Study of Acute Toxicity of a New Veterinary Drug for Inttrammary Introduction

Preclinical studies of veterinary medicinal products are important and compulsory studies in the development of new dosage forms. The aim of preclinical research is to determine the toxic effect and therapeutic efficacy of the test substance-the future dosage form, its effect on the body\u27s basic systems, as well as the identification of possible side effects.This work is part of the research on the development of the composition and technology of the veterinary drug - a solution for intramammary application, conventionally called "Argocide", intended for the treatment of mastitis in cattle.A study of the acute toxicity of the intramammary veterinary drug was carried out in experiments on white rats of both sexes, according to the requirements for potential medicines. The establishment of the value of the average lethal dose (LD50) of the veterinary drug "Argocide" with intramuscular single administration to white mature rats is impossible due to the absence of animal death even when the drug is administered at doses exceeding 5.0 ml/kg. This experiment allows the veterinary preparation "Argocide" to be classified as practically non-toxic compounds (V class).The analysis of the results of the conducted studies indicates the relative harmlessness of the potential drug for veterinary medicine and allows us to foresee that the "Argocide" preparation can be classified as low-risk substances, which justifies the expediency of its further study and introduction into practice

Factors modifying the risk for developing acute skin toxicity after whole-breast intensity modulated radiotherapy

Background: After breast-conserving radiation therapy most patients experience acute skin toxicity to some degree. This may impair patients' quality of life, cause pain and discomfort. In this study, we investigated treatment and patient-related factors, including genetic polymorphisms, that can modify the risk for severe radiation-induced skin toxicity in breast cancer patients. Methods: We studied 377 patients treated at Ghent University Hospital and at ST.-Elisabeth Clinic and Maternity in Namur, with adjuvant intensity modulated radiotherapy (IMRT) after breast-conserving surgery for breast cancer. Women were treated in a prone or supine position with normofractionated (25 x 2 Gy) or hypofractionated (15 x 2.67 Gy) IMRT alone or in combination with other adjuvant therapies. Patient-and treatment-related factors and genetic markers in regulatory regions of radioresponsive genes and in LIG3, MLH1 and XRCC3 genes were considered as variables. Acute dermatitis was scored using the CTCAEv3.0 scoring system. Desquamation was scored separately on a 3-point scale (0-none, 1-dry, 2-moist). Results: Two-hundred and twenty patients (58%) developed G2+ dermatitis whereas moist desquamation occurred in 56 patients (15%). Normofractionation (both p = D (p = 0.001 and p = 0.043) and concurrent hormone therapy (p = 0.001 and p = 0.037) were significantly associated with occurrence of acute dermatitis and moist desquamation, respectively. Additional factors associated with an increased risk of acute dermatitis were the genetic variation in MLH1 rs1800734 (p=0.008), smoking during RT (p = 0.010) and supine IMRT (p = 0.004). Patients receiving trastuzumab showed decreased risk of acute dermatitis (p < 0.001). Conclusions: The normofractionation schedule, supine IMRT, concomitant hormone treatment and patient related factors (high BMI, large breast, smoking during treatment and the genetic variation in MLH1 rs1800734) were associated with increased acute skin toxicity in patients receiving radiation therapy after breast-conserving surgery. Trastuzumab seemed to be protective

Development and validation of Triticum phytobiological method as an alternative procedure for investigating in vivo acute toxicity on mice

The goal of this study was to validate an alternative method for determining in vivo acute toxicity using vegetal material instead of laboratory animals, starting from the phytobiological method known also as the Triticum technique. We set out to demonstrate that vegetal cells have similar sensitivity to some toxic agents as animal cells, in which case a statistical correlation could be established. A series of new compounds synthesized by the Romanian National Institute for Chemical Pharmaceutical Research and Development as potential β3 adrenergic receptors agonists were tested for their acute toxicity using classic animal exposure models, before investigating possible anti-diabetic and anti-obesity effects. We then determined whether similar conclusions might be reached exposing vegetal material to the same agents. We successfully demonstrated that plants are affected in a very similar way as animals when exposed to some potentially toxic agents, providing new possibilities for ending unethical animal experiments

Antioxidant,antimicrobial and toxicological properties of Schinus molle L. essential oils

Ethnopharmacological relevance: Schinus molle L. has been used in folk medicine as antibacterial, antiviral, topical antiseptic, antifungal, antioxidant, anti-inflammatory, anti-tumoural as well as antispasmodic and analgesic; however, there are few studies of pharmacological and toxicological properties of S. molle essential oils. Aim of the study: The aim of this study was to evaluate the antioxidant and antimicrobial activities of S. molle leaf and fruit essential oils, correlated with their chemical composition and evaluate their acute toxicity. Materials and methods: The chemical composition of S. molle leaf and fruit essential oils were evaluated by GC-FID and GC-MS. Antioxidant properties were determined using the 2,2-diphenyl-1-picryl-hydrazyl (DPPH) free radical and β-carotene/linoleic acid methods. Antimicrobial properties were evaluated by the agar disc diffusion method and minimal inhibitory concentration assay. Toxicity in Artemia salina and acute toxicity with behavioural screening in mice were evaluated. Results: The dominant compounds found in leaf and fruit essential oils (EOs) were monoterpene hydrocarbons, namely -phellandrene, β-phellandrene, β-myrcene, limonene and α-pinene. EOs showed low scavenging antioxidant activity by the DPPH free radical method and a higher activity by the β-carotene/linoleic acid method. Antimicrobial activity of EOs was observed for Gram+, Gram– pathogenic bacteria and food spoilage fungi. EOs showed cytotoxicity for Artemia salina and lower toxicity in Swiss mice. Conclusions: The result showed that EOs of leaves and fruits of S. molle demonstrated antioxidant and antimicrobial properties, suggesting their potential use in food or pharmaceutical industries

The Effect of Natural Dissolved Organic Carbon on the Acute Toxicity of Copper to Larval Freshwater Mussels (\u3cem\u3eGlochidia\u3c/em\u3e)

The present study examined the effect of dissolved organic carbon (DOC), both added and inherent, on Cu toxicity in glochidia, the larvae of freshwater mussels. Using incremental additions of natural DOC concentrate and reconstituted water, a series of acute copper toxicity tests were conducted. An increase in DOC from 0.7 to 4.4 mg C/L resulted in a fourfold increase (36–150 μg Cu/L) in the 24-h median effective concentration (EC50) and a significant linear relationship (r2=0.98, p=0.0008) between the DOC concentration and the Cu EC50 of Lampsilis siliquoidea glochidia. The ameliorating effect of added DOC on Cu toxicity was confirmed using a second mussel species, the endangered (in Canada) Lampsilis fasciola. The effect of inherent (i.e., not added) DOC on Cu toxicity was also assessed in eight natural waters (DOC 5–15 mg C/L). These experiments revealed a significant relationship between the EC50 and the concentration of inherent DOC (r2=0.79, p=0.0031) with EC50s ranging from 27 to 111 μg Cu/L. These laboratory tests have demonstrated that DOC provides glochidia with significant protection from acute Cu toxicity. The potential risk that Cu poses to mussel populations was assessed by comparing Cu and DOC concentrations from significant mussel habitats in Ontario to the EC50s. Although overall mean Cu concentration in the mussel’s habitat was well below the acutely toxic level given the concentration of DOC, episodic Cu releases in low DOC waters may be a concern for the recovery of endangered freshwater mussels. The results are examined in the context of current Cu water quality regulations including the U.S. Environmental Protection Agency’s (U.S. EPA) biotic ligand model

Acute toxicity of synyhetic resin effluent to African Catfish, Clarias gariepinus [BURCHELL, 1822].

Aquatic pollution as a field has gained a lot of attention over the decades majorly because of the vital role the aquatic environment plays in the human lifecycle. Indusrial wastewaters are often generated and discharged into the environment without treatment. Toxicity of effluents from Synythetic Resin production plant were evaluated in this study. Acute toxicity (96-h LC50) was evaluated using 0.23, 0.31, 0.35 and 0.39 mg/L of the effluent in a renewal bioassay procedure. Physicochemical parameters of the effluent were also evaluated, the values obtained for lead, cyanide, total suspened solid, total hadness, total dissolved solids and alkalinity were higher than the Federal Environmental Protection Agency standard specification for effluent discharge into aquatic environment and as such contributed to the effluent's toxicity. Mortality increased as the concentrations of the effluent increases and 0.355mg/L was obtained as LC50. The research eventually revealed that the synthetic resin effluent has a high level of toxicity to catfish. Deleterious effects such as biomagnification and other abberations may occur in man if exposed to substantial concentration of the effluent

A new sighting study for the fixed concentration procedure to allow for gender differences

The fixed concentration procedure (FCP) has been proposed as an alternative to the median lethal concentration (LC50) test (organisation for economic co-operation and development (OECD) test guideline [TG] 403) for the assessment of acute inhalation toxicity. The FCP tests animals of a single gender (usually females) at a number of fixed concentration levels in a sequential fashion. It begins with a sighting study that precedes the main FCP study and is used to determine the main study starting concentration. In this paper, we propose a modification to the sighting study and suggest that it should be conducted using both male and female animals, rather than just animals of a single gender. Statistical analysis demonstrates that, when females are more sensitive, the new procedure is likely to give the same classification as the original FCP, whereas, if males are more sensitive, the new procedure is much less likely to lead to incorrect classification into a less toxic category. If there is no difference in the LC50 for females and males, the new procedure is slightly more likely to classify into a more stringent class than the original FCP. Overall, these results show that the revised sighting study ensures gender differences in sensitivity do not significantly impact on the performance of the FCP, supporting its use as an alternative test method for assessing acute inhalation toxicity

The microbiotest battery as an important component in the assessment of snowmelt toxicity in urban watercourses—preliminary studies

The aim of the study was to use a battery of biotests composed of producers (Selenastrum capricornutum, Sorghum saccharatum, Lepidium sativum, and Sinapis alba), consumers (Thamnocephalus platyurus), and decomposers (Tetrahymena thermophila) to evaluate the toxicity of snowmelt and winter storm water samples. The toxicity of the samples collected in the winter period December to February (2010–2011), in one of the largest agglomerations in Poland, the city of Lodz, was compared to that of storm water samples taken under similar conditions in June. The most toxic snowmelt samples were found to be high acute hazard (class IV), while the remaining samples were rated as slight acute hazard (class II). L. sativum (in the Phytotox test) was the most sensitive test organism, giving 27 % of all toxic responses, followed by S. capricornutum with 23 % of all responses. T. thermophila was the least sensitive, with only 2 % of all toxic responses. The greatest range of toxicity was demonstrated by samples from the single family house catchment: no acute hazard (class I) to high acute hazard (class IV

The surface reactivity of iron oxide nanoparticles as a potential hazard for aquatic environments: A study on Daphnia magna adults and embryos

open5noNano-ecotoxicology is extensively debated and nanomaterial surface reactivity is an emerging topic. Iron oxide nanoparticles are widely applied, with organic or inorganic coatings for stabilizing their suspensions. Surface active maghemite nanoparticles (SAMNs) are the unique example of naked iron oxide displaying high colloidal and structural stability in water and chemical reactivity. The colloidal behavior of SAMNs was studied as a function of the medium salinity and protocols of acute and chronic toxicity on Daphnia magna were consequently adapted. SAMN distribution into the crustacean, intake/depletion rates and swimming performances were evaluated. No sign of toxicity was detected in two model organisms from the frst trophic level (P. subcapitata and L. minor). In D. magna, acute EC50 values of SAMN was assessed, while no sub-lethal efects were observed and the accumulation of SAMNs in the gut appeared as the sole cause of mortality. Fast depuration and absence of delayed efects indicated no retention of SAMNs within the organism. In spite of negligible toxicity on D. magna adults, SAMN surface reactivity was responsible of membrane bursting and lethality on embryos. The present study ofers a contribution to the nascent knowledge concerning the impact of nanoparticle surface reactivity on biological interfaces.openMassimiliano Magro, Marco De Liguoro, Eleonora Franzago, Davide Baratella, Fabio VianelloMagro, Massimiliano; DE LIGUORO, Marco; Franzago, Eleonora; Baratella, Davide; Vianello, Fabi

Safety evaluation of Sapindus laurifolius leaf extract in Wistar rats

Objectives:The present work was aimed to study the phytochemical composition of the Sapindus laurifolius leaves andtoxicological effect of the Sapindus laurifolius leaf extract in a systematic way using Wistar albino rats as a model animal.Materials and Methods :The identification of phytoconstituents present in the leaf extract was performed using Highperformance thin layer chromatography (HPTLC). In toxicity studies, the acute oral toxicity study was conducted as per theguidelines of Organization for Economic Co-operation and Development (OECD 423 Acute Toxic Class Method) for testingof chemicals. In repeated dose 28-day oral toxicity study (OECD 407), methanolic leaf extract administered at the dose of 50,200 and 800 mg/kg BWand limit dose of 1000 mg/kg BW.Results: Saponins, flavanoids, glycosides and bitter principles were the major phytoconstituents identified. In acute toxicitystudy, the LD cut-off values were found to be more than 2g/kg in leaf extract. In repeated dose 28-day oral toxicity, significant 50(P<0.05) increase in AST, ALT, BUN and creatinine, significant (P<0.05) increase in total protein was noticed. Thehistopathological changes confined to liver, kidney and intestine, revealed mild to moderate hepatotoxicity, severenephrotoxicity and increased goblet cell activity. The changes were found to correlate with increased dose of leaf extract.Conclusion:The phytochemical analysis of Sapindus laurifolius revealed the presence of saponins, glycosides, flavonoidsand bitter principles.The acute oral toxicity study of S. laurifolius methanolic leaf extract in rats resulted in no toxicity even atthe highest dose, but in repeated 28-day oral toxicity study revealed mild to moderate hepatotoxicity, severe nephrotoxicityand intestinal damage