Lead was phased out of gasoline and PCBs were phased out of use in electrical equipment in the 1970s. Since that time, environmental concentrations and human body burdens of both “legacy” contaminants have been slowly decreasing. In contrast, human exposure to other chemicals, including brominated flame retardants (Sjodin et al. 2008
), bisphenol A (BPA) (Calafat et al. 2008
), phthalates (Hauser and Calafat 2005
), certain pesticides (Barr et al. 2005
), and polyfluoroalkylated chemicals (PFCs) (Jensen and Leffers 2008
), has become ubiquitous. The studies reviewed herein demonstrate a risk to children’s neurobehavioral development from lead and PCB exposure. Whether the risks of altered neurodevelopment from PCB exposure will continue into the future is unknown. However, childhood lead exposure is likely to remain an important public health issue because of the lead contamination in older housing in the United States and the significantly higher contamination that still exists in developing countries (Meyer et al. 2008
). Although additional research to more fully delineate the role of lead and PCB exposure in the etiology of ADHD would be valuable, it is equally if not more important to gain a better understanding of potential neurodevelopmental effects of other “emerging” contaminants, of which relatively little is known.
Chemicals such as polybrominated diphenyl ethers (PBDEs) and BPA, which have been shown to disrupt dopamine signaling in vitro
(Jones and Miller 2008
; Mariussen and Fonnum 2003
), should be investigated as possible contributing factors in ADHD. Although the effects of PBDE exposures in animal studies are observed at higher levels than those to which humans are exposed, some BPA studies have demonstrated adverse effects at levels comparable to those humans encounter daily (Richter et al. 2007
; Vandenberg et al. 2010
). Studies of attention or executive function after PBDE exposure are limited, but Driscoll et al. (2009)
found that mice postnatally exposed to the commercial PBDE mixture DE-71 exhibited impulsivity and inattention, as evidenced by more premature responses and omission errors, respectively, on the five-choice serial reaction time task. Prenatal PBDE exposure also has been associated with impaired vigilance in a study of 62 children 5–6 years of age (Roze et al. 2009
). PBDEs have been shown to reduce vesicular and, to a lesser extent, synaptosomal dopamine uptake in vitro
(Mariussen and Fonnum 2003
), paralleling what has been reported with PCBs (Caudle et al. 2006
; Fonnum et al. 2006
) and further supporting the idea that PBDE exposure could potentially be a risk factor for ADHD. BPA, a component in polycarbonate plastics, has been shown to reduce dopamine synthesis, release, and turnover, as well as dopamine transporter expression, in rodents [reviewed by Jones and Miller (2008)
], but only a few studies have evaluated the effects of developmental exposure on cognitive function and none to date has employed tests relevant to ADHD.
A recently published study reported that prenatal exposure to low-molecular-weight phthalates was associated with poorer parent-rated scores on attention and externalizing problems (including impulsivity and hyperactivity) in 188 children 4–9 years of age using the Behavior Assessment System for Children scales (Engel et al. 2010
). Preceding this, Kim et al. (2009)
reported that higher urine phthalate metabolites at the time of testing in 261 children 8–11 years of age were associated with higher teacher-rated scores on both the inattention and hyperactivity-impulsivity subscales of the ADHD Rating Scale, whereas CPT testing revealed more omission and commission errors, suggestive of impaired vigilance and response inhibition, but no increases in reaction time, suggesting that alertness was not affected.
A study of an inner-city minority population (n
= 288) reported an association between prenatal chlorpyrifos exposure and scores in the clinical problems range on both the Attention Problems scale and ADHD scale of the Child Behavior Checklist at 3 years of age (Rauh et al. 2006
). Although a study of 356 organophosphate-exposed children of farmworkers did not find a significant association with scores on either of these scales at 2 years of age (Eskenazi et al. 2007
), the children were followed up at 3.5 years (n
= 331) and 5 years (n
= 323), with several significant associations observed at 5 years of age (Marks et al. 2010
). Specifically, prenatal organophosphate exposure (as measured by maternal urinary dialkyl metabolites during pregnancy) was associated with increased scores on the Attention Problems scale and ADHD scale of the Child Behavior Checklist and with an increased ADHD confidence index on the Conners Kiddie CPT task. Finally, a cross-sectional study using NHANES data found that parentally reported ADHD was positively associated with urinary organophosphate metabolite levels (Bouchard et al. 2010
). Only a few animal studies have addressed effects of pesticides on behavioral end points relevant to ADHD. Adult exposure of rats to chlorpyrifos impaired vigilance on a visual signal detection task (Bushnell et al. 2001
; Samsam et al. 2005
), whereas acute juvenile exposure transiently impaired performance on a DSA working memory task (Stanton et al. 1994
Very recently, a positive association between parentally reported ADHD and serum PFC levels was reported based on an analysis of NHANES data (Hoffman et al. 2010
). To our knowledge, this is the first study to examine a potential association between childhood PFC exposure and ADHD. A few animal studies have assessed neurobehavioral outcomes after PFC exposure, but we are not aware of any that have directly assessed cognitive functions relevant to ADHD.
Although in this review we focus on environmental contaminants, a number of other potential environmental factors, including premature birth, low birth weight, and psychosocial adversity, are known or suspected to be risk factors in the development of ADHD on their own and could potentially interact with environmental exposures to modify risk (Banerjee et al. 2007
; Swanson et al. 2007
). Converging evidence from a number of clinical and population-based studies also links both maternal smoking and maternal alcohol consumption during pregnancy with ADHD (Braun et al. 2006
; Pennington et al. 2009
), with Froehlich et al. (2009)
demonstrating that children with combined lead and prenatal tobacco exposure have a greater risk of ADHD than would be predicted if the individual risks were multiplied. Whether other risk factors interact with chemical exposures to increase ADHD risk is an area that should be further explored.