Investigating the fate and toxicity of green synthesized gold nanoparticles in albino mice.

OBJECTIVE: This study aims to investigate the acute and chronic adverse effects of ∼50 nm (nanometer) gold nanoparticles (AuNPs) synthesized using Ziziphus zizyphus leaf extract in mice. SIGNIFICANCE: AuNPs have shown promise for medical applications, but their safety and biocompatibility need to be addressed. Understanding the potential adverse effects of AuNPs is crucial to ensure their safe use in medical applications. METHODS: The ∼50 nm AuNPs were synthesized using Ziziphus zizyphus leaf extract and characterized using scanning electron microscopy, dynamic light scattering, and zeta potential analysis. Mice were subjected to a single intraperitoneal injection of AuNPs at a dose of 1 g/mg (grams per milligram) or a daily dose of 1 mg/kg for 28 days. Various parameters, including gold bioaccumulation, survival, behavior, body weight, and blood glucose levels, were measured. Histopathological changes and organ indices were assessed. RESULTS: Gold levels in the blood and heart did not significantly increase with daily administration of AuNPs. However, there were proportional increases in gold content observed in the liver, spleen, and kidney, indicating effective tissue uptake. Histopathological alterations were predominantly observed in the kidney, suggesting potential tissue injury. CONCLUSIONS: The findings of this study indicate that ∼50 nm AuNPs synthesized using Z. zizyphus leaf extract can induce adverse effects, particularly in the kidney, in mice. These results highlight the importance of addressing safety concerns when using AuNPs in medical applications. Further investigations that encompass a comprehensive set of toxicological parameters are necessary to confirm the long-term adverse effects of AuNP exposure.

Individual and combined effects of amoxicillin and carbamazepine to the marine copepod Tigriopus fulvus.

Pharmaceuticals can be considered a global threat to aquatic ecosystems due to their pseudo-persistence and their potential toxicity towards non-target species. Amoxicillin (AMX) and carbamazepine (CBZ) and their mixture (1:1) were investigated on the marine copepod Tigriopus fulvus (Fischer, 1860) considering both acute and chronic endpoints. While acute and chronic exposure did not directly affect survival, reproductive endpoints were affected like the mean egg hatching time that was significantly longer than the negative control for treatments with AMX (0.789 ± 0.079 µg/L), CBZ (8.88 ± 0.89 µg/L), and AMX and CMZ as a mixture (1.03 ± 0.10 µg/L and 0.941 ± 0.094 µg/L), in that order.

Experimental Studies on Zooplankton-Toxic Cyanobacteria Interactions: A Review.

Cyanobacterial blooms have been recognized as a problem in fresh water for about 150 years. Over the past 50 years, experimental studies on the subject have gained importance considering the increasing need to control toxic cyanobacterial blooms. This article presents information on the different lines of research that have been undertaken on zooplankton-cyanobacteria interactions over the past 50 years. These include information on filtering/ingestion rates and phytoplankton preferences of small and large rotifers, cladocerans, and copepods; growth rates of zooplankton on cyanobacterial diets; feeding rates of other freshwater invertebrates on cyanobacteria; role of zooplankton in top-down biomanipulation efforts; effect of cyanotoxins on zooplankton; bioaccumulation of cyanotoxins; and physical and chemical control of cyanobacterial blooms. We also highlight measures that have led to successful lake management and improvement of water quality in selected waterbodies.

The amphipod Parhyale hawaiensis as a promising model in ecotoxicology.

Near-shore marine/estuarine environments play an important role in the functioning of the marine ecosystem and are extremely vulnerable to the presence of chemical pollution. The ability to investigate the effects of pollution is limited by a lack of model organisms for which sufficient ecotoxicological information is available, and this is particularly true for tropical regions. The circumtropical marine amphipod Parhyale hawaiensis has become an important model organism in various disciplines, and here we summarize the scientific literature regarding the emergence of this model within ecotoxicology. P. hawaiensis is easily cultured in the laboratory and standardized ecotoxicity protocols have been developed and refined (e.g., miniaturized), and effects of toxicants on acute toxicity (Cd, Cu, Zn, Ag, ammonia, dyes, pesticides, environmental samples), genotoxicity as comet assay/micronuclei, and gene expression (Ag ion and Ag nanoparticles) and regeneration (pesticides) have been published. Methods for determination of internal concentrations of metals (Cu and Ag) and organic substances (synthetic dye) in hemolymph were successfully developed providing sources for the establishment of toxicokinetics models in aquatic amphipods. Protocols to evaluate reproduction and growth, for testing immune responses and DNA damage in germ cells are under way. The sensitivity of P. hawaiensis, measured as 50% lethal concentration (LC50), is in the same range as other amphipods. The combination of feasibility to culture P. hawaiensis in laboratory, the recent protocols for ecotoxicity evaluation and the rapidly expanding knowledge on its biology make it especially attractive as a model organism and promising tool for risk assessment evaluations in tropical environments.

Azithromycin effects on the European sea bass (Dicentrarchus labrax) early life stages following acute and chronic exposure: Laboratory bioassays.

The purpose of this study was to assess the acute and chronic effects of the macrolide azithromycin (AZI) on the European sea bass (Dicentrarchus labrax) early life stages. Azithromycin is a semi-synthetic antibiotic frequently detected in the aquatic environment, despite this few information about its effects on aquatic organisms were reported. Investigations of AZI acute toxicity on D. labrax early life stages were made using six increasing concentrations (0.625, 1.25, 2.5, 5, 10 and 20 mg/l) during 96 h of exposure. The chronic toxicity was tested at one year old juveniles using two sublethal concentrations (C1 = 0.05 µg/l and C2 = 0.8 µg/l) during 4 and 14 days. Malondialdehyde (MDA), glutathione S-transferase (GST), catalase (CAT) and acetylcholinesterase (AChE) activities were measured in gill and liver tissues of juveniles. The half lethal concentration (LC50), 96 h value of AZI for the European sea bass was determined as 31 mg/l. Results showed that short-time exposure to 20 mg/l of azithromycin induces 18% and 7.5% of larvae mortality and morphological abnormalities, respectively. Azithromycin provoked oxidative stress, peroxidative damage, and neurotoxicity in juveniles D. labrax. Overall, the CAT and AChE activities decreased in gill and liver tissues, while dissimilarity in response in both organs depending on AZI concentrations and time of exposure was observed in MDA and GST levels.

Comparison of Joint Effect of Acute and Chronic Toxicity for Combined Assessment of Heavy Metals on Photobacterium sp.NAA-MIE.

Predicting the crucial effect of single metal pollutants against the aquatic ecosystem has been highly debatable for decades. However, dealing with complex metal mixtures management in toxicological studies creates a challenge, as heavy metals may evoke greater toxicity on interactions with other constituents rather than individually low acting concentrations. Moreover, the toxicity mechanisms are different between short term and long term exposure of the metal toxicant. In this study, acute and chronic toxicity based on luminescence inhibition assay using newly isolated Photobacterium sp.NAA-MIE as the indicator are presented. Photobacterium sp.NAA-MIE was exposed to the mixture at a predetermined ratio of 1:1. TU (Toxicity Unit) and MTI (Mixture Toxic Index) approach presented the mixture toxicity of Hg2+ + Ag+, Hg2+ + Cu2+, Ag+ + Cu2+, Hg2+ + Ag+ + Cu2+, and Cd2+ + Cu2+ showed antagonistic effect over acute and chronic test. Binary mixture of Cu2+ + Zn2+ was observed to show additive effect at acute test and antagonistic effect at chronic test while mixture of Ni2+ + Zn2+ showing antagonistic effect during acute test and synergistic effect during chronic test. Thus, the strain is suitable and their use as bioassay to predict the risk assessment of heavy metal under acute toxicity without abandoning the advantage of chronic toxicity extrapolation.

Taxon-toxicity study of fish to typical transition metals: Most sensitive species are edible fish.

Transition metals are widespread in aquatic environments and can be harmful when concentrations exceed thresholds. Especially for fish, an important component of the human diet, low concentrations of transition metals will directly affect their well-being. Different taxa are protected by unified water quality criteria (WQC) thresholds, which rarely consider the ecological status and economic value of different species. There is therefore an urgent need to study taxon-specific sensitivity. The present study established the species sensitivity distributions of nine typical transition metals (Cr, Mn, Fe, Ni, Cu, Zn, Ag, Cd and Hg) for protecting freshwater and seawater fish based on non-parametric kernel density estimation methods, and then derived their acute and chronic HC5-values. The results showed that Ag and Hg have the highest acute toxic potency to fish in freshwater as well as seawater. Compared with marine fish, freshwater fish were more tolerant to acute exposure to Cr, Fe, Ni and Zn, whilst being more sensitive to Ag and Cd. Moreover, edible fish are more sensitive than other fish to these metals in both freshwater and seawater, encouraging more protection of economically valuable fish that may potentially affect human health. The study provides a strong reference for future research on taxon-specific WQC for transition metals.

Growth and reproduction effects and transgenerational effects of nonylphenol in Moina mongolica Daday (Crustacea: Cladocera).

An experimental ecology method was used to study the acute toxicity of nonylphenol (NP) and the effects of NP on growth, reproduction, and population growth in Moina mongolica. The effects were studied in a parent generation exposed to NP and three generations of offspring (F1, F2, and F3) not exposed to NP. The acute 24- and 48-h median lethal concentrations (LC50) of M. mongolica were 0.066 and 0.046 mg L-1, respectively, indicating that NP is very toxic to M. mongolica. In chronic exposure experiments using parent M. mongolica, NP clearly inhibited the lifespan, reproductive volume, total molting time, end-body length, and population growth parameters. In the recovery generations in a clean environment, three generations still suffered from toxic effects, with toxic amplification in generation F1. Generations F2 and F3 clearly followed a recovery trend in the groups in which the parents were exposed to 0.001-0.007 mg L-1 NP but recovered slowly in the groups in which the parents were exposed to 0.009 and 0.011 mg L-1 NP. The results indicated that NP has overt reproductive toxic and transgenerational effects on M. mongolica. Further studies of the damage caused to the aquatic environment by hormone-like chemicals such as NP should therefore be performed.

Health effect and risk assessment of the populations exposed to different arsenic levels in drinking water and foodstuffs from four villages in arsenic endemic Gaighata block, West Bengal, India.

Health exposure and perception of risk assessment have been evaluated on the populations exposed to different arsenic levels in drinking water (615, 301, 48, 20 µg/l), rice grain (792, 487, 588, 569 µg/kg) and vegetables (283, 187, 238, 300 µg/kg) from four villages in arsenic endemic Gaighata block, West Bengal. Dietary arsenic intake rates for the studied populations from extremely highly, highly, moderately, and mild arsenic-exposed areas were 56.03, 28.73, 11.30, and 9.13 µg/kg bw/day, respectively. Acute and chronic effects of arsenic toxicity were observed in ascending order from mild to extremely highly exposed populations. Statistical interpretation using 'ANOVA' proves a significant relationship between drinking water and biomarkers, whereas "two-tailed paired t test" justifies that the consumption of arsenic-contaminated dietary intakes is the considerable pathway of health risk exposure. According to the risk thermometer (SAMOE), drinking water belongs to risk class 5 (extremely highly and highly exposed area) and 4 (moderately and mild exposed area) category, whereas rice grain and vegetables belong to risk class 5 and 4, respectively, for all the differently exposed populations. The carcinogenic (ILCR) and non-carcinogenic risks (HQ) through dietary intakes for adults were much higher than the recommended threshold level, compared to the children. Supplementation of arsenic-safe drinking water and nutritional food is strictly recommended to overcome the severe arsenic crisis.

Exposure to perfluorooctanesulfonate (PFOS) but not perflurorooctanoic acid (PFOA) at ppb concentration induces chronic toxicity in Daphnia carinata.

Widespread environmental contamination of per- and polyfluoroalkyl substances (PFAS) is well established. Nevertheless, few studies have reported on the aquatic toxicity of PFAS, especially in indicator species such as Daphnia. In this study, the toxicity of two major PFAS, namely perfluorooctanoic acid (PFOA) and perfluorooctanesulfonate (PFOS), was investigated on water flea (Daphnia carinata) using a battery of comprehensive toxicity tests, including a 48 h acute and a 21-day chronic assays. The survival, growth, and reproduction of D. carinata were monitored over a 21-day life cycle. PFOS exhibited higher toxicity than PFOA. The 48 h LC50 values (confidence interval) based on acute toxicity for PFOA and PFOS were 78.2 (54.9-105) mg L-1 and 8.8 (6.4-11.6) mg L-1, respectively. Chronic exposure to PFOS for 21 days displayed mortality and reproductive defects in D. carinata at a concentration as low as 0.001 mg L-1. Genotoxicity assessment using comet assay revealed that exposure for 96 h to PFOS at 1 and 10.0 mg L-1 significantly damaged the organism's genetic makeup. The results of this study have great implications for risk assessment of PFOS and PFOA in aquatic ecosystems, given the potential of PFOS to pose a risk to Daphnia even at lower concentrations (1 µg L-1).

Acute Polychlorinated Biphenyl Benthic Invertebrate Toxicity Testing to Support the 2017 Chronic Dose-Response Sediment Injury Model.

As managers and decision makers evaluate pollutant risk, it is critical that we are able to measure an assessment of the injury. Often, these estimates are difficult to determine for benthic organisms, so in 2017 a chronic polychlorinated biphenyl (PCB) sediment dose-response model to predict benthic invertebrate injury was proposed. Given both natural resource trustee and consultant questions following publication concerning that the aqueous chronic toxicity testing data used in the 2017 model development were primarily from the 1970s and 1980s, this follow-up short communication is meant to provide the user some additional data that are more recent. With the advances in analytical and quantitative environmental chemistry (i.e., better detection limits and congener separation), we chose to complete acute aquatic toxicity testing using 3 estuarine invertebrates and lethal endpoints (20 and 50% lethal concentrations). This acute testing was selected because chronic aquatic testing for PCBs outside of the data used in the 2017 study was not available to us. The aquatic results used in the present study were changed to sediment using equilibrium partitioning, as done in the 2017 chronic model, after using the same organic-carbon partition coefficient and total organic carbon for our equilibrium partitioning (EqP)-measured calculations. Based on these acute aquatic toxicity results and a general acute-to-chronic injury concentration ratio of approximately 10, we found that the 2017 model was valid and, hence, that a 1.0 µg/g chronic PCB sediment criterion is a reasonable estimation of potential benthic invertebrate injury. This was followed by spiked sediment tests where percent acute sediment injury was compared to the EqP-derived chronic value and the results from 2017; modest agreement is shown. Environ Toxicol Chem 2021;40:1188-1193. Published 2020. This article is a U.S. Government work and is in the public domain in the USA.

The effects of 1-hexyl-3-methylimidazolium bromide on embryonic development and reproduction in Daphnia magna.

Ionic liquids (ILs) are acknowledged as green chemicals and favorable substitutes for volatile organic solvents, which are currently used. However, previous studies have shown that these compounds had toxicological impacts on aquatic organisms. To investigate the effects of 1-hexyl-3- methylimidazolium bromide ionic liquid ([C6mim]Br) on embryonic development and reproduction in water flea (Daphnia magna), a series of exposure experiments were conducted, including acute toxicity, maternal exposure, and chronic exposure tests. In acute toxicity experiment, D. magna neonates exhibited developmental abnormalities in the shell spine and the second antennae in a concentration-dependent manner after exposure to [C6mim]Br. The results in maternal exposure test also revealed a certain embryo-toxicity in response to [C6mim]Br in D. magna. However, the toxicity was lower than that conveyed by direct acute exposure, this indicated that the IL could act directly on organism. During the 21 days chronic exposure, the 1.6 mg/L exposure caused marked drop in the survival, molts and the number of the first brood of D. magna. Meanwhile, the total number of offspring was significantly declined in 1.6 mg/L concentration treatment groups, whereas increased in 0.2 mg/L groups. Generally, abnormalities in the offspring were significantly increased across all of the treatment groups in contrast to the control. No effect on sex differentiation was found during the experiments. These findings suggested that [C6mim]Br could affect embryonic development and reproduction in D. magna, and provided references for further study on the mechanisms underlying toxicological effects of ILs and the assessment of their potential environmental risks.

Multi-parametric analysis of ciprofloxacin toxicity at ecologically relevant levels: Short- and long-term effects on Daphnia magna.

The increased presence of emergent compounds, such as pharmaceuticals drugs, in the aquatic compartment has been acknowledged as an evolving environmental issue whose consequences are not yet fully characterized. Specific classes of pharmaceutical drugs, such as fluoroquinolone antibiotics, can exert toxic effects to non-target species with ecological significance, since these compounds are environmentally stable and persistent, and may interact with some of the key physiologic processes of organisms. Despite such characteristics, knowledge about the effects of these drugs is still scarce, especially to non-target organisms. The present study aimed to evaluate the effects of chronic and acute exposures of the cladoceran Daphnia magna to the fluoroquinolone antibiotic ciprofloxacin. Putative toxic effects were assessed, following acute and chronic exposures to ecologically relevant concentrations of ciprofloxacin, through enzymatic (cholinesterase - ChEs, catalase - CAT, glutathione S-transferases - GSTs) and non-enzymatic (thiobarbituric acid reactive substances - TBARS, glycogen - Gly) biomarkers. In addition, we also determined behavioural (swimming distance - SD) and morphological (body length of the first brood - BL1B) endpoints in animals exposed to this drug. Ciprofloxacin acute exposure resulted in increased CAT and ChEs activities, and inhibited GSTs activity. After chronic exposure, ChEs activity was significantly inhibited, while GSTs activity was significantly enhanced. TBARS levels were only increased at higher concentrations of ciprofloxacin. CAT activity and Gly content did not evidence a clear and significant pattern of variation. SD was slightly inhibited during dark cycles. BL1B presented a significant decrease for animals subjected to an intermediate concentration. Results showed that even ecologically relevant concentrations of ciprofloxacin may cause oxidative stress in individuals of D. magna. The present study showed important data that corroborate the occurrence of significant biochemical alterations in key features of an aquatic organism when exposed to relevant levels of a widely used antibiotic, establishing essential links between environmental exposure to this specific drug and putative toxic challenges that may result in irreversible changes and damages, especially at the individual level. However, changes in the size of neonates suggest that population alterations are likely to occur under real scenarios of chronic contamination by this drug.

Behavioral and biochemical effects of the antifouler and antidandruff zinc pyrithione on the freshwater fish Gambusia holbrooki.

The presence of pharmaceutical residues in the aquatic environment is receiving great attention since the levels of these substances have significantly increased in this compartment, potentially leading to adverse ecological effects. Zinc pyrithione (ZnPt) is a widely used organometallic biocide, which is incorporated into antifouling formulas, such as paints, to prevent the establishment of biofilms on surfaces exposed to the aquatic environment. It is also used in cosmetics, such as antidandruff shampoos and soaps. Considering this wide use, and the absence of a significant amount of data on the toxicity of ZnPt especially towards non-target organisms, the objective of this study was to characterize the toxicity of ZnPt, on several ecological relevant endpoints assessed in the fish Gambusia holbrooki. For this purpose, we measured traits related to feeding and aggressive behavior, as well as indicators of oxidative stress (CAT and GSTs), neurotoxicity (AChE), and anaerobic metabolism (LDH), after acute and chronic exposures to ZnPt. In terms of behavioral features, the feeding test showed the occurrence of significant differences between the control animals and those exposed to a concentration of ZnPt of 45 µg/L. In addition, ZnPt caused changes in terms of oxidative stress biomarkers (CAT and GSTs), for both exposure periods. ZnPt was also capable of causing changes in the cholinergic neurotransmission functioning and anaerobic metabolism, but only following the chronic exposure.

Can the surface modification and/or morphology affect the ecotoxicity of zinc oxide nanomaterials?

Among nanomaterials, zinc oxide (ZnO) is notable for its excellent biocidal properties. In particular, it can be incorporated in mortars to prevent biofouling. However, the morphology of these nanomaterials (NMs) and their impact on the action against biofouling are still unknown. This study aimed to assess how the morphology and surface modification can affect the ecotoxicology of ZnO NMs. The morphologies evaluated were nanoparticles (NPs) and nanorods (NRs), and the ZnO NMs were tested pure and with surface modification through amine functionalization (@AF). The toxic effects of these NMs were evaluated by acute and chronic ecotoxicity tests with the well-established model microcrustacean Daphnia magna. The ZnO NMs were characterized by transmission electron microscopy, X-ray diffraction and infrared spectroscopy. The EC5048h to D. magna indicated higher acute toxicity of ZnO@AF NRs compared to all tested NMs. Regarding the chronic test with D. magna, high toxic effects on reproduction and longevity were observed with ZnO@AF NRs and effects on growth were observed with ZnO NRs. In general, all tested ZnO NMs presented high toxicity when compared to the positive control, and the NRs presented higher toxicity than NPs in all tested parameters, regardless of the form tested (pure or with surface modification). Additionally, the pathways of ecotoxicity of the tested ZnO NMs was found to be related to combined factors of Zn ion release, effective diameter of particles and NM internalization in the organism.

Disinfection by-Products and Ecotoxic Risk Associated with Hypochlorite Treatment of Tramadol.

In recent years, many studies have highlighted the consistent finding of tramadol (TRA) in the effluents from wastewater treatment plants (WTPs) and also in some rivers and lakes in both Europe and North America, suggesting that TRA is removed by no more than 36% by specific disinfection treatments. The extensive use of this drug has led to environmental pollution of both water and soil, up to its detection in growing plants. In order to expand the knowledge about TRA toxicity as well as the nature of its disinfection by-products (DBPs), a simulation of the waste treatment chlorination step has been reported herein. In particular, we found seven new by-products, that together with TRA, have been assayed on different living organisms (Aliivibrio fischeri, Raphidocelis subcapitata and Daphnia magna), to test their acute and chronic toxicity. The results reported that TRA may be classified as a harmful compound to some aquatic organisms whereas its chlorinated product mixture showed no effects on any of the organisms tested. All data suggest however that TRA chlorination treatment produces a variety of DBPs which can be more harmful than TRA and a risk for the aquatic environment and human health.

Photo-Fenton treatment of saccharin in a solar pilot compound parabolic collector: Use of olive mill wastewater as iron chelating agent, preliminary results.

The aim of this work was to investigate the treatment of the artificial sweetener saccharin (SAC) in a solar compound parabolic collector pilot plant by means of the photo-Fenton process at pH 2.8. Olive mill wastewater (OMW) was used as iron chelating agent to avoid acidification of water at pH 2.8. For comparative purposes, Ethylenediamine-N, N-disuccinic acid (EDDS), a well-studied iron chelator, was also employed at circumneutral pH. Degradation products formed along treatment were identified by LC-QTOF-MS analysis. Their degradation was associated with toxicity removal, evaluated by monitoring changes in the bioluminescence of Vibrio fischeri bacteria. Results showed that conventional photo-Fenton at pH 2.8 could easily degrade SAC and its intermediates yielding k, apparent reaction rate constant, in the range of 0.64-0.82 L kJ-1, as well as, eliminate effluent's chronic toxicity. Both OMW and EDDS formed iron-complexes able to catalyse H2O2 decomposition and generate HO. OMW yielded lower SAC oxidation rates (k = 0.05-0.1 L kJ-1) than EDDS (k = 2.21-7.88 L kJ-1) possibly due to its higher TOC contribution. However, the degradation rates were improved (k = 0.13 L kJ-1) by increasing OMW dilution in the reactant mixture. All in all, encouraging results were obtained by using OMW as iron chelating agent, thus rendering this approach promising towards the increase of process sustainability.

Characterization of Acute and Chronic Toxicity of DBP to Daphnia magna.

As a commonly used phthalate compound, di(n-butyl) phthalate (DBP) is an emerging group of polyvinyl chloride plasticizers. The acute toxicity of DBP has been extensively studied using the aquatic indicator organism, Daphnia magna. However, little is known about chronic and transgenerational toxicity of DBP. In this study, acute LC50 values were 3.04 mg/L (24 h) and 2.55 mg/L (48 h). Chronic toxicity tests in the case of maternal exposure to DBP revealed that DBP had negligible effects on growth and reproduction of F3 generation of D. magna, although the growth rate of body length and the intrinsic rate of increase were prominently reduced, to a pretty small extent. At specific concentrations, DBP generated beneficial effects on the parental generation of D. magna and no obvious impacts on the F1 generation. This study showed that maternal exposure to DBP did not cause any transgenerational effects on D. magna.

Evaluation of cytotoxic effects and acute and chronic toxicity of aqueous extract of the seeds of Calycotome villosa (Poiret) Link (subsp. intermedia) in rodents.

OBJECTIVE: The present investigation was carried out to evaluate the safety of an aqueous extract of the seeds of Calycotome villosa (Poiret) Link (subsp. intermedia) by determining its cytotoxicity and potential toxicity after acute and sub-chronic administration in rodents. MATERIALS AND METHODS: Cytotoxic activity was tested in cancer and non-cancer cell lines HeLa, Mel-5, HL-60 and 3T3. Acute toxicity tests were carried out in mice by a single oral administration of Calycotome seed-extract (0 - 12 g/kg) as well as intraperitoneal doses of 0 - 5 g/kg. Sub-chronic studies were conducted in Wistar rats by administration of oral daily doses for up to 90 days. Changes in body and vital organ weights, mortality, haematology, clinical biochemistry and histologic morphology were evaluated. RESULTS: The lyophilized aqueous extract of C. villosa exhibited a low cytotoxicity in all cell lines tested with an IC50 > 100 µg/ml. In the acute study in mice, intra-peritoneal administration caused dose-dependent adverse effects and mortality with an LD50 of 4.06 ± 0.01 g/kg. In the chronic tests, neither mortality nor visible signs of lethality was seen in rats. Even AST and ALT were not affected while a significant decrease in serum glucose levels, at 300 and 600 mg/kg was detected. Histopathological examination of the kidney and liver did not show any alteration or inflammation at the end of treatment. CONCLUSION: In conclusion, the aqueous extract of C. villosa seed appeared to be non-toxic and did not produce mortality or clinically significant changes in the haematological and biochemical parameters in rats.

Acute and chronic toxicity assessment of benzylpenicillin G residue in heat-treated animal food products.

The current level of penicillin use and its persisting residue in livestock is potentially concerning; the toxicity of penicillin residue in heat-treated animal food products (HAFP) is yet to be elucidated. In this study, the acute and chronic toxicity of benzylpenicillin G (BPG) residue in HAFP was investigated in a mouse model. The calculated LD50 of BPG heated to cooking temperature (BPHCT) was 933.04 mg kg-1 [b.w.] intraperitoneally corresponding to 3.75 times lower than its prototype. Mice fed on the experimental diet containing heat-treated beef with high BPG levels for 6 months displayed a reduction in body weight and altered serum values indicating for liver and renal function. Further, the organ ratios of intestinal and spleen were increased. Histopathological changes were observed in the liver, lung and parenchyma testis tissue. BPHCT residue induced sperm aberration and micronucleated polychromatic erythrocytes formation. Present results indicate that prolonged exposure of BPHCT at higher residue levels might have an impact on public health. Importantly the toxic concentrations of BPHCT are relatively high compared with levels that would result from the degradation of antibiotic residues in meat from animals that have received a therapeutic dose of BPG.