Abstract：
The gradual increase in the global population has led to the rising demand for agricultural products worldwide. This required the introduction of environment- and public health-friendly advanced technologies for plant protection to guard yields from pest destruction in a sustainable way. Encapsulation technology is a promising procedure to increase the effectiveness of pesticide active ingredients while reducing human exposure and environmental impact. Despite the presumed favorable properties of encapsulated pesticide formulations on human health, it is necessary to systematically assess whether they are less harmful to human health than conventional pesticide products.
We aim to systematically review the literature to answer the question of whether micro- or nano-encapsulated pesticide formulations exert different degrees of toxicity than their conventional (not-encapsulated) counterparts in in vivo animal and in vitro (human, animal, and bacterial cell) non-target models. The answer is important to estimate the possible differences in the toxicological hazards of the two different types of pesticide formulations. Because our extracted data will come from different models, we also aim to perform subgroup analyses to investigate how toxicity varies across different models. A pooled toxicity effect estimate will also be performed by meta-analysis when appropriate.
The systematic review will follow the guidelines developed by the National Toxicology Program\'s Office of Health Assessment and Translation (NTP/OHAT). The protocol adheres to the Preferred Reporting Items for Systematic Reviews and meta-analyses Protocol (PRISMA-P) statement. PubMed (NLM), Scopus (Elsevier), Web of Science Core Collection (Clarivate), Embase (Elsevier), and Agricola (EBSCOhost) electronic databases will be comprehensively searched in September 2022 to identify eligible studies using multiple search terms of \"pesticide\", \"encapsulation\" and \"toxicity\" along with their synonyms and other words that are semantically related. The reference lists of all eligible articles and retrieved reviews will be manually screened to identify additional relevant papers.
We will include peer-reviewed experimental (non-target in vivo animal model and in vitro human, animal, and bacterial cell cultures) studies published as full-text articles in English language that simultaneously investigate the effect of any micro- or nano-encapsulated pesticide formulation, applied in all ranges of concentrations, duration, and routes of exposure, and its corresponding active ingredient(s) or its conventional non-encapsulated product formulation(s) used in the same ranges of concentrations, duration, and routes of exposure on the same pathophysiological outcome. We will exclude studies that examine pesticidal activity on target organisms, cultures of cells isolated from target organisms exposed in vivo or in vitro, and those using biological materials isolated from target organisms/cells.
Studies identified by the search will be screened and managed according to the review inclusion and exclusion criteria in the Covidence systematic review tool by two reviewers, who will also blindly extract the data and assess the risk of bias of included studies. The OHAT risk of bias tool will be applied to evaluate the quality and risk of bias in the included studies. Study findings will be synthesized narratively by important features of the study populations, design, exposure, and endpoints. If findings make it possible, a meta-analysis will be performed on identified toxicity outcomes. To rate the certainty in the body of evidence, we will use the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
We aim to systematically review the literature to answer the question of whether micro- or nano-encapsulated pesticide formulations exert different degrees of toxicity than their conventional (not-encapsulated) counterparts in in vivo animal and in vitro (human, animal, and bacterial cell) non-target models. The answer is important to estimate the possible differences in the toxicological hazards of the two different types of pesticide formulations. Because our extracted data will come from different models, we also aim to perform subgroup analyses to investigate how toxicity varies across different models. A pooled toxicity effect estimate will also be performed by meta-analysis when appropriate.
The systematic review will follow the guidelines developed by the National Toxicology Program\'s Office of Health Assessment and Translation (NTP/OHAT). The protocol adheres to the Preferred Reporting Items for Systematic Reviews and meta-analyses Protocol (PRISMA-P) statement. PubMed (NLM), Scopus (Elsevier), Web of Science Core Collection (Clarivate), Embase (Elsevier), and Agricola (EBSCOhost) electronic databases will be comprehensively searched in September 2022 to identify eligible studies using multiple search terms of \"pesticide\", \"encapsulation\" and \"toxicity\" along with their synonyms and other words that are semantically related. The reference lists of all eligible articles and retrieved reviews will be manually screened to identify additional relevant papers.
We will include peer-reviewed experimental (non-target in vivo animal model and in vitro human, animal, and bacterial cell cultures) studies published as full-text articles in English language that simultaneously investigate the effect of any micro- or nano-encapsulated pesticide formulation, applied in all ranges of concentrations, duration, and routes of exposure, and its corresponding active ingredient(s) or its conventional non-encapsulated product formulation(s) used in the same ranges of concentrations, duration, and routes of exposure on the same pathophysiological outcome. We will exclude studies that examine pesticidal activity on target organisms, cultures of cells isolated from target organisms exposed in vivo or in vitro, and those using biological materials isolated from target organisms/cells.
Studies identified by the search will be screened and managed according to the review inclusion and exclusion criteria in the Covidence systematic review tool by two reviewers, who will also blindly extract the data and assess the risk of bias of included studies. The OHAT risk of bias tool will be applied to evaluate the quality and risk of bias in the included studies. Study findings will be synthesized narratively by important features of the study populations, design, exposure, and endpoints. If findings make it possible, a meta-analysis will be performed on identified toxicity outcomes. To rate the certainty in the body of evidence, we will use the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
摘要：
背景：全球人口的逐渐增加导致全球对农产品的需求不断增长。这就需要引进有利于环境和公共卫生的先进植物保护技术，以可持续的方式保护虫害的产量。封装技术是一个有前途的程序，以提高农药活性成分的有效性，同时减少人体暴露和环境影响。尽管胶囊化农药制剂对人类健康具有良好的性能，有必要系统地评估它们对人体健康的危害是否比常规农药产品小。
目的：我们旨在系统地回顾文献，以回答以下问题：在体内动物和体外（人，动物,和细菌细胞)非靶标模型。答案对于估计两种不同类型的农药制剂的毒理学危害可能存在的差异非常重要。因为我们提取的数据将来自不同的模型，我们还旨在进行亚组分析,以研究不同模型的毒性差异.适当时，还将通过荟萃分析进行汇总毒性效应估计。
方法：系统评价将遵循国家毒理学计划健康评估和翻译办公室（NTP/OHAT）制定的指南。该方案符合系统审查和荟萃分析方案（PRISMA-P）声明的首选报告项目。PubMed(NLM),Scopus(Elsevier),WebofScience核心合集(Clarivate)，Embase(Elsevier),和Agricola（EBSCOhost）电子数据库将于2022年9月进行全面搜索，以使用“农药”的多个搜索词来识别符合条件的研究，“封装”和“毒性”以及它们的同义词和其他语义相关的单词。将手动筛选所有符合条件的文章和检索到的评论的参考列表，以识别其他相关论文。
方法：我们将包括同行评审的实验（非目标体内动物模型和体外人，动物,和细菌细胞培养）研究以英语全文文章形式发表，同时研究任何微米或纳米封装的农药制剂的效果，适用于所有浓度范围，持续时间,和暴露的途径，及其相应的活性成分或以相同浓度范围使用的常规非包封产品制剂，持续时间,以及相同病理生理结果的暴露途径。我们将排除对目标生物的杀虫活性的研究，从体内或体外暴露的目标生物体中分离的细胞培养物，以及使用从目标生物体/细胞分离的生物材料的那些。
方法：将根据Covidence系统审查工具中的审查纳入和排除标准，由两名审查人员筛选和管理搜索确定的研究。他们还将盲目地提取数据并评估纳入研究的偏倚风险。OHAT风险偏倚工具将用于评估纳入研究的质量和偏倚风险。研究结果将根据研究人群的重要特征进行叙述综合，设计,暴露,和端点。如果发现有可能，将对确定的毒性结果进行荟萃分析.为了评估证据的确定性，我们将使用建议等级评估，开发和评估(等级)方法。
目的：我们旨在系统地回顾文献，以回答以下问题：在体内动物和体外（人，动物,和细菌细胞)非靶标模型。答案对于估计两种不同类型的农药制剂的毒理学危害可能存在的差异非常重要。因为我们提取的数据将来自不同的模型，我们还旨在进行亚组分析,以研究不同模型的毒性差异.适当时，还将通过荟萃分析进行汇总毒性效应估计。
方法：系统评价将遵循国家毒理学计划健康评估和翻译办公室（NTP/OHAT）制定的指南。该方案符合系统审查和荟萃分析方案（PRISMA-P）声明的首选报告项目。PubMed(NLM),Scopus(Elsevier),WebofScience核心合集(Clarivate)，Embase(Elsevier),和Agricola（EBSCOhost）电子数据库将于2022年9月进行全面搜索，以使用“农药”的多个搜索词来识别符合条件的研究，“封装”和“毒性”以及它们的同义词和其他语义相关的单词。将手动筛选所有符合条件的文章和检索到的评论的参考列表，以识别其他相关论文。
方法：我们将包括同行评审的实验（非目标体内动物模型和体外人，动物,和细菌细胞培养）研究以英语全文文章形式发表，同时研究任何微米或纳米封装的农药制剂的效果，适用于所有浓度范围，持续时间,和暴露的途径，及其相应的活性成分或以相同浓度范围使用的常规非包封产品制剂，持续时间,以及相同病理生理结果的暴露途径。我们将排除对目标生物的杀虫活性的研究，从体内或体外暴露的目标生物体中分离的细胞培养物，以及使用从目标生物体/细胞分离的生物材料的那些。
方法：将根据Covidence系统审查工具中的审查纳入和排除标准，由两名审查人员筛选和管理搜索确定的研究。他们还将盲目地提取数据并评估纳入研究的偏倚风险。OHAT风险偏倚工具将用于评估纳入研究的质量和偏倚风险。研究结果将根据研究人群的重要特征进行叙述综合，设计,暴露,和端点。如果发现有可能，将对确定的毒性结果进行荟萃分析.为了评估证据的确定性，我们将使用建议等级评估，开发和评估(等级)方法。
