INTRODUCTION

To date, the National Toxicology Program (NTP) cellphone study is the most comprehensive animal experiment on the health effects of chronic radiofrequency electromagnetic radiation (RF‐EMR) exposure at high levels. Since the outcome of the study is considered to be of high relevance for human health, the final reports have attracted international attention. The strengths and weaknesses of the study have been reviewed by several scientists (e.g. Lin [2018]; Melnick [2019]), institutions (e.g. Australian Radiation Protection and Nuclear Safety Agency (ARPANSA) [2018]; Food and Drug Administration (FDA) [2018]; Bundesamt für Strahlenschutz (BfS) [2019]; Food and Drug Administration (FDA) [2020]), and organizations (e.g. Beratende Expertengruppe NIS (BERENIS) [2018]; International Commission on Non‐Ionizing Radiation Protection (ICNIRP) [2020]).

In the main NTP study, Sprague–Dawley (SD) rats and B6C3F1 mice of both sexes were exposed to GSM (TDMA) and IS‐95 (CDMA) RF‐EMR at 900 MHz (rats) and 1,900 MHz (mice) for 2 years. The unrestrained, individually housed animals were exposed in reverberation chambers that ensured a high time‐average spatial homogeneity of the exposure [Capstick et al., 2017; Gong et al., 2017]. During the 2‐year phase the animals were exposed to whole‐body specific absorption rates (wbSAR) of up to 6 W/kg (rats) and 10 W/kg (mice) in an intermittent 10‐min field on, 10‐min field off scheme with two long exposure breaks from 7 am to 11 am and from 2 pm to 3:40 pm each day, resulting in a daily net exposure duration of 9 h 10 min. The average wbSAR during field on times was kept constant throughout the whole life of the animals by adjusting the applied RF‐EMR power according to the body mass of the animals. The most prominent findings were observed in exposed male rats, including increased incidence of malignant schwannomas in the heart (GSM and IS‐95: statistically significant positive trend with increasing wbSAR; IS‐95: statistically significant increase in the 6 W/kg exposure group), reduced severity of chronic progressive nephropathy (CPN), and a number of symptoms that were judged to be correlated to this kidney disease, as well as a higher survival rate compared with sham‐exposed rats. In female rats, the number of lesions and severity of health effects was significantly lower compared with male rats. The smallest effect size was observed in mice of both sexes, although mice were exposed to nearly twice the wbSAR used in the rat studies. On the basis of the incidence of malignant schwannomas in the heart of RF‐EMR‐exposed male rats, the NTP concluded that under the whole‐body exposure conditions of the 2‐year study, there is clear evidence (highest evidence level in NTP classification) of carcinogenic activity of GSM (TDMA) and IS‐95 (CDMA) RF‐EMR in male rats. For a detailed description of the study design and findings, the reader is referred to the original technical reports [National Toxicology Program (NTP), 2018a,b].

In the main 2‐year study, body temperature measurements were not recorded. In order to select appropriate wbSAR levels for the main study, temperature measurements were carried out in pilot studies [Wyde et al., 2018]. In these pilot studies, rats and mice of different sex and age were exposed to GSM and IS‐95 RF‐EMR at wbSAR levels of up to 12 W/kg in the same intermittent scheme as applied in the main study. Body temperatures were measured individually for each rat and mouse via interscapular subcutaneously implanted microchips and readers shortly (within 1–2 min acc. to the authors) after the end of a 10‐min field‐on period at nine time points (distributed over the 5‐day study duration), as well as 3 h after initiation of the 4‐h exposure break (see Fig. 1). A wbSAR of 6 W/kg was the highest exposure level that did not lead to average subcutaneous (SC) body temperature elevations of more than 1°C in rats and was therefore selected as maximal exposure level during the 2‐year chronic exposure rat study. However, the following analysis of the published data suggests that the average values of the temperature increase at 6 W/kg can only be regarded as lower bounds of the maximum (exposure pattern‐related) temperature fluctuation (compared with sham‐exposed) of the 2‐year study.

中文翻译：

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体温调节应激作为NTP手机肿瘤研究中的潜在中介因子。

介绍

迄今为止，美国国家毒理学计划（NTP）手机研究是最全面的动物实验，旨在研究长期暴露于慢性射频电磁辐射（RF-EMR）对健康的影响。由于该研究的结果被认为与人类健康高度相关，因此最终报告已引起国际关注。几位科学家（例如Lin [ 2018]； Melnick [ 2019]）和机构（例如澳大利亚辐射防护和核安全局（ARPANSA）[ 2018]；食品和药物管理局（FDA））对该研究的优缺点进行了评论。[ 2018]；联邦议院（BfS）[ 2019]；美国食品药物管理局（FDA）[ 2020]）和组织（例如Beratende Expertengruppe NIS（BERENIS）[ 2018]；国际非电离辐射防护委员会（ICNIRP）[ 2020]）。

在主要的NTP研究中，两性的Sprague-Dawley（SD）大鼠和B6C3F1小鼠在900 MHz（大鼠）和1,900 MHz（小鼠）处暴露于GSM（TDMA）和IS-95（CDMA）RF-EMR，持续2年份。将不受约束的，单独饲养的动物暴露在混响室中，以确保暴露的时间平均高度均一性[Capstick et al。，  2017 ; 龚等人，  2017]。在2年阶段中，动物在10分钟的间歇性10分钟视野中暴露于高达6 W / kg（大鼠）和10 W / kg（小鼠）的全身比吸收率（wbSAR）每天两次，从上午7点至上午11点以及从下午2点至下午3:40 pm进行两次长时间的暴露休息，每天的净暴露时间为9小时10分钟。通过根据动物的体重调节施加的RF-EMR功率，在整个野外生存期间的平均wbSAR保持恒定。在暴露的雄性大鼠中观察到最突出的发现，包括心脏恶性神经鞘瘤的发生率增加（GSM和IS-95：wbSAR升高具有统计学上的显着正趋势； IS-95：6 W / kg暴露组具有统计学上的显着增加），降低了慢性进行性肾病（CPN）的严重程度，并确定了许多与这种肾脏疾病相关的症状，并且与假暴露的大鼠相比，存活率更高。与雄性大鼠相比，雌性大鼠的病变数量和健康影响的严重性明显降低。尽管小鼠暴露于大鼠研究中使用的wbSAR的几乎两倍，但在男女小鼠中观察到的效应大小最小。根据RF-EMR暴露的雄性大鼠心脏恶性神经鞘瘤的发生率，NTP得出结论，在为期两年的全身暴露条件下，有明确的证据（NTP分类中证据水平最高） ）GSM（TDMA）和IS‐95（CDMA）RF‐EMR对雄性大鼠的致癌活性。有关研究设计和发现的详细说明，2018a，b ]。

在主要的为期2年的研究中，没有记录体温的测量值。为了为主要研究选择合适的wbSAR水平，在试点研究中进行了温度测量[Wyde et al。，  2018]。在这些先导研究中，不同性别和年龄的大鼠和小鼠以与主要研究相同的间歇方案，以高达12 W / kg的wbSAR水平暴露于GSM和IS‐95 RF‐EMR。在10分钟的田间实验结束后的9个时间点，很快（通过作者在1-2分钟之内）通过肩inter骨皮下植入的微芯片和阅读器分别测量了每只大鼠和小鼠的体温。研究时间为5天），以及4小时的暴露中断开始后的3小时（见图1）。wbSAR为6 W / kg是最高暴露水平，不会导致大鼠的平均皮下（SC）体温升高超过1°C，因此在2年慢性暴露大鼠研究中被选择为最大暴露水平。然而，