Immune stimulation following dermal exposure to unsintered indium tin oxide

Abstract

In recent years, several types of pulmonary pathology, including alveolar proteinosis, fibrosis, and emphysema, have been reported in workers in the indium industry. To date, there remains no clear understanding of the underlying mechanism(s). Pulmonary toxicity studies in rats and mice have demonstrated the development of mediastinal lymph node hyperplasia and granulomas of mediastinal lymph nodes and bronchus-associated lymphoid tissues following exposure to indium tin oxide. Given the association between exposure to other metals and the development of immune-mediated diseases, these studies were undertaken to begin to investigate the immuno-modulatory potential of unsintered indium tin oxide (uITO) in a mouse model. Using modifications of the local lymph node assay, BALB/c mice (five animals/group) were exposed topically via intact or breached skin or injected intradermally at the base of the ear pinnae with either vehicle or increasing concentrations 2.5–10% uITO (90:10 indium oxide/tin oxide, particle size <50 nm). Dose-responsive increases in lymphocyte proliferation were observed with a calculated EC3 of 4.7% for the intact skin study. Phenotypic analysis of draining lymph node cells following intradermal injection with 5% uITO yielded a profile consistent with a T-cell-mediated response. These studies demonstrate the potential for uITO to induce sensitization and using lymphocyte proliferation as a biomarker of exposure, and demonstrate the potential for uITO to penetrate both intact and breached skin.

Comparison of the toxicity of sintered and unsintered indium-tin oxide particles in murine macrophage and epidermal cells

“…In the workplace, reduced integrity or a barrier dysfunction of the skin can lead to increased dermal absorption of chemicals allowing for the entrance of larger molecules (Anderson and Meade, 2014). There is some evidence on the ability of UITO to stimulate an immune response in mice upon dermal exposure (Brock et al, 2014). In addition, Tinkle et al have shown that particles as large as 1 μm in size can penetrate the intact epidermis (Tinkle et al, 2003).…”

“…Solubilazion by macrophages in vitro of ITO compounds via the phagolysomal acidification pathway, resulting in cell death and release of indium ions has also been shown (Gwinn et al, 2013). Though much work has been done in recent years studying the effects of ITO toxicity (Lison et al, 2009; Badding et al, 2015, 2016,2014; Brock et al, 2014), the amount of conflicting data in relation to UITO- and SITO-mediated responses makes it apparent that the pathogenesis of ITO-mediated disease warrants further research.…”

“…The Centers for Disease Control estimates that > 13 million workers in the United States are occupationally exposed to > 82,000 chemicals that can be absorbed through the skin (U.S.G.A.O, 2005). Studies done in mice have shown that topical exposure to UITO does in fact cause immune stimulation and has the potential to penetrate both intact and breached skin (Brock et al, 2014). With occupational exposure to indium on the rise (Tolcin, 2016; Hines et al, 2013), a better understanding ITO toxicity is needed to allow for improved worker health and safety.…”

The toxicology of indium tin oxide

“…Penetration through the breached skin was also demonstrated. Phenotypic analysis of draining lymph node cells following intradermal injection with 5% UITO yielded a profile consistent with a T-cell-mediated response (Brock et al, 2014).…”

“…Exposure produced no changes in body weight, no systemic signs of toxicity or visual signs of inflammation at the exposure sites (Brock et al, 2014).…”