In Vitro Toxicity Testing of Food Contact Materials: State‐of‐the‐Art and Future Challenges

Currently, toxicological testing of food contact materials (FCMs) is focused on single substances and their genotoxicity. However, people are exposed to mixtures of chemicals migrating from food contact articles (FCAs) into food, and toxic effects other than genotoxic damage may also be relevant. Since FCMs can be made of more than 8 thousand substances, assessing them one‐by‐one is very resource‐consuming. Moreover, finished FCAs usually contain non‐intentionally added substances (NIAS). NIAS toxicity can only be tested if a substance's chemical identity is known and if it is available as a pure chemical. Often, this is not the case. Nonetheless, regulations require safety assessments for all substances migrating from FCAs, including NIAS, hence new approaches to meet this legal obligation are needed. Testing the overall migrate or extract from an FCM/FCA is an option. Ideally, such an assessment would be performed by means of in vitro bioassays, as they are rapid and cost‐effective. Here, we review the studies using in vitro bioassays to test toxicity of FCMs/FCAs. Three main categories of in vitro assays that have been applied include assays for cytotoxicity, genotoxicity, and endocrine disruption potential. In addition, we reviewed studies with small multicellular animal‐based bioassays. Our overview shows that in vitro testing of FCMs is in principle feasible. We discuss future research needs and FCM‐specific challenges. Sample preparation procedures need to be optimized and standardized. Further, the array of in vitro tests should be expanded to include those of highest relevance for the most prevalent human diseases of concern.     

Endocrine modulating chemicals in food packaging: A review of phthalates and bisphenols

Phthalates and bisphenol chemicals have been widely used globally in packaging materials and consumer products for several decades. These highly functional chemicals have become a concern due to their toxicity (i.e., endocrine/hormone modulators) and ability to migrate from food contact materials (FCMs) into food matrices and the environment resulting in human and environmental health risks. FCMs, composed of postconsumer materials, are particularly high risk for containing these compounds. The evaluation of postconsumer recycled feedstocks in FCMs is compulsory and selection of an appropriate detection method to comply with applicable regulations is necessary to evaluate human and environmental safety. Numerous regulations have been proposed and passed globally for both compound classes that are recognized as priority pollutants by the United States Environmental Protection Agency and the European Union. Several brand owners and retailers have also released their own “restricted substance lists” due to the mounting consumer and regulatory concerns. This review article has two goals: (1) discuss the utilization, toxicology, human exposure routes, and occurrence levels of phthalates and bisphenols in FCMs and associated legislation in various countries and (2) discuss critical understanding and updates for detection/quantification techniques. Current techniques discussed include extraction and sample preparation methods (solid-phase microextraction [SPME], headspace SPME, Soxhlet procedure, ultrasound-assisted extraction), chromatographic techniques (gas, liquid, detectors), and environmental/blank considerations for quantification. This review complements a previous review of phthalates in foods from 2009 by discussing phthalate and bisphenol characteristics, analytical methods of determining concentrations in packaging materials, and their influence on the migration potential into food.     

高度关注化学物质(SVHC)的替代研究进展(一)

高度关注化学物质是欧盟REACH法规的重点监控对象,必须经授权才能在欧盟市场销售和使用,申请授权时需提出其替代品和替代计划。针对欧洲化学品管理局提出的高度关注物质候选清单中的49种化学物质,阐述了国内外对它们的替代研究和进展,有助于我国产品顺利进入欧盟市场。     

Mutagenicity assessment of food contact material migrates with the Ames MPF assay

ABSTRACT

A major challenge in the safety assessment of food contact materials (FCM) is the evaluation of unknown non-intentionally added substances (NIAS). Even though consumer exposure levels may be quantitatively low, these substances are considered to be of high toxicological concern if they act as DNA reactive mutagens. From a safety assessment perspective, it is therefore important to detect their presence in FCM migrates. The present study applied the Ames MPF assay to assess the mutagenicity of migrates obtained from 30 food contact material samples out of 3 categories: plastics, composite materials and coatings. As a food simulant, 95% ethanol (EtOH) had a superior performance to less volatile simulants when evaluating recovery rates of representative model substances in different volatility categories. To monitor possible interference of the FCM matrix with Ames MPF results, migrates were spiked with reference substances and recovery rates were established. Out of 30 samples tested, two caused significant inhibition of revertant formation in the presence of the spiking control. Overall detection limits of the applied test method were estimated by determination of the lowest effective concentrations (LEC) for 10 Ames-positive substances. Even though the current limits of detection are not sufficient to entirely fulfil regulatory and safety requirements, three out of 30 FCMs showed evidence of dose-dependent effects in the Ames MPF assay. Overall, the data obtained supported the relevance of testing FCM migrates for DNA reactive contaminants and showed the value of the Ames MPF assay for the safety assessment of FCMs.     

Suitability of the Ames test to characterise genotoxicity of food contact material migrates

ABSTRACT

Non-intentionally added substances (NIAS) are chemical impurities which can migrate from packaging materials (FCM) into food. Safety assessment of NIAS is required by European law, but currently there is no comprehensive testing strategy available. In this context, one key element is to get insight on the potential presence of genotoxic NIAS in FCM migrates. This raises questions about the limit at which genotoxins can be detected in complex mixtures such as FCM migrates, and if such limits of detection (LOD) would be compatible with safety. In this context, the present review assesses the suitability of the Ames assay to address genotoxicity of FCM migrates. Lowest effective concentrations of packaging-related and other chemicals in test media were retrieved from scientific literature and used as surrogates of LODs to be benchmarked against a value of 0.01 mg kg^?1 (10 ppb) in migrates. This is a pragmatic threshold used in FCM safety evaluation to prioritise substances requiring proper identification and risk assessment. The analysis of the data shows that only potent genotoxins can theoretically be detectable at a level of 0.01 mg kg^?1 in migrates or food. Only a minority (10%) of genotoxic chemicals reported to be associated with FCMs could be picked up at a level of 0.01 mg kg^?1 or lower. Overall, this review shows that the Ames test in its present form cannot be used as standalone method for evaluating the genotoxic potential of FCM migrates, but must be used together with other information from analytical chemistry and FCM manufacturing.     

中国和欧盟食品接触材料新品种管理模式研究

食品接触材料新品种的风险评估及风险管理对保障食品安全、促进行业创新具有重要意义。本文通过对比我国和欧盟食品接触材料风险管理机构、法规管理框架、原料管理模式和新品种风险评估等方面的优缺点,梳理欧盟模式中值得我国借鉴的内容,为优化我国食品接触材料新品种风险评估及风险管理模式提出建议。     

离子迁移谱快速测定纺织品内高关注物质

随着欧盟REACH法规的实施,受限的高关注物质不断增加。针对法规对这些物质限量0．1％的要求,介绍了一种使用离子迁移谱技术定性筛选纺织品中此类物质的方法。与经典方法如气相色谱一质谱联用法和高效液相色谱法相比,该方法具有方便快捷的特点,可应用于多种高关注物质的筛查分析,大大缩短了检测周期,并为现场检测提供了可能。     

食品接触材料中非有意添加物及其来源研究进展

食品接触材料（Food Contact Materials, FCMs）在生产、使用和回收过程中都可能引入非有意添加物（Non-Intentionally Added Substances,NIAS）。NIAS的复杂性和未知性给FCMs的安全评估和监管带来严峻的挑战。近些年来,FCMs中NIAS的迁移作为影响食品安全的重要因素而备受关注。本文介绍了FCMs中NIAS的研究流程、分类及主要来源;从目标物及研究目的出发,归纳总结了NIAS的主要分析策略;重点描述了近年来不同类型FCMs中主要NIAS及其来源的研究进展,以期为今后FCMs中NIAS的深入研究提供科学指导。     

European experience in chemicals management: integrating science into policy

The European Union (EU) adopted the first legislation on chemicals management in 1967 with the Dangerous Substances Directive (DSD). Over time the underlying concepts evolved: from hazard identification over risk assessment to safety assessment. In 1981 a premarketing notification scheme was introduced. Approximately 10 years later a risk assessment program started for existing substances following a data collection and prioritization exercise. Integration of science into EU chemicals legislation occurred via several technical committees managed by the European Chemicals Bureau (ECB) and resulted in the Technical Guidance Document on Risk Assessment (TGD), which harmonized the risk assessment methodology. The TGD was revised several times to adapt to scientific developments. The revision process, and the risk assessments for new and existing substances, led to scientific research on chemical risk assessment and thus increased in complexity. The new EU chemicals policy REACH (Registration, Evaluation, Authorization and Restriction of CHemicals) builds on previous experiences and aims to further enhance health and safety. REACH places the burden of proof for chemical safety on industry focusing on managing risks. REACH formalizes the precautionary principle. Furthermore, it underlines a continued scientific underpinning in its implementation, also via stakeholder involvement, and a focus on aligning with international fora.     

国内外食品接触用纸安全管理现状与分析

食品接触用纸安全是保障食品安全的重要组成部分。目前,欧盟、美国和中国关于食品接触用纸安全管理基本搭建了涵盖原材料控制、生产过程监管和产品检测的全程管理模式。本文通过介绍欧盟、美国和中国关于食品接触用纸安全管理的基本要求、食品接触用纸生产用物质和食品接触用纸安全卫生要求,对食品接触用纸安全管理现状进行了综述。通过对比欧盟、美国和中国关于食品接触用纸相关法规及标准,分析各个国家和地区食品接触用纸的安全管理模式,针对各管理模式的相同点和不同点进行综合比较,旨在深入、全面了解各国关于食品接触用纸的安全管理模式和发展趋势,分析其中可被我国在完善食品接触用纸安全管理模式中所用的先进内容和经验。     

Fractionation of extracts from paper and board food contact materials for in vitro screening of toxicity

Paper and board used as food contact materials (FCMs) are chemically complex matrices, partly due to the naturally occurring substances in paper and board, but also due to the chemical treatment of the paper used to make it suitable for food contact. In order to assure the safety of packaging materials, information on the exposure as well as on the toxicity of substances in the packaging must be obtained. This study describes a comprehensive method for the extraction and fractionation of substances present in paper and board FCMs for further investigation by in vitro testing and chemical analysis. The extraction efficiency and the fractionation process were validated by determining recoveries in extracts from paper and board fortified with five surrogates of known concentration. The recoveries for the five surrogates were between 20% and 104% in the raw extract and between 21% and 109% after extraction and fractionation. The fractionation both reduces the number of compounds to be identified and works as a sample clean-up by reducing matrix effects. Raw extracts and fractions from two paper and board FCMs were furthermore tested in the aryl hydrocarbon receptor (AhR) reporter gene assay. Both raw extracts and two of the fractions of the raw extracts gave a positive response in the AhR assay. The strategy of extraction followed by fractionation offers a powerful tool in order to make the workflow for screening FCMs for potentially adverse effects more efficient.     

Presentation and comments on EU legislation related to food industries–environment interactions: organic contaminants (chemicals, pesticides, dioxins, furans, biocides and their waste management)

The first part of this review on European Union (EU) legislation related to food industries–environment interactions deals with chemicals which, in their majority, make their way to food. Such substances are the pesticides and fertilizers the residues of which abound in many agricultural produces (both of plant or animal origin). Another crucial issue is the unintentional release of dioxins and furans through combustion. Detergents or sanitizers in conjunction with compounds considered hazardous or corrosive or flammable stand for other topics falling in the general category of chemicals employed in the food industry. The aim of this review is to cover all the current EU legislation in the field of chemicals (dioxins, furans, pesticides, biocides products, fertilizers, sanitizers) coming directly or indirectly in contact with food and their waste management by providing six comprehensive and easy‐to‐use tables, and a synopsis of the main points of the currently in force EU legislation.     

我国食品接触材料安全性评估体系构建

食品接触材料中所有可能迁移到食品中的物质均需要评估,包括单体、起始物和添加剂等有意添加物,以及杂质、生产过程中产生的副反应产物和降解物等非有意添加物。食品接触材料的安全性评估主要分为上市前的安全性评估和上市后的监测评估。目前,国际上食品接触材料上市前的安全性评估主要有美国和欧盟两种评估模式,两种方法各有优缺点。我国目前尚未建立食品接触材料上市前安全性评估的基本参数。构建我国食品接触材料安全性评估体系是国家食品安全风险评估专家委员会确定的"十三五"期间的重点工作。本文介绍了我国食品接触材料安全性评估体系的构成、预期目标以及食品接触材料风险评估面临的挑战。     

纺织品及纺织化学品中的高关注度物质(SVHC)

通过结合REACH法规的最新73种候选物质清单和附件要求,主要介绍了纺织品及纺织化学品中可能涉及的邻苯二甲酸酯类增塑剂、阻燃剂、挥发性有机化合物(VOC)、致癌芳香胺重金属、其他类型环境荷尔蒙等高关注度物质的来源、相关标准的限制要求。这将有利于企业了解生态环保的国际技术要求,及早制定策略,改进产品环保性能,积极应对各类贸易技术壁垒。     

The European system for the control of the safety of food-contact materials needs restructuring: a review and outlook for discussion

ABSTRACT

The present European system to assure the safety of migrates from food-contact materials (FCMs) needs improvement. It is proposed to implement better the self-control by the producers through improved official control and more attractive listing of approved substances and materials (the latter being subject of another discussion paper). The initial concept of a positive list for the substances used, a limit for the overall migration and regulation of compliance testing was recognised as insufficient long ago, as it does not properly cover reaction products (including oligomers) and impurities. It also turned out to be unrealistic to cover all 17 types of FCMs owing to lack of resources by the authorities. Therefore, European Union legislation shifted the focus to the compliance work carried out by the business operators (in-house documentation and declaration of compliance). However, this approach has not been properly implemented. This is partly due to lack or unsuccessful control by authorities. A suitable structure of this control still needs to be built. It is proposed that specialised document-collection centres working with dedicated tools harmonised throughout Europe be created. Further, since most migrating substances are not listed, the toxicological evaluation reported by industry must be checked by risk-assessment authorities. Finally, effective and harmonised measures are needed to react in case of non-compliance. The currently large gap between the legal requirements and reality must be bridged by introducing flexibility: authorised work plans by industry are proposed. It is also proposed to encourage certified private institutes to approve compliance work, driven by the attractive listing of approved materials and exploiting market forces. In the long run, the focus of the authorities might change from evaluating the substances used and regulating migration testing to the evaluation of the compliance work performed by industry, which means moving from legislation supporting industry towards checking self-control.     

纺织助剂领域中新高度关注物质的替代研究和进展

高度关注化学物质是欧盟REACH法规的重点监控对象,必须经授权才能在欧盟市场销售和使用,申请授权时需提出其替代计划.文中针对欧洲化学品管理局提出的高度关注物质候选清单中的纺织助剂领域的22种新物质,阐述了国内外对它的替代研究和进展,有助于我国产品顺利地进入欧盟市场和整个国际市场.     

Long-term wear effects on nanosilver release from commercially available food contact materials

ABSTRACT

Potential consumer exposure to nanoparticles (NPs) from nanoenabled food contact materials (FCMs) has been a driving force for migration studies of NPs from FCMs. Although NP migration from fresh, unused FCMs was not previously observed, conditions that result in significant changes to the surface of FCMs have not been investigated for NP migration into food. Therefore, a quantitative assessment of nanoparticle release from commercially available nanosilver-enabled FCMs was performed using an abrasion protocol to simulate cleaning, cutting, scraping and other stressful use conditions. Laser scanning confocal microscopy (LSCM) analysis showed a general increase in root mean square (RMS) roughness after FCM abrasion, and particle count (for particle sizes from 80 nm to 960 nm) at the surface was 4 orders of magnitude higher for the abraded FCMs. Migration was evaluated using both water and 3% (v/v, volume fraction) acetic acid as food simulants. Low concentrations of total Ag were detected in water simulants with a small portion (<10 ng dm^?2) in the form of silver nanoparticles (AgNPs). Median particle diameter ranged from 39 nm to 50 nm with particle number concentrations on the order of 10⁶ particles dm^{? 2}. Total Ag migration into 3% (v/v) acetic acid was significantly higher than in water; however, 3% (v/v) acetic acid was not suitable for evaluation of NP release due to dissolution of AgNPs to Ag⁺ under acidic solution chemistries.     

塑料食品接触材料中非有意添加物检测方法研究进展

食品接触材料(Food contact materials, FCMs) 与食品安全密切相关。FCMs能有效保护食品,防止其腐败变质,但在生产过程中可能会由于一些原因引发食品安全问题,其中从FCMs中迁移出的非有意添加物(non intentionally added substance,NIAS)成为影响食品安全的重要因素而引起社会各界的广泛关注。由于NIAS非常复杂,且相当数量未知,其检测成为我国乃至全球食品接触材料安全评价的关键点及难点。在这篇综述中,以塑料食品接触材料和NIAS为主,介绍塑料材料中的NIAS来源、种类、国内外相关法律法规、近年来研究现状以及分析方法,最后对NIAS检测以及Orbitrap高分辨质谱检测技术的未来发展方向进行了展望。     

皮革工业面临的REACH条款与挑战

REACH是欧盟关于化学品注册、评估、授权和限制的制度。于2007年6月1日正式生效。为了保护环境和人类的健康,避免人们受到化学品的伤害,REACH法规从原来的立法基础上进一步提高了对人类的保护。介绍了REACH法规的背景信息以及对皮革工业的一些可行性建议,有利于皮革行业能够在REACH法规实行后同样能够与欧洲国家保持或建立业务往来。     

欧美纺织品有害物质限制趋势

欧盟与纺织品有害物质相关的限制法规和标准主要包括REACH法规、《生物杀灭剂指令》和欧盟生态纺织品标签.在美国,对纺织品有害物质管控影响最大的是美国服饰和鞋类协会制订的《限制物质清单》.Oeko-Tex Standard 100标准则是目前国际上最权威和影响最广的自愿性认证的纺织品生态标签.通过研究这些法规和标准的修订和更新历程,推断出欧美纺织品有害物质的限制趋势,主要表现为更新频繁、范围扩大化、限制严格化和影响扩大化等4个方面.