Lead and PCBs: A Toxic Legacy in Anniston

1. 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

2. 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

3. 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.

5. 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

6. 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

7. Lead in Anniston Metal foundries in Anniston milled and cast metal objects, presumably some with leaded alloys Leaded gasoline use Lead paint use

8. 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

10. Lead

11. 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

12. Lead�s impact on verbal IQ

13. Lead blood levels vs. IQ

14. Result of a 5 point reduction in average IQ

15. 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.

16. 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.

17. 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

18. 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

19. 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

20. 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

21. 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

22. 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

23. PCB Toxic Effects Suspected Acute exposure Chloracne Birth defects Hepatic dysfunction Subacute & chronic exposure Neurotoxicity, child and adult Low birth weight Cancer Immunologic dysfunction

24. 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

25. 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

26. 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

27. 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

32. 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)

33. 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 delayed psychomotor development

34. 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

35. 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

38. 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

39. 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)

40. 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

41. 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

42. 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.

43. 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

44. 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.