Mixtures of nickel and cobalt chlorides induce synergistic cytotoxic effects: implications for inhalation exposure modeling.
Workers are often simultaneously exposed to two or more chemicals, yet little is known about the toxicity of most chemical mixtures. The traditional assumption, in the absence of further information, has been that the chemical components of a mixture have mutually independent effects, and the toxic response to multiple chemicals is additive. The data presented here show that mixtures of NiCl(2) and CoCl(2) induce a synergistic (that is, greater than additive) toxic response in cell culture. Immortalized alveolar epithelial type II cells were incubated for 4 h with various concentrations of either NiCl(2), CoCl(2), or NiCl(2) and CoCl(2) together, and cell viability assessed 24 h later. The LD(50) for NiCl(2) was 5.7 mM. CoCl(2), with an LD(50) of 1.1 mM, was about five times more potent than NiCl(2). Mixtures of NiCl(2) and CoCl(2) decreased cell viability synergistically. For example, a mixture of 750 microM NiCl(2) and 750 microM CoCl(2) reduced cell viability by more than three times the value predicted by the additive approach. We used concentration-response data from these studies in a mathematical model; this model describes the equivalent inhalation exposure to an aerosol composed of a mixture of chemicals with different toxicities and also accounts for synergistic responses to these chemicals. Our results along with previous studies using an animal model suggest that these synergisms should be taken into account when conducting future exposure assessments.
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Division of Environmental and Occupational Health, School of Public Health, University of Minnesota, Mayo Mail Code 807, 420 Delaware Street SE, 55455, Minneapolis, MN, USA.
Ramachandran
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Wattenberg
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D000393:Air Pollutants; D000818:Animals; D002470:Cell Survival; D002477:Cells / Q000187:drug effects*; D002478:Cells, Cultured; D003035:Cobalt / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006801:Humans; D008962:Models, Theoretical; D009532:Nickel / Q000633:toxicity*; D016273:Occupational Exposure; D011650:Pulmonary Alveoli / Q000166:cytology
D000393:Air Pollutants; D003035:Cobalt; C022838:nickel chloride; D009532:Nickel; C018021:cobaltous chloride