Animal toxicology experiments abstracts

This page gives the abstracts from whole-animal experiments on mice and rats of 50 or 60 Hz fields.  Other experiments, not included here, have looked at exposure to these fields combined with other carcinogens.

See also a summary of these studies and a discussion of their significance.

 

Leuk Res. 1991;15(10):899-902.
Effect of pulsed magnetic fields on leukemia-prone AKR mice. No-effect on mortality through five generations.Bellossi A.Laboratoire de Biophysique, Faculté de Médecine, Rennes, France.

Leukemia-prone AKR mice were exposed twice a week to a 6 mT, 12 Hz or 460 Hz pulsed magnetic field for 30 min. If we take into account the five consecutive generations of mice, the above exposure actually took place in utero and, or during their life span. There was no difference in the incidence of leukemia or in the actuarial survival curves or in the average spleen or thymus weights.

 

Cancer Lett. 1996 Aug 2;105(2):257-69.
Lymphoma induced in mice chronically exposed to very strong low-frequency electromagnetic field.
Fam WZ, Mikhail EL.Department of Electrical Engineering, Technical University of Nova Scotia, Halifax, Canada.

Three successive generations of CFW mice were exposed to a 25-mT (250,000 mG), 60-Hz electromagnetic field for prolonged periods. At the end of the exposure period, animals from both the exposed and control groups were sacrificed for tests. A complete autopsy was performed and tissue sections were taken from the main organs for histopathological examination. The results from the pathological findings in the various animals were classified under the following categories: (1) normal; (2) lymphoid hyperplasia; (3) premalignant changes; (4) early lymphoma; (5) advanced lymphoma. The three first-generation animals developed generalized lymphoid hyperplasia. In the second-generation animals, 5% developed premalignant changes, and 15.8% had lymphoid hyperplasia. In addition, 4 female mice left in the field for 418 days developed malignant lymphoma. In the third-generation animals, 58% developed premalignant changes or malignant lymphoma. An additional 30% had lymphoid hyperplasia. Statistical analysis of the data using the Mantel-Haenszel test for the difference in the prevalence of lymphoma between the exposed and control groups shows a very significant difference for the male groups (P < 0.001), the female groups (P < 0.001), and all animals combined (P < 0.001). The results suggest a cause-effect relationship between chronic exposure to very strong 60-Hz magnetic field for prolonged period and the development of malignant lymphoma in CFW mice.

 

FASEB J. 1997 Nov;11(13):1127-36.
Evaluation of the potential carcinogenicity of 60 Hz linear sinusoidal continuous-wave magnetic fields in Fischer F344 rats.Mandeville R, Franco E, Sidrac-Ghali S, Paris-Nadon L, Rocheleau N, Mercier G, Désy M, Gaboury L.

Immunology Research Center, Institut Armand-Frappier, University of Quebec, Laval, Canada.

Electric and magnetic fields (EMFs) associated with the production, transmission, and use of electricity are ubiquitous in industrialized societies. These fields are predominantly of low frequency (50/60 Hz) and are generally of low intensity. Review of the epidemiological evidence shows that the association between exposure to EMFs and cancer is weak and inconsistent, and generally fails to show a dose-response relationship. Moreover, in view of the methodological problems of these epidemiological studies, animal and laboratory studies are urgently needed to determine whether EMFs could be initiators and/or promoters of cancers. The objective of the present study was to determine whether chronic exposure to 60 Hz linear (single axis) sinusoidal, continuous-wave magnetic fields (MFs) of different intensities might increase the risk of leukemia and solid tumor development in rodents born and raised under these fields. Five groups of 50 female F344 rats were exposed for 20 h/day to 60 Hz MFs at intensities of <0.02 (sham controls), 2, 20, 200, and 2000 microT. Full body exposure to the different fields was administered for 104 wk starting from the prenatal period (2 days before birth) and continuing during lactation and weaning until late adult life. Body weight, survival, and clinical observations were evaluated in all groups of animals during in-life exposure. Necropsy was performed on all exposed and control animals that died, were found moribund, or were killed at termination of the study. To preserve and demonstrate the absence of any experimental bias, all clinical observations and pathological evaluations were conducted under "blinded" conditions. Fifty organs and tissues were evaluated in each animal, with special attention to the incidence of mononuclear cell leukemia, brain tumors, and mammary tumors. The findings from this chronic carcinogenicity study demonstrate that, under our defined experimental conditions, exposure to 60 Hz linear (single axis) sinusoidal, continuous wave MFs did not affect animal survival, solid tumor, or mononuclear cell leukemia development in female F344 rats. No statistically significant, consistent, positive dose-related trends with the number of tumor-bearing animals per study group could be attributed to MF exposure.

 

Bioelectromagnetics. 1997;18(8):531-40.
Carcinogenicity test of 50 Hz sinusoidal magnetic fields in rats.Yasui M, Kikuchi T, Ogawa M, Otaka Y, Tsuchitani M, Iwata H.

Engineering Development Center, Tokyo Electric Power Co., Japan.

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.

 

Radiat Res. 1998 Mar;149(3):300-7.
A test of lymphoma induction by long-term exposure of E mu-Pim1 transgenic mice to 50 Hz magnetic fields.Harris AW, Basten A, Gebski V, Noonan D, Finnie J, Bath ML, Bangay MJ, Repacholi MH.

Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.

E mu-Pim1 transgenic mice expressing a dysregulated Pim1 oncogene in their lymphoid cells were used to test whether exposure to 50 Hz magnetic fields can increase the frequency of malignant lymphoma in mice of a strain predisposed to develop such tumors spontaneously at low incidence. Specific-pathogen-free female mice were allocated randomly into groups of approximately 100 at 6-8 weeks of age and then exposed for 20 h/day for up to 18 months to sinusoidal magnetic fields of 0, 1, 100 or 1000 microT, or 1000 microT pulsed 15 min on and 15 min off. Additional E mu-Pim1 mice were injected with ethylnitrosourea (50 mg/kg body weight) as positive controls for enhanced lymphomagenesis; these yielded a cumulative incidence of lymphoma of 60% in 9 months. A lethal, transgene-dependent renal glomerular disease occurred at a frequency that varied from 9% to 19% among the groups, but the increase was statistically significant only at the 1000-microT exposure. Lymphoblastic and non-lymphoblastic (predominantly follicular) lymphomas were seen in 26 to 35% of the exposed mice, but at no significantly higher incidence than the 29% found in the sham-exposed mice. Hence we conclude that the lymphoma-prone mice did not reveal any tumorigenic effect of long-term exposure to 50 Hz magnetic fields.

 

Carcinogenesis. 1998 Sep;19(9):1649-53.
Exposure to 60 Hz magnetic fields and risk of lymphoma in PIM transgenic and TSG-p53 (p53 knockout) mice.McCormick DL, Ryan BM, Findlay JC, Gauger JR, Johnson TR, Morrissey RL, Boorman GA.

Life Sciences Department, IIT Research Institute, Chicago, IL 60616, USA.

The results of a number of epidemiology studies suggest that exposure to power frequency (50 and 60 Hz) magnetic fields may be a risk factor for hematopoietic neoplasia. To generate experimental data to test this hypothesis, the influence of magnetic field exposure on lymphoma induction was determined in two strains of mice that are genetically predisposed to the disease. PIM mice, which carry the pim-1 oncogene, are highly sensitive to lymphoma induction by N-ethyl-N-nitrosourea (ENU); ENU-treated PIM mice were studied as a 'high incidence' lymphoma model. TSG-p53 (p53 knockout) mice, in which the p53 tumor suppressor gene has been deleted from the germ line, develop lymphoma as an age-related change; hemizygous TSG-p53 mice were studied as a 'low incidence' lymphoma model. Beginning 1 day after a single i.p. injection of 25 mg ENU/kg body wt, groups of 30 PIM mice/sex were exposed for 18.5 h/day to pure, linearly polarized, transient-free 60 Hz magnetic fields at field strengths of 0 (sham control), 0.02, 2.0 or 10.0 Gauss (G). An additional group of 30 PIM mice/sex was exposed intermittently (1 h on, 1 h off) to 10.0 G fields. Groups of 30 TSG-p53 mice/sex were exposed continuously to magnetic field strengths of 0 (sham control) or 10.0 G; TSG-p53 mice received no ENU. Studies were terminated after 23 weeks of magnetic field exposure. Lymphoma incidence in male PIM mice exposed continuously to 10.0 G magnetic fields was significantly reduced from that seen in sex-matched sham controls; survival, lymphoma incidence and lymphoma latency in other groups of PIM mice did not differ from sham controls. Survival and lymphoma incidence in all groups of TSG-p53 mice was 7% or less, regardless of magnetic field exposure regimen. These data do not support the hypothesis that exposure to magnetic fields is a significant risk factor for lymphoid neoplasia in mice with a genetic predisposition to the disease.

Toxicol Pathol. 1999 May-Jun;27(3):279-85.
Chronic toxicity/oncogenicity evaluation of 60 Hz (power frequency) magnetic fields in B6C3F1 mice.

McCormick DL, Boorman GA, Findlay JC, Hailey JR, Johnson TR, Gauger JR, Pletcher JM, Sills RC, Haseman JK.

Illinois Institute of Toxicology Research Institute, Chicago 60616-3799, USA.

A 2-yr whole-body exposure study was conducted to evaluate the chronic toxicity and possible oncogenicity of 60 Hz (power frequency) magnetic fields in mice. Groups of 100 male and 100 female B6C3F1 mice were exposed to pure, linearly polarized, transient-free 60 Hz magnetic fields at flux densities of 0 Gauss (G) (sham control), 20 milligauss (mG), 2 G, and 10 G; an additional group of 100 male and 100 female B6C3F1 mice received intermittent (1 hr on/1 hr off) exposure to 10 G fields. A small but statistically significant increase in mortality was observed in male mice exposed continuously to 10 G fields; mortality patterns in all other groups of mice exposed to magnetic fields were comparable to those found in sex-matched sham controls. Body weight gains and the total incidence and number of malignant and benign tumors were similar in all groups. Magnetic field exposure did not increase the incidence of neoplasia in any organ, including those sites (leukemia, breast cancer, and brain cancer) that have been identified in epidemiology studies as possible targets of magnetic field action. A statistically significant decrease in the incidence of malignant lymphoma was observed in female mice exposed continuously to 10 G fields, and statistically significant decreases in the incidence of lung tumors were seen in both sexes exposed continuously to 2 G fields. These data do not support the hypothesis that chronic exposure to pure, linearly polarized 60 Hz magnetic fields is a significant risk factor for neoplastic development in mice.

 

Toxicol Pathol. 1999 May-Jun;27(3):267-78.
Chronic toxicity/oncogenicity evaluation of 60 Hz (power frequency) magnetic fields in F344/N rats.Boorman GA, McCormick DL, Findlay JC, Hailey JR, Gauger JR, Johnson TR, Kovatch RM, Sills RC, Haseman JK.

National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA.

A 2-yr whole-body exposure study was conducted to evaluate the chronic toxicity and possible oncogenicity of 60 Hz (power frequency) magnetic fields in rats. Groups of 100 male and 100 female F344/N rats were exposed continuously to pure, linearly polarized, transient-free 60 Hz magnetic fields at flux densities of 0 Gauss (G) (sham control), 20 milligauss (mG), 2 G, and 10 G; an additional group of 100 male and 100 female F344/N rats received intermittent (1 hr on/1 hr off) exposure to 10 G fields. Mortality patterns, body weight gains throughout the study, and the total incidence and number of malignant and benign tumors in all groups exposed to magnetic fields were similar to those found in sex-matched sham controls. Statistically significant increases in the combined incidence of C-cell adenomas and carcinomas of the thyroid were seen in male rats chronically exposed to 20 mG and 2 G magnetic fields. These increases were not seen in male rats exposed continuously or intermittently to 10 G fields or in female rats at any magnetic field exposure level. No increases in the incidence of neoplasms, which have been identified in epidemiology studies as possible targets of magnetic field action (leukemia, breast cancer, and brain cancer), were found in any group exposed to magnetic fields. There was a decrease in leukemia in male rats exposed to 10 G intermittent fields. The occurrence of C-cell tumors at the 2 lower field intensities in male rats is interpreted as equivocal evidence of carcinogenicity; data from female rats provides no evidence of carcinogenicity in that sex. These data, when considered as a whole, are interpreted as indicating that chronic exposure to pure linearly polarized 60 Hz magnetic fields has little or no effect on cancer development in the F344/N rat.

 

Carcinogenesis. 1999 May;20(5):899-904.
Effect of 26 week magnetic field exposures in a DMBA initiation-promotion mammary gland model in Sprague-Dawley rats.Boorman GA, Anderson LE, Morris JE, Sasser LB, Mann PC, Grumbein SL, Hailey JR, McNally A, Sills RC, Haseman JK.

National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.

Several studies have suggested that exposure to 50 Hz magnetic fields promote chemically induced breast cancer in rats. Groups of 100 female Sprague-Dawley rats were initiated with a single 10 mg gavage dose of 7,12-dimethylbenz[a]anthracene (DMBA) at 50 days of age followed by exposure to ambient fields (sham exposed), 50 Hz magnetic fields at either 1 or 5 Gauss (G) field intensity or 60 Hz fields at 1 G for 18.5 h/day, 7 days/week for 26 weeks. A vehicle control group without DMBA was included. Rats were palpated weekly for the presence of tumors. There was no effect of magnetic field exposure on body weight gains or the time of appearance of mammary tumors. At the end of 26 weeks, the animals were killed and the mammary tumors counted and measured. Mammary gland masses found grossly were examined histologically. The mammary gland carcinoma incidence was 96, 90, 95 and 85% (P < 0.05, decrease) for the DMBA controls, 1 G 50 Hz, 5 G 50 Hz and 1 G 60 Hz groups, respectively. The total numbers of carcinomas were 649, 494 (P < 0.05, decrease), 547 and 433 (P < 0.05, decrease) for the DMBA controls, 1 G 50 Hz, 5 G 50 Hz and 1 G 60 Hz groups, respectively. The number of fibroadenomas varied from 276 to 319, with the lowest number in the 1 G 60 Hz exposure group. Measurement of the tumors revealed no difference in tumor size between groups. In this breast cancer initiation-promotion study in female Sprague-Dawley rats, there was no evidence that 50 or 60 Hz magnetic fields promoted breast cancer under the conditions of this assay. This study does not support the hypothesis that magnetic field exposure can promote breast cancer in this rat model.

 

Bioelectromagnetics. 2002 Apr;23(3):206-13.
Carcinogenicity test in B6C3F1 mice after parental and prenatal exposure to 50 Hz magnetic fields.Otaka Y, Chida T, Yamagishi Y, Kitamura S.

Mitsubishi Chemical Safety Institute, Ibaraki, Japan.

Some epidemiological studies suggest association of childhood cancer with occupational exposure of the parents to magnetic fields. To test this relationship, 50 each of C57BL/6J female and C3H/HeJ male mice were exposed for 2 and 9 weeks, respectively, to 50 Hz sham (group A), 0.5 (group B), and 5 mT (group C) sinusoidal alternating magnetic fields. They were mated under the exposure for up to 2 weeks, and the exposure was continued until parturition. All the B6C3F1 offspring, without adjusting numbers of animals, were clinically observed without exposure to magnetic field for a nominal 78 weeks from 6-8 weeks of age after weaning and then euthanized for pathological examination according to a routine carcinogenicity test. 540 pups entered the test, and the survival rate was 96.7%. No F1 mouse died of tumoral diseases before a male in A group died of stomach cancer at 43 weeks of age. The first animal death in the exposed groups due to tumor occurred at 71 weeks of age. Eighteen animals died before necropsy at 84-86 weeks of age. No significant difference was detected in the final number of survivors and incidence of tumors between groups A and B, or A and C. Concerning reproduction total implants in group B were less than in group A and the difference was on the borderline of significance (P=.05). This difference was not reproduced in a later duplicate experiment.

Radiat Res. 2004 Aug;162(2):194-200.
The risk of lymphoma in AKR/J mice does not rise with chronic exposure to 50 Hz magnetic fields (1 microT and 100 microT).

Sommer AM, Lerchl A.

School of Engineering and Science, International University Bremen, Bremen, Germany.

Some epidemiological studies suggest that exposure to 50 or 60 Hz magnetic fields might increase the risk of leukemia, especially in children with a comparable high residential exposure. To investigate this possibility experimentally, the influence of 50 Hz magnetic-field exposure on lymphoma induction was determined in a mouse strain that is genetically predisposed to this disease. The AKR/J mouse genome carries the AK virus, which leads within 1 year to spontaneous development of thymic lymphoblastic lymphoma. Beginning at an age of 4-5 weeks, groups of 160 female mice were sham-exposed or exposed to 50 Hz magnetic fields at 1 or 100 microT for 24 h per day, 7 days per week, for 38 weeks. Animals were checked visually daily and were weighed and palpated weekly. There was no effect of magnetic-field exposure on body weight gain or survival rate, and lymphoma incidence did not differ between exposed and sham-exposed animals. Therefore, these data do not support the hypothesis that chronic exposure to 50 Hz magnetic fields is a significant risk factor for developing hematopoietic malignancy.