The two faces of antibiotics: an overview of the effects of antibiotic residues in foodstuffs.

Antibiotics, which have been used for many years to treat infections, also play an important role in food contamination with antibiotic residues. There is also unnecessary use of antibiotics, particularly to increase production efficiency. Non-compliance with withdrawal periods and maximum residue limits (MRLs) for antibiotics used in food-producing animals results in undesirable events, such as allergic reactions, teratogenicity, carcinogenicity, changes in the microbiota and, in particular, antibiotic resistance. Therefore, it may be useful to avoid unnecessary use of antibiotics, to limit the use of antibiotics and to turn to alternatives that can be used instead of antibiotics. The aim of this review is to provide information on the undesirable effects of antibiotic residues in food-producing organisms and in the environment, their determination, and the precautions that can be taken.

Adsorbents Reduce Aflatoxin M1 Residue in Milk of Healthy Dairy Cow Exposed to Moderate Level Aflatoxin B1 in Diet and Its Exposure Risk for Humans.

This study investigated the effect of moderate risk level (8 µg/kg) AFB1 in diet supplemented with or without adsorbents on lactation performance, serum parameters, milk AFM1 content of healthy lactating cows and the AFM1 residue exposure risk in different human age groups. Forty late healthy lactating Holstein cows (270 ± 22 d in milk; daily milk yield 21 ± 3.1 kg/d) were randomly assigned to four treatments: control diet without AFB1 and adsorbents (CON), CON with 8 µg/kg AFB1 (dry matter basis, AF), AF + 15 g/d adsorbent 1 (AD1), AF + 15 g/d adsorbent 2 (AD2). The experiment lasted for 19 days, including an AFB1-challenge phase (day 1 to 14) and an AFB1-withdraw phase (day 15 to 19). Results showed that both AFB1 and adsorbents treatments had no significant effects on the DMI, milk yield, 3.5% FCM yield, milk components and serum parameters. Compared with the AF, AD1 and AD2 had significantly lower milk AFM1 concentrations (93 ng/L vs. 46 ng/L vs. 51 ng/L) and transfer rates of dietary AFB1 into milk AFM1 (1.16% vs. 0.57% vs. 0.63%) (p < 0.05). Children aged 2-4 years old had the highest exposure risk to AFM1 in milk in AF, with an EDI of 1.02 ng/kg bw/day and a HI of 5.11 (HI > 1 indicates a potential risk for liver cancer). Both AD1 and AD2 had obviously reductions in EDI and HI for all population groups, whereas, the EDI (≥0.25 ng/kg bw/day) and HI (≥1.23) of children aged 2-11 years old were still higher than the suggested tolerable daily intake (TDI) of 0.20 ng/kg bw/day and 1.00 (HI). In conclusion, moderate risk level AFB1 in the diet of healthy lactating cows could cause a public health hazard and adding adsorbents in the dairy diet is an effective measure to remit AFM1 residue in milk and its exposure risk for humans.

Genotoxicity of selected pharmaceuticals, their binary mixtures, and varying environmental conditions - study with human adenocarcinoma cancer HT29 cell line.

Pharmaceutical residues are present in the environment in mixtures and their adverse effects may also result from interactions that occur between compounds. Studies presented in this work focus on genotoxicity of pharmaceuticals from different therapeutic groups in mixtures and in individual solutions impacted with different environmental conditions assessed using comet assay (alkaline approach). Binary mixtures of pharmaceuticals (in different concentration ratios) and in individual solutions impacted with pH change (range from 5.5 to 8.5) or addition of inorganic ions, were incubated with HT29 cells and after 24 h time period cells were tested for the presence of DNA damage. To estimate whether mixtures act more (synergistic) or less (antagonistic) efficiently Concentrations Addition (CA) and Independent Action (IA) approaches were applied followed by a calculation of the Model Deviation Ratio (MDR) to determine deviation from the predicted values. Addition of inorganic ions mainly reduced their genotoxicity. Diclofenac s. was the most susceptible to potassium, fluoride, and bromide ions. Change of the pH of pharmaceutical solutions had significant impact on genotoxicity of diclofenac s. and fluoxetine h. Among mixtures, more commonly observed interactions were synergistic ones, exactly twenty-five cases (ten pairs containing chloramphenicol or oxytetracycline h.) and ten cases of antagonism (four for pairs containing chloramphenicol or fluoxetine h.). The results obtained indicate that interactions between tested compounds occur frequently and can lead to DNA damage. This topic especially concerning in vitro tests using cells is still rare, however, it should not be neglected.

Health risk assessment of toxicologically relevant residues in emerging countries: A pilot study on Malachite Green residues in farmed freshwater fish of Armenia.

Malachite Green (MG) has a worldwide application in aquaculture as a therapeutic agent; however, its use in food producing animals is illegal, due to potential carcinogenicity and persistence of residues. This pilot study, the first conducted in Armenia, aimed to determine the concentration of MG residues in flesh of fish grown in artificial ponds of Armenia and conduct dietary exposure assessment to characterize possible health risks to consumers. Detection of MG residues, including the major metabolite leucomalachite, was carried out in 29 fish composite samples by ELISA. The results were confirmed by LC-MS/MS. To determine fish consumption values, a food frequency questionnaire was used. Possible health risks were evaluated by calculating the Margin of Exposure (MOE) based on BMDL of 13 (neoplastic effects) and 6 (non-neoplastic effects) mg/kg bw. In 34.5% of the investigated fish samples MG residues exceeded the minimum required performance limit. For BMDL10 and BMDL0.5, the MOEs ranged 3.36E+06-3.37E+07 and 1.55E+06-1.55E+07, respectively. The MOE for neoplastic effects was more than 10,000 and for non-neoplastic effects was more than 100. The results do not indicate public health concerns. However, the results highlight issues concerning the illegal use of MG in Armenian aquaculture, which deserves further attention.

Implications of Endectocide Residues on the Survival of Aphodiine Dung Beetles: A Meta-Analysis.

It is often difficult to compare studies examining the effects of endectocides on dung fauna because of different experimental approaches, for example, active ingredients (eprinomectin, doramectin, ivermectin, moxidectin) and formulations (injectable, pour-on, spiked). To gain a better understanding, we performed a quantitative meta-analysis using 22 studies to assess the overall effect of endectocide residues on the occurrence (presence or absence) and abundance of aphodiine dung beetles. Our results document a positive effect on the occurrence of adult beetles, indicating that adults tend to be attracted to dung with residues. Conversely, larvae are less likely to occur in the presence of residues. Thus, either adults that colonize dung with residues do not lay eggs or, more likely, the larvae that hatch from these eggs die early in development. Abundance of adult and larval stages was shown to be significantly reduced in dung containing residues. When individual endectocides were compared, only ivermectin demonstrated a significantly negative effect on the abundance of both adults and larvae, possibly owing to a small sample size for other agents. In laboratory studies, only dung "spiked" with endectocides reduced the abundance of larvae, whereas during field research, only pour-on applications were shown to reduce the abundance of larvae. The present study further documents the nontarget effects of endectocide residues on dung-dwelling organisms, provides robust evidence on the consequences of different application methods, and emphasizes the need for standardized methodological techniques in future studies. Environ Toxicol Chem 2020;39:863-872. © 2020 SETAC.

[Review of national and international legal and regulatory mechanisms on the management of drugs and the residues thereof]. / Revisão dos dispositivos legais e normativos internacionais e nacionais sobre gestão de medicamentos e de seus resíduos.

This paper presents a descriptive review of laws and regulations on the management of drugs and the residues thereof adopted by countries in Europe, the Americas and Australia. This review integrates relevant points of official documents of regulatory agencies in these countries, as well as important scientific works. All countries surveyed carry out drug management concomitant with the management of the residues thereof, ranging from awareness programs on the rational use and the risks of drugs through to the collection and safe disposal of such residues. Germany, the USA and Sweden demand a prior assessment of the environmental impact caused by a given drug as a criterion for its registration. Sweden is noteworthy in that it periodically updates a list of essential drugs based on risk assessment and the environmental risks posed by the residues thereof. In Brazil, the legal measures proposed including rational prescription and reverse logistics have not yet been effectively implemented. Prior environmental impact assessment safeguards the risks to human health and the wild biota caused by exposure to drug residues. Therefore, these international models could serve as a basis for discussion and/or legal and regulatory changes in Brazil.

Este trabalho apresenta uma revisão descritiva de leis e normas adotadas pelos países da Europa, das Américas e Austrália sobre gestão de medicamentos e de seus resíduos. Esta revisão integra pontos relevantes de documentos oficiais das agências reguladoras desses países, bem como de trabalhos científicos importantes. Todos os países pesquisados realizam gestão de medicamentos concomitantemente com a gestão de seus resíduos, atuando desde programas de conscientização sobre o uso racional e os riscos dos medicamentos até na coleta e disposição segura de seus resíduos. A Alemanha, os EUA e a Suécia exigem uma avaliação prévia do impacto ambiental provocado pelo medicamento como critério de seu registro. Em destaque, a Suécia que periodicamente atualiza uma lista de medicamentos essenciais baseada na avaliação do risco e do perigo ambiental de seus resíduos. No Brasil, as medidas legais propostas como prescrição racional e logística reversa ainda não foram efetivamente implementadas. A avaliação prévia de impacto ambiental resguarda os riscos à saúde humana e da biota selvagem causados pela exposição aos resíduos de medicamentos. Portanto, esses modelos internacionais poderiam servir de base para discussões e/ou alterações legais e normativas no Brasil.

Revisão dos dispositivos legais e normativos internacionais e nacionais sobre gestão de medicamentos e de seus resíduos / Review of national and international legal and regulatory mechanisms on the management of drugs and the residues thereof

Resumo Este trabalho apresenta uma revisão descritiva de leis e normas adotadas pelos países da Europa, das Américas e Austrália sobre gestão de medicamentos e de seus resíduos. Esta revisão integra pontos relevantes de documentos oficiais das agências reguladoras desses países, bem como de trabalhos científicos importantes. Todos os países pesquisados realizam gestão de medicamentos concomitantemente com a gestão de seus resíduos, atuando desde programas de conscientização sobre o uso racional e os riscos dos medicamentos até na coleta e disposição segura de seus resíduos. A Alemanha, os EUA e a Suécia exigem uma avaliação prévia do impacto ambiental provocado pelo medicamento como critério de seu registro. Em destaque, a Suécia que periodicamente atualiza uma lista de medicamentos essenciais baseada na avaliação do risco e do perigo ambiental de seus resíduos. No Brasil, as medidas legais propostas como prescrição racional e logística reversa ainda não foram efetivamente implementadas. A avaliação prévia de impacto ambiental resguarda os riscos à saúde humana e da biota selvagem causados pela exposição aos resíduos de medicamentos. Portanto, esses modelos internacionais poderiam servir de base para discussões e/ou alterações legais e normativas no Brasil.

Abstract This paper presents a descriptive review of laws and regulations on the management of drugs and the residues thereof adopted by countries in Europe, the Americas and Australia. This review integrates relevant points of official documents of regulatory agencies in these countries, as well as important scientific works. All countries surveyed carry out drug management concomitant with the management of the residues thereof, ranging from awareness programs on the rational use and the risks of drugs through to the collection and safe disposal of such residues. Germany, the USA and Sweden demand a prior assessment of the environmental impact caused by a given drug as a criterion for its registration. Sweden is noteworthy in that it periodically updates a list of essential drugs based on risk assessment and the environmental risks posed by the residues thereof. In Brazil, the legal measures proposed including rational prescription and reverse logistics have not yet been effectively implemented. Prior environmental impact assessment safeguards the risks to human health and the wild biota caused by exposure to drug residues. Therefore, these international models could serve as a basis for discussion and/or legal and regulatory changes in Brazil.

Antibiotic residues in livestock manure: Does the EU risk assessment sufficiently protect against microbial toxicity and selection of resistant bacteria in the environment?

Antibiotic residues that reach the environment via land application of livestock manure could impact structure and function of microbial communities and promote the spread of antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARGs). To assess whether there is a risk, we have reviewed extensive data on five veterinary antibiotics (VAs) that are commonly used in livestock farming (amoxicillin, enrofloxacin, sulfadiazine, tetracycline, trimethoprim). Predicted environmental concentrations (PECs) after the medication of pigs were derived using (i) a total residue approach and (ii) the VetCalc model to account for additional fate parameters and regional scenarios specific to Germany. Predicted no effect concentrations (PNECs) for microbial toxicity and ARB selection were derived from available concentration-response data. Except for enrofloxacin, the total residue PECs exceeded 100 µg kg-1 in soil and risk quotients indicated a high risk for soil porewater and surface water (PEC/PNEC > 1). After PEC refinement, the risk in surface water was generally low. However, in soil porewater still a high risk was indicated for sulfadiazine, tetracycline, and trimethoprim that could persist up to 100 days after the manure application. These findings suggest an urgent need for regulatory action to mitigate the risk resulting from the presence of antibiotic residues in soil.

Occurrence and potential human health risk of pharmaceutical residues in drinking water from Putrajaya (Malaysia).

Occurrence of pharmaceutical residues in drinking water has been widely reported in countries that have registered steady economic growth. This can exert concerns among the general consumers, prompting them to explore the potential human health risks associated with continuous exposure to pharmaceuticals. However, such an occurrence is rarely reported in developing or under-developed countries. To give more contexts, this study looked at the presence of nine pharmaceutical residues in drinking water (amoxicillin, caffeine, chloramphenicol, ciprofloxacin, dexamethasone, diclofenac, nitrofurazone, sulfamethoxazole, and triclosan) at Putrajaya residential area in Malaysia. Additionally, the potential health risks associated with contaminated drinking water were investigated. This study has found the presence of pharmaceutical residue concentrations up to 0.38 ng/L, with the highest concentration of caffeine (0.38 ng/L) and the lowest concentration of diclofenac (0.14 ng/L). In comparison, all the nine pharmaceutical residues were substantially lower than previously reported studies. In general, Hazard Quotient (HQ) values indicated that low potential health hazards were present for all age groups. Nevertheless, quantitative occurrences of pharmaceutical residues in drinking water will help guide future toxicological studies to examine other chronic effects, while canvassing for proper framework to look into the water risk management and regulation in Malaysia.

Response of Freshwater Biofilms to Antibiotic Florfenicol and Ofloxacin Stress: Role of Extracellular Polymeric Substances.

Antibiotic residues have been detected in aquatic environments worldwide. Biofilms are one of the most successful life forms, and as a result are ubiquitous in natural waters. However, the response mechanism of freshwater biofilms to the stress of various antibiotic residues is still unclear. Here, the stress of veterinary antibiotic florfenicol (FF) and fluoroquinolone antibiotic ofloxacin (OFL) on freshwater biofilms were investigated by determining the changes in the key physicochemical and biological properties of the biofilms. The results showed that the chlorophyll a content in biofilms firstly decreased to 46⁻71% and then recovered to original content under the stress of FF and OFL with high, mid, and low concentrations. Meanwhile, the activities of antioxidant enzymes, including superoxide dismutase and catalase, increased between 1.3⁻6.7 times their initial values. FF was more toxic to the biofilms than OFL. The distribution coefficients of FF and OFL binding in extracellular polymeric substances (EPS)-free biofilms were 3.2 and 6.5 times higher than those in intact biofilms, respectively. It indicated that EPS could inhibit the FF and OFL accumulation in biofilm cells. The present study shows that the EPS matrix, as the house of freshwater biofilms, is the primary barrier that resists the stress from antibiotic residues.

Importance of antibiotic residues in animal food.

Veterinary medicines, especially antibiotics, are among the most important components related to animal feed production. Generally, the main use of antibiotics in animals is for the treatment and prevention of diseases and growth promotion. Antibiotic usage in animals may result antibiotic residues in foodstuffs such as milk, egg and meat. These residues may cause various side effects such as transfer of antibiotic resistant bacteria to humans, immunopathological effects, allergy, mutagenicity, nephropathy (gentamicin), hepatotoxicity, reproductive disorders, bone marrow toxicity (chloramphenicol) and even carcinogenicity (sulphamethazine, oxytetracycline, furazolidone). The most important adverse effect of antibiotic residues is the transfer or antibiotic resistant bacteria to the humans due to the mobile properties of resistance. Because of these undesirable effects, it is important to regulate the use of antibiotics in food animals. The individuals and the local procedures should be aware of the problem through education by authorities. In this review, antibiotic use in the foodstuffs and their effects on the human health will be discussed.

Percentage of faecal excretion of meloxicam in the Cape vultures (Gyps corprotheres).

Asian Gyps vulture species are gradually recovering from the devastating effect of diclofenac being present in contaminated carcasses. This drug was responsible for the death of over 10 million vultures in India, Nepal and Pakistan. To prevent the extinction of vultures, meloxicam was introduced after the ban of veterinary diclofenac. Meloxicam's safety in vultures was attributed to its short elimination half-life in contrast with diclofenac. The reason for the rapid elimination of meloxicam is yet to be explained. The aim of this study was to evaluate the role of biotransformation in the elimination of meloxicam. Six Cape griffon vultures (Gyps coprotheres) were treated with 2 mg/kg meloxicam intramuscularly for faecal and plasma quantification of meloxicam concentration over time. In the plasma meloxicam was characterised by a half-life, mean residence time, clearance and volume of distribution at steady state of 0.37 ±â€¯0.10 h, 0.90 ±â€¯0.12 h, 0.02 ±â€¯0.00 l/h kg and 0.02 ±â€¯0.00 l/kg respectively (presented as geometric mean). Over the 24 h monitoring period, the total non-metabolised meloxicam in the faeces was 1.35 ±â€¯0.71% of the total concentration in the plasma. Based on the short meloxicam elimination half-life and low cumulative concentration of total faecal meloxicam over a period in excess of 10 half-lives, this study indicates that Cape griffon vultures are efficient metaboliser of meloxicam, which is suggestive of different set of cytochrome enzymes being involved in the metabolism to that for diclofenac in this species. Identification of orthologous human CYP2C9 and CYP3A4 enzyme families in vultures will be an important further step in explaining the differences in the metabolic pathway(s) of meloxicam and diclofenac for the species.

Development and optimization of confirmatory liquid chromatography-Orbitrap mass spectrometry method for the determination of 17 anticoccidials in poultry and eggs.

A new sensitive and selective multi-residue method based on liquid chromatography - Orbitrap high resolution mass spectrometry (LC-Orbitrap-HRMS) was developed and validated for the determination of 17 anticoccidials in poultry and eggs. Instrumental parameters were optimized by the means of statistical experimental designs to improve the sensitivity, precision, and repeatability of the method. Further optimization of auto-tuned MS parameters led to an increase of signal intensity by 10% to 99% for 16 out of 17 analytes. The sample preparation procedure included extraction from muscle tissue and egg samples with acetonitrile, followed by preconcentration, reconstitution, and filtration. Validation was performed according to the Commission Decision 2002/657/EC. The occurrence of anticoccidials in eggs and poultry was assessed by using the developed analytical procedure within the Latvian national monitoring program, revealing quantifiable residues for 6 analytes (marker residue of nicarbazin - 4,4'-dinitrocarbanilide (DNC), salinomycin, narasin, toltrazuril, and its two metabolites).

Mechanisms and toxicity evaluation of the degradation of sulfamethoxazole by MPUV/PMS process.

In this work, a sulfate radical (SO4-)-based advanced oxidation process was applied to the degradation of sulfamethoxazole (SMX). In these experiments, a medium pressure UV (MPUV) lamp was employed to active peroxymonosulfate (PMS). It was found that 98% of SMX was removed by MPUV/PMS at a UV dose of 200 mJ cm-2 (3.95 µM SMX, 0.2 mM PMS, pH0 = 3.7). Direct MPUV photolysis played a remarkable role in SMX removal by MPUV/PMS process. As for the indirect photolysis, SO4- was the major reactive species under acidic and neutral conditions in MPUV/PMS system, while the hydroxyl radical (OH) became the predominant radical under alkaline conditions. The transformation products (TPs) of SMX that formed in the MPUV-only and MPUV/PMS experiments were identified, and the possible degradation pathways were proposed. Photoisomerization of the isoxazole ring was the major pathway of SMX during MPUV-only process. Hydroxylation/oxidation of the aniline and isoxazole ring was the predominant degradation mechanism of SMX by MPUV/PMS. Toxicity evaluation showed that MPUV/PMS was effective at reducing the antibacterial activity of SMX solutions, while MPUV-only was not. However, some TPs with equivalent or even higher antibacterial activity than SMX were formed during the initial degradation period in MPUV/PMS system. Ecotoxicity of SMX and its TPs was also hypothetically predicted via the ECOSAR program, and the results indicated that some TPs could be more toxic than SMX.

Sublethal chronic effects of oral dietary exposure to deltamethrin in Swiss albino mice.

The hazards of dietary exposure to environmentally relevant levels of deltamethrin are poorly understood though studies enunciate the acute toxicity hazards. In this study, prolonged exposure to low levels of deltamethrin in mice was investigated. The mice were exposed daily via gavage method for 60 days. Four doses (0.1, 0.05, 0.01, and 0.005 mg/kg bwt/d) were selected, which are equal to or less than the maximum residue limits for deltamethrin permitted in animal food/feed. Liver, kidney, lungs, spleen, and testes were collected on day 61 for histology, residue, and biochemical analysis (aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALKP), total bilirubin (TBIL), total proteins (TPs), cholesterol (CHOL), urea, and creatinine). No significant changes were observed in body weight gain in all treatment groups ( p > 0.05). The gas chromatography analysis indicated that none of the tissue samples contained deltamethrin residues above the limits of quantification. The significant differences in biochemical profile (AST, ALT, TBIL, and creatinine) reported in animals exposed to 0.1 and 0.05 mg/kg bwt/d deltamethrin ( p < 0.05) suggest respective tissue injury and lipid peroxidation; however, few significant changes in urea and CHOL were also reported in doses 0.01 and 0.005 mg/kg bwt. No significant differences in TP and ALKP were observed ( p > 0.05). The target organs for deltamethrin toxicity showed prominent histopathological changes in concentrations of 0.1 and 0.05 mg/kg bwt. Other two doses showed no or sporadic changes. Our findings suggest that chronic exposure to environmentally relevant levels of deltamethrin can have detrimental effects on vital organs in the circumstances allowing daily exposure, in congruence with available literature.

Assessment of endocrine disruption and oxidative potential of bisphenol-A, triclosan, nonylphenol, diethylhexyl phthalate, galaxolide, and carbamazepine, common contaminants of municipal biosolids.

The use of biosolids as a soil conditioner and fertiliser is hindered by the limited knowledge on the risks of micro-contaminants they contain. This study investigated the binding of six organic contaminants commonly found in biosolids, to the estrogen (ER), androgen (AR), aryl hydrocarbon (AhR), and transthyretin (TTR) receptors and their redox activity. Triclosan (TCS), bisphenol-A (BPA), and technical nonylphenol (TNP) had affinity for the TTR with relative potencies of 0.3, 0.03, and 0.076 respectively. Further, binding to TTR was the only toxicological response observed for carbamazepine, which induced sub-maximal response and relative potency of 0.0017. Estrogenic activity was induced by BPA, galaxolide (HHCB), diethylhexyl phthalate (DEHP) and TNP with BPA having the strongest potency of 5.1 × 10-6 relative to estradiol. Only BPA showed androgenic activity but it was not quantifiable. BPA also showed anti-androgenic activity along with TCS, HHCB, and TNP in the order of TNP > HHCB > TCS ~ BPA (relative potencies 0.126, 0.042, 0.032, 0.03). No compounds exhibited anti-estrogenic or AhR activity, or were redox-active in the dithiothreitol assay. The results highlight the multiple modes of action through which these compounds may impact exposed organisms, and the concentrations at which effects may occur. This allows assessment of the likelihood of effects being observed at environmental concentrations, and the potential contribution of these compounds.

Food additives, contaminants and other minor components: effects on human gut microbiota-a review.

Gut bacteria play an important role in several metabolic processes and human diseases, such as obesity and accompanying co-morbidities, such as fatty liver disease, insulin resistance/diabetes, and cardiovascular events. Among other factors, dietary patterns, probiotics, prebiotics, synbiotics, antibiotics, and non-dietary factors, such as stress, age, exercise, and climatic conditions, can dramatically impact the human gut microbiota equilibrium and diversity. However, the effect of minor food constituents, including food additives and trace contaminants, on human gut microbiota has received less attention. Consequently, the present review aimed to provide an objective perspective of the current knowledge regarding the impacts of minor food constituents on human gut microbiota and consequently, on human health.

Residual ethylene glycol and dimethyl sulphoxide concentration in human ovarian tissue during warming/thawing steps following cryopreservation.

There have been 60 births after transplantation of cryopreserved ovarian tissue: 58 using the slow freezing method, and two using the vitrification method. DMSO and EG are widely used as cryoprotectants. However DMSO is a known epimutagen, and EG has been reported to be toxic in high concentrations. In this study, we measured residual DMSO and EG in ovarian tissue after vitrification and slow freezing. Cryoprotectants remained at a high concentration in the vitrified/warmed ovarian tissue just before transplantation (DMSO: 9.8 mg/g, EG: 9.8 mg/g). We must consider the impact of the cryoprotectants on the mother and the baby.

Neurotoxic effects, molecular responses and oxidative stress biomarkers in Nile tilapia, Oreochromis niloticus (Linnaeus, 1758) exposed to verapamil.

Pharmaceutical drugs and their metabolites are detected in aquatic ecosystems and have been reported to cause ecotoxicological consequences to resident aquatic organisms. The study investigated the effects of acute and long-term exposure to verapamil on activities of acetylcholinesterase and antioxidant enzymes as well as mRNA expression of stress-related genes in brain and muscle tissues of Nile tilapia, Oreochromis niloticus. The 96h LC50 of verapamil to O. niloticus was 2.29mgL-1. Exposure to sub-lethal concentrations of verapamil (0.14, 0.29 and 0.57mgL-1) for period of 15, 30, 45 and 60days, led to inhibition of acetylcholinesterase activities in the brain and muscle of the fish. The activities of the oxidative enzymes such as the catalase, superoxide dismutase and glutathione peroxidase were also inhibited in both the tissues while there was an increase in the activities of glutathione-S-transferase and reduced glutathione in the muscle after 15 days at 0.29mgL-1. Lipid peroxidation and carbonyl protein showed elevated level, indicating a positive correlation with both time and concentration. The activities of energy-related biomarker (Na+-K+-ATPase) in both the tissues were significantly inhibited (p<0.05) compared with the control. Transcription of catalase (cat), superoxide dismutase (sod) and heat shock proteins 70 (hsp70) were up-regulated in both the tissues after the study period. Prolonged exposure to sub-lethal verapamil can result in oxidative stress, up-regulation of stress-related genes and neurotoxicity in O. niloticus.

Usage, residue, and human health risk of antibiotics in Chinese aquaculture: A review.

Aquaculture is a booming industry in the world and China is the largest producer and exporter of aquatic products. To prevent and treat diseases occurred in aquaculture, antibiotics are widely applied. However, the information of antibiotics used in Chinese aquaculture is still limited. Based on peer-reviewed papers, documents, reports, and even farmer surveys, this review summarized antibiotics used in Chinese aquaculture. In 2014, more than 47.4 million tonnes of farmed aquatic products were produced in mainland China. The outputs in the east and south parts of China can reach as much as 600 times higher than those in the northwest areas, which is clearly separated by the "Hu Line" - a line that marks a striking difference in the distribution of population. A total of 20 antibiotics belonging to eight categories have been reported for use, mainly via oral administration. However, only 13 antibiotics have been authorized for application in Chinese aquaculture and 12 antibiotics used are not authorized. Totally, 234 cases on antibiotic residues in Chinese aquatic products were recorded, including 24 fish species, eight crustacean species, and four mollusk species. Thirty-two antibiotics have been detected in aquatic products; quinolones and sulfonamides were the dominated residual chemicals. For specific compound, ciprofloxacin, norfloxacin, and sulfisoxazole have the highest concentrations. Except for a few cases, all residual concentrations were lower than the maximum residue limits. Through the consumption of aquatic products tainted by antibiotics, humans may acquire adverse drug reactions or antibiotic-resistant bacteria. However, the risk of antimicrobial resistance in human body, when exposed to antibiotics at sub-inhibitory concentrations, has not been exhaustively considered in the risk assessment. In addition, a national comprehensive investigation on the amount of antibiotics used in Chinese aquaculture is still needed in future studies.