Synergism Between Sinusoidal-50 Hz Magnetic Field and Formaldehyde in Triggering Carcinogenic Effects in Male SpragueDawley Rats Morando Soffritti, MD, 1 Eva Tibaldi, PhD, 1 Michela Padovani, MPH, 1 David G. Hoel, PhD, 2 Livio Giuliani, PhD, 3 Luciano Bua, MD, 1 Michelina Lauriola, PhD, 1 Laura Falcioni, DMV, 1 Marco Manservigi, PhD, 1 Fabiana Manservisi, PhD, 1 and Fiorella Belpoggi, PhD 1 Background Experimental rodent bioassays performed up to now have failed to provide conclusive conrmation of the carcinogenicity of extremely low frequency magnetic elds (ELFMF). Objectives To evaluate the potential synergistic carcinogenic effects of concurrent exposure to ELFMF and formaldehyde in four groups of male and female SpragueDawley rats. Methods One group was exposed from prenatal life until natural death to S-50 Hz MF and to formaldehyde in drinking water from 6 weeks of age for 104 weeks, two groups were treated only with formaldehyde or only with MF and one group served as untreated control. Results Compared to untreated controls, exposure to MF and formaldehyde causes in males a statistically signicant increased incidence of malignant tumors (P 0.01), thyroid C-cell carcinomas (P 0.01), and hemolymphoreticular neoplasias (P 0.05). No statistically signicant differences were observed among female groups. Conclusions Life-span exposure to MF and formaldehyde induces statistically signicant carcinogenic effects in male rats. Am. J. Ind. Med. ß 2016 Wiley Periodicals, Inc. KEY WORDS: carcinogenic synergism between S-50 Hz MF plus formaldehyde; SpragueDawley rats; life-span bioassays; hemolymphoreticular neoplasias; thyroid C-cell carcinomas INTRODUCTION Early epidemiological studies have shown that human exposure to extremely low frequency magnetic elds (ELFMF) increases the risk of leukemia in children [Wertheimer and Leeper, 1979], as well as lymphomas/ leukemias in adults [Milham, 1982], breast cancer in women aged less than 55 years [Wertheimer and Leeper, 1979] and also in men [Matanoski and Breysse 1989; Demers et al., 1991; Matanoski et al., 1991; Tynes et al., 1992]. Experimental long-term bioassays in which ELFMF were administered alone to rodents, failed to conrm the carcinogenic potential of ELFMF exposure [Margonato et al., 1995; Mandeville et al., 1997; Yasui et al., 1997; Boorman et al., 1999; McCormick et al., 1999]. Moreover, several short-term studies were conducted to evaluate the carcinogenic effects of combined exposure to ELFMF and well-known physical and chemical carcinogenic 1 Cesare Maltoni Cancer Research Center, Ramazzini Institute, Bologna, Italy 2 Medical University of South Carolina, Chapel Hill, South Carolina 3 National Institute for Insurance Against Injuries at Work (INAIL), Florence, Italy Correspondence to: Morando Soffritti, MD, Cesare Maltoni Cancer Research Center, Ramazzini Institute, Castello di Bentivoglio,Via Saliceto, 3, 40010 Bentivoglio, Bologna, Italy. E-mail: soffrittim@ramazzini.it Accepted 13 April 2016 DOI 10.1002/ajim.22598. Published online in Wiley Online Library (wileyonlinelibrary.com). AMERICAN JOURNAL OF INDUSTRIAL MEDICINE ß 2016 Wiley Periodicals, Inc.