Determination of lethal and mutation induction doses of gamma rays for gladiolus (Gladiolus grandifloras Hort.) genotypes.

Gladiolus is a highly allogamous flower plant, but owing to the prolonged juvenile phase, asexual propagation is preferred, which acts as a barrier for the induction of natural genetic variability in gladiolus. Therefore, the induced mutagenesis could be utilized for the creation of desirable genotypes, without altering their basic agronomic features. An analysis of the optimum doses of γ radiation for the induction of fruitful mutations could be achieved in short period of time, compared with the conventional method of breeding. The objectives of this study were to perform radiosensitivity tests on various gladiolus genotypes using different doses of gamma rays and to determine the optimal dose of radiation dose for obtaining the greatest number of mutants. The present experiment was carried out during the winter-spring seasons, for the four consecutive years of 2017-18, 2018-19, 2019-20, and 2020-21. The seven genotypes of gladiolus were exposed to seven doses of gamma rays (60Cobalt). Plants irradiated with radiation doses lower than 4.5 Kr (G1) had greater plant survivability than the higher doses of gamma rays (≥5.0 Kr). The radiation of G0 (0 Kr) result in highest plant survivability, while radiation dose of G6 (6.5 Kr) resulted lowest survivability. LD25 and BD50 for all the genotypes were achieved except for V5 and V7, similarly the median lethal doses (LD50) for V3 and V4 genotypes had been achieved. The highest flower blindness percent and percent abnormal plants were observed at G5 and G6 and between the 4.0 Kr (G1) and 5.5 Kr (G4) gamma ray doses, respectively. The flower colour mutation frequency was recorded highest in genotypes Tiger Flame at 5.0 Kr (V7G3), while the Flower colour mutation spectrum was identified between 4.0 Kr (G1) to 5.5 Kr (G4) in all the genotypes except for genotypes V5 and V7. For the generation of higher phenotypic variations, radiation dose between 4.0 Kr (G1) and 5.5 Kr (G4) were found the most prominent. Specifically the gamma rays radiation dose of 5.5 Kr (G4) resulted in the highest flower colour mutation frequency. These isolated mutant lines will broaden the gladiolus gene pool and support future gladiolus breeding experiments.

Lethal effects and sex-specific tolerance of copper and cadmium in the buff-tailed bumble bee.

Exposure to environmental pollutants, including trace metals, is a major driver of bee decline worldwide. While pesticides undergo standardised risk assessments (i.e., LD50) and the implementation of online databases, no such approaches exist for trace metals. Here, using acute oral exposure, we determined the LC50, LD50, and mass-standardised LD50 of copper and cadmium, essential and non-essential metals, respectively, in workers and males of the buff-tailed bumble bee. We also evaluated gut damage and sucrose consumption in workers post-exposure. Cadmium was more toxic than copper for workers at same doses, although both metals induced severe gut melanisation and reduced sucrose consumption at high concentrations. Males displayed higher tolerance to cadmium, but it was correlated to their higher body mass, emphasising the necessity for reporting mass-standardised LD50 for genuine sex comparisons in risk assessments. Our findings advocate for the establishment of databases focusing on metal-induced lethal effects on model bee species.

Cytotoxicity, pro-inflammatory cytokines gene expression and antioxidant activity of Acmella oleracea extract treated with active charcoal.

This work reports for the first time the evaluation of the cytotoxicity and inflammatory potential of Acmella oleracea extract treated with active charcoal in THP-1 monocytes. A. oleracea flower ethanolic extract was treated with 4% activated charcoal (TCEE). Later, THP-1 human monocyte cytotoxicity assay was performed using resazurin fluorometric method. Gene expression of inflammatory cytokines in THP-1 cells were evaluated through RT-PCR by ΔΔCt method using IL-1ß, IL-6, IL-8, and TNF genes primers. Finally, antioxidant assay was carried out with DPPH radical scavenging method. TCEE had a LD50 of 592.5 µg/mL and did not induce pro-inflammatory gene expression in THP-1 cells after 6 h of treatment. Lastly, TCEE (AA% of 69.4 ± 1.4%) and CEE (AA% of 63.0 ± 0.9%) showed moderate antioxidant activity. A. oleracea treated flower extract showed low cytotoxicity in THP-1 monocytes and does not induce inflammation in THP-1 cells, in addition to presenting antioxidant potential.

Honey bee larval toxicity study designs: Applicability of the current study protocols and endpoints as a predictor of pesticide hazard for pollinators.

The assessment of pesticide risks to bees in North America currently relies in part on Tier 1 honey bee laboratory toxicity studies to support the registration and registration review processes for crop protection chemicals. For immature stages, the studies follow two standardized test designs recommended by the Organization for Economic Cooperation (OECD), evaluating acute (seven-day single-dose, TG OECD 237) and chronic (22-day repeated-dose, GD OECD 239) toxicity in bee larvae. In this article, we aim to evaluate the current approach for generating and interpreting honey bee larval toxicity data, enhancing pesticide risk assessment for pollinators. First, by considering that the repeated-dose larval study covers all stages of honey bee brood development up to adult emergence, we compared endpoints (larval LD/ED50 and LC/EC50 values) from seven-day acute exposure studies with the 22-day chronic exposure studies. Our goal was to identify the study design offering greater sensitivity in assessing pesticide toxicity to immature bees. Our second objective involved analyzing available weight data from emerged adults and comparing it to survival endpoints (e.g., NOEL and LD50) to determine if the weight after adult emergence would accurately represent a sensitive indicator of pesticide effects on developing honey bees. Our analysis determined that the use of a single 22-day chronic exposure study adequately covers all immature stages and that the toxicity values based on cumulative dose are more accurate and representative measures of exposure for immature bees than using endpoints based on estimated daily doses. Furthermore, our analysis suggests that measuring the weight of emerged adults was a more sensitive indicator than mortality of treatment-related effects in 22% of the compounds included in our analysis. Here we also discuss the importance of standardized protocols for proper collection of weight after emergence and the need for further discussion on the relevance of this parameter at risk assessment scheme. Integr Environ Assess Manag 2024;00:1-11. © 2024 SETAC.

Transgenerational phenotypic responses to herbicide stress are more rapid than to shade and simulated herbivory in Arabidopsis.

Weeds in agricultural settings continually adapt to stresses from ecological and anthropogenic sources, in some cases leading to resistant populations. However, consequences of repeated sub-lethal exposure of these stressors on fitness and stress "memory" over generations remain poorly understood. We measured plant performance over a transgenerational experiment with Arabidopsis thaliana where plants were exposed to sub-lethal stress induced by the herbicides glyphosate or trifloxysulfuron, stresses from clipping or shading in either one (G1) or four successive generations (G1-G4), and control plants that never received stress. We found that fourth-generation (G4) plants that had been subjected to three generations of glyphosate or trifloxysulfuron stress produced higher post-stress biomass, seed weight, and rosette area as compared to that produced by plants that experienced stress only in the first generation (G1). By the same measure, clipping and shade were more influential on floral development time (shade) and seed weight (clipping) but did not show responsive phenotypes for vegetative metrics after multiple generations. Overall, we found that plants exhibited more rapid transgenerational vegetative "stress memory" to herbicides while reproductive plasticity was stressor dependent and similar between clipping/shade and anthropogenic stressors. Our study suggests that maternal plant stress memory aids next-generation plants to respond and survive better under the same stressors.

Topical Toxicity and Repellency Profiles of 17 Essential Oil Components against Insecticide-Resistant and Susceptible Strains of Adult Musca domestica (Diptera: Muscidae).

The house fly is a significant pest in agriculture and human health that is increasingly difficult to manage due to multiple limitations including resistance development. To explore alternative pesticides, the topical toxicity and repellency profiles of 17 essential oil components (EOCs) were evaluated against a resistant and a susceptible strain of house fly, Musca domestica L., using topical application and Y-tube olfactometers, respectively. Six of the most toxic EOCs based on the LD50 were further investigated against a susceptible strain of house fly. Thymol, (+)-pulegone, eugenol, and carvacrol were always the top four most toxic chemicals tested against the resistant house fly strain. Little to no resistance was observed to the top six EOCs based on the comparison of the results between resistant and susceptible house fly strains. P-Cymene, citronellic acid, R-(+)-limonene, linalool, γ-terpinene, estragole, and eugenol were repellent to adult house flies at certain concentrations while (-)-carvone and thymol were attractive to adult house flies. This screening of a wide variety of individual EOCs provides a stronger foundation of information for further research. This should encourage further investigation into the topical toxicity and repellency in field studies, which will provide more insight into the performance of biopesticides for house fly management and potential commercialization.

Point estimation of the 100p percent lethal dose using a novel penalised likelihood approach.

Estimation of the 100p percent lethal dose (LD100p) is of great interest to pharmacologists for assessing the toxicity of certain compounds. However, most existing literature focuses on the interval estimation of LD100p and little attention has been paid to its point estimation. Currently, the most commonly used method for estimating the LD100p is the maximum likelihood estimator (MLE), which can be represented as a ratio estimator, with the denominator being the slope estimated from the logistic regression model. However, the MLE can be seriously biased when the sample size is small, a common nature in such studies, or when the dose-response curve is relatively flat (i.e. the slope approaches zero). In this study, we address these issues by developing a novel penalised maximum likelihood estimator (PMLE) that can prevent the denominator of the ratio from being close to zero. Similar to the MLE, the PMLE is computationally simple and thus can be conveniently used in practice. Moreover, with a suitable penalty parameter, we show that the PMLE can (a) reduce the bias to the second order with respect to the sample size and (b) avoid extreme estimates. Through simulation studies and real data applications, we show that the PMLE generally outperforms the existing methods in terms of bias and root mean square error.

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.

Cholinergic Crisis with Normal Serum Cholinesterase Levels due to Excessive Galantamine Ingestion: A Case Report.

Galantamine is a cholinesterase inhibitor employed in Alzheimer's disease management. Cholinesterase inhibitors are associated with potential cholinergic side effects that, when severe, can result in cholinergic crises. Although crises induced by other cholinesterase inhibitors, such as distigmine and rivastigmine, have been reported, cases of galantamine-induced cholinergic crises remain undocumented. This study presents a case of cholinergic crisis triggered by galantamine overdose in an 89-year-old woman weighing 37 kg with Alzheimer's disease history, even though her serum cholinesterase levels were normal. The patient overdosed on 264 mg of galantamine, leading to rapid deterioration, marked by restlessness, tremors, sweating, diarrhea, pharyngeal gurgling, and severe hypoxia. Upon arrival at the emergency department, the patient exhibited pinpoint pupils, compromised airway, and low oxygen saturation, necessitating immediate intubation and transfer to the intensive care unit. After 72 h, the patient successfully recovered and was weaned off mechanical ventilation, maintaining normal serum cholinesterase levels. Animal studies suggest a lethal galantamine threshold of 3 to 6 mg/kg in humans. Unlike other cholinesterase inhibitors that typically reduce serum cholinesterase levels during cholinergic crises, galantamine appears to selectively inhibit acetylcholinesterase, possibly sparing butyrylcholinesterase. This selectivity may explain the normal serum cholinesterase levels.

Harnessing the Cross-Neutralisation Potential of Existing Antivenoms for Mitigating the Outcomes of Snakebite in Sub-Saharan Africa.

Over 32,000 individuals succumb to snake envenoming in sub-Saharan Africa (sSA) annually. This results from several factors, including a lack of antivenom products capable of neutralising the venoms of diverse snake species in this region. Most manufacturers produce polyvalent antivenoms targeting 3 to 16 clinically important snake species in sSA. However, specific products are unavailable for many others, especially those with a restricted geographic distribution. While next-generation antivenoms, comprising a cocktail of broadly neutralising antibodies, may offer an effective solution to this problem, given the need for their clinical validation, recombinant antivenoms are far from being available to snakebite victims. One of the strategies that could immediately address this issue involves harnessing the cross-neutralisation potential of existing products. Therefore, we assessed the neutralisation potency of PANAF-Premium antivenom towards the venoms of 14 medically important snakes from 13 countries across sSA for which specific antivenom products are unavailable. Preclinical assays in a murine model of snake envenoming revealed that the venoms of most snake species under investigation were effectively neutralised by this antivenom. Thus, this finding highlights the potential use of PANAF-Premium antivenom in treating bites from diverse snakes across sSA and the utility of harnessing the cross-neutralisation potential of antivenoms.

Evaluation of acute intravenous toxicity of HEPES: Is Good's buffer good and safe enough for clinical utilization in nuclear medicine?

OBJECTIVE: Good's buffer or HEPES has advantages over other buffers commonly used in radiopharmaceutical preparation as it exhibits significantly lower complexation tendency with metal ions. However, use of HEPES buffer for radiolabeling reactions, meant for clinical applications, has been underrated due to the non-availability of sufficient toxicity data. The objective of the present study is to find the evidences towards safety of intravenous administration of HEPES through systemic toxicological studies in small animal model to support its safe application for clinical exploitation. EXPERIMENTAL: A pilot study was performed to investigate the lethal dose of HEPES in female Sprague Dawley rats by administering seven different doses of HEPES solution (150 to 2000 mg/kg), through intravenous pathway. Similarly, for determining maximum tolerated dose (MTD), gradually increasing doses of HEPES (50 to 950 mg/kg) were administered in the same species via similar pathway. Various hematological and clinical pathological investigations were carried out in order to find out the safe administration dose of HEPES in rats. RESULTS: No mortality was observed up to 2000 mg/kg doses of HEPES. The doses beyond 300 mg/kg resulted few temporary adverse effects, though these were found to disappear within 4-5 days of dosing. CONCLUSION: The amount of HEPES to be administered during clinical intervention is usually much lower (typically 1-2.5 mg per kg of body weight of healthy adult) than the MTD determined in rat model during present report. Hence, the utilization of this buffer for preparation of radiolabeled drugs for human investigation may be safe. However, further detailed investigations may be warranted for supporting the candidature of Good's buffer for regular clinical exploitation.

Differential responses to avian pathogenic E. coli and the regulatory role of splenic miRNAs in APEC infection in Silkie chickens.

Avian pathogenic Escherichia coli (APEC) is a bacterial disease that harms the poultry industry worldwide, but its effect on Chinese Silkie has not been reported. Studies on whether there are differences in Silkie individual resistance to APEC and the regulatory role of spleen miRNAs lay the foundation for strategies against APEC. Therefore, 270 Silkie chickens were infected with the median lethal dose of an E. coli O1, O2, and O78 mixture. These chickens were divided into a susceptible group (Group S) and a recovery group (Group R) according to whether they survived 15 days postinfection (dpi). Moreover, 90 uninfected APEC Silkie served as controls (Group C). The splenic miRNA expression profile was examined to evaluate the role of miRNAs in the APEC infection response. Of the 270 Silkies infected with APEC, 144 were alive at 15 dpi. Cluster analysis and principal component analysis (PCA) of splenic miRNAs revealed that the four Group R replicates were clustered with the three Group C replicates and were far from the three Group S replicates. Differentially expressed (DE) miRNAs, especially gga-miR-146b-5p, play essential roles in immune and inflammatory responses to APEC. Functional enrichment analyses of DEmiRNAs suggested that suppression of immune system processes (biological processes) might contribute to susceptibility to APEC and that FoxO signaling pathways might be closely associated with the APEC infection response and postinfection repair. This study paves the way for screening anti-APEC Silkies and provides novel insights into the regulatory role of miRNAs in APEC infection.

Determination of the median lethal dose of zinc gluconate in mice and safety evaluation.

BACKGROUND: Zinc Gluconate (ZG) is a safe and effective supplement for zinc. However, there is limited research on the optimal dosage for intravenous injection and the safety evaluation of animal models for ZG. This study aims to determine the safe dose range of ZG for intravenous injection in C57BL/6J mice. METHODS: A Dose titration experiment was conducted to determine the LD50 and 95% confidence interval (95%CI) of ZG in mice. Based on the LD50, four sub-lethal doses (SLD) of ZG were evaluated. Following three injections of each SLD and monitoring for seven days, serum zinc levels were measured, and pathological changes in the liver, kidney, and spleen tissues of mice were determined by histological staining. RESULTS: The dose titration experiment determined the LD50 of ZG in mice to be 39.6 mg/kg, with a 95%CI of 31.8-49.3 mg/kg. There was a statistically significant difference in the overall serum zinc levels (H = 36.912, P < 0.001) following SLD administration. Pairwise comparisons showed that the serum zinc levels of the 1/2 LD50 and 3/4 LD50 groups were significantly higher than those of the control group (P < 0.001); the serum zinc level of the 3/4 LD50 group was significantly higher than those of the 1/8 LD50 and 1/4 LD50 groups (P < 0.05). There was a positive correlation between the different SLDs of ZG and the serum zinc levels in mice (rs = 0.973, P < 0.001). H&E staining showed no significant histological abnormalities or lesions in the liver, kidney, and spleen tissues of mice in all experimental groups. CONCLUSION: The appropriate dose range of ZG for intravenous injection in C57BL/6J mice was clarified, providing a reference for future experimental research.

Research on phytotoxicity assessment and photosynthetic characteristics of nicosulfuron residues on Beta vulgaris L.

Nicosulfuron is a common herbicide used to control weeds in maize fields. In northeast China, sugar beet is often grown as a subsequent crop after maize, and its frequently suffers from soil nicosulfuron residue damage, but the related toxicity evaluation and photosynthetic physiological mechanisms are not clear. Therefore, we experimented to evaluate the impacts of nicosulfuron residues on beet growth, photochemical properties, and antioxidant defense system. The results showed that when the nicosulfuron residue content reached 0.3 µg kg-1, it inhibited the growth of sugar beet. When it reached 36 µg kg-1 (GR50), the growth stagnated. Compared to the control group, a nicosulfuron residue of 36 µg kg-1 significantly decreased beet plant height (70.93 %), leaf area (91.85 %), dry weights of shoot (70.34 %) and root (32.70 %). It also notably reduced the potential photochemical activity (Fv/Fo) by 12.41 %, the light energy absorption performance index (PIabs) by 46.09 %, and light energy absorption (ABS/CSm) by 6.56 %. It decreased the capture (TRo/CSm) by 9.30 % and transferred energy (ETo/CSm) by 16.13 % per unit leaf cross-section while increasing the energy flux of heat dissipation (DIo/CSm) by 22.85 %. This ultimately impaired the photochemical capabilities of PSI and PSII, leading to a reduction in photosynthetic performance. Furthermore, nicosulfuron increased malondialdehyde (MDA) content while decreasing superoxide dismutase (SOD) and catalase (CAT) activities. In conclusion, this research clarified the toxicity risk level, lethal dose, and harm mechanism of the herbicide nicosulfuron residue. It provides a theoretical foundation for the rational use of herbicides in agricultural production and sugar beet planting management.

An improved method for toxicological profiling of chemical substances.

Toxicity profiling is an integral part of the drug discovery pipeline. The 3Rs principle-Replacement, Reduction, and Refinement, is considered a golden rule in determining the most appropriate approach for toxicity studies. The acute toxicity study with proper estimate of median lethal dose (LD50) is usually an initial procedure for the determination of most suitable test doses for preclinical toxicological and pharmacological profiling. Several methods, which have been devised to determine the LD50, are faced with the challenge of using a large number of animals and time constraints. Despite the inherent advantage of the newer OECD Test Guidelines, the increasing concerns among toxicologists, the regulatory authorities and the general public, on the need to adhere to 3Rs principle, necessitated the need for an improved approach. Such an approach should not only minimize the time and number of animals required, but also take into cognizance animal welfare, and give accurate, comparable, and reproducible results across laboratories. While taking advantage of the inherent merits of the existing methods, here is presented the mathematical basis and evaluation of an improved method for toxicity profiling of test substances and estimation of LD50. The method makes use of the generated Table of values for the selection of appropriate test doses. Our proposed method has capacities to optimize the time and number of animal use, ensure more reliable and reproducible results across laboratories, allow for easy selection of doses for subsequent toxicity profiling, and be adaptable to other biological screening beyond toxicity studies.

Testing the heat treatment dose for Agrilus planipennis (Coleoptera: Buprestidae) prepupae using the Humble water bath.

The lethal heat treatment dose (time and temperature) for the prepupal life stage of Agrilus planipennis Fairmaire (Coleoptera: Buprestidae), emerald ash borer (EAB), was determined through an in vitro application using a carefully calibrated heat treatment apparatus. The lethal and sublethal effects of heat on A. planipennis prepupae were assessed through a ramped heat delivery application, simulating industrial kilns and conventional heat chamber operations, for treatments combining target temperatures of 54 °C, 55 °C, and 56 °C, and exposure durations of 0 min (i.e., kiln temperature ramp only), 15 min, or 30 min. Prepupal EAB larvae did not survive exposure to 56 °C for 15 min or longer, or to 55 °C for 30 min. Sublethal effects were observed for all other treatments. Sublethal effects included delayed development and failure to complete the pupal and adult life stages.

Propidium monoazide PCR, a method to determine OsHV-1 undamaged capsids and to estimate virus Lethal Dose 50.

Ostreid herpes virus 1 (OsHV-1) has been classified within the Malacoherpesviridae family from the Herpesvirales order. OsHV-1 is the etiological agent of a contagious viral disease of Pacific oysters, C. gigas, affecting also other bivalve species. Mortality rates reported associated with the viral infection vary considerably between sites and countries and depend on the age of affected stocks. A variant called µVar has been reported since 2008 in Europe and other variants in Australia and in New Zealand last decade. These variants are considered as the main causative agents of mass mortality events affecting C. gigas. Presently there is no established cell line that allows for the detection of infectious OsHV-1. In this context, a technique of propidium monoazide (PMA) PCR was developed in order to quantify "undamaged" capsids. This methodology is of interest to explore the virus infectivity. Being able to quantify viral particles getting an undamaged capsid (not only an amount of viral DNA) in tissue homogenates prepared from infected oysters or in seawater samples can assist in the definition of a Lethal Dose (LD) 50 and gain information in the experiments conducted to reproduce the viral infection. The main objectives of the present study were (i) the development/optimization of a PMA PCR technique for OsHV-1 detection using the best quantity of PMA and verifying its effectiveness through heat treatment, (ii) the definition of the percentage of undamaged capsids in four different tissue homogenates prepared from infected Pacific oysters and (iii) the approach of a LD50 during experimental viral infection assays on the basis of a number of undamaged capsids. Although the developped PMA PCR technique was unable to determine OsHV-1 infectivity in viral supensions, it could greatly improve interpretation of virus positive results obtained by qPCR. This technique is not intended to replace the quantification of viral DNA by qPCR, but it does make it possible to give a form of biological meaning to the detection of this DNA.

Effect of gamma-irradiated honey bee venom on blood parameter and histopathological observations of liver and kidney in a mice animal model.

Honey bee venom is a valuable product with a wide range of biological effects, whose use is rapidly increasing in apitherapy. In this study, the effect of gamma-irradiated honey bee venom (doses of 0, 2, 4, 6, and 8 kGy, volume of 0.1 ml, and concentration of 0.2 mg/ml) was evaluated on median lethal dose (LD50) determinations, liver and kidney histology, biochemical marker level, and serum protein analyses. Hence, the LD50 induced by the honey bee venom irradiated at 4, 6, and 8 kGy was increased, compared with the one at 0 and 2 kGy. Normal histology was observed in the liver and kidney of the mice receiving the honey bee venom irradiated at 4, 6, and 8 kGy. The serum levels of alanine aminotransferase (ALT) and all serum proteins were reduced at 4, 6, and 8 kGy compared with 0 and 2 kGy. Therefore, gamma irradiation at 4, 6, and 8 kGy had no negative effect on LD50, liver and kidney tissues, ALT, and serum protein levels by decreasing the allergen compounds of the honey bee venom.

Safety Assessment of Schleichera oleosa Lour. Leaves Extract: Acute and Subchronic Studies.

<b>Background and Objective:</b> <i>Schleichera oleosa</i> (Sapindaceae) has been reported to be useful in traditional medicine and it has some potential pharmacological activities, such as anticancer, antioxidant and antimicrobial activities. This study aimed to assess its safety to provide complete data required for the development of <i>S. oleosa</i> as herbal medicine. <b>Materials and Methods:</b> The safety assessment of the extract was carried out by testing acute and subchronic toxicity in mice (male and female) and rats (male and female), respectively. The doses used in the acute toxicity test were 1000, 2000, 3000, 4000 and 5000 mg kg¹ of body weight and those in the subchronic treatment were 100, 200 and 400 mg kg¹ of body weight. <b>Results:</b> In the acute toxicity test, the <i>S. oleosa</i> leaf extract at all doses indicated that the LD₅₀ value of the extract was higher than 5000 mg kg¹ b.wt., which suggested that this extract is practically non-toxic according to the toxicity criteria. Furthermore, the subchronic toxicity test found that the administration of the extract to male and female rats at a daily dose of 100 and 200 mg kg¹ b.wt., for 90 days did not cause any significant change in blood haematology, blood biochemistry and histopathological picture of liver, kidney, heart, lymph and lung. Despite there being a significant increase in white blood counts, long-term use of the <i>S. oleosa</i> leaf extract is relatively safe. <b>Conclusion:</b> The results provided evidence regarding the potential of <i>S. oleosa</i> leaves to be used as herbal medicine. However, further research needs to be done to verify that activity and its safety in long-term use.

Effect of ethyl methanesulfonate mediated mutation for enhancing morpho-physio-biochemical and yield contributing traits of fragrant rice.

Background: Chemical mutagenesis has been successfully used for increasing genetic diversity in crop plants. More than 800 novel mutant types of rice (Oryza sativa L.) have been developed through the successful application of numerous mutagenic agents. Among a wide variety of chemical mutagens, ethyl-methane-sulfonate (EMS) is the alkylating agent that is most commonly employed in crop plants because it frequently induces nucleotide substitutions as detected in numerous genomes. Methods: In this study, seeds of the widely consumed Basmati rice variety (Super Basmati, Oryza sativa L.) were treated with EMS at concentrations of 0.25%, 0.50%, 0.75%, 1.0%, and 1.25% to broaden its narrow genetic base. Results: Sensitivity to a chemical mutagen such as ethyl methanesulfonate (EMS) was determined in the M1 generation. Results in M1 generation revealed that as the levels of applied EMS increased, there was a significant reduction in the germination percent, root length, shoot length, plant height, productive tillers, panicle length, sterile spikelet, total spikelet, and fertility percent as compared to the control under field conditions. All the aforementioned parameters decreased but there was an increase in EMS mutagens in an approximately linear fashion. Furthermore, there was no germination at 1.25% of EMS treatment for seed germination. A 50% germination was recorded between 0.50% and 0.75% EMS treatments. After germination, the subsequent parameters, viz. root length and shoot length had LD50 between 05.0% and 0.75% EMS dose levels. Significant variation was noticed in the photosynthetic and water related attributes of fragrant rice. The linear increase in the enzymatic attributes was noticed by the EMS mediated treatments. After the establishment of the plants in the M1 generation in the field, it was observed that LD50 for fertility percentage was at EMS 1.0% level, for the rice variety. Conclusion: Hence, it is concluded that for creating genetic variability in the rice variety (Super Basmati), EMS doses from 0.5% to 0.75% are the most efficient, and effective.