基于证据权重的邻苯二甲酸二丁酯的危害评估研究
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1南方医科大学公共卫生学院,广东 广州 510515;2国家卫生健康委员会食品安全风险评估重点实验室,国家食品安全风险评估中心,北京 100021;3山东第二医科大学公共卫生学院,山东 潍坊 261053

作者简介:

周佩金 女 在读研究生 研究方向为卫生毒理学 E-mail: 2762801732@qq.com

通讯作者:

王小红 女 副研究员 研究方向为营养与食品卫生 E-mail: wangxiaohong@cfsa.net.cn
隋海霞 女 研究员 研究方向为食品安全风险评估 E-mail: suihaixia@cfsa.net.cn

中图分类号:

R155

基金项目:

国家重点研发计划(2024YFF1106701)


Hazard assessment of dibutyl phthalate based on weight of evidence
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1School of Public Health, Southern Medical University, Guangzhou, Guangdong 510515, China;2NHC Key Laboratory of Food Safety Risk Assessment, China National Center for Food Safety Risk Assessment, Beijing 100021, China;3School of Public Health, Shandong Second Medical University, Weifang, Shandong 261053, China

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    摘要:

    目的 应用证据权重法系统评估邻苯二甲酸二丁酯(DBP)的健康危害,明确其关键毒性效应及证据强度,为风险管理提供科学依据。方法 系统检索中英文数据库自DBP相关研究首次发表以来至2024年9月20日的文献。采用国家食品安全风险评估中心制定的毒理学数据评价指南对体内外实验研究与人群研究进行可靠性与相关性评价,依据证据权重原则构建实验与人群证据流,并从一致性、关联强度、生物合理性等维度进行证据整合,对同质的人群研究进行Meta分析。结果 共纳入423篇实验研究及62篇可合并的人群研究。证据权重整合表明:DBP的生殖与发育毒性证据充分,动物实验关键效应的最小可见损害作用水平[LOAEL:2 mg/(kg?BW?d)],其人群早产风险显著增加(合并OR=1.10,95% CI:1.01~1.20)。免疫毒性证据有限但关键,动物实验显示在低于生殖毒性LOAEL的剂量0.4 mg/(kg?BW?d)下仍可诱发效应。神经与代谢毒性证据有限,心血管、遗传毒性等证据不足。Meta分析未发现DBP与男性精子质量存在显著关联。结论 基于证据权重的系统评估,生殖与发育毒性是DBP当前证据最充分的关键效应终点,现有数据支持其健康指导值维持0.01 mg/(kg?BW)。同时,免疫毒性被识别为需高度关注的潜在敏感终点。本研究展示的证据权重整合框架,可为DBP及其他化学物的综合危害评估提供方法学参考。

    Abstract:

    Objective To systematically evaluate the health hazards of dibutyl phthalate (DBP) using the weight of evidence approach, identify its key toxicological effects and evidence strength, and provide scientific basis for risk management.Methods Literature in Chinese and English databases was retrieved from the earliest available records of DBP-related research up to September 20, 2024. The reliability and relevance of experimental and epidemiological studies were assessed in accordance with the toxicological data evaluation guidelines developed by the China National Center for Food Safety Risk Assessment. Based on the weight of evidence, the evidence streams for experimental and population studies were established, and comprehensive evidence integration was conducted from multiple dimensions including consistency, association strength, and biological plausibility. Meta-analysis was performed for homogeneous epidemiological studies.Results A total of 423 experimental studies and 62 eligible epidemiological studies were included. Weight of evidence integration indicated that sufficient evidence supported the reproductive and developmental toxicity of DBP, with a critical lowest observed adverse effect level (LOAEL) at 2 mg/(kg?BW?d). Epidemiological evidence revealed that DBP exposure significantly increased the risk of preterm birth in humans (pooled OR=1.10, 95% CI: 1.01-1.20). Evidence for immunotoxicity was limited yet critical, where animal studies demonstrated adverse immunological effects induced at a dose of 0.4 mg/(kg?BW?d), which was lower than the LOAEL for reproductive toxicity. Limited evidence was obtained for neurotoxicity and metabolic toxicity, while evidence regarding cardiovascular toxicity and genotoxicity was insufficient. No significant correlation was identified between DBP exposure and male sperm quality via meta-analysis.Conclusion Systematic assessment based on the weight of evidence approach confirms that reproductive and developmental toxicity represents the key effect endpoints with the strongest evidence for DBP currently. Existing toxicological data supports the maintaining of its tolerable daily intake at 0.01 mg/(kg?BW). Meanwhile, immunotoxicity is recognized as a potentially sensitive endpoint requiring high priority attention. The weight of evidence integration framework demonstrated in this study provides a methodological reference for comprehensive hazard assessments of DBP and other chemicals.

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周佩金,孔建博,耿雪,张倩男,王小红,隋海霞,杨辉,贾旭东.基于证据权重的邻苯二甲酸二丁酯的危害评估研究[J].中国食品卫生杂志,2026,38(6):547-566.

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  • 收稿日期:2026-05-09
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