Lead and PCBs: A Toxic Legacy in Anniston
Robert J. Geller, MD
SE Pediatric Environmental Health Specialty Unit,
Associate Professor of Pediatrics, Emory University, and
Medical Director, Georgia Poison Center
SE PEHSU - Emory
With the collaboration of
 Howard Frumkin, MD, Occupational & Environmental
Med, Emory Univ. Rollins School of Public Health
 Leslie Rubin, MD, Pediatric Developmental Med,
Emory Univ. School of Medicine
 Gerald Teague, MD, Pediatric Pulmonary Med, Emory
Univ. School of Medicine
Disclaimer
 Dr.
Geller does not have any commercial interest in
any of the products to be discussed, and has not
been retained as an expert in any PCB-related
litigation.
Lead and PCB’s: A Toxic Legacy in
Anniston
 Reasons
for presence of PCB’s and lead in
Anniston
 Toxicology of lead
 Diagnosis and management of lead toxicity
 Toxicology of PCB’s
 Diagnosis and management of PCB toxicity
Q&A
PCB’s in Anniston
 PCBs
(polychlorinated
biphenyls) manufactured in
Anniston till mid 1970’s
 Small percent (pounds to
hundreds of pounds) of
manufactured product
and/or byproducts lost into
the environment
surrounding the plant
Lead in Anniston
 Metal
foundries in Anniston milled and
cast metal objects, presumably some
with leaded alloys
 Leaded gasoline use
 Lead paint use
Lead
Lead initially recognized as a multi-system poison at
levels exceeding 40 g/dL (anemia, abd cramps,
seizures, encephalopathy, renal colic)
 Only later recognized as a developmental toxin
 Lead sources: lead-based paint, gasoline, crafts,
lead industries (smelters, automotive, others)
 Initial concern raised in 1920’s about lead addition
to gasoline, but lead only removed in late 1970’s

Lead
Lead and IQ

Lead’s impact clearly established at BLL 10 g/dL

Data suggest impact at BLL 5 g/dL
“Normal” BLL calculated to be <0.1 g/dL
 IQ seems to display “catch-up” to the expected
norm in the child whose lead is mitigated and who
is in a socially advantaged setting

Lead’s impact on verbal IQ
Lead blood levels vs. IQ
Result of a 5 point reduction in average IQ
Lead and behavior
 High
lead children recognized to be more
aggressive, more hyperactive than low lead children
 Behavior does NOT regress toward the expected
over time, even in a socially advantaged setting
Mendelsohn AL et al. Pediatrics 1998; 101:e10-e17.
Burns JM et al. Am J Epidemiol 1999; 149:740-749.
Lead mechanisms proposed
Probably a combination of mechanisms
 Lead activation of protein kinase C at the synaptic
level
 Alteration of other calcium-regulated processes
 Altering dopaminergic (HVA,homovanillic acid) and
serotonergic (5-HIAA) neurotransmitter activity

Bressler J et al. Neurochem Res 1999; 24:595-600
Tang HW et al. J Appl Toxicol 1999; 19:167-172.
Which children are at high risk from lead?
Children in homes built 1920’s - early 1960’s,
particularly those that are being renovated
 Children inhaling lead dust produced by
industrial or craft activities
 Children whose parents work in lead industries
 Children of parents with lead poisoning
 Children whose siblings have high lead
 Children inhaling fumes of leaded gasoline

So, who should we screen?
 “Screen
all”
– the “in vogue” approach in late 80’s and early ‘90’s
– low yield noted
– still recommended for highest risk areas of US, such as
the “rust belt” of the NE
 “Selective screening”
– screen those with 1 or more risk factors at 9 months,
consider repeat at 24 months of age
How to screen
Goal: detect BLL of 10 g/dL and intervene to
prevent BLL getting any higher
 Method: need BLL
– venous sample less likely to be contaminated with
surface debris
– fingerstick sample requires less technical skill to
obtain
 Erythrocyte protoporphyrin (EPP or ZPP) not
sensitive at this level of detection,  not useful

Dealing with the results - 1
 Remember,
 BLL
national population mean now  3 g/dL
< 10 g/dL: do nothing
10 - 15 g/dL: repeat sample in 3 mo, discuss
lead prevention with family
 BLL
15- 20 g/dL: repeat sample now, discuss lead
prevention
 BLL
Dealing with the results - 2
20-25 g/dL: repeat sample, send public health
or industrial hygiene to house to look for cause
 BLL
25 g/dL or more: as above, chelate if result
confirmed
 BLL 40 or more: consider inpatient chelation, to
remove patient from reexposure during chelation
 BLL
Chelation for lead
 Succimer
is usually lead chelator of choice (a.k.a.
DMSA or Chemet®)
– oral agent, comes as powder in capsule
– tid dosing schedule x 5 days, then bid x 14 days
– watch renal and hepatic function during chelation
– best dosed as 350 mg/m2 /dose, particularly in young
children or obese, else 10 mg/kg/dose
 Alternatives: CaEDTA ± BAL, penicillamine
PCB Toxic Effects Suspected
 Acute
exposure
– Chloracne
– Birth defects
– Hepatic dysfunction
 Subacute & chronic exposure
– Neurotoxicity, child and adult
– Low birth weight
– Cancer
– Immunologic dysfunction
PCB Characteristics
 209
congeners of PCBs, varying in extent of
chlorination of biphenyl rings (24-60%)
 More heavily chlorinated congeners are more viscous
 Low reactivity, poor flammability, good heat
conductance, poor water solubility
 Long persistence in the environment
 Travel with silt and soil movement
 Poor volatility
PCB Toxicokinetics
 Present
in blood, in lipophilic tissues, in breast milk
 Half life of congeners from 1 - 8+ years
 Toxicity also thought to vary by congener
 Absorbed well by ingestion and by inhalation, poorly
dermally
 Accumulates up the food chain
 Major source of PCB’s for most people is by
ingestion of meat, poultry, fish
PCB measurements in Anniston residents -1
 Blood
levels have been measured by several
community groups, by EPA, by ATSDR
 All of these studies congruent
 Assay methods vary from lab to lab; levels
(depending on method) vary by factor of 2 - 3 x
 Blood values also elevated by elevated serum lipids
 Preferred sample source is blood; body fat less well
studied, others not well correlated
PCB measurements in Anniston residents -2
 US
population PCB blood avg.= 3 - 7 ppb (ng/L)
 US 95%ile  1980 = 20 ppb
 Lowest toxic level generally thought to be > 20 ppb;
one source cites >200 ppb
 PCB levels in Anniston residents correlate with:
– age (few elevated levels, none very elevated, in
children)
– length of residence near the plant, even when adjusted
for age
– pica
16 children
tested= 2.5%
sample of
children living
within 1 mile
of the plant
PCB Developmental neurotoxicity - 1
 First
suspected based on subacute ingestion of rice
oil contaminated with PCBs and breakdown
products PCDFs and PCDDs (dibenzofurans and
dibenzodioxins) in Japan (Yusho disease, 1968)
and Taiwan (Yu-Cheng disease, 1979)
 Neurobehavioral deficits
– increased “hyperactive” behaviors
 Impaired cognitive skills (Bayley, WISC-R)
PCB Developmental neurotoxicity -2
 PCB
developmental effects studied extensively
– in Michigan residents eating Great Lakes fish
– in NC residents with background levels
– in Hudson Bay (Alaska) Inuits
– in New Bedford MA
– in Netherlands
 Neurobehavioral effects noted:
– impaired recall of faces in 6-7 month infants (Fagan
test)
– depressed responsiveness
PCB Developmental neurotoxicity -3
 Studies
criticized for failing to control for some (less
likely) confounders, for patient selection, for
possibility that effects were caused by other
unmeasured neurotoxins like methylmercury or lead
 Abnormalities do not correlate directly with maternal
or infant levels
MI and NC Studies
NC (Rogan et al)
 Breast milk PCB 1800 ppb median




Cord serum PCB 80% <3 ppb
Cord serum PCB max 410 ppb
Maternal serum 9 ppb
4 yr. serum PCB not measured
MI (Jacobsen et al)
 836 ppb mean

PCB 66% < 3 ppb
max 12.3 ppb

5.5 ± 3.7 ppb

2.1 ± 3.3 ppb

Age at Assessmt
Endpoints Meas
Birth
Gestat age
Birth wt
Head circ
BNBAS scores
3 -6 mo
Growth & maturity
5 -6 mo
Bayley scales
7 mo
Visual recognition
(Fagan test)
NC Results +
MI Results +
NO
4.9 - 8.8 days less
NO
160 - 190 g less
NO
0.6 cm less
tone,  reflexes  autonomic
at high PCB levels maturity and
 abnl reflexes at
high fish intake
NO
not measured
 psychomotor
scores
not significantly
different
not measured
 for both cord
PCB and fish
consumption
Age at Assessmt
Endpoints Meas
NC Results +
MI Results +
12, 18, and 24
mo
Bayley scales
psychomoto
r scores
not measured
3 yr
McCarthy
scales
NO
not measured
4 yr
McCarthy
NO
memory + visual
discrimination in
high prenatal PCB
5 yr
Peabody
McCarthy
not
measured
NO
NO
not measured
Grades 3 -5
School
achievement
NO
not measured
PCB Developmental neurotoxicity -4
 Studies
inconsistent between studies about exactly
what was abnormal, but generally consistent in
finding abnl neurodevelopment
 Developmental neurotoxicity likely caused by
transplacental passage of PCBs
 Likely that there is a more vulnerable period at
some point(s) during development
 Unclear what effect from ingestion by the infant of
PCBs in breast milk; current thinking is benefit
outweighs risk
PCBs and infant birth weight
 MI
and Inuit studies suggest lower birth wt to
mothers with heavier body burdens of PCB, NC
studies don’t
 Magnitude of effect comparable to maternal
cigarette smoking
 Lower birth wt may be a function of shorter
gestations (avg. 4 - 8 days)
PCBs and cancer
 Multiple
different cancer types studied
 Many studies show a small increase in various
cancers, but findings not consistent between studies
 Clearly carcinogenic in animal models, but unclear
to what extent this applies to human cancer
PCBs and Immunologic Effects
 Implicated
as causing in a Dutch cohort:
– less wheezing
– less allergic reactions
– higher prevalence of recurrent middle ear infections
– higher prevalence of varicella
 Inuit infants:
– decreased CD4 / CD8 ratio at 6 and 12 mo of age
PCBs: Other effects?
 Much
of our knowledge of PCB effects is
incomplete.
 Other organ systems with suspected effects include
endocrine (thyroid) and increased complaints of
joint pains.
 All of the PCB data needs further investigation to
determine its true significance.
PCBs: So what to do?
 No
effective method for removing PCB from the
body has been proven.
 Watch for known problems
 Intervene early where problems are suspected,
particularly in children with learning or behavior
difficulties.
 Rule out other etiologies that are treatable -- e.g.,
lead toxicity, hearing, vision problems
In conclusion...
 Help
your patients by giving them the most accurate
information available on the subjects.
 Be an empathetic listener to their frustrations
 Treat problems where they exist.