Elsevier

Neurotoxicology and Teratology

Volume 30, Issue 3, May–June 2008, Pages 175-185
Neurotoxicology and Teratology

Risk of learning and behavioral disorders following prenatal and early postnatal exposure to tetrachloroethylene (PCE)-contaminated drinking water

https://doi.org/10.1016/j.ntt.2008.01.007Get rights and content

Abstract

This population-based retrospective cohort study examined the association between developmental disorders of learning, attention and behavior and prenatal and early postnatal drinking water exposure to tetrachloroethylene (PCE) on Cape Cod, Massachusetts. Subjects were identified through birth records from 1969 through 1983. Exposure was modeled using information from town water departments, a PCE leaching and transport algorithm, EPANet water flow modeling software, and a Geographic Information System (GIS). Mothers completed a questionnaire on disorders of attention, learning and behavior in their children and on potential confounding variables. The final cohort consisted of 2086 children. Results of crude and multivariate analyses showed no association between prenatal exposure and receiving tutoring for reading or math, being placed on an Individual Education Plan, or repeating a school grade (adjusted Odds Ratios (OR) = 1.0–1.2). There was also no consistent pattern of increased risk for receiving a diagnosis of Attention Deficit Disorder (ADD) or Hyperactive Disorder (HD), special class placement for academic or behavioral problems, or lower educational attainment. Modest associations were observed for the latter outcomes only in the low exposure group (e.g., adjusted ORs for ADD were 1.4 and 1.0 for low and high exposure, respectively). (All ORs are based on an unexposed referent group.) Results for postnatal exposure through age five years were similar to those for prenatal exposure. We conclude that prenatal and early postnatal PCE exposure is not associated with disorders of attention, learning and behavior identified on the basis of questionnaire responses and at the exposure levels experienced by this population.

Introduction

Tetrachloroethylene (PCE, Perc or perchloroethylene) is a manufactured chemical used mainly for fabric dry cleaning and metal degreasing. PCE is one of the most commonly detected solvents in groundwater [30] and at United States Environmental Protection Agency (USEPA) Superfund sites [35]. As of 1997, 771 National Priority List (NPL) sites around the United States had evidence of PCE contamination [35]. In addition, PCE had been found in 38% of the 9232 surface water sampling sites in the United States [35].

PCE and its main metabolite dichloroacetylene (DCA) are recognized human and animal neurotoxicants [44], [45], [23], [42], [16]. These fat soluble substances have a high affinity for the lipophilic tissues of the central nervous system [2]. PCE also readily crosses both the placental and blood brain barriers [23].

Most of the relevant epidemiological literature has examined neurological sequelae among adults with occupational exposures to mixtures of organic solvents. Impairments in cognition and vision have been observed, as have mood changes [50], [21], [37], [17], [33], [31], [32], [9], [39], [22], [10], [11], [12], [46], [34], [19], [49]. The cognitive sequelae observed following mixed organic solvent exposures included diminished performance on measures of memory, attention/executive function, and motor skills. The results from the few studies examining adult occupational exposures to only PCE are mixed. Some studies found diminished performance on measures of attention/executive function among the PCE exposed subjects compared to unexposed controls [44], [19], while other studies did not find adverse effects [12], [19]. All studies that examined visuospatial abilities found a diminished performance in the PCE exposed group compared to unexposed controls [44], [12].

The maturation of the nervous system is more complex than any other organ, thus making it exquisitely vulnerable to chemical insults. Depending on timing, type, and dose, an exposure occurring during the developmental period can result in long-term alterations in brain structure and function. The vulnerable window for neurotoxic agents is long, extending from the prenatal period through adolescence and early adulthood. The functional domains of the nervous system (language, visuospatial, learning and memory and motor abilities) develop at different times with different windows of vulnerability and different sensitivities to environmental agents [[29], [1], [38], [18], [14], [24]–[25], [8], [7]].

To date, three studies have examined effects of maternal occupational mixed solvent exposure during the prenatal period on neurodevelopment. The study by Eskenazi et al. [15] showed no significant difference in general mental abilities, using the McCarthy Scales of Children's Abilities, between exposed and unexposed children at ages 3–4 years. Domain specific functions (i.e. memory or language specific tests) were not examined.

In contrast, Till et al. [43] found that prenatal maternal exposure to organic solvent mixtures was associated with worse performance on measures of expressive and receptive language, and reduced graphomotor skills (using NEPSY tests) among children at ages 3–7 years. Study parents also rated exposed children as having more behavioral problems on the child behavior checklist than unexposed children.

Laslo-Baker et al. [27] examined children exposed to organic solvent mixtures during the prenatal period and neurobehavioral performance at ages 3–7 years. Exposed children scored lower on neurobehavioral tests of general intelligence, language and motor abilities. General intelligence was assessed with the Wechsler Preschool and Primary Scale of Intelligence (WPPSI) and Wechsler Intelligence Scale for Children III (WISC III). Language was assessed using the Preschool Language Scale 3 (PSL 3) and Clinical Evaluation of Language Fundamentals 3 (CELF 3). Motor abilities were assessed with the grooved pegboard test.

Unlike the occupational studies described above, the present study examined PCE exposure from an unusual environmental scenario. In early 1980 it was discovered that PCE had been leaching into the drinking water supplies of many New England towns during the previous 15 years. Investigations revealed that the public water distribution systems in many of these towns had installed vinyl-lined asbestos-cement (VL/AC) pipes and that PCE had leached into the water from the liner. Approximately 660 miles of these pipes were installed in Massachusetts from 1968 through early 1980; a large proportion was installed in eight Cape Cod towns [26] (Fig. 1). The pipe manufacturing practice involved spraying a mixture of vinyl toluene resin and PCE onto the interior of the pipe. It was believed that the PCE would volatilize and disappear before the pipes were installed. However, PCE measurements taken in 1980 from Cape Cod public drinking water supplies ranged from 1.5 µg/L to 7750 µg/L [13]. State officials decided that the most appropriate remedy was to flush and bleed the VL/AC pipes in order to reduce the PCE concentrations to levels determined to be safe at the time. The 1980 action level was set to 40 µg/L to address this problem; the current United States Environmental Protection Agency (USEPA) maximum contaminant level (MCL) is 5 µg/L [45].

This scenario presented a unique and valuable setting for examining the health effects of PCE exposure because many people were exposed to a large range of levels, and other water contaminants were rare. Furthermore, the VL/AC pipes were irregularly distributed according to the replacement and expansion needs of the towns. As part of a population-based study that examined the connection between exposure to PCE-contaminated drinking water and adverse reproductive and developmental outcomes, the current study investigated the impact of prenatal and early postnatal PCE exposure on learning, attention and behavior.

Section snippets

Study population selection

All children born between 1969 and 1983 whose mothers lived in one of eight Cape Cod towns with VL/AC water distribution pipes at the time of birth were eligible for the study. These towns were Barnstable, Brewster, Bourne, Chatham, Falmouth, Mashpee, Provincetown, and Sandwich (Fig. 1). Eligible children were identified by reviewing Massachusetts birth certificates. The residence listed on the birth certificate was cross-matched with a database of all street locations with VL/AC pipes to

Results

A total of 2086 subjects were available for the final analysis. According to the initial exposure designation, there were 1063 exposed and 1023 unexposed children. Following the in-depth exposure assessment, there were 1349 exposed and 737 unexposed children (Table 1). A total of 444 subjects switched exposure groups: 365 unexposed children switched to the exposed group and 79 exposed children switched to unexposed group. The primary reason for switching from the unexposed to exposed group was

Discussion

The results of this study suggest that prenatal and early postnatal exposure to PCE are not associated with later disorders of attention, learning and behavior using questionnaire-based outcome measures and at the exposure levels experienced by this study population. While modest associations were seen for some outcomes (i.e., received a diagnosis of ADD or HD, special class placement for academic or behavioral problems, and lower educational attainment, being placed on an IEP), the

Conflict of interest

All authors (Patricia Janulewicz, Roberta White, Michael Winter, Janice Weinberg, Lisa Gallagher, Veronica Vieira, Thomas Webster, and Ann Aschengrau) attest to having no conflict of interest.

Acknowledgements

This research was supported by a grant from the National Institute of Environmental Health Sciences, Superfund Basic Research Program (5 P42 ES007381). The study sponsors have had no role in study design, data collection, analysis, interpretation of results, manuscript writing or the decision to submit this paper for publication. This paper's contents are solely the responsibility of the authors and do not necessarily represent the official views of NIEHS, NIH. This study was approved by the

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