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滑石粉与人类癌症:实验动物和机制证据的系统评价。

Talc and human cancer: a systematic review of the experimental animal and mechanistic evidence.

机构信息

Gradient, Seattle, WA, USA.

Gradient, Boston, MA, USA.

出版信息

Crit Rev Toxicol. 2024 Jul;54(6):359-393. doi: 10.1080/10408444.2024.2349668. Epub 2024 Jul 9.

Abstract

The potential carcinogenicity of talc has been evaluated in many studies in humans and experimental animals published in the scientific literature over the last several decades, with a number of these studies reporting no associations between talc exposure and any type of cancer. In order to fully understand the current state of the science regarding the potential for talc to induce human cancers, we conducted a comprehensive and systematic review of the available experimental animal and mechanistic evidence (in conjunction with a systematic review of the epidemiology evidence in a companion analysis) to evaluate whether it supports talc as being carcinogenic to humans. We considered study quality and its impact on the interpretation of results and evaluated all types of cancer and all exposure routes. We also evaluated the evidence on the potential for talc to migrate in the body to potential tumor sites. We identified seven experimental animal carcinogenicity studies and 11 mechanistic studies of talc to systematically review. We found that several of the experimental animal carcinogenicity studies of talc have limitations that preclude their sensitivity to detect increases in tumor incidence. Regardless, the studies cover multiple exposure routes, species, and exposure durations, and none indicate that talc is a carcinogen in experimental animals except in rats under conditions of extremely high exposure that likely resulted in lung particle overload, a nonspecific effect of high exposures to poorly soluble particles, and not from any carcinogenic properties of talc. Lung particle overload leading to lung tumor formation has only been observed in rats and not in any other species, including humans. The mechanistic studies indicate that talc is not genotoxic or mutagenic, but can induce some effects that could be events on a possible pathway to carcinogenicity, mainly at high exposures or in studies with exposures of unclear relevance , but these effects are not consistent across studies and cell types. This systematic review of the experimental animal carcinogenicity and mechanistic evidence for talc indicates that an association between talc exposure and cancer is not expected in humans. Talc carcinogenicity is not plausible in any species except rats, and only when the exposure conditions are high enough to induce lung particle overload, which is not relevant to human exposures.

摘要

滑石的潜在致癌性已在过去几十年中在科学文献中发表的许多人类和实验动物研究中进行了评估,其中一些研究报告滑石暴露与任何类型的癌症之间没有关联。为了全面了解滑石是否有可能导致人类癌症的当前科学状况,我们对现有的实验动物和机制证据进行了全面系统的审查(同时对伴随分析中的流行病学证据进行了系统审查),以评估它是否支持滑石被认为对人类具有致癌性。我们考虑了研究质量及其对结果解释的影响,并评估了所有类型的癌症和所有暴露途径。我们还评估了滑石在体内向潜在肿瘤部位迁移的潜力的证据。我们确定了七项滑石致癌性的实验动物研究和十一项滑石的机制研究进行系统评价。我们发现,一些滑石的实验动物致癌性研究存在局限性,无法检测到肿瘤发病率的增加。尽管如此,这些研究涵盖了多种暴露途径、物种和暴露时间,没有一项表明滑石在实验动物中是致癌物质,除非在大鼠中暴露于极高水平下,这种情况下可能导致肺部粒子过载,这是对难溶性粒子高暴露的一种非特异性效应,而不是滑石的致癌特性所致。导致肺部肿瘤形成的肺部粒子过载仅在大鼠中观察到,而在其他物种中均未观察到,包括人类。机制研究表明,滑石没有遗传毒性或致突变性,但可以诱导一些可能是致癌途径上的事件的效应,主要在高暴露或在与暴露相关性不明确的研究中,但这些效应在不同的研究和细胞类型中并不一致。这项对滑石的实验动物致癌性和机制证据的系统评价表明,滑石暴露与癌症之间的关联在人类中是不会发生的。除了大鼠以外,滑石在任何物种中都没有致癌性,只有在暴露条件足够高以致诱导肺部粒子过载时才会发生,而这种情况与人类暴露无关。

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