Palladium-doped and undoped polystyrene nanoplastics in a chronic toxicity test for higher plants: Impact on soil, plants and ammonium oxidizing bacteria.

There is a lack of knowledge about the fate and impact of microplastics (MPs) and nanoplastics (NPs), as well as their potential uptake and impact on plants and microorganisms. The predicted environmental concentrations (PEC) of frequent polymers in soils are low, and therefore, difficult to detect with the available techniques, which explains the knowledge gaps. Therefore, model particles (polystyrene particles (PS-P), 343 nm) and palladium (Pd) nanoparticle-doped polystyrene particles (PS-Pd-PS-P, 442 nm) were synthesized, characterized, and subsequently applied to agricultural soils (Cambisol, Podzol, PS target contents: 25 mg kg-1, 75 mg kg-1, 225 mg kg-1). A combination of different techniques, such as inductively coupled plasma-mass spectrometry (ICP-MS), pyrolysis-gas chromatography-mass spectrometry (Pyr-GC-MS), dynamic light scattering (DLS), and scanning electron microscopy (SEM), were used to characterize the particles in the dispersions, soils and plants. The spiked soils were applied to a chronical plant toxicity test with oat (Avena sativa). The applied particle contents could be recovered from both soils by ICP-MS (Pd, 89% - 99%), and Pyr-GC-MS (PS, 73% - 120%). Moreover, non-aggregated particles in soils and on oat roots were visualized through SEM. The ratio obtained for the Pd contents in oat roots to that in the Cambisol (2.2-2.7) and the Podzol (2.3-2.6) implied that particles accumulated on the root surface or in the roots. No Pd was detected in the oat shoots, which indicated that no translocation occurred from the roots to the shoots. Despite particle accumulation at or in the roots, no clear effects on plant growth were observed. Furthermore, the soil microorganisms (Podzol) and the soil water repellency (Cambisol, Podzol) showed no clear monotone concentration-response relationship after exposure to PS-P and PS-Pd-PS-P. The findings are complex and illustrate the urgent need for further sophisticated experimental studies to elucidate the impacts of NPs on physicochemical soil function, plants, and soil organisms. The model PS-P doped with Pd nanoparticles significantly enhanced the development and validation of methods for investigating MPs and NPs in environmental matrices, highlighting their considerable potential for further studies.

Physical and chemical characterization of drill cuttings: A review.

Drill cuttings comprise a mixture of rocks generated during drilling activities of exploration and production of oil and gas. These residues' properties are variable, depending on several drilling parameters and drilled rock composition. Many scientific studies have been published regarding the characterization of these residues. Articles summarizing these residues' characteristics and toxicity data are poorly explored in the literature. This work reviews the principal methods used to characterize drill cuttings and data about these residues' properties. Some authors have reported the large content of Zn in drill cuttings. These cuttings can be associated with base fluids (as olefins, varying from C11 to C18), and some time crude oil (high range of TPH, unresolved complex mixtures, and PAH compounds). Acute and chronic toxicity tests have shown negative impacts of different types of fluids, the components of these fluids, and cuttings on other marine organisms.

Proposal of a chronic toxicity test using the tropical epibenthic amphipod Parhyale hawaiensis.

Chronic toxicity tests with representative organisms are essential for ecological risk assessment. The circumtropical marine amphipod Parhyale hawaiensis is a promising test organism in ecotoxicology. This study aimed to develop a chronic toxicity protocol for liquid samples testing with P. hawaiensis using reproduction and growth as endpoints. In the proposed protocol, organisms (≤52 days old) are placed in 5 replicates each containing 100 mL of solution, 10 organisms, and 5 g of crushed coral for 42 days of exposure. The protocol was successfully developed but reproduction showed better performance than growth rate. NOECs based on reproduction were determined for zinc (0.10 mg Zn L-1) and 3,4-DCA (0.50 mg L-1), and they are of the same order of magnitude compared with the values of other amphipods. The developed test based on reproduction can be considered a promising tool for hazard characterizations although more tests with different substances are still needed.

Evaluation of in vitro toxicity information for zebrafish as a promising alternative for chemical hazard and risk assessment.

In vitro assays are widely proposed as a test alternative to traditional in vivo standard acute and chronic toxicity tests. However, whether toxicity information derived from in vitro assays instead of in vivo tests could provide sufficient protection (e.g., 95 % of protection) for chemical risks remain evaluated. To investigate the feasibility of zebrafish (Danio rerio) cell-based in vitro test method as a test alternative, we comprehensively compared sensitivity differences among endpoints, among test methods (in vitro, FET and in vivo), and between zebrafish and rat (Rattus norvegicus), respectively using chemical toxicity distribution (CTD) approach. For each test method involved, sublethal endpoints were more sensitive than lethal endpoints for both zebrafish and rat, respectively. Biochemistry (zebrafish in vitro), development (zebrafish in vivo and FET), physiology (rat in vitro) and development (rat in vivo) were the most sensitive endpoints for each test method. Nonetheless, zebrafish FET test was the least sensitive one compared to its in vivo and in vitro tests for either lethal or sublethal responses. Comparatively, rat in vitro tests considering cell viability and physiology endpoints were more sensitive than rat in vivo test. Zebrafish was found to be more sensitive than rat regardless of in vivo or in vitro tests for each pairwise endpoint of concern. Those findings indicate that zebrafish in vitro test is a feasible test alternative to zebrafish in vivo and FET test and traditional mammalian test. It is suggesting that zebrafish in vitro test can be optimized by choosing more sensitive endpoints, such as biochemistry to provide sufficient protection for zebrafish in vivo test and to establish applications of zebrafish in vitro test in future risk assessment. Our findings are vital for evaluating and further application of in vitro toxicity toxicity information as an alternative for chemical hazard and risk assessment.

Acute and Chronic Toxicity of Uncured Resin Feedstocks for Vat Photopolymerization 3D Printing to a Cladoceran (Ceriodaphnia Dubia).

The accessibility and popularity of additive manufacturing (AM) has increased over the past decade. Environmental hazard assessment and safety data sheets for 3D printer feedstocks has lagged technology development. Vat photopolymerization may have unique risks relative to other AM technologies due to mishandling of uncured monomers/oligomer feedstocks and its decreasing cost enabling uninformed residential use. The acute and chronic toxicity of six uncured resins to Ceriodaphnia dubia was explored. Two-day acute toxicity (LC50) ranged from 2.6 to 33 mg/L and inhibition concentrations (IC25) values for reproduction ranged from 0.33 to 16 mg/L. Cleaning and waste management procedures recommended in user guides could be the most hazardous handling scenario as use of isopropyl alcohol increases miscibility and thus the fate, transport and bioavailability of the uncured resins. Residential users may often be poorly informed about potential toxicity and the need for a plan for use, handling, and waste management of uncured resins.

Life history traits of low-toxicity alternative bisphenol S on Daphnia magna with short breeding cycles: A multigenerational study.

Due to relatively lower toxicity, bisphenol S (BPS) has become an alternative to previously used bisphenol A. Nevertheless, the occurrence of BPS and its ecological impact have recently attracted increasing attentions because the toxicology effect of BPS with life cycle or multigenerational exposure on aquatic organisms remains questionable. Herein, Daphnia magna (D. magna) multigenerational bioassays spanning four generations (F0-F3) and single-generation recovery (F1 and F3) in clean water were used to investigate the ecotoxicology of variable chronic BPS exposure. For both assays, four kinds of life-history traits (i.e., survival, reproduction, growth and ecological behavior) were examined for each generation. After an 18-day exposure under concentration of 200 µg/L, the survival rate of D. magna was less than 15 % for the F2 generation, whereas all died for the F3 generation. With continuous exposure of four generations of D. magna at environmentally relevant concentrations of BPS (2 µg/L), inhibition of growth and development, prolonged sexual maturity, decreased offspring production and decreased swimming activity were observed for the F3 generation. In particular, it is difficult for D. magna to return to its normal level through a single-generation recovery in clean water in terms of reproductive function, ecological behavior and population health. Hence, multi-generational exposure to low concentrations of BPS can have adverse effects on population health of aquatic organisms with short breeding cycles, highlighting the necessity to assess the ecotoxicology of chronic BPS exposure for public health.

Ecotoxicological assessment of the effects of fluoxetine on Daphnia magna based on acute toxicity, multigenerational reproduction effects, and attraction-repellence responses.

Fluoxetine, a common pharmaceutical used as an antidepressant, is already considered potentially hazardous to biota due to its increasing use and detection in European, North American, and Asian rivers. We studied the effects of fluoxetine on Daphnia magna, as we hypothesized that fluoxetine might have harmful effects, short and long-term, at different levels: survival, behaviour, and reproduction (offspring production). We applied two different approaches: (i) a scenario at environmentally relevant concentrations (0.1-1.0 µg/L) and (ii) a scenario simulating a future worsening of contamination (1-800 µg/L) until the reach of lethal concentrations. In the former, we examined whether there are multigenerational effects on reproduction and on the avoidance/colonisation behaviour in previously exposed populations. In the latter, three responses were assessed: survival, avoidance behaviour and reproduction. We did not detect differences in the reproduction output of D. magna among the treatments over the three generations examined. Irrespective of the multigenerational treatment, D. magna colonised the environments with fluoxetine in a similar way. In the second scenario, we determined the lethal concentration for 50% of the population (96 h-LC50 = 365 µg/L), which, in spite of the toxic effect, was attractive to organisms during the avoidance tests (24 h); in fact, D. magna were attracted (no repellence) even to the highest concentrations of fluoxetine tested (800 µg/L). Lastly, in a 21-day chronic toxicity test the reproduction output of D. magna increased with higher concentrations of fluoxetine. This effect might be related to the fact that the organisms in the contaminated treatment began their first reproduction earlier, when compared to that in the control treatments. In conclusion, this study discusses an identified hazard for aquatic biota due to the fluoxetine attraction effect and a predictive assessment of the consequences expected if its indiscriminate use increases.

Intoxicación cronica por metales tóxicos en supervivientes de artefactos explosivos improvisados con fragmentos incorporados y su potencial neoplásico. Revisión sistemática exploratoria / Chronic heavy metal intoxication in survivors of improvised explosive devices with embedded fragments and its neoplastic potential. Exploratory systematic review

Resumen Introducción: Los artefactos explosivos improvisados son armas no convencionales que pueden provocar múltiples lesiones y dejar esquirlas a modo de cuerpos extraños que pueden contener metales tóxicos, con potencial afectación a la salud de las víctimas según reportes datados desde 1977, los cuales mencionan alta mortalidad por cáncer y otros síntomas compatibles con toxicidad crónica Objetivo: Describir los resultados de investigación que informen sobre la toxicidad crónica producida por metales en personas víctimas de artefactos explosivos improvisados con esquirlas internalizadas, y sus posibles relaciones con cáncer. Metodología: Revisión sistemática exploratoria de literatura publicada y gris que se realizó entre los meses de marzo a mayo de 2021 en diferentes repositorios de tesis y bases de datos (Scielo, Pubmed, Academic Search Complete, JSTOR, Biblioteca Virtual en Salud, Freepdf, Google Académico, Open Grey); sin límite temporal o geográfico. Se incluyeron artículos originales de revistas indexadas o informes finales no publicados, correspondientes a investigaciones científicas con texto completo, en inglés, español y portugués. Resultados: De 56 documentos evaluados, solamente tres cumplieron criterios de inclusión. Todos estaban escritos en idioma inglés. Solo un estudio iraquí abordó población civil y los otros trabajos aludían a veteranos norteamericanos. Los niveles elevados de metales tóxicos, asociados con alteraciones tisulares circunscritas, fueron hallazgos recurrentes. No hubo reportes de patologías instauradas o manejos clínicos. Conclusión: Fue escasa la evidencia científica recabada; sin embargo, sí se han reportado cambios tisulares circundantes a esas esquirlas. Se considera necesario realizar más estudios relacionados con el tema, incluyendo seguimientos a largo plazo de las afectaciones tisulares detectadas.

Abstract Introduction: Improvised explosive devices are unconventionalweapons that can cause multiple injuries and splinters internalized containing heavy metals, potentially affecting the victim's health, according to reports dating from 1977, which mention high mortality from cancer and other symptoms suggestive of chronic metal toxicity. Objective: To describe the research results that report on the chronic toxicity produced by heavy metals in people who are victims of improvised explosive devices with internalized splinters, and its possible links with cancer. Methodology: Systematic exploratory review of published and grey literature which was carried out between march and may of 2021, in thesis repositories and different databases (Scielo, Pubmed, Academic Search Complete, JSTOR, Biblioteca Virtual en Salud, Freepdf, Google Académico, Open Grey); without time or geographical limit. Original articles from indexed scientific research journals or unpublished final reports were included, corresponding to scientific research with full text, in english, spanish and portuguese. Results: 56 documents were evaluated, three were selected fulfilling the inclusion criteria. They were all written in the english language. Only one Iraqi study addressed the civilian population and the other studies referred to North American veterans. Elevated heavy metal levels, associated with circumscribed tissue abnormalities, were recurrent findings. There were no reports of established pathologies or clinical management. Conclusion: The scientific evidence was scarce; as well as its relationship with established cancer, however, tissue changing surrounding these splinters have been reported. It is considered necessary to carry out more studies related to the subject, including long-term follow-up of detected tissue damage.

Synergistic effect of chloroquine and copper to the euryhaline rotifer Proales similis.

Chloroquine (CQ) has been widely used for many years against malaria and various viral diseases. Its important use and high potential to being persistent make it of particular concern for ecotoxicological studies. Here, we evaluated the toxicity of CQ alone and in combination with copper (Cu) to the euryhaline rotifer Proales similis. All experiments were carried out using chronic toxicity reproductive five-day tests and an application factor (AF) of 0.05, 0.1, 0.3, and 0.5 by multiplying the 24-h LC50 values of CQ (4250 µg/L) and Cu (68 µg/L), which were administered in solution. The rate of population increase (r, d-1) ranged from 0.50 to 52 (controls); 0.20 to 0.40 (CQ); 0.09 to 0.43 (Cu); and -0.03 to 0.30 (CQ-Cu) and showed significant decrease as the concentration of both chemicals in the medium increased. Almost all tested mixtures induced synergistic effects, mainly as the AF increased. We found that the presence of Cu intensifies the vulnerability of organisms to CQ and vice versa. These results stress the potential hazard that these combined chemicals may have on the aquatic systems. This research suggests that P. similis is sensitive to CQ as other standardized zooplankton species and may serve as a potential test species in the risk assessment of emerging pollutants in marine environments.

Acute and chronic toxicities of prothioconazole and its metabolite prothioconazole-desthio in Daphnia magna.

Current research on prothioconazole (PTC), a broad-spectrum triazole fungicide, mainly focuses on its efficacy and residues; only a few studies have been assessing its toxicological effects. Using acute and chronic toxicity tests, we assessed the effects of PTC and its metabolite prothioconazole-desthio (PTCd) on the inhibition of the activity, growth, and reproduction of Daphnia magna. A dose-response relationship was established to determine sensitive biological indicators. In the acute and chronic toxicity tests, the 48-h EC50 (concentration for 50% of the maximal effect) of PTC and PTCd for D. magna were 2.82 and 5.19 mg/L and 0.0807 and 0.132 mg/L, respectively; in the latter test, PTC was 1.64 times more toxic than PTCd. Acute-to-chronic toxicity ratios were calculated using chronic toxicity data; the ratios were 227 and 27.5 for PTC and PTCd, respectively. Our results indicate that both PTC and PTCd affect the growth and reproduction of D. magna and that the toxicity of PTC is greater than that of PTCd. In conclusion, the metabolites of PTD are toxic to D. magna at certain concentrations, and their environmental risks should not be neglected.

Daphnia magna and Ceriodaphnia dubia Have Similar Sensitivity in Standard Acute and Chronic Toxicity Tests.

The cladocerans Daphnia magna and Ceriodaphnia dubia have been used for decades to assess the hazards of chemicals and effluents, but toxicity data for these species have traditionally been treated separately. Numerous standard acute and chronic test guidelines have been developed for both species. In the present study, data were compiled and curated for acute survival (48 h) and growth and reproduction tests with D. magna (21 days chronic) and C. dubia (7 days chronic) toxicity assays. Orthogonal regressions were developed to statistically compare the acute and chronic sensitivity of D. magna and C. dubia across a diversity of chemicals and modes of action. Acute orthogonal regressions between D. magna and D. pulex, a widely accepted surrogate species, were used to set a data-driven benchmark for what would constitute a suitable D. magna surrogate. The results indicate that there is insufficient evidence to suggest a difference in acute or chronic sensitivity of D. magna and C. dubia in standard toxicity tests. Further, the variability in the acute D. magna and C. dubia regressions were of the same magnitude as that in D. magna and D. pulex regressions. Slope and y-intercept values were also comparable. The absence of significant differences in toxicity values suggests similar species sensitivity in standard tests across a range of chemical classes and modes of action. Environ Toxicol Chem 2022;41:134-147. © 2021 SETAC.

The Longitudinal Profile of a Stream Contaminated With 2,4-D and its Effects on Non-Target Species.

Pesticides can cause harmful effects to aquatic communities, even at concentrations below the threshold limit established as guidelines for the water bodies by environmental agencies. In this research, an input of the herbicide 2,4-dichlorophenoxyacetic acid (i.e., 2,4-D) was simulated under controlled conditions in a 500-m-long reach of a first-order tropical stream in Southeastern Brazil. Two water samplings at eight stations investigated the stream longitudinal contamination profile. The ecotoxicological effects were analyzed using Eruca sativa L. seed germination assays and the acute and chronic toxicity tests with the neotropical cladoceran Ceriodaphnia silvestrii. Physicochemical parameters of water quality were evaluated to characterize the study area and quantify 2,4-D concentrations along the stream to assess pesticide retention. The 2,4-D concentration was reduced by approximately 50% downstream in the samplings, indicating that the herbicide was retained along the stream. Moreover, C. silvestrii reproduction in long-term assays decreased approximately 50% in the stations with higher concentrations of 2,4-D than the laboratory control. After contamination, E. sativa L. showed a lower average root growth (1.0 cm), statistically different from the control (2.2 cm). On the other hand, similar growth values were obtained among the background and the most downstream stations. Our study highlighted the relevance of reviewing and updating herbicide guidelines and criteria to prevent possible ecological risks.

Fluoride sensitivity in freshwater snail, Bellamya bengalensis (Lamarck, 1882): An integrative biomarker response assessment of behavioral indices, oxygen consumption, haemocyte and tissue protein levels under environmentally relevant exposure concentrations.

There is limited information on fluoride toxicity and risk overview on ecotoxicological risks to aquatic invertebrate populations particularly molluscan taxa. This necessitated the assessment of toxicity responses in the freshwater snail, Bellamya bengalensis exposed to environmentally relevant concentrations of sodium fluoride. Under lethal exposures (150, 200, 250, 300, 400 and 450 mg/l), the median lethal concentrations (LC50) were determined to be 422.36, 347.10, 333.33 and 273.24 mg/l for B. bengalensis at 24, 48, 72 and 96 h respectively. The rate of mortality of the snails was increased significantly with elevated concentrations of the toxicant. The magnitude of toxicity i.e., toxicity factor at different time scale was also higher with increased exposure duration. Altered behavioural changes i.e., crawling movement, tentacle movement, clumping tendency, touch reflex and mucous secretion in exposed snail with elevated concentrations and exposure duration. Similarly, oxygen consumption rate of the treated snail also lowered significantly during 72 and 96 h of exposure. Under 30-day chronic exposures (Control-0.00 mg/L; T1-27.324 mg/L; T2-54.648 mg/L), protein concentrations in gonad and hepatopancreas of exposure groups was significantly lowered. Chronic exposures also revealed lowered haemocytes counts in exposure groups. The potential for loss of coordination, respiratory distress and physiological disruption in organisms exposed to environmentally relevant concentrations of fluoride was demonstrated by this study. The estimation and magnitude of toxicity responses are necessary for a more accurate estimation of ecological risks to molluscan taxa and invertebrate populations under acute and chronic fluoride exposures in the wild.

In vivo Toxicity Assessment of Refined Red Palm-pressed Mesocarp Olein in Sprague-Dawley Rats.

Refined red palm-pressed mesocarp olein (PPMO) is recovered from palm-pressed mesocarp fiber, which is a by-product from palm oil mill. Its utilization in food industry is extremely limited even though it contains various phytonutrients. Thus, this study aimed to evaluate its toxicity effects by using the male Sprague-Dawley rat model. The rats were administered with a single dose of 2 g/kg PPMO in an acute toxicity study while administered with 2, 1, or 0.5 g/kg PPMO daily for 28 days in a sub-chronic toxicity study. The mortality, oral LD50 value, clinical observation, body and organ weight, hematological and biochemical analyses, pathological and histopathological examinations were assessed. The overall outcomes indicated that PPMO is non-toxic up to 2 g/kg and considered safe to be used in food application, especially as functional food ingredient and supplement attributed to its phytonutrients. Besides, this study provides an insight in alternative utilization of the wastes from palm oil mill.

Effects of the endocrine disruptor 4-nonylphenol on the demography of rotifers Plationus patulus and Brachionus havanaensis: a multigenerational study.

The emerging contaminant 4-nonylphenol is an active ingredient in many surfactants. Though 4-nonylphenol has been reported in Mexican waterbodies, no stringent law is available to establish its permissible limits. Most ecotoxicological assays using zooplankton species are based on previously unexposed populations, and multigenerational experiments are rare. Plationus patulus and Brachionus havanaensis are widely distributed species in Mexico and have been used in ecotoxicological assessments. In this work, the median lethal concentration of 4-nonylphenol (LC50, 24 h) for both rotifer species was derived. Based on our acute toxicity data (24 h LC50 of 4-nonylphenol for P. patulus and B. havanaensis were 500 and 250 µg L-1, respectively), three sublethal concentrations (µg L-1) (7.81, 15.82 and 31.25 for B. havanaensis and 15.62, 31.25 and 62.5 for P. patulus) were used in the life table demography tests for two successive generations (F0 and F1) of either rotifer species. Regardless of the concentrations used, 4-nonylphenol had an adverse effect on both rotifer species over two successive generations. P. patulus was more sensitive than B. havanaensis in chronic toxicity tests. F1 generation of both rotifer species was far more adversely affected than the F0 in all toxicant treatments.

Assessment of acute, sub-acute, chronic and genotoxicity of polyherbal formulation DCD-684 in mice.

Digas colic drops (DCD-684) a polyherbal formulation containing Carum carvi, Foeniculum vulgare, Mentha arvensis, Mentha piperita and Zingiber officinale is widely used in Pakistan against gastrointestinal ailments including infantile colic. The DCD-684 (0.03-3ml/kg.bw) administered orally in acute (7-days) and sub-acute toxicity (14-days) tests, displayed neither mortality nor toxicological changes in physical, behavioral, biochemical and histopathological parameters. In chronic study (90-days), DCD-684 (0.3-12ml/kg.bw) also revealed no changes. However, at 18 and 36 ml/kg.bw, liver demonstrated mild inflammation correlating with raised aspartate transaminase (AST), alkaline phosphatase (ALP) and alpha fetoprotein (AFP) levels. Increased levels of urea and inflamed renal parenchyma indicated mild nephro-toxicity with high alanine aminotransferase (ALT) at 36ml/kg.bw. The LD50 of DCD-684 in mice was 27.5 ml/kg.bw. In hepatocytes at 36ml/kg.bw, elevated mRNA expression of pro-inflammatory chemokines and cytokines were evident. DCD-684 neither damaged DNA nor induced cytotoxicity in micronucleus assay. In conclusion, polyherbal DCD-684 caused neither hepatic, renal, genotoxicity nor any undesirable effect in mice. Higher doses administered for 90 days showed mild toxic effects with no sign of necrosis, fibrosis or genotoxicity. Thus, in mice DCD-684 demonstrated a wide margin of safety to be used for the relief of infantile colic.

The Sensitivity of a Unionid Mussel (Lampsilis Siliquoidea) to a Permitted Effluent and Elevated Potassium in the Effluent.

Freshwater mussels are one of the most imperiled groups of animals in the world and are among the most sensitive species to a variety of chemicals. However, little is known about the sensitivity of freshwater mussels to wastewater effluents. The objectives of the present study were to (1) assess the toxicity of a permitted effluent, which entered the Deep Fork River, Oklahoma (USA), to a unionid mussel (Lampsilis siliquoidea) and to two standard test species (cladoceran Ceriodaphnia dubia; and fathead minnow Pimephales promelas) in short-term 7-day effluent tests; (2) evaluate the relative sensitivities of the three species to potassium (K), an elevated major ion in the effluent, using 7-day toxicity tests with KCl spiked into a Deep Fork River upstream reference water; (3) determine the potential influences of background water characteristics on the acute K toxicity to the mussel (96-h exposures) and cladoceran (48-h exposure) in four reconstituted waters that mimicked the hardness and ionic composition ranges of the Deep Fork River; and (4) determine the potential influence of temperature on acute K toxicity to the mussel. The effluent was found to be toxic to mussels and cladocerans, and it contained elevated concentrations of major cations and anions relative to the upstream Deep Fork River reference water. The K concentration in the effluent was 48-fold greater than in the upstream water. Compared with the standard species, the mussel was more than 4-fold more sensitive to the effluent in the 7-day effluent tests and more than 8-fold more sensitive to K in the 7-day K toxicity tests. The acute K toxicity to the mussel decreased by a factor of 2 when the water hardness was increased from soft (42 mg/L as CaCO3 ) to very hard (314 mg/L as CaCO3 ), whereas the acute K toxicity to the cladoceran remained almost the same as hardness increased from 84 to 307 mg/L as CaCO3 . Acute K toxicity to the mussel at 23 °C was similar to the toxicity at an elevated temperature of 28 °C. The overall results indicate that the two standard test species may not represent the sensitivity of the tested mussel to both the effluent and K, and the toxicity of K was influenced by the hardness in test waters, but by a limited magnitude. Environ Toxicol Chem 2021;40:3410-3420. Published 2021. This article is a U.S. Government work and is in the public domain in the USA.

Evaluation of chronic toxicity of cyclocreatine in beagle dogs after oral gavage administration for up to 23 weeks.

Cyclocreatine (LUM-001) was evaluated for chronic toxicity (23 weeks) in beagle dogs to support clinical development in patients with creatine transporter deficiency (CTD) disorder. Deionized water (vehicle control) or cyclocreatine was administered by oral gavage twice daily (12 ± 1 h apart) at 20, 40 and 75 mg/kg/dose followed by a recovery period. Due to severe toxicity, the study was terminated earlier than the planned 39 weeks of dosing. Animals in the 20, 40 and 75 mg/kg/dose groups completed 160, 106, and 55 days of dosing, respectively, followed by 30, 55 and 106 days of a recovery period, respectively. Three (25%), 7 (58%), and 7 (58%) animals were euthanized and/or found dead in the 40, 80, and 150 mg/kg/day dose groups, respectively. Clinical signs observed were inappetence, frequent emesis, stool abnormalities, weight loss, lethargy and respiratory distress. Histopathological evaluation revealed congestion, edema, cellular infiltration, fibrin, and/or hemorrhage in the lungs of all dose groups. Additionally, animals in all cyclocreatine treatment groups had perinuclear cytoplasmic vacuoles in the heart, kidneys, skeletal and smooth muscles. After the recovery period, the vacuoles were still observed in the cardiac and renal tissues. Cyclocreatine was absorbed rapidly with mean Tmax within 1 to 2 h and half-life ranged between 2.17 and 2.79 h on Day 1, however, on the final day of dosing, it ranged between 5.80 and 8.77 h (males) and 10.3 to 13.1 h (females). To conclude, in this study the lungs, kidneys, heart, skeletal and smooth muscles were identified as the target organs of cyclocreatine toxicity in beagle dogs.

Biomarkers for assessing chronic toxicity of carbamazepine, an anticonvulsants drug on Pangasianodon hypophthalmus (Sauvage, 1878).

In recent times, carbamazepine (CBZ) as an anticonvulsants drug has raised attention because of its safety concern in the aquatic environment. The present study aimed to evaluate the sub-lethal effects of CBZ (1%, 0.1 % and 0.01 % of 96 h LC50) on P. hypophthalmus for 60 days based on haematological, biochemical, and genotoxicity biomarkers. Chronic exposure of CBZ altered blood profiles (total erythrocyte count, packed cell volume, haemoglobin) and serum biomarkers such as alkaline phosphates, cholesterol, lactate dehydrogenase and transaminase enzymes. Oxidative stress biomarkers such as superoxide dismutase (SOD) and catalase (CAT) activity were also substantially affected in all treatments. Genotoxicity study revealed the formation of micronucleus in erythrocytes of exposed fish. Integrated Biomarker Response (IBR) study showed cholesterol, serum glutamic oxaloacetic transaminase (SGOT) in serum and SOD, CAT in liver tissue are the best organ-based enzyme biomarkers. The present report concludes that an environmentally realistic concentration of CBZ can pose a serious threat to aquatic organisms.

A systematic approach to evaluate plausible modes of actions for mouse lung tumors in mice exposed to 4-methylimidozole.

The National Toxicology Program (NTP) reported that chronic dietary exposure to 4-methylimidazole (4-MeI) increased the incidence of lung adenomas/carcinomas beyond the normally high spontaneous rate in B6C3F1 mice. To examine plausible modes of action (MoAs) for mouse lung tumors (MLTs) upon exposure to high levels of 4-MeI, and their relevance in assessing human risk, a systematic approach was used to identify and evaluate mechanistic data (in vitro and in vivo) in the primary and secondary literature, along with high-throughput screening assay data. Study quality, relevance, and activity of mechanistic data identified across the evidence-base were organized according to key characteristics of carcinogens (KCCs) to identify potential key events in known or novel MLT MoAs. Integration of these evidence streams provided confirmation that 4-MeI lacks genotoxic and cytotoxic activity with some evidence to support a lack of mitogenic activity. Further evaluation of contextual and chemical-specific characteristics of 4-MeI was consequently undertaken. Due to lack of genotoxicity, along with transcriptomic and histopathological lung changes up to 28 and 90 days of exposure, the collective evidence suggests MLTs observed following exposure to high levels of 4-MeI develop at a late stage in the mouse chronic bioassay, albeit the exact MoA remains unclear.