Superfund Research Program

Consequences of Arsenic and Manganese Exposure on Children

Project Leader: Joseph H. Graziano
Grant Number: P42ES010349
Funding Period: 2000-2017

Project-Specific Links

Final Progress Reports

Year:   2016  2010  2005 

This project builds upon Dr. Joseph Graziano's discovery that arsenic (As) and manganese (Mn) exposure from drinking water have adverse effects on intelligence in children. Two studies, in Bangladesh and New England, are in progress. Four years ago, the research group launched a study of elementary-school children in New Hampshire (NH) to determine whether exposure to As impairs intellectual functioning in a U.S. population. Because recruitment in NH was not proceeding at a sufficient rate, the researchers expanded their study into Maine (ME), where recruitment is excellent and As exposure is more prevalent. To date, 307 children have been recruited and have completed the protocol. Of these, 150 have been recruited in the past year, thanks to an Administrative Supplement that enabled them to hire a new staff member in ME.

Of the 250 children in the interim analysis, 80 had water As levels greater than the EPA standard of 10 ppb. Child IQ scores range from 81-147. Thus far, the mean IQ of those with water As < 10 ppb is 109.2 while the mean for those with water As > 10 ppb is 105.5. These very preliminary analyses are not conclusive, as they must still employ appropriate regression modeling to control for covariates.

The second portion of this project takes place in Bangladesh, where the researchers seek to determine whether exposure to As and Mn has an adverse effect on motor function and on intelligence. This study involves a 2 x 2 design — i.e., high/low (<10 ppb) drinking water As and high/low (< 400 ppb) water Mn, with 75 children in each cell. Thus, half of the children in the study are drinking water with As and Mn levels below the World Health Organization guideline. The researchers completed the recruitment of all 300 children, 7-9 years of age. Their first publication, submitted, relates to child intelligence: When adjusted only for each other, both As and Mn in blood (BAs; BMn) were significantly negatively related to most Wechsler Intelligence Scale for Children IV (WISC-IV) subscale scores. With further adjustment for socio-demographic features and ferritin, BMn remained significantly associated with reduced Perceptual Reasoning and Working Memory scores; associations for BAs, and for other subscales, were expectably negative, but largely non-significant. Urinary As (per gram creatinine) was significantly negatively associated with Verbal Comprehension scores, even with adjustment for BMn and other contributors. Mn by As interactions were not significant in adjusted or unadjusted models.

A second submitted manuscript describes a novel finding: BMn (but not BAs) is adversely associated with child behavior. Using the Child Behavior Checklist and Teacher’s Report Form, the researchers observed that water manganese (WMn) was positively and significantly associated with TRF internalizing, externalizing and total TRF scores in models adjusted for WAs and sociodemographic covariates. They also observed a dose-response relationship between WMn and TRF externalizing and TRF total scores among the participants of the study. They did not find any associations between WAs and various scales of TRF scores. These observations reinforce the growing concern regarding the neurotoxicologic effects of WMn in children.

A third manuscript that is nearly completed is described in Dr. Hei's research, Genotoxic and Cell Signaling Pathways of Arsenic in Mammalian Cells. In short, BAs (but not BMn) is adversely associated with motor function in these same 300 children.

The next phase of the Bangladesh work involves remediation of the ongoing As and Mn exposures via the installation of deep tube wells in each child’s village by Dr. Alexander Van Geen. The researchers will reassess motor function and intelligence over time to determine whether the consequences of exposure are reversible. The installation of deep wells low in As and Mn has been completed.