Effects of prenatal exposure to 50 Hz magnetic fields on development in mice: I. Implantation rate and fetal development

Pregnant CD1 mice were exposed or sham-exposed from day 0 to day 17 of gestation to a 50 Hz sinusoidal magnetic field at 20 mT (rms). Preimplantation and postimplantation survival were assessed and fetuses examined for the presence of gross external, internal, and skeletal abnormalities. There were no statistically significant field-dependent effects on preimplantation or postimplantation survival, sex ratio, or the incidence of fetuses with internal or skeletal abnormalities. Magnetic field exposure was, however, associated with longer and heavier fetuses at term, with fewer external abnormalities. The results lend no support to suggestions of increased rates of spontaneous abortion or congenital malformation following prenatal exposure to power frequency magnetic fields. © 1994 Wiley-Liss, Inc.     

Effects of prenatal exposure to 50 Hz magnetic fields on development in mice: II. Postnatal development and behavior

To investigate the potential of magnetic fields to act as a behavioral teratogen, pregnant CD1 mice were exposed or sham-exposed for all of gestation to a 50 Hz/20 mT magnetic field. Maturation of offspring was assessed using a range of standard developmental indices (eye opening, pinna detachment, hair coat, tooth eruption, sexual maturity, and weight) and simple reflexive behaviors (air righting, surface righting, forepaw grasp, cliff avoidance, and negative geotaxis). Activity and coordination levels were explored in juvenile and adult mice using an open field arena, a head-dip board, an accelerating Rotarod, and a residential activity wheel. All assessments were carried out without knowledge of exposure condition. Results from 168 sham-exposed mice from 21 litters and from 184 exposed mice from 23 litters were compared using survival analysis techniques and multivariate regression methods. Three possible field-dependent effects were found: Exposed animals performed the air righting reflex earlier (P < 0.01); exposed males (but not females) were significantly lighter in weight (P = 0.008) at 30 days of age; and exposed animals remained on a Rota-rod for less time as juveniles (P = 0.03). Some of these results have not been reported in other studies and may reflect spurious statistical significance, although some effect of magnetic field exposure cannot be ruled out. Overall, these results suggest that prenatal exposure to a 50 Hz magnetic field does not engender any gross impairments in the postnatal development or behavior of mice. This does not preclude such exposure affecting more subtle aspects of behavior. Published 1994 by Wiley-Liss, Inc.     

The effects of feed restriction during organogenesis on embryo-fetal development in the rat

BACKGROUND: Given the role of nutrition and body weight gain in normal development, pharmaceuticals intended to reduce appetite and promote weight loss will generate safety data that may be challenging to interpret. To aid with this, the effects of feed restriction and subsequent body weight reductions on embryo-fetal development were investigated in the rat. METHODS: Groups of 20 timed pregnant female Sprague-Dawley rats were offered Certified Rodent Diet 5002 either ad libitum or in restricted amounts of 20, 15, 10, and 7.5 g/day from Gestation Day (GD) 6-17. Clinical signs, body weights, and food consumption were recorded. Cesarean sections were performed on GD 21 and fetuses were sexed, weighed, and examined for external, visceral, and skeletal development. RESULTS: Mean maternal body weights at the end of the feed restriction period, GD 18, were reduced 0.87 x, 0.80 x, 0.69 x, and 0.63 x control mean in the 20, 15, 10, and 7.5 g/day groups, respectively. Mean body weight gains for the restriction period inclusive, GD 6-18, were 0.49 x and 0.24 x control at 10 and 7.5 g/day, respectively, and a mean body weight loss occurred at 10 and 7.5 g/day (0.95 x and 0.85 x mean GD 6 body weight, respectively). Fetal body weights were reduced 0.95 x, 0.93 x, 0.90 x, and 0.76 x control at 20, 15, 10, and 7.5 g/day, respectively. This resulted in a reduction in gravid uterine weight at 10 and 7.5 g/day. There were no external, visceral, or skeletal malformations attributed to feed restriction. There was an increase in the skeletal variation of wavy ribs and a decrease in ossification at 7.5 g/day. CONCLUSIONS: These data demonstrate that feed restriction-induced reductions in maternal gestational body weight gain of approximately 50% compared to ab lib fed rats only caused a reduction in fetal body weight. Even up to a 15% maternal gestational body weight loss had no effect on embryo viability in rats, but retarded fetal growth significantly enough to induce minor changes in skeletal development. There were no external, visceral, or skeletal malformations associated with any of the levels of maternal body weight reduction or loss.     

Effects of feed restriction during organogenesis on embryo-fetal development in rabbit

BACKGROUND: Appropriate maternal nutrition and body weight gain during pregnancy is well established as a major factor in healthy prenatal development in humans. Given the role of nutrition and body weight gain in normal development, pharmaceuticals intended to reduce appetite and promote weight loss will generate developmental toxicity data that may be challenging to interpret. To aid with this, the effects of feed restriction, and subsequent reduction in maternal body weight gain, on embryo-fetal development was investigated in the rabbit. METHODS: Groups of 15 pregnant New Zealand White rabbits were offered 150 (control), 110, 75, 55, 35, and 15 g feed/day from gestation day (GD) 7-19. Cesarean sections were carried out on GD 29 and fetuses were examined for external, visceral, and skeletal development. RESULTS: Maternal body weights at the end of the feed restriction period (GD 20) were 0.97, 0.98, 0.93, 0.94, and 0.86 x control for the 110, 75, 55, 35, and 15 g feed/day groups, respectively. Only at 15 g feed/day was there a net maternal body weight loss (the GD 20 body weight was 0.93 x the GD 6 body weight) at the end of the feed restriction period. Six does aborted in the 15 g feed/day group; there were no other abortions associated with feed restriction. Fetal body weight was significantly reduced at 75, 55, 35, and 15 g feed/day (0.95, 0.90, 0.86, and 0.84 x control, respectively). There were no external or visceral malformations or variations, and no skeletal malformations associated with feed restriction. The incidence of fetuses with sternebrae 5 or 6 unossified was increased at feed levels < or = 75 g/day. At a feed level of 35 g/day there was an increase in unossified metatarsals and metacarpals, and an increase in the number of fetuses with a reduced number of caudal vertebrae ossified. Although these findings were not increased at a feed level of 15 g/day, the lack of dose response was likely due to increased abortion and subsequent decrease in fetuses available for evaluation at 15 g feed/day. CONCLUSION: These data demonstrate that feed restriction to feed levels that produce substantial reductions in maternal body weight gain can result in developmental toxicity expressed by abortion, reduced fetal weight, and alterations in ossification. Abortion only occurred when feed was restricted to an amount that produced maternal body weight loss (15 g feed/day) whereas reduced fetal weight and increased incidence of fetuses with unossified sternebrae, metatarsals, metacarpals, or caudal vertebrae were noted at feed levels of < or = 75 g/day. There were no fetal malformations associated with feed restriction.     

Effects of low-frequency magnetic fields on fetal development in CBA/Ca mice

Effects of alternating magnetic fields (MFs) on the embryonic and fetal development in CBA/Ca mice were studied. Mated females were exposed continuously to a sinusoidal 50 Hz (13 μT or 0.13 mT root mean square) or a sawtooth 20 kHz (15 μT peak-to-peak) MF from day 0 to day 18 of pregnancy for 24 h/day until necropsied on day 18. Control animals were kept under the same conditions without the MF. MFs did not cause maternal toxicity. No adverse effects were seen in maternal hematology and the frequency of micronuclei in maternal bone marrow erythrocytes did not change. The MFs did not increase the number of resorptions or fetuses with major or minor malformations in any exposure group. The mean number of implantations and living fetuses per litter were similar in all groups. The corrected weight gain (weight gain without uterine content) of dams, pregnancy rates, incidences of resorptions and late fetal deaths, and fetal body weights were similar in all groups. There was, however, a statistically significant increase in the incidence of fetuses with at least three skeletal variations in all groups exposed to MFs. In conclusion, the 50 Hz or 20 kHz MFs did not increase incidences of malformations or resorptions in CBA/Ca mice, but increased skeletal variations consistently in all exposure groups. Bioelectromagnetics 19:477–485, 1998. © 1998 Wiley-Liss, Inc.     

Comparison of the developmental toxicity of aspirin in rabbits when administered throughout organogenesis or during sensitive windows of development

BACKGROUND: A review of the nonsteroidal anti‐inflammatory drug (NSAID) literature suggested occurrences of low‐level incidences of cardiovascular and midline defects in rabbit fetuses exposed in utero. Aspirin (acetylsalicylic acid, ASA) is a widely used NSAID that irreversibly inhibits cyclooxygenases (COXs) 1 and 2. ASA has been studied extensively in rats and has consistently increased low‐incidence cardiovascular malformations and defects in midline closure. The objectives of the current study were to comprehensively define the developmental toxicology profile of ASA in rabbits by using a dosing paradigm encompassing the period of organogenesis and to test the hypothesis that maternal gastrointestinal toxicity after repeated dose administrations hampers the detection of low‐incidence malformations with ASA in rabbits by limiting ASA administration to sensitive windows for cardiovascular development and midline closure. METHODS: ASA was administered to pregnant New Zealand White rabbits from gestation days (GDs) 7 to 19 at dose levels of 125, 250, and 350 mg/kg per day and as single doses of 500, 750, or 1000 mg/kg on GD 9, 10, or 11. Cesarean sections were performed on GD 29, and the fetuses were examined for external, visceral, and skeletal development. RESULTS: In the repeated dose study, maternal toxicity was exhibited in the 250‐ and 350‐mg/kg per day groups by mortality and decreased food consumption and body weight gain. In the single dose studies, maternal toxicity was exhibited at all doses by reductions in body weight gain and food consumption for 3 days after treatment. Fetal body weight was significantly reduced in the repeated dose study at 350 mg/kg per day. Fetal weights were not affected by single doses of ASA on GD 9, 10, or 11. There were no treatment‐related external, visceral, or skeletal malformations associated with ASA administration throughout organogenesis or with single doses administered during critical developmental windows. CONCLUSION: These findings supported previous work demonstrating that ASA is not teratogenic in rabbits, as opposed to rats, even when large doses are administered on single days during specific windows of development. Birth Defects Research (Part B) 68:38–46, 2003. © 2003 Wiley‐Liss, Inc.     

Circularly polarized,sinusoidal, 50 Hz magnetic field exposure does not influence plasma testosterone levels of rats

We exposed rats to circularly polarized 50 Hz magnetic fields to determine if plasma testosterone concentration was affected. Previous experiments indicate that magnetic fields suppress the nighttime rise in melatonin, suggesting that other neuroendocrine changes might occur as well. Male Wistar-King rats were exposed almost continuously for 6 weeks to magnetic flux densities of 1,5, or 50 μT. Blood samples were obtained by decapitation at 12:00 h and 24:00 h. Plasma testosterone concentration showed a significant day-night difference, with a higher level at 12:00 h when studied in July and December, but the day-night difference disappeared when concentrations were studied in April. In three experiments, magnetic field exposure had no statistically significant effect on plasma testosterone levels compared with the sham-exposed groups. These findings indicate that 6 weeks of nearly continuous exposure to circularly polarized, 50 Hz magnetic fields did not change plasma testosterone concentration in rats. © 1994 Wiley-Liss, Inc.     

Carcinogenicity test of 50 Hz sinusoidal magnetic fields in rats

Male and female F344 rats, 48 per exposure group, were sham exposed (Group A) or exposed to 0.5 (Group B) and 5 mT (Group C) magnetic fields for two years. Animals were exposed from 5–109 weeks of age in SPF conditions according to the OECD test guideline No. 451. Average exposure was 22.6 hr/day. No significant differences in body weight and food consumption were observed between the sham and exposed groups. At the end of the exposure period, survival rates of the male rats were 73, 83, and 79%, and those of the females, 77, 79, and 75% for Groups A, B, and C, respectively, with no significant differences between groups. Differential counts of leukocytes were measured at the 52nd, 78th, and 104th weeks of exposure and no significant differences were observed between the exposure groups. All survivors were euthanized on schedule, and all the organs and tissues suspected of tumoral lesions were examined histopathologically. Incidences of mononuclear cell leukemia in the male and the female rats were 5, 4, 4 and 8, 6, 7 for Groups A, B and C, respectively; incidences of malignant lymphoma in the female rats were 0, 1 and 1. Neither significant increases nor acceleration of incidence of leukemia were observed. Incidences of brain and intracranial tumors did not increase in the exposed groups. Incidences of both benign and malignant neoplasms showed no significant difference between the exposed and sham exposed groups with one exception: fibroma of the subcutis in the male rats, which was considered not to be a statistically significant when evaluated with respect to the historical control data in our laboratory. Bioelectromagnetics 18:531–540, 1997. © Wiley-Liss, Inc.     

Biological effects of prolonged exposure to ELF electromagnetic fields in rats: III. 50 Hz electromagnetic fields

Groups of adult male Sprague Dawley rats (64 rats each) were exposed for 8 months to electromagnetic fields (EMF) of two different field strength combinations: 5μT - 1kV/m and 100μT - 5kV/m. A third group was sham exposed. Field exposure was 8 hrs/day for 5 days/week. Blood samples were collected for hematology determinations before the onset of exposure and at 12 week intervals. At sacrifice, liver, heart, mesenteric lymph nodes, bone marrow, and testes were collected for morphology and histology assessments, while the pineal gland and brain were collected for biochemical determinations. At both field strength combinations, no pathological changes were observed in animal growth rate, in morphology and histology of the collected tissue specimens (liver, heart, mesenteric lymph nodes, testes, bone marrow), and in serum chemistry. An increase in norepinephrine levels occurred in the pineal gland of rats exposed to the higher field strength. The major changes in the brain involved the opioid system in frontal cortex, parietal cortex, and hippocampus. From the present findings it may be hypothesized that EMF may cause alteration of some brain functions. Bioelectromagnetics 19:57–66, 1998. © 1998 Wiley-Liss, Inc.     

Effects of low-frequency magnetic fields on fetal development in rats

We studied effects of alternating magnetic fields on the embryonic and fetal development of rats. Mated females of the Han:Wistar-strain were sham exposed or exposed continuously to a 50-Hz field or to a 20,000 pulse-per-second (pps) sawtooth magnetic field from day 0 to day 20 of pregnancy for 24 h/day until necropsied on day 20. The respective peak-to-peak intensities of the fields were 35.6 μT (sinewave) and 15.0 μT (sawtooth). Each treatment group contained 72 bred females. Control animals were kept under the same conditions without the magnetic field. No adverse effects were seen in the dams. The mean numbers of implantations and living fetuses per litter were statistically significantly increased in the 50-Hz group. There were, however, three total resorptions of litters in dams of the control group, which contributed to the difference in the number of living fetuses. The corrected body-mass gains (gains without uterine content) of dams were similar in all groups. Pregnancy rates, incidences of resorptions. late fetal deaths, and fetal body masses were similar in all groups. The incidence of fetuses with minor skeletal anomalies was statistically significantly increased in both exposed groups. Only one serious malformation (anophthalmia, sawtooth-exposed group) and a few minor visceral malformations were found. In conclusion, the magnetic fields used in this study did not increase the incidence of major malformations or resorptions in Wistar rats. The increased number of skeletal anomalies and implantations we observed indicates, however, that some developmental effects in rats may attend exposure to time-varying magnetic fields. © 1993 Wiley-Liss. Inc.     

Brief exposure to a 50 Hz, 100 microT magnetic field: effects on reaction time, accuracy, and recognition memory

The present study investigated both the direct and delayed effects of a 50 Hz, 100 microT magnetic field on human performance. Eighty subjects completed a visual duration discrimination task, half being exposed to the field and the other half sham exposed. The delayed effects of this field were also examined in a recognition memory task that followed immediately upon completion of the discrimination task, Unlike our earlier studies, we were unable to find any effects of the field on reaction time and accuracy in the visual discrimination task. However, the field had a delayed effect on memory, producing a decrement in recognition accuracy. We conclude that after many years of experimentation, finding a set of magnetic field parameters and human performance measures that reliably yield magnetic field effects is proving elusive. Yet the large number of significant findings suggests that further research is warranted.     

Biologic effects of prolonged exposure to ELF electromagnetic fields in rats: II. 50 Hz magnetic fields

To provide possible laboratory support to health risk evaluation associated with long-term, low-intensity magnetic field exposure, 256 male albino rats and an equal number of control animals (initial age 12 weeks) were exposed 22 h/day to a 50 Hz magnetic flux density of 5 μmT for 32 weeks (a total of about 5000 h). Hematology was studied from blood samples before exposure to the field and at 12 week intervals. Morphology and histology of liver, heart, mesenteric lymph nodes, and testes as well as brain neurotransmitters were assessed at the end of the exposure period. In two identical sets of experiments, no significant differences in the investigated variables were found between exposed and sham-exposed animals. It is concluded that continuous exposure to a 50 Hz magnetic field of 5 μT from week 12 to week 44, which makes up ?70% of the life span of the rat before sacrifice, does not cause changes in growth rate, in the morphology and histology of liver, heart, mesenteric lymph nodes, testes, and bone marrow, in hematology and hematochemistry, or in the neurotransmitters dopamine and serotonin. © 1995 Wiley-Liss, Inc.     

Enhanced NOR-1 gene expression by exposure of Chinese hamster cells to high-density 50 Hz magnetic fields

Enhanced expression of neuron derived orphan receptor (NOR-1) gene was observed by exposure of Chinese hamster ovary K1 (CHO-K1) cells to an extremely low frequency magnetic field (ELFMF) of 50 Hz at 400 mT, but not at 5 mT. The enhanced expression, reaching the maximum at 6 h, was transient and reduced to the control level after exposure to 400 mT ELFMF for 24 h. The NOR-1 expression induced by treatment with forskolin and TPA was further enhanced by the simultaneous treatment with 400 mT ELFMF, in which the maximum response was at 3 h. The NOR-1 expression by these treatments was induced more earlier than that by 400 mT ELFMF alone. When cells were treated with an inhibitor of the protein kinase C (calphostin C or crocetin) and Ca²⁺ entry blockers (nifedipin and dantrolen) during the 400 mT ELFMF exposure, the enhanced NOR-1 expression was not observed. Exposure of CHO-K1 cells to the high-density 400 mT ELFMF may affect the signal transduction in the cells, resulting in the enhanced NOR-1 gene expression.     

Effects of exposure to a circularly polarized 50-Hz magnetic field on plasma and pineal melatonin levels in rats

We sought to determine whether a 6-week exposure to a 50-Hz rotating magnetic field influences melatonin synthesis by 11–18 week-old Wistar-King male rats. Rats were exposed continuously to a rotating magnetic field at 1, 5, 50, or 250 μT (spatial vector rms) for 6 weeks, except for twice-weekly breaks of about 2 h for cleaning of cages and feeding. The rats were housed in exposure and sham-exposure facilities, which were located in the same room, under a 12:12 light-dark photoperiod (lights on at 06:00 h). The room was constantly illuminated by 4 small, dim red lights (< 0.07 lux in dark period). Levels of plasma and pineal gland melatonin were determined by radioimmunoassay. A significant decrease of melatonin was observed between the control group and groups exposed to a magnetic field at a flux density in excess of l μT during the night time, but no statistical differences were found among the exposed groups. These results indicate that subchronic exposure of albino rats to a 50-Hz rotating magnetic field influences melatonin production and secretion by the pineal gland. © 1993 Wiley-Liss, Inc.     

Analysis of induced currents in a rat exposed to 50 Hz linearly and circularly polarized magnetic fields

This paper presents a numerical analysis of currents induced in a rat by linearly and circularly polarized magnetic fields of 50 Hz. Special focus was placed on pineal gland and retina of rats since these organs were often associated with the changes of melatonin synthesis and concentration. Induced currents in two MRI-based rat models with resolutions of up to 0.125 mm(3) were calculated by using the impedance method. We characterized the induced currents by amplitude and polarization. Calculated induced current densities were extremely small, i.e., < 30 microA/m(2) for both linearly and circularly polarized magnetic fields of 1.41 microT (peak). There were no significant differences in amplitude nor polarization of induced currents in the pineal gland between the linearly and the circularly polarized magnetic fields when the polarization was in a vertical plane. In contrast, the magnetic fields rotating in the horizontal plane produced most circularly polarized currents both in the pineal gland and in the retina.     

Inability of 50 Hz magnetic fields to regulate PKC- and Ca(2+)-dependent gene expression in Jurkat cells

We have previously reported that the T cell line Jurkat registers the exposure of a sinusoidal extremely low frequency magnetic field at the level of the plasma membrane, resulting in activation of the tyrosine kinase p56(lck), increase in inositol-3-phosphate levels and increase in intracellular calcium concentration within minutes. To elucidate if these events associated with changes in intracellular calcium ion levels were biologically significant, transient transfections of Jurkat cells were performed with calcium-ion dependent reporter constructs. Three different enhancer/promoter constructs were studied coupled to the luciferase reporter gene. The luciferase activity of each construct was measured after treatment of transfected cells to EMF exposure alone, or in combination with ionomycin, phorbol ester or cross-linking anti-CD3 antibodies. There was no indication that the used EMFs could influence any of these reporter constructs.     

Lack of a co‐promotion effect of 60 Hz circularly polarized magnetic fields on spontaneous development of lymphoma in AKR mice

The present study was conducted to investigate the possible effect of 60 Hz circularly polarized magnetic fields (MFs) as promoters of genetically initiated lymphoma in AKR mice. One hundred sixty female animals were divided into four different groups. They were exposed to four different intensities of circularly polarized MFs. Animals received exposure to 60 Hz circularly polarized MF at field strengths (rms‐value) of 0 µT (sham control, T1, Group I), 5 µT(T2, Group II), 83.3 µT (T3, Group III), or 500 µT(T4, Group IV), for 21 h/day from the age of 4–6 weeks to the age of 44–46 weeks. There were no exposure‐related changes in mean survival time, clinical signs, body weights, hematological values, micronucleus assay, gene expression arrays, analysis of apoptosis, and necropsy findings. At histopathological examination, lymphoma was seen in all the groups. The tumor incidence was 31/40(78%), 30/40(75%), 32/40(80%), and 31/40(78%) in sham control, 5, 83.3, and 500 µT groups, respectively. However, there were no differences in the tumor incidence between the sham control (T1) and circularly polarized MF exposure groups (T2–T4). In conclusion, there was no evidence that exposure to 60 Hz circularly polarized MF strengths up to 500 µT promoted lymphoma in AKR mice. Bioelectromagnetics 31:130–139, 2010. © 2009 Wiley‐Liss, Inc.     

Studies on prenatal and postnatal development in rats exposed to 60-Hz electric fields

A series of three experiments was performed to determine the effects of 30-day exposures to uniform 60-Hz electric fields (100 kV/m) on reproduction and on growth and development in the fetuses and offspring of rats. In the first experiment, exposure of females for 6 days prior to and during the mating period did not affect their reproductive performance, and continued exposure through 20 days of gestation (dg) did not affect the viability, size, or morphology of their fetuses. In the second experiment, exposure of the pregnant rat was begun on 0 dg and continued until the resulting offspring reached 8 days of age. In the third experiment, exposure began at 17 dg and continued through 25 days of postnatal life. In the second and third experiments, no statistically significant differences suggesting impairment of the growth or survival of exposed offspring were detected. In the second experiment, a significantly greater percentage of the exposed offspring showed movement, standing, and grooming at 14 days of age than among-sham-exposed offspring. There was a significant decrease at 14 days in the percentage of exposed offspring displaying the righting reflex in the second experiment and negative geotropism in the third experiment. These differences were all transient and were not found when the animals were tested again at 21 days of age. Evaluation of the reproductive integrity of the offspring of the second experiment did not disclose any deficits.     

Influence of 50 Hz electric and magnetic fields on the human heart

This investigation studied the effect of 50 Hz electric and magnetic fields on the human heart. The electrocardiograms of 27 transmission-line workers and 26 male volunteers were recorded with a Holter recorder both in and outside the fields. The measurements took from half an hour to a few hours. The electric field strength varied from 0.14 to 10.21 kV/m and the magnetic flux density from 1.02 to 15.43 μT. Analysis of the ECG recordings showed that extrasystoles or arrhythmias were as frequent outside the field as in the field. In some cases a small decrease in heart rate was observed after field exposure. © 1993 Wiley-Liss, Inc.