Lucia Ardoino

To meet the ever‐growing demands of wireless communication and enable new applications, the 5th generation (5G) New Radio (NR) cellular system was developed to offer better connectivity, to reduce latency, and enable higher data transfer rates. The use of the 5G frequency spectrum is divided into two frequency ranges, Frequency Range 1 (5G NR FR1) from 0.41 GHz to 7.125 GHz, operating in the same frequency range as the 2G–4G cellular systems and WLAN systems, and Frequency Range 2 (5G NR FR2) from 24.25 to 52.60 GHz using millimetre waves (mmWaves) to enable fast transfer of large amounts of data. Since 2019, FR1 has been rapidly deployed in Europe. Until today, in Europe, FR2 has very limited applications. The objective of SEAWave project was to conduct two risk assessments, one for FR1 and one for FR2. Risk assessment procedure included evaluation of evidence of an association between skin cancer and exposure to FR1 and FR2 radiofrequency electromagnetic field (RF‐EMF), with the skin being the most exposed organ during use. Both assessments are based on: a comprehensive review of the scientific literature available before the end of the project and the consolidated findings from research studies generated within the SEAWave project. Experiments conducted within SEAWave project included: (i) In vivo experiments on Carcinogenesis‐susceptible (Car‐S) mice and Patched heterozygous knockout mice (Ptch1 +/−) to investigate the effects of prolonged exposure to 5G FR2 RF‐EMF at 27.5 GHz on the development of squamous cell carcinoma (SCC) and basal cell carcinoma (BCC), two of the most common skin tumours. In addition, skin inflammation and nociceptive signalling were analysed in dorsal skin samples taken from mice after early stage whole‐body exposure in the first 21 days of postnatal life and after 100 days and 6 months of exposure; (ii) Clinical trial where participants' inner arms were exposed to 5G FR2 RF‐EMF at 27.5 GHz to study transcriptomic changes in skin samples induced by 5G FR2 RF‐EMF exposure, with particular attention to inflammatory processes; (iii) In vitro experiments using different primary human skin cell lines, that is, light‐pigmented primary epidermal juvenile and adult keratinocytes (NHEK‐f.c. and NHEK‐c.) and light‐pigmented primary epidermal adult melanocytes (NHEM) exposed to 5G FR2 RF‐EMF at 27.5 GHz to study several endpoints including genotoxicity, aneugenicity, telomere measurement, DNA methylation and transcriptomics. The overall evidence for an association between skin cancer and 5G FR1 has been classified as ‘inconclusive’ based on the evaluations of human evidence, evidence from animal studies and mechanistic studies classified as ‘inadequate’. 5G FR1 evaluations were mainly based on literature review. The overall evidence for an association between skin cancer and 5G FR2 has been classified as ‘inconclusive’ based on the evaluations of human evidence, and evidence from animal studies and mechanistic studies classified as ‘inadequate’. 5G FR2 evaluations were mainly based on findings from the SEAWave project. All classifications were unanimous except for the 5G FR2 mechanistic evidence which a minority considered ‘limited’; even with limited evidence the overall assessment for 5G FR2 would have remained ‘inconclusive’. An impact evaluation completes the risk assessment, as for inconclusive evidence no quantitative risk assessment could be carried out.

In this systematic review, the potential role of in vivo RF–EMF exposure combined with the administration of well-known carcinogens in tumor promotion/progression is assessed. A total of 25 papers were included in the review. Each paper was assessed for Risk of Bias and for the attribution of the quality category. A meta-analysis was conducted on 18 studies, analyzing data for nine different organs/tumors to assess the potential increased risk for the onset of tumors as well as the effects on survival. A descriptive review was performed for the remaining seven eligible papers. In most cases, the results of the meta-analysis did not reveal a statistically significant difference in tumor onset between the sham and co-exposed samples. There was a numerically small increase in the risk of malignant tumors observed in the kidney and liver, as well as benign lung tumors. The level of evidence for health effects indicated “inadequate” evidence for an association between in vivo co-exposure to RF–EMF and known carcinogens and the onset of malignant or benign tumors in most of the analyzed tissues. Nevertheless, the limited number of eligible papers/studies for most of the analyzed tissues suggests that these results cannot be considered definitively conclusive.

The increasing exposure of the human population to radiofrequency electromagnetic fields has increased concern about its possible health effects. The aim of this systematic review is to provide an update of the state of the research on this topic, through a quantitative analysis, to assess the increased risk of tumor incidence in laboratory animals (rodents) without limitations of species, strain, sex or genotype. The review was conducted according to the PRISMA guideline and individual studies were assessed by referring to the OHAT Risk of Bias Rating Tool for Human and Animal Studies. A total of 27 studies were considered eligible for the evaluation of tumor incidence; a meta-analysis was carried out on 23 studies to assess the possible increased risk of both malignant and benign tumors onset at the systemic level or in different organs/tissues. A significant association between exposure to RF and the increased/decreased risk of cancer does not result from the meta-analysis in most of considered tissues. A significant increased/decreased risk can be numerically observed only in heart, CNS/brain, and intestine for malignant tumors. Nevertheless, the assessment of the body of evidence attributes low or inadequate evidence for an association between RF exposure and the onset of neoplasm in all tissues.

Background: An Italian project aims to review the scientific literature on the possible carcinogenicity of radiofrequency (100 kHz–300 GHz) electromagnetic field (RF-EMF) exposure. The ENEA team has to carry out a systematic review of the in vivo studies on this topic. Objectives: Development of a protocol for a systematic review (meta-analysis included) to investigate the potential carcinogenic risk following RF-EMF in vivo exposure to doses above or within legal limits. The aims of this review are (1) to provide a descriptive and, if possible, a quantitative summary of the results of the examined RF-EMF in vivo studies, together with an assessment of the consistency of observations and of the causes of heterogeneity, and (2) to assess the weight of evidence to support or refute the hypothesis of carcinogenic effects caused by RF-EMF exposure and to draw conclusions about the potential for carcinogenicity of RF-EMF exposure. Methods: We will search for relevant studies in electronic academic databases and in the reference list of selected papers and reviews on the topic, including the descriptive reviews on RF-EMF carcinogenic effect carried out by international panels of experts since 2011. The following elements of the PECO question were defined: experimental studies on rodents of both sexes, all ages and species, all genetic backgrounds (Population) exposed to RF-EMF alone, or in combination with other physical or chemical agents (Exposure); only studies reporting outcome data in exposed and sham control groups (Comparison); and all types of cancer with all tumor-related outcome measures (Outcome) will be included. Only peer-reviewed articles written in English will be considered without limit in the publication date. Eligibility criteria were defined for papers to be included. A risk of bias assessment will be performed using a tool specifically developed for animal studies. A meta-analysis will be performed, if feasible, for all outcome measures; for subgroup analysis, a minimum of 3 studies per subgroup will be required. If meta-analysis will not be possible, a narrative synthesis of the results will be reported. Systematic review registration: PROSPERO CRD42020191105 Highlights: An Italian collaborative research agreement aims to review the scientific literature on the possible carcinogenicity of RF-EMF (100 kHz – 300 GHz). The ENEA team will systematically review and, if possible, meta-analyse estimates the effects of in vivo exposure to RF-EMF exposure on cancer. The ENEA group is a multidisciplinary team of researchers with a consolidated experience both in carcinogenicity experiments and radiofrequency dosimetric assessment. The proposed protocol uses the NTP OHAT Approach for Systematic Review as an organizing framework. The proposed protocol aims to lead to the first systematic review providing a strength of evidence assessment on this topic.

In June 2016, with the aim of ensuring a global improvement in the performance of the Italian System of the Environmental Agencies (SNPA) and its homogeneity on the national territory, an intercomparison circuit (IC) was planned and conducted concerning the measurements of electromagnetic fields associated with Long Term Evolution (LTE) mobile communications, which were very recently introduced at that time. The intercomparison circuit, designed and built according to the criteria of ISO 17043, was organized as part of a consolidated collaboration between the Institute for Environmental Protection and Research (ISPRA) and the Piedmont Regional Agency for Environmental Protection (Arpa Piemonte). The results obtained, preceded by a brief description of the entire process of organization and analysis, are the subject of this work. The IC covered in particular: the narrow band measurement procedures used in the field; the choice of decoding, measurement and extrapolation of the synthesis result; the response of the instrumentation, limited to the models in the field. The site chosen by the organizers, primarily characterized through measurements and theoretical evaluation of the field, is the roof of the Lingotto Building in Turin. A total of 27 groups participated in the circuit: 25 SNPA departments (including the organizers Arpa Piemonte and ISPRA) and 2 private labs. All participants provided the results. The outcome of the comparison was decidedly positive: only 2 participants, for whom a joint assessment of possible causes will also be illustrated (according to ISO 5725:2), achieved significantly different results.

In actual conditions of use, the power radiated from cellular phones changes during conversation depending on several factors. Upon request from the radio base station (RBS), the phone in fact, reduces, its power to a level that is deemed optimum for the quality of conversation. In this study, special phones, which had been modified to allow the continuous logging of power emitted during the calls have been used. Off-line processing of recorded data allowed the analysis of the behaviour of mobile phones under real-use conditions. Further data recorded by operators at selected base stations were used for the purposes of comparison and checking of the effectiveness of the experimental method. The results indicate a high proportion of use of the highest power levels, under any circumstance. Such behaviour is mainly due to frequent handovers requested by the control software to optimise the communication traffic.