"RFR Exposure Facility

The exposure facility was specifically designed to expose rats in reverberation chambers to three different power levels of modulated cell phone RFR [Global System for Mobile Communications (GSM) or Code Division Multiple Access (CDMA)] at 900 MHz for up to 2 years to evaluate toxicity and carcinogenicity. The completed exposure facility consisted of a total of 21 RFR reverberation exposure chambers (14 designated for rats); the RFR signal generation, amplification, and monitoring systems; software for chamber operation; and hardware and software for monitoring of environmental and exposure conditions within each chamber. All system hardware and software was installed by the IT’IS Foundation. During exposures, modulated (GSM or CDMA) RFR signals were generated by a signal generator, amplifiers amplified the signals, and the signals were delivered by antennas in the reverberation chambers. RFR field strengths were monitored in real time and were adjusted throughout the studies to achieve specific exposure levels [based on SARs quantitated in watts (W) per kg body weight]. Environmental conditions were also monitored and controlled in real time throughout the study. RFR exposures and environmental conditions were monitored and controlled by a computer in a control room at the study laboratory at IITRI; the IT’IS Foundation was also capable of remote system monitoring and control.

Facility Design and Reverberation Chambers

Each reverberation chamber was permanently programmed for a specified modulation (GSM or CDMA) of the 900 MHz RFR specified for the rat studies. Designated SARs for each chamber were selected prior to exposures. The field strength required to achieve a given target SAR (W/kg) exposure level is a function of animal body weight (kg) and were adjusted to provide consistent SARs as the animals grew. However, separate chambers were required for male and female rats because their body weights differ by almost a factor of two after a few weeks of development. To conduct robust toxicology studies with three exposure groups (low, medium, and high), six chambers were required for different levels of exposures for GSM modulation and six for CDMA modulation. Two sham exposure chambers without any cell phone RFR signal provided shared control groups for the parallel studies of the two modulations. As per these requirements, the cell phone RFR exposure facility consisted of 14 reverberation chambers for exposures in rats including: • Three power levels for F0 females and F1 males exposed to GSM-modulated cell phone RFR at 900 MHz. • Three power levels for F1 females exposed to GSM-modulated cell phone RFR at 900 MHz. • Three power levels for F0 females and F1 males exposed to CDMA-modulated cell phone RFR at 900 MHz. • Three power levels for F1 females exposed to CDMA-modulated cell phone RFR at 900 MHz. • One sham control chamber for F0 females and F1 males with no RFR exposure. • One sham control chamber for F1 females with no RFR exposure. The chamber size was designed to accommodate the RF field stirring paddles (described below), approximately 110 individually housed rats, and a minimum distance (3/4 of a wavelength) between the cages and the walls, floor, ceiling and stirrers, respectively. The interior of the chamber was suitable for cleaning using high-pressure water (after the RF antennas were protected). The internal dimensions of the chambers were 2.2 m (width) × 3.7 m (length) × 2.6 m (height); the exterior dimensions were 2.3 m (width) × 3.8 m (length) × 2.85 m (height). A floorplan for the exposure facility and images of the interior and exterior of the chambers are presented in Figure 4 and Figure 5. Each chamber contained two motor-controlled stirring paddles (one vertical and one horizontal) with adjustable speed control (1 to 50 rpm) and large asymmetrical reflecting surfaces. Stirring paddles were placed off center in the chamber for maximum scattering of the RFR fields to generate a statistically homogeneous field distribution when averaged over time. The horizontal stirrer was mounted on the ceiling of the chamber. The vertical stirrer was at the rear of the chamber and was protected by rack guides that prevented contact with the animal cage racks.

Cage Racks and Watering System

Cages, cage racks, and watering systems for standard laboratory use contain elements that have the ability to alter the exposure of the animals or introduce potential confounding factors. Because cage racks and the drinking water delivery system were contained inside the chambers during exposure periods, it was required that these components be constructed of durable materials that had essentially no impact on the RF fields generated in the chamber. Metallic cage rack components, cage lids, feed dispensers, and cage grommets all needed to be eliminated. Hence, custom engineering was required to overcome the challenges regarding potential RFR exposure-altering aspects of the caging and cage racks used to house the animals during the studies. The safe provision of drinking water provided the largest challenge for the studies. The absorption of RFR energy by water if supplied by nonmetallic sipper tubes and distribution systems or bottles, could lead to dose-dependent elevated water temperatures. At the same time, the potential for enhanced exposure fields by metallic sipper tubes or lixits precluded the use of water bottles or a standard automatic watering system in the reverberation chambers. The absorption of RFR energy by water could result in significant heating of the drinking water, thereby decreasing water palatability, and increasing the required RFR power to achieve the desired exposure field strength, potentially to the extent that the exposure levels could not be met. To overcome theses challenges, adaptations were made to an automatic watering system so that the delivery of drinking water to the animals would not interfere with RFR dosimetry. The water system was constructed from stainless steel ensuring no dose-dependent energy absorption in the water (avoiding exposure-dependent water temperature) and in structures around the lixits to ensure no enhanced fields that could lead to excessive SAR in the animals while drinking. Customized, nonmetallic animal cage racks for the reverberation chambers were designed by IITRI to minimize any absorption of RFR or disruption of RF field homogeneity. Cage racks were constructed primarily of box beam fiberglass (with some angle beam fiberglass used in nonweight-bearing areas of the rack). The shelves/cage lids were constructed of a clear polycarbonate sheet with slots for increased airflow. The potential impact of the racks on RF fields was evaluated in the prototype reverberation chamber by the IT’IS Foundation. Cage racks were designed to accommodate the automatic watering system and position the perimeter of each animal cage at least one-half wavelength from any reflecting surface. The specific considerations for design and further details of the custom-designed cage racks and adapted automated watering system are provided in Capstick et al.148 and in the video presentatione by Dr. Myles Capstick3.

RFR Exposure System Control

The hardware and chambers designated for rats (using an exposure frequency of 900 MHz) were connected to a dedicated computer control system using an Ethernet protocol. The computerized control system managed and monitored the RFR exposures and environmental conditions in the chambers. A more detailed description of the computer control of RFR exposure is provided in Capstick et al.148. The control computer managed the exposure schedule, stirrer rotation speeds, exposure signal and level, and monitored air flow, temperature, humidity, light, and the electric and magnetic fields (E- and H-fields, respectively) in each chamber. The hardware for the exposure system consisted of the control computer and a rack containing communications interfaces and instrumentation for signal generation, data acquisition, signal monitoring, signal amplifiers, and the chamber hardware (which included the stirrer motors and environmental and RFR sensors). The instrumentation rack contained the equipment that generated the RFR signal, acquired RFR field strengths and environmental data, and provided an interface between the components and the control computer.

RFR Signal Generation

GSM-modulated and CDMA-modulated cell phone RFR signals were generated experimentally via a SMIQ02B vector signal generator with options SMIQB11 and SMIQB20 and software options 100421–100423 (Rohde and Schwarz, Munich, Germany). Signals were amplified using 12 LSE™ amplifiers (LSE, Spanga, Sweden) in the exposure system. The outputs of each individual amplifier were set by real-time controllers on a slot-by-slot basis for GSM or CDMA modulation to control the E-field strength in each chamber. Each chamber contained at least one standard gain antenna (two half-wave dipoles) that was mounted a quarter of a wavelength in front of a reflector plate. Antennas were directed towards one of the two stirrers to maximize scattering and obtain acceptable E-field homogeneity within the chamber space. The computerized control system managed the exposure schedule, stirrer rotation speeds, and exposure signal type and level. The RFR power introduced into a given chamber was adjusted to achieve target field strengths: to maintain constant exposure levels (W/kg) in a given chamber, the field strengths [measured in volts (V) per meter] were regularly adjusted to reflect changes in the average mass of the exposed animals. The relationship between animal mass, field strength, and SAR was determined from numerical dosimetry and programmed into the control software, hence the required exposure field strength was computed from the average animal weights entered for each exposure group. The interval at which animal weights were updated was determined on how rapidly the animals were growing, at the start of the exposure period this was once per week, and as long as up to every 4 weeks later in the studies.

Verification of RFR Exposure

Prior to initiation of the animal studies, the RF Fields Group in the Communications Technology Laboratory at the NIST performed an independent, detailed evaluation of each of the reverberation chambers (excluding the sham control chambers; Figure 4) to verify the RFR exposure fields, chamber characteristics (field uniformity), and signal quality to determine the accuracy of field values reported by the developers of the exposure system (IT’IS Foundation). This information provided in the videof (day 1 p.m. at 0 minutes) by John Ladbury3. Full reports detailing the procedures for measurements and calculations are available from the NTP. NIST performed two additional detailed evaluations: 1) in the interim period between completion of the 28-day studies and prior to initiation of the 2-year studies, and 2) following completion of the 2-year studies. All E-field measurements were within the estimated uncertainty bounds, indicating that the chamber fields measured by the NIST agreed with the measurements provided by the IT’IS Foundation probes. During validation, it was determined that the H-field probes at higher signal levels in the mid- and high-power GSM chambers reported higher fields than indicated by other measurements, potentially leading to a modest overestimation of chamber field strengths. In these chambers, H-field probes were replaced with E-field probes, which provided more accurate measurements of the RF fields. The magnitude of field variation throughout the volume of a fully loaded chamber was consistent with earlier values reported for the prototype chamber. However, it was determined that there may have been up to ± 2.5 dB of variation in the exposure field depending on location in the cage racks. To mitigate this positional variation, cages were routinely rotated to various locations within and between the cage racks. The quality of the modulated signals was found to be acceptable with regard to distortion and harmonic content. Overall, NIST confirmed that the RFR reverberation chamber exposure system was operating correctly and RFR exposures were within specifications.

RFR Exposure Monitoring

During all exposure periods, experimentally generated RFR was continuously monitored by the control system via two RF sensors (E- and/or H-field probes) in each exposure chamber that measured real-time signal strengths. The use of two probes provided two independent measurements of RF field strengths and ensured that appropriate quantitation of experimentally generated RF fields continued even in the unlikely event that one probe failed. The E-field sensor measured electric field strength (V/m). The H-field sensor measured magnetic field strength [measured in amperes (A) per meter]. All chambers were instrumented either with one E-field sensor (ER3DV6) and one H-field sensor (H3DV6) [both from Schmid and Partner Engineering AG (SPEAG), Zurich, Switzerland], except for the medium- and high-power GSM chambers. These chambers were instrumented with two E-field probes because H-field probes saturated at high field strengths. This change in hardware did not result in the loss of monitoring capability. The measured E- and H-fields were communicated to the control computer in order to maintain exposure to selected levels of RFR. During daily shutdown periods when RFR exposures were not active, RF sensors monitored ambient RF fields in the exposure chambers. RF sensors were calibrated twice by the manufacturer (SPEAG); once prior to initiation of any of the animal studies and once prior to initiation of the 2-year studies. All E-field probes were calibrated in air from 100 MHz to 3.0 GHz, and had an absolute accuracy of ± 6.0% (k = 2) with a spherical isotropy of better than ± 0.4 dB. All H-field probes were calibrated in air from 200 MHz to 3.0 GHz and had an absolute accuracy of ± 6.0% (k = 2) with a spherical isotropy of better than ± 0.2 dB. Placement of probes within the chambers is discussed in the videog (day 1 a.m. at 1 hours, 31 minutes)3. Data collected by the RF sensors were transmitted to the exposure and monitoring system on a real-time basis and were recorded throughout the studies. Chamber field strengths are reported as V/m and animal exposure levels (SAR values) are reported as W/kg. The chamber field strength is the average effective E-field strength from both probes. E- and H-field strengths are related by the impedance of free space which is ~377 Ohms. Where an H-field probe was used, the value in A/m was multiplied by 377 to calculate the equivalent E-field strength in V/m; it is this effective E-field value that was used to report the chamber field strength. Field strength data reported for each day of exposure included mean ± standard deviation, minimum field strength, maximum field strength, total number of readings in range/total number of readings for the period, and percentage of readings in range. After each exposure day, RFR exposure data were downloaded onto DVDs for long-term archival. Summaries of the 2-year RFR exposure data from the studies are presented in Appendix I. The SAR and chamber-fields in the exposure chambers were within the target ranges (defined as ± 2 dB) for >99.97% of recorded measurements over the course of the 2-year study; ≥99.25% of recorded E-field and H-field measurements were within the target ranges. All recorded broadband field measurements (<40 MHz to >6 GHz) were below the limit of detection of the probes within the sham chamber showing that there was no significant confounding exposure. In the 28-day studies, the performance of the sham control and exposure chambers was similar for SAR and field measurements as in the 2-year studies (data not shown). As previously stated, the performance of the RFR exposure and monitoring system was independently validated by engineers from the NIST prior to the initiation of the animal studies."

Sprague-Dawley rats, male

HAWC