Our intention was to evaluate the neurological health effects of low levels of 2,4,5-TCP and 2,4,6-TCP among school-aged children. We found that exposure to 2,4,6-TCP was associated with parental report of a diagnosis of ADHD. We also demonstrated a significant dose–response relationship between exposure to 2,4,6-TCP and ADHD. In contrast, we did not find a significant association between exposure to 2,4,5-TCP and ADHD. These findings suggest that 2,4,6-TCP may have different health effects than 2,4,5-TCP, which is consistent with patterns of association previously reported in the literature. Experimental evidence suggests that 2,4,6-TCP but not 2,4,5-TCP is associated with increased risks of multiple cancers.28 29
Both 2,4,6-TCP and 2,4,5-TCP are members of a family of organochlorine pesticides which are a large class of multipurpose chlorinated hydrocarbon chemicals that break down slowly in the environment and accumulate in fatty tissue. The presence of urinary TCPs indicates direct exposure to these chemicals or other organochlorine pesticides including hexachlorobenzene (HCB) and hexachlorocyclohexanes (HCH) which metabolise to TCPs in humans.30 31
Although many organochlorine pesticides are no longer widely used in the USA, children can be exposed to these chemicals through diet and contaminated air because of the intensive use of these chemicals in the past, and their lipophilic and chemically stable characters.32
Exposure to these chemicals may occur early in life.33
Although information on the potential health effects of HCB and HCH on child neurodevelopment is limited, evidence of neurotoxicity in humans exposed to organochlorine compounds including HCB and HCH has previously been presented.34 35
Several studies suggest that prenatal exposure to organochlorine compounds is associated with an increase in ADHD symptoms among children at 4 years of age.36–39
Therefore, the observed association between urinary 2,4,6-TCP and ADHD in our study does not exclude the possibility that the ADHD is caused by HCB and/or HCH exposures.
The observed association also suggests that direct exposure to 2,4,6-TCP directly affects child neurodevelopment. However, there is limited information on the neurological health effects of 2,4,6-TCP in humans. Because 2,4,6-TCP is one of the major chlorinated organic compounds which are formed during water disinfection, children can be exposed to the chemical through drinking water.40
Confirmation of a direct health effect of 2,4,6-TCP on child behavioural development would underscore the importance of further examining the potential neurological health effects of prenatal and postnatal exposure to 2,4,6-TCP through chlorinated drinking water.
Our study has several strengths. First, a large population-based sample was used to examine the neurological effects of TCPs and valuable information on the effect of background exposure to TCPs on child neurodevelopment in the general population was collected. Second, we used biomarkers in urine to measure exposures to organochlorine compounds. This method provided an overall measurement of chemical exposures from all sources and a more accurate measurement of body burden of exposure. Third, a wide of range of potential confounders including demographic factors and other environmental toxins such as lead and ETS, was included in the models. Moreover, the exposures to environmental toxins were measured using biomarkers in serum, which could minimise misclassification errors. Fourth, to test the reliability of our estimation we constructed several models with different covariates and found consistent results. Our analyses provided reasonably consistent findings, which are strengthened by an observed dose–response relationship.
Several potential limitations should be considered when interpreting the results of our study. First, although the use of urine as a matrix to determine biomarkers of exposure is especially suitable for compounds such as TCPs and other metabolites, urinary levels may reflect recent exposure. In addition, the large variation in TCP levels between data cycles suggests data errors during testing and/or data processing unless urinary TCPs varied greatly between different cycles. Second, since this is a cross-sectional study, we cannot interpret our results as providing evidence of a causal relationship between early exposure to TCPs and subsequent risk of developing ADHD. Third, ascertainment of ADHD was solely based on parental report without confirmation of diagnosis through medical record abstraction or administration of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). Administration of the DSM would provide information on ADHD subtypes and behavioural symptom counts, and increase specificity in detecting behavioural problems. Although data from the DSM-based ADHD diagnostic instruments are available in NHANES, there is limited access to this information. In addition, misclassification of ADHD from parental report would mostly likely result in underestimation of the true association between TCPs and ADHD. Future prospective cohort studies with better measures of TCP exposure and better ascertainment of ADHD are needed to validate our findings. Fourth, the data available on covariates such as socioeconomic status and early childhood factors were obtained through personal interview of a proxy respondent of a child's family and may be inaccurate. Finally, although many important covariates and potential confounders were included in our analysis, we were unable to adjust for the potential effects of other important covariates including parental education, breastfeeding, genetic factors, psychosocial stressors, other prenatal and/or postnatal environmental factors such as prenatal alcohol drinking, exposure to polychlorinated biphenyls, dioxins, phthalate and bisphenol A, and parental psychopathology.
Nevertheless, our results suggest that exposure to organochlorine compounds may be associated with increased risk of ADHD among school-aged children. Our findings underscore the potential behavioural health effects of these chemicals and highlight the need to strengthen public health efforts to reduce prenatal and postnatal exposure to these compounds, especially in countries where organochlorine pesticides are still commonly used.