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

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.

Maternal exposure to ultrafine particles enhances influenza infection during pregnancy.

BACKGROUND: Interactions between air pollution and infectious agents are increasingly recognized and critical to identify, especially to protect vulnerable populations. Pregnancy represents a vulnerable period for influenza infection and air pollution exposure, yet interactions during pregnancy remain unclear. Maternal exposure to ultrafine particles (UFPs, [Formula: see text] 100 nm diameter), a class of particulate matter ubiquitous in urban environments, elicits unique pulmonary immune responses. We hypothesized that UFP exposure during pregnancy would lead to aberrant immune responses to influenza enhancing infection severity. RESULTS: Building from our well-characterized C57Bl/6N mouse model employing daily gestational UFP exposure from gestational day (GD) 0.5-13.5, we carried out a pilot study wherein pregnant dams were subsequently infected with Influenza A/Puerto Rico/8/1934 (PR8) on GD14.5. Findings indicate that PR8 infection caused decreased weight gain in filtered air (FA) and UFP-exposed groups. Co-exposure to UFPs and viral infection led to pronounced elevation in PR8 viral titer and reduced pulmonary inflammation, signifying potential suppression of innate and adaptive immune defenses. Pulmonary expression of the pro-viral factor sphingosine kinase 1 (Sphk1) and pro-inflammatory cytokine interleukin-1ß (IL-1 [Formula: see text]) was significantly increased in pregnant mice exposed to UFPs and infected with PR8; expression correlated with higher viral titer. CONCLUSIONS: Results from our model provide initial insight into how maternal UFP exposure during pregnancy enhances respiratory viral infection risk. This model is an important first step in establishing future regulatory and clinical strategies for protecting pregnant women exposed to UFPs.

Occupational exposure to asbestos in the steel industry (1972-2006).

BACKGROUND: Historically, the use of asbestos in steelmaking has been limited to a few applications. Due to its physical and chemical properties, asbestos was not necessary or suitable for most purposes in a steel mill. The few applications where asbestos were used (i.e., certain gaskets, brakes, protective cloth, refractory materials, insulation materials, and hot top products) were replaced by alternative materials as they became available. OBJECTIVE: We discuss historical uses of asbestos in steel manufacturing and the associated airborne asbestos concentrations collected at sixteen U. S. Steel facilities between 1972 and 2006. METHODS: A total of 495 personal airborne asbestos samples from the U. S. Steel industrial hygiene records were analyzed across four time periods corresponding to changes in the OSHA permissible exposure limit (PEL) for asbestos. 68% of the samples (n = 337) were considered representative of an employee's workday. The remaining samples (n = 158) represented task samples. Samples were grouped by facility, department, and job category within the four time periods. RESULTS: The average fiber concentrations measured for each facility and department over time were below the contemporaneous OSHA PEL. The mean representative workday asbestos air concentration from 1972 and 1975 was 1.09 f/cc. The mean representative workday concentration decreased to 0.13 f/cc between 1976 and 1985, then decreased again to 0.02 f/cc between 1986 and 1993 and 0.03 f/cc between 1994 and 2006. For task samples, the mean air concentration from 1972 to 1975 was 3.29 f/cc. The mean task sample concentration decreased to 0.48 f/cc between 1976 and 1985, then decreased again to 0.01 f/cc between 1986 and 1993 and 0.03 f/cc between 1994 and 2006. Only eleven out of the 495 samples (2.2%), for both task and representative workday samples, were in exceedance of the contemporaneous PEL(as an 8-hour TWA), ten of which occurred prior to 1978. Eight of these eleven PEL exceeding samples were task samples. Of the remaining three representative workday samples, two had unknown sampling times. IMPACT: This paper presents an analysis of all the available personal sampling data for airborne asbestos across 16 facilities of the U. S. Steel Corporation between 1972 and 2006. This dataset has previously never been publicly shared or analyzed. It represents one of the more complete industrial hygiene datasets from a corporation to be presented in a scientific journal and, due to the similarities in the processes at each mill, it should reflect analogous exposures throughout the steelmaking industry in the United States. One of the benefits of presenting these data is that it also provides insight into where asbestos-containing materials (ACMs) were used in the steel making process. This is just one example of a large firm that released information that had previously remained in file cabinets for decades. We believe that another benefit of publishing this paper is that it may encourage the largest firms in industry to assemble and analyze their industrial hygiene data to benefit the occupational hygiene, medical, and epidemiology communities. This can support future epidemiology studies and improve the design of future industrial hygiene programs.