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      Occupational Carcinogens: ELF MFs

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          Abstract

          Siemiatycki et al. (2004) published a list of occupational carcinogens based largely on the evaluations published by the International Agency for Research on Cancer (IARC), augmented with additional information on the extent of workplace exposure. They considered 28 agents as definite human occupational carcinogens (IARC group 1), 27 agents as probable occupational carcinogens (group 2A), and 113 agents as possible occupational carcinogens (group 2B). However, missing from their list of occupational carcinogens is magnetic fields (MFs) at extremely low frequencies (ELF; 3–3000-Hz), which were classified as group 2B by IARC (2002). IARC’s final conclusion (IARC 2002) is as follows: Overall, extremely low frequency magnetic fields were evaluated as possibly carcinogenic to humans (IIB), based on the statistical association of higher level residential ELF magnetic fields and increased risk for childhood leukaemia. Thus, although the evaluation is based on epidemiologic studies of childhood leukemia, the classification applies to all human exposure to ELF MFs, and thus also to occupational exposure. This interpretation has been discussed and confirmed with an IARC representative on their ELF MF panel (Cardis E, personal communication). Because enough workers are exposed to ELF MFs to clearly meet the criteria for occupational exposures set by Siemiatycki et al. (2004), we are surprised that they did not include it in their list of possible occupational carcinogens. Other groups and agencies have applied IARC’s criteria to the evaluation of ELF MF carcinogenicity. The National Institute of Environmental Health Sciences working group (NIEHS 1998) evaluated the research in that era and classified ELF EMFs (electric and magnetic fields) as possibly carcinogenic (group 2B); this classification was based on the occurrence of chronic lymphocytic leukemia (CLL) associated with occupational exposure. The California Department of Health Services also evaluated the cancer risks of EMF in 2002, and their reviewers classified it as at least group 2B, including childhood leukemia and adult brain cancer (Neutra et al. 2002). Since the IARC evaluation, several relevant studies have been published—both in vitro and in vivo work, as well as epidemiologic studies, including the following examples. Tynes et al. (2003) reported an association between exposure to calculated residential MFs and cutaneous malignant melanoma. In a cohort including all female workers, Weiderpass et al. (2003) found an association between exposure to electromagnetic fields and stomach and pancreatic cancer; Villeneuve et al. (2002) found that occupational MF exposure increased the risk of glioblastoma multiforme; Håkansson et al. (2002) investigated cancer incidence in resistance welding workers exposed to high levels of MF and found that men in the very high exposure group showed an increased incidence of tumors of the kidney, pituitary gland, biliary passages, and liver; an exposure–response relationship was indicated for these cancer sites. Women in the very high exposure group showed an increased incidence of astrocytoma I–IV, with a clear exposure–response pattern. Ivancsits et al. (2002, 2003a, 2003b) have shown that human lymphocytes exposed to ELF MFs can generate DNA single and double strand breaks from a flux density as low as 35 μT and with a strong correlation between both the intensity and duration of the MF exposure. The IARC evaluation (IARC 2002) ruled out a probable carcinogen classification (group 2A) because the expert panel found the animal studies were “inadequate evidence of carcinogenicity.” This judgment was due to many conflicting results in the repetition of long-term animal experiments. In particular, Löscher and Mevissen (1995) reported that MF exposure to Sprague-Dawley (SD) rats after 7,12-dimethylbenz[a]anthracene (DMBA) initiation increased breast tumors in the exposed animals at 50 μT compared with the control group (see also Thun-Battersby et al. 1999). However, in a similar study Anderson et al. (1999) found no evidence for a cocarcinogenic or tumor-promoting effect of MF exposure, but the study used different substrains of SD rats than used in the original study. Anderson et al. (2000) stated that “the U.S. rats were more susceptible to DMBA than the European rats”; diet and DMBA were from different sources, and there were differences in environmental conditions and in MF exposure metrics. Fedrowitz et al. (2004) compared two sub-strains of SD outbred rats; MF exposure significantly increased mammary tumor development and growth in one of the strains of rats but not in the other. These data suggest that genetic background may play a pivotal role in effects of MF exposure; this which might explain the difficulties in replicating the original animal studies of breast tumor promotion. According to the criteria used by Siemiatycki et al. (2004), a complete list of occupational agents classified as possible human carcinogens would include ELF MFs.

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          Most cited references13

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          Occupational exposures and gastrointestinal cancers among Finnish women.

          A cohort including all female workers born 1906 through 1945 (n = 413,877) in Finland was identified through the Population Census of Finland of 1970. Incident cases of cancers of the gastrointestinal tract were explored during 1971 to 1995. Job titles in census records were converted to exposures of 31 occupational agents through a job-exposure matrix. For each agent, the product of level and probability of exposures was calculated and subdivided in three categories: zero, low and medium/high. Poisson regression models estimated relative risks (RR) for each agent, standardized for birth cohort, follow-up period, and socioeconomic status. Adjustment at job title level was done for alcohol use for cancers of the esophagus and liver and smoking for pancreatic cancer. The results showing either statistically significant RR at the medium/high level of exposure (RRH) or statistically significant trend (P < 0.05) over the exposure categories were considered as positive findings. Colon cancer risk (2009 cases) was positively associated with sedentary work (RRH 1.3, 95% CI = 1.1-1.6; P trend 0.001) and negatively associated with perceived workload (P trend = 0.007). For stomach cancer (1881 cases), we observed an association with exposure to electromagnetic fields (RRH 1.44, 95% CI = 1.01-2.05) and man-made vitreous fibers (MMVF) (p trend 0.03). Rectal cancer (1323 cases) showed an association with chromium (RRH 1.9, 95% CI = 1.2-3.1) and oil mist (RR 2.0; 95% CI = 1.0-3.9). For pancreas cancer (1302 cases) we found associations with exposure to chromium (RRH 1.8; 95% CI = 1.0-3.1; P trend 0.01), electromagnetic fields (RRH 1.8; 95% CI = 1.2-2.8; P trend 0.02), and sedentary work (RRH 1.3; 95% CI = 1.0-1.7; P trend 0.05). We found no significant associations between any FINJEM agents and cancers of the esophagus (389 cases), liver (389 cases), and gallbladder (651 cases). Having examined the associations between seven cancer sites and over 30 exposures there exists the real possibility that some of the associations detected are chance findings. Therefore, the associations observed should need to be confirmed in other studies.
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            Induction of DNA strand breaks by intermittent exposure to extremely-low-frequency electromagnetic fields in human diploid fibroblasts.

            Results of epidemiological research show low association of electromagnetic field (EMF) with increased risk of cancerous diseases and missing dose-effect relations. An important component in assessing potential cancer risk is knowledge concerning any genotoxic effects of extremely-low-frequency-EMF (ELF-EMF). Human diploid fibroblasts were exposed to continuous or intermittent ELF-EMF (50Hz, sinusoidal, 24h, 1000microT). For evaluation of genotoxic effects in form of DNA single- (SSB) and double-strand breaks (DSB), the alkaline and the neutral comet assay were used. In contrast to continuous ELF-EMF exposure, the application of intermittent fields reproducibly resulted in a significant increase of DNA strand break levels, mainly DSBs, as compared to non-exposed controls. The conditions of intermittence showed an impact on the induction of DNA strand breaks, producing the highest levels at 5min field-on/10min field-off. We also found individual differences in response to ELF-EMF as well as an evident exposure-response relationship between magnetic flux density and DNA migration in the comet assay. Our data strongly indicate a genotoxic potential of intermittent EMF. This points to the need of further studies in vivo and consideration about environmental threshold values for ELF exposure.
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              Intermittent extremely low frequency electromagnetic fields cause DNA damage in a dose-dependent way.

              Epidemiological studies have reported an association between exposure to extremely low frequency electromagnetic fields (ELF-EMFs) and increased risk of cancerous diseases, albeit without dose-effect relationships. The validity of such findings can be corroborated only by demonstration of dose-dependent DNA-damaging effects of ELF-EMFs in cells of human origin in vitro. Cultured human diploid fibroblasts were exposed to intermittent ELF electromagnetic fields. DNA damage was determined by alkaline and neutral comet assay. ELF-EMF exposure (50 Hz, sinusoidal, 1-24 h, 20-1,000 mu T, 5 min on/10 min off) induced dose-dependent and time-dependent DNA single-strand and double-strand breaks. Effects occurred at a magnetic flux density as low as 35 mu T, being well below proposed International Commission of Non-Ionising Radiation Protection (ICNIRP) guidelines. After termination of exposure the induced comet tail factors returned to normal within 9 h. The induced DNA damage is not based on thermal effects and arouses concern about environmental threshold limit values for ELF exposure.
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                Author and article information

                Journal
                Environ Health Perspect
                Environmental Health Perspectives
                National Institute of Environmental Health Sciences
                0091-6765
                November 2005
                : 113
                : 11
                : A726-A727
                Affiliations
                National Institute for Working Life, Umeå, Sweden
                Örebro University, Örebro, Sweden
                National Institute for Occupational, Safety and Health, Cincinnati, Ohio, E-mail: jdb0@ 123456cdc.gov
                Medical University of Vienna, Vienna, Austria
                Author notes

                The authors declare they have no competing financial interests.

                K.H.M. was a member of IARC’s 2001 group of experts. M.O.M. and J.D.B. were members of the NIEHS working group.

                Article
                ehp0113-a00726
                1310936
                16263490
                ff20055a-a56f-41f7-8b18-82b8214e027d
                This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose.
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