Lead and PCBs: A Toxic Legacy in Anniston

Robert J. Geller, MDSE 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; 24:595-600Tang 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 the “in vogue” approach in late 80’s and early

‘90’s‘90’s– low yield notedlow yield noted– still recommended for highest risk areas of US, still recommended for highest risk areas of US,

such as the “rust belt” of the NEsuch as the “rust belt” of the NE “Selective screening”

– screen those with 1 or more risk factors at 9 screen those with 1 or more risk factors at 9 months, consider repeat at 24 months of agemonths, 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 venous sample less likely to be contaminated

with surface debriswith surface debris– fingerstick sample requires less technical skill fingerstick sample requires less technical skill

to obtainto obtain Erythrocyte protoporphyrin (EPP or ZPP) not

sensitive at this level of detection, not useful

Dealing with the results - 1

Remember, national population mean now 3 g/dL

BLL < 10 g/dL: do nothing BLL 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

Dealing with the results - 2

BLL 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

Chelation for lead Succimer is usually lead chelator of choice (a.k.a.

DMSA or Chemet®)– oral agent, comes as powder in capsuleoral agent, comes as powder in capsule– tid dosing schedule x 5 days, then bid x 14 daystid dosing schedule x 5 days, then bid x 14 days– watch renal and hepatic function during watch renal and hepatic function during

chelationchelation– best dosed as 350 mg/mbest dosed as 350 mg/m2 2 /dose, particularly in /dose, particularly in

young children or obese, else 10 mg/kg/doseyoung children or obese, else 10 mg/kg/dose Alternatives: CaEDTA ± BAL, penicillamine

PCB Toxic Effects Suspected Acute exposure

– ChloracneChloracne– Birth defectsBirth defects– Hepatic dysfunctionHepatic dysfunction

Subacute & chronic exposure– Neurotoxicity, child and adultNeurotoxicity, child and adult– Low birth weightLow birth weight– CancerCancer– Immunologic dysfunctionImmunologic 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 age (few elevated levels, none very elevated, in children)children)

– length of residence near the plant, even when length of residence near the plant, even when adjusted for ageadjusted for age

– picapica

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” behaviorsincreased “hyperactive” behaviors

Impaired cognitive skills (Bayley, WISC-R)

PCB Developmental neurotoxicity -2

PCB developmental effects studied extensively– in Michigan residents eating Great Lakes in Michigan residents eating Great Lakes

fishfish– in NC residents with background levelsin NC residents with background levels– in Hudson Bay (Alaska) Inuitsin Hudson Bay (Alaska) Inuits– in New Bedford MAin New Bedford MA– in Netherlandsin Netherlands

Neurobehavioral effects noted:– impaired recall of faces in 6-7 month infants impaired recall of faces in 6-7 month infants

(Fagan test)(Fagan test)– depressed responsivenessdepressed responsiveness– delayed psychomotor developmentdelayed psychomotor development

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 NC Results + MI Results +

Birth Gestat ageBirth wtHead circBNBAS scores

NONONO tone, reflexes

at high PCB levels

4.9 - 8.8 days less160 - 190 g less0.6 cm less autonomic

maturity and abnl reflexes athigh fish intake

3 -6 mo Growth & maturity NO not measured

5 -6 mo Bayley scales psychomotorscores

not significantlydifferent

7 mo Visual recognition(Fagan test)

not measured for both cordPCB and fishconsumption

Age at Assessmt Endpoints Meas NC Results + MI Results +

12, 18, and 24mo

Bayley scales psychomotor scores

not measured

3 yr McCarthyscales

NO not measured

4 yr McCarthy NO memory + visualdiscrimination inhigh prenatal PCB

5 yr PeabodyMcCarthy

notmeasuredNO

NOnot measured

Grades 3 -5 Schoolachievement

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 wheezingless wheezing– less allergic reactionsless allergic reactions– higher prevalence of recurrent middle ear higher prevalence of recurrent middle ear

infectionsinfections– higher prevalence of varicellahigher prevalence of varicella

Inuit infants:

– decreased CDdecreased CD44 / CD / CD88 ratio at 6 and 12 mo of ratio at 6 and 12 mo of ageage

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.