Background: Salivary duct carcinoma (SDC), one subtype of the 22 different salivary gland cancers, is a rare malignancy. Risk factors for the development of salivary gland cancer and SDC are largely unknown, although pollution has been described as one of the risk factors. In other cancers, especially in lung cancer, the carcinogenicity of chromium VI [Cr(VI)] is well-known. Here we report on two SDC patients who were occupationally exposed to Cr(VI) and discuss a potential relation between their Cr(VI) exposure and the occurrence of SDC. Case Presentation: The work history of two SDC patients was analyzed for chemical exposures. Both patients had a history of Cr(VI) exposure, with maintenance of military equipment considered as the source for this exposure. Inhalation of Cr(VI) containing particles from the removal of old paint by mechanical abrasion was identified as a probable source of exposure for both patients, and one of these patients also applied new paint. Both patients reported not to have used any respiratory protection which may have resulted in substantial inhalation of Cr(VI)-containing chromates. Furthermore, in one patient inhalation of fumes from soldering may have resulted in relevant co-exposure. Conclusion: A causal relation between Cr(VI) exposure and SDC, a rare cancer, cannot be demonstrated on an individual basis but detection in a population-based study is also unlikely because of the extremely low prevalence. Nevertheless, the work history is considered a relevant risk factor in the onset of SDC as occupational exposures to Cr(VI) occurred in poorly ventilated working environment and without using appropriate respiratory protective equipment.

Small intestinal (SI) tumors are relatively uncommon outcomes in rodent cancer bioassays, and limited information regarding chemical-induced SI tumorigenesis has been reported in the published literature. Herein, we propose a cytotoxicity-mediated adverse outcome pathway (AOP) for SI tumors by leveraging extensive target species- and site-specific molecular, cellular, and histological mode of action (MOA) research for three reference chemicals, the fungicides captan and folpet and the transition metal hexavalent chromium (Cr(VI)). The gut barrier functions through highly efficient homeostatic regulation of SI epithelial cell sloughing, regenerative proliferation, and repair, which involves the replacement of up to 1011 cells per day. This dynamic turnover in the SI provides a unique local environment for a cytotoxicity mediated AOP/MOA. Upon entering the duodenum, cytotoxicity to the villous epithelium is the molecular initiating event, as indicated by crypt elongation, villous atrophy/blunting, and other morphologic changes. Over time, the regenerative capacity of the gut epithelium to compensate declines as epithelial loss accelerates, especially at higher exposures. The first key event (KE), sustained regenerative crypt proliferation/hyperplasia, requires sufficient durations, likely exceeding 6 or 12 months, due to extensive repair capacity, to create more opportunities for the second KE, spontaneous mutation/transformation, ultimately leading to proximal SI tumors. Per OECD guidance, biological plausibility, essentiality, and empirical support were assessed using modified Bradford Hill considerations. The weight-of-evidence also included a lack of induced mutations in the duodenum after up to 90 days of Cr(VI) or captan exposure. The extensive evidence for this AOP, along with the knowledge that human exposures are orders of magnitude below those associated with KEs in this AOP, supports its use for regulatory applications, including hazard identification and risk assessment.

The migration and redox transformation processes of toxic Cr(VI) in the upper and deep soil of chromate-polluted site are of great importance for the environmental risk control and soil remediation. In this study, soils from surface to deep (around 30-60 m) and the groundwater in a typical abandoned chromate production plant site which has experienced decades of contamination were both sampled and analyzed. The results show that the soil in the leaching workshop of Cr(VI), dichromate transformation workshop and chromium slag dumping ground exhibits severe contamination of chromium and the pollution has extended to the groundwater, causing serious pollution in groundwater too. The vertical migration and transformation of Cr(VI) in the soil layer are mainly affected by the soil permeability, organic matter content and the amount of water passing through the soil layer. During the downward migration, Cr(VI) tends to be retained by the clay layer and further accumulates around the depth of 5-10 m where the concentrations of both hexavalent and total Cr reach maximum values, and then continues to diffuse from the accumulation layer towards the deeper soil. Accompanying with the reduction of Cr(VI) by organic matter in the soil, the Cr(III) exists at various depths. When the depth is below the groundwater level of saturated aquifer, the distribution of chromium in the soil and groundwater reaches leaching and redox equilibrium due to the long-term interaction between the soil and groundwater.

Recent analyses-highlighted by the International Workshops on Genotoxicity Testing Working Group on Quantitative Approaches to Genetic Toxicology Risk Assessment-have identified a correlation between (log) estimates of a carcinogen\'s in vivo genotoxic potency and in vivo carcinogenic potency in typical laboratory animal models, even when the underlying data have not been matched for tissue, species, or strain. Such a correlation could have important implications for risk assessment, including informing the mode of action (MOA) of specific carcinogens. When in vivo genotoxic potency is weak relative to carcinogenic potency, MOAs other than genotoxicity (e.g., endocrine disruption or regenerative hyperplasia) may be operational. Herein, we review recent in vivo genotoxicity and carcinogenicity data for hexavalent chromium (Cr(VI)), following oral ingestion, in relevant tissues and species in the context of the aforementioned correlation. Potency estimates were generated using benchmark doses, or no-observable-adverse-effect-levels when data were not amenable to dose-response modeling. While the ratio between log values for carcinogenic and genotoxic potency was ≥1 for many compounds, the ratios for several Cr(VI) datasets (including in target tissue) were less than unity. In fact, the ratios for Cr(VI) clustered closely with ratios for chloroform and diethanolamine, two chemicals posited to have non-genotoxic MOAs. These findings suggest that genotoxicity may not play a major role in the cancers observed in rodents following exposure to high concentrations of Cr(VI) in drinking water-a finding consistent with recent MOA and adverse outcome pathway (AOP) analyses concerning Cr(VI). This semi-quantitative analysis, therefore, may be useful to augment traditional MOA and AOP analyses. More case examples will be needed to further explore the general applicability and validity of this approach for human health risk assessment.

In recent years, high concentrations of hexavalent chromium, Cr(VI), have been observed in the groundwater system of the Asopos River Basin, raising public concern regarding the quality of drinking and irrigation water. The work described herein focuses on the development of a groundwater flow and Cr(VI) transport model using hydrologic, geologic, and water quality data collected from various sources. An important dataset for this goal comprised an extensive time series of Cr(VI) concentrations at various locations that provided an indication of areas of high concentration and also served as model calibration locations. Two main sources of Cr(VI) contamination were considered in the area: anthropogenic contamination originating from Cr-rich industrial wastes buried or injected into the aquifer and geogenic contamination from the leaching process of ophiolitic rocks. The aquifer\'s response under climatic change scenario A2 was also investigated for the next two decades. Under this scenario, it is expected that rainfall, and thus infiltration, will decrease by 7.7 % during the winter and 15 % during the summer periods. The results for two sub-scenarios (linear and variable precipitation reduction) that were implemented based on A2 show that the impact on the study aquifer is moderate, resulting in a mean level decrease less than 1 m in both cases. The drier climatic conditions resulted in higher Cr(VI) concentrations, especially around the industrial areas.

The potential of magnetite nanoparticles to be applied in drinking water treatment for the removal of hexavalent chromium is discussed. In this study, a method for their preparation which combines the use of low-cost iron sources (FeSO4 and Fe2(SO4)3) and a continuous flow mode, was developed. The produced magnetite nanoparticles with a size of around 20 nm, appeared relatively stable to passivation providing a removal capacity of 1.8 μg Cr(VI)/mg for a residual concentration of 50 μg/L when tested in natural water at pH7. Such efficiency is explained by the reducing ability of magnetite which turns Cr(VI) to an insoluble Cr(OH)3 form. The successful operation of a small-scale system consisting of a contact reactor and a magnetic separator demonstrates a way for the practical introduction and recovery of magnetite nanoparticles in water treatment technology.