Gill alterations of whiteleg shrimp (Litopenaeus vannamei) exposed to cadmium under different experimental salinities.

BACKGROUND: Heavy metals are one of the most important environmental pollutants in marine coastal ecosystems. Cadmium is a heavy metal that enters to marine environments via industrial wastes and oil production activities. OBJECTIVES: This study were done to determine the toxicity of cadmium to Litopenaeus vannamei and to evaluate the histological changes in gill tissues after exposure to sublethal concentrations of cadmium at different salinities. METHODS: For this reason, toxicity test was done to determine the lethal concentration (LC50) of cadmium for whiteleg shrimp. According to the calculated LC50 amount, sublethal doses of cadmium were used to determine its histological effects in different salinity during 2 weeks exposing period. RESULTS: LC50 of cadmium for 96 h for whiteleg shrimp was 6.56 mg/L. Histological alterations in the gill were observed in L. vannamei after 14 days exposure to different concentrations of cadmium and salinity. Histopathological index was increased in a dose-dependent manner. CONCLUSION: Our findings showed that doses lower than 2 mg/L have repairable effects on gill structure, but the concentration of 2 mg/L cadmium leaves irreparable and destructive effects on the gill tissue.

Taking it with a grain of salt: tolerance to increasing salinization in Culex pipiens (Diptera: Culicidae) across a low-lying delta.

BACKGROUND: Salinity, exacerbated by rising sea levels, is a critical environmental cue affecting freshwater ecosystems. Predicting ecosystem structure in response to such changes and their implications for the geographical distribution of arthropod disease vectors requires further insights into the plasticity and adaptability of lower trophic level species in freshwater systems. Our study investigated whether populations of the mosquito Culex pipiens, typically considered sensitive to salt, have adapted due to gradual exposure. METHODS: Mesocosm experiments were conducted to evaluate responses in life history traits to increasing levels of salinity in three populations along a gradient perpendicular to the North Sea coast. Salt concentrations up to the brackish-marine transition zone (8 g/l chloride) were used, upon which no survival was expected. To determine how this process affects oviposition, a colonization experiment was performed by exposing the coastal population to the same concentrations. RESULTS: While concentrations up to the currently described median lethal dose (LD50) (4 g/l) were surprisingly favored during egg laying, even the treatment with the highest salt concentration was incidentally colonized. Differences in development rates among populations were observed, but the influence of salinity was evident only at 4 g/l and higher, resulting in only a 1-day delay. Mortality rates were lower than expected, reaching only 20% for coastal and inland populations and 41% for the intermediate population at the highest salinity. Sex ratios remained unaffected across the tested range. CONCLUSIONS: The high tolerance to salinity for all key life history parameters across populations suggests that Cx. pipiens is unlikely to shift its distribution in the foreseeable future, with potential implications for the disease risk of associated pathogens.

Enantioselective toxicity of the neonicotinoid dinotefuran on honeybee (Apis mellifera) larvae.

The threat of neonicotinoids to insect pollinators, particularly honeybees (Apis mellifera), is a global concern, but the risk of chiral neonicotinoids to insect larvae remains poorly understood. In the current study, we evaluated the acute and chronic toxicity of dinotefuran enantiomers to honeybee larvae in vitro and explored the mechanism of toxicity. The results showed that the acute median lethal dose (LD50) of S-dinotefuran to honeybee larvae was 30.0 µg/larva after oral exposure for 72 h, which was more toxic than rac-dinotefuran (92.7 µg/larva) and R-dinotefuran (183.6 µg/larva). Although the acute toxicity of the three forms of dinotefuran to larvae was lower than that to adults, chronic exposure significantly reduced larval survival, larval weight, and weight of newly emerged adults. Analysis of gene expression and hormone titer indicated that dinotefuran affects larval growth and development by interfering with nutrient digestion and absorption and the molting system. Analysis of hemolymph metabolome further revealed that disturbances in the neuroactive ligand-receptor interaction pathway and energy metabolism are the key mechanisms of dinotefuran toxicity to bee larvae. In addition, melatonin and vitellogenin are used by larvae to cope with dinotefuran-induced oxidative stress. Our results contribute to a comprehensive understanding of dinotefuran damage to bees and provide new insights into the mechanism of enantioselective toxicity of insecticides to insect larvae.

Toxicity comparison and risk assessment of two chlorinated organophosphate flame retardants (TCEP and TCPP) on Polypedates megacephalus tadpoles.

Tris(2-chloroethyl) phosphate (TCEP) and tris(1­chloro-2-propyl) phosphate (TCPP) are widely used as chlorinated organophosphate flame retardants (OPFRs) due to their fire-resistance capabilities. However, their extensive use has led to their permeation and pollution in aquatic environments. Using amphibians, which are non-model organisms, to test the toxic effects of OPFRs is relatively uncommon. This study examined the acute and chronic toxicity differences between TCEP and TCPP on Polypedates megacephalus tadpoles and evaluated the potential ecological risks to tadpoles in different aquatic environments using the risk quotient (RQ). In acute toxicity assay, the tadpole survival rates decreased with increased exposure time and concentrations, with TCEP exhibiting higher LC50 values than TCPP, at 305.5 mg/L and 70 mg/L, respectively. In the chronic assay, prolonged exposure to 300 µg/L of both substances resulted in similar adverse effects on tadpole growth, metamorphosis, and hepatic antioxidant function. Based on RQ values, most aquatic environments did not pose an ecological risk to tadpoles. However, the analysis showed that wastewater presented higher risks than rivers and drinking water, and TCPP posed a higher potential risk than TCEP in all examined aquatic environments. These findings provide empirical evidence to comprehend the toxicological effects of OPFRs on aquatic organisms and to assess the safety of aquatic environments.

Comparability of comparative toxicity: insect sensitivity to imidacloprid reveals huge variations across species but also within species.

Pesticides have been identified as major drivers of insect biodiversity loss. Thus, the study of their effects on non-pest insect species has attracted a lot of attention in recent decades. In general toxicology, the 'gold standard' to assess the toxicity of a substance is to measure mass-specific LD50 (i.e. median lethal dose per unit body mass). In entomology, reviews attempting to compare these data across all available studies are lacking. To fill this gap in knowledge, we performed a systematic review of the lethality of imidacloprid for adult insects. Imidacloprid is possibly the most extensively studied insecticide in recent times, yet we found that little is comparable across studies, owing to both methodological divergence and missing estimates of body mass. By accounting for body mass whenever possible, we show how imidacloprid sensitivity spans across an apparent range of approximately six orders of magnitude across insect species. Very high variability within species can also be observed owing to differences in exposure methods and observation time. We suggest that a more comparable and comprehensive approach has both biological and economic relevance. Ultimately, this would help to identify differences that could direct research towards preventing non-target species from being negatively affected.

Temperate Versus Arctic: Unraveling the Effects of Temperature on Oil Toxicity in Gammarids.

Shipping activities are increasing with sea ice receding in the Arctic, leading to higher risks of accidents and oil spills. Because Arctic toxicity data are limited, oil spill risk assessments for the Arctic are challenging to conduct. In the present study, we tested if acute oil toxicity metrics obtained at temperate conditions reflect those at Arctic conditions. The effects of temperature (4 °C, 12 °C, and 20 °C) on the median lethal concentration (LC50) and the critical body residue (CBR) of the temperate invertebrate Gammarus locusta exposed to water accommodated fractions of a fuel oil were determined. Both toxicity metrics decreased with increasing temperature. In addition, data for the temperate G. locusta were compared to data obtained for Arctic Gammarus species at 4 °C. The LC50 for the Arctic Gammarus sp. was a factor of 3 higher than that for the temperate G. locusta at 4 °C, but its CBR was similar, although both the exposure time and concentration were extended to reach lethality. Probably, this was a result of the larger size and higher weight and total lipid content of Arctic gammarids compared to the temperate gammarids. Taken together, the present data support the use of temperate acute oil toxicity data as a basis for assessing risks in the Arctic region, provided that the effects of temperature on oil fate and functional traits (e.g., body size and lipid content) of test species are considered. As such, using the CBR as a toxicity metric is beneficial because it is independent of functional traits, despite its temperature dependency. To the best of our knowledge, the present study is the first to report CBRs for oil. Environ Toxicol Chem 2024;43:1627-1637. © 2024 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Preclinical Safety Assessment of Lepidium sativum L. Seed Extract and its Nanoparticles via Acute and Subacute Oral Administration.

BACKGROUND: Lepidium sativum (LS) seed extract has various pharmacological properties, such as antioxidant, hepatoprotective, and anticancer activities. However, the translation of L. sativum seed extract to the clinical phase is still tedious due to its bioavailability and stability issues. This problem can be solved by encapsulating it in a nanodelivery system to improve its therapeutic potency. METHODS: In this study, we have determined and compared the in vivo toxicity of ethanolic extracts of L. sativum seeds (EELS) and solid lipid nanoparticles (SLNs). To conduct toxicity (acute and subacute toxicity) assessments, EELS and SLNs were orally administered to Swiss albino mice. Animal survival, body weight, the weight of vital organs in relation to body weight, haematological profile, biochemistry profile, and histopathological alterations were examined. RESULTS: Animals administered with 2000 mg/kg and 5000 mg/kg in an acute toxicity study exhibited no toxicological symptoms regarding behaviour, gross pathology, and body weight. As per a study on acute toxicity, the LD50 (lethal dose) for SLNs and EELS was over 400 mg/kg and over 5000 mg/kg, respectively. When animals were given SLNs (50 and 100 mg/kg, orally) and EELS (250, 500, and 1000 mg/kg, orally) for 28 days, subacute toxicity study did not exhibit any clinical changes. There were no differences in weight gain, haematological parameters, or biochemical parameters compared to the control groups (p > 0.05). The organs of the treated animals showed no abnormalities in the histological analysis (liver, heart, kidney, and spleen). CONCLUSION: The result confirms ethanolic extracts of L. sativum seeds and their SLNs to not have harmful effects following acute and subacute administration to mice. For further studies, patents available on Lepidium may be referred for its preclinical and clinical applications.

Oral exposure to polystyrene nanoplastics altered the hypothalamic-pituitary-testicular axis role in hormonal regulation, inducing reproductive toxicity in albino rats.

BACKGROUND: Nanoplastics can be considered a novel contaminant for the environment because of their extensive applications in modern society, which represents a possible threat to humans. Nevertheless, the negative effect of polystyrene nanoplastics (PS-NPs) on male reproduction, fertility, and progeny outcomes is not well known. Thus, the aim of the present work was to calculate the median lethal dose (LD50) and investigate the consequences of exposure to PS-NPs (25 nm) on male reproductive toxicity. METHODS: This investigation first determined the LD50 of PS-NPs in male Wistar rats, and then in a formal study, 24 rats were distributed into three groups (n = 8): the control group; the low-dose group (3 mg/kg bw); and the high-dose group (10 mg/kg bw) of PS-NPs administered orally for 60 days. On the 50th day of administration, the fertility test was conducted. RESULTS: The LD50 was determined to be 2500 mg/kg. PS-NP administration induced significant alternations, mainly indicating mortality in the high-dose group, a significant elevation in body weight gain, declined sperm quality parameters, altered reproductive hormonal levels, thyroid endocrine disruption, an alternation of the normal histo-architecture and the histo-morphometric analysis of the testes, and impaired male fertility. CONCLUSION: Altogether, the current findings provide novel perspectives on PS-NP general toxicity with specific reference to male reproductive toxicity.

A Validation of the Equivalence of the Cell-Based Potency Assay Method with a Mouse LD50 Bioassay for the Potency Testing of OnabotulinumtoxinA.

(1) Background: At present, the only potency assay approved in China for the in-country testing of botulinum toxin type A for injection products is the mouse bioassay (MBA). The Chinese market for neurotoxin products is rapidly expanding, but MBAs are subject to high variability due to individual variations in mice, as well as variations in injection sites, in addition to the limited number of batches tested for one MBA. Compared with the mLD50 method, the cell-based potency assay (CBPA) developed for the potency testing of onabotulinumtoxinA (BOTOX) by AbbVie not only does not use any experimental animals but also allows for significant time and cost savings. Due to the significant benefits conferred by the replacement of the mLD50 assay with CBPA in China, the CBPA method has been transferred, validated, and cross-validated to demonstrate the equivalence of the two potency methods. (2) Methods: The differentiated SiMa cells were treated with both BOTOX samples and the reference standard, and the cleaved SNAP25197 in the cell lysates was quantified using Chemi-ECL ELISA. A 4-PL model was used for the data fit and sample relative potency calculation. The method accuracy, linearity, repeatability, and intermediate precision were determined within the range of 50% to 200% of the labeled claim. A statistical equivalence of the two potency methods (CBPA and mLD50) was initially demonstrated by comparing the AbbVie CBPA data with NIFDC mLD50 data on a total of 167 commercial BOTOX lots (85 50U lots and 82 100U lots). In addition, six lots of onabotulinumtoxinA (three 50U and three 100U) were re-tested as cross-validation by these two methods for equivalence. (3) Results: The overall assay's accuracy and intermediate precision were determined as 104% and 9.2%, and the slope, R-square, and Y-intercept for linearity were determined as 1.071, 0.998, and 0.036, respectively. The repeatability was determined as 6.9%. The range with the acceptable criteria of accuracy, linearity, and precision was demonstrated as 50% to 200% of the labeled claim. The 95% equivalence statistic test using margins [80%, 125%] indicates that CBPA and mLD50 methods are equivalent for both BOTOX strengths (i.e., 50U and 100U). The relative potency data from cross-validation were within the range of ≥80% to ≤120%. (4) Conclusions: The CBPA meets all acceptance criteria and is equivalent to mLD50. The replacement of mLD50 with CBPA is well justified in terms of ensuring safety and efficacy, as well as for animal benefits.

Toxic effects of commercial grade indoxacarb and endosulfan on Gammarus kischineffensis (Schellenberg, 1937) (Crustacea: Amphipoda).

This study was designed to investigate the toxic effects of two frequently used commercial insecticides containing endosulfan and indoxacarb on a freshwater amphipod Gammarus kischineffensis. In this context, the 24, 48, 72 and 96 h LC50 values of these pesticides were determined for G. kischineffensis. Then the histopathological effects of these pesticides on the gill tissues of this species were evaluated. At the end of the study, the 96 h LC50 values of commercial-grade endosulfan and indoxacarb for G. kischineffensis were determined as 1.861 µg L-1 and 20.212 mg L-1, respectively. Histopathologically, the most common histopathological alterations in individuals exposed to sublethal concentrations of commercial-grade endosulfan and indoxacarb were pillar cell hypertrophy resulting in atrophy of the hemocoelic space and hemocytic infiltration. Considering these results, it can be said that commercial-grade endosulfan is extremely and indoxacarb is slightly toxic to G. kischineffensis.

Biocontrol potential of six Heterorhabditis bacteriophora strains isolated in the Azores Archipelago.

Entomopathogenic nematodes (EPNs) are closely associated with Popillia japonica and potentially used as their biological control agents, although field results proved inconsistent and evoked a continual pursuit of native EPNs more adapted to the environment. Therefore, we surveyed the Azorean Archipelago to isolate new strains of Heterorhabditis bacteriophora and to evaluate their virulence against the model organism Galleria mellonella under laboratory conditions. Six strains were obtained from pasture and coastal environments and both nematode and symbiont bacteria were molecularly identified. The bioassays revealed that Az172, Az186, and Az171 presented high virulence across the determination of a lethal dose (LD50) and short exposure time experiments with a comparable performance to Az29. After 72 hours, these virulent strains presented a mean determination of a lethal dose of 11 infective juveniles cm-2, a lethal time (LT50) of 34 hours, and achieved 40% mortality after an initial exposure time of only 60 minutes. Az170 exhibited an intermediate performance, whereas Az179 and Az180 were classified as low virulent strains. However, both strains presented the highest reproductive potential with means of 1700 infective juveniles/mg of larvae. The bioassays of the native EPNs obtained revealed that these strains hold the potential to be used in biological control initiatives targeting P. japonica because of their high virulence and locally adapted to environmental conditions.

Comparative analysis of Streptococcus agalactiae serotypes Ia and II isolates from China and Pakistan in a murine model: A focus on pathogenesis and immune response.

Bovine mastitis, caused by Streptococcus agalactiae (Group B Streptococcus; GBS), poses significant economic challenges to the global dairy industry. Mouse models serves as valuable tools for assessing GBS-induced infections as an alternative to large animals. This study aimed to investigate the LD50 dose, organ bacterial load, and quantification of peritoneal leukocyte populations for GBS serotypes Ia and II isolates from China and Pakistan. Additionally, we measured indicators such as lactoferrin, albumin, and myeloperoxidase (MPO) activity. Pro-inflammatory cytokines (TNF-α, IL-1ß, IL-6, and IL-2) and anti-inflammatory cytokines (IL-10 and TGF-ß) in serum and tissue samples were evaluated using ELISA and qPCR, respectively. BALB/c mice (4 mice per group) received individual intraperitoneal injections of 100 µl containing specific bacterial inoculum concentrations (ranging from 105 to 109 CFU per mouse) of Chinese and Pakistani GBS isolates (serotypes Ia and II). Control groups received 100 µL of sterile PBS. Results revealed that the LD50 bacterial dose causing 50 % mortality in mice was 107 CFU. The highest bacterial load in all experimental groups was quantified in the peritoneum, followed by blood, mammary gland, liver, spleen, lungs, and brain. The most significant bacterial dissemination was observed in mice inoculated with Pakistani serotype Ia at 24 h, with a subsequent notable decline in bacterial counts at day 3. Notably, infection with Pakistani serotype Ia showed a trend of increased total leukocyte counts, significantly higher than Pakistani serotype II, Chinese Serotype Ia, and Chinese serotype II. A substantial influx of neutrophils and lymphocytes was observed in response to all tested serotypes, with Pakistani serotype Ia inducing a significantly higher influx compared to other groups (Pakistani serotype II, Chinese serotype Ia, and Chinese serotype II). Furthermore, TNF-α, IL-1ß, IL-2, and IL-6 expressions were significantly increased in mice one day after infection with the Pakistani serotype Ia. Compared to mice infected with the Pakistani serotype II, Chinese Serotype Ia, and Chinese serotype II, those infected with the Pakistani serotype Ia isolate exhibited the highest production of IL-10 and TGF-ß, along with significantly increased concentrations of lactoferrin, albumin, and MPO. These findings suggest that the persistence and severity of infection caused by the Pakistani serotype Ia may be linked to its ability to spread to deeper tissues. This study enhances our understanding of the clinical characteristics of bovine mastitis caused by S. agalactiae in China and Pakistan.

Effects of ivermectin on development of Calliphora vicina, Robineau-Desvoidy 1830 (Diptera, Calliphoridae).

Ivermectin is one of the most widely used drugs for parasite control. Previous studies have shown a reduction in the abundance and diversity of "non-target" coprophilous organisms due to the presence of ivermectin (IVM) in bovine faecal matter (FM). Due to its breadth of behavioural habits, Calliphora vicina is a suitable dipteran species to evaluate the effects of IVM in FM. The aim of this work was to evaluate the effect of five concentrations of IVM in FM (3000, 300, 100, 30, and 3 ng/g) on the development of C. vicina. The following endpoints were evaluated: survival (between the first larval stage and emergence of new adults), larval development times to pupation and pupation times to adult, and adult emergence (% sex) and LC50. Sampling was performed from larval hatching at 60 and 120 min and at 3, 4, 5, and 12 h, and every 24 h specimens were weighed until pupae were observed. Data were analysed by ANOVA using a non-parametric Kruskal-Wallis test and as a function of elapsed development time and accumulated degree hours (ADH). Mortality at 3000 and 300 ng/g was 100% and 97%, respectively. There were statistically significant delays in adult emergence time (p = 0.0216) and in the ADH (p = 0.0431) between the control group (C) and 100 ng/g. The LC50 was determined at 5.6 ng/g. These results demonstrate the lethal and sub-lethal effects of IVM on C. vicina, while highlighting the usefulness of this species as a bioindicator for ecotoxicological studies.

Acute toxicity appraisal of Saussurea heteromalla extract and development of its chemotherapeutic herbal dosage form.

Ethnopharmacological relevance of Saussurea species for anti-cancer compounds instigated us to develop chemotherapeutic herbal tablets. This study was an ongoing part of our previous research based on the scientific evaluation of Saussurea heteromalla (S. heteromalla) for anti-cancer lead compounds. In the current study, S. heteromalla herbal tablets (500 /800 mg) were designed and evaluated for anti-cancer activity. Arctigenin was found as a bioactive lead molecule with anti-cancer potential for cervical cancer. The in vitro results on the HeLa cell line supported the ethnopharmacological relevance and traditional utilization of S. heteromalla and provided the scientific basis for the management of cervical cancer as proclaimed by traditional practitioners in China. LD50 of the crude extract was established trough oral acute toxicity profiling in mice, wherein the minimum lethal dose was noticed as higher than 1000 mg/kg body weight orally. Chromatographic fingerprint analysis ensured the identity and consistency of S. heteromalla in herbal tablets in terms of standardization of the herbal drug. About 99.15% of the drug (S. heteromalla crude extract) was recovered in herbal tablets (RSD: 0.45%). In vitro drug release profile was found to be more than 87% within 1 h, which was also correlated with different mathematical kinetic models of drug release (r2 = 0.992), indicating that drug release from matrix tablets into the blood is constant throughout the delivery. The dosage form was found stable after an accelerated stability parameters study which may be used for anti-cervical cancer therapy in the future, if it qualifies successful preclinical investigation parameters.

Proteomic analysis and lethality of the venom of Aegaeobuthus nigrocinctus, a scorpion of medical significance in the Middle East.

The scorpion Aegaeobuthus nigrocinctus inhabits areas in Turkey and the Levant region of the Middle East where severe/lethal envenomings have been reported. Previous research indicated its extreme venom lethality to vertebrates and distinct envenomation syndrome. We report on the composition of A. nigrocinctus venom from Lebanese specimens using nESI-MS/MS, MALDI-TOF MS, SDS-PAGE and RP-HPLC. Venom lethality in mice was also assessed (LD50 = 1.05 (0.19-1.91) mg/kg, i.p), confirming A. nigrocinctus venom toxicity from Levantine populations. Forty-seven peaks were resolved using RP-HPLC, 25 of which eluted between 20 and 40 % acetonitrile. In reducing SDS-PAGE, most predominant components were <10 kDa, with minor components at higher molecular masses of 19.6, 26.1, 46.3 and 57.7 kDa. MALDI-TOF venom fingerprinting detected 20 components within the 1,000-12,000 m/z range. Whole venom 'shotgun' bottom-up nLC-MS/MS approach, combined with in-gel tryptic digestion of SDS-PAGE bands, identified at least 67 different components belonging to 15 venom families, with ion channel-active components (K+ toxins (23); Na+ toxins (20); Cl- toxins (2)) being predominant. The sequence of a peptide (named α-KTx9.13) ortholog to Leiurus hebraeus putative α-KTx9.3 toxin was fully determined, which exhibited 81-96 % identity to other members of the α-KTx9 subfamily targeting Kv1.x and Ca2+-activated K+ channels. Chlorotoxin-like peptides were also identified. Our study underscores the medical significance of A. nigrocinctus in the region and reveals the potential value of its venom components as lead templates for biomedical applications. Future work should address whether available antivenoms in the Middle East are effective against A. nigrocinctus envenoming in the Levant area.

Bioproduction of yeast single cell oil with acute oral toxicity study intended for edible oil application.

Human nutrition and health rely on edible oils. Global demand for edible oils is expanding, necessitating the discovery of new natural oil sources subjected to adequate quality and safety evaluation. However, in contrast to other agricultural products, India's edible oil supply is surprisingly dependent on imports. The microbial oil is generated by fermentation of oleaginous yeast Rhodotorula mucilaginosa IIPL32 MTCC 25056 using biodiesel plant byproduct crude glycerol as a fermentable carbon source. Enriched with monounsaturated fatty acid, nutritional indices mapping based on the fatty acid composition of the yeast SCO, suggested its plausible use as an edible oil blend. In the present study, acute toxicity evaluation of the yeast SCO in C57BL/6 mice has been performed by randomly dividing the animals into 5 groups with 50, 300, 2000, and 5000 mg/Kg yeast SCO dosage, respectively, and predicted the median lethal dose (LD50). Detailed blood biochemistry and kidney and liver histopathology analyses were also reported. The functions of the liver enzymes were also evaluated to check and confirm the anticipated toxicity. To determine cell viability and in vitro biocompatibility, the 3T3-L1 cell line and haemolysis tests were performed. The results suggested the plausible use of yeast SCO as an edible oil blend due to its non-toxic nature in mice models.

Short-term immunotoxicity induced by florpyrauxifen-benzyl herbicide exposure in the spleen of male albino mice.

Florpyrauxifen-benzyl (FPB) is a new arylpicolinate systemic herbicide that has been used to control or suppress the majority of herbicide-resistant biotype weeds in rice. To our knowledge, the impact of FPB on the immune system remains undetected thus far. Hence, this work aimed to address the toxic effects of FPB and the possible related mechanisms on the spleen of exposed mice. Initially, an acute toxicological test was performed to ascertain the median lethal dose (LD50) of FPB for 24 h which was found to be 371.54 mg/kg b.wt. For mechanistic evaluation of FPB toxicity, three sublethal doses (1/20th, 1/10th, and 1/5th LD50) were orally administered to mice for 21 consecutive days. Changes in spleen relative weight, oxidative status, apoptotic and inflammatory markers, histopathological alterations were evaluated. Following the FPB exposure, significant (p < 0.05) decline in spleen index, apoptotic features, histolopathological changes were observed. Additionally, excessive oxidative stress in spleen tissues was monitored by downregulating antioxidant enzymes and upregulating the oxidant parameters. Furthermore, exposure to FPB resulted in notable activation of the NF-қB signaling pathway, accompanied by elevated levels of pro-inflammatory cytokines (namely, IL-1ß and TNF-α) as well as CD3 and CD19 levels have decreased significantly in spleen tissues. Collectively, FPB exposure exhibited apoptosis, oxidative stress, immunosuppression, and inflammatory response in a dose-dependent manner, leading to spleen tissue damage and immunotoxicity. Further studies on FPB is recommended to outstand its hazards on ecosystems.

Assessment of the in vitro acaricidal activity of Bravecto® (fluralaner) and a proposed orange oil-based formulation vehicle for the treatment of Sarcoptes scabiei.

BACKGROUND: Sarcoptic mange is a serious animal welfare concern in bare-nosed wombats (Vombatus ursinus). Fluralaner (Bravecto®) is a novel acaricide that has recently been utilised for treating mange in wombats. The topical 'spot-on' formulation of fluralaner can limit treatment delivery options in situ, but dilution to a volume for 'pour-on' delivery is one practicable solution. This study investigated the in vitro acaricidal activity of Bravecto, a proposed essential oil-based diluent (Orange Power®), and two of its active constituents, limonene and citral, against Sarcoptes scabiei. METHODS: Sarcoptes scabiei were sourced from experimentally infested pigs. In vitro assays were performed to determine the lethal concentration (LC50) and survival time of the mites when exposed to varying concentrations of the test solutions. RESULTS: All compounds were highly effective at killing mites in vitro. The LC50 values of Bravecto, Orange Power, limonene and citral at 1 h were 14.61 mg/ml, 4.50%, 26.53% and 0.76%, respectively. The median survival times of mites exposed to undiluted Bravecto, Orange Power and their combination were 15, 5 and 10 min, respectively. A pilot survival assay of mites collected from a mange-affected wombat showed survival times of < 10 min when exposed to Bravecto and Orange Power and 20 min when exposed to moxidectin. CONCLUSIONS: These results confirm the acaricidal properties of Bravecto, demonstrate acaricidal properties of Orange Power and support the potential suitability of Orange Power and its active constituents as a diluent for Bravecto. As well as killing mites via direct exposure, Orange Power could potentially enhance the topical delivery of Bravecto to wombats by increasing drug penetration in hyperkeratotic crusts. Further research evaluating the physiochemical properties and modes of action of Orange Power and its constituents as a formulation vehicle would be of value.

Evaluation of in silico model predictions for mammalian acute oral toxicity and regulatory application in pesticide hazard and risk assessment.

The United States Environmental Protection Agency (USEPA) uses the lethal dose 50% (LD50) value from in vivo rat acute oral toxicity studies for pesticide product label precautionary statements and environmental risk assessment (RA). The Collaborative Acute Toxicity Modeling Suite (CATMoS) is a quantitative structure-activity relationship (QSAR)-based in silico approach to predict rat acute oral toxicity that has the potential to reduce animal use when registering a new pesticide technical grade active ingredient (TGAI). This analysis compared LD50 values predicted by CATMoS to empirical values from in vivo studies for the TGAIs of 177 conventional pesticides. The accuracy and reliability of the model predictions were assessed relative to the empirical data in terms of USEPA acute oral toxicity categories and discrete LD50 values for each chemical. CATMoS was most reliable at placing pesticide TGAIs in acute toxicity categories III (>500-5000 mg/kg) and IV (>5000 mg/kg), with 88% categorical concordance for 165 chemicals with empirical in vivo LD50 values ≥ 500 mg/kg. When considering an LD50 for RA, CATMoS predictions of 2000 mg/kg and higher were found to agree with empirical values from limit tests (i.e., single, high-dose tests) or definitive results over 2000 mg/kg with few exceptions.

Carbon Dioxide Toxicity to Zebra Mussels (Dreissena polymorpha) is Dependent on Water Chemistry.

Carbon dioxide (CO2) is gaining interest as a tool to combat aquatic invasive species, including zebra mussels (Dreissena polymorpha). However, the effects of water chemistry on CO2 efficacy are not well described. We conducted five trials in which we exposed adult zebra mussels to a range of CO2 in water with adjusted total hardness and specific conductance. We compared dose-responses and found differences in lethal concentration to 50% of organisms (LC50) estimates ranging from 108.3 to 179.3 mg/L CO2 and lethal concentration to 90% of organisms (LC90) estimates ranging from 163.7 to 216.6 mg/L CO2. We modeled LC50 and LC90 estimates with measured water chemistry variables from the trials. We found sodium (Na+) concentration to have the strongest correlation to changes in the LC50 and specific conductance to have the strongest correlation to changes in the LC90. Our results identify water chemistry as an important factor in considering efficacious CO2 concentrations for zebra mussel control. Additional research into the physiological responses of zebra mussels exposed to CO2 may be warranted to further explain mode of action and reported selectivity. Further study could likely develop a robust and relevant model to refine CO2 applications for a wider range of water chemistries. Environ Toxicol Chem 2024;43:1312-1319. Published 2024. This article is a U.S. Government work and is in the public domain in the USA. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.