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Doxycycline, a structural isomer of tetracycline, has been used in human medicine since 1966. The molecule, obtained semi-synthetically from oxytetracycline or methacycline, is highly lipophilic permitting excellent penetration into tissues. In vitro antimicrobial activity of doxycycline is superior to that of the older tetracyclines (chlortetracycline, oxytetracycline, tetracycline). In laboratory animals, the protective dose for 50% of the subjects (PD50) demonstrates a better in vivo activity than that of all other members of the tetracycline family. Clinical use in human medicine has confirmed the efficacy of doxycycline for a variety of infectious conditions. High lipophilicity results in a large volume of distribution, substantial binding to plasma proteins, and reabsorption in the renal tubules and gastrointestinal tract, thereby conferring a long elimination half-life to the drug. Excellent absorption after oral administration allows small oral doses and minimizes the known side effects of tetracyclines on the gastrointestinal tract--irritation and suprainfection. The contrast to the other tetracyclines, doxycycline does not accumulate in renal failure due to a compensatory gastrointestinal secretion. The pharmacology, toxicology and therapeutics of doxycycline in laboratory animals and man indicate that this drug may be a valuable antimicrobial for use in veterinary medicine.

Polychlorinated biphenyls (PCBs) are industrial compounds that have been detected as contaminants in almost every component of the global ecosystem including the air, water, sediments, fish, and wildlife and human adipose tissue, milk, and serum. PCBs in commercial products and environmental extracts are complex mixtures of isomers and congeners that can now be analyzed on a congener-specific basis using high-resolution gas chromatographic analysis. PCBs are metabolized primarily via mixed-function oxidases into a broad spectrum of metabolites. The results indicate that metabolic activation is not required for PCB toxicity, and the parent hydrocarbons are responsible for most of the biochemical and toxic responses elicited by these compounds. Some of these responses include developmental and reproductive toxicity, dermal toxicity, endocrine effects, hepatotoxicity, carcinogenesis, and the induction of diverse phase I and phase II drug-metabolizing enzymes. Many of the effects observed for the commercial PCBs are similar to those reported for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related compounds. Structure-function relationships for PCB congeners have identified two major structural classes of PCBs that elicit "TCDD-like" responses, namely, the coplanar PCBs (e.g., 3,3',4,4'-tetraCB, 3,3'4,4',5-pentaCB and 3,3',4,4',5,5'-hexaCB) and their mono-ortho coplanar derivatives. These compounds competitively bind to the TCDD or aryl hydrocarbon (Ah) receptor and exhibit Ah receptor agonist activity. In addition, other structural classes of PCBs elicit biochemical and toxic responses that are not mediated through the Ah receptor. The shor-term effects of PCBs on occupationally exposed humans appear to be reversible, and no consistent changes in overall mortality and cancer mortality have been reported. Recent studies have demonstrated that some developmental deficits in infants and children correlated with in utero exposure to PCBs; however, the etiologic agent(s) or structural class of PCBs responsible for these effects have not been delineated. In contrast, based on a toxic equivalency factor approach, the reproductive and developmental problems in certain wildlife populations appear to be related to the TCDD-like PCB congeners.

Part 1 Principles of poison management: the clinical approach diagnostic procedures gut decontamination elimination enhancement antidotes supportive care toxicokinetics the pregnant patient. Part 3 Drugs: analgesics - newer analgesics, nonsteroidal anti-inflammatory drugs, phenazopyridrine salicylate update anti-infectivedrugs - AIDS drugs, antifungal drugs, antiparasitic drugs, antiviral drugs drugs of abuse - amphetamines and designer drugs, cocaine, hallucinogenic drugs, marijuana and other cannabinoids, phencyclidine, opiates systems toxicology - bone drug toxicology, blood and blood forming products, anticoagulants, antifibrinolytics, thrombolytics, blood transfusions and citrate intoxication, cytokines, plasma volume expanders, ticlopidine, cardiovascular toxicology, antiarrhthmic drugs, antihypersensitive agents, vasodilators, lipid lowering drugs, central nervous system drugs, anticonvulsants, the psychotropic agents, antidepressant agents, cyclic antidepressants, monoamine oxidase inhibitors, the neuroleptics, sedative hypnotics, endocrine drugs, gastrointestinal tract drugs, immunotoxicology, respiratory tract drugs receptor toxicology - antimuscarines, dopamine receptor drugs, H1 receptor drugs, serotonin receptor agents, muscle relaxants unclassified drugs. Part 3 The home: over-the-counter products, food poisonings, household poisonings. Part 4 Chemicals: the alcohols, anaesthetics, antiseptics and disinfectants, chemical disasters, chemical warfare, contrast media, cancer chemotherapeutic agents (cytoxic drugs), disulfiram, explosives, hobbies, arts and crafts, the hydrocarbon products, respiratory toxicology, metals and related compounds, pesticides, plastics and plasticizers and epoxy resins, radiation poisoning, veterinary product poisonings in man. Part 5 Natural toxins: envenomations - bites and stings, indigenous toxicology, folk medicine, plants - mycotoxins - mushrooms.

OBJECTIVE: To review the use of IV lipid emulsion (ILE) for the treatment of toxicities related to fat-soluble agents; evaluate current human and veterinary literature; and to provide proposed guidelines for the use of this emerging therapy in veterinary medicine and toxicology. DATA SOURCES: Human and veterinary medical literature. HUMAN DATA SYNTHESIS: Human data are composed mostly of case reports describing the response to treatment with ILE as variant from mild improvement to complete resolution of clinical signs, which is suspected to be due to the variability of lipid solubility of the drugs. The use of ILE therapy has been advocated as an antidote in cases of local anesthetic and other lipophilic drug toxicoses, particularly in the face of cardiopulmonary arrest and unsuccessful cardiopulmonary cerebral resuscitation. VETERINARY DATA SYNTHESIS: The use of ILE therapy in veterinary medicine has recently been advocated by animal poison control centers for toxicoses associated with fat-soluble agents, but there are only few clinical reports documenting successful use of this therapy. Evidence for the use of ILE in both human and veterinary medicine is composed primarily from experimental animal data. CONCLUSIONS: The use of ILE appears to be a safe therapy for the poisoned animal patient, but is warranted only with certain toxicoses. Adverse events associated with ILE in veterinary medicine are rare and anecdotal. Standard resuscitation protocols should be exhausted before considering this therapy and the potential side effects should be evaluated before administration of ILE as a potential antidote in cases of lipophilic drug toxicoses. Further research is waranted.

Human and veterinary drug development addresses absorption, distribution, metabolism, elimination and toxicology (ADMET) of the Active Pharmaceutical Ingredient (API) in the target species. Metabolism is an important factor in controlling circulating plasma and target tissue API concentrations and in generating metabolites which are more easily eliminated in bile, faeces and urine. The essential purpose of xenobiotic metabolism is to convert lipid-soluble, non-polar and non-excretable chemicals into water soluble, polar molecules that are readily excreted. Xenobiotic metabolism is classified into Phase I enzymatic reactions (which add or expose reactive functional groups on xenobiotic molecules), Phase II reactions (resulting in xenobiotic conjugation with large water-soluble, polar molecules) and Phase III cellular efflux transport processes. The human-fish plasma model provides a useful approach to understanding the pharmacokinetics of APIs (e.g. diclofenac, ibuprofen and propranolol) in freshwater fish, where gill and liver metabolism of APIs have been shown to be of importance. By contrast, wildlife species with low metabolic competency may exhibit zero-order metabolic (pharmacokinetic) profiles and thus high API toxicity, as in the case of diclofenac and the dramatic decline of vulture populations across the Indian subcontinent. A similar threat looms for African Cape Griffon vultures exposed to ketoprofen and meloxicam, recent studies indicating toxicity relates to zero-order metabolism (suggesting P450 Phase I enzyme system or Phase II glucuronidation deficiencies). While all aspects of ADMET are important in toxicity evaluations, these observations demonstrate the importance of methods for predicting API comparative metabolism as a central part of environmental risk assessment.

Mycotoxins are well established toxic metabolic entities produced when fungi invade agricultural/farm produce, and this happens especially when the conditions are favourable. Exposure to mycotoxins can directly take place via the consumption of infected foods and feeds; humans can also be indirectly exposed from consuming animals fed with infected feeds. Among the hundreds of mycotoxins known to humans, around a handful have drawn the most concern because of their occurrence in food and severe effects on human health. The increasing public health importance of mycotoxins across human and livestock environments mandates the continued review of the relevant literature, especially with regard to understanding their toxicological mechanisms. In particular, our analysis of recently conducted reviews showed that the toxicological mechanisms of mycotoxins deserve additional attention to help provide enhanced understanding regarding this subject matter. For this reason, this current work reviewed the mycotoxins' toxicological mechanisms involving humans, livestock, and their associated health concerns. In particular, we have deepened our understanding about how the mycotoxins' toxicological mechanisms impact on the human cellular genome. Along with the significance of mycotoxin toxicities and their toxicological mechanisms, there are associated health concerns arising from exposures to these toxins, including DNA damage, kidney damage, DNA/RNA mutations, growth impairment in children, gene modifications, and immune impairment. More needs to be done to enhance the understanding regards the mechanisms underscoring the environmental implications of mycotoxins, which can be actualized via risk assessment studies into the conditions/factors facilitating mycotoxins' toxicities.

Mycotoxins are secondary metabolites of molds that have adverse effects on humans, animals, and crops that result in illnesses and economic losses. The worldwide contamination of foods and feeds with mycotoxins is a significant problem. Aflatoxins, ochratoxins, trichothecenes, zearalenone, fumonisins, tremorgenic toxins, and ergot alkaloids are the mycotoxins of greatest agro-economic importance. Some molds are capable of producing more than one mycotoxin and some mycotoxins are produced by more than one fungal species. Often more than one mycotoxin is found on a contaminated substrate. Mycotoxins occur more frequently in areas with a hot and humid climate, favourable for the growth of molds, they can also be found in temperate zones. Exposure to mycotoxins is mostly by ingestion, but also occurs by the dermal and inhalation routes. The diseases caused by exposure to mycotoxins are known as mycotoxicoses. However, mycotoxicoses often remain unrecognized by medical professionals, except when large numbers of people are involved. Factors influencing the presence of mycotoxins in foods or feeds include environmental conditions related to storage that can be controlled. Other extrinsic factors such as climate or intrinsic factors such as fungal strain specificity, strain variation, and instability of toxigenic properties are more difficult to control. Mycotoxins have various acute and chronic effects on humans and animals (especially monogastrics) depending on species and susceptibility of an animal within a species. Ruminants have, however, generally been more resistant to the adverse effects of mycotoxins. This is because the rumen microbiota is capable of degrading mycotoxins. The economic impact of mycotoxins include loss of human and animal life, increased health care and veterinary care costs, reduced livestock production, disposal of contaminated foods and feeds, and investment in research and applications to reduce severity of the mycotoxin problem. Although efforts have continued internationally to set guidelines to control mycotoxins, practical measures have not been adequately implemented.

. Antimicrobial resistance (AMR) has recently increased due to the overuse and misuse of antibiotics, and their use in animals (food-producing and companion) has also resulted in the selection and transmission of resistant bacteria. The epidemiology of resistance is complex, and factors other than the overall quantity of antibiotics consumed may influence it. Nowadays, AMR has a serious impact on society, both economically and in terms of healthcare. This narrative review aimed to provide a scenario of the state of the AMR phenomenon in veterinary medicine related to the use of antibiotics in different animal species; the impact that it can have on animals, as well as humans and the environment, was considered. Providing some particular instances, the authors tried to explain the vastness of the phenomenon of AMR in veterinary medicine due to many and diverse aspects that cannot always be controlled. The veterinarian is the main reference point here and has a high responsibility towards the human-animal-environment triad. Sharing such a burden with human medicine and cooperating together for the same purpose (fighting and containing AMR) represents an effective example of the application of the One Health approach.

Accidental and intended Ricinus communis intoxications in humans and animals have been known for centuries but the causative agent remained elusive until 1888 when Stillmark attributed the toxicity to the lectin ricin. Ricinus communis is grown worldwide on an industrial scale for the production of castor oil. As by-product in castor oil production ricin is mass produced above 1 million tons per year. On the basis of its availability, toxicity, ease of preparation and the current lack of medical countermeasures, ricin has gained attention as potential biological warfare agent. The seeds also contain the less toxic, but highly homologous Ricinus communis agglutinin and the alkaloid ricinine, and especially the latter can be used to track intoxications. After oil extraction and detoxification, the defatted press cake is used as organic fertilizer and as low-value feed. In this context there have been sporadic reports from different countries describing animal intoxications after uptake of obviously insufficiently detoxified fertilizer. Observations in Germany over several years, however, have led us to speculate that the detoxification process is not always performed thoroughly and controlled, calling for international regulations which clearly state a ricin threshold in fertilizer. In this review we summarize knowledge on intended and unintended poisoning with ricin or castor seeds both in humans and animals, with a particular emphasis on intoxications due to improperly detoxified castor bean meal and forensic analysis.

Toxicological Effects of Veterinary Medicinal Products in Humans is the first definitive guide to discuss the adverse effects of veterinary medicinal products in humans. The chapters focus on occupational safety and consumer issues and examine the circumstances under which exposure is likely to occur. To be in context, it reviews this against the background of adverse health effects from other sources in the veterinary and farming professions. The book examines adverse drug effects reported to regulatory agencies (mainly the FDAÆs Center for Veterinary Medicine) and then considers a series of individual drugs, including antibiotics, anaesthetics and organophosphorus compounds. The chapters also discuss the fundamental aspects of regulatory issues relating to safety assessment, and examine the manner in which user safety is assessed prior to authorisation/approval and what measures can be taken after authorisation/approval in the light of findings from pharmacovigilance activities. There is growing concern over the issue of antimicrobial resistance and the contribution made by veterinary medicinal products. This too is addressed along with the significance to human health and measures that can be taken to mitigate the effects (if any) of the use of antibiotics in animals e.g. prudent use measures. The book will be an essential resource for medical practitioners in hospitals and general practice, pharmaceutical industry scientists, analysts, regulators and risk managers.

This is the third rendition of this landmark work, the first and second editions having appeared in 1998 and 2005, respectively. It is produced in four hardbound volumes containing 1200 alphabetically arranged topics followed by the index. In addition to the editor-in-chief, there were 9 associate editors and nearly 1400 contributors. The topics comprise not just entries for specific chemicals and drugs (antimony, benomyl, carbamazepine, ethylene glycol, fluoxetine, etc.), but also numerous general headings for topics such as absorption, excretion, fetal alcohol syndrome, global environmental change, life cycle assessment, pharmacokinetic models, risk management and veterinary toxicology. The former type of entry is often just 2–3 pages; it lists the specific authors and their affiliations, the CAS number, synonyms, molecular formula, chemical structure, uses, brief history, routes of exposure, toxicokinetics, toxic mechanism, toxic effects in animals and humans, clinical management, environmental fate, exposure limits and a bibliography. The latter type may run from 1 to 10 or more pages and varies in scope depending on the topic in question. Some of the general heading contributions, Excretion, for example, are quite limited in their depth of coverage, but they do provide suggestions for further reading and this is an encyclopedia, of course, and not a textbook. The reader may find it worthwhile to first consult the index when searching for information, since many substances are listed in the contents under a general heading. Doxazosin, for instance, appears not under its own generic name but in a section on alpha blockers. Some other substances are not where you might expect them, for example, n-butyl alcohol was placed alphabetically among the N's. The Contents section is repeated in each of the four volumes, while the Index is only printed at the end of the fourth volume. A digital version has not been made available to purchasers of the hardbound edition, but rather restricted to subscribers to Elsevier's ScienceDirect. Obvious advantages of digital access include the ability to print a pdf section when needed and to quickly perform a global search of the entire text for specific terms. However, possession of the physical book is also advantageous, since one can come to appreciate the layout, scope and style of this invaluable resource much more readily. Furthermore, when time permits, just browsing through the volumes can be quite educational. Many general topics such as Bhopal Incident, Great Smog of London, Killer Lakes and Notorious Poisoners and Poisoning Cases make for engaging reading. The individual sections are remarkably uniform in their presentation and coverage, given the numerous authors. This is a truly encyclopedic work that represents a monumental compilation of up-to-date information; all of the people involved in its preparation and publication are to be congratulated. It is a set of volumes that should be available to every practicing toxicologist and to many pharmacologists and clinicians as well.

Persistent inflammation and the generation of reactive oxygen and nitrogen species play pivotal roles in tissue injury during disease pathogenesis and as a reaction to toxicant exposures. The associated oxidative and nitrative stress promote diverse pathologic reactions including neurodegenerative disorders, atherosclerosis, chronic inflammation, cancer, and premature labor and stillbirth. These effects occur via sustained inflammation, cellular proliferation and cytotoxicity and via induction of a proangiogenic environment. For example, exposure to the ubiquitous air pollutant ozone leads to generation of reactive oxygen and nitrogen species in lung macrophages that play a key role in subsequent tissue damage. Similarly, studies indicate that genes involved in regulating oxidative stress are altered by anesthetic treatment resulting in brain injury, most notable during development. In addition to a role in tissue injury in the brain, inflammation, and oxidative stress are implicated in Parkinson's disease, a neurodegenerative disease characterized by the loss of dopamine neurons. Recent data suggest a mechanistic link between oxidative stress and elevated levels of 3,4-dihydroxyphenylacetaldehyde, a neurotoxin endogenous to dopamine neurons. These findings have significant implications for development of therapeutics and identification of novel biomarkers for Parkinson's disease pathogenesis. Oxidative and nitrative stress is also thought to play a role in creating the proinflammatory microenvironment associated with the aggressive phenotype of inflammatory breast cancer. An understanding of fundamental concepts of oxidative and nitrative stress can underpin a rational plan of treatment for diseases and toxicities associated with excessive production of reactive oxygen and nitrogen species.

Fluoroquinolone antibiotics are widely used in human and veterinary medicine and are ubiquitous in the environment worldwide. This paper recapitulates the occurrence, fate, and ecotoxicity of fluoroquinolone antibiotics in various environmental media. The toxicity effect is reviewed based on in vitro and in vivo experiments referring to many organisms, such as microorganisms, cells, higher plants, and land and aquatic animals. Furthermore, a comparison of the various toxicology mechanisms of fluoroquinolone antibiotic residues on environmental organisms is made. This study identifies gaps in the investigation of the toxic effects of fluoroquinolone antibiotics and mixtures of multiple fluoroquinolone antibiotics on target and nontarget organisms. The study of the process of natural transformation toward drug-resistant bacteria is also recognized as a knowledge gap. This review also details the combined toxicity effect of fluoroquinolone antibiotics and other chemicals on organisms and the adsorption capacity in various environmental matrices, and the scarcity of data on the ecological toxicology evaluation system of fluoroquinolone antibiotics is identified. The present study entails a critical review of the literature providing guidelines for the government to control the discharge of pollutants into the environment and formulate policy coordination. Future study work should focus on developing a standardized research methodology for fluoroquinolone antibiotics to guide enterprises in the design and production of drugs with high environmental biocompatibility.

An expert meeting was organized by the World Health Organization (WHO) and held in Stockholm on 15-18 June 1997. The objective of this meeting was to derive consensus toxic equivalency factors (TEFs) for polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) and dioxinlike polychlorinated biphenyls (PCBs) for both human, fish, and wildlife risk assessment. Based on existing literature data, TEFs were (re)evaluated and either revised (mammals) or established (fish and birds). A few mammalian WHO-TEFs were revised, including 1,2,3,7,8-pentachlorinated DD, octachlorinated DD, octachlorinated DF, and PCB 77. These mammalian TEFs are also considered applicable for humans and wild mammalian species. Furthermore, it was concluded that there was insufficient in vivo evidence to continue the use of TEFs for some di-ortho PCBs, as suggested earlier by Ahlborg et al. [Chemosphere 28:1049-1067 (1994)]. In addition, TEFs for fish and birds were determined. The WHO working group attempted to harmonize TEFs across different taxa to the extent possible. However, total synchronization of TEFs was not feasible, as there were orders of a magnitude difference in TEFs between taxa for some compounds. In this respect, the absent or very low response of fish to mono-ortho PCBs is most noticeable compared to mammals and birds. Uncertainties that could compromise the TEF concept were also reviewed, including nonadditive interactions, differences in shape of the dose-response curve, and species responsiveness. In spite of these uncertainties, it was concluded that the TEF concept is still the most plausible and feasible approach for risk assessment of halogenated aromatic hydrocarbons with dioxinlike properties.

The rise in incidence of antimicrobial resistance, consumer demands and improved understanding of antimicrobial action has encouraged international agencies to review the use of antimicrobial drugs. More detailed understanding of relationships between the pharmacokinetics (PK) of antimicrobial drugs in target animal species and their action on target pathogens [pharmacodynamics (PD)] has led to greater sophistication in design of dosage schedules which improve the activity and reduce the selection pressure for resistance in antimicrobial therapy. This, in turn, may be informative in the pharmaceutical development of antimicrobial drugs and in their selection and clinical utility. PK/PD relationships between area under the concentration time curve from zero to 24 h (AUC(0-24)) and minimum inhibitory concentration (MIC), maximum plasma concentration (C(max)) and MIC and time during which plasma concentrations exceed the MIC have been particularly useful in optimizing efficacy and minimizing resistance. Antimicrobial drugs have been classified as concentration-dependent where increasing concentrations at the locus of infection improve bacterial kill, or time-dependent where exceeding the MIC for a prolonged percentage of the inter-dosing interval correlates with improved efficacy. For the latter group increasing the absolute concentration obtained above a threshold does not improve efficacy. The PK/PD relationship for each group of antimicrobial drugs is 'bug and drug' specific, although ratios of 125 for AUC(0-24):MIC and 10 for C(max):MIC have been recommended to achieve high efficacy for concentration-dependent antimicrobial drugs, and exceeding MIC by 1-5 multiples for between 40 and 100% of the inter-dosing interval is appropriate for most time-dependent agents. Fluoroquinolones, aminoglycosides and metronidazole are concentration-dependent and beta-lactams, macrolides, lincosamides and glycopeptides are time-dependent. For drugs of other classes there is limited and conflicting information on their classification. Resistance selection may be reduced for concentration-dependent antimicrobials by achieving an AUC(0-24):MIC ratio of greater than 100 or a C(max):MIC ratio of greater than 8. The relationships between time greater than MIC and resistance selection for time-dependent antimicrobials have not been well characterized.

Oxidative stress is a phenomenon caused by an imbalance between production and accumulation of oxygen reactive species (ROS) in cells and tissues and the ability of a biological system to detoxify these reactive products. ROS can play, and in fact they do it, several physiological roles (i.e., cell signaling), and they are normally generated as by-products of oxygen metabolism; despite this, environmental stressors (i.e., UV, ionizing radiations, pollutants, and heavy metals) and xenobiotics (i.e., antiblastic drugs) contribute to greatly increase ROS production, therefore causing the imbalance that leads to cell and tissue damage (oxidative stress). Several antioxidants have been exploited in recent years for their actual or supposed beneficial effect against oxidative stress, such as vitamin E, flavonoids, and polyphenols. While we tend to describe oxidative stress just as harmful for human body, it is true as well that it is exploited as a therapeutic approach to treat clinical conditions such as cancer, with a certain degree of clinical success. In this review, we will describe the most recent findings in the oxidative stress field, highlighting both its bad and good sides for human health.

Antibiotic resistance in bacteria that cause disease in man is an issue of major concern. Although misuse of antibiotics in human medicine is the principal cause of the problem, antibiotic-resistant bacteria originating in animals are contributory factors, with some types of resistance in some species of bacteria. Antibiotics are added to animal feeds to treat and prevent infections and to improve growth and production. Until recently, the major concerns about incorporation of antibiotics in animal feeds related to antibiotic residues in products from treated animals. Although, in 1969, the Swann (1969) report drew attention to the potential for antibiotic-resistant bacteria to spread from treated animals via the food chain, there was little response until the detection of vancomycin-resistant enterococci in animals fed a related glycopeptide, avoparcin. Subsequently, attention started to focus on the issue and other examples of transfer of resistant bacteria through the food chain, such as enterococci resistant to quinupristin-dalfopristin or to everninomicin, fluoroquinolone-resistant campylobacters and multiresistant Escherichia coli, and salmonella such as Salmonella typhimurium DT104. Reviews and committees in many countries have highlighted the need for better control of licensing of antibiotics, and codes for prudent use of antibiotics by veterinary practitioners and farmers. The continued use of antibiotic growth promoters has been questioned and there is a need to ensure that antibiotics important in human medicine are not used therapeutically or prophylactically in animals.

Fipronil (FIP) is widely used across the world as a broad-spectrum phenylpyrazole insecticide and veterinary drug. FIP was the insecticide to act by targeting the γ-aminobutyric acid (GABA) receptor and has favorable selective toxicity towards insects rather than mammals. However, because of accidental exposure, incorrect use of FIP or widespread FIP use leading to the contamination of water and soil, there is increasing evidence that FIP could cause a variety of toxic effects on animals and humans, such as neurotoxic, hepatotoxic, nephrotoxic, reproductive, and cytotoxic effects on vertebrate and invertebrates. In the last decade, oxidative stress has been suggested to be involved in the various toxicities induced by FIP. To date, few reviews have addressed the toxicity of FIP in relation to oxidative stress. The focus of this article is primarily intended to summarize the progress in research associated with oxidative stress as a possible mechanism for FIP-induced toxicity as well as metabolism. The present review reports that studies have been conducted to reveal the generation of reactive oxygen species (ROS) and oxidative stress as a result of FIP treatment and have correlated them with various types of toxicity. Furthermore, the metabolism of FIP was also reviewed, and during this process, various CYP450 enzymes were involved and oxidative stress might occur. The roles of various compounds in protecting against FIP-induced toxicity based on their anti-oxidative effects were also summarized to further understand the role of oxidative stress in FIP-induced toxicity.

The administration of antimicrobial agents to livestock creates potential for antibiotic residues to enter the food supply and be consumed by humans. Therefore, as a process of food animal drug registration, national regulatory agencies and international committees evaluate data regarding the chemical, microbiologic, pharmacokinetic, pharmacodynamic, pharmacologic, toxicologic, and antimicrobial properties of veterinary drugs to assess the safety of ingested antimicrobial residues to consumers. Currently, European, Australian and United States guidelines for veterinary drug registration require a safety assessment of microbiologic hazards from consumption of antimicrobial residues taking into account the potentially adverse effects on human intestinal microflora. The main concerns addressed are selection of resistant bacteria in the gastrointestinal tract and disruption of the colonization barrier of the resident intestinal microflora. Current requirements differ among national agencies. Efforts are ongoing internationally to review and harmonize approaches and test methods and protocols for application to these microbiologic safety evaluations of antimicrobial drug residues in food. This review describes the background to current regulatory approaches used in applying in vitro and in vivo methods to set a microbiologic acceptable daily intake for residues in food derived from animals treated with an antimicrobial agent. This paper also examines the current research needs to support these evaluations.