Trinickel disulphide

Immunotoxicity

Description of key information

Available data may contribute to a weight of the evaluation, additional studies are required to characterize this endpoint, particularly as it relates to interspecies differences as well as route-specific effects.

Additional information

Three studies characterizing immunotoxicity following exposures to Ni3S2 were identified. These studies evaluated a wide variety of endpoints in monkeys, mice, and human lymphocytes, though because of the variable study design and exposure methods, the findings were not directly comparable. No studies evaluating neurotoxicity or other special investigations were identified. Haley et al. (1987) examined the immunotoxicity of Ni3S2 in monkeys that were previously immunized and repeatedly challenged with sheep red blood cells (SRBCs) in specific lung lobes. Bronchoalveolar lavage samples (BAL) were assessed for alterations in cell number and function. Exposure-related effects included decreased macrophage phagocytic activity, increased target cell killing, and tissue damage (e.g., mild focal accumulations of macrophages and lymphocytes). The authors concluded that alveolar macrophages were sensitive to the toxic effects of nickel and that local instillation of Ni3S2 in primate lung resulted in suppression of pulmonary alveolar macrophage function accompanied by a secondary increase in NK cell-mediated killing of target cells. The same group of researchers examined the immunological effects of up to 13 weeks of Ni3S2 exposure via inhalation (0.11, 0.45, and 1.8 mg Ni/m3) in mice (Haley et al. 1990). Mice were exposed 6 hr/day, 5 d/wk for 13 weeks. Treatment-related effects included decreased thymus weight, increased nucleated cells in lung lavage fluid and lung-associated lymph nodes (LALN), increased antibody forming cell (AFC) response in LALN and decrease in spleen cells, reduction of thymidine uptake in spleen cells, reduced phagocytic activity in alveolar macrophages, and decreased splenic natural killer cell cytolytic activity. Based on these findings, the authors concluded that inhalation of nickel compounds at occupationally relevant concentrations could result in significant alterations of pulmonary and systemic immune defenses. Zeromski et al. (1995) examined a variety of immunotoxicity endpoints associated with Ni3S2 exposures in human lymphocytes. Initially, a dose-finding study was conducted to identify doses of Ni3S2 that did not affect short-term cell viability in culture. Second, a series of assays was conducted to assess the natural killer activity Ni3S2 exposure in vitro. Findings led the authors to conclude that nickel subsulfide had deleterious effects on human peripheral blood mononuclear cells in short-term in vitro culture, but the presence and magnitude of these effects was dependent on the cell subsets. In this in vitro study, Ni3S2 selectively depleted helper/inducer T lymphocytes and natural killer cells, while also reducing natural killer cell function. Collectively, data indicate that Ni3S2 exposures can result in immunotoxicity in rodents and monkeys, and potential effects may also occur in humans. Though these data may contribute to a weight of the evaluation, additional studies are required to characterize this endpoint, particularly as it relates to interspecies differences as well as route-specific effects.