbackia imbecillis, while often proposed as a standard unionid mussel test species, did not always qualify as a sufficient surrogate (i.e., a substitute organism that often elicits similar sensitivity responses to the same contaminant exposure) for other species of mussels, since it was usually one of the more tolerant species in our rankings. U. imbecillis should be used as a surrogate species only with this caution on its relative insensitivity. ?? 2005 Springer Science+Business Media, Inc.
Alves, Romulo Nepomuceno; Mariz, Célio Freire; Paulo, Driele Ventura de; Carvalho, Paulo S M
2017-07-01
Used petroleum hydrocarbons and gasoline stations runoff are significant sources of polycyclic aromatic hydrocarbons (PAHs) to aquatic ecosystems. Samples of the final effluent of oil-water-separators were collected at gasoline stations in the metropolitan region of Recife, Brazil, before release to sewage or rainwater systems. Effluent soluble fractions (ESF) were prepared and bioassays were performed according to the Fish Embryo Toxicity Test. The test involved exposing zebrafish Danio rerio embryos to dilutions of the ESFs for 96 h, with daily examination of lethality and sublethal morphological effects integrated through the General Morphology Score (GMS), based on the achievement of developmental hallmarks. Frequencies of abnormalities were recorded after exposures. ESF LC50-96h (lethal concentration to 50% of exposed embryos) in the most toxic effluent achieved 8.9% (v/v), equivalent to 11 μg phenanthrene equivalents L -1 . GMS scores indicated significantly delayed embryo-larval development at ESF dilutions of 10% and 20% from effluents of all gas stations. Major abnormalities detected after the 96 h exposure included the presence of a yolk sac not fully absorbed coupled with the lack of an inflated swim bladder, lack of both pectoral fins, and the failure to develop a protruding mouth. Effective equivalent PAH concentrations that induce a 50% frequency of larvae without an inflated swim bladder (EC50) were 4.9 μg phenanthrene L -1 , 21.8 μg naphthalene L -1 , and 34.1 μg chrysene L -1 . This study shows that PAHs in ESFs from gas stations oil water separators are toxic to zebrafish, contributing to the toxicity of urban storm waters. Copyright © 2017 Elsevier Ltd. All rights reserved.
Maternal Separation Does Not Produce a Significant Behavioral Change in Mice
Tan, Shawn; Ho, Hin San; Song, Anna Yoonsu; Low, Joey
2017-01-01
Early life adversities together with genetic predispositions have been associated with elevated risks of neuropsychiatric disorders during later life. In order to investigate the underlying mechanisms, many chronic, early-life stress paradigms in multiple animal models have been developed. Previously, studies reported that maternal separation (MS) in the early postnatal stages triggers depression-and/or anxiety-like behaviors in rats. However, similar studies using mice have reported inconsistent behavioral outcomes. In this study, we sought to assess behavioral outcomes from two different early-life stress paradigms; a conventional 3-hour MS and a maternal separation with early weaning (MSEW) paradigm using C57BL/6J male mice with independent cohorts. Our data demonstrated that both MS and MSEW paradigms did not produce reported behavioral anomalies. Therefore, MS paradigms in mice require further validation and modification. PMID:29302206
Czesny, Sergiusz; Dettmers, John M; Rinchard, Jacques; Dabrowski, Konrad
2009-12-01
The natural reproduction of lake trout Salvelinus namaycush in Lake Michigan is thought to be compromised by nutritional deficiency associated with inadequate levels of thiamine (vitamin B1) in their eggs. However, mortality driven by thiamine deficiency (commonly referred to as early mortality syndrome [EMS]) is not the only significant cause of low lake trout survival at early life stages. In this study, we sought to better understand the combined effects of variable levels of thiamine and fatty acids in lake trout eggs on prehatch, posthatch, and swim-up-stage mortality. We sampled the eggs of 29 lake trout females from southwestern Lake Michigan. The concentrations of free thiamine and its vitamers (e.g., thiamine monophosphate [TMP] and thiamine pyrophosphate [TPP]) as well as fatty acid profiles were determined in sampled eggs. Fertilized eggs and embryos were monitored through the advanced swim-up stage (1,000 degree-days). Three distinct periods of mortality were identified: prehatch (0-400 degree-days), immediately posthatch (401-600 degree-days), and swim-up (601-1,000 degree-days). Stepwise multiple regression analysis revealed (1) that cis-7-hexadecenoic acid in both neutral lipids (NL) and phospholipids (PL) correlated with prehatch mortality, (2) that docosapentaenoic acid in PL and docosahexaenoic acid in NL correlated with posthatch mortality, and (3) that total lipids, TPP, and palmitoleic acid in NL, linoleic acid, and palmitic acid in PL correlated with the frequency of EMS. These results indicate the complexity of early life stage mortality in lake trout and suggest that inadequate levels of key fatty acids in eggs, along with variable thiamine content, contribute to the low survival of lake trout progeny in Lake Michigan.
'Making the best you can of it': living with early-stage Alzheimer's disease.
Macrae, Hazel
2008-04-01
Drawing upon data from a qualitative study of persons who are in the early stage of the condition, this paper examines the meaning of Alzheimer's disease. It contrasts the meaning of the disease as portrayed in popular culture with its meaning as interpreted by persons living with it. Findings show that persons with the illness do not necessarily accept the negative cultural meaning of the disease, nor the helpless 'victim' role in which they are generally cast. With a determination to 'make the best of it', strategies such as humour, normalisation, present-time orientation, and life review are employed to create a meaningful life.
Effects of Offshore Wind Farms on the Early Life Stages of Dicentrarchus labrax.
Debusschere, Elisabeth; De Coensel, Bert; Vandendriessche, Sofie; Botteldooren, Dick; Hostens, Kris; Vincx, Magda; Degraer, Steven
2016-01-01
Anthropogenically generated underwater noise in the marine environment is ubiquitous, comprising both intense impulse and continuous noise. The installation of offshore wind farms across the North Sea has triggered a range of ecological questions regarding the impact of anthropogenically produced underwater noise on marine wildlife. Our interest is on the impact on the "passive drifters," i.e., the early life stages of fish that form the basis of fish populations and are an important prey for pelagic predators. This study deals with the impact of pile driving and operational noise generated at offshore wind farms on Dicentrarchus labrax (sea bass) larvae.
[Circadian rhythm disruption and human development].
Kohyama, Jun
2013-12-01
Ontogenetic developments of rest-activity, sleep-wakefulness, temperature and several hormone rhythms in humans were reviewed. The reported effects of environment on these alterations were also summarized. Then, disorders or conditions which often encounter during early stage of life and reveal circadian rhythm disruptions were described. These disorders or conditions included severe brain damage, visual disturbance, developmental disorders(autistic spectrum disorder and attention deficit/hyperactivity disorder), Rett syndrome, Angelman syndrome, Smith-Magenis syndrome, epilepsy, Yonaki, and inadequate sleep hygiene. Finally, it was emphasized that we should pay special attention on the development of youngsters who showed sleep disturbance during early stage of life with special reference to the later occurrence of developmental disorders.
Domingues, Inês; Oliveira, Rhaul; Lourenço, Joana; Grisolia, Cesar Koppe; Mendo, Sónia; Soares, A M V M
2010-09-01
The present work aims to compare the sensitivity of embryos and adult zebrafish to chromium (VI) (as potassium dichromate) focusing on biomarkers (cholinesterase, glutathione S-transferase and lactate dehydrogenase) as endpoints. Zebrafish eggs showed less sensitivity to Cr (VI) (96 h-LC50=145.7 mg/L) than adults (96 h-LC50=39.4 mg/L) probably due to the protective action of the chorion. However, biomarkers were much more responsive in larvae than in adults and gave clear indications about Cr (VI) mode of action: it seems to be neurotoxic (inhibited cholinesterase), to inhibit glutathione S-transferase activity and to interfere with cellular metabolic activity (changes in lactate dehydrogenase activity) in larvae. In adults, only glutathione S-transferase was responsive, showing a clear inhibition. The responsiveness of the analyzed biomarkers in larvae reinforces the idea of the usefulness of early life stage assays in the assessment of chemicals effects. Moreover, early life stage assays also contributed with relevant information regarding anomalies in larvae development and behavior. Further research should focus on the use of biomarkers to assess long term effects which are ecologically more relevant. Copyright (c) 2010 Elsevier Inc. All rights reserved.
NASA Astrophysics Data System (ADS)
Peck, M. A.
2016-02-01
Gaining a cause-and-effect understanding of climate-driven changes in marine fish populations at appropriate spatial scales is important for providing robust advice for ecosystem-based fisheries management. Coupling long-term, retrospective analyses and 3-d biophysical, individual-based models (IBMs) shows great potential to reveal mechanism underlying historical changes and to project future changes in marine fishes. IBMs created for marine fish early life stages integrate organismal-level physiological responses and climate-driven changes in marine habitats (from ocean physics to lower trophic level productivity) to test and reveal processes affecting marine fish recruitment. Case studies are provided for hindcasts and future (A1 and B2 projection) simulations performed on some of the most ecologically- and commercially-important pelagic and demersal fishes in the North Sea including European anchovy, Atlantic herring, European sprat and Atlantic cod. We discuss the utility of coupling biophysical IBMs to size-spectrum models to better project indirect (trophodynamic) pathways of climate influence on the early life stages of these and other fishes. Opportunities and challenges are discussed regarding the ability of these physiological-based tools to capture climate-driven changes in living marine resources and food web dynamics of shelf seas.
Telomere correlations during early life in a long-lived seabird.
Schmidt, Jacob E; Sirman, Aubrey E; Kittilson, Jeffrey D; Clark, Mark E; Reed, Wendy L; Heidinger, Britt J
2016-12-01
Telomere dynamics in blood cells have been linked to aging in a variety of organisms. However, whether blood telomeres are correlated with telomeres in other parts of the body is not well known, especially during early life when telomere loss is expected to be most rapid. We investigated this question in Franklin's gulls (Leucophaeus pipixcan) by measuring telomere lengths in blood and several other tissues including: heart, liver, and skeletal muscle at the end of embryonic (n=31) and post-natal development (n=20). In late-stage embryos, blood telomeres were significantly positively correlated with heart and skeletal muscle, but not liver telomeres. However, at the end of post-natal development, there were no significant correlations among blood telomeres and telomeres in any other tissues. In late-stage embryos, heart telomeres were significantly longer than blood, liver, and skeletal muscle telomeres, but at the end of post-natal development telomere lengths did not significantly differ among tissues. These results suggest that blood telomere length is not necessarily indicative of other tissues at all stages of development and highlights the importance of understanding any functional consequences of tissue specific telomere dynamics in early life. Copyright © 2016 Elsevier Inc. All rights reserved.
Ramsdell, John S.; Zabka, Tanja S.
2008-01-01
California sea lions have been a repeated subject of investigation for early life toxicity, which has been documented to occur with increasing frequency from late February through mid-May in association with organochlorine (PCB and DDT) poisoning and infectious disease in the 1970’s and domoic acid poisoning in the last decade. The mass early life mortality events result from the concentrated breeding grounds and synchronization of reproduction over a 28 day post partum estrus cycle and 11 month in utero phase. This physiological synchronization is triggered by a decreasing photoperiod of 11.48 h/day that occurs approximately 90 days after conception at the major California breeding grounds. The photoperiod trigger activates implantation of embryos to proceed with development for the next 242 days until birth. Embryonic diapause is a selectable trait thought to optimize timing for food utilization and male migratory patterns; yet from the toxicological perspective presented here also serves to synchronize developmental toxicity of pulsed environmental events such as domoic acid poisoning. Research studies in laboratory animals have defined age-dependent neurotoxic effects during development and windows of susceptibility to domoic acid exposure. This review will evaluate experimental domoic acid neurotoxicity in developing rodents and, aided by comparative allometric projections, will analyze potential prenatal toxicity and exposure susceptibility in the California sea lion. This analysis should provide a useful tool to forecast fetal toxicity and understand the impact of fetal toxicity on adult disease of the California sea lion. PMID:18728728
Edwards, Joshua R.
2012-01-01
Cadmium is an important industrial agent and environmental pollutant that is a major cause of kidney disease. With chronic exposure, cadmium accumulates in the epithelial cells of the proximal tubule, resulting in a generalized reabsorptive dysfunction characterized by polyuria and low-molecular-weight proteinuria. The traditional view has been that as cadmium accumulates in proximal tubule cells, it produces a variety of relatively nonspecific toxic effects that result in the death of renal epithelial cells through necrotic or apoptotic mechanisms. However, a growing volume of evidence suggests that rather than merely being a consequence of cell death, the early stages of cadmium-induced proximal tubule injury may involve much more specific changes in cell-cell adhesion, cellular signaling pathways, and autophagic responses that occur well before the onset of necrosis or apoptosis. In this commentary, we summarize these recent findings, and we offer our own perspectives as to how they relate to the toxic actions of cadmium in the kidney. In addition, we highlight recent findings, suggesting that it may be possible to detect the early stages of cadmium toxicity through the use of improved biomarkers. Finally, some of the therapeutic implications of these findings will be considered. Because cadmium is, in many respects, a model cumulative nephrotoxicant, these insights may have broader implications regarding the general mechanisms through which a variety of drugs and toxic chemicals damage the kidney. PMID:22669569
Toxicity of sulfide to early life stages of wild rice (Zizania palustris).
Fort, Douglas J; Todhunter, Kevin; Fort, Troy D; Mathis, Michael B; Walker, Rachel; Hansel, Mike; Hall, Scott; Richards, Robin; Anderson, Kurt
2017-08-01
The sensitivity of wild rice (Zizania palustris) to sulfide is not well understood. Because sulfate in surface waters is reduced to sulfide by anaerobic bacteria in sediments and historical information indicated that 10 mg/L sulfate in Minnesota (USA) surface water reduced Z. palustris abundance, the Minnesota Pollution Control Agency established 10 mg/L sulfate as a water quality criterion in 1973. A 21-d daily-renewal hydroponic study was conducted to evaluate sulfide toxicity to wild rice and the potential mitigation of sulfide toxicity by iron (Fe). The hydroponic design used hypoxic test media for seed and root exposure and aerobic headspace for the vegetative portion of the plant. Test concentrations were 0.3, 1.6, 3.1, 7.8, and 12.5 mg/L sulfide in test media with 0.8, 2.8, and 10.8 mg/L total Fe used to evaluate the impact of iron on sulfide toxicity. Visual assessments (i.e., no plants harvested) of seed activation, mesocotyl emergence, seedling survival, and phytoxicity were conducted 10 d after dark-phase exposure. Each treatment was also evaluated for time to 30% emergence (ET30), total plant biomass, root and shoot lengths, and signs of phytotoxicity at study conclusion (21 d). The results indicate that exposure of developing wild rice to sulfide at ≥3.1 mg sulfide/L in the presence of 0.8 mg/L Fe reduced mesocotyl emergence. Sulfide toxicity was mitigated by the addition of Fe at 2.8 mg/L and 10.8 mg/L relative to the control value of 0.8 mg Fe/L, demonstrating the importance of iron in mitigating sulfide toxicity to wild rice. Ultimately, determination of site-specific sulfate criteria taking into account factors that alter toxicity, including sediment Fe and organic carbon, are necessary. Environ Toxicol Chem 2017;36:2217-2226. © 2017 SETAC. © 2017 SETAC.
Herborn, Katherine A.; Heidinger, Britt J.; Boner, Winnie; Noguera, Jose C.; Adam, Aileen; Daunt, Francis; Monaghan, Pat
2014-01-01
Exposure to stressors early in life is associated with faster ageing and reduced longevity. One important mechanism that could underlie these late life effects is increased telomere loss. Telomere length in early post-natal life is an important predictor of subsequent lifespan, but the factors underpinning its variability are poorly understood. Recent human studies have linked stress exposure to increased telomere loss. These studies have of necessity been non-experimental and are consequently subjected to several confounding factors; also, being based on leucocyte populations, where cell composition is variable and some telomere restoration can occur, the extent to which these effects extend beyond the immune system has been questioned. In this study, we experimentally manipulated stress exposure early in post-natal life in nestling European shags (Phalacrocorax aristotelis) in the wild and examined the effect on telomere length in erythrocytes. Our results show that greater stress exposure during early post-natal life increases telomere loss at this life-history stage, and that such an effect is not confined to immune cells. The delayed effects of increased telomere attrition in early life could therefore give rise to a ‘time bomb’ that reduces longevity in the absence of any obvious phenotypic consequences early in life. PMID:24648221
Treatment of ovarian cancer with surgery, short-course chemotherapy and whole abdominal radiation.
Buser, K; Bacchi, M; Goldhirsch, A; Greiner, R; Diener, P; Sessa, C; Jungi, W F; Forni, M; Leyvraz, S; Engeler, V
1996-01-01
The primary aim was to induce a high number of pCR in early (FIGO IC, IIB + C) - and advanced (FIGO III-IV) - stage ovarian cancer with a surgery plus 4 cycles of cisplatin and melphalan (PAMP) regimen. The second objective was to prevent relapse with WAR in patients in remission after chemotherapy. 218 eligible patients were treated after staging laparotomy with cisplatin 80 mg/sqm i.v. on day 1 and melphalan 12 mg/sqm i.v. on day 2 q 4 weeks. Response was verified by second-look laparotomy. WAR was carried out with the open field technique on a linear accelerator (daily dose: 1.3 Gy, total dose: 29.9 Gy) in patients with pathological or clinical CR or pathological PR with microscopical residual disease. 146/218 patients (67%, 95% CI: 61%-73%) responded to PAMP: 56 (26%) achieved pCR, 24 (11%), cCR, 56 (26%) pPR and 10 (5%) cPR (c = clinical, p = pathological). Multivariate analyses revealed that in advanced stages (92 cases in remission), the achievement of pCR was the most important factor for longer time to failure (TTF) and survival. Only 51/118 (43%) patients in remission received WAR. Early-stage patients <= 55 years were more likely to have WAR than patients older than 55 years (77% vs. 23%; p = 0.02). Advanced-stage patients with cCR were less likely to be irradiated than patients with pCR or pPR (10% vs. 51%; p = 0.003). Toxicity of PAMP was acceptable with 10% of WHO grade 4 hematologic toxicity. Acute hematological toxicity of WAR caused interruption (33%) or incompleteness (33%) of irradiation in the majority of patients. PAMP is an effective treatment for advanced ovarian cancer with a 67% response rate after 4 cycles. For the majority of patients in remission, WAR as a consolidation treatment was hardly feasible. For these patients new treatment modalities to consolidate remission are needed.
Carr, Robert S.; Nipper, Marion; Field, Michael; Biedenbach, James M.
2006-01-01
Toxicity tests are commonly conducted as a measure of the bioavailability of toxic chemicals to biota in an environment. Chemical analyses alone are insufficient to determine whether contaminants pose a threat to biota. Porewater toxicity tests are extremely sensitive to a broad range of contaminants in marine environments and provide ecologically relevant data on sensitive life stages. The inclusion of porewater toxicity testing as an additional indicator of sediment quality provides a more comprehensive picture of contaminant effects in these sensitive habitats. In this study purple-spined sea urchin (Arbacia punctulata) fertilization and embryological development porewater toxicity tests were used to evaluate the sediments collected from the coastal environment around Hanalei Bay, Kaua’i, Hawaii. These tests have been used previously to assess the bioavailability of contaminants associated with sediments in the vicinity of coral reefs.
Acute toxicity and synergism of cadmium and zinc in white shrimp, Penaeus setiferus, Juveniles
DOE Office of Scientific and Technical Information (OSTI.GOV)
Vanegas, C.; Espina, S.; Botello, A.V.
1997-01-01
Toxic effects of individual heavy metals on decapod crustaceans have been reported frequently, but little information exists concerning interactions. Among the non-essential heavy metals, cadmium is one of the most hazardous elements in the aquatic environment; on the other hand, zinc is an essential element, but toxic when present in greater than trace amounts. Biological effects of cadmium in aquatic organisms are complex due to the interactions with both environmental variables and other toxic agents. In decapod crustaceans, the toxicity of cadmium and zinc is modified by salinity, temperature, hypoxia, calcium ion concentrations and life-cycle stage. Heavy metal pollution hasmore » increased in the coastal waters of the Gulf of Mexico, particularly in shrimp habitat. This study examined the toxicity of cadmium and zinc to white shrimp juveniles and looked at the interaction of the metals. 16 refs., 2 tabs.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Maluta, Sergio; Dall'Oglio, Stefano, E-mail: stefano.dalloglio@ospedaleuniverona.it; Marciai, Nadia
2012-10-01
Background: We report the results of a single-institution, phase II trial of accelerated partial breast irradiation (APBI) using a single dose of intraoperative electron radiation therapy (IOERT) in patients with low-risk early stage breast cancer. Methods and Materials: A cohort of 226 patients with low-risk, early stage breast cancer were treated with local excision and axillary management (sentinel node biopsy with or without axillary node dissection). After the surgeon temporarily reapproximated the excision cavity, a dose of 21 Gy using IOERT was delivered to the tumor bed, with a margin of 2 cm laterally. Results: With a mean follow-up ofmore » 46 months (range, 28-63 months), only 1 case of local recurrence was reported. The observed toxicity was considered acceptable. Conclusions: APBI using a single dose of IOERT can be delivered safely in women with early, low-risk breast cancer in carefully selected patients. A longer follow-up is needed to ascertain its efficacy compared to that of the current standard treatment of whole-breast irradiation.« less
Beiras, R; Tato, T
2018-04-07
Pentachlorophenol (PCP) is a organochlorine biocide that, unlike most other organochlorines, is still in use as timber preservative. Its water solubility, high toxicity, bioaccumulation potential, and the concentrations reported in estuarine waters (up to 0.1 µg L -1 ) indicate it may pose a risk in coastal environments. Aquatic environrmental regulations are commonly based on standard freshwater organisms that may not represent the sensitivity of marine species. The present study consists of a water quality criteira reevalutation of PCP in coastal waters based on toxicity tests conducted recording sensitive endpoints of marine species representative of coastal ecosystems, following QA/QC standard procedures. The toxicity thresholds (EC 10 ) found were 4.69 µg L -1 for Paracentrotus lividus sea-urchin embryos, 6.47 µg L -1 for Mytilus galloprovincialis mussel larvae, and 78.4 µg L -1 for Isochrysis galbana cells. Therefore, there is only one order of magnitude between the predicted no-effect concentration (PNEC) for early life stages of bivalves and echinoderms and the maximum concentrations actually recorded in coastal water, which yields a remarkable risk quotient for PCP in these highly productive marine habitats. In addition, we have reviewed the ecotoxicological data on PCP toxicity on marine species representative of the main systematic groups, from algae to chordates, and derived a probabilistic acute saltwater quality criterion of 2.66 µg L -1 , intended to protect 95% of the marine species. Lack of adequate protection for marine ecosystems in some current PCP national guidelines has been identified.
Stieglitz, John D; Mager, Edward M; Hoenig, Ronald H; Alloy, Matthew; Esbaugh, Andrew J; Bodinier, Charlotte; Benetti, Daniel D; Roberts, Aaron P; Grosell, Martin
2016-11-01
Key differences in the developmental process of pelagic fish embryos, in comparison to embryos of standard test fish species, present challenges to obtaining sufficient control survival needed to successfully perform traditional toxicity testing bioassays. Many of these challenges relate to the change in buoyancy, from positive to negative, of pelagic fish embryos that occurs just prior to hatch. A novel exposure system, the pelagic embryo-larval exposure chamber (PELEC), has been developed to conduct successful bioassays on the early life stages (ELSs; embryos/larvae) of pelagic fish. Using this unique recirculating upwelling system, it was possible to significantly improve control survival in pelagic fish ELS bioassays compared to commonly used static exposure methods. Results demonstrate that control performance of mahi-mahi (Coryphaena hippurus) embryos in the PELEC system, measured as percent survival after 96-hrs, significantly outperformed agitated static exposure and static exposure systems. Similar significant improvements in 72-hr control survival were obtained with yellowfin tuna (Thunnus albacares). The PELEC system was subsequently used to test the effects of photo-induced toxicity of crude oil to mahi-mahi ELSs over the course of 96-hrs. Results indicate a greater than 9-fold increase in toxicity of Deepwater Horizon (DWH) crude oil during co-exposure to ambient sunlight compared to filtered ambient sunlight, revealing the importance of including natural sunlight in 96-hr DWH crude oil bioassays as well as the PELEC system's potential application in ecotoxicological assessments. Copyright © 2016 Elsevier Ltd. All rights reserved.
Ryu, Tae Kwon; Lee, Gunsup; Rhee, Yong; Park, Heung-Sik; Chang, Man; Lee, Sukchan; Lee, Jaean; Lee, Taek-Kyun
2012-10-01
Bioassays and biomarkers have been previously developed to assess the effects of heavy metal contaminants on the early life stages of the sea urchin. In this study, malformation in the early developmental processes was observed in sea urchin (Strongylocentrotus intermedius) larvae exposed to 10 ppm Ni for over 30 h. The most critical stage at which the triggering of nickel effects takes place is thought to be the blastula stage, which occurs after fertilization in larval development. To investigate the molecular-level responses of sea urchin exposed to heavy metal stress and to explore the differentially expressed genes that are induced or repressed by nickel, differential display polymerase chain reaction (DD-PCR) was used with sea urchin mRNAs. The malformation-related genes expressed in the early life stages of the sea urchin were cloned from larvae exposed to 10 ppm of nickel for 15 h, and accessed via DD-PCR. Sequence analysis results revealed that each of the genes evidenced high homology with EGF2, PCSK9, serine/threonine protein kinase, apolipophorin precursor protein, and MGC80921 protein/transcript variant 2. This result may prove useful in the development of novel biomarkers for the assessment of heavy metal stresses on sea urchin embryos. Copyright © 2012 Elsevier Inc. All rights reserved.
Cumulative early life adversity predicts longevity in wild baboons
Tung, Jenny; Archie, Elizabeth A.; Altmann, Jeanne; Alberts, Susan C.
2016-01-01
In humans and other animals, harsh circumstances in early life predict morbidity and mortality in adulthood. Multiple adverse conditions are thought to be especially toxic, but this hypothesis has rarely been tested in a prospective, longitudinal framework, especially in long-lived mammals. Here we use prospective data on 196 wild female baboons to show that cumulative early adversity predicts natural adult lifespan. Females who experience ≥3 sources of early adversity die a median of 10 years earlier than females who experience ≤1 adverse circumstances (median lifespan is 18.5 years). Females who experience the most adversity are also socially isolated in adulthood, suggesting that social processes partially explain the link between early adversity and adult survival. Our results provide powerful evidence for the developmental origins of health and disease and indicate that close ties between early adversity and survival arise even in the absence of health habit and health care-related explanations. PMID:27091302
Eichelberger, Jennifer S.; Braaten, P. J.; Fuller, D. B.; Krampe, Matthew S.; Heist, Edward J.
2014-01-01
Spawning of the federally endangered Pallid Sturgeon Scaphirhynchus albus is known to occur in the upper Missouri River basin, but progeny from natural reproductive events have not been observed and recruitment to juvenile or adult life stages has not been documented in recent decades. Identification of Pallid Sturgeon progeny is confounded by the fact that Shovelnose Sturgeon S. platorynchus occurs throughout the entire range of Pallid Sturgeon and the two species are essentially indistinguishable (morphometrically and meristically) during early life stages. Moreover, free embryos of sympatric Paddlefish Polyodon spathula are very similar to the two sturgeon species. In this study, three single-nucleotide polymorphism (SNP) assays were employed to screen acipenseriform free embryos and larvae collected from the upper Missouri River basin in 2011, 2012, and 2013. A mitochondrial DNA SNP discriminates Paddlefish from sturgeon, and specific multilocus genotypes at two nuclear DNA SNPs occurred in 98.9% of wild adult Pallid Sturgeon but only in 3% of Shovelnose Sturgeon sampled in the upper Missouri River. Individuals identified as potential Pallid Sturgeon based on SNP genotypes were further analyzed at 19 microsatellite loci for species discrimination. Out of 1,423 free embryos collected over 3 years of sampling, 971 Paddlefish, 446 Shovelnose Sturgeon, and 6 Pallid Sturgeon were identified. Additionally, 249 Scaphirhynchus spp. benthic larvae were screened, but no Pallid Sturgeon were detected. These SNP markers provide an efficient method of screening acipenseriform early life stages for the presence of Pallid Sturgeon in the Missouri River basin. Detection of wild Pallid Sturgeon free embryos in the upper Missouri and Yellowstone rivers supports the hypothesis that the failure of wild Pallid Sturgeon to recruit to the juvenile life stage in the upper Missouri River basin is caused by early life stage mortality rather than by lack of successful spawning.
Ammonia and urea handling by early life stages of fishes.
Zimmer, Alex M; Wright, Patricia A; Wood, Chris M
2017-11-01
Nitrogen metabolism in fishes has been a focus of comparative physiologists for nearly a century. In this Review, we focus specifically on early life stages of fishes, which have received considerable attention in more recent work. Nitrogen metabolism and excretion in early life differs fundamentally from that of juvenile and adult fishes because of (1) the presence of a chorion capsule in embryos that imposes a limitation on effective ammonia excretion, (2) an amino acid-based metabolism that generates a substantial ammonia load, and (3) the lack of a functional gill, which is the primary site of nitrogen excretion in juvenile and adult fishes. Recent findings have shed considerable light on the mechanisms by which these constraints are overcome in early life. Perhaps most importantly, the discovery of Rhesus (Rh) glycoproteins as ammonia transporters and their expression in ion-transporting cells on the skin of larval fishes has transformed our understanding of ammonia excretion by fishes in general. The emergence of larval zebrafish as a model species, together with genetic knockdown techniques, has similarly advanced our understanding of ammonia and urea metabolism and excretion by larval fishes. It has also now been demonstrated that ammonia excretion is one of the primary functions of the developing gill in rainbow trout larvae, leading to new hypotheses regarding the physiological demands driving gill development in larval fishes. Here, we highlight and discuss the dramatic changes in nitrogen handling that occur over early life development in fishes. © 2017. Published by The Company of Biologists Ltd.
1987-08-01
total recoverable trivalent - ambient water, the estimated level is 2 more sensitive than those tested. No chromium the avallabe data indicate - mg/L...freshwater aquatic chronic toxicity of trivalent chromium to life occurs at concentrations as low as sensitive saltwater aquatic life...epoxide Lindane Nethoxyohlor Diazinon Malathion Parathion Toxaphene 2.4- 2,A.5-T 2,JI,5-TP (silvex) barsenic barium cadmiumn chromium (total). copper Iron
Cruz, Gonzalo; Foster, Warren; Paredes, Alfonso; Yi, Kun Don; Uzumcu, Mehmet
2014-01-01
Estrogens play an important role in development and function of the brain and reproductive tract. Accordingly, it is thought that developmental exposure to environmental estrogens can disrupt neural and reproductive tract development potentially resulting in long-term alterations in neurobehavior and reproductive function. Many chemicals have been shown to have estrogenic activity whereas others affect estrogen production and turnover resulting in disruption of estrogen signaling pathways. However, these mechanisms and the concentrations required to induce these effects cannot account for the myriad adverse effects of environmental toxicants on estrogen sensitive target tissues. Hence, alternative mechanisms are thought to underlie the adverse effects documented in experimental animal models and thus could be important to human health. In this review, the epigenetic regulation of gene expression is explored as a potential target of environmental toxicants including estrogenic chemicals. We suggest that toxicant-induced changes in epigenetic signatures are important mechanisms underlying disruption of ovarian follicular development. In addition, we discuss how exposure to environmental estrogens during early life can alter gene expression through effects on epigenetic control potentially leading to permanent changes in ovarian physiology. PMID:25040227
Cruz, G; Foster, W; Paredes, A; Yi, K D; Uzumcu, M
2014-09-01
Oestrogens play an important role in development and function of the brain and reproductive tract. Accordingly, it is considered that developmental exposure to environmental oestrogens can disrupt neural and reproductive tract development, potentially resulting in long-term alterations in neurobehaviour and reproductive function. Many chemicals have been shown to have oestrogenic activity, whereas others affect oestrogen production and turnover, resulting in the disruption of oestrogen signalling pathways. However, these mechanisms and the concentrations required to induce these effects cannot account for the myriad adverse effects of environmental toxicants on oestrogen-sensitive target tissues. Hence, alternative mechanisms are assumed to underlie the adverse effects documented in experimental animal models and thus could be important to human health. In this review, the epigenetic regulation of gene expression is explored as a potential target of environmental toxicants including oestrogenic chemicals. We suggest that toxicant-induced changes in epigenetic signatures are important mechanisms underlying the disruption of ovarian follicular development. In addition, we discuss how exposure to environmental oestrogens during early life can alter gene expression through effects on epigenetic control potentially leading to permanent changes in ovarian physiology. © 2014 British Society for Neuroendocrinology.
Meeuwig, M.H.; Bayer, J.M.; Seelye, J.G.
2005-01-01
We examined the effects of temperature (10, 14, 18, and 22??C) on survival and development of Pacific lampreys Lampetra tridentata and western brook lampreys L. richardsoni during embryological and early larval stages. The temperature for zero development was estimated for each species, and the response to temperature was measured as the proportion of individuals surviving to hatch, surviving to the larval stage, and exhibiting abnormalities at the larval stage (i.e., malformations of the body). The estimated temperature for zero development was 4.850C for Pacific lampreys and 4.97??C for western brook lampreys. Survival was greatest at 18??C, followed by 14, 10, and 22??C, significant differences being observed between 22??C and the other temperatures. Overall survival was significantly greater for western brook lampreys than for Pacific lampreys; however, the overall difference in proportion of individuals surviving was only 0.02. Overall survival significantly decreased from the time of hatch (proportion surviving = 0.85) to the larval stage (0.82; i.e., during the free-embryo stage). The proportion of individuals exhibiting abnormalities at the larval stage was greatest at 22??C, followed by 18, 10, and 14??C, significant differences being observed between 22??C and the other temperatures. These data provide baseline information on the thermal requirements of early life stage Pacific and western brook lampreys and will aid in assessment and prediction of suitable spawning and rearing habitats for these species.
Stressful Life Events and Predictors of Post-traumatic Growth among High-Risk Early Emerging Adults.
Arpawong, Thalida E; Rohrbach, Louise A; Milam, Joel E; Unger, Jennifer B; Land, Helen; Sun, Ping; Spruijt-Metz, Donna; Sussman, Steve
2016-01-01
Stressful life events (SLEs) may elicit positive psychosocial change among youth, referred to as Post-traumatic Growth (PTG). We assessed types of SLEs experienced, degree to which participants reported PTG, and variables predicting PTG across 24 months among a sample of high risk, ethnically diverse early emerging adults. Participants were recruited from alternative high schools ( n = 564; mean age=16.8; 65% Hispanic). Multi-level regression models were constructed to examine the impact of environmental (SLE quantity, severity) and personal factors (hedonic ability, perceived stress, developmental stage, future time orientation) on a composite score of PTG. The majority of participants reported positive changes resulted from their most life-altering SLE of the past two years. Predictors of PTG included fewer SLEs, less general stress, having a future time perspective, and greater identification with the developmental stage of Emerging Adulthood. Findings suggest intervention targets to foster positive adaptation among early emerging adults who experience frequent SLEs.
Gagliano, Monica; McCormick, Mark I; Meekan, Mark G
2007-07-07
For organisms with complex life cycles, variation among individuals in traits associated with survival in one life-history stage can strongly affect the performance in subsequent stages with important repercussions on population dynamics. To identify which individual attributes are the most influential in determining patterns of survival in a cohort of reef fish, we compared the characteristics of Pomacentrus amboinensis surviving early juvenile stages on the reef with those of the cohort from which they originated. Individuals were collected at hatching, the end of the planktonic phase, and two, three, four, six and eight weeks post-settlement. Information stored in the otoliths of individual fish revealed strong carry-over effects of larval condition at hatching on juvenile survival, weeks after settlement (i.e. smaller-is-better). Among the traits examined, planktonic growth history was, by far, the most influential and long-lasting trait associated with juvenile persistence in reef habitats. However, otolith increments suggested that larval growth rate may not be maintained during early juvenile life, when selective mortality swiftly reverses its direction. These changes in selective pressure may mediate growth-mortality trade-offs between predation and starvation risks during early juvenile life. Ontogenetic changes in the shape of selectivity may be a mechanism maintaining phenotypic variation in growth rate and size within a population.
Cotton, Mark F; Violari, Avy; Otwombe, Kennedy; Panchia, Ravindre; Dobbels, Els; Rabie, Helena; Josipovic, Deirdre; Liberty, Afaff; Lazarus, Erica; Innes, Steve; van Rensburg, Anita Janse; Pelser, Wilma; Truter, Handre; Madhi, Shabir A; Handelsman, Edward; Jean-Philippe, Patrick; McIntyre, James A; Gibb, Diana M; Babiker, Abdel G
2014-01-01
Background Interim results from the CHER trial showed that early antiretroviral therapy (ART) was life-saving for HIV-infected infants. Given limited options and potential for toxicity with life-long ART, CHER compared early limited ART with deferred ART. Methods CHER was an open 3-arm trial in HIV-infected asymptomatic infants aged <12 weeks with CD4% ≥25%. Infants were randomized to deferred (ART-Def) or immediate ART for 40weeks (ART-40W) or 96weeks (ART-96W), followed by interruption. Criteria for ART initiation in ART-Def and re-initiation after interruption were CD4% <25% in infancy; otherwise <20% or CDC severe stage B or stage C disease. Lopinavir-ritonavir, zidovudine, lamivudine was the first-line regimen at ART initiation and re-initiation. The primary endpoint was time-to-failure of first-line ART (immunological/clinical/virological) or death. Comparisons were by intent-to-treat, using time-to-event methods. Findings 377 infants were enrolled: median age 7.4weeks; CD4% 35% and HIV RNA log 5.7copies/ml. Median follow-up was 4.8 years; 34 (9%) were lost-to-follow-up. Median time to ART initiation in ART-Def was 20 (IQR 16–25) weeks. Time to restarting ART after interruption was 33 (26–45) weeks in ART-40W and 70 (35–109) weeks in ART-96W; at trial end 19% and 32% respectively, remained off ART. Proportions of follow-up time spent on ART were 81%, 70% and 69% in ART-Def, ART-40W and ART-96W arms. 48/125(38%), 32/126(25%) and 26/126(21%) children reached the primary endpoint; hazard ratio (95%CI), relative to ART-Def, was 0.59(0.38-0.93, p=0.02) for ART-40W and 0.47(0.27-0.76, p=0.002) for ART-96W. Seven children (3 ART-Def, 3 ART-40W, 1 ART-96W) switched to second-line ART. Interpretation Early limited ART had superior clinical/immunological outcome with no evidence of excess disease progression during subsequent interruption and less overall ART exposure than deferred ART. Longer time on primary ART permits longer subsequent interruption with marginally better outcomes. PMID:24209829
High-Resolution Lipidomics of the Early Life Stages of the Red Seaweed Porphyra dioica.
da Costa, Elisabete; Azevedo, Vitor; Melo, Tânia; Rego, Andreia M; V Evtuguin, Dmitry; Domingues, Pedro; Calado, Ricardo; Pereira, Rui; Abreu, Maria H; Domingues, Maria R
2018-01-17
Porphyra dioica is a commercial seaweed consumed all over the world, mostly in the shape of nori sheets used for "sushi" preparation. It is a well-known part of the Asian diet with health benefits, which have been associated, among others, to the high levels of n -3 and n- 6 fatty acids in this red alga. However, other highly valued lipids of Porphyra are polar lipids that remain largely undescribed and can have both nutritional value and bioactivity, thus could contribute to the valorization of this seaweed. In this context, the present work aims to identify the lipidome of two life cycle stages of the Atlantic species Porphyra dioica : the early life stage conchocelis produced in an indoor-nursery, and young blades produced outdoors using an integrated multitrophic aquaculture (IMTA) framework. Both the blades (gametophyte) and conchocelis (sporophyte) are commercialized in the food and cosmetics sectors. Liquid chromatography coupled to Q-Exactive high resolution-mass spectrometry (MS) platform was used to gain insight into the lipidome of these species. Our results allowed the identification of 110 and 100 lipid molecular species in the lipidome of the blade and conchocelis, respectively. These lipid molecular species were distributed as follows (blade/conchocelis): 14/15 glycolipids (GLs), 93/79 phospholipids (PLs), and 3/6 betaine lipids. Both life stages displayed a similar profile of GLs and comprised 20:4( n -6) and 20:5( n -3) fatty acids that contribute to n -3 and n -6 fatty acid pool recorded and rank among the molecular species with higher potential bioactivity. PLs' profile was different between the two life stages surveyed, mainly due to the number and relative abundance of molecular species. This finding suggests that differences between both life stages were more likely related with shifts in the lipids of extraplastidial membranes rather than in plastidial membranes. PLs contained n -6 and n -3 precursors and in both life stages of Porphyra dioica the n -6/ n -3 ratio recorded was less than 2, highlighting the potential benefits of using these life stages in human diet to prevent chronic diseases. Atherogenic and thrombogenic indexes of blades (0.85 and 0.49, respectively) and conchocelis (0.34 and 0.30, respectively) are much lower than those reported for other Rhodophyta, which highlights their potential application as food or as functional ingredients. Overall, MS-based platforms represent a powerful tool to characterize lipid metabolism and target lipids along different life stages of algal species displaying complex life cycles (such as Porphyra dioica ), contributing to their biotechnological application.
Discussing the challenges associated with estimating and interpreting toxicant exposures and health risks from biomonitoring data. This extended abstract was translated in Spanish and published in Acta Toxicologica Argentina.
Federal Register 2010, 2011, 2012, 2013, 2014
2013-04-01
... means adverse outcomes to the nervous system resulting from exposure during any life stage. Special... critical to the development and/or function of the nervous system. The NTP is also interested in receiving... to act as toxicants to the developing or adult nervous systems. Request for Information 1...
Life stage is an important risk factor for toxicity. Children and aging adults, for example, are more susceptible to certain chemicals than are young adults. In comparison to children, relatively little is known about susceptibility in older adults. Additionally, few studies have...
A manuscript summarizes a workshop aimed at developing a framework to determine the relevancy of animal modes-of-action for extrapolation to humans. A complete mode of action human relevance analysis - as distinct from mode of action (MOA) analysis alone - depends on robust info...
Metabolic homeostasis of the organism is maintained by the liver's ability to detoxify and eliminate xenobiotics. This is accomplished, in part, by the expression of XMEs, which metabolize xenobiotics and determine whether exposure will result in toxicity. Some evidence indicates...
The Larval Amphibian Growth and Development Assay (LAGDA) is an internationally harmonized testing guideline for evaluating effects of chronic chemical exposure in amphibians. To evaluate the utility of the assay design during the development phase antiandrogen prochloraz was te...
Kłym, Maria; Cieciuch, Jan
2015-01-01
The existing models and measurement instruments concerning identity appear to primarily focus on adolescence and early adulthood, and studies extending identity research to younger stages of life are scarce. There has been a particular lack of instruments measuring the early stages of identity formation, especially the process of exploration, which has been portrayed as a central process during this particular period of life. Our aim is to help fill the gap in the literature and facilitate further studies of the exploration process by providing an appropriate instrument to measure exploration in breadth during early adolescence. As a coherent and mature sense of identity is closely associated with psychosocial well-being, an effective identity exploration scale will enable researchers to assess the predictors of young adolescents' well-being. We propose a model of identity exploration domains based on the literature and considering 12 exploration domains: physical appearance, free time, family, work, boyfriend-girlfriend relationships, own opinion formation, perception of own place in the life cycle, self-reflection, future, future family, outlook on life, and attitude toward rules. The study was conducted on a group of N = 454 adolescents (50% males, M age = 13.04, SD = 0.98). Both reliability and structural validity, as verified by confirmatory factor analysis were satisfactory. The instrument is invariant across gender groups at the scalar level of measurement invariance.
Kłym, Maria; Cieciuch, Jan
2015-01-01
The existing models and measurement instruments concerning identity appear to primarily focus on adolescence and early adulthood, and studies extending identity research to younger stages of life are scarce. There has been a particular lack of instruments measuring the early stages of identity formation, especially the process of exploration, which has been portrayed as a central process during this particular period of life. Our aim is to help fill the gap in the literature and facilitate further studies of the exploration process by providing an appropriate instrument to measure exploration in breadth during early adolescence. As a coherent and mature sense of identity is closely associated with psychosocial well-being, an effective identity exploration scale will enable researchers to assess the predictors of young adolescents' well-being. We propose a model of identity exploration domains based on the literature and considering 12 exploration domains: physical appearance, free time, family, work, boyfriend-girlfriend relationships, own opinion formation, perception of own place in the life cycle, self-reflection, future, future family, outlook on life, and attitude toward rules. The study was conducted on a group of N = 454 adolescents (50% males, Mage = 13.04, SD = 0.98). Both reliability and structural validity, as verified by confirmatory factor analysis were satisfactory. The instrument is invariant across gender groups at the scalar level of measurement invariance. PMID:25983707
van Helvoort, Hanneke Ac; Willems, Laura M; Dekhuijzen, Pn Richard; van Hees, Hieronymus Wh; Heijdra, Yvonne F
2016-10-13
In patients with chronic obstructive pulmonary disease (COPD), exercise capacity is reduced, resulting over time in physical inactivity and worsened health status. It is unknown whether ventilatory constraints occur during activities of daily life (ADL) in early stages of COPD. The aim of this study was to assess respiratory mechanics during ADL and to study its consequences on dyspnoea, physical activity and health status in early-stage COPD compared with healthy controls. In this cross-sectional study, 39 early-stage COPD patients (mean FEV 1 88±s.d. 12% predicted) and 20 controls performed 3 ADL: climbing stairs, vacuum cleaning and displacing groceries in a cupboard. Respiratory mechanics were measured during ADL. Physical activity was measured with accelerometry. Health status was assessed by the Nijmegen Clinical Screening Instrument. Compared with controls, COPD patients had greater ventilatory inefficiency and higher ventilatory requirements during ADL (P<0.05). Dyspnoea scores were increased in COPD compared with controls (P<0.001). During ADL, >50% of the patients developed dynamic hyperinflation in contrast to 10-35% of the controls. Higher dyspnoea was scored by patients with dynamic hyperinflation. Physical activity was low but comparable between both groups. From the patients, 55-84% experienced mild-to-severe problems in health status compared with 5-25% of the controls. Significant ventilatory constraints already occur in early-stage COPD patients during common ADL and result in increased dyspnoea. Physical activity level is not yet reduced, but many patients already experience limitations in health status. These findings reinforce the importance of early diagnosis of COPD and assessment of more than just spirometry.
Development of the vertebrate nervous system proceeds through a number of critical processes, ultimately concluding with the extension of neurites and establishment of synaptic networks. Early-life exposure to toxicants that perturb these critical developmental processes can po...
Mortality Dynamics of Spodoptera frugiperda (Lepidoptera: Noctuidae) Immatures in Maize.
Varella, Andrea Corrêa; Menezes-Netto, Alexandre Carlos; Alonso, Juliana Duarte de Souza; Caixeta, Daniel Ferreira; Peterson, Robert K D; Fernandes, Odair Aparecido
2015-01-01
We characterized the dynamics of mortality factors affecting immature developmental stages of the fall armyworm, Spodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae). Multiple decrement life tables for egg and early larval stages of S. frugiperda in maize (Zea mays L.) fields were developed with and without augmentative releases of Telenomus remus Nixon (Hymenoptera: Platygastridae) from 2009 to 2011. Total egg mortality ranged from 73 to 81% and the greatest egg mortality was due to inviability, dislodgement, and predation. Parasitoids did not cause significant mortality in egg or early larval stages and the releases of T. remus did not increase egg mortality. Greater than 95% of early larvae died from predation, drowning, and dislodgment by rainfall. Total mortality due to these factors was largely irreplaceable. Results indicate that a greater effect in reducing generational survival may be achieved by adding mortality to the early larval stage of S. frugiperda.
Mortality Dynamics of Spodoptera frugiperda (Lepidoptera: Noctuidae) Immatures in Maize
Varella, Andrea Corrêa; Menezes-Netto, Alexandre Carlos; Alonso, Juliana Duarte de Souza; Caixeta, Daniel Ferreira; Peterson, Robert K. D.; Fernandes, Odair Aparecido
2015-01-01
We characterized the dynamics of mortality factors affecting immature developmental stages of the fall armyworm, Spodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae). Multiple decrement life tables for egg and early larval stages of S. frugiperda in maize (Zea mays L.) fields were developed with and without augmentative releases of Telenomus remus Nixon (Hymenoptera: Platygastridae) from 2009 to 2011. Total egg mortality ranged from 73 to 81% and the greatest egg mortality was due to inviability, dislodgement, and predation. Parasitoids did not cause significant mortality in egg or early larval stages and the releases of T. remus did not increase egg mortality. Greater than 95% of early larvae died from predation, drowning, and dislodgment by rainfall. Total mortality due to these factors was largely irreplaceable. Results indicate that a greater effect in reducing generational survival may be achieved by adding mortality to the early larval stage of S. frugiperda. PMID:26098422
Research on conceptual/innovative design for the life cycle
NASA Technical Reports Server (NTRS)
Cagan, Jonathan; Agogino, Alice M.
1990-01-01
The goal of this research is developing and integrating qualitative and quantitative methods for life cycle design. The definition of the problem includes formal computer-based methods limited to final detailing stages of design; CAD data bases do not capture design intent or design history; and life cycle issues were ignored during early stages of design. Viewgraphs outline research in conceptual design; the SYMON (SYmbolic MONotonicity analyzer) algorithm; multistart vector quantization optimization algorithm; intelligent manufacturing: IDES - Influence Diagram Architecture; and 1st PRINCE (FIRST PRINciple Computational Evaluator).
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kemmerer, Eric; Hernandez, Enrique; Ferriss, James S.
2013-01-01
Purpose: Retrospective analysis of patients with invasive endometrial neoplasia who were treated with external beam radiation therapy followed by stereotactic body radiation therapy (SBRT) boost because of the inability to undergo surgery or brachytherapy. Methods and Materials: We identified 11 women with stage I-III endometrial cancer with a median age of 78 years that were not candidates for hysterectomy or intracavitary brachytherapy secondary to comorbidities (91%) or refusal (9%). Eight patients were American Joint Committee on Cancer (AJCC) stage I (3 stage IA, 5 stage IB), and 3 patients were AJCC stage III. Patients were treated to a median ofmore » 4500 cGy at 180 cGy per fraction followed by SBRT boost (600 cGy per fraction Multiplication-Sign 5). Results: The most common side effect was acute grade 1 gastrointestinal toxicity in 73% of patients, with no late toxicities observed. With a median follow-up of 10 months since SBRT, 5 patients (45%) experienced locoregional disease progression, with 3 patients (27%) succumbing to their malignancy. At 12 and 18 months from SBRT, the overall freedom from progression was 68% and 41%, respectively. Overall freedom from progression (FFP) was 100% for all patients with AJCC stage IA endometrial carcinoma, whereas it was 33% for stage IB at 18 months. The overall FFP was 100% for International Federation of Obstetrics and Gynecology grade 1 disease. The estimated overall survival was 57% at 18 months from diagnosis. Conclusion: In this study, SBRT boost to the intact uterus was feasible, with encouragingly low rates of acute and late toxicity, and favorable disease control in patients with early-stage disease. Additional studies are needed to provide better insight into the best management of these clinically challenging cases.« less
Low-Dose Consolidation Radiation Therapy for Early Stage Unfavorable Hodgkin Lymphoma
DOE Office of Scientific and Technical Information (OSTI.GOV)
Torok, Jordan A., E-mail: jordan.torok@dm.duke.edu; Wu, Yuan; Prosnitz, Leonard R.
Purpose: The German Hodgkin Study Group (GHSG) trial HD11 established 4 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and 30 Gy of radiation therapy (RT) as a standard for early stage (I, II), unfavorable Hodgkin lymphoma (HL). Additional cycles of ABVD may allow for a reduction in RT dose and improved toxicity profile. Methods and Materials: Patients treated with combined modality therapy at the Duke Cancer Institute for early stage, unfavorable HL by GHSG criteria from 1994 to 2012 were included. Patients who did not undergo post-chemotherapy functional imaging (positron emission tomography or gallium imaging) or who failed to achievemore » a complete response were excluded. Clinical outcomes were estimated using the Kaplan-Meier method. Late effects were also evaluated. Results: A total of 90 patients met inclusion criteria for analysis. Median follow-up was 5 years. Chemotherapy consisted primarily of ABVD (88%) with a median number of 6 cycles. The median dose of consolidation RT was 23.4 Gy. Four patients had relapses, 2 of which were in-field. Ten-year progression-free survival (PFS) and overall survival (OS) were 93% (95% confidence interval [CI]: 0.82-0.97) and 98% (95% CI: 0.92-0.99), respectively. For the subset of patients (n=46) who received 5 to 6 cycles of chemotherapy and ≤24 Gy, the 10-year PFS and OS values were 88% (95% CI: 70%-96%) and 98% (95% CI: 85% - 99%), respectively. The most common late effect was hypothyroidism (20%) with no cardiac complications. Seven secondary malignancies were diagnosed, with only 1 arising within the RT field. Conclusions: Lower doses of RT may be sufficient when combined with more than 4 cycles of ABVD for early stage, unfavorable HL and may result in a more favorable toxicity profile than 4 cycles of ABVD and 30 Gy of RT.« less
Environmental estrogens alter early development in Xenopus laevis.
Bevan, Cassandra L; Porter, Donna M; Prasad, Anita; Howard, Marthe J; Henderson, Leslie P
2003-04-01
A growing number of environmental toxicants found in pesticides, herbicides, and industrial solvents are believed to have deleterious effects on development by disrupting hormone-sensitive processes. We exposed Xenopus laevis embryos at early gastrula to the commonly encountered environmental estrogens nonylphenol, octylphenol, and methoxychlor, the antiandrogen, p,p-DDE, or the synthetic androgen, 17 alpha-methyltestosterone at concentrations ranging from 10 nM to 10 microM and examined them at tailbud stages (approximately 48 hr of treatment). Exposure to the three environmental estrogens, as well as to the natural estrogen 17 beta-estradiol, increased mortality, induced morphologic deformations, increased apoptosis, and altered the deposition and differentiation of neural crest-derived melanocytes in tailbud stage embryos. Although neural crest-derived melanocytes were markedly altered in embryos treated with estrogenic toxicants, expression of the early neural crest maker Xslug, a factor that regulates both the induction and subsequent migration of neural crest cells, was not affected, suggesting that the disruption induced by these compounds with respect to melanocyte development may occur at later stages of their differentiation. Co-incubation of embryos with the pure antiestrogen ICI 182,780 blocked the ability of nonylphenol to induce abnormalities in body shape and in melanocyte differentiation but did not block the effects of methoxychlor. Our data indicate not only that acute exposure to these environmental estrogens induces deleterious effects on early vertebrate development but also that different environmental estrogens may alter the fate of a specific cell type via different mechanisms. Finally, our data suggest that the differentiation of neural crest-derived melanocytes may be particularly sensitive to the disruptive actions of these ubiquitous chemical contaminants.
Sheele, J M; Barrett, E; Dash, D; Ridge, G E
2017-11-01
Little is known about the epidemiology of bed bugs within the healthcare system, but nymphal stages predominate in natural infestations. This study determined the life stages of bed bugs captured within a medical centre, and found that older bed bugs were more likely to be captured than younger insects. The numbers of first instars, third-fifth instars and adult females captured were significantly different compared with the numbers of each life stage found in a natural infestation (P<0.01). A significant number of early-instar bed bugs introduced into the medical centre may go unnoticed by hospital staff. Copyright © 2017 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.
Avila-Poveda, Omar Hernando; Abadia-Chanona, Quetzalli Yasú
2013-01-01
This study describes and recognises, using histological and microscopical examinations on a morphometrical basis, several gonad traits through the early life stages of Chiton articulatus and C. albolineatus. Gonadal ontogenesis, gonad development stages, sexual differentiation, onset of the first sexual maturity, and growth sequences or “early life stages” were determined. In addition, allometry between lengths and body weight pooled for both sexes per each chiton were calculated using equation Y = aXb. A total of 125 chitons (4≤TL≤40 mm, in total length “TL”) were used. All allometric relations showed a strong positive correlation (r), close to 1, with b-values above three, indicating an isometric growth. Gonadal ontogenesis and gonad development stages were categorised into three periods (“Pw” without gonad, “Pe” gonad emergence, and “Pf” gonadal sac formed) and four stages (“S0” gametocytogenesis, “S1” gametogenesis, “S2” mature, and “S3” spawning), respectively. Compound digital images were attained for each process. Periods and stages are overlapped among them and between species, with the following overall confidence intervals in TL: Pw 6.13–14.32 mm, Pe 10.32–16.93 mm, Pf 12.99–25.01 mm, S0 16.08–24.34 mm (females) and 19.51–26.60 mm (males), S1 27.15–35.63 mm (females) and 23.45–32.27 mm (males), S2 24.48–40.24 mm (females) and 25.45–32.87 mm (males). Sexual differentiation (in S0) of both chitons occurs first as a female then as a male; although, males reach the onset of the first sexual maturity earlier than females, thus for C. articulatus males at 17 mm and females at 32 mm, and for C. albolineatus males at 23.5 mm and females at 28 mm, all in TL. Four early life stages (i.e., subjuvenile, juvenile, subadult, and adult) are described and proposed to distinguish growth sequences. Our results may be useful to diverse disciplines, from developmental biology to fisheries management. PMID:23936353
Spatial variations in mortality in pelagic early life stages of a marine fish (Gadus morhua)
NASA Astrophysics Data System (ADS)
Langangen, Øystein; Stige, Leif C.; Yaragina, Natalia A.; Ottersen, Geir; Vikebø, Frode B.; Stenseth, Nils Chr.
2014-09-01
Mortality of pelagic eggs and larvae of marine fish is often assumed to be constant both in space and time due to lacking information. This may, however, be a gross oversimplification, as early life stages are likely to experience large variations in mortality both in time and space. In this paper we develop a method for estimating the spatial variability in mortality of eggs and larvae. The method relies on survey data and physical-biological particle-drift models to predict the drift of ichthyoplankton. Furthermore, the method was used to estimate the spatially resolved mortality field in the egg and larval stages of Barents Sea cod (Gadus morhua). We analyzed data from the Barents Sea for the period between 1959 and 1993 when there are two surveys available: a spring and a summer survey. An individual-based physical-biological particle-drift model, tailored to the egg and larval stages of Barents Sea cod, was used to predict the drift trajectories from the observed stage-specific distributions in spring to the time of observation in the summer, a drift time of approximately 45 days. We interpreted the spatial patterns in the differences between the predicted and observed abundance distributions in summer as reflecting the spatial patterns in mortality over the drift period. Using the estimated mortality fields, we show that the spatial variations in mortality might have a significant impact on survival to later life stages and we suggest that there may be trade-offs between increased early survival in off shore regions and reduced probability of ending up in the favorable nursing grounds in the Barents Sea. In addition, we show that accounting for the estimated mortality field, improves the correlation between a simulated recruitment index and observation-based indices of juvenile abundance.
From Trust to Intimacy: A New Inventory for Examining Erikson's Stages of Psychosocial Development.
ERIC Educational Resources Information Center
Rosenthal, Doreen A.; And Others
1981-01-01
A new inventory for examining the first six of Erikson's psychosocial stages is described. It is concluded that the Erikson Psychosocial Stage Inventory (EPSI), a self-report questionnaire, is a useful measure for researchers interested in development from early adolescence and in mapping changes as a function of life events. (Author/GK)
ERIC Educational Resources Information Center
Darcy, Colette; McCarthy, Alma
2007-01-01
Purpose--The purpose of this article is to explore the impact of life cycle stage, specifically parenting stage, on work-family conflict among working parents to determine whether discernible differences are evident among those individuals at the early stage of their parenting cycle compared with those with older children.…
NASA Astrophysics Data System (ADS)
LaVigne, M.; Hill, T. M.; Sanford, E.; Gaylord, B.; Russell, A. D.; Lenz, E. A.; Hosfelt, J. D.; Young, M. K.
2013-06-01
Ocean acidification will likely have negative impacts on invertebrates producing skeletons composed of calcium carbonate. Skeletal solubility is partly controlled by the incorporation of "foreign" ions (e.g. magnesium) into the crystal lattice of these skeletal structures, a process that is sensitive to a variety of biological and environmental factors. Here we explore effects of life stage, oceanographic region of origin, and changes in the partial pressure of carbon dioxide in seawater (pCO2) on trace elemental composition in the purple sea urchin (Strongylocentrotus purpuratus). We show that, similar to other urchin taxa, adult purple sea urchins have the ability to precipitate skeleton composed of a range of biominerals spanning low- to high-Mg calcites. Mg / Ca and Sr / Ca ratios were substantially lower in adult spines compared to adult tests. On the other hand, trace elemental composition was invariant among adults collected from four oceanographically distinct regions spanning a range of carbonate chemistry conditions (Oregon, Northern California, Central California, and Southern California). Skeletons of newly settled juvenile urchins that originated from adults from the four regions exhibited intermediate Mg / Ca and Sr / Ca between adult spine and test endmembers, indicating that skeleton precipitated during early life stages is more soluble than adult spines and less soluble than adult tests. Mean skeletal Mg / Ca or Sr / Ca of juvenile skeleton did not vary with source region when larvae were reared under present-day, global-average seawater carbonate conditions (400 μatm; pHT = 8.02 ± 0.03 1 SD; Ωcalcite = 3.3 ± 0.2 1 SD). However, when reared under elevated pCO2 (900 μatm; pHT = 7.73 ± 0.03; Ωcalcite = 1.8 ± 0.1), skeletal Sr / Ca in juveniles exhibited increased variance across the four regions. Although larvae from the northern populations (Oregon, Northern California, Central California) did not exhibit differences in Mg or Sr incorporation under elevated pCO2 (Sr / Ca = 2.10 ± 0.06 mmol mol-1; Mg / Ca = 67.4 ± 3.9 mmol mol-1), juveniles of Southern California origin partitioned ~8% more Sr into their skeletons when exposed to higher pCO2 (Sr / Ca = 2.26 ± 0.08 vs. 2.09 ± 0.005 mmol mol-1 1 SD). Together these results suggest that the diversity of carbonate minerologies present across different skeletal structures and life stages in purple sea urchins does not translate into an equivalent geochemical plasticity of response associated with geographic variation or temporal shifts in seawater properties. Rather, composition of S. purpuratus skeleton precipitated during both early and adult life history stages appears relatively robust to spatial gradients and predicted future changes in carbonate chemistry. An exception to this trend may arise during early life stages, where certain populations of purple sea urchins may alter skeletal mineral precipitation rates and composition beyond a given pCO2 threshold. This potential for geochemical plasticity during early development in contrast to adult stage geochemical resilience adds to the growing body of evidence that ocean acidification can have differing effects across organismal life stages.
Jeremić, Branislav; Milicić, Biljana
2008-02-15
The authors' single-institution experience in patients with early-stage (I and II) nonsmall cell lung cancer (NSCLC) who were treated between 1980 and 1998 with either conventionally fractionated (CF) radiation therapy (RT), or hyperfractionated (HFX) RT, or HFX RT with concurrent paclitaxel/carboplatin (HFX RT-Pac/C) was reviewed. Seventy-eight patients received 60 grays (Gy) in 30 daily fractions (CF), 116 patients received 69.6 Gy (1.2 Gy twice daily), and 56 patients received 67.6 Gy (1.3 Gy twice daily) with concurrent, low-dose, daily C (25 mg/m2) and Pac (10 mg/m2). Biologically equivalent doses for the 3 groups were 72 Gy, 78 Gy, and 76 Gy, respectively, for acute effects (alpha/beta = 10 Gy) and 120 Gy, 111 Gy, and 111 Gy, respectively, for late effects (alpha/beta = 2 Gy). For all 250 patients, the overall median survival was 27 months, the cause-specific survival was 27 months, the local progression-free survival was 32 months, and distant metastasis-free survival was not achieved; and the respective 5-year survival rates were 27%, 32%, 45%, and 68%. CF achieved significantly inferior survival than either HFX RT alone or HFX RT-Pac/C (P = .0332 and P = .0013, respectively), and no difference was observed between the 2 HFX RT regimens (P = .1934). Only acute hematologic high-grade toxicity (grade >or=3) was more frequent with HFX RT-Pac/C than with either RT alone, whereas other toxicities were similar between the 3 treatment groups. HFX RT with or without concurrent chemotherapy may be better than CF in patients with early-stage NSCLC. The role of chemotherapy deserves further investigation, because the group that received chemotherapy in the current study had a higher incidence of acute high-grade hematologic toxicity. Cancer 2008. (c) 2008 American Cancer Society.
Chang, Joe Y; Liu, Yung-Hsien; Zhu, Zhengfei; Welsh, James W; Gomez, Daniel R; Komaki, Ritsuko; Roth, Jack A; Swisher, Stephen G
2013-09-15
Surgical resection has been the standard treatment for early stage multiple primary lung cancer (MPLC). However, a significant proportion of patients with MPLC cannot undergo surgery. For this report, the authors explored the role of stereotactic ablative radiotherapy (SABR) for patients with MPLC. Patients with MPLC who received SABR (50 grays [Gy] in 4 fractions or 70 Gy in 10 fractions) for the second tumor were reviewed. Four-dimensional, computed tomography-based, planning/volumetric image-guided treatment was used for all patients. Treatment outcomes/toxicities were analyzed. For the 101 patients who received SABR, at a median follow-up of 36 months and with a median overall survival (OS) of 46 months, the 2-year and 4-year in-field local control rates were 97.4% and 95.7%, respectively. The 2-year and 4-year OS rates were 73.2% and 47.5%, respectively; and the progression-free survival (PFS) rates were 67% and 58%, respectively. Patients who had metachronous tumors had better OS and PFS than patients who had synchronous tumors (2-year OS: 80.6% metachronous vs 61.5% synchronous; 4-year OS: 52.7% vs 39.7%, respectively; P = .047; 2-year PFS: 84.7% vs 49.4%, respectively; 4-year PFS: 75.6% vs 30.4%, respectively; P = .0001). For patients who either underwent surgery or received SABR for an index tumor, the incidence of grade ≥ 3 radiation pneumonitis was 3% (2 of 71 patients); however, this increased to 17% (5 of 30 patients) for those who received conventional radiotherapy for an index tumor. Other grade ≥ 3 toxicities included grade 3 chest wall pain (3 of 101 patients; 3%) and grade 3 skin toxicity (1 of 101 patients; 1%). SABR achieves promising long-term tumor control and survival and may be a potential curative treatment for early stage MPLC. © 2013 American Cancer Society.
Incorporating children's toxicokinetics into a risk framework.
Ginsberg, Gary; Slikker, William; Bruckner, James; Sonawane, Babasaheb
2004-01-01
Children's responses to environmental toxicants will be affected by the way in which their systems absorb, distribute, metabolize, and excrete chemicals. These toxicokinetic factors vary during development, from in utero where maternal and placental processes play a large role, to the neonate in which emerging metabolism and clearance pathways are key determinants. Toxicokinetic differences between neonates and adults lead to the potential for internal dosimetry differences and increased or decreased risk, depending on the mechanisms for toxicity and clearance of a given chemical. This article raises a number of questions that need to be addressed when conducting a toxicokinetic analysis of in utero or childhood exposures. These questions are organized into a proposed framework for conducting the assessment that involves problem formulation (identification of early life stage toxicokinetic factors and chemical-specific factors that may raise questions/concerns for children); data analysis (development of analytic approach, construction of child/adult or child/animal dosimetry comparisons); and risk characterization (evaluation of how children's toxicokinetic analysis can be used to decrease uncertainties in the risk assessment). The proposed approach provides a range of analytical options, from qualitative to quantitative, for assessing children's dosimetry. Further, it provides background information on a variety of toxicokinetic factors that can vary as a function of developmental stage. For example, the ontology of metabolizing systems is described via reference to pediatric studies involving therapeutic drugs and evidence from in vitro enzyme studies. This type of resource information is intended to help the assessor begin to address the issues raised in this paper. PMID:14754583
DOE Office of Scientific and Technical Information (OSTI.GOV)
Watson, Linda C., E-mail: Linda.watson@albertahealthservices.ca; Gies, Donna; Thompson, Emmanuel
Purpose: Standard skin care instructions regarding the use of antiperspirants during radiotherapy to the breast varies across North America. Women have articulated that when instructed to not use antiperspirant, the potential for body odor is distressing. Historical practices and individual opinions have often guided practice in this field. The present study had 2 purposes. To evaluate whether the use of aluminum-based antiperspirant while receiving external beam radiotherapy for stage 0, I, or II breast cancer will increase axilla skin toxicity and to evaluate whether the use of antiperspirant during external beam radiotherapy improves quality of life. Methods: A total ofmore » 198 participants were randomized to either the experimental group (antiperspirant) or control group (standard care-wash only). The skin reactions in both groups were measured weekly and 2 weeks after treatment using the National Cancer Institute Common Toxicity Criteria Adverse Events, version 3, toxicity grading criteria. Both groups completed the Functional Assessment for Chronic Illness Therapy's questionnaire for the breast population quality of life assessment tool, with additional questions evaluating the effect of underarm antiperspirant use on quality of life before treatment, immediately after treatment, and 2 weeks after treatment during the study. Results: The skin reaction data were analyzed using the generalized estimating equation. No statistically significant difference was seen in the skin reaction between the 2 groups over time. The quality of life data also revealed no statistically significant difference between the 2 groups over time. Conclusions: Data analysis indicates that using antiperspirant routinely during external beam radiotherapy for Stage 0, I, or II breast cancer does not affect the intensity of the skin reaction or the self-reported quality of life. This evidence supports that in this particular population, there is no purpose to restrict these women from using antiperspirants during their treatment, and the decision to use an antiperspirant or not in this setting should be left to the discretion of the patient.« less
Hippocampal Plasticity During the Progression of Alzheimer’s disease
Mufson, Elliott J.; Mahady, Laura; Waters, Diana; Counts, Scott E.; Perez, Sylvia E.; DeKosky, Steven; Ginsberg, Stephen D.; Ikonomovic, Milos D.; Scheff, Stephen; Binder, Lester
2015-01-01
Neuroplasticity involves molecular changes in central nervous system (CNS) synaptic structure and function throughout life. The concept of neural organization allows for synaptic remodeling as a compensatory mechanism to the early pathobiology of Alzheimer’s disease (AD) in an attempt to maintain brain function and cognition during the onset of dementia. The hippocampus, a crucial component of the medial temporal lobe memory circuit, is affected early in AD and displays synaptic and intraneuronal molecular remodeling against a pathological background of extracellular amyloid-beta (Aβ) deposition and intracellular neurofibrillary tangle (NFT) formation in the early stages of AD. Here we discuss human clinical pathological findings supporting the concept that the hippocampus is capable of neural plasticity during mild cognitive impairment (MCI), a prodromal stage of AD and early stage AD. PMID:25772787
Unique aspects of the perinatal immune system.
Zhang, Xiaoming; Zhivaki, Dania; Lo-Man, Richard
2017-08-01
The early stages of life are associated with increased susceptibility to infection, which is in part due to an ineffective immune system. In the context of infection, the immune system must be stimulated to provide efficient protection while avoiding insufficient or excessive activation. Yet, in early life, age-dependent immune regulation at molecular and cellular levels contributes to a reduced immunological fitness in terms of pathogen clearance and response to vaccines. To enable microbial colonization to be tolerated at birth, epigenetic immune cell programming and early life-specific immune regulatory and effector mechanisms ensure that vital functions and organ development are supported and that tissue damage is avoided. Advancement in our understanding of age-related remodelling of immune networks and the consequent tuning of immune responsiveness will open up new possibilities for immune intervention and vaccine strategies that are designed specifically for early life.
Jack, Katharine M.; Schoof, Valérie A.M.; Sheller, Claire R.; Rich, Catherine I.; Klingelhofer, Peter P.; Ziegler, Toni E.; Fedigan, Linda
2014-01-01
Much attention has been paid to hormonal variation in relation to male dominance status and reproductive seasonality, but we know relatively little about how hormones vary across life history stages. Here we examine fecal testosterone (fT), dihydrotestosterone (fDHT), and glucocorticoid (fGC) profiles across male life history stages in wild white-faced capuchins (Cebus capucinus). Study subjects included 37 males residing in three habituated social groups in the Área de Conservacíon Guanacaste, Costa Rica. Male life history stages included infant (0 to <12 months; N = 3), early juvenile (1 to <3 years; N = 10), late juvenile (3 to <6 years; N = 9), subadult (6 to <10 years; N = 8), subordinate adult (≥10 years; N = 3), and alpha adult (≥ 10 years; N = 4, including one recently deposed alpha). Life history stage was a significant predictor of fT; levels were low throughout the infant and juvenile phases, doubled in subadult and subordinate adults, and were highest for alpha males. Life history stage was not a significant predictor of fDHT, fDHT:fT, or fGC levels. Puberty in white-faced capuchins appears to begin in earnest during the subadult male phase, indicated by the first significant rise in fT. Given their high fT levels and exaggerated secondary sexual characteristics, we argue that alpha adult males represent a distinctive life history stage not experienced by all male capuchins. This study is the first to physiologically validate observable male life history stages using patterns of hormone excretion in wild Neotropical primates, with evidence for a strong association between fT levels and life history stage. PMID:24184868
Walser, Tobias; Juraske, Ronnie; Demou, Evangelia; Hellweg, Stefanie
2014-01-01
A pronounced presence of toluene from rotogravure printed matter has been frequently observed indoors. However, its consequences to human health in the life cycle of magazines are poorly known. Therefore, we quantified human-health risks in indoor environments with Risk Assessment (RA) and impacts relative to the total impact of toxic releases occurring in the life cycle of a magazine with Life Cycle Assessment (LCA). We used a one-box indoor model to estimate toluene concentrations in printing facilities, newsstands, and residences in a best, average, and worst-case scenario. The modeled concentrations are in the range of the values measured in on-site campaigns. Toluene concentrations can be close or even surpass the occupational legal thresholds in printing facilities in realistic worst-case scenarios. The concentrations in homes can surpass the US EPA reference dose (69 μg/kg/day) in worst-case scenarios, but are still at least 1 order of magnitude lower than in press rooms or newsstands. However, toluene inhaled at home becomes the dominant contribution to the total potential human toxicity impacts of toluene from printed matter when assessed with LCA, using the USEtox method complemented with indoor characterization factors for toluene. The significant contribution (44%) of toluene exposure in production, retail, and use in households, to the total life cycle impact of a magazine in the category of human toxicity, demonstrates that the indoor compartment requires particular attention in LCA. While RA works with threshold levels, LCA assumes that every toxic emission causes an incremental change to the total impact. Here, the combination of the two paradigms provides valuable information on the life cycle stages of printed matter.
Dai, Die; Gao, Yiqiao; Chen, Jiaqing; Huang, Yin; Zhang, Zunjian; Xu, Fengguo
2016-10-03
Lipopolysaccharide (LPS) can lead to uncontrollable cytokine production and eventually cause fatal sepsis syndrome. Individual toxicity difference of LPS has been widely reported. In our study we observed that two thirds of the rats (24/36) died at a given dose of LPS, while the rest (12/36) survived. Tracking the dynamic metabolic change in survival and non-survival rats in the early stage may reveal new system information to understand the inter-individual variation in response to LPS. As the time-resolved datasets are very complex and no single method can elucidate the problem clearly and comprehensively, the static and dynamic metabolomics methods were employed in combination as cross-validation. Intriguingly, some common results have been observed. Lipids were the main different metabolites between survival and non-survival rats in pre-dose serum and in the early stage of infection with LPS. The LPS treatment led to S-adenosly-methionine and total cysteine individual difference in early stage, and subsequent significant perturbations in energy metabolism and oxidative stress. Furthermore, cytokine profiles were analyzed to identify potential biological associations between cytokines and specific metabolites. Our collective findings may provide some heuristic guidance for elucidating the underlying mechanism of individual difference in LPS-mediated disease.
NASA Astrophysics Data System (ADS)
Bruno, Daniel O.; Delpiani, Sergio M.; Acha, Eduardo M.
2018-05-01
This study aimed to assess the diel changes of ichthyoplankton occurrence, during a known recruitment period, to a wind-dominated coastal lagoon (Argentina). We collected plankton samples at three sites of the lagoon's inlet area every 3 h during four 24 h cycles in mid austral summer. For each early-life history stage (eggs, yolk sac, preflexion larvae, postflexion larvae and early juveniles), the relationship between the abundance and possible combinations of the time of sampling, the wind effect, the wave period and the tidal state was evaluated by fitting generalized linear mix-effects models (GLMM). The wind effects depending on the time of sampling mainly affected fish abundance in all developmental stages. Overall, the highest abundances were collected at nocturnal hours when low-speed offshore winds blew. In addition, higher abundances of eggs, yolk sac and preflexion larvae were related to the incoming flood tide; whereas higher abundances of postflexion larvae and early juveniles were related to longer wave periods. We argued that the daily variation in the abundance of early-life history stages of fishes is related to the sea-land breeze cycle. Therefore, a conceptual framework of the recruitment process of eggs, larvae and early juveniles of fishes into this estuarine system considering the daily effect of winds is proposed.
USDA-ARS?s Scientific Manuscript database
Stem (black) rust, caused by Puccinia graminis, has plagued cereal crop production (wheat, barley, rye and oat) since the early days of agriculture. P. graminis is an obligate biotroph with a complex life cycle that includes five spore stages and two hosts. The asexual stage (uredinal) has a broad h...