Lead neurotoxicity in children: Decomposing the variability in dose-effect relationships

American Journal of Industrial Medicine

Volumn 50, Issue 10, 2007, Pages 720-728

  Bellinger, David C ^a,b,c  

^a HARVARD MEDICAL SCHOOL   (United States)

^b HARVARD SCHOOL OF PUBLIC HEALTH   (United States)

^c BOSTON CHILDREN S HOSPITAL   (United States)

Author keywords

Children; Lead; Neurotoxicity

Indexed keywords

APOLIPOPROTEIN E; DOPAMINE 4 RECEPTOR; HFE PROTEIN; LEAD; NITRIC OXIDE SYNTHASE; VITAMIN D RECEPTOR;

ALZHEIMER DISEASE; CONFERENCE PAPER; DISEASE PREDISPOSITION; DOSE RESPONSE; ENVIRONMENTAL EXPOSURE; FRAGILE X SYNDROME; GENETIC POLYMORPHISM; HUMAN; HUNTINGTON CHOREA; LEAD BLOOD LEVEL; LEAD POISONING; NEUROTOXICITY; NUCLEAR MAGNETIC RESONANCE IMAGING; PARKINSON DISEASE; QUALITY OF LIFE; RISK FACTOR;

ANIMALS; BIOLOGICAL MARKERS; CHILD; DISEASE MODELS, ANIMAL; DOSE-RESPONSE RELATIONSHIP, DRUG; ENVIRONMENTAL EXPOSURE; ENVIRONMENTAL POLLUTANTS; GENETIC PREDISPOSITION TO DISEASE; HUMANS; LEAD; LEAD POISONING, NERVOUS SYSTEM, CHILDHOOD;

EID: 36849079337     PISSN: 02713586     EISSN: 10970274     Source Type: Journal    
DOI: 10.1002/ajim.20438     Document Type: Conference Paper

References (72)

1. Artola A, von Frijtag JC, Fermont PC, Gispen WH, Schrama H, Kamal A, Spruijt BM. 2006. Long-lasting modulation of the induction of LTD and LTP in rat hippocampal CA1 by behavioural stress and environmental enrichment. Europ J Neurosci 23:261-272.
2. Bellinger DC. 2000. Effect modification in epidemiologic studies of low-level neurotoxicant exposures and health outcomes. Neurotoxicol Teratol 22:133-140.
3. Bellinger D, Leviton A, Waternaux C, Allred E. 1985. Methodological issue in modeling the relationship between low-level lead exposure and infant development: Examples from the Boston lead Study. Environ Res 38:119-129.
4. Bellinger D, Leviton A, Waternaux C, Needleman H, Rabinowitz M. 1988. Low-level lead exposure, social class, and infant development. Neurotoxicol Teratol 10:497-503.
5. Bellinger D, Leviton A, Sloman J. 1990. Antecedents and correlates of improved cognitive performance in children exposed in utero to low levels of lead. Environ Health Perspect 89:5-11.
6. Bennett JC, McRae PA, Levy LJ, Frick KM. 2006. Long-term continuous, but not daily, environmental enrichment reduces spatial memory decline in aged male mice. Neurobio Learn Mem 85:139-152.
7. Bergdahl IA, Vahter M, Counter SA, Schutz A, Buchanan LH, Ortega F, Laurell G, Skerfving S. 1999. Lead in plasma and whole blood from lead-exposed children. Environ Res 80:25-33.
8. Chen X, Li Y, Kline AE, Dixon CE, Zafonte RD, Wagner AK. 2005. Gender and environmental effects on regional brain-derived neurotrophic factor expression after experimental traumatic brain injury. Neuroscience 135:11-17.
9. Chia SE, Huijun Z, Theng TM, Yap E. In press. Possibilities of newer ALAD polymorphism influencing human susceptibility to effects of inorganic lead on the neurobehavioral functions. Neurotoxicology.
10. Chia SE, Yap E, Chia KS. 2004. Delta-aminolevulinic acid dehydratase (ALAD) polymorphism and susceptibility of workers exposed to inorganic lead and its effects on neurobehavioral functions. Neurotoxicology 25:1041-1047.
11. Chuang HY, Schwartz J, Gonzalez-Cossio T, Lugo MC, Palazuelos E, Aro A, Hu H, Hernandez-Avila M. 2001. Interrelations of lead levels in bone, venous blood, and umbilical cord blood with exogenous lead exposure through maternal plasma lead in peripartum women. Environ Health Perspect 109:527-532.
12. Cremin JD, Luck ML, Laughlin NK, Smith DR. 1999. Efficacy of succimer chelation for reducing brain lead in a primate model of human lead exposure. Toxicol Appl Pharmacol 161:283-293.
13. Cohen S, Doyle WJ, Baum A. 2006. Socioeconomic status is associated with stress hormones. Psychosom Med 68:414-420.
14. Cory-Slechta DA. 2005. Studying toxicants as single chemicals: Does this strategy adequately identify neurotoxic risk? Neurotoxicology 26:491-510.
15. Costa DA, Cracchiolo JR, Bachstetter AD, Hughes TF, Bales KR, Paul SM, Mervis RF, Arendash GW, Potter H. In press. Enrichment improves cognition in AD mice by amyloid-related and unrelated mechanisms. Neurobiol Aging.
16. Ernhart CB. 1995. Inconsistencies in the lead-effects literature exist and cannot be explained by "effect modification". Neurotoxicol Teratol 17:227-233.
17. Faherty CJ, Raviie Shepherd K, Herasimtschuk A, Smeyne RJ. 2005. Environmental enrichment in adulthood eliminates neuronal death in experimental Parkinsonism. Brain Res Mol Brain Res 134:170-179.
18. Froehlich TE, Lanphear BP, Dietrich KN, Cory-Slechta DA, Kahn RS. 2006. Effects of DRD4, lead, and sex on ADHD-related executive function. Presented at the Pediatric Academic Societies.
19. Frank DA, Rose-Jacobs R, Beeghly M, Wilbur M, Bellinger D, Cabral H. 2005. Level of prenatal cocaine exposure and 48-month IQ: Importance of preschool enrichment. Neurotoxicol Teratol 27:15-28.
20. Gallo LC, Matthews KA. 2003. Understanding the association between socioeconomic status and physical health: Do negative emotions play a role? Psychol Bull 129:10-51.
21. Gochfeld M. In press. Framework for gender differences in human and animal toxicology. Environ Res.
22. Grandjean P. 2005. Non-precautionary aspects of toxicology. Toxicol Appl Pharmacol 1; 207: (2 Suppl):652-657.
23. Grandjean P, Budtz-Jorgensen E, Keiding N, Weihe P. 2004. Underestimation of risk due to exposure misclassification. Int J Occup Med Environ Health 17:131-136.
24. Greene T, Ernhart CB. 1991. Adjustment for cofactors in pediatric research. J Dev Behav Pediatr 12:378-385.
25. Guilarte TR, Toscano CD, McGlothan JL, Weaver SA. 2003. Environmental enrichment reverse cognitive and molecular deficits induced by developmental lead exposure. Ann Neurol 53:50-56.
26. Harvey PG, Hamlin MW, Kumar R, Delves HT. 1984. Blood lead, behaviour and intelligence test performance in preschool children. Sci Tot Environ 40:45-60.
27. Hu H, Tellez-Rojo M, Bellinger D, Smith D, Ettinger AS, Lamadrid-Figueroa H, Schwartz J, Schnaas L, Mercado-Garcia A, Hernandez-Avila M. 2006. Fetal lead exposure at each stage of pregnancy as a predictor of infant mental development. Environ Health Perspect 114: 1730-1735.
28. Jankowsky JL, Melnikova T, Fadale DJ, Xu GM, Slunt HH, Gonzales V, Younkin LH, Younkin SG, Borchelt DR, Savonenko AV. 2005. Environmental enrichment mitigates cognitive deficits in a mouse model of Alzheimer's disease. J Neurosci 25:5217-5224.
29. Jurek AM, Greenland S, Maldonado G, Church TR. 2005. Proper interpretation of nondifferential misclassification effects: Expectations vs. observations. Int J Epidemiol 34:680-687.
30. Kamel F, Umbach DM, Lehman TA, Park LP, Munsat TL, Shefner JM, Sandler DP, Hu H, Taylor JA. 2003. Amyotrophic lateral sclerosis, lead, and genetic susceptibility: Polymorphisms in the delta-aminolevulinic acid dehydratase and vitamin D receptor genes. Environ Health Perspect 111:1335-1339.
31. Kamel F, Umbach DM, Hu H, Munsat TL, Shefner JM, Taylor JA, Sandler DP. 2005. Lead exposure as a risk factor for amyotrophic lateral sclerosis. Neurodegener Dis 2:195-201.
32. Komitova M, Mattsson B, Johansson BB, Eriksson PS. 2005. Enriched environment increases neural stem/progenitor cell proliferation and neurogenesis in the subventricular zone of stroke-lesioned adult rats. Stroke 36:1278-1282.
33. Lansdown R, Yule W, Urbanowicz MA, Hunter J. 1986. The relationship between blood-lead concentrations, intelligence, attainment and behaviour in a school population: The second London study. Int Arch Occup Environ Health 57:225-235.
34. Lazic SE, Grote HE, Blakemore C, Hannan AJ, van Dellen A, Phillips W, Barker RA. 2006. Neurogenesis in the R6/1 transgenic mouse model of Huntington's disease: Effects of environmental enrichment. Europ J Neurosci 23:1829-1838.
35. Leggett RW. 1993. An age-specific kinetic model of lead metabolism in humans. Environ Health Perspect 101:598-616.
36. Lewis MH. 2004. Environmental complexity and central nervous system development and function. Ment Retard Develop Disabilities Res Rev 10:91-95.
37. Li L, Tang BL. 2005. Environmental enrichment and neurodegenerative diseases. Biochem Biophys Res Comm 26:334:293-297.
38. Louis ED, Applegate L, Graziano JH, Parides M, Slavkovich V, Bhat HK. 2005. Interaction between blood lead concentration and delta-amino-levulinic acid dehydratase gene polymorphisms increases the odds of essential tremor. Movement Disord 20:1170-1177.
39. Maegele M, Lippert-Gruener M, Ester-Bode T, Garbe J, Bouillon B, Neugebauer E, Klug N, Lefering R, Neiss WF, Angelov DN. 2005. Multimodal early onset stimulation combined with enriched environment is associated with reduced CNS lesion volume and enhanced reversal of neuromotor dysfunction after traumatic brain injury in rats. Europ J Neurosci 21:2406-2418.
40. McMichael AJ. 1999. Prisoners of the proximate: Loosening the constraints on epidemiology in an age of change. Am J Epidemiol 149: 887-897.
41. Meng XM, Zhu DM, Ruan DY, She Q, Luo L. 2005. Effects of chronic lead exposure on 1H MRS of hippocampus and frontal lobes in children. Neurology 64:1644-1647.
42. Montenegro MF, Barbosa F, Sandrim VC, Gerlach RF, Tanus-Santos JE. 2005. A polymorphism in the delta-aminolevulinic acid dehydratase gene modifies the plasma/whole blood lead ratio. Arch Toxicol 9:1-5.
43. Morello-Frosch R, Pastor M, Porras C, Sadd J. 2002. Environmental justice and regional inequality in southern California: Implications for future research. Environ Health Perspect 110: (Suppl 2):149-154.
44. Neugebauer NM, Cunningham ST, Zhu J, Bryant RI, Middleton LS, Dwoskin LP. 2004. Effects of environmental enrichment on behavior and dopamine transporter function in medial prefrontal cortex in adult rats prenatally treated with cocaine. Brain Res Develop Brain Res 153:213-223.
45. O'Flaherty EJ. 1993. Physiologically based models for bone-seeking elements. IV. Kinetics of lead disposition in humans. Toxicol Appl Pharmacol 118:16-29.
46. O'Flaherty EJ. 1995. Physiologically based models for bone-seeking elements: V. Lead absorption and disposition in childhood. Toxicol Appl Pharmacol 131:297-308.
47. Onalaja AO, Claudio L. 2000. Genetic susceptibility to lead poisoning. Environ Health Perspect 108:23-28.
48. Payne-Sturges D, Gee GC, Crowder K, Hurley BJ, Lee C, Morello-Frosch R, Rosenbaum A, Schulz A, Wells C, Woodruff T, Zenick H. 2006. Workshop Summary: Connecting social and environmental factors to measure and track environmental health disparities. Environ Res 102:146-153.
49. Rauh VA, Parker FL, Garfinkel RS. 2003. Biological, social, and community influences on third-grade reading levels of minority Head start children: A multilevel approach. J Comm Psychol 31:255-278.
50. Restivo L, Ferrari F, Passino E, Sgobio C, Bock J, Oostra BA, Bagni C, Ammassari-Teule M. 2005. Enriched environment promotes behavioral and morphological recovery in a mouse model for the fragile X syndrome. Proc Nat Acad Sci USA 102:11557-11562.
51. Rothman KJ, Greenland S. 1998. Causation and causal inference. In Rothman KJ, Greenland S. (Eds.) Modern Epidemiology. 2nd Edition. Philadelphia: Lippincott Williams & Wilkins, pp 7-28.
52. Schneider T, Turczak J, Przewlocki R. 2006. Environmental enrichment reverses behavioral alterations in rats prenatally exposed to valproic acid: Issues for a therapeutic approach in autism. Neuropsychopharmacol 31:36-46.
53. Smith D, Hernandez-Avila M, Tellez-Rojo M, Mercado A, Hu H. 2002. The relationship between lead in plasma and whole blood in women. Environ Health Perspect 110:263-268.
54. Soobader M, Cubbin C, Gee GC, Rosenbaum A, Laurenson J. 2006. Levels of analysis for the study of environmental health disparities. Environ Res 102:172-180.
55. Spires TL, Hannan AJ. 2005. Nature, nurture and neurology: Gene-environment interactions in neurodegenerative disease. FEBS J 272: 2347-2361.
56. Stangle DR, Strawderman MS, Smith D, Kuypers M, Strupp BJ. 2004. Reductions in blood lead overestimate reductions in brain lead after repeated succimer regiments in a rodent model of childhood lead exposure. Environ Health Perspect 112:302-308.
57. Stewart WF, Schwartz BS, Simon D, Kelsey K, Todd AC. 2002. ApoE genotype, past adult lead exposure, and neurobehavioral function. Environ Health Perspect 110:501-505.
58. Tong S, Lu Y. 2001. Identification of confounders in the assessment of the relationship between lead exposure and child development. Ann Epidemiol 11:38-45.
59. Trope I, Lopez-Villegas D, Cecil KM, Lenkinski RE. 2001. Exposure to lead appears to selectively alter metabolism of cortical gray matter. Pediatrics 107:1437-1443.
60. U.S. Environmental Protection Agency. 2005. All ages lead model [draft version 1.05]. Research Triangle Park, NC: National Center for Environmental Assessment.
61. Virgolini MB, Chen K, Weston DD, Bauter MR, Cory-Slechta DA. 2005. Interactions of chronic lead exposure and intermittent stress: Consequences for brain catecholamine systems and associated behaviors and HPA axis function. Toxicol Sci 87:469-482.
62. Virgolini MB, Bauter MR, Weston DD, Cory-Slechta DA. 2006. Permanent alterations in stress responsivity in female offspring subjected to combined maternal lead exposure and/or stress. Neurotoxicology 27:11-21.
63. Wallace CS, Reitzenstein J, Withers GS. 2003. Diminished experience-dependent neuroanatomical plasticity: Evidence for an improved biomarker of subtle neurotoxic damage to the developing rat brain. Environ Health Perspect 111:1294-1298.
64. Weiss B, Bellinger DC. 2006. Social ecology of children's vulnerability to environmental pollutants. Environ Health Perspect 114:1479-1485.
65. Weisskopf MG, Hu H, Mulkern RV, White R, Aro A, Oliveira S, Wright RO. 2004. Cognitive deficits and magnetic resonance spectroscopy in adult monozygotic twins with lead poisoning. Environ Health Perspect 112:620-625.
66. Weuve J, Kelsey KT, Schwartz J, Bellinger D, Wright RO, Rajan P, Spiro A, Sparrow D, Aro A, Hu H. 2006. Delta-aminolevulinic acid dehydratase polymorphism and the relation between low level lead exposure and the Mini-Mental Status Examination in older men: The Normative Aging Study. Occup Environ Med 63:746-753.
67. White PD, Van Leeuwan P, Davis BD, Maddaloni M, Hogan KA, Marcus AH, Elias RW. 1998. The conceptual structure of the integrated exposure uptake biokinetic model for lead in children. Environ Health Perspect 106suppl. (6):1513-1530.
68. Wilson MA, Johnston MV, Goldstein GW, Blue ME. 2000. Neonatal lead exposure impairs development of rodent barrel field cortex. Proc Natl Acad Sci 97:5540-5545.
69. Wilson MA, Blue ME, Patra RC, Gordon-Lipkin EM, Johnston MW. 2006. Neonatal lead exposure impairs plasticity in developing rat somatosensory cortex. Paper presenteds at the XXIII International Neurotoxicology Conference, Little Rock, Arkansas.
70. Winneke G, Kraemer U. 1984. Neuropsychological effects of lead in children: Interactions with social background variables. Neuropsychobiol 11:195-202.
71. Wright RO, Hu U, Silverman E, Tsaih S, Schwartz J, Bellinger D, Palazuelos E, Weiss ST, Hernandez M. 2003. Apolipoprotein E genotype predicts 24-month Bayley Scales Infant Development score. Pediatric Res 54:819-825.
72. Yuan W, Holland SK, Cecil KM, Dietrich KN, Wessel SD, Altaye M, Hornung RW, Ris MD, Egelhoff JC, Lanphear BP. 2006. The impact of early childhood lead exposure on brain organization-An fMRI study of language function. Pediatrics 118:971-977.