Development of health-based exposure limits for radiofrequency radiation from wireless devices using a benchmark dose approach

Background Epidemiological studies and research on laboratory animals link radiofrequency radiation (RFR) with impacts on the heart, brain, and other organs. Data from the large-scale animal studies conducted by the U.S. National Toxicology Program (NTP) and the Ramazzini Institute support the need for updated health-based guidelines for general population RFR exposure. Objectives The development of RFR exposure limits expressed in whole-body Specific Absorption Rate (SAR), a metric of RFR energy absorbed by biological tissues. Methods Using frequentist and Bayesian averaging modeling of non-neoplastic lesion incidence data from the NTP study, we calculated the benchmark doses (BMD) that elicited a 10% response above background (BMD10) and the lower confidence limits on the BMD at 10% extra risk (BMDL10). Incidence data for individual neoplasms and combined tumor incidence were modeled for 5% and 10% response above background. Results Cardiomyopathy and increased risk of neoplasms in male rats were the most sensitive health outcomes following RFR exposures at 900 MHz frequency with Code Division Multiple Access (CDMA) and Global System for Mobile Communications (GSM) modulations. BMDL10 for all sites cardiomyopathy in male rats following 19 weeks of exposure, calculated with Bayesian model averaging, corresponded to 0.27–0.42 W/kg whole-body SAR for CDMA and 0.20–0.29 W/kg for GSM modulation. BMDL10 for right ventricle cardiomyopathy in female rats following 2 years of exposure corresponded to 2.7–5.16 W/kg whole-body SAR for CDMA and 1.91–2.18 W/kg for GSM modulation. For multi-site tumor modeling using the multistage cancer model with a 5% extra risk, BMDL5 in male rats corresponded to 0.31 W/kg for CDMA and 0.21 W/kg for GSM modulation. Conclusion BMDL10 range of 0.2—0.4 W/kg for all sites cardiomyopathy in male rats was selected as a point of departure. Applying two ten-fold safety factors for interspecies and intraspecies variability, we derived a whole-body SAR limit of 2 to 4 mW/kg, an exposure level that is 20–40-fold lower than the legally permissible level of 0.08 W/kg for whole-body SAR under the current U.S. regulations. Use of an additional ten-fold children’s health safety factor points to a whole-body SAR limit of 0.2–0.4 mW/kg for young children.

Quantitative analysis of mutagenicity and carcinogenicity of 2-amino-3-methylimidazo[4,5-f]quinoline in F344 gpt delta transgenic rats

Quantitative analysis of the mutagenicity and carcinogenicity of the low doses of genotoxic carcinogens present in food is of pressing concern. The purpose of the present study was to determine the mutagenicity and carcinogenicity of low doses of the dietary genotoxic carcinogen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ). Male F344 gpt delta transgenic rats were fed diets supplemented with 0, 0.1, 1, 10 or 100 ppm IQ for 4 weeks. The frequencies of gpt transgene mutations in the liver were significantly increased in the 10 and 100 ppm groups. In addition, the mutation spectra was altered in the 1, 10 and 100 ppm groups: frequencies of G:C to T:A transversion were significantly increased in groups administered 1, 10 and 100 ppm IQ in a dose-dependent manner, and the frequencies of G:C to A:T transitions, A:T to T:A transversions and A:T to C:G transversions were significantly increased in the 100 ppm group. Increased frequencies of single base pair deletions and Spi− mutants in the liver, and an increase in glutathione S-transferase placental form (GST-P)-positive foci, a preneoplastic lesion of the liver in rats, was also observed in the 100 ppm group. In contrast, neither mutations nor mutation spectra or GST-P-positive foci were statistically altered by administration of IQ at 0.1 ppm. We estimated the point of departure for the mutagenicity and carcinogenicity of IQ using the no-observed-effect level approach and the Benchmark dose approach to characterise the dose–response relationship of low doses of IQ. Our findings demonstrate the existence of no effect levels of IQ for both in vivo mutagenicity and hepatocarcinogenicity. The findings of the present study will facilitate an understanding of the carcinogenic effects of low doses of IQ and help to determine a margin of exposure that may be useful for practical human risk assessment.

Use of the benchmark dose approach for evaluation of dose and time-dependent response to 7-hydroxycoumarin 90-day exposure in rat females

Benchmark dose (BMD) analysis of existing data sets from experimental studies on animal for which NOAEL/LOAEL information is available allows to satisfy the need for quantifiable, scientifically justifiable approach to risk assessment. Previous study of 7-hydroxycoumarin (7-HOC) 3 months toxicity on rats revealed carbohydrates and lipids metabolism disturbance (blood glucose level (BGL) decrease, serum triglyceride level (STL) rise) as biologically relevant parameters to set up NOEL (20 mg/kg). Purpose. To conduct the dose and time of exposure effect dependence comparative analysis of BGL and STL published data set of 7-HOC subchronic toxicity in rats using BMD and NOAEL/LOAEL methodologies. Materials and methods. The available continuous data of STL and BGL from subchronic 7-HOC toxicity study data set for rat females were analyzed by means United States Environmental Protection Agency proposed software, BMDS 2.6.0.1. The response level was set as 10 %. Results. Hill’s model appropriately reflected BGL and STL dependence on 7-HOC dose. The BMDs estimates of STL rise were similar (46–49 mg/kg) in 1, 2, and 3 months of exposure. Coincident dependence was foundfor the lower-bound confidence limits on the BMDs (BMDLs) ranged 21–22 mg/kg at all the studied time points, whereas NOEL for this end point was defined as 50, 20, and 20 mg/kg in 1, 2, and 3 months respectively. BMDs of the BGL decrease were rising with time of exposure amounting 48, 93, 486 mg/kg after 1, 2, and 3 months respectively. BMDLs estimates were 24, 21, 207 mg/kg in 1, 2, and 3 months respectively, while NOEL for this end point were 50, 200, and 200 mg/kg at correspond time points. Conclusion. The benchmark dose method was more powerful statistical tool to analyze 7-HOC effects dose dependence in comparison to traditional approach. The observed BMDs and theirs derivatives changes indicated no enhancement of studied treatment related responses within the exposure time. Key words: benchmark dose approach, 7-hydroxycoumarin, subchronic toxicity.