Dealing with uncertainty in formulating occupational and public exposure limits.

Scientists are forced to address many sources of uncertainty in the setting of exposure limits. This paper discusses the rationale for some of the approaches that have been used for many years to address uncertainties encountered in the setting of occupational and public exposure limits to protect against non-cancer effects of chemicals. These approaches are quite different from the methodology that has been adopted for the setting of exposure limits to power-frequency electric and magnetic fields to avoid adverse effects of induced electric fields and currents. The limitations of the non-standard electric and magnetic fields guideline methodology are described. To address these limitations, a probabilistic approach to developing exposure limits for electric and magnetic fields has been proposed. As a demonstration, this approach has been applied to the estimation of magnetic field exposures that would not pose significant risks of cardiac stimulation from electric fields induced in the torso. The results of this probabilistic analysis demonstrate the importance of explicitly characterizing potential sources of uncertainty and variability. Furthermore, the use of fixed, single point estimates of dosimetric parameters by electric and magnetic fields guideline-setting organizations provides more than adequate protection to individuals from the risk of cardiac stimulation. The mean magnetic field level that would increase the risk of cardiac stimulation is shown by this approach to be about three times higher than is predicted by dosimetric formulas used by the ACGIH and ICNIRP. If input data for parameters affecting the risk of adverse effects with lower thresholds, i.e., nerve stimulation, are developed and validated, this method could be used in the setting of electric and magnetic fields standards based more strongly on quantitative assessments of experimental data.

Evaluation of biological effects, dosimetric models, and exposure assessment related to ELF electric- and magnetic-field guidelines.

Several organizations worldwide have issued guidelines to limit occupational and public exposure to electric and magnetic fields and contact currents in the extremely low frequency range (<3 kilohertz). In this paper, we evaluate relevant developments in biological and health research, computational methods for estimating dosimetric quantities, and exposure assessment, all with an emphasis on the power frequency (60 hertz in North America, 50 hertz in Europe). The aim of each guideline is to prevent acute neural effects of induced electric fields. An evaluation of epidemiological and laboratory studies of neurobiological effects identified peripheral nerve stimulation as the response most suitable for establishing a magnetic-field guideline. Key endpoints that merit further study include reversal of evoked potentials; cardiovascular function, as measured by heart rate and heart rate variability; and sleep patterns. High-resolution computations of induced electric fields and current densities in anatomically correct human models are now achieved with finite-difference methods. The validity and limitations of these models have been demonstrated by computations in regular geometric shapes, using both analytic and numeric computations. Calculated values for average dosimetric quantities are typically within a few percent for the two approaches. However, maximum induced quantities are considerably overestimated by numerical methods, particularly at air interfaces. Overestimates are less pronounced for the upper 99th percentile level of a dosimetric quantity, making this measure a more useful indicator of maximum dose. Neural stimulation thresholds are dependent on the electric field around the excitable cell rather than on the current density, making the former preferable for expression of basic restrictions based on nervous system function. Furthermore, modeling data indicate that the induced electric field is much less strongly influenced by tissue conductivity than is the induced current density. In the electric utility industry, most magnetic-field exposures at or near guideline levels occur in highly nonuniform fields. Two methods are described for simplified estimation of induced quantities in such fields, with each method using as input modeling results for uniform field exposure. These methods have practical value for assessing occupational exposures relative to guideline levels.

Probabilistic approach to ranking sources of uncertainty in ELF magnetic field exposure limits.

There is a need to improve the biological data, dosimetry, and risk assessment methodology used for setting guidelines for occupational exposures to extreme-low-frequency magnetic fields. This paper illustrates how a probabilistic approach can be used to determine priorities for future research based upon the analysis of biological and dosimetric variables that affect stimulation of the heart by magnetically-induced currents. A model was constructed to predict a level of whole-body magnetic-field exposure below which no cardiac stimulation is expected (Bncs). For each iteration of the model, a value was selected from cardiac stimulation threshold, shape factor, and conductivity distributions by Latin Hypercube sampling, and a value for Bncs was computed. The very wide range of simulated Bncs magnetic-field values obtained indicates that there is considerable uncertainty about what constitutes a "safe" level of exposure. The results show that the major occupational-exposure guidelines are very conservative with respect to risks of cardiac stimulation. The minimum Bncs value computed (0.01 T) by either a circular-loop model or an ellipsoid dosimetric model is ten times the highest recommended workday exposure value in a guideline. The lowest 5% Bncs value calculated for a circular-loop model is about 50-times the ICNIRP occupational exposure limit; the lowest 5% Bncs value calculated for an ellipsoid model is more than 100 times the ACGIH occupational exposure limit. A new finding is that the method specified by several guidelines for determining guideline compliance when exposures occur at multiple frequencies (additive weighting of harmonics) leads to substantially lower Bncs estimates relative to a probably more valid rms-weighting method. Probabilistic sensitivity analyses indicate that lack of knowledge of the threshold for cardiac stimulation is the greatest source of uncertainty as to what is a "safe" level of exposure to extreme-low-frequency magnetic fields. Additional research to address this source of uncertainty may be expected to have the greatest potential impact to reduce overall uncertainty about safe magnetic field exposures.

Summary and evaluation of guidelines for occupational exposure to power frequency electric and magnetic fields.

Major U.S. and international guidelines for limiting occupational exposures to EMF are evaluated. These safety guidelines are designed to prevent short-term adverse effects by maintaining bulk-tissue current densities below 10 mA m(-2) (rms). Above this level, effects of induced currents and electric fields can include stimulation of neural and cardiac tissues. The models and input data used by guideline-setting organizations to relate 50/60-Hz magnetic-field exposures to induced current densities differ significantly. In order to develop a better understanding of such differences, the current densities derived from exposure guideline models are compared to minimum thresholds for cardiac stimulation and fibrillation. The nominal minimum thresholds for cardiac stimulation and ventricular fibrillation are 100 times and 200 times greater, respectively, than the current density of 10 mA m(-2) used as a dosimetric limit. However, the assumed relationship between the 10 mA m(-2) dose limit and magnetic field exposure limits introduces additional uncertainty. The ratios between the threshold for cardiac stimulation and the calculated induced current density at the exposure limit vary between a low of 50 and a high of 526, depending upon the guideline. These ratios, as indicators of implicit safety factors, are larger than those recommended to protect against adverse effects of induced current density, including cardiac stimulation, in magnetic resonance imaging or against adverse effects of toxic chemical exposures. This review and assessment of EMF occupational exposure guidelines suggests that several scientific and compliance issues remain ambiguous or unresolved. Recommendations are made for guideline organizations to strengthen and clarify the scientific basis for the guideline process. These recommendations include the documentation of supporting data, development of operational definitions for guidelines, examination of dosimetric models, clarification of safety factors, and identification of high priority topics for future research.

Human perception of electric fields and ion currents associated with high-voltage DC transmission lines.

The objective of this study was to assess the ability of humans to detect the presence of DC electric field and ion currents. An exposure chamber simulating conditions present in the vicinity of high-voltage DC (HVDC) lines was designed and built for this purpose. In these experiments, the facility was used to expose observers to DC electric fields up to 50 kV/m and ion current densities up to 120 nA/m2. Forty-eight volunteers (25 women and 23 men) between the ages of 18 and 57 years served as observers. Perception of DC fields was examined by using two psychophysical methods: an adaptive staircase procedure and a rating method derived from signal-detection theory. Subjects completed three different series of observations by using each of these methods; one was conducted without ion currents, and the other two involved various combinations of electric fields and ion currents. Overall, subjects were significantly more likely to detect DC fields as the intensity increased. Observers were able to detect the presence of DC fields alone, but only at high intensities; the average threshold was 45 kV/m. Except in the most sensitive individuals, ion current densities up to 60 nA/m2 did not significantly facilitate the detection of DC fields. However, higher ion current densities were associated with a substantial lowering of sensory thresholds in a large majority of observers. Data analysis also revealed large variations in perceptual thresholds among observers. Normative data indicating DC field and ion current intensities that can be detected by 50% of all observers are provided. In addition, for the most sensitive observers, several other detection proportions were derived from the distribution of individual detection capabilities. These data can form the basis for environmental guidelines relating to the design of HVDC lines.

Analysis of radionuclide arthrograms, radiographic arthrograms, and sequential plain radiographs in the assessment of painful hip arthroplasty.

An analysis of sequential plain radiographs (XR), radionuclide arthrography, (RNA), and radiographic arthrography (RGA) was performed to determine the efficacy and usefulness of each study in the diagnosis of loosening of prosthetic hip components. Over a 2-year-period, 65 hip prostheses were assessed before operation using each type of study; these results were compared to the intraoperative assessment of the status of the components. Of the three studies, sequential plain radiographs were overall the most accurate, sensitive, and specific. Radionuclide arthrography was of no use on the acetabular side but quite useful on the femoral side, especially in cases with only minimal femoral component loosening. Radiographic arthrography was overall the least accurate or sensitive of the three studies performed.

Differential glucose utilization in the parafascicular region during slow-wave sleep, the still-alert state and locomotion.

Regional cerebral glucose utilization (CGU), detectable by the uptake of 2-deoxy-[14C]glucose [( 14C]2DG), was examined during 3 behavioral states--slow-wave sleep (SWS), the still-alert state (SAL) and locomotion (LOC). Examination of the autoradiograms, generated by exposing the [14C]2DG incorporated brain sections to Kodak Royal X Pan film revealed a high level of uptake bilaterally and discretely in the parafascicular (PF) region during these behaviors. This pattern of [14C]2DG uptake does not correspond to any of the anatomical structures previously identified by histo- and cytochemical methods, including the [14C]2DG method. Further, optical density measurements of this region indicated that the [14C]2DG uptake was significantly lower during SWS than during SAL or LOC. The present finding is compatible with the interpretations of previous physiological and behavioral studies that there is an inhibition by cells at the PF relay to the dentate gyrus that is lowered during the SWS compared to the SAL state, thus allowing preferential brain-stem activation of the dentate gyrus.

Acute exposure of rats to air ions: effects on the regional concentration and utilization of serotonin in brain.

Exposure to electrically charged gas molecules (air ions) has been reported to influence physiological and behavioral functions in animals and humans although there is controversy as to whether these findings are valid. A popular hypothesis concerning the reported effects of air ions is that alterations in serotonin (5HT) metabolism, particularly in the brain, are involved. We measured the concentration and turnover of 5HT in rats exposed to 5.0 X 10(5) ions/cm3 for up to 66 hours. Contrary to previous reports of other investigators, we were unable to demonstrate any effect of exposure to air ions or associated DC electric fields on the concentration or turnover of 5HT in rats under carefully controlled and characterized exposure conditions.

Behavioral monitoring of rats during exposure to air ions and DC electric fields.

Air ions and direct current (DC) electric fields have been reported to exert subtle behavioral and biological effects on rodents and humans. These effects often appear inconsistent, yet there have been few attempts to resolve these inconsistencies by experimental replication. Rats exposed to negatively or positively charged air ions over a wide range of concentrations and exposure periods have been reported to show alterations in their level of locomotor activity. In this study, locomotor activity of Sprague-Dawley rats was quantified during exposure to either unipolar air ions and DC fields of the same polarity or DC fields alone. Both polarities were studied. Air ion concentrations were 5.0 X 10(3), DC fields were 3 kV/m, and exposures lasted 2, 18, or 66 h. In one experiment rats were exposed to DC fields of 12 kV/m. No exposure condition exerted any effect on locomotor activity or rearing behavior. In addition, no behavioral perturbations were observed after the onset of any of the exposure conditions, suggesting that the rats may have failed to detect the altered environment.

Ion exposure chambers for small animals.

Ion exposure chambers that have been designed and tested for use in biological and behavioral research with small animals are described in this report. The chambers exhibit an acceptable degree of uniformity in ion concentration, current density, and electric field within the exposure area. Gaseous by-products of corona discharge (O3 and NO2) have been measured and found to be less than .01 ppm and less than .1 ppm, respectively. Filtered air is fed to the individual exposure chambers, and temperature and humidity are well controlled. Noise due to corona and the air delivery system has been measured.

Regional turnover of norepinephrine and dopamine in rat brain following acute exposure to air ions.

Exposure to air ions has been reported to influence serotonin (5HT), although critical reviews of these studies and previous measurements in our laboratory of the concentration, release, and utilization of brain 5HT indicate that neither the data nor the interpretations of the data are particularly convincing. Measurements of other possibly relevant neurotransmitter systems--norepinephrine (NE) and dopamine (DA)--were made in brain regions selected because of their importance in the modulation of brain functions relating to motivation, arousal, endocrine function, and motor activity, all responses that have been reported to be influenced by air ion exposure. Results indicate that exposure of male Holtzman rats to high concentrations (5.0 X 10(5)/cm3) of positive or negative air ions or to DC electric fields (3.0 kV/m) for periods up to 66 h failed to affect the concentration of NE or DA significantly in any of the brain regions.

Release of histamine by sympathetic nerve stimulation in the guinea pig heart and modulation of adrenergic responses. A physiological role for cardiac histamine?

Histamine has been reported to attenuate adrenergic responses in cardiovascular tissues. In guinea pig atria preloaded with [3H]norepinephrine, histamine diminishes the field stimulation-induced efflux of radioactivity; this effect has been attributed to an inhibition of norepinephrine release from nerve endings. To assess the possible physiological relevance of these findings, we have reinvestigated the effects of histamine on cardiac sympathetic responses and on the release of endogenous norepinephrine in the guinea pig heart isolated with its intact sympathetic innervation. Heart rate, left ventricular contractile force, and perfusion pressure all increased with increasing frequencies of sympathetic nerve stimulation (2-8 Hz). Histamine (3 X 10(-8) to 3 X 10(-7) M) caused dose-dependent attenuation of the responses to sympathetic stimulation. The ability of histamine to modulate nerve stimulation-induced norepinephrine overflow into the coronary effluent was dependent on whether the heart had been preloaded with norepinephrine. Whereas histamine did not cause a significant reduction in nerve stimulation-induced norepinephrine overflow in hearts from untreated animals, histamine significantly reduced stimulation-induced norepinephrine overflow in hearts from guinea pigs that had been pretreated with norepinephrine before sacrifice. Histamine also attenuated the increases in left ventricular contractile force, perfusion pressure, and heart rate, which result from the intracardiac administration of norepinephrine (0.16-microgram bolus injection). In this respect, histamine was as effective as it was in inhibiting the responses elicited by nerve stimulation. Thus, in normal animals, the negative modulatory effect of histamine on adrenergic responses can be attributed largely, if not totally, to a postjunctional mechanism. In contrast, a prejunctional action of histamine may contribute significantly to the negative modulation observed in norepinephrine-preloaded hearts. Since we have observed a large increase in the amount of endogenous histamine present in the coronary effluent after sympathetic stimulation (930 pg during the 30 seconds poststimulation vs. 240 pg during 30 seconds prestimulation), as well as a prolongation of nerve stimulation-induced cardiac responses in the presence of the H2 receptor antagonist tiotidine, we postulate that histamine plays a physiological role as a modulator of sympathetic responses in the heart.

Unicompartmental knee replacement.

The results of unicompartmental knee replacement in a series of 83 knees were reviewed for the period of 1970 to 1978; 30.1 percent achieved good or excellent results; 48.2 percent fair or poor results; 21.7 percent were failures. The vast majority of failures and poor results were due to technical errors. Only 9.6 percent of the nonoperated contralateral compartments required further surgery.

Revision of total knee replacement.

In the London and Toronto areas between 1969 and 1978, 597 patients had 661 cemented knee replacements. Eighty-nine (13.5%) prostheses failed; 73 of them were revised. Nineteen (2.9%) failed primarily because of infection. The revised replacements were examined and rated using a modification of the British rating system. The overall results of revision were excellent or good in 30% and fair or poor in 52%. Fusion was attempted in two patients after revision. In 16 patients with failed replacements that were not revised, fusion was attempted in 9; 4 of the 16 patients had amputation. The results of failure in knee replacement surgery are similar to those of hip replacement, but are helped considerably by lower patient expectation.

Stress-induced depression of motor activity correlates with regional changes in brain norepinephrine but not in dopamine.

This experiment examined how inescapable tail shock alters the level of dopamine and norepinephrine within various brain regions of the rat and the relationship of these changes to the depression of motor activity produced by the shock. Following exposure to tail shock that is known to interfere with acquisition of active behavioral tasks, animals were briefly tested for spontaneous motor activity and then sacrificed for neurochemical measures. Norepinephrine and dopamine levels in the frontal cortex, brain stem, striatum, olfactory tubercle, hypothalamus, hippocampus, septum, and amygdala were measured by a sensitive radioenzymatic technique. Exposure to 45 min of tail shock did not alter motor activity significantly, but shock sessions of 60 and 75 min duration produced a marked decrease in motor activity. Levels of dopamine were found to be very little changed in all brain regions studied except for the hypothalamus, in which a substantial rise in dopamine level was observed. Norepinephrine levels, in contrast, fell in many brain regions in response to shock. The fall in norepinephrine levels observed in two brain regions was significantly correlated with the decline in motor activity (brain stem r = +0.70, hypothalamus r = +0.60). These data suggest that deficits in active motor behavior produced by shock parameters similar to those used in this study may reflect concomitant disturbances of noradrenergic function in specific brain regions.

The results of revision of total hip arthroplasty.

The results of 140 total hip revision procedures for "non-septic" loosening, dislocation, and fracture of the femoral stem or shaft have been personally reviewed and rated by the Harris method. The minimum follow-up period was six months: thirty-three (24 per cent) showed excellent or good results, seventy-two (51 per cent) showed fair or poor results. Subsequent excision arthroplasty was performed in thirty-one patients. The infection rate for these revision procedures was very high, suggesting that many were already infected at the time of revision, and that every "loose" hip must be assumed to be infected until proved otherwise. The mortality rate of 3 per cent was surprisingly low after more than one major surgical procedure in these elderly patients.