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

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Uloma Igara Uche ◽  
Olga V. Naidenko

Abstract 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.

2021 ◽  
Vol 22 (7) ◽  
pp. 3762
Author(s):  
Sarah M. Kedziora ◽  
Kristin Kräker ◽  
Lajos Markó ◽  
Julia Binder ◽  
Meryam Sugulle ◽  
...  

Preeclampsia (PE) is characterized by the onset of hypertension (≥140/90 mmHg) and presence of proteinuria (>300 mg/L/24 h urine) or other maternal organ dysfunctions. During human PE, renal injuries have been observed. Some studies suggest that women with PE diagnosis have an increased risk to develop renal diseases later in life. However, in human studies PE as a single cause of this development cannot be investigated. Here, we aimed to investigate the effect of PE on postpartum renal damage in an established transgenic PE rat model. Female rats harboring the human-angiotensinogen gene develop a preeclamptic phenotype after mating with male rats harboring the human-renin gene, but are normotensive before and after pregnancy. During pregnancy PE rats developed mild tubular and glomerular changes assessed by histologic analysis, increased gene expression of renal damage markers such as kidney injury marker 1 and connective-tissue growth factor, and albuminuria compared to female wild-type rats (WT). However, four weeks postpartum, most PE-related renal pathologies were absent, including albuminuria and elevated biomarker expression. Only mild enlargement of the glomerular tuft could be detected. Overall, the glomerular and tubular function were affected during pregnancy in the transgenic PE rat. However, almost all these pathologies observed during PE recovered postpartum.


2000 ◽  
Vol 19 (2) ◽  
pp. 69-83 ◽  
Author(s):  
William J. Brock ◽  
David P. Kelly ◽  
Susan M. Munley ◽  
Karin S. Bentley ◽  
Kathy M. McGown ◽  
...  

The acute, subchronic, and developmental and genetic toxicity of hydrofluorocarbon (HFC)-236fa and HFC-236ea were evaluated to assist in establishing proper handling guidance. In acute inhalation studies, rats were exposed whole body for 4 hours to various concentrations of each isomer. Based on the lack of mortality, the approximate lethal concentration for HFC-236ea for male rats was > 85,000 ppm. For HFC-236fa, the LC50 for males and females (combined) was > 457,000 ppm. Narcotic-like effects, e.g., prostration, incoordination, and reduced motor activity, were observed only during exposure to either isomer, but were not evident after termination of exposure. In cardiac sensitization studies, HFC-236ea induced cardiac sensitization at ≥ 35,000 ppm, with fatal responses occurring at 50,000 ppm and greater. For HFC-236fa, a cardiac sensitization response was observed at 150,000 ppm and greater but not at 100,000 ppm. A fatal cardiac sensitization response was observed in one dog exposed to 150,000 ppm HFC-236fa. In 90-day subchronic inhalation studies, male and female rats were exposed whole body to HFC-236ea at concentrations of 0, 5000, 20,000, or 50,000 ppm for 6 hours/day, 5 days/week. Similarly, male and female rats were exposed whole body to HFC-236fa at concentrations of 0, 5000, 20,000, or 50,000 ppm for 6 hours/day, 5 days/week. During exposure, narcotic-like effect (reduced acoustic startle response) was observed at 50,000 ppm with both isomers, although there appeared to be an adaptive response to this effect as the study progressed. With HFC-236ea, dilatation of the seminiferous tubules, without effects on germ or Sertoli cells, was observed only in rats at 50,000 ppm. No other effects on in-life measures or on clinical or anatomic pathology, including histopathology, were observed for either isomer. In rat developmental toxicity studies, no evidence of embryotoxicity or teratogenicity was observed with either isomer exposed up to 50,000 ppm during gestational days 7 to 16. Also, no developmental toxicity was observed in rabbits exposed to HFC-236fa at concentrations of up to 50,000 ppm during gestational days 7 to 19. Neither of the HFC-236 isomers was mutagenic in the Ames reverse mutation assay or clastogenic in the chromosomal aberration assay with human lymphocytes. No increase in chromosomal aberrations was observed in in vivo micronucleus studies with either isomer.


2021 ◽  
pp. 019262332110536
Author(s):  
Debra A. Tokarz ◽  
Margarita M. Gruebbel ◽  
Gabrielle A. Willson ◽  
Jerry F. Hardisty ◽  
Gail Pearse ◽  
...  

Spontaneous primary pleural mesotheliomas in Fischer 344 (F344) or other rat strains have rarely been reported. The objectives of this retrospective study were to develop historical incidence data and better characterize the light-microscopic morphology of these naturally occurring neoplasms in a large cohort of rats of several strains. A retrospective review was performed of National Toxicology Program (NTP) studies in rats conducted between 1980 and 2019 and comprising a total of 104,029 rats (51,326 males, 52,703 females), predominantly (90%) of the F344 strain. Of the 94,062 F344 rats surveyed, there were 30 cases of primary pleural mesotheliomas (22 males, 8 females). Of the 2998 Wistar Han rats surveyed, primary pleural mesotheliomas were present in 2 male rats. No primary pleural mesotheliomas were noted in male and female rats of other strains (6669 Sprague Dawley; 300 Osborne-Mendel). All primary pleural mesotheliomas in control and treated F344 and Wistar Han rats were considered spontaneous and unrelated to treatment. Based on light-microscopic evaluation of paraffin-embedded hematoxylin and eosin stained sections, only epithelioid and biphasic histologic subtypes were observed: 18 and 12 in F344 rats, respectively, and one each in Wistar Han rats. No sarcomatoid subtype cases were noted in any strain of rat.


2021 ◽  
Author(s):  
Fariborz Nowzari ◽  
Farhad Rahmanifar ◽  
Nader Tanideh ◽  
Mohammad Reza Dorvash ◽  
Arezoo Khoradmehr ◽  
...  

Abstract Effects of cottonseed flour in male and female rats’ fertility based on hormonal and histomorphometry changes were studied. Sixty-four Sprague-Dawley adult male and female rats were randomly divided into control and treatment groups. Treatment group was received diets containing cottonseed flour for 35 days. Control group was given standard rat food. Body and testis weights, epididymis semen evaluation indices and serum sex steroid hormones were determined. Histomorphometry alterations of testes and ovary were evaluated. Then, normal female and male rats were mated by rats in both groups and after 35 days, number of pups was measured. However, there was no significant difference in whole body and testes weights, sperm concentration and viability between the control and treatment groups, respectively. Moreover, sperm motility in the treatment rats was significantly lower than the control group. Serum hormones alterations were not significant, but histomorphometry evaluations of testes showed significant changes in the testis structures after chronic consumption of cottonseed flour. In the female rats, body weight did not have significant difference between the treatment and control groups. Histomorphometry data in female ovary showed significant reduction of primary follicle volume and number in the treatment group against control. Follicle stimulating hormone showed insignificant reduction in the treatment group. Number of pups was significantly reduced in the female rats fed by cottonseed flour. Cottonseed flour in rat diet had adverse effects on rat reproduction. Therefore, it can be used as an efficient product for control of the rat population as a natural rodenticide agent.


2021 ◽  
Author(s):  
Alyson Deprez ◽  
Zakaria Orfi ◽  
Alexandra Radu ◽  
Ying He ◽  
Daniela Ravizzoni Dartora ◽  
...  

Individuals born preterm show reduced exercise capacity and increased risk for pulmonary and cardiovascular diseases, but the impact of preterm birth on skeletal muscle, an inherently critical part of cardiorespiratory fitness, remains unknown. We evaluated the impacts of preterm birth-related conditions on the development, growth, and function of skeletal muscle using a recognized preclinical rodent model in which newborn rats are exposed to 80% oxygen from day 3 to 10 of life. We analyzed different hindlimb muscles of male and female rats at 10 days (neonatal), 4 weeks (juvenile) and 16 weeks (young adults). Neonatal high oxygen exposure increased the generation of reactive oxygen species and the signs of inflammation in skeletal muscles, which was associated with muscle fiber atrophy, fiber type shifting (reduced proportion of type I slow fibers and increased proportion of type IIb fast-fatigable fibers), and impairment in muscle function. These effects were maintained until adulthood. Fast-twitch muscles were more vulnerable to the effects of hyperoxia than slow-twitch muscles. Male rats, which expressed lower antioxidant defenses, were more susceptible than females to oxygen-induced myopathy. Overall, preterm birth-related conditions have long-lasting effects on the composition, morphology, and function of skeletal muscles; and these effects are sex-specific. Oxygen-induced changes in skeletal muscles could contribute to the reduced exercise capacity and to increased risk of diseases of preterm born individuals.


2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 120-120
Author(s):  
Yaqi Li ◽  
Ayasa Tajima ◽  
Floyd Mattie ◽  
Erin Dexheimer ◽  
Elizabeth Soucy ◽  
...  

Abstract Objectives We investigated the impact of pregnancy and lactation on vitamin A (VA) metabolism and kinetics in rats, hypothesizing that this changed physiological status would perturb whole-body VA kinetics. Such information may be informative for future dietary recommendations. Methods Ten female rats (7 wk of age) and 6 male rats (9 wk of age) were fed an AIN-93 G diet upon arrival. After 1 week of acclimation, female rats received an oral dose of 3H-labeled retinol as the tracer to initiate the kinetic study. On d 21 after dosing (when 3H-retinol was expected to reach a log-linear terminal slope), 6 female rats were mated and checked daily for a vaginal plug to determine the date of pregnancy. On the day of delivery, litter size was adjusted to 10 pups/dam. Serial blood samples were collected from each female rat at 27–28 time points after dose administration until dams and pups were euthanized on d 14 of lactation. Hematocrit was measured, plasma tracer level was determined, and plasma fraction of dose vs. time was plotted. Model-based compartmental analysis will be applied to the plasma tracer data to develop VA kinetic models. Results All mated female rats became pregnant (pregnant group, PG, n = 6). Non-mated female rats were studied as non-pregnant controls (CN, n = 4). No difference was observed in hematocrit between PG and CN rats, suggesting no significant change in plasma volume expansion. Before breeding, plasma tracer response profiles were similar to CN rats. However, a consistent decline in plasma tracer levels was observed in PG rats during the middle of pregnancy, followed by a rise in late pregnancy, whereas such a change did not occur in CN rats. Moreover, during lactation, PG rats exhibited a steeper terminal slope compared to CN rats, indicating a more rapid utilization of VA in these lactating rats. Conclusions Pregnancy and lactation resulted in altered VA metabolism and kinetics in rats. Further analysis using mathematical modeling will explore the changes in kinetic parameters that underlie the perturbations we have observed in VA kinetics. Funding Sources National Institutes of Health.


1956 ◽  
Vol 187 (2) ◽  
pp. 307-311 ◽  
Author(s):  
James L. Leitch ◽  
Virginia G. Debley ◽  
Thomas J. Haley

Studies have been made on a spasmogen from rat urine. This material has been identified as histamine. It has been shown that both acute whole body x-ray irradiation and compound 48/80 significantly increase the quantity of endogenous urinary histamine. Endogenous histamine excretion in female rats is approximately 9–10 times greater than in male rats. Neither x-ray irradiation nor compound 48/80 elevate the amount of urinary histamine of the males to that of the female. Histamine liberation is of little or no importance insofar as lethality from acute whole body irradiation is concerned. The amount of histamine liberated by such irradiation is independent of radiation dosage within the range 600–1200 r. After radiation injury, significant levels of urinary histamine were detected only during the first 24 hours. Histamine depletion by chronic administration of compound 48/80 did not prevent further liberation of histamine by acute whole body irradiation. Irradiated animals are much more susceptible to the toxic effects of compound 48/80 than normal animals. Gonadectomy followed by α-estradiol injection did not increase the output of urinary histamine in male rats. Similar treatment of female rats with testosterone did not reduce their urinary histamine output, but a reduction was observed 140 days after surgery. Administration of cortisone acetate to male rats did not increase their excretion of endogenous histamine. Inactivation of diamine oxidase with aminoguanidine had little or no effect on urinary histamine output in male rats, but caused a threefold increase in females. Further elevation in urinary histamine was produced by irradiation or compound 48/80.


1978 ◽  
Vol 77 (3) ◽  
pp. 397-403 ◽  
Author(s):  
A. J. THODY ◽  
H. DIJKSTRA

Sexually experienced male rats were used to test for whole body and preputial gland odours of female rats. The male rats clearly preferred whole body odours of intact female rats to those of preputialectomized female rats. The male rats also preferred the odour of preputial gland tissue of intact female rats to that of ovariectomized female rats and were especially attracted to the preputial gland odours of female rats in pro-oestrus and oestrus. The preputial gland odours of ovariectomized rats that had received oestradiol benzoate for 7 days were attractive to male rats, although similar treatment with progesterone was ineffective. However, a single injection of progesterone given 72 h after a single injection of oestradiol benzoate not only made ovariectomized rats receptive, but also made their preputial gland odours attractive to male rats. The results suggest that the preputial gland of the female rat is responsible for odours that serve to attract sexually experienced male rats. Ovarian steroids, as well as controlling receptivity in the female rat, would also appear to control the production of sex attractants in the preputial gland. There was no relationship between the size of the preputial glands and their ability to attract male rats which suggests that preputial gland growth and production of sex attractants are not under the same hormonal control.


2018 ◽  
pp. 47-54 ◽  
Author(s):  
Lennart Hardell ◽  
Michael Carlberg ◽  
Lena K. Hedendahl ◽  
Tarmo Koppel ◽  
Mikko Ahonen

Radiofrequency (RF) radiation in the frequency range 30 kHz to 300 GHz was evaluated in 2011 by the International Agency for Research on Cancer (IARC) at WHO to be a 'possible human carcinogen' Group 2B. The conclusion was based on human epidemiological studies on an increased risk of glioma and acoustic neuroma. In previous measurement studies, we found high environmental RF radiation levels at certain public places and also in an apartment in Stockholm, Sweden. One such place was the Järntorget square in the Stockholm Old Town. The EME Spy exposimeter was used for these studies. We have now conducted a field spatial distribution measurement with a radiofrequency broadband analyser. The maximum E-field topped at 11.6 V/m at the centre of the square, where the antenna was focused. Järntorget's mean value was 5.2 V/m, median 5.0 V/m, range 1.2-11.6 V/m. Of interest is that this level can be compared to a lifespan carcinogenicity study on rats exposed to 1.8 GHz GSM environmental radiation performed at the Ramazzini Institute (RI) in Italy. A statistically significant increase in the incidence of malignant schwannoma in the heart was found in male rats at the highest dose, 50 V/m. In treated female rats at the highest dose, the incidence of malignant glial tumours was increased, although this was not statistically significant. On the whole, the findings of this study showed that RF radiation levels at one square, Järntorget, in Sweden, were only one order of magnitude lower than those showing an increased incidence of tumours in the RI animal study. An increased cancer risk cannot be excluded for those working in the proximity of Järntorget for longer time periods.


2018 ◽  
Author(s):  
LENNART HARDELL ◽  
MICHAEL CARLBERG ◽  
LENA K. HEDENDAHL ◽  
TARMO KOPPEL ◽  
MIKKO AHONEN

Radiofrequency (RF) radiation in the frequency range 30 kHz to 300 GHz was evaluated in 2011 by the International Agency for Research on Cancer (IARC) at WHO to be a 'possible human carcinogen' Group 2B. The conclusion was based on human epidemiological studies on an increased risk of glioma and acoustic neuroma. In previous measurement studies, we found high environmental RF radiation levels at certain public places and also in an apartment in Stockholm, Sweden. One such place was the Järntorget square in the Stockholm Old Town. The EME Spy exposimeter was used for these studies. We have now conducted a field spatial distribution measurement with a radiofrequency broadband analyser. The maximum E-field topped at 11.6 V/m at the centre of the square, where the antenna was focused. Järntorget's mean value was 5.2 V/m, median 5.0 V/m, range 1.2-11.6 V/m. Of interest is that this level can be compared to a lifespan carcinogenicity study on rats exposed to 1.8 GHz GSM environmental radiation performed at the Ramazzini Institute (RI) in Italy. A statistically significant increase in the incidence of malignant schwannoma in the heart was found in male rats at the highest dose, 50 V/m. In treated female rats at the highest dose, the incidence of malignant glial tumours was increased, although this was not statistically significant. On the whole, the findings of this study showed that RF radiation levels at one square, Järntorget, in Sweden, were only one order of magnitude lower than those showing an increased incidence of tumours in the RI animal study. An increased cancer risk cannot be excluded for those working in the proximity of Järntorget for longer time periods.


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