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Abstract and Introduction
Abstract
Background Use of pyrethroid insecticides has increased dramatically over the past decade; however, data on their potential health effects, particularly on children, are limited.
Objective We examined the cross-sectional association between postnatal pyrethroid exposure and parental report of learning disability (LD) and attention deficit/hyperactivity disorder (ADHD) in children 6–15 years of age.
Methods Using logistic regression, we estimated associations of urinary metabolites of pyrethroid insecticides with parent-reported LD, ADHD, and both LD and ADHD in 1,659–1,680 children participating in the National Health and Nutrition Examination Survey (1999–2002).
Results The prevalence rates of parent-reported LD, ADHD, and both LD and ADHD were 12.7%, 10.0%, and 5.4%, respectively. Metabolite detection frequencies for 3-PBA [3-phenoxybenzoic acid], cis-DCCA [cis-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylicacid], and trans-DCCA [trans-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylicacid] were 77.1%, 35.6%, and 33.9%, respectively. The geometric mean 3-PBA concentration was 0.32 μg/L (median = 0.31 μg/L; interquartile rage = 0.10–0.89 μg/L). cis- and trans-DCCA 75th-percentile concentrations were 0.21 μg/L and 0.68 μg/L, respectively. Log10-transformed 3-PBA concentrations were associated with adjusted odds ratios (ORs) of 1.18 (95% CI: 0.92, 1.51) for parent-reported LD, 1.16 (95% CI: 0.85, 1.58) for ADHD, and 1.45 (95% CI: 0.92, 2.27) for both LD and ADHD. Adjusted ORs remained nonsignificant and decreased after controlling for creatinine and other environmental chemicals previously linked to altered neurodevelopment. Similarly, no significant associations were observed for cis- and trans-DCCA.
Conclusions Postnatal pyrethroid exposure was not associated with parental report of LD and/or ADHD. Given the widespread and increasing use of pyrethroids, future research should evaluate exposures at current levels, particularly during critical windows of brain development.
Introduction
Pyrethroid insecticides account for > 30% of insecticides used worldwide (Barr et al. 2010). They are used to control pests in residential and agricultural settings, to treat head lice and scabies in humans and fleas in pets, for public health vector control, and for disinsection of commercial aircrafts [U.S. Environmental Protection Agency (EPA) 2013a, 2013b; Wei et al. 2012]. These synthetic insecticides act by altering the permeability of sodium ion channels in excited nerve cells, causing repetitive nerve impulses that may vary in intensity depending on the chemical structure of the individual pyrethroid (Barr et al. 2010; Mandhane and Chopde 1997; Nasuti et al. 2003). In humans, pyrethroid insecticides are rapidly metabolized and excreted (elimination half time: ~ 6–17 hr) [Agency for Toxic Substances and Disease Registry (ATDSR) 2003].
Use of pyrethroids, particularly in residential settings, has increased dramatically over the past decade and will likely increase further as they are replacing other pesticides (e.g., organophosphate pesticides) that are considered to have higher mammalian toxicity and are linked to adverse health effects in children (Barr et al. 2010; Horton et al. 2011a; U.S. EPA 2013b; Williams et al. 2008). Hence, exposure to pyrethroids in the U.S. general population is widespread (Barr et al. 2010) mostly from diet and indoor residential uses (via ingestion, dermal, and inhalation pathways) (ATDSR 2003; Lu et al. 2009). In the U.S. general population, higher pyrethroid exposures have been reported in children compared with adolescents and adults (Barr et al. 2010). Human exposure to pyrethroids is primarily assessed by measures of nonspecific urinary metabolites such as 3-phenoxybenzoic acid (3-PBA), and cis- and trans-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylicacid (cis- and trans-DCCA) (Barr et al. 2010).
Although pyrethroids are considered to be safer than other insecticides, rodent studies suggest that early-life and pubertal pyrethroid exposures alter neurobehavioral functioning (Farag et al. 2007; Shafer et al. 2005; Sinha et al. 2006). For example, one study reported that early prenatal and postnatal pyrethroid exposure led to oxidative stress in various areas of the brain, with the hippocampal area exhibiting cholinergic dysfunction. Neurochemical changes were accompanied by impaired learning and memory (Sinha et al. 2006). Another rodent study reported associations of pyrethroid exposure during puberty with spatial learning and memory impairments that were more severe in females, increased anxiety in females, and inhibition of aggressive behavior in males (Meng et al. 2011). Pubertal pyrethroid exposure has also been reported to disrupt testosterone and estradiol synthesis and expression of androgen receptor in the cerebral cortex, which may impair neurobehavioral development (Liu et al. 2011). Select pyrethroids have also shown greater toxicity in neonatal than in adult rats, possibly due to incomplete development of detoxifying enzymes (Cantalamessa 1993).
In humans, symptoms of systemic pyrethroid poisoning resulting from accidental exposure or intentional ingestion are well characterized (ATDSR 2003; Ray and Forshaw 2000; Soderlund et al. 2002). However, data on the human health effects of pyrethroids (particularly neuro-developmental effects) at the lower environmental doses encountered by the general public are limited, and data on developing children are particularly sparse. Only two studies to date have evaluated the effects of prenatal pyrethroid exposure on children's neurodevelopment. Horton et al. (2011b) examined the relationship of prenatal exposure to permethrin, a pyrethroid, and piperonyl butoxide (PBO), a synergist commonly formulated with pyrethroids, on children's neurodevelopment at 3 years of age (n = 230–342). Children in the highest PBO exposure group, as assessed in personal air samples, scored approximately four points lower on the Bayley Mental Developmental Index than children in the lowest exposure group. Prenatal exposure to permethrin in air and/or blood was not associated with altered neurodevelopment, although the authors noted difficulty measuring permethrin in these media (Horton et al. 2011b). Another study reported an inverse association between prenatal pyrethroid exposure, using urinary metabolites, and measures of motor function, social adaptation, and intelligence in 1-year-old Chinese infants (n = 497) (Xue et al. 2013). Neither of these studies controlled for postnatal pyrethroid exposures.
Two other studies have considered the potential effects of childhood pyrethroid exposure on neurodevelopment. A study of 7- to 9-year-old Nicaraguan children (n = 110) living in an agricultural community (Rodríguez 2012) found that parent-reported hours of pyrethroid use during the first year of life was associated with poorer perceptual reasoning using the Wechsler Intelligence Scale for Children IV and teacher-reported hyperactivity and attention deficit/hyperactivity disorder (ADHD) using the revised Conner's Teachers Rating Scale short version. In a subset of these children (n = 74), child's 3-PBA urinary concentration levels were associated with impaired cognition and ADHD in girls but not boys (Rodríguez 2012). Most recently, a nationally representative Canadian study found an association between urinary concentrations of cis-DCCA and parent-reported total behavioral problems on the Strengths and Difficulties Questionnaire in 6- to 11-year-olds (n = 779). However, urine 3-PBA concentrations were not associated with behavioral problems in the study population (Oulhote and Bouchard 2013).
Herein, we examine the cross-sectional association between children's pyrethroid exposures and parent-reported learning disability (LD) and/or ADHD in a representative sample of U.S. 6- to 15-year-olds participating in the National Health and Nutrition Examination Survey (NHANES). LDs encompass various difficulties in receptive and expressive language, reading, and mathematics, which may affect scholastic performance (Pastor and Reuben 2002); ADHD is a neurobehavioral disorder characterized by a persistent pattern of inattention, impulsivity, and/or hyperactivity that interferes with functioning or development (American Psychiatric Association 2013).
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