Oral LD50 Research Articles

Toxicological safety evaluation of 3,3′-diselenodipropionic acid (DSePA), a pharmacologically important derivative of selenocystine

Diselenodipropionic acid (DSePA), a pharmacologically important derivative of selenocystine was evaluated for acute toxicity, mutagenic safety and metabolic stability. The estimated median oral lethal dose (LD50) cut-off of DSePA in mice and rat models was ∼200 mg/kg and ∼25 mg/kg respectively, which is considerably higher than the reported oral LD50 dose of its parent compound. Subsequently DSePA treatment in absence and presence of rat liver S9 fraction was found to be non-mutagenic at the tested doses up to 1 mM in rifampicin resistance assay and up to 6 mM in Ames test. In vitro degradation studies indicated that DSePA was more stable in S9 fraction of human compared to rat. The kinetic parameters Km and Vmax of DSePA degradation estimated using rat S9 fraction was 9.81 μM and 1.06 nmol/ml/min respectively. Further, DSePA treatment (1–50 μM) with or without rat S9 fraction did not induce any toxicity in human intestinal epithelial cells (Int 407) while showing comparable bioactivity of glutathione peroxidase (GPx) level. In conclusion, superior metabolic stability of DSePA in human S9 fraction with a concomitant lack of mutagenic effects suggests that it may be a suitable derivative of selenocytine for future biological studies.

ANTIPLASMODIAL ACTIVITY OF CAESALPINIA CRISTA SEED EXTRACTS

Objective: To evaluate antiplasmodial activity of Caesalpinia crista seed extracts
 Methods: Antiplasmodial activity of the seed extracts of Caesalpinia crista against rodent malaria infections in chloroquine sensitive Plasmodium falcipuram strain was investigated, and oral acute toxicity of seed extracts of Caesalpinia crista was also evaluated.
 Results: The findings of this study revealed significant (P < 0.05) and dose dependent decrease in parasitaemia in the parasitized groups treated with varying doses of the extract (50-200 mg/kg p.o.) in both suppressive and curative tests. There was also significant decrease in parasitaemia density in the chloroquine treated group. The alcoholic extract was found no toxicity in wistar rats and the oral LD50 was determined to be greater than 5000 mg/kg.
 Conclusion: Seed extracts of Caesalpinia crista extract possesses potent antiplasmodial activity and may therefore, serve as potential sources of new antimalarial agents
 Keywords: Plasmodium falcipuram, Caesalpinia crista, Plant extracts, Phytochemicals, Toxicity tests, malaria.

Assessment of acute, 14-day, and 13-week repeated oral dose toxicity of Tiglium seed extract in rats

BackgroundSeed of mature Croton tiglium Linne, also known as Tiglium seed (TS), has been widely used as a natural product due to its several health beneficial properties including anti-tumor and antifungal activities. Despite its ethnomedicinal beneficial properties, toxicological information regarding TS extract, especially its long-term toxicity, is currently limited. Therefore, the objective of the present study was to evaluate acute and subchronic toxicity of TS extract in rats after oral administration following test guidelines of the Organization for Economic Cooperation and Development (OECD).MethodsToxicological properties of TS extract were evaluated by toxicity assays to determine its single-dose acute toxicity (125, 250, 500, 1000, or 2000 mg/kg), 14-day repeated-dose toxicity (125, 250, 500, 1000, or 2000 mg/kg) and 13-week repeated-dose toxicity (31.25, 62.5, 125, 250, and 500 mg/kg) in Sprague-Dawley rats and F344 rats. Hematological, serum biochemical, and histopathological parameters were analyzed to determine its median lethal dose (LD50) and no-observed-adverse-effect-level (NOAEL).ResultsOral single dose up to 2000 mg/kg of TS extract resulted in no mortalities or abnormal clinical signs. In 13-week toxicity study, TS extract exhibited no dose-related changes (mortality, body weight, food/water consumption, hematology, clinical biochemistry, organ weight, or histopathology) at dose up to 500 mg/kg, the highest dosage level suggested based on 14-day repeat-dose oral toxicity study.ConclusionAcute oral LD50 of TS extract in rats was estimated to be greater than 2000 mg/kg. NOAEL of TS extract administered orally was determined to be 500 mg/kg/day in both male and female rats. Results from these acute and subchronic toxicity assessments of TS extract under Good Laboratory Practice regulations indicate that TS extract appears to be safe for human consumption.

Design, molecular docking, synthesis, characterization, biological activity evaluation (against MES model), in-silico biological activity spectrum (PASS analysis), toxicological and predicted oral rat LD50 studies of novel sulphonamide derivatives

Among the reported potential agents to treat the epilepsy, sulphonamides are important and their significance cannot be ignored. A series of substituted 4-amino-benzene sulfonamides were designed, keeping in view the structural requirement of pharmacophore. Lipinski rule of five has been calculated; failure to Lipinski rule was not observed. Docking was performed through AutoDock Vina. Molecules have been screened out through docking. Compounds were synthesized and characterized through IR, 1HNMR, 13C NMR, Mass and elemental analysis. The anticonvulsant activity of the synthesized compounds was assessed using the Maximal Electroshock Seizure (MES) model. In-silico biological activity spectrum, toxicological studies, predicted oral rats LD50 were performed. Docking studies showed good interaction with lyase (Oxo-acid) - human carbonic anhydrase-I (1AZM). The in-silico studies proved them to be with good drug-likeness properties, especially 4-(3-Acetyl-phenylamino)-methyl)-benzenesulfonamide (2g). These results revealed that the synthesized compounds (1a-1c, 2a-2q) exhibited promising anticonvulsant effect against MES model for inhibition of Lyase- Human Carbonic Anhydrase-I. After investigating all the results, the compound 4-(3-Acetyl-phenylamino)-methyl)-benzenesulfonamide (2g) is found to be best in the series. A comparatively good activity of compound 2g suggests us that sulphonamide can be leads to further optimization for building potent and chemically diversified anti-convulsant agents.

Safety Assessment of Mentha mozaffarianii Essential Oil: Acute and Repeated Toxicity Studies.

Mentha mozaffarianii, an endemic species from the Labiatae family, is used in Iranian traditional medicine. This study evaluated the acute and repeated oral toxicity of the Mentha mozaffarianii essential oil (MMEO) in rats and mice. To assess the toxicity profile of the MMEO, we administered the essential oil to 48 rats and mice of both sexes by gavage in acute and repeated models. In acute toxicity, the animals were administered the MMEO (2000 mg/kg) and were monitored for 14 days. In the repeated toxicity, the MMEO was administered (100 mg/kg) daily for 4 weeks. On the 28th day, all the animals were scarified and blood and tissue samples were prepared. All the clinical, biochemical, and histopathological changes were assessed and compared with those in the controls. Statistical significance was determined by one- and two-way analyses of variance, followed by the Tukey test using GraphPad Prism 6. In the acute test, there was no mortality; therefore, the oral LD50 value determined in the mice and rats of both sexes was greater than 2000 mg/kg. In the repeated test, the animals received the MMEO and there was no mortality. In the biochemical analysis, there were significant increases in blood glucose, cholesterol, ALT, AST, ALP, and TSH in the female rats and also in BUN in the male rats. The histopathological studies revealed evidence of microscopic lesions in the liver, kidney, stomach, and small intestine tissues of the MMEO group. The results indicated that the acute toxicity of the MMEO in the mice and rats was of a low order and it revealed slight tissue damage to several organs when given subchronically at a dose of 100 mg/kg.

Detection of Pesticide Residues in Selected Bee Products of Honeybees (Apis melllifera L.) Colonies in a Preliminary Study from Seychelles Archipelago.

Pesticide residues in honey and pollen from Seychelles against a target of 108 pesticides using LC-MS/MS were analyzed. Fifteen pesticides were detected, at trace levels (< 15ppb) and below the acceptable maximum residue limits (MRLs) as per EU regulations. In honey, six insecticide and three fungicide residues were detected. Eight insecticide and four fungicide residues were detected in the pollen matrix. The least contaminated honey and pollen samples had three and nine chemical residues respectively while the most contaminated honey and pollen samples had eight and eleven chemical residues respectively. Contact and oral LD50 values were used to calculate Pollen Hazard Quotients (PHQ) = concentration in ppb ÷ LD50 as µg/bee. The pollen hazard quotients (PHQ) obtained are way below those reported in literature. Residues were detected in low quantities, however, their high frequency and diversity and possible synergistic interactions may lead to negative impact on honeybees' health in Seychelles.

Ultraviolet-visible phototransformation of dehydroacetic acid - Structural characterization of photoproducts and global ecotoxicity.

The present work is devoted to the structural elucidation of by-products issued from the direct ultraviolet-visible (UV-vis) irradiation of dehydroacetic acid (DHA) in solution and in cosmetic emulsion. Analyses were carried out using gas chromatography coupled with ion trap mass spectrometry and by high-performance liquid chromatography coupled with ultrahigh-resolution Fourier transform ion cyclotron resonance mass spectrometry (LC/UHRMS). The potential toxicities of by-products were estimated by in silico calculations based on a QSAR (Quantitative Structure-Activity Relationship) approach and by in vitro bioassays conducted on Vibrio fischeri bacteria. Three photoproducts were detected by LC/MS while one photoproduct was detected by GC/MS. The first photoproduct (PP1) corresponds to an isomer of DHA while two isomeric compounds correspond to dimeric structures. The oral rat LD50 of PP1 was evaluated to be 4.5 times lower than that of the parent molecule which classes it in the category 'moderately toxic' on the Hodge and Sterne toxicity classification. In vitro assays on Vibrio fischeri bacteria showed that the global ecotoxicity of the DHA solution increases with irradiation time. With the exception of one photoproduct, the structures proposed for the photoproducts on the basis of mass spectral interpretation have not been reported in previous studies. All photoproducts, with the exception of dimers, were detected after irradiation in the cosmetic emulsion. This result shows that personal care products containing DHA must be protected from direct sunlight to prevent photodegradation.

Safety and clinical efficacy of tenvermectin, a novel antiparasitic 16-membered macrocyclic lactone antibiotics

Tenvermectin (TVM) is a novel 16-membered macrocyclic lactone antibiotics, which contains component TVM A and TVM B. However there is not any report on safety and clinical efficacy of TVM for developing as a potential drug. In order to understand the part of safety and clinical efficacy of TVM, we conducted the acute toxicity test, the standard bacterial reverse mutation (Ames) test and the clinical deworming test. In the acute toxicity studies, TVM, TVM A and ivermectin (IVM) were administrated once by oral gavage to mice and rats. Results showed that the oral LD50 values of TVM, TVM A and IVM in mice were 74.41, 106.95 and 53.06 mg/kg respectively. The oral LD50 values of TVM and TVM A in rats were determined to be 164.22 and 749.34 mg/kg respectively. TVM and IVM are moderately toxic substances, meanwhile the TVM A belongs to low toxic compounds, implying that the acute toxicity is highly related to the length of side chain of TVM at position C25. In the Ames test, results showed that TVM did not induce mutagenicity in Salmonella typhimurium TA97a, TA98, TA100, TA102 and TA1535 with and without metabolic activation system, speculating that the mutagenicity is probably not related to the side chain at position C25 of 16-membered macrocyclic lactone antibiotics. In the efficacy trail of TVM against swine nematodes, growing pigs natural infection of Ascaris suum and Trichuris suis were treated with a single subcutaneous injection 0.3 mg/kg b.w.. Results showed that TVM and IVM had excellent effect in expelling Ascaris suum, and TVM had potential efficacy against Trichuris suis, however IVM had no effect on Trichuris suis. This study suggests that the side chain of TVM at position C25 may have important biological functions, which is one of the key sites of the studies on structure-activity relationship of 16-membered macrocyclic lactone compounds. TVM is a new compound exhibited some advantages worthy of developing.

Galleria mellonella larvae allow the discrimination of toxic and non-toxic chemicals

The acute toxicities of 19 chemicals were assessed using G. mellonella larvae. The results obtained were compared against LD50 values derived from in vitro cytotoxicity tests and against in vivo acute oral LD50 values. In general, cell culture systems overestimated the toxicity of chemicals, especially low toxicity chemicals. In contrast, toxicity testing in G. mellonella larvae was found to be a reliable predictor for low toxicity chemicals. For the 9 chemicals tested which were assigned to Globally Harmonised System (GHS) category 5, the toxicity measured in G. mellonella larvae was consistent with their GHS categorisation but cytotoxicity measured in 3T3 or NHK cells predicted 4 out of 9 chemicals as having low toxicity. A more robust assessment of the likely toxicity of chemicals in mammals could be made by taking into account their toxicities in both cell cultures and in G. mellonella larvae.

Comparative safety evaluation of riot control agents of synthetic and natural origin

Riot control agents (RCA) are lachrymatory, irritating compounds which temporarily incapacitate the uncontainable crowd. Ortho-Chlorobenzylidene-malononitrile (CS), 2-chloroacetophenone (CN), dibenz[b,f]1:4-oxazepine (CR), and nonivamide (PAVA) are synthetic RCAs, while oleoresin extract of chili known as oleoresin capsicum (OC) a natural irritant has been in use by various law enforcement agencies. Though efficacy of these agents is beyond doubt, they suffer from certain drawbacks including toxicity, production cost, and ecological compatibility. Presently, we have evaluated the safety of CR, OC, and PAVA on inhalation variables along with oral lethality. Additionally, the liver function test (LFT) in serum and lungs function was evaluated in broncho-alveolar-lavage fluid (BALF), both collected on the 14th day after RCA exposure. Animals then sacrificed and histopathology of liver and lungs was carried out. Results showed OC and PAVA to be more toxic than CR with an oral LD50 of 150 and 200 mg/kg body weight, respectively, while CR was safe at >3 g/kg body weight. All three agents caused severe impairment of respiratory variables bringing down normal respiration by >80% with rise in sensory irritation. Recovery from the irritating effect of CR was more rapid than OC and PAVA. LFT and BALF variables were not significantly different from that of control. There were no remarkable histopathological changes in liver and lungs. Hence, as per results, CR is safest among all synthetic and natural origin RCAs and can be safely used for effective dispersion of disobedient mob.

Acetonic extract of Vernonia amygdalina (Del.) attenuates Cd-induced liver injury: Potential application in adjuvant heavy metal therapy.

Exposure to cadmium (Cd), even at low doses, is of serious health concern because it does not undergo metabolic degradation to less toxic metabolite. Liver injury/disease, with a world-wide increasing incidence, is one of the consequences of exposure to Cd toxicity. This study aimed at determining the effects of acetonic extract of Vernonia amygdalina leaf (AEVAL) in a Wistar rat model of Cd-induced liver injury. Phytochemical screening of the extract was carried out and its oral LD50 was determined to guide the choice of therapeutic doses. Thereafter, thirty male Wistar rats were recruited for this study. The experimental groups received 4 weeks oral graded doses of the extract (100, 200 and 400 mg/kg) following Cd-induced liver injury. Cd-induced liver injury (5 mg/kg i.p for 5 consecutive days) was characterized by deleterious alterations in the levels of AST, ALT, ALP, total bilirubin and hepatic total protein (p ˂ 0.05). Also, deleterious alteration of oxidative stress indicators (GSH, SOD and CAT) and lipid peroxidation index (TBARS) was observed in the liver homogenates. Histopathological examination showed evidence of degenerated hepatocytes as well as inflammation with disseminated steatosis. These conditions were significantly attenuated (p ˂ 0.05) following treatment with graded doses of the extract, with the highest dose expressing least therapeutic effects. This study concluded that AEVAL attenuated Cd-induced liver injury and is, potentially, a suitable option in adjuvant therapy for heavy metal toxicity.

Design, Synthesis and Pharmacological Evaluation of Sulfonamide Derivatives Screened Against Maximal Electroshock Seizure Test

A series of substituted 4-amino-benzene sulfonamides were designed, keeping in view the structural requirement of pharmacophore. Lipinski rule of five has also been calculated; failure to Lipinski rule was not observed. The synthesized compounds were evaluated for anticonvulsant. Docking was performed through AutoDock Vina. Molecules have been screened out through docking. Compounds were synthesized and characterized through IR, 1HNMR, 13C NMR, Mass and elemental analysis. The anticonvulsant activity of the synthesized compounds was assessed using the MES model. In-silico biological activity spectrum, toxicological studies, predicted oral rat LD50 and possible mechanism of action were investigated. The compound, 4-[2-(4-Acetyl-phenylamino)-ethyl]-benzenesulfonamide (K23) is found most active among the synthesized compounds.

In vivo and in vitro Toxicity Studies of Crude and Partially Purified Leaf Extracts of Jatropha curcas in Wistar Albino Rats

Aims: Jatropha curcas (J. curcas) is a plant that has numerous medicinal and industrial applications. Evaluation of in vitro and in vivo acute/sub chronic hepato-renal toxicity of crude methanol J. curcas leaf extract on albino rats, in vitro toxicity of the fractions and characterization of these fractions were carried out in this study. Study Design: Twenty albino rats were grouped into four, orally administered; 0, 100, 200, and 250 mg/kg daily of the crude extract for 28 days. Place and Duration of Study: Department of Biochemistry, Bayero University Kano and Department of Pure and Applied Chemistry, Bayero University Kano between July 2016 and April 2017. Methodology: Partially purified fractions of the extract were obtained by column chromatography. Brine Shrimp Lethality assay of the crude extract and fractions were carried out. FTIR, GC-MS and LC-MS were used to characterize the fractions, one-way anova and probit analysis were used for data analysis. Results: The oral LD50 of J. curcas extract was found to be 2,391.65 mg/kg. Alkaline phosphatase (ALP), Direct bilirubin (D. BIL) and Albumin (ALB) showed significant (p < 0.05) differences while Alanine amino transferase (ALT), Aspartate amino transferase (AST), Total bilirubin (T. BIL) and Total protein (T.P) showed slight variations in some of the treated groups. Histological features of the liver showed dose dependent mild toxic effect of the extract. Creatinine and potassium levels showed significant (p < 0.05) differences while urea, chloride, sodium and bicarbonate levels slightly differ in some of the treated groups when compared to the control. Abnormal kidney histological features were only observed in the highest dose group. The crude leaf extract, fraction 1, and fraction 2 gave LC50 values of 109.07 µg/ml, 100 µg/ml, and 883.26 µg/ml respectively. Fraction 1 indicated the presence of ursolic acid, betulinic acid, and oleanolic acid while fraction 2 showed fragments of hydroxyl hopanone. Conclusion: This study showed various toxicity indices that revealed slight toxic effect of the crude methanol leaf extract.

Aqueous extract of Persea americana leaves ameliorates alloxan-induced hyperglycaemia and hyperlipidaemia in rats

Decoctions of Persea americana Mill (Lauraceae) leaves are employed to manage diabetes mellitus among the Ibo communities of Eastern Nigeria. In this study, we studied the ameliorative effects of the aqueous extract of P. americana leaves (AEPAL) on alloxan-induced hyperglycaemia and hyperlipidaemia in Wistar rats. The oral median lethal dose (LD50) of AEPAL was determined in rats. The effects of extract on blood glucose and lipids levels; and biochemical parameters were evaluated. The effects of AEPAL on relative organs weights, body weight changes as well as food and water consumption were monitored for 28 days in alloxan-induced hyperglycaemic rats and histopathological changes of the pancreas examined. The estimated oral LD50 of AEPAL was greater than 5000 mg kg–1. AEPAL (125–500 mg kg–1) significantly reduced the fasting blood glucose levels and hyperlipidaemia in the alloxan-induced hyperglycaemic rats. The extract significantly reversed the decreased body weight, increased food and water intake; and attenuated elevated levels of aspartate transaminase (AST), urea, total protein (TP), albumin (ALB), alanine transaminase (ALT) and alkaline phosphatase (ALP) in alloxan-induced hyperglycaemic rat. Histological examination of the pancreas showed regeneration of the β–cells of the Islet of Langerhans in the extract treated alloxan-induced hyperglycaemic rat. Our findings revealed that AEPAL contains biologically active components with potential hypoglycaemic activity, thus supporting its further development for the management of diabetic mellitus. Key words: Persea americana, acute toxicity, antidiabetic, β–cells, metformin.

Evaluation of an acute oral gavage method for assessment of pesticide toxicity in terrestrial amphibians.

Development of an acute oral toxicity test with a terrestrial-phase amphibian was considered necessary to remove the uncertainty within the field of agrochemical risk assessments. The bullfrog (Lithobates catesbeianus) was selected for use as it is a representative of the family Ranidae and historically this species has been used as an amphibian test model species. Prior to definitive study, oral gavage methods were developed with fenthion and tetraethyl pyrophosphate. Dimethoate and malathion were subsequently tested with both male and female juvenile bullfrogs in comprehensive acute oral median lethal dose (LD50) studies. Juvenile bullfrogs were administered a single dose of the test article via oral gavage of a single gelatin capsule of dimethoate technical (dimethoate) or neat liquid Fyfanon® Technical (synonym malathion), returned to their respective aquaria, and monitored for survival for 14 d. The primary endpoint was mortality, whereas behavioral responses, food consumption, body weight, and snout-vent length (SVL) were used to evaluate indications of sublethal toxicity (secondary endpoints). Acute oral LD50 values (95% fiducial interval) for dimethoate were 1459 (1176-1810, males) and 1528 (1275-1831, females), and for malathion they were 1829 (1480-2259, males) and 1672 (1280-2183, females) mg active substance/kg body weight, respectively. Based on the results of these studies, the methodology for the acute oral gavage administration of test items to terrestrial-phase amphibians was demonstrated as being a practical method of providing data for risk assessments. Environ Toxicol Chem 2018;37:436-450. © 2017 SETAC.

Toxicological investigation of acute and chronic treatment with Gnidia stenophylla Gilg root extract on some blood parameters and histopathology of spleen, liver and kidney in mice

BackgroundIn southeast Ethiopia, people locally use the roots of Gnidia stenophylla Gilg (Thymelaeaceae) to cure malaria and other diseases with no literature evidence substantiating its safety. The aim of this study was, therefore, to investigate the safety of the aqueous root extract of G. stenophylla after acute (single dose) and repeated sub chronic oral administration in mice.ResultsA single oral administration of the extract at 500, 1000, 2000 and 4000 mg/kg body weight did not induce any behavioral change and mortality in both sexes. The oral LD50 of the extract was found to be above 6000 mg/kg body weight in mice. Chronic treatment with the extract for 13 weeks did not induce any sign of illness and/or death and had no adverse effect on the body weight. Dose-related elevations of erythrocytes, hematocrit, hemoglobin, platelets and neutrophils differential and significant decrease in the number of lymphocyte were observed. Liver sections of mice treated with 800 mg/kg body weight, revealed mild inflammations around the portal triads and central veins; whereas the spleen and kidneys appeared normal with no detectable gross morphological and histopathological alteration at both doses.ConclusionsThe results of this study revealed that aqueous root extract of G. stenophylla Gilg at antimalarial dose is safe even when taken for a longer period. At a higher dose, the extract may have a potential to increase some hematological indices but may induce mild hepatotoxicity as a side effect.

Nitroguanidine (NQ) (2016).

1-Nitroguanine (NG), also known as picrate, guanidine nitro, and N'-nitroguanidine, is used by the military as a propellant. Oral rodent LD50 data are generally >5000 mg/kg. NG is neither an eye nor a skin irritant, and it is not a skin sensitizer. NG is not genotoxic. No inhalation data are available; however, there are data from both 14- and 90-day oral (feed) toxicity studies in male and female Sprague Dawley rats at dosages up to 1000 mg/kg/day. There were no deaths on these studies and the only effect considered possibly related to treatment was decreased weight in females at the high-dose level in the 90-day study. Mice at similar dosages were even less affected. The NOAEL for both rats and mice (oral) was 316 mg/kg/day. There was no evidence of developmental toxicity in Sprague-Dawley rats administered NG by oral gavage, and the free-standing NOAEL was 1000 mg/kg with material toxicity. In Wistar rats, there was high mortality (50%) at 500 mg/kg NG administered by oral gavage; there was decreased body weight, feed consumption, and notable clinical signs in the dams at this dose level. Fetal toxicity could not be determined in this group. NG demonstrated maternal toxicity at 1000 mg/kg in rabbits; however, there were no evident differences in the rate of fetal malformations across the test groups. A NOAEL of 316 mg/kg was identified for maternal and fetal toxicity in this study. In a two-generation study, it was concluded the NG did not cause reproductive or fertility effects at dosages up to 1000 mg/kg/day. Absorption was rapid, non-dose dependent, and resulted in an apparent volume of distribution (VD) of between 0.66 (IV) and 0.85-0.87 (oral) l/kg. Elimination was primarily through the urine as unchanged compound. Human experience with NG dates back 100 years; however, no actual studies on humans have been reported. Non-military uses include automotive airbags, anti-corrosive coatings, and pharmaceutical manufacturing. The point of departure for Workplace Environmental Exposure Level (WEEL) derivations was 316 mg/kg, and a WEEL of 7 mg/m3 as an 8-h time-weighted average (TWA) was recommended.

Safety of methionine, a novel biopesticide, to adult and larval honey bees (Apis mellifera L.)

Methionine is an essential/indispensible amino acid nutrient required by adult and larval honey bees (Apis mellifera L. [Hymenoptera: Apidae]). Bees are unable to rear broods on pollen deficient in methionine, and reportedly behaviorally avoid collecting pollen or nectar from florets deficient in methioinine. In contrast, it has been demonstrated that methionine is toxic to certain pest insects; thus it has been proposed as an effective biopesticide. As an ecofriendly integrated pest management agent, methionine boasts a novel mode of action differentiating it from conventional pesticides, while providing non-target safety. Pesticides that minimize collateral effects on bees are desirable, given the economic and ecological concerns about honey bee health. The aim of the present study was to assess the potential impact of the biopesticide methionine on non-target adult and larval honey bees. Acute contact adult toxicology bioassays, oral adult assessments and chronic larval toxicity assessments were performed as per U.S. Environmental Protection Agency (EPA) requirements. Our results demonstrated that methionine fits the U.S. EPA category of practically nontoxic (i.e. lethal dose to 50% mortality or LD50 > 11µg/bee) to adult honey bees. The contact LD50 was > 25µg/bee and the oral LD50 was > 100µg/bee. Mortality was observed in larval bees that ingested DL-methionine (effective concentration to 50% mortality or EC50 560µg/bee). Therefore, we conclude that methionine poses little threat to the health of the honey bee, due to unlikely exposure at concentrations shown to elicit toxic effects.

Anti-hyperglycaemic activity of tuber extract of Chlorophytum alismifolium Baker in streptozotocin-induced hyperglycaemic rats

The tubers of Chlorophytum alismifolium (Liliaceae) are widely used in Nigerian Herbal Medicine to treat diabetes mellitus and their efficacy is widely acclaimed among the rural communities of Northern Nigeria. This study was aimed at investigating the antihyperglycaemic potential of the tuber extract of Chlorophytum alismifolium (CAE) in streptozotocin-induced hyperglycaemic rats. Phytochemical screening and oral median lethal dose (LD50) estimation of CAE in rats were carried out. Antihyperglycaemic screening of the extract (at oral doses of 150, 300 and 600 mg/kg) was performed using normal and streptozotocin-induced hyperglycaemic rats for 28 days. Fasting blood glucose levels were measured and serum lipids were analyzed. Liver, kidney, heart and pancreatic tissues were examined for histopathological damages using standard histological processing. Phytochemical screening revealed the presence alkaloids, saponins, flavonoids, triterpenes and glycosides. Oral LD50 was estimated to be >5000 mg/kg body weight in rats. C. alismifolium extract at all the doses tested showed blood glucose lowering effect. Statistical significant (p < .01) blood glucose lowering effect at 150 mg/kg on day 21, at 300 mg/kg on days 21 and 28 (p < .001 and p < .01 respectively) and 600 mg/kg on days 7, 14, 21 and 28 (p < .05, p < .01, p < .001 and p < .01 respectively) was produced by the extract. The extract also reduced the levels of total cholesterol, triglycerides and low density lipoprotein. Histopathological examination of the pancreas showed restoration of pancreatic islet cells at the doses of 300 and 600 mg/kg of the extract. In conclusion, the results obtained suggest the tuber extract of Chlorophytum alismifolium possesses antihyperglycaemic activity.

Enzymatic extract from Ecklonia cava: Acute and subchronic oral toxicity and genotoxicity studies

Ecklonia cava (EC) is known to have antioxidant, anti-inflammatory, antidiabetic, and anticancer properties. Despite its wide use and beneficial properties, comprehensive toxicological information regarding EC extract is currently limited. Therefore, the purpose of this study was to investigate acute toxicity, subchronic toxicity, and genotoxicity of enzymatic EC extract according to test guidelines published by Organization for Economic Cooperation and Development. The acute oral LD50 values of this EC extract administered to rats and dogs were estimated to be more than 3000 mg/kg BW. In an oral 13-week toxicity study, changes in body weights of rats exposed to the EC extract up to 3000 mg/kg BW were found to be normal. In addition, repeated doses of EC extract failed to influence any systematic parameters of treatment-related toxic symptoms such as food/water consumption, mortality, urinalysis, hematology, serum biochemistry, organ weight, or histopathology. These results indicated that the no-observed-adverse-effect level for the EC extract was 3000 mg/kg/day for male and female rats. Data obtained from Ames test, chromosome aberration assay, and micronucleus assay indicated that EC extract was not mutagenic or clastogenic. Taken together, these results support the safety of enzymatic EC extract as a potential therapeutic for human consumption against various diseases.