childhood leukemia, emf and contact current• emdex ii converted to voltmeter (1 mv sensitivity)...
TRANSCRIPT
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WHO Workshop on Sensitivity of Children to EMF
Istanbul, Turkey
June 9, 2004
Childhood Leukemia, EMF and Contact Current
Robert Kavet, ScD, MEEEPRI
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Background• Epidemiologic association between childhood
leukemia and residential magnetic fields despite– negative bioassays– biophysical plausibility issues
• Explanatory possibilities– control selection bias – under investigation– another exposure, requires
• dose to target tissue (bone marrow)• association with residential field• frequent exposure
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Limitations
• Engineering relationships based on multi-ground neutral distribution systems characteristic of the US
• Electrical systems in Europe and Asia uninvestigated thus far (research is now beginning)
• Apartments require investigation
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Contact Current
IContact
RS
RP
V2
V1
SPContact
RRVVI
+−
=21
Dose metric: electric field in tissueexpressed in units of mV/mCurrent perception threshold ~ roughly 130 µA for men; 50 µA for children
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Role of Bone Marrow in Leukemia• “The universal common denominator of pediatric
B-lineage ALL is a BM [bone marrow] origin of the disease.” (LeBien, 2000)
• Most childhood leukemias initiated in utero(translocation, hyperdiploidy); secondary posnatalevents (infection, other) trigger leukemictransformation
• “The earliest stages of clonal expansion in B-lineage ALL…may be characterized by a dependency on BM stromal cells for survival and growth…By the time a patient is diagnosed with B-lineage ALL a physical displacement of normal lymphohematopoiesis and BM architecture will have occurred.” (LeBien, 2000)
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Bone Marrow
Wilpshaar et al., 2000
Unlike children, adults lack red marrow in their long bones
21-week fetusRadiograph MRI
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BM stromal cell–derived molecules that could transduce survival/growth, differentiation, or chemotactic signals to CLP*, early-B, or pro-B cells
LeBien, 2000
* common lymphoid progenitor
Stromal cells orchestrate hematopoiesis and may upregulate intercellular communication with other stromal cells during development and periods ofimmunological response (infection); interconnected stromal cell networks result in higher membrane potential when current flows through marrow.
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Comparative Dosimetry for Bone Marrow: B-field vs contact current
Model Site Exposure Average (mV/m)
99th pctl (mV/m)
1 µT 0.0095 0.056 10 µA 4.6 34.9 Body
CC:B Ratio 484 623 Child
Lower Arm 10 µA 50.7 149 1 µT 0.013 0.077
10 µA 1.75 12.6 Body CC:B Ratio 135 164
Adult
Lower Arm 10 µA 16.6 46.3 Dawson et al, 2001, 2002 Caputa et al, 2002
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Residential Electrical Service
Earth
Magnetic field induction on neutral (ground)
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Basic Residential Grounding in US
Water pipeBath tub
Earth
Drain Pipe
Water Main
Grounding wire(required by NEC)
VW-E
Vbath’
INet Load
IUtility Neutral
IGW
InsideOutside
Panel
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Equivalent Circuit
VS
RPersonRW-DRW-E
Ip
RD-E
Earth Drain
Faucet/Spout/Stream
RWater
RContact
Vbath
VW-E
VS
RPersonRW-DRW-E
Ip
RD-E
Earth Drain
Faucet/Spout/Stream
RWater
RContact
Vbath
VW-E
Vbath is a variable fraction of VW-E depending on soil conditions and relative positioning of drain and water lines; Vbath negligible if either drain or residential water pipe is non conductive
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Bathtub Exposure Scenario
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Relationship Between Residential Magnetic Field and Contact Voltage
• Measurements– spot measurements in regional population samples– long-term (6 days) measurements within homes
• Computer Simulation– dissect contributions to B and V from primary, secondary,
and transmission lines– examine possible effects of other variables (e.g., water
main, neutral conductivity)– economy of resources
• Analysis– correlation of B with V: expression of relationship without
respect to cutpoint; scatter plot may shed light on mechanism
– association: examines whether high-tail observations co-exist; relevant to plausibility of confounding
– small to moderate correlation does not eliminate possibility of strong association
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Key Measurement/Modeling Parameters
• Bavg: the average magnetic field measured at the center of inhabited rooms
• VW-E: the voltage from the water pipe to the earth under open circuit conditions: represents the interaction of the utility system with the residential grounding system; source of Vbath
• Vbath: the voltage between the water fixtures and the drain with a 1 kΩ resistor across the voltmeter (represents “live” current flow)
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Pilot Study in Pittsfield, MA (N=36): VW-E vs Bavg(Kavet and Zaffanella, 2002)
1
10
100
1,000
10,000
0.01 0.1 1
B avg (µT)
V W-E
(mV)
R 2 = 0.29p < 0.001
red points: HVTL
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Denver Measurement Study(Kavet et al, in press)
• Objective: Measure magnetic fields and contact voltages in homes that would have qualified for the Savitz study of childhood cancer in Denver, Colorado
• Denver was the site of the earliest and influential childhood cancer studies
• Quantify the association between the residential magnetic field and the voltage of the source for contact current
• 191 homes measured across the full spectrum of outdoor wiring configurations
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Denver Study: Association of VW-E with BavgAcross VW-E Cutpoints (from: Kavet et al, in press)
OR (500 mV cutpoint: 12.0%)
0.1
1
10
100
< 0.1 0.1-<0.3 >= 0.3
Odd
s R
atio
(+/-
95%
CI)
p (trend) <0.05
OR (625 mV cutpoint: 7.9%)
0.1
1
10
100
< 0.1 0.1-<0.3 >= 0.3
Odd
s R
atio
(+/-
95%
CI)
p (trend) <0.001
OR (750 mV cutpoint: 4.2%)
0.01
0.1
1
10
100
< 0.1 0.1-<0.3 >= 0.3O
dds
Rat
io (+
/- 95
% C
I)
p (trend) <0.01
OR (500 mV cutpoint: 12.0%)
0.1
1
10
100
< 0.1 0.1-<0.3 >= 0.3
Odd
s R
atio
(+/-
95%
CI)
p (trend) <0.05
OR (625 mV cutpoint: 7.9%)
0.1
1
10
100
< 0.1 0.1-<0.3 >= 0.3
Odd
s R
atio
(+/-
95%
CI)
p (trend) <0.001
OR (750 mV cutpoint: 4.2%)
0.01
0.1
1
10
100
< 0.1 0.1-<0.3 >= 0.3O
dds
Rat
io (+
/- 95
% C
I)
p (trend) <0.01
Bavg (µT)
Bavg (µT)
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Denver Study: Association of Vbath with BavgAcross Vbath Cutpoints (from: Kavet et al, in press)
OR (10 mV cutpoint: 11.5%)
0.1
1
10
< 0.1 0.1-<0.3 >= 0.3
Odd
s R
atio
(+/-
95%
CI)
p (trend) <0.2
OR (30 mV cutpoint: 8.4%)
0.1
1
10
100
< 0.1 0.1-<0.3 >= 0.3
Odd
s R
atio
(+/-
95%
CI)
p (trend) <0.05
OR (100 mV cutpoint: 4.2%)
0.1
1
10
100
< 0.1 0.1-<0.3 >= 0.3O
dds
Rat
io (+
/- 95
% C
I)
p (trend) <0.05
OR (10 mV cutpoint: 11.5%)
0.1
1
10
< 0.1 0.1-<0.3 >= 0.3
Odd
s R
atio
(+/-
95%
CI)
p (trend) <0.2
OR (30 mV cutpoint: 8.4%)
0.1
1
10
100
< 0.1 0.1-<0.3 >= 0.3
Odd
s R
atio
(+/-
95%
CI)
p (trend) <0.05
OR (100 mV cutpoint: 4.2%)
0.1
1
10
100
< 0.1 0.1-<0.3 >= 0.3O
dds
Rat
io (+
/- 95
% C
I)
p (trend) <0.05
Bavg (µT)
Bavg (µT)
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Computer Simulation: Categories of Features
• Study area geography (block size, street width, housing density)
• House lot/size/setback • Outdoor line location (backyard, street-side)• Outdoor line configuration (primaries, secondaries,
neutrals, transformers)• System neutral (location relative to phases, resistance)• Electrical service (service drop, panel locations)• Residential load (based on 1,000 home study)• Ground path/resistance (routing and resistance of
residential grounding elements)• Water main type (conductive, nonconductive)
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Overview of 3x4 Block Sample Study Area w/Backyard Lines (N = 152)
Substation
3-Φ 1°(feeder)
B
A
C
B
B
C
A
A B
B
B
B
1-Φ 1° (lateral)
3-Φ TL
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Computer Simulation• 3x4 Blocks• Backyard or front distribution, combined with either• Conductive or non-conductive water mains• 13 kV primaries• Range of feeder currents, each with 25% unbalance
– 25 A– 50 A– 100 A– 200A
• Each house “visited” 4 times for each feeder load• Net Load = 4.34 A (GM); 1.87 GSD (from 1,000 home
study); the same four random seeds used for each feeder load
• Bavg and VW-E averaged over the four visits; of 2,792 points, 1,000 selected randomly for visual purposes
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Composite Simulation Result
0.01
0.1
1
10
0.001 0.01 0.1 1
VW-E (V)
Bavg (µT)
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Simulation Result by Primary Load
0.01
0.1
1
10
0.001 0.01 0.1 1
25 A 50 A 100 A 200 A
VW-E (V)
Bavg (µT)
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Simulation Result by Primary Load
0.01
0.1
1
10
0.001 0.01 0.1 1
25 A 50 A 100 A 200 A
VW-E (V)
Bavg (µT)
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Simulation Result by Primary Load
0.01
0.1
1
10
0.001 0.01 0.1 1
25 A 50 A 100 A 200 A
VW-E (V)
Bavg (µT)
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Simulation Result by Primary Load
0.01
0.1
1
10
0.001 0.01 0.1 1
25 A 50 A 100 A 200 A
VW-E (V)
Bavg (µT)
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Simulation: Association of VW-E with Bavg
OR (1.35 V cutpoint: 10%)
1
10
100
< 0.1 0.1-<0.3 >= 0.3
Odd
s R
atio
(+/-
95%
CI)
p (trend) <0.0001
Bavg (µT)
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Long-Term Measurements Within Homes in San Jose, CA
• Continuous measurements for 6+ days• Recording every minute
– Magnetic field (Broom)• EMDEX Lite (0.1 mG sensitivity)• In room with median field at screening
– Faucet to drain voltage (Vbath)• EMDEX II converted to voltmeter (1 mV sensitivity)• All readings with 1,000 ohms from faucet to drain
– Water line to earth voltage (VW-E)• EMDEX II converted to voltmeter (1 mV sensitivity)• No resistor
• Analysis– Data combined for each 30 minute segment of the 24-hr cycle (i.e., 48
segments per variable)– 24-hr graphs normalized to grand means; correlations computed (n = 48)– Unusual events censored (e.g., power outage)
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House 5
0.4
0.6
0.8
1.0
1.2
1.4
1.6
1.8
2.0
12:00 AM 3:00 AM 6:00 AM 9:00 AM 12:00 PM 3:00 PM 6:00 PM 9:00 PM 12:00 AM
B_3rdBR VW-E Vbath
Long-Term Measurements Within Homes in San Jose, CA: Results
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House 8
0.6
0.8
1.0
1.2
1.4
1.6
12:00 AM 3:00 AM 6:00 AM 9:00 AM 12:00 PM 3:00 PM 6:00 PM 9:00 PM 12:00 AM
B_MBR VW-E Vbath
Long-Term Measurements Within Homes in San Jose, CA: Results
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Summary of Correlations Among B, VW-E & Vbath over 6-day measurement period
6-day Average Pearson Correlation Spearman Correlation House Bavg (µT) VW-E (mV) Vbath (mV) Bavg:VW-E Bavg:Vbath VW-E:Vbath Bavg:VW-E Bavg:Vbath VW-E:Vba
1 0.28 243 103 0.976 0.935 0.977 0.958 0.910 0.968 2 0.17 91 13 0.463 0.538 0.990 0.379 0.482 0.979 3 0.02 173 10 0.883 0.635 0.556 0.912 0.686 0.635 4 0.35 -- 107 -- 0.667 -- -- 0.725 -- 5 0.02 104 12 0.428 0.596 0.935 0.479 0.640 0.903 6 0.15 411 68 0.863 0.858 0.982 0.903 0.894 0.968 7 0.02 116 -- 0.542 -- -- 0.630 -- -- 8 0.07 231 263 0.789 0.801 0.998 0.767 0.772 0.997 9 0.08 250 24 0.937 0.797 0.849 0.853 0.836 0.878
In every case to date, all three quantities are statistically significantly correlated with each other over 6-day long measurement periods
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Northern California Childhood Leukemia Studyat U Cal Berkeley
• 17 Bay Area counties
• 18 Central Valley counties
• Since 1995
• EMF/contact current component: 2003-06
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Children’s Bathing Behavior
Prior to launch of EMF/contact voltage study in the NCCLS,
• Recall survey of parents conducted by telephone (N=40)
• Bathing diary survey administered to separate set of parents (N=40), with recall survey preceding diary (N=39)
• Roughly 75-80% children >12 months old engage in contact behavior (~contact every two baths); lower for <12 months old (~contact every three baths)
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Conclusion• Thus far, exposure to contact current has
demonstrated features that qualify it as a plausible factor that could be responsible for the association of childhood leukemia with residential magnetic fields:– dose to bone marrow– association with residential magnetic fields– children’s bathing behavior consistent with frequent exposure
• Further investigation needed to characterize– electrical systems across nations– structures with multiple residences
• Investigation to identify candidate laboratory systems in progress– in vitro– in vivo