Characterizing chronic and acute health risks of residues of veterinary drugs in food: latest methodological developments by the joint FAO/WHO expert committee on food additives

The risk assessment of residues of veterinary drugs in food is a field that continues to evolve. The toxicological end-points to be considered are becoming more nuanced and in light of growing concern about the development of antimicrobial resistance, detailed analysis of the antimicrobial activity of the residues of veterinary drugs in food is increasingly incorporated in the assessment. In recent years, the Joint FAO/WHO Expert Committee on Food Additives (JECFA) has refined its approaches to provide a more comprehensive and fit-for-purpose risk assessment. This publication describes in detail the consideration of acute and chronic effects, the estimation of acute and chronic dietary exposure, current approaches for including microbiological endpoints in the risk assessment, and JECFA’s considerations for the potential effects of food processing on residues from veterinary drugs. JECFA now applies these approaches in the development of health-based guidance values (i.e. safe exposure levels) for residues of veterinary drugs. JECFA, thus, comprehensively addresses acute and chronic risks by using corresponding estimates for acute and chronic exposure and suitable correction for the limited bioavailability of bound residues by the Gallo-Torres model. On a case-by-case basis, JECFA also considers degradation products that occur from normal food processing of food containing veterinary drug residues. These approaches will continue to be refined to ensure the most scientifically sound basis for the establishment of health-based guidance values for veterinary drug residues.     

Real and perceived risks for mycotoxin contamination in foods and feeds: challenges for food safety control

Mycotoxins are toxic compounds, produced by the secondary metabolism of toxigenic moulds in the Aspergillus, Alternaria, Claviceps, Fusarium, Penicillium and Stachybotrys genera occurring in food and feed commodities both pre- and post-harvest. Adverse human health effects from the consumption of mycotoxins have occurred for many centuries. When ingested, mycotoxins may cause a mycotoxicosis which can result in an acute or chronic disease episode. Chronic conditions have a much greater impact, numerically, on human health in general, and induce diverse and powerful toxic effects in test systems: some are carcinogenic, mutagenic, teratogenic, estrogenic, hemorrhagic, immunotoxic, nephrotoxic, hepatotoxic, dermotoxic and neurotoxic. Although mycotoxin contamination of agricultural products still occurs in the developed world, the application of modern agricultural practices and the presence of a legislatively regulated food processing and marketing system have greatly reduced mycotoxin exposure in these populations. However, in developing countries, where climatic and crop storage conditions are frequently conducive to fungal growth and mycotoxin production, much of the population relies on subsistence farming or on unregulated local markets. Therefore both producers and governmental control authorities are directing their efforts toward the implementation of a correct and reliable evaluation of the real status of contamination of a lot of food commodity and, consequently, of the impact of mycotoxins on human and animal health.     

潜在的食品污染剂和与之相关的健康危险(英文)

The potential toxicants in food are derived from natural or industrial sources. Compounds like lectins and glycoalkaloids that are toxic to man are naturally present in some vegetables like potatoes or legumes. A wide variety of marine toxins mostly produced by dinoflagel-lates occuring secondarily in molluscs and mussels are usually ingested by human beings causing poisoning. On the other hand, toxic compounds find their way into food during manufacture, storage, or transportation. These include largely the industrial contaminants, persistent organic pollutants (POP), pesticides, heavy metals, and toxins of fungal and bacterial origin. Further, toxic compounds like higher alcohols may be produced as byproducts during processing. Migration of compounds from packaging materials into packaged food like contamination with lead from solder in certain metal cans is well known. Additives (emulsifiers, preservatives, and antioxidants) could also influence the quality of foods. Solvent residues may find their w     

The use of in vitro methods in assessing human health risks associated with short-chain perfluoroalkyl and polyfluoroalkyl substances (PFAS)

Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are a large class of industrial chemicals with a ubiquitous and persistent presence in the environment. Of the thousands of PFAS used by consumers and industry, very few have been thoroughly characterized for potential adverse effects. This is especially true for the novel short-chain (C < 8) alternatives that replaced legacy PFAS. Perfluoroalkyl and polyfluoroalkyl substances have revealed inconsistencies in the toxicokinetics predicted by animal models and empirical findings in humans. To adequately assess the possible health effects of short-chain PFAS, there is a need for robust aggregated data sets on the mechanistic underpinnings and physiochemical properties of these alternatives. Acquiring relevant data on the health effects of short-chain PFAS can be achieved through high-throughput methods supported by in vitro human cell-based models. This review briefly summarizes some of the toxicity data obtained using human cells in vitro, discusses the advantages and limitations of cell-based models, and provides insights on potential solutions to challenges presented with the use of these methods for use in safety assessments.     

餐饮服务食品微生物风险评估研究进展

目的为餐饮服务食品安全风险评估体系的建设提供参考。方法整理分析国内外相关法规和文献。结果与结论餐饮服务食品微生物风险评估可以有效预警与控制餐饮服务食品的安全风险,有利于及时发现和控制食品安全危害的发生。     

Simultaneous determination of some common food dyes in commercial products by digital image analysis

A simple and relatively fast image-analysis method using digital images, obtained with a flatbed scanner, has been described. The method was used for the simultaneous determination of four common food dyes, namely, carmoisine, brilliant blue, sunset yellow, and quinoline yellow, in binary mixtures in commercial products without a need for any prior separation steps. The results obtained were validated against a standard high-performance liquid chromatography method and a good agreement was obtained. The parameters affecting the experimental results were optimized. Under the optimal conditions, the method provided acceptable linear ranges (20–250 mg/L) with correlation coefficients higher than 0.998, suitable precision (relative standard deviation ≤ 4.5%), and limits of detection between 4.82 and 8.05 mg/L.     

A review of the toxicological and environmental hazards and risks of tetrahydrofuran

Abstract

We present in this paper a review of the toxicological and environmental hazards, exposures and risks of tetrahydrofuran (THF; CASRN 109-99-9). THF is a polar solvent and monomer that is easily absorbed by all routes of exposure. The acute toxicity of THF is low to moderate by all routes. Irreversible corrosive damage to the eye can result from direct contact. However, THF is neither a skin irritant, nor sensitizer. Studies in vitro and in vivo have shown that THF is not mutagenic. Chronic studies have found benign tumors in the kidneys of male rats and in the livers of female mice. These findings have been examined, and although a mode of action is not known, the weight of evidence suggests that these tumors are likely not relevant to human health, but instead secondary to rodent-specific modes of action. THF produces transient sedative effects in rats at high concentrations but no significant neurobehavioral changes or neuropathology in sub-chronic studies. There were no specific effects reported on reproduction or developmental toxicity in rats or mice, with non-specific developmental toxicity observed only in the presence of significant maternal toxicity. The log K_ow value for THF is less than 3, indicating a low potential for bioaccumulation. THF is inherently biodegradable, thus is not expected to be environmentally persistent. THF does not present an ecotoxicity hazard based on test results in fish, aquatic invertebrates and plants. Exposures to THF in the workplace, to consumers and via environmental releases were modeled and all found to fall below the derived toxicity thresholds.     

Managing the risks of therapeutic products: proceedings of a workshop

Traditional tools available to the Food and Drug Administration for managing known risks of therapeutic products (drugs, devices and biological products) have limited effectiveness. This report presents the recommendations of a multidisciplinary workshop focused on managing these risks. This is the last in a series of five workshops coordinated by the Centers for Education and Research on Therapeutics (CERTs) on assessing, communicating and managing the risks and benefits of therapeutic products. Workshop participants included experts from government, academia, industry and healthcare organizations, including consumers. Using a modified nominal group process, participants developed a consensus on principles that should govern future risk management (RM) programs, specifically: in order to protect the public health, risk management programs (RMPs) should be evidence-based, science-driven and patient-focused. A plan to manage the risks of each new therapeutic product should be developed prior to its approval. Evaluation of both the processes and outcomes of RM is essential; these evaluations should be in the public domain. Participants also identified and prioritized research and policy gaps related to RM. Recommended research areas included determining the effectiveness of each element of RMPs, finding the best ways to inform healthcare consumers and determining the best way to present risk information in drug labeling. Policy questions included defining the criteria for requiring a RMP, determining the effect of privacy legislation on RMPs and determining how the continuum of risk across therapeutic products should be classified. As this workshop demonstrated, it is possible to develop a prioritized research and policy agenda to meet the needs of all constituencies. Collaboration across diverse government, academic, industry and constituency-based organizations can lead to solutions for the perplexing problems involved in balancing the risks and benefits of therapeutic products. Patients deserve no less as we strive to protect their safety.     

Towards quantitative uncertainty assessment for cancer risks: central estimates and probability distributions of risk in dose-response modeling

Regulatory agencies and the scientific community have been engaged in a long-term effort to strengthen health risk assessment procedures. Recently the momentum of this effort has accelerated to increasing biological information for a variety of toxic compounds and emphasis on the policy goal of broader characterization of scientific uncertainty (in contrast to providing only a single risk estimate). For example, the OMB Regulatory Analysis Guidelines [OMB, 2003. Office of Management and Budget. Circular A-4. Available from: ] suggest that a formal quantitative uncertainty analysis be performed for economic assessments in support of major regulatory analyses, a process that can utilize both expected values and probability distributions for risk estimates. Some efforts have been made in the past to provide probability distributions of risk estimates. In this article, we examine a procedure for constructing probability distributions and expected values of risk estimates using a Bayesian framework. This approach has the advantage of mathematical soundness and computational feasibility, given the Markov chain Monte Carlo software tools that are available today. Importantly, the Bayesian framework can serve as a unifying platform for uncertainty analysis in cancer risk assessment. This paper provides some initial applications of Bayesian methods in quantitative analysis of uncertainty in cancer risk assessment, including implementation with cancer dose-response data sets for two chemicals. The Bayesian expected risk calculations provide an approach to generating a central estimate of risk that does not have the instability problems that have often limited utility of MLE risk estimates.     

The applicability of in vitro-derived data in hazard identification and characterisation of chemicals

Toxicological hazard and risk assessments for chemicals presently are mainly based on highly standardised protocols for animal experimentation and exposure assessment. In this paper the possibilities are being discussed of developing systems in which the systemic (acute and chronic) toxicity of chemicals can be quantified, without the heavy reliance on animal experiments. On the basis of a chemical's structure, in vitro data on its toxicity, and biokinetic modelling a decision/flow scheme is presented. Key elements are the evaluation of chemical functionalities representing structural alerts for toxic actions, the construction of biokinetic models on the basis of non-animal data (e.g. tissue–blood partition coefficients (PCs), in vitro biotransformation parameters), tests or batteries of tests for determining basal cytotoxicity and more specific tests for evaluating tissue- or organ toxicity. It is concluded that such a flow chart is a useful tool for different steps in the toxicological hazard and risk assessment, especially for those forms of toxicity for which validated in vitro and other non-animal tests have already been developed.     

正确认识绿色食品、有机食品与化肥

生产和消费绿色食品、有机食品正在成为我国的一种时尚。本文主要讨论了以下内容 :(1)绿色食品、有机食品的基本意义 ;(2 )绿色食品、有机食品的发展与农业现代化 ;(3)化肥不是农药 ,两者不能同样对待 ;(4)发展绿色食品、有机食品的积极意义和可能面临的问题。笔者认为 ,发展无污染、洁净而面向公众的农产品 ,提高农产品的公众信誉度 ,可能是一个真正的“商机     

Mineral oil in food,cosmetic products,and in products regulated by other legislations

Abstract

For a few years, mineral oils and their potential adverse health effects have been a constant issue of concern in many regulatory areas such as food, cosmetics, other consumer products, and industrial chemicals. Analytically, two fractions can be distinguished: mineral oil saturated hydrocarbons (MOSH) and mineral oil aromatic hydrocarbons (MOAH). This paper aims at assessing the bioaccumulative potential and associated histopathological effects of MOSH as well as the carcinogenic potential of MOAH for consumer-relevant mineral oils. It also covers the absorption, distribution, metabolism, and excretion of MOSH and MOAH upon oral and dermal exposures. The use and occurrence of consumer-relevant, highly refined mineral oils in food, cosmetics and medicinal products are summarized, and estimates for the exposure of consumers are provided. Also addressed are the challenges in characterizing the substance identity of mineral oil products under REACH. Evidence from more recent autopsy and biopsy studies, along with information on decreasing food contamination levels, indicates a low risk for adverse hepatic lesions that may arise from the retention of MOSH in the liver. With respect to MOAH, at present there is no indication of any carcinogenic effects in animals dermally or orally exposed to highly refined mineral oils and waxes. Such products are used not only in cosmetics but also in medicinal products and as additives in food contact materials. The safety of these mineral oil-containing products is thus indirectly documented by their prevalent and long-term use, with a simultaneous lack of clinical and epidemiological evidence for adverse health effects.     

Benefit assessment of therapeutic products: the Centers for Education and Research on Therapeutics

The ability to manage risk depends critically on an understanding of the degree to which a known risk is balanced by the probability of a clinical benefit. Despite the massive emphasis on risk and risk management in the past few years and the long-term focus on defining benefit in the regulatory system, considerable uncertainty remains about the methods of defining benefit and how to operationalize this knowledge. In this 'think tank,' part of a larger series on risk management, issues were divided into those that can be identified before a study is initiated, those that commonly arise after a study is completed, biomarkers and surrogates, use of benefit findings in defining quality and performance indicators, implementation of findings into health systems and formularies, and methods of comparative trials. Key categories for the establishment of a research agenda to fill in gaps in our understanding of assessing benefit were developed by the group.     

Development of the dietary fiber functional food and studies on its toxicological and physiologic properties

Dietary fiber (DF) obtained from wheat bran by microbial fermentation was used as a food additive to cookies. The cookies were evaluated sensorally through an orthogonal test to gain the optimized production conditions as follows: the suitable DF content 8%, leavening agent 1.5%, standing time 5 min, and baking time of the cookies is 8 min.     

Overview of Recent Liquid Chromatography Mass Spectrometry-Based Methods for Natural Toxins Detection in Food Products

Natural toxins include a wide range of toxic metabolites also occurring in food and products, thus representing a risk for consumer health. In the last few decades, several robust and sensitive analytical methods able to determine their occurrence in food have been developed. Liquid chromatography mass spectrometry is the most powerful tool for the simultaneous detection of these toxins due to its advantages in terms of sensitivity and selectivity. A comprehensive review on the most relevant papers on methods based on liquid chromatography mass spectrometry for the analysis of mycotoxins, alkaloids, marine toxins, glycoalkaloids, cyanogenic glycosides and furocoumarins in food is reported herein. Specifically, a literature search from 2011 to 2021 was carried out, selecting a total of 96 papers. Different approaches to sample preparation, chromatographic separation and detection mode are discussed. Particular attention is given to the analytical performance characteristics obtained in the validation process and the relevant application to real samples.     

我国药品与保健食品、特医食品、新资源食品的界定和监管比较

围绕国内现行相关法律及监管规章,对药品、保健食品、特医食品和新资源食品的基本内涵、适用范围、配方组成等进行梳理,并对4类物品的监管制度进行比较分析。旨在帮助人们提高对4类物品的认知与分辨能力,提醒生产厂商明确四者相应的监管要求,杜绝违法违规行为。