toxic mixtures: Associations of Early Childhood Manganese and Lead Coexposure with Neurodevelopment

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Associations of Early Childhood Manganese and Lead Coexposure

with Neurodevelopment

EHP 2012

http://ehp03.niehs.nih.gov/article/fetchArticle.action?articleURI=info%3Adoi%2F1\

0.1289%2Fehp.1003300

Background: Most toxicologic studies focus on a single agent, although

this does not reflect real-world scenarios in which humans are exposed

to multiple chemicals.

Objectives: We prospectively studied manganese--lead interactions in

early childhood to examine whether manganese--lead coexposure is

associated with neurodevelopmental deficiencies that are more severe

than expected based on effects of exposure to each metal alone.

Methods: Four hundred fifty-five children were enrolled at birth in an

longitudinal cohort study in Mexico City, provided blood samples, and

were followed until 36 months of age. We measured lead and manganese at

12 and 24 months and assessed neurodevelopment at 6-month intervals from

12 to 36 months of age using Bayley Scales of Infant Development--II.

Results: Mean (± SD) blood concentrations at 12 and 24 months were,

respectively, 24.7 ± 5.9 ?g/L and 21.5 ± 7.4 ?g/L for manganese and 5.1

± 2.6 ?g/dL and 5.0 ± 2.9 ?g/dL for lead. Mixed-effects models,

including Bayley scores at five time points, showed a significant

interaction over time: highest manganese quintile × continuous lead;

mental development score, ? = --1.27 [95% confidence interval (CI):

--2.18, --0.37]; psychomotor development score, ? = --0.92 (95% CI:

--1.76, --0.09). Slopes for the estimated 12-month lead effect on

18-month mental development and 24- through 36-month psychomotor

development scores were steeper for children with high manganese than

for children with midrange manganese levels.

Conclusions: We observed evidence of synergism between lead and

manganese, whereby lead toxicity was increased among children with high

manganese coexposure. Findings highlight the importance of understanding

health effects of mixed exposures, particularly during potentially

sensitive developmental stages such as early childhood.

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Most toxicologic studies focus on a single agent and either do not

measure or do not adjust for potential confounding or modifying effects

of other chemicals. Although such an approach has identified toxicities

associated with various chemicals, it does not reflect real-world

scenarios in which humans are exposed to multiple chemicals

(Cory-Slechta 2005

<http://ehp03.niehs.nih.gov/article/fetchArticle.action?articleURI=info%3Adoi%2F\

10.1289%2Fehp.1003300#r20>;

1995

<http://ehp03.niehs.nih.gov/article/fetchArticle.action?articleURI=info%3Adoi%2F\

10.1289%2Fehp.1003300#r36>).

Human exposure to chemical mixtures is particularly widespread in

socioeconomically disadvantaged populations (Naess et al. 2007

<http://ehp03.niehs.nih.gov/article/fetchArticle.action?articleURI=info%3Adoi%2F\

10.1289%2Fehp.1003300#r29>)

and among populations living near hazardous waste sites (Hu et al. 2007

<http://ehp03.niehs.nih.gov/article/fetchArticle.action?articleURI=info%3Adoi%2F\

10.1289%2Fehp.1003300#r23>).

The customary approach of examining chemicals in isolation may constrain

our ability to understand neurologic sequelae (Bellinger 2008a

<http://ehp03.niehs.nih.gov/article/fetchArticle.action?articleURI=info%3Adoi%2F\

10.1289%2Fehp.1003300#r5>;

Cory-Slechta et al. 2008

<http://ehp03.niehs.nih.gov/article/fetchArticle.action?articleURI=info%3Adoi%2F\

10.1289%2Fehp.1003300#r21>).

Despite the importance of examining joint exposures to toxicants, few

epidemiologic studies have done so. Metals, in particular, are common

neurotoxicants occurring within the environments of children.

Concomitant exposure to several metals may have more severe (i.e.,

synergistic) effects on cognition than expected based on effects of

exposure to each metal alone ( et al. 2006

<http://ehp03.niehs.nih.gov/article/fetchArticle.action?articleURI=info%3Adoi%2F\

10.1289%2Fehp.1003300#r44>)....

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