Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland; Swiss Centre for Applied Human Toxicology (SCAHT), University of Basel, Basel, Switzerland.
University Medical Library, University of Basel, Basel, Switzerland.
Environ Int. 2023 Jun;176:107978. doi: 10.1016/j.envint.2023.107978. Epub 2023 May 15.
The presence of polyethylene terephthalate (PET) oligomers in food contact materials (FCMs) is well-documented. Consumers are exposed through their migration into foods and beverages; however, there is no specific guidance for their safety evaluation.
This systematic evidence map (SEM) aims to identify and organize existing knowledge and associated gaps in hazard and exposure information on 34 PET oligomers to support regulatory decision-making.
The methodology for this SEM was recently registered. A systematic search in bibliographic and gray literature sources was conducted and studies evaluated for inclusion according to the Populations, Exposures, Comparators, Outcomes, and Study type (PECOS) framework. Inclusion criteria were designed to record hazard and exposure information for all 34 PET oligomers and coded into the following evidence streams: human, animal, organism (non-animal), ex vivo, in vitro, in silico, migration, hydrolysis, and absorption, distribution, metabolism, excretion/toxicokinetics/pharmacokinetics (ADME/TK/PK) studies. Relevant information was extracted from eligible studies and synthesized according to the protocol.
Literature searches yielded 7445 unique records, of which 96 were included. Data comprised migration (560 entries), ADME/TK/PK-related (253 entries), health/bioactivity (98 entries) and very few hydrolysis studies (7 entries). Cyclic oligomers were studied more frequently than linear PET oligomers. In vitro results indicated that hydrolysis of cyclic oligomers generated a mixture of linear oligomers, but not monomers, potentially allowing their absorption in the gastrointestinal tract. Cyclic dimers, linear trimers and the respective smaller oligomers exhibit physico-chemical properties making oral absorption more likely. Information on health/bioactivity effects of oligomers was almost non-existent, except for limited data on mutagenicity.
This SEM revealed substantial deficiencies in the available evidence on ADME/TK/PK, hydrolysis, and health/bioactivity effects of PET oligomers, currently preventing appropriate risk assessment. It is essential to develop more systematic and tiered approaches to address the identified research needs and assess the risks of PET oligomers.
聚对苯二甲酸乙二醇酯（PET）低聚物在食品接触材料（FCM）中的存在已得到充分证实。消费者通过其向食品和饮料中的迁移而暴露于其中，但目前对其安全评估尚无具体指导。
本系统证据图谱（SEM）旨在确定并组织有关 34 种 PET 低聚物的危害和暴露信息方面现有的知识和相关差距，以支持监管决策。
本 SEM 的方法学最近已注册。在文献和灰色文献来源中进行了系统搜索，并根据人群、暴露、对照、结局和研究类型（PECOS）框架评估了纳入研究。纳入标准旨在记录所有 34 种 PET 低聚物的危害和暴露信息，并编码为以下证据流：人体、动物、生物体（非动物）、离体、体外、计算、迁移、水解和吸收、分布、代谢、排泄/毒代动力学/药代动力学（ADME/TK/PK）研究。从合格研究中提取相关信息，并按照方案进行综合。
文献搜索产生了 7445 个独特的记录，其中 96 个被纳入。数据包括迁移（560 项）、ADME/TK/PK 相关（253 项）、健康/生物活性（98 项）和很少的水解研究（7 项）。环状低聚物比线性 PET 低聚物研究得更频繁。体外研究表明，环状低聚物的水解会生成线性低聚物的混合物，但不会生成单体，这可能使其能够在胃肠道中被吸收。环状二聚体、线性三聚体及其较小的相应低聚物具有使口服吸收更有可能的物理化学性质。关于低聚物的健康/生物活性影响的信息几乎不存在，除了有限的关于致突变性的数据。
本 SEM 揭示了关于 PET 低聚物的 ADME/TK/PK、水解和健康/生物活性影响的现有证据存在重大缺陷，目前无法进行适当的风险评估。必须制定更系统和分层的方法来解决已确定的研究需求，并评估 PET 低聚物的风险。
