Ingestion of titanium dioxide as an excipient in medicines and the risk of cancer: a nationwide study within the French National health data system.

IF 7.7 1区 医学 Q1 PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH
Manon Cairat,Gianluca Severi,Inge Huybrechts,Agnès Fournier
{"title":"Ingestion of titanium dioxide as an excipient in medicines and the risk of cancer: a nationwide study within the French National health data system.","authors":"Manon Cairat,Gianluca Severi,Inge Huybrechts,Agnès Fournier","doi":"10.1007/s10654-025-01263-4","DOIUrl":null,"url":null,"abstract":"Concerns about the safety of titanium dioxide (TiO2), including potential carcinogenicity, have prompted its ban in foods in the European Union, while remaining allowed as pharmaceutical excipient. We aimed to evaluate whether ingesting increasing quantities of TiO2 through medicines is associated with higher cancer risk. Data were derived from the French National Health Data System, a nationwide medico-administrative database. A case-control study was nested within two cohorts: users of metformin (all doses) and users of 200 mg acebutolol, both available in TiO2-containing and TiO2-free formulations. During 2013-2021, 293,101 cancer cases were identified and matched to 2,930,633 controls. TiO2 exposure through metformin and acebutolol consumption was calculated based on drug claims from 2006 up to five years before the index date. Conditional logistic regression models estimated linear associations between TiO2 exposure and cancer risk. RRs of overall cancer per 1000 TiO2-containing tablets and per 10,000 mg of TiO2 increments were both 1.00 (95% CI: 0.99-1.01). Analyses by cancer site also yielded RRs very close to 1.00 or slightly different but not statistically significant, except for breast (RR per 10,000 mg: 1.03, 95% CI:1.00-1.07) and lymphoid/hematopoietic (RR per 1000 tablets: 0.97, 95% CI: 0.95-1.00) cancers, which however lost significance after Bonferroni correction. There was a suggestion of non-linear positive association for central nervous system cancers. This first epidemiological study on TiO2 ingestion and cancer found no meaningful linear association between increasing TiO2 exposure through medicines and overall or site-specific cancer risk. Non-linear associations cannot be excluded.","PeriodicalId":11907,"journal":{"name":"European Journal of Epidemiology","volume":"2 1","pages":""},"PeriodicalIF":7.7000,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Epidemiology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s10654-025-01263-4","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH","Score":null,"Total":0}
引用次数: 0

Abstract

Concerns about the safety of titanium dioxide (TiO2), including potential carcinogenicity, have prompted its ban in foods in the European Union, while remaining allowed as pharmaceutical excipient. We aimed to evaluate whether ingesting increasing quantities of TiO2 through medicines is associated with higher cancer risk. Data were derived from the French National Health Data System, a nationwide medico-administrative database. A case-control study was nested within two cohorts: users of metformin (all doses) and users of 200 mg acebutolol, both available in TiO2-containing and TiO2-free formulations. During 2013-2021, 293,101 cancer cases were identified and matched to 2,930,633 controls. TiO2 exposure through metformin and acebutolol consumption was calculated based on drug claims from 2006 up to five years before the index date. Conditional logistic regression models estimated linear associations between TiO2 exposure and cancer risk. RRs of overall cancer per 1000 TiO2-containing tablets and per 10,000 mg of TiO2 increments were both 1.00 (95% CI: 0.99-1.01). Analyses by cancer site also yielded RRs very close to 1.00 or slightly different but not statistically significant, except for breast (RR per 10,000 mg: 1.03, 95% CI:1.00-1.07) and lymphoid/hematopoietic (RR per 1000 tablets: 0.97, 95% CI: 0.95-1.00) cancers, which however lost significance after Bonferroni correction. There was a suggestion of non-linear positive association for central nervous system cancers. This first epidemiological study on TiO2 ingestion and cancer found no meaningful linear association between increasing TiO2 exposure through medicines and overall or site-specific cancer risk. Non-linear associations cannot be excluded.
作为药物辅料的二氧化钛的摄入与癌症风险:法国国家卫生数据系统内的一项全国性研究。
由于担心二氧化钛(TiO2)的安全性,包括潜在的致癌性,欧盟已禁止其在食品中使用,但仍允许其作为药物辅料。我们的目的是评估通过药物摄入越来越多的TiO2是否与更高的癌症风险有关。数据来源于法国国家健康数据系统,这是一个全国性的医疗管理数据库。一项病例对照研究嵌套在两个队列中:二甲双胍(所有剂量)使用者和200mg乙酰丁醇使用者,两种剂型均有含tio2和不含tio2剂型。在2013-2021年期间,发现了293101例癌症病例,并与2930633例对照进行了匹配。根据2006年至指标日期前5年的药品声明,计算通过二甲双胍和乙丁醇摄入的TiO2暴露量。条件逻辑回归模型估计TiO2暴露与癌症风险之间的线性关联。每1000片含TiO2片和每10000毫克TiO2增量的总癌症风险比均为1.00 (95% CI: 0.99-1.01)。对癌症部位的分析也得出了非常接近1.00或略有不同但无统计学意义的风险比,除了乳腺癌(每10000毫克的风险比:1.03,95% CI:1.00-1.07)和淋巴/造血癌(每1000片的风险比:0.97,95% CI: 0.95-1.00),但在Bonferroni校正后,它们失去了显著性。中枢神经系统癌症有非线性正相关。这是第一个关于TiO2摄入和癌症的流行病学研究,发现通过药物增加TiO2暴露与整体或特定部位的癌症风险之间没有有意义的线性关联。不能排除非线性关联。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
European Journal of Epidemiology
European Journal of Epidemiology 医学-公共卫生、环境卫生与职业卫生
CiteScore
21.40
自引率
1.50%
发文量
109
审稿时长
6-12 weeks
期刊介绍: The European Journal of Epidemiology, established in 1985, is a peer-reviewed publication that provides a platform for discussions on epidemiology in its broadest sense. It covers various aspects of epidemiologic research and statistical methods. The journal facilitates communication between researchers, educators, and practitioners in epidemiology, including those in clinical and community medicine. Contributions from diverse fields such as public health, preventive medicine, clinical medicine, health economics, and computational biology and data science, in relation to health and disease, are encouraged. While accepting submissions from all over the world, the journal particularly emphasizes European topics relevant to epidemiology. The published articles consist of empirical research findings, developments in methodology, and opinion pieces.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信