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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 EC

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., PROMOS scholarship of the DAAD, MCIN/AEI RYC-2017-22324 PID 2019-105868RA-I00, ESF Investing in your future

A review of nickel (Ni) toxicity to aquatic organisms was conducted to determine the primary water quality factors that affect Ni toxicity and to provide information for the development and testing of a biotic ligand model (BLM) for Ni. Acute and chronic data for 66 aquatic species were compiled for the present review. The present review found that dissolved organic carbon (DOC) and hardness act as toxicity-modifying factors (TMFs) because they reduced Ni toxicity to fish and aquatic invertebrates, and these effects were consistent in acute and chronic exposures. The effects of pH on Ni toxicity were inconsistent, and for most organisms there was either no effect of pH or, in some cases, a reduction in toxicity at low pH. There appears to be a unique pH effect on Ceriodaphnia dubia that results in increased toxicity at pHs above 8, but otherwise the effects of TMFs were consistent enough across all organisms and endpoints that a single set of parameters in the Ni BLM worked well with all acute and chronic toxicity data for fish, amphibians, aquatic invertebrates, and aquatic plants and algae. The unique effects of pH on C. dubia may be due to mixture toxicity involving both Ni and bicarbonate. The implications of this mixture effect on BLM modeling and a proposed set of BLM parameters for C. dubia are addressed in the review. Other than this exception, the Ni BLM with a single set of parameters could successfully predict toxicity to all acute and chronic data compiled in the present review. Environ Toxicol Chem 2021;40:2121-2134. © 2021 SETAC.

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). The rate of population increase (r, d-1) ranged from 0.50 to 52 (controls); 0.19 to 0.39 (CQ); 0.09 to 0.42 (Cu); and -0.03 to 0.29 (CQ-Cu) and decreased significantly 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.

Water quality standards for cobalt (Co) have yet to be developed for the European Union or the United States. The primary objective of the present study was to produce a data set comprising marine Co toxicity data that could be used by both the European Union and the United States to determine a predicted-no-effect concentration and ambient water quality criteria, respectively. Ten marine species, ranging from algae to fish, were subjected to chronic Co toxicity tests that were designed to meet international water quality testing standards. Chronic 10% effect concentration values ranged from a low of 1.23 µg dissolved Co/L for red algae (Champia parvula) to a high of 31 800 µg dissolved Co/L for sheepshead minnow (Cyprinodon variegatus). The species sensitivity ranking for chronic marine Co exposure was as follows (from most to least sensitive): C. parvula > Neanthes arenaceodentata (polychaete) > Americamysis bahia (mysid shrimp) > Skeletonema costatum (marine diatom) > Dendraster excentricus (sand dollar) > Mytilus galloprovincialis (mussel) > Strongylocentrotus purpuratus (purple sea urchin) > Crassostrea gigas (oyster) > Dunaliella tertiolecta (marine flagellate) > C. variegatus. Chronic test results indicated that invertebrate and plant species were substantially more sensitive to Co exposure than fish. The chronic toxicity data were used to calculate a species sensitivity distribution, from which a hazardous concentration 5th percentile of 7.09 µg dissolved Co/L (95% CI 0.025-47.3 µg Co/L) was derived. Environ Toxicol Chem 2021;40:1405-1418. © 2021 SETAC.

Multigenerational toxicological effects of a binary mixture of silver nanoparticles (AgNPs) with glyphosate were identified in Daphnia magna using acute and chronic toxicity tests. Acute toxicity interactions were analyzed with the Abbott method. In the chronic tests, the survival, growth, reproduction, and age at first brood were evaluated for the parents and the exposed (F1E) and non-exposed (F1NE) descendants. The scales tested for binary mixture, at the acute level, presented antagonistic and additive interactions, possibly associated with the complexation of the AgNPs by glyphosate. Multigenerational chronic effects related to the parameters, reproduction, and age at first brood were observed in the descendants tested with the individual compounds, with no recovery for F1E and F1NE. In organisms exposed to binary mixture, there was a delay in the age at first brood and also a significant change in the reproduction parameter, with a strong reduction for the parents, F1E, and F1NE, indicating a higher toxicity than the compounds tested individually. Although the results for acute interactions between AgNP and glyphosate did not provide clear evidence, multigenerational chronic binary mixture trials have resulted in unexpected toxicity compared with individual treatments, increasing the concerns associated with this co-exposure in other scenarios. Therefore, the interaction of binary mixture with the organisms merits further investigation and the results reported in the present study will be useful in this regard. Environ Toxicol Chem 2021;40:1123-1131. © 2020 SETAC.

Background. The liver is one of the most commonly affected organs in multiple organ dysfunction syndrome (MODS). In recent years, there have been many studies on Ganoderma lucidum polysaccharides (GLP), but the role of GLP in MODS is still unclear. The purpose of this work was to explore the antioxidant, anti-inflammatory, and protective effects of GLP on the liver in MODS model mice. Methods. The characteristic properties of GLP were processed by physicochemical analysis. The MODS models were successfully established with intraperitoneal injection of zymosan in Kunming strain mice. The antioxidant, anti-inflammatory, and hepatoprotective effects of GLP were processed both in vitro and in vivo by evaluating the oxidative parameters, inflammatory factors, and liver pathological observations. Results. The characterization analysis revealed that GLP was a pyranose mainly composed of glucose with the molecular weights (Mw) of 8309 Da. The experimental results proved that GLP had potential hepatoprotection possibly by improving the antioxidant status (scavenging excessive oxygen radicals, increasing the antioxidant enzyme activities, and reducing the lipid peroxide), alleviating the inflammatory response (reducing the inflammatory factor levels), and guaranteeing the liver functions. Conclusions. This research suggested that GLP had the potential to be developed as a natural medicine for the treatment of multiple organ failure.

The US Environmental Protection Agency (USEPA) is reviewing the protectiveness of the national ambient water quality criteria (WQC) for nickel (Ni) and zinc (Zn) and compiling toxicity databases to update the WQC. An amphipod (Hyalella azteca) and a unionid mussel (Lampsilis siliquoidea) have shown high sensitivity to Ni and Zn in previous studies. However, there remained uncertainties regarding the influence of test duration (48 vs 96 h) and the presence and absence of food in acute exposures with the amphipod, and there were also concerns about poor control of amphipod growth and reproduction and mussel growth in chronic exposures. We conducted acute 48- and 96-h water-only toxicity tests to evaluate the influence of feeding and test durations on the toxicity of dissolved Ni and Zn to the amphipod; we also used recently refined test methods to conduct chronic Ni and Zn toxicity tests to evaluate the sensitivity of the amphipod (6-wk exposure) and the mussel (4- and 12-wk exposures). The 96-h 50% effect concentrations (EC50s) of 916 µg Ni/L and 99 µg Zn/L from acute amphipod tests without feeding decreased from the 48-h EC50s by 62 and 33%, respectively, whereas the 96-h EC50s of 2732 µg Ni/L and 194 µg Zn/L from the tests with feeding decreased from the 48-h EC50s by 10 and 26%, indicating that the presence or absence of food had apparent implications for the 96-h EC50. Our chronic 6-wk EC20s for the amphipod (4.5 µg Ni/L and 35 µg Zn/L) were 50 to 67% lower than the 6-wk EC20s from previous amphipod tests, and our chronic 4-wk EC20s for the mussel (41 µg Ni/L and 66 µg Zn/L) were similar to or up to 42% lower than the 4-wk EC20s from previous mussel tests. The lower EC20s from the present study likely reflect more accurate estimates of inherent sensitivity to Ni and Zn due to the refined test conditions. Finally, increasing the chronic test duration from 4 to 12 wk substantially increased the toxicity of Zn to the mussel, whereas the 4- and 12-wk Ni effect needs to be re-evaluated to understand the large degree of variation in organism responses observed in the present study. Environ Toxicol Chem 2020;39:2256-2268. © 2020 SETAC.

It is growingly concerned about methamphetamine (MA)‐induced lung toxicity. IMP1 is identified as a key molecule for cell life processes, but the role of IMP1 in MA‐induced senescence remains unclear. The purpose of this study was to investigate whether chronic exposure to MA can cause autophagy and senescence of the lungs, whether there are interactions between Mammalian target of rapamycin (mTOR) and IMP1 and whether IMP1 is involved in pulmonary senescence promoted by mTOR‐autophagy. The rats were randomly divided into control group and MA group, following by H&E staining, immunohistochemistry staining and Western blot. The alveolar epithelial cells were proceeded by ß‐galactosidase staining, cell cycle detection, transfection and co‐immunoprecipitation. Long‐term exposure to MA led to the thickening of alveolar septum and more compact lungs. MA promoted the conversion of LC3‐I to LC3‐II and inhibited the activation of mTOR to induce autophagy. Bioinformatics and co‐immunoprecipitation results presented the interactions between IMP1 and mTOR. MA induced cell senescence by decreasing IMP1, up‐regulating p21 and p53, arresting cell cycle and increasing SA‐β‐gal. Overexpression of IMP1 reduced p21 and SA‐β‐gal to inhibit the senescence of alveolar epithelial cells. These results demonstrated that mTOR‐autophagy promotes pulmonary senescence through IMP1 in chronic toxicity of methamphetamine.

Brazil is the largest producer of sugarcane and the world’s top pesticide market. Therefore, environmental consequences are of concern. The aim of the present study was to evaluate the acute and chronic toxicity of pesticide formulations largely used in sugarcane crops: the herbicide DMA® 806 BR (a.i. 2,4-D) and the insecticide Regent® 800 WG (a.i. fipronil), isolated and in mixture, to the Neotropical cladoceran Ceriodaphnia silvestrii. Toxicity tests with the individual formulated products indicated 48h-EC50 values of 169 ± 18 mg a.i./L for 2,4-D and 3.9 ± 0.50 µg a.i./L for fipronil. In the chronic tests, the 8d-EC50 values for reproduction were 55 mg a.i./L (NOEC/LOEC: 50/60 mg a.i./L) and 1.6 µg a.i./L (NOEC/LOEC: 0.40/0.80 µg a.i./L) for 2,4-D and fipronil, respectively. A significant decrease in reproduction of C. silvestrii in all concentrations tested of fipronil, except at the lowest, was observed. Regarding 2,4-D, the organisms had total inhibition of reproduction in the two highest concentrations. Probably your energy reallocation was focused (trade-off) only on its survival. The acute pesticide mixture toxicity (immobility) revealed a dose level dependent deviation with antagonism at low and synergism at high concentrations. For chronic mixture (reproduction) toxicity, antagonism occurred as a result of the interaction of the pesticides. Based on our results and concentrations measured in Brazilian water bodies, fipronil represents ecological risks for causing direct toxic effects on C. silvestrii. These results are worrisome given that agricultural production is likely to increase in the coming years.

Aquatic environments are constantly exposed to a cocktail of contaminants mainly due to human activities. As polluted ecosystems may simultaneously present other multiple natural stressors, the objective of the present study was to evaluate joint effect of stressors (natural and anthropogenic) on life history traits of the Neotropical cladoceran, Ceriodaphnia silvestrii. For this purpose, the effects of water conditioned with predator kairomones (fish) and environmental concentrations (sublethal) of two pesticides widely used in sugarcane monoculture in Brazil, the insecticide Regent® 800 WG (active ingredient—a.i. fipronil) and the herbicide DMA® 806 BR (a.i. 2,4-D) were evaluated using chronic toxicity testing, isolated and in mixture, for this cladoceran species. The environmental risks of pesticides for tropical freshwater biota were also estimated from the risk quotient MEC/PNEC. Among the characteristics of the life history of C. silvestrii evaluated after 8 days of exposure, compared with the mean value of control, the age of primiparous females was not affected by any evaluated treatment. However, species average survival decreased in the treatment of kairomones mixed with fipronil (FK) and in the treatment with a mixture of fipronil, 2,4-D, and kairomones (MFKD). The body length of maternal females was shorter than in the control after exposure in treatments with only kairomones (K) and FK. Fecundity of this cladoceran was reduced when exposed to FK and MFKD treatments, and the intrinsic rate of population increase significantly decreased for organisms exposed to treatment with fipronil (F) and to mixtures of fipronil and 2,4-D (MFD), MFDK, and FK. The results indicated that the combination of anthropogenic and natural stressors causes changes in C. silvestrii life history traits, which can contribute to the decline in populations, and our preliminary risk assessment results are a matter of concern regarding biota conservation.

Smoking cessation is the most effective measure for reducing the risk of smoking-related diseases. However, switching to less harmful products (modified-risk tobacco products [MRTP]) can be an alternative to help reduce the risk for adult smokers who would otherwise continue to smoke. In an 18-month chronic carcinogenicity/toxicity study in A/J mice (OECD Test Guideline 453), we assessed the aerosol of Tobacco Heating System 2.2 (THS 2.2), a candidate MRTP based on the heat-not-burn principle, compared with 3R4F cigarette smoke (CS). To capture toxicity- and disease-relevant mechanisms, we complemented standard toxicology endpoints with in-depth systems toxicology analyses. In this part of our publication series, we report on integrative assessment of the apical and molecular exposure effects on the respiratory tract (nose, larynx, and lungs). Across the respiratory tract, we found changes in inflammatory response following 3R4F CS exposure (eg, antimicrobial peptide response in the nose), with both shared and distinct oxidative and xenobiotic responses. Compared with 3R4F CS, THS 2.2 aerosol exerted far fewer effects on respiratory tract histology, including adaptive tissue changes in nasal and laryngeal epithelium and inflammation and emphysematous changes in the lungs. Integrative analysis of molecular changes confirmed the substantially lower impact of THS 2.2 aerosol than 3R4F CS on toxicologically and disease-relevant molecular processes such as inflammation, oxidative stress responses, and xenobiotic metabolism. In summary, this work exemplifies how apical and molecular endpoints can be combined effectively for toxicology assessment and further supports findings on the reduced respiratory health risks of THS 2.2 aerosol.

The knowledge of cytochrome P450 (CYP) expression involved in chemical exposure are necessary in clinical applications for the medication and prediction of adverse effects. The aim of this study was to evaluate the mRNA expression of CYP1-CYP3 families in cats exposed to BDE-209 for one year. All selected CYP isoforms showed no significant difference in mRNA expressions between control and exposure groups, however, CYP3A12 and CYP3A131 revealed tend to be two times higher in the exposure group compared to control group. The present results indicate that the chronic exposure of BDE209 could not alter CYP expression in the liver of cats. This result considered caused by the deficiency of CYP2B subfamily which is major metabolism enzyme of polybrominated diphenyl ethers ( PBDEs) in cat.

Multiple linear regression (MLR) models for predicting chronic aluminum toxicity to a cladoceran (Ceriodaphnia dubia) and a fish (Pimephales promelas) as a function of 3 toxicity-modifying factors (TMFs)-dissolved organic carbon (DOC), pH, and hardness-have been published previously. However, the range over which data for these TMFs were available was somewhat limited. To address this limitation, additional chronic toxicity tests with these species were subsequently conducted to expand the DOC range up to 12 mg/L, the pH range up to 8.7, and the hardness range up to 428 mg/L. The additional toxicity data were used to update the chronic MLR models. The adjusted R

There is global concern regarding the fate and effects of microplastics in the environment, particularly in aquatic systems. In the present study, ethylene acrylic acid copolymer particles were evaluated in a chronic toxicity study with the aquatic invertebrate Daphnia magna. The study design included a natural particle control treatment (silica) to differentiate any potential physical effects of a particle from the intrinsic toxicity of the test material. In addition to the standard endpoints of survival, growth, and reproduction, the transcriptomic profiles of control and ethylene acrylic acid copolymer-exposed D. magna were evaluated at the termination of the 21-d toxicity study. No significant effects on D. magna growth, survival, or reproduction were observed in comparison with both particle and untreated control groups. Significant transcriptomic alterations were induced at the highest treatment level of 2.3 × 1012 particles of the ethylene acrylic acid copolymer/L in key pathways linked to central metabolism and energy reserves, oxidative stress, and ovulation and molting, indicating a global transcriptomic response pattern. To put the results in perspective is challenging at this time, because, to date, microplastic environmental monitoring approaches have not been equipped to detect particles in the nanosize range. However, our results indicate that ethylene acrylic acid copolymer microplastics in the upper nanosize range are not expected to adversely affect D. magna growth, survival, or reproductive outcomes at concentrations of up to 1012 particles/L. Environ Toxicol Chem 2020;39:1578-1589. © 2020 SETAC.

Aquatic insects are poorly represented in water quality criteria, and previous studies have suggested a lack of sensitivity in acute toxicity tests despite observational studies demonstrating the contrary. Our objectives were to determine the toxicity of nickel (Ni) and zinc (Zn) to the mayfly Neocloeon triangulifer in fed acute (96-h) and chronic exposures to estimate aqueous effect concentrations while acknowledging the importance of dietary exposure for these insects. For the chronic tests, we conducted preliminary full-life cycle (~25-30 d) and subchronic (14 d) exposures to compare the relative sensitivity of the 2 test durations under similar conditions (i.e., feeding rates). Observing similar sensitivity, we settled on 14 d as the definitive test duration. Furthermore, we conducted experiments to determine how much food could be added to a given volume of water while minimally impacting dissolved metal recovery; a ratio of food dry mass to water volume (

Elevated nitrate (NO3 ) and sulfate (SO4 ) in surface water are of global concern, and studies are needed to generate toxicity data to develop environmental guideline values for NO3 and SO4 . The present study was designed to fill existing gaps in toxicity databases by determining the acute and/or chronic toxicity of NO3 (tested as NaNO3 ) to a unionid mussel (Lampsilis siliquoidea), a midge (Chironomus dilutus), a fish (rainbow trout, Oncorhynchus mykiss), and 2 amphibians (Hyla versicolor and Lithobates sylvaticus), and to determine the acute and/or chronic toxicity of SO4 (tested as Na2 SO4 ) to 2 unionid mussels (L. siliquoidea and Villosa iris), an amphipod (Hyalella azteca), and 2 fish species (fathead minnow, Pimephales promelas and O. mykiss). Among the different test species, acute NO3 median effect concentrations (EC50s) ranged from 189 to >883 mg NO3 -N/L, and chronic NO3 20% effect concentrations (EC20s) based on the most sensitive endpoint ranged from 9.6 to 47 mg NO3 -N/L. The midge was the most sensitive species, and the trout was the least sensitive species in both acute and chronic NO3 exposures. Acute SO4 EC50s for the 2 mussel species (2071 and 2064 mg SO4 /L) were similar to the EC50 for the amphipod (2689 mg SO4 /L), whereas chronic EC20s for the 2 mussels (438 and 384 mg SO4 /L) were >2-fold lower than the EC20 of the amphipod (1111 mg SO4 /L), indicating the high sensitivity of mussels in chronic SO4 exposures. However, the fathead minnow, with an EC20 of 374 mg SO4 /L, was the most sensitive species in chronic SO4 exposures whereas the rainbow trout was the least sensitive species (EC20 > 3240 mg SO4 /L). The high sensitivity of fathead minnow was consistent with the finding in a previous chronic Na2 SO4 study. However, the EC20 values from the present study conducted in test water containing a higher potassium concentration (3 mg K/L) were >2-fold greater than those in the previous study at a lower potassium concentration (1 mg K/L), which confirmed the influence of potassium on chronic Na2 SO4 toxicity to the minnow. Environ Toxicol Chem 2020;39:1071-1085. © 2020 SETAC.

Background Combretum molle R.B/G. Don (Combretaceae) is a graceful deciduous shrub, distributed especially in tropical Africa and used in traditional medicine in the treatment of malaria, diabetes, and bacterial, liver and cardiovascular deseases. To our knowledge, no long-term toxicity studies of C. molle has ever been realized yet. Methods The long-term toxicity study was conducted in accordance with OECD 408 guidelines with slight modifications. In fact, rats were divided in groups and treated orally with CMAE at doses of 62.5, 125 and 250 mg/kg for 6 months. The general behavior and signs of toxicity of the rats were daily observed. Body weight, food and water intake were recorded every 2 months for 6 months. At the end of treatment period, urine and blood samples were collected for hematological, biochemical and antioxidant estimations. Immediately, internal organs were collected and weighed. Results The results showed that no mortality and visible signs of the toxicity were recorded in all experimental animals. The administration of CMAE had no significant effects on body weight, organ weights, serum electrolyte, and food and water intake. However, all doses of CMAE produced an increase in high density lipoprotein cholesterol, white blood cells, platelets, glutathione, and a decrease in low density lipoprotein cholesterol and malondialdehyde rate. CMAE at doses of 125 and 250 mg/kg decreased in serum proteins and the activity of aspartate amino transferase, and increased the activity of catalase. In addition, CMAE (250 mg/kg) significantly decreased the alanine aminotransferase activity and the level of triglycerides, very low density cholesterol, total proteins and creatinine, and increased in renal clearance, red blood cells, hemoglobin, hematocrit and superoxide dismutase activity. Conclusions At the end of this study, no signs of major intoxication was noted during 6 months of treatment. These results suggest that long-term consumption of CMAE at the therapeutic dose (250 mg/kg) presents low risks to human health.

The present study investigated the reproductive toxicity of furan in an Extended One-Generation Reproductive Toxicity Study in rats. Sprague Dawley F0 weaning rats (30 per sex per group) were exposed to furan orally at 0, 1, 2.5, 5, and 10 mg kg−1 for 10 weeks (males) and 2 weeks (females) and then mated. Results of F0 indicated that in the furan-treated groups (5 mg kg−1 and 10 mg kg−1), body weight (bw) gain decreased during prebreed and gestational period while increased during lactation periods. F0 animals prebreeding exposure resulted in head tilt and foot splay at 10 mg kg−1. Number of live pups at birth were decreased ( p < 0.001) at 10 mg kg−1. At postnatal day (PND) 70, a significant ( p = 0.03) decrease in testosterone levels of male rats and estrogen levels of female rats ( p = 0.05) was observed in 10 mg kg−1 furan-treated group in F1 generation. Luteinizing hormone, follicle-stimulating hormone, and progesterone levels were also reduced, but their reduction was not statistically significant in all groups. In higher dose furan group (10 mg kg−1), testicular and ovarian weights were reduced in F1 generation at PND 70, with decreased daily sperm production ( p = 0.01) and disturbed estrous cyclicity ( p < 0.01). Some histopathological changes were also observed in testis and ovaries in groups whose parents were previously exposed to 10 mg kg−1 bw of furan group. Based on the above results, it is suggested that exposure to food-based contaminant furan induced remarkable changes in the F0 (parental stage) and F1 (offspring, pubertal, and adult stage) generations of Sprague Dawley rats.

Chlorpyrifos (CPF) and cadmium (Cd) are widespread environmental pollutants, which are often present in drinking water and foods. However, the combined effects of CPF and Cd were not entirely clear at present. There was also no biomarker available to diagnose the poisoning of the two chemicals at low dose for long-term exposures. In this study, we investigated the change of serum metabolites of rats with subchronic exposure to CPF, Cd, and CPF plus Cd using gas chromatography-mass spectrometer-based metabolomics approach. We performed a stepwise optimization algorithm based on receiver operating characteristic to identify serum metabolite biomarkers for toxic diagnosis of the chemicals at different doses after 90-day exposure. We found that aminomalonic acid was the biomarker for the toxicity of Cd alone administration, and serine and propanoic acid were unique biomarkers for the toxicities of CPF plus Cd administrations. Our results suggest that subchronic exposure to CPF and Cd alone, or in combination at their low doses, could cause disturbance of energy and amino acid metabolism. Overall, we have shown that analysis of serum metabolomics can make exceptional contributions to the understanding of the toxic effects following long-term low-dose exposure of the organophosphorus pesticide and heavy metal.

Since the introduction of glyphosate-tolerant genetically-modified plants, the global use of glyphosate has increased dramatically making it the most widely used pesticide on the planet. There is considerable controversy concerning the carcinogenicity of glyphosate with scientists and regulatory authorities involved in the review of glyphosate having markedly different opinions. One key aspect of these opinions is the degree to which glyphosate causes cancer in laboratory animals after lifetime exposure. In this review, twenty-one chronic exposure animal carcinogenicity studies of glyphosate are identified from regulatory documents and reviews; 13 studies are of sufficient quality and detail to be reanalyzed in this review using trend tests, historical control tests and pooled analyses. The analyses identify 37 significant tumor findings in these studies and demonstrate consistency across studies in the same sex/species/strain for many of these tumors. Considering analyses of the individual studies, the consistency of the data across studies, the pooled analyses, the historical control data, non-neoplastic lesions, mechanistic evidence and the associated scientific literature, the tumor increases seen in this review are categorized as to the strength of the evidence that glyphosate causes these cancers. The strongest evidence shows that glyphosate causes hemangiosarcomas, kidney tumors and malignant lymphomas in male CD-1 mice, hemangiomas and malignant lymphomas in female CD-1 mice, hemangiomas in female Swiss albino mice, kidney adenomas, liver adenomas, skin keratoacanthomas and skin basal cell tumors in male Sprague-Dawley rats, adrenal cortical carcinomas in female Sprague-Dawley rats and hepatocellular adenomas and skin keratocanthomas in male Wistar rats.

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.

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 LD

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.

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.

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.

Chronic arsenic exposure causes cancers in multiple organs in humans. However, the mechanisms underlying arsenic-induced carcinogenesis remain obscure. Here, we examined whether chronic arsenite (As(III)) exposure promotes cell migration induced by heparin-binding EGF-like growth factor (HB-EGF) in human esophageal immortalized Het1A cells. When Het1A cells were exposed to 0.5 μM As(III) for 4 months, HB-EGF-induced migration was enhanced in As(III)-exposed Het1A cells compared to controls. To elucidate the mechanisms underlying the promotion of HB-EGF-induced migration by chronic exposure to As(III), we compared ERK phosphorylation between As(III)-exposed and control Het1A cells and found that HB-EGF-induced ERK phosphorylation was enhanced in the As(III)-exposed cells. We next measured mRNA levels of 88 genes related to cell cycle regulation. The results showed elevated cyclin D1 mRNA levels in As(III)-exposed Het1A cells. The inhibitors of ERK and cyclin D/Cdk4 markedly suppressed HB-EGF-induced upregulation of cyclin D1 and the migration of Het1A cells, respectively, suggesting that cyclin D1 is located downstream of ERK and is required for HB-EGF-induced migration of Het1A cells. Collectively, these findings indicate that the promotion of HB-EGF-induced migration of Het1A cells chronically exposed to submicromolar As(III) might be caused by increased expression of cyclin D1 mediated by enhanced activation of the ERK pathway.

To understand the toxic mechanism of ammonia and identify effective biomarkers on the oxidative stress for the fish Carassius auratus red var., acute and chronic toxicity tests were conducted. The 96-h LC50 of total ammonia nitrogen (TAN) for C. auratus was 135.4 mg L−1, the corresponding unionized ammonia (NH3) concentration was 1.5 mg L−1. The activities of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), glutathione-peroxidase (GSH-Px) and glutathione (GSH) showed an increase with a subsequent falling, while the malondialdehyde (MDA) increased during the chronic test. The SOD, MDA, and GSH could be effective biomarkers to evaluate the TAN oxidative stress, the maximum acceptable toxicant concentration (MATC) was 11.3 mg L−1 for TAN. To our knowledge, this is the first study to propose biomarkers to evaluate potential environmental risk and establish a risk threshold for TAN in C. auratus.

We determined the effect of acute and chronic toxicity of cadmium (Cd) on Pseudodiaptomus annandalei, according to their developmental and reproductive stages. Firstly, to estimate the 50% lethal concentration (LC50), acute exposure of nauplii and copepodids to 20, 40, 80, 150, and 300 μg/L of Cd was tested, and the effects of 5 μg/L and 40 μg/L of Cd on copepod developmental rate was done. Female lifespan and number of nauplii produced were compared. Secondly, one generation of copepod was exposed to dissolved (WCd) and dietary (DCd) Cd, and sex-specific Cd uptake and population density were estimated. 96 h LC50 was 40 μg/L Cd for nauplii and 120 μg/L Cd for copepodids. Duration of copepod development was 3.5 days and 5.5 days longer than the control when exposed to 5 μg/L and 40 μg/L of Cd, respectively. Female lifespan in both treatments were 9 and 8 days shorter than in the control, respectively. Total number of nauplii produced per female lifespan was 440 (control), 450 (5 μg/L Cd), and 365 (40 μg/L Cd). Cd uptake in copepods increased from nauplii to adults when exposed to dietary Cd and decreased when exposed to dissolved Cd. Dietary uptake of Cd was significantly higher in males than in females and Cd uptake from water was higher in males than in females, but not statistically significant. The total population of copepods were significantly affected by Cd. The toxic effects of Cd in copepods appear to depend on developmental stage, sex, duration and uptake route.