Environmental Toxins Research: Lead

Blood lead concentrations < 10 microg/d: and child intelligence at 6 years of age.

Jusko TA, Henderson CR, Lanphear BP, Cory-Slechta DA, Parsons PJ, Canfield RL.

Department of Epidemiology, School of Public Health and Community Medicine, University of Washington, Seattle, WA, USA.  Environ Health Perspect. 2008 Feb;116(2):243-8.  Comment in:   Environ Health Perspect. 2008 Feb;116(2):A60-1.

BACKGROUND: Few studies provide data directly relevant to the question of whether blood lead concentrations < 10 microg/dL adversely affect children’s cognitive function. OBJECTIVE: We examined the association between blood lead concentrations assessed throughout early childhood and children’s IQ at 6 years of age.

METHODS: Children were followed from 6 months to 6 years of age, with determination of blood lead concentrations at 6, 12, 18, and 24 months, and 3, 4, 5, and 6 years of age. At 6 years of age, intelligence was assessed in 194 children using the Wechsler Preschool and Primary Scale of Intelligence-Revised. We used general linear and semiparametic models to estimate and test the association between blood lead concentration and IQ.

RESULTS: After adjustment for maternal IQ, HOME scale scores, and other potential confounding factors, lifetime average blood lead concentration (mean = 7.2 microg/dL; median = 6.2 microg/dL) was inversely associated with Full-Scale IQ (p = 0.006) and Performance IQ scores (p = 0.002). Compared with children who had lifetime average blood lead concentrations < 5 microg/dL, children with lifetime average concentrations between 5 and 9.9 microg/dL scored 4.9 points lower on Full-Scale IQ (91.3 vs. 86.4, p = 0.03). Nonlinear modeling of the peak blood lead concentration revealed an inverse association (p = 0.003) between peak blood lead levels and Full-Scale IQ down to 2.1 microg/dL, the lowest observed peak blood lead concentration in our study. CONCLUSIONS: Evidence from this cohort indicates that children’s intellectual functioning at 6 years of age is impaired by blood lead concentrations well below 10 microg/dL, the Centers for Disease Control and Prevention definition of an elevated blood lead level.



Decreased brain volume in adults with childhood lead exposure.

Cecil KM, Brubaker CJ, Adler CM, Dietrich KN, Altaye M, Egelhoff JC, Wessel S, Elangovan I, Hornung R, Jarvis K, Lanphear BP.  Cincinnati Children’s Environmental Health Center, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, United States of America. kim.cecil@cchmc.org  PLoS Med. 2008 May 27;5(5):e112.  Comment in:  PLoS Med. 2008 May 27;5(5):e115.

BACKGROUND: Although environmental lead exposure is associated with significant deficits in cognition, executive functions, social behaviors, and motor abilities, the neuroanatomical basis for these impairments remains poorly understood. In this study, we examined the relationship between childhood lead exposure and adult brain volume using magnetic resonance imaging (MRI). We also explored how volume changes correlate with historic neuropsychological assessments.

METHODS AND FINDINGS: Volumetric analyses of whole brain MRI data revealed significant decreases in brain volume associated with childhood blood lead concentrations. Using conservative, minimum contiguous cluster size and statistical criteria (700 voxels, unadjusted p < 0.001), approximately 1.2% of the total gray matter was significantly and inversely associated with mean childhood blood lead concentration. The most affected regions included frontal gray matter, specifically the anterior cingulate cortex (ACC). Areas of lead-associated gray matter volume loss were much larger and more significant in men than women. We found that fine motor factor scores positively correlated with gray matter volume in the cerebellar hemispheres; adding blood lead concentrations as a variable to the model attenuated this correlation. CONCLUSIONS: Childhood lead exposure is associated with region-specific reductions in adult gray matter volume. Affected regions include the portions of the prefrontal cortex and ACC responsible for executive functions, mood regulation, and decision-making. These neuroanatomical findings were more pronounced for males, suggesting that lead-related atrophic changes have a disparate impact across sexes. This analysis suggests that adverse cognitive and behavioral outcomes may be related to lead’s effect on brain development producing persistent alterations in structure. Using a simple model, we found that blood lead concentration mediates brain volume and fine motor function.



Exposures to environmental toxicants and attention deficit hyperactivity disorder in U.S. children.

Braun JM, Kahn RS, Froehlich T, Auinger P, Lanphear BP.  College of Nursing, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin, USA.  Environ Health Perspect. 2006 Dec;114(12):1904-9.  Comment in:  Environ Health Perspect. 2007 Aug;115(8):A398-9; author reply A399.  Environ Health Perspect. 2007 Aug;115(8):A398; author reply A399.

OBJECTIVE: The purpose of this study was to examine the association of exposures to tobacco smoke and environmental lead with attention deficit hyperactivity disorder (ADHD).

METHODS: Data were obtained from the National Health and Nutrition Examination Survey 1999-2002. Prenatal and postnatal tobacco exposure was based on parent report; lead exposure was measured using blood lead concentration. ADHD was defined as having current stimulant medication use and parent report of ADHD diagnosed by a doctor or health professional.

RESULTS: Of 4,704 children 4-15 years of age, 4.2% were reported to have ADHD and stimulant medication use, equivalent to 1.8 million children in the United States. In multivariable analysis, prenatal tobacco exposure [odds ratio (OR) = 2.5; 95% confidence interval (CI), 1.2-5.2] and higher blood lead concentration (first vs. fifth quintile, OR = 4.1; 95% CI, 1.2-14.0) were significantly associated with ADHD. Postnatal tobacco smoke exposure was not associated with ADHD (OR = 0.6; 95% CI, 0.3-1.3; p = 0.22). If causally linked, these data suggest that prenatal tobacco exposure accounts for 270,000 excess cases of ADHD, and lead exposure accounts for 290,000 excess cases of ADHD in U.S. children.

CONCLUSIONS: We conclude that exposure to prenatal tobacco and environmental lead are risk factors for ADHD in U.S. children.


Impaired neuropsychological functioning in lead-exposed children.

Canfield RL, Gendle MH, Cory-Slechta DA.  Division of Nutritional Sciences, College of Human Ecology, Cornell University, Savage Hall, Ithaca, NY 14853, USA. rlc@cornell.edu  Dev Neuropsychol. 2004;26(1):513-40.

Neuropsychological functions were assessed in 174 children participating in a longitudinal study of low-level lead exposure. At age 5 1/2 years, children were administered the Working Memory and Planning Battery of the Cambridge Neuropsychological Testing Automated Battery. Measures of sociodemographic characteristics of the family, prenatal and perinatal risk, quality of caregiving and crowding in the home, and maternal and child intelligence were used as covariates to test the hypothesis that children with higher lifetime average blood lead concentrations would perform more poorly on tests of working memory, attentional flexibility, and planning and problem solving. The lifetime average blood lead level in this sample was 7.2 micrograms per deciliter (mug/dL; range: 0-20 mug/dL). Children with greater exposure performed more poorly on tests of executive processes. In both bivariate and multivariate analyses, children with higher lifetime average blood lead concentrations showed impaired performance on the tests of spatial working memory, spatial memory span, intradimensional and extradimensional shifts, and an analog of the Tower of London task. Many of the significant associations remained after controlling for children’s intelligence test scores, in addition to the other covariates. These findings indicate that the effects of pediatric lead exposure are not restricted to global indexes of general intellectual functioning, and executive processes may be at particular risk of lead-induced neurotoxicity.



Intellectual impairment in children with blood lead concentrations below 10 microg per deciliter.

Canfield RL, Henderson CR Jr, Cory-Slechta DA, Cox C, Jusko TA, Lanphear BP.

Division of Nutritional Sciences, College of Human Ecology, Cornell University, Ithaca, NY 14853, USA. rlc5@cornell.edu  N Engl J Med. 2003 Apr 17;348(16):1517-26.

Comment in:  J Pediatr. 2003 Nov;143(5):687-8.  N Engl J Med. 2003 Apr 17;348(16):1515-6.  N Engl J Med. 2003 Jul 31;349(5):500-2; author reply 500-2.

BACKGROUND: Despite dramatic declines in children’s blood lead concentrations and a lowering of the Centers for Disease Control and Prevention’s level of concern to 10 microg per deciliter (0.483 micromol per liter), little is known about children’s neurobehavioral functioning at lead concentrations below this level.

METHODS: We measured blood lead concentrations in 172 children at 6, 12, 18, 24, 36, 48, and 60 months of age and administered the Stanford-Binet Intelligence Scale at the ages of 3 and 5 years. The relation between IQ and blood lead concentration was estimated with the use of linear and nonlinear mixed models, with adjustment for maternal IQ, quality of the home environment, and other potential confounders. RESULTS: The blood lead concentration was inversely and significantly associated with IQ. In the linear model, each increase of 10 microg per deciliter in the lifetime average blood lead concentration was associated with a 4.6-point decrease in IQ (P=0.004), whereas for the subsample of 101 children whose maximal lead concentrations remained below 10 microg per deciliter, the change in IQ associated with a given change in lead concentration was greater. When estimated in a nonlinear model with the full sample, IQ declined by 7.4 points as lifetime average blood lead concentrations increased from 1 to 10 microg per deciliter.

CONCLUSIONS: Blood lead concentrations, even those below 10 microg per deciliter, are inversely associated with children’s IQ scores at three and five years of age, and associated declines in IQ are greater at these concentrations than at higher concentrations. These findings suggest that more U.S. children may be adversely affected by environmental lead than previously estimated.



Low-level environmental lead exposure and children’s intellectual function: an International pooled analysis.

Lanphear BP, Hornung R, Khoury J, Yolton K, Baghurst P, Bellinger DC, Canfield RL, Dietrich KN, Bornschein R, Greene T, Rothenberg SJ, Needleman HL, Schnaas L, Wasserman G, Graziano J, Roberts R.  Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA. bruce.lamphear@cchmc.org  Environ Health Perspect. 2005 Jul;113(7):894-9.  Comment in:  Environ Health Perspect. 2006 Feb;114(2):A85-6; author reply A86-7.

Lead is a confirmed neurotoxin, but questions remain about lead-associated intellectual deficits at blood lead levels < 10 microg/dL and whether lower exposures are, for a given change in exposure, associated with greater deficits. The objective of this study was to examine the association of intelligence test scores and blood lead concentration, especially for children who had maximal measured blood lead levels < 10 microg/dL. We examined data collected from 1,333 children who participated in seven international population-based longitudinal cohort studies, followed from birth or infancy until 5-10 years of age. The full-scale IQ score was the primary outcome measure. The geometric mean blood lead concentration of the children peaked at 17.8 microg/dL and declined to 9.4 microg/dL by 5-7 years of age; 244 (18%) children had a maximal blood lead concentration < 10 microg/dL, and 103 (8%) had a maximal blood lead concentration < 7.5 microg/dL. After adjustment for covariates, we found an inverse relationship between blood lead concentration and IQ score. Using a log-linear model, we found a 6.9 IQ point decrement [95% confidence interval (CI), 4.2-9.4] associated with an increase in concurrent blood lead levels from 2.4 to 30 microg/dL. The estimated IQ point decrements associated with an increase in blood lead from 2.4 to 10 microg/dL, 10 to 20 microg/dL, and 20 to 30 microg/dL were 3.9 (95% CI, 2.4-5.3), 1.9 (95% CI, 1.2-2.6), and 1.1 (95% CI, 0.7-1.5), respectively. For a given increase in blood lead, the lead-associated intellectual decrement for children with a maximal blood lead level < 7.5 microg/dL was significantly greater than that observed for those with a maximal blood lead level > or = 7.5 microg/dL (p = 0.015). We conclude that environmental lead exposure in children who have maximal blood lead levels < 7.5 microg/dL is associated with intellectual deficits.



Low-level lead exposure, executive functioning, and learning in early childhood.

Canfield RL, Kreher DA, Cornwell C, Henderson CR Jr.  Division of Nutritional Sciences, Cornell University, Ithaca, NY 14850, USA. rlc5@cornell.edu  Child Neuropsychol. 2003 Mar;9(1):35-53.

The current paper presents evidence relating low-level lead exposure to impaired executive functioning in young children. Using the Shape School task, we assessed focused attention, attention switching, working memory, and the ability to inhibit automatic responses in a cohort of 170 children. Participants performed the Shape School task at both 48 and 54 months of age; the mean blood lead level was 6.49 microg/dl at 48 months. After controlling for a wide range of sociodemographic, prenatal, and perinatal variables, blood lead level was negatively associated with children’s focused attention while performing the tasks, efficiency at naming colors, and inhibition of automatic responding. In addition, children with higher blood lead levels completed fewer phases of the task and knew fewer color and shape names. There was no association between blood lead and performance on the most difficult tasks, those requiring attention switching or the combination of inhibition and switching. Children’s IQ scores were strongly associated with blood lead and Shape School performance, and when entered as a covariate, only color knowledge and the number of tasks completed remained significant. Results provide only weak support for impaired executive functioning, but the deficits in color knowledge may indicate a primary sensory deficit or difficulty with forming conditional associations, both implicating disruptions in dopamine system function.



Metal concentrations in rural topsoil in South Carolina: potential for human health impact.

Aelion CM, Davis HT, McDermott S, Lawson AB.  University of South Carolina, Department of Environmental Health Sciences, 921 Assembly Street, Columbia, SC 29208, United States. aelionm@sc.edu  Sci Total Environ. 2008 Sep 1;402(2-3):149-56. Epub 2008 Jun 6.

Rural areas are often considered to have relatively uncontaminated soils; however few studies have measured metals in surface soil from low population areas. Many metals, i.e., arsenic (As), lead (Pb), and mercury (Hg), have well-documented negative neurological effects, and the developing fetus and young children are particularly at risk. Using a Medicaid database, two areas were identified: one with no increased prevalence of mental retardation and developmental delay (MR/DD) (Strip 1) and one with significantly higher prevalence of MR/DD (Strip 2) in children compared to the state-wide average. These areas were mapped and surface soil samples were collected from 0-5 cm depths from nodes of a uniform grid laid out across the sampling areas. Samples were analyzed for As, barium (Ba), beryllium (Be), chromium (Cr), copper (Cu), Pb, manganese (Mn), nickel (Ni), and Hg. Inverse distance weighting (IDW) was used to estimate concentrations throughout each strip area, and a principal component analysis (PCA) was used to identify common sources. All metal concentrations in Strip 2, the MR/DD cluster area, were significantly greater than those in Strip 1 and similar to those found in more urban and highly agricultural areas. Both Strips 1 and 2 had a high number of significant correlations between metals (33 for Strip 1 and 25 for Strip 2), suggesting possible similar natural or anthropogenic sources which was corroborated by PCA. While exposures were not assessed and direct causation between environmental soil metal concentrations and MR/DD cannot be concluded, the high metal concentrations in areas with an elevated prevalence of MR/DD warrants further consideration.



Neuropsychological function in children with blood lead levels <10 microg/dL.

Surkan PJ, Zhang A, Trachtenberg F, Daniel DB, McKinlay S, Bellinger DC.

Department of Environmental Health, Harvard School of Public Health, Landmark Building, 4th Floor, 401 Park Drive, Boston, MA 02115, USA.  Neurotoxicology. 2007 Nov;28(6):1170-7. Epub 2007 Jul 25.

Clear adverse effects of blood lead levels >or=10 microg/dL have been documented in children. Given that the majority of US children have levels below 10 microg/dL, clarification of adverse effects below this cutoff value is needed. Our study evaluated the associations between blood lead levels <10 microg/dL and a broad spectrum of children’s cognitive abilities. Data were analyzed from 534 children aged 6-10, enrolled in the New England Children’s Amalgam Trial (NECAT) from the urban area of Boston, Massachusetts and rural Farmington, Maine. Adjusting for covariates (age, race, socioeconomic status, and primary caregiver IQ), children with 5-10 microg/dL had 5.0 (S.D. 2.3) points lower IQ scores compared to children with blood lead levels of 1-2 microg/dL (p=0.03). Verbal IQ was more negatively affected than performance IQ, with the most prominent decrement occurring in children’s vocabulary. Wechsler Individual Achievement Test scores were strongly negatively associated with blood lead levels of 5-10 microg/dL. In adjusted analyses, children with levels of 5-10 microg/dL scored 7.8 (S.D. 2.4) and 6.9 (S.D. 2.2) points lower on reading and math composite scores, respectively, compared to children with levels of 1-2 microg/dL (p<0.01). Finally, levels of 5-10 microg/dL were associated with decreased attention and working memory. Other than associations of lead exposure with achievement, which even persisted after adjustment for child IQ, the most pronounced deficits were in the areas of spatial attention and executive function. Overall, our analyses support prior research that children’s blood levels <10 microg/dL are related to compromised cognition and highlight that these may especially be related to academic achievement.



Use of a general toxicity test to predict heavy metal concentrations in residential soils.

Aelion CM, Davis HT.  Department of Environmental Health Sciences, Room 401, University of South Carolina, 921 Assembly Street, Columbia, SC 29208, USA. aelionm@sc.edu  Chemosphere. 2007 Mar;67(5):1043-9. Epub 2006 Nov 30.

Significant clusters of developmental delay and mental retardation (DD/MR) were identified in children born in South Carolina. Although it is difficult to identify one factor that causes DD/MR, environmental insult including exposure of pregnant women to heavy metals can induce DD/MR in their children. Because it is expensive to measure the concentrations of individual metals in large numbers of environmental samples, the general Microtox toxicity test was used to identify highly toxic soil samples. Approximately 100 soil samples were collected from residential areas and analyzed to determine an effective concentration (EC(50)) of soil required to inhibit 50% light emission of the luminescent bacterial test organism (Vibrio fischeri). The EC(50) values were then transformed to relative toxicity units (RTU). A subset of 56 high and low toxicity soil samples was then analyzed by inductively coupled plasma-atomic emission spectrometry (EPA method 6010) for arsenic, lead, and chromium, which are known neurotoxins. The highest measured arsenic concentration was 30 times higher than the South Carolina residential soil limit. Significant correlations were found between the RTU and soil arsenic and chromium concentrations. Microtox also identified some low arsenic and chromium samples as toxic, presumably because additional unidentified toxicants were present in the soil. In general, however, the Microtox test was effective in identifying soils with elevated concentrations of arsenic and chromium, even in residential neighborhoods where limited soil toxicity was expected.