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 litt le is known about the toxicity of most chemical mixtures. The traditional a ssumption, in the absence of further information, has been that the chemica l components of a mixture have mutually independent effects, and the toxic response to multiple chemicals is additive. The data presented here show th at mixtures of NiCl2 and CoCl2 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 NiCl2, CoCl2, or NiCl2 and CoCl2 together, and cell viability assessed 24 h later. The LD50 for NiCl2 was 5.7 mM. CoCl2, with an LD50 of 1.1 mM, was a bout five times more potent than NiCl2. Mixtures of NiCl2 and CoCl2 decreas ed cell viability synergistically. For example, a mixture of 750 muM NiCl2 and 750 muM CoCl2 reduced cell viability by more than three times the value predicted by the additive approach. We used concentration-response data fr om these studies in a mathematical model; this model describes the equivale nt inhalation exposure to an aerosol composed of a mixture of chemicals wit h 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. (C) 2001 British Occupational Hygiene Society. Published by Elsevier Science Ltd. All rights reserved.