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 in vitro studies with exposures of unclear relevance in vivo, 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：
在过去几十年的科学文献中发表的许多关于人类和实验动物的研究已经评估了滑石的潜在致癌性。许多研究报告说，滑石粉暴露与任何类型的癌症之间没有关联。为了充分了解有关滑石粉诱发人类癌症的潜力的科学现状，我们对现有的实验动物和机制证据进行了全面和系统的回顾(同时对伴随分析中的流行病学证据进行了系统回顾),以评估滑石粉是否对人类具有致癌性.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。我们还评估了滑石粉在体内迁移到潜在肿瘤部位的可能性的证据。我们确定了7项实验动物致癌性研究和11项滑石粉机理研究，以进行系统回顾。我们发现，一些滑石粉的实验性动物致癌性研究具有局限性，使其无法检测肿瘤发病率增加的敏感性。无论如何,这些研究涵盖了多种暴露途径，物种,和暴露持续时间，并且没有表明滑石粉在实验动物中是致癌物，除了在极高暴露条件下可能导致肺颗粒超负荷的大鼠中，高暴露于难溶颗粒的非特异性效应，而不是来自滑石的任何致癌特性。导致肺部肿瘤形成的肺颗粒超负荷仅在大鼠中观察到，而在任何其他物种中均未观察到，包括人类。机理研究表明，滑石没有遗传毒性或诱变性，但可以诱导一些可能是致癌途径的事件，主要是在高暴露或体外研究中，体内暴露的相关性不明确，但是这些影响在研究和细胞类型之间并不一致。这项对实验动物致癌性和滑石粉机理证据的系统评价表明，在人类中不会出现滑石粉暴露与癌症之间的关联。滑石致癌性在除大鼠以外的任何物种中都是不可能的,只有当暴露条件高到足以诱发肺颗粒超负荷时，这与人类暴露无关。
