Tetrachloroethylene (PCE), also known as PERC, is a volatile organic compound widely used in industrial processes such as dry cleaning, metal degreasing, and chemical synthesis. PCE is also an ingredient in many household products, such as paint removers, furniture strippers, wood cleaners, water repellents, silicone lubricants, spot removers, suede protectors, glues, and wood cleaners (Wisconsin DHS, 2022). Once released into the environment, PCE breaks down slowly, with a half-life of approximately 100 days in the air (Atkinson, 1989). In groundwater, its half-life is generally considered to be between 9 months and 6 years (Dilling et al., 1975; Pearson and McConnell, 1975). Workers in the dry-cleaning industry or metal degreasing operations may be exposed to PCE at levels much higher than those encountered in non-occupational settings, where exposure to PCE could occur as a result of off-gassing from dry-cleaned clothes and the use of household products in an indoor environment. Due to the wide use of PCE and poor waste management, PCE has been found at many contamination sites. According to the U.S. Environmental Protection Agency (EPA), PCE has been identified in at least 949 of 1854 Superfund sites designated by the National Priorities List (Agency for Toxic Substances and Disease Registry (ATSDR), 2019; Liu et al., 2022), representing locations that need significant federal cleanup efforts to remediate environmental contaminations. PCE is also found in many unlisted hazardous waste sites. The primary exposure pathways for people residing near the contaminated sites include drinking contaminated water, inhaling contaminated water vapor (e.g., during a shower or doing laundry), and inhaling indoor air that is contaminated due to vapor intrusion. Vapor intrusion is a phenomenon that occurs when chemical vapors migrate from the subsurface into buildings, a process similar to the transport of radon (a radioactive gas) into homes (Forand et al., 2012; Pennell et al., 2013).

Exposure to PCE has been associated with various health effects such as liver, kidney, respiratory, and neurological disorders. PCE is classified as “probably” carcinogenic to humans (Group 2A) by the International Agency for Research on Cancer (IARC, 2014), with the exposure being shown to increase the risk of bladder cancer, multiple myeloma, and non-Hodgkin’s lymphoma (Blair et al., 2003; Colt et al., 2011; Gold et al., 2011; Pesch et al., 2000; Radican et al., 2008). Additionally, PCE targets the central nervous system, which leads to alterations in neural conduction velocity by interfering with neuronal receptors (Briving et al., 1986; Kyrklund et al., 1990), particularly in the frontal cerebral cortex where complex organizational behavior, attention, executive functioning, and reasoning are centered (Kyrklund et al., 1988; Wang et al., 1993). Signs and symptoms of acute high-dose exposure in occupational or accidental exposure settings include headache, dizziness, drowsiness, ataxia, mood changes, coma, and seizures (Agency for Toxic Substances and Disease Registry (ATSDR), 2019). A growing body of evidence from animal and human studies link chronic PCE exposure with neurotoxic outcomes such as schizophrenia, visual and neurological disturbances, cognitive impairments impacting memory and processing speed, and motor deficits compromising coordination and reaction time (Agency for Toxic Substances and Disease Registry (ATSDR), 2019; Bale et al., 2011; Cavalleri et al., 1994; Echeverria et al., 1995; Gobba et al., 1998; Guyton et al., 2014; Perrin et al., 2007; White et al., 1995). Specifically, neurobehavioral effects observed with prolonged occupational exposure to PCE include deficits in short-term memory for visual designs, reaction times, perceptual function, attention, and intellectual function in dry cleaning workers exposed to PCE (Altmann et al., 1995; Cavalleri et al., 1994; Echeverria et al., 1995). These detrimental outcomes are not restricted to occupational exposures. Individuals living in close vicinity to dry cleaning operations with low levels of PCE exposure were observed to have altered visual acuity, color discrimination, and contrast sensitivity (Schreiber et al., 2002; Storm et al., 2011). However, health effects, especially neurological effects, among people living in communities near PCE contaminated sites, which impact many people, remain poorly understood.

Children may be more susceptible to the negative health consequences of PCE exposure due to their unique physiology and developmental stage. For instance, their developing nervous system tissues are more susceptible to damage (Guzelian et al., 1992; National Research Council (U.S.), 1993). Immature metabolic pathways reduce the ability to metabolize PCE to less toxic metabolites during the early stages of life (Clewell et al., 2004; Sarangapani et al., 2003). Some investigations reported associations between maternal occupational exposure to PCE and behavioral disorders as well as adverse effects on intelligence, language, and motor skills among offspring (Laslo-Baker et al., 2004; Till et al., 2001). Prenatal and early childhood exposure to contaminated drinking water was linked to long-term subclinical visual dysfunction and increased frequency of risky behaviors such as drug use, as well as increased risk of mental illness in early adulthood (Aschengrau et al., 2011, 2012, 2016; Getz et al., 2012; Janulewicz et al., 2012; Perrin et al., 2007). In contrast, others reported no significant associations between PCE exposure during pregnancy and neurobehavioral outcomes among children of occupationally exposed mothers (Eskenazi et al., 1988). Similarly, Janulewicz et al. (2008) reported no behavioral impairments among children exposed to PCE through contaminated drinking water. Nevertheless, the literature is scarce regarding the neurobehavioral effects of low-level PCE exposure in children living at or near contamination sites.

This study aimed to assess the effect of PCE exposure on neurobehavioral performance among children living in or near PCE-contaminated areas in Martinsville, Indiana, with a hypothesis that low-level exposure to PCE was associated with adverse effects on children’s neurobehavioral performance. Martinsville represents many similar communities facing the challenge of PCE contaminations in groundwater, soil, and indoor air. The city overlays four groundwater contamination sites, including an EPA-designated Superfund site and three other known contamination sites (Liu et al., 2022). The total size of the groundwater contamination is over 60 acres, all located in the same aquifer, with PCE being identified as a primary contaminant. This pilot study adds knowledge about the impact of low-level environmental exposure on children’s neurobehavioral outcomes. The findings can be used to inform and guide future investigations. The project also provides an opportunity to build a sustainable academic-community partnership to address community concerns about the exposure and potential health impacts related to the PCE contamination in Martinsville, as well as in other communities in a similar situation.

This study offers insights into the impact of PCE exposure on children’s neurobehavioral performance. Notably, the two higher PCE exposure groups had lower cognitive performance involving tasks that assess working memory, episodic memory, processing speed, executive function-cognitive flexibility, and overall cognitive function than the lowest exposure group. However, statistical significance was observed only in the highest exposure group for tasks involved in the Early Childhood Composite assessment. In contrast, no significant associations were observed for the behavioral or academic performance tasks. These results suggest that PCE, a common environmental contaminant, might subtly affect how the central nervous system functions at the PCE exposure levels observed in this study.

The PCE concentrations in exhaled breath found in children in this study are lower than those reported in several previously published studies of dry cleaners, industrial workers, and those living near dry cleaning operations (Dias et al., 2017; McKernan et al., 2008; Scheepers et al., 2019; Schreiber et al., 2002; Solet et al., 1990; Storm et al., 2011). The average exposure level observed in our study was 2.17 μg/m³, substantially lower than those reported for individuals living in the same building with dry cleaning operations and even lower than reported levels in the control groups of previous studies (Delfino et al., 2003; Storm et al., 2011). Only the average of the highest exposure group in this study (4.78 μg/m³) was slightly higher than reported control group exposure of 4.4 μg/ m³ (Delfino et al., 2003) and 4.6 μg/ m³ for adults and 3.7 μg/ m³ for children (Storm et al., 2011). The exposure levels observed in the current study were also lower than we observed in our feasibility study (Liu et al., 2022). Despite the relatively low exposure levels, we observed statistically significant associations between PCE exposure and lower neurobehavioral performance among children. This suggests that the impact on neurobehavioral performance of children may occur at PCE exposure levels lower than previously expected and thus public health impacts may be more widespread and applicable to children in the general population rather than just those living at or near contaminated areas. This warrants further investigation.

The analysis of the NIH Toolbox test scores provides insight into the distinctive cognitive domains affected in children by PCE exposure, indicating declines in attention and memory. In our exploration of cognitive performance assessments, we investigated the association between the NIH Toolbox tests and PCE exposure groups. The NIH Toolbox Cognition Battery is composed of seven tests that are aggregated into four composites, as shown in Fig. 3. The Total Composite incorporates all seven tests. The Early Childhood Composite uses short fluid (2 tests) and crystallized (one test) measures that are applicable to 4–6-year-old children. Two of the seven tests are related to vocabulary and reading measures that contribute to crystallized abilities, while the five other measures contribute to fluid abilities. These are mainly related to memory, attention, and processing speed (Akshoomoff et al., 2013). Three out of these five fluid measures are impacted by PCE exposure. One is related to attention, with a statistically significant difference for the highest versus lowest exposure group. The two others are related to memory; both episodic and working memory tests had lower performance with a statistically significant difference for the two higher versus the lowest exposure group. It is worth mentioning that a statistical significance was observed in the Total Composite and the Fluid Composite even with a smaller sample size of fifty-seven participants, which represent 7–11 years old children in our participants.

Previous research has linked PCE exposure to neurobehavioral problems. Several occupational studies suggested that exposure to PCE leads to decreased cognitive function, disturbances in ocular function, reaction time, deficits in short-term memory for visual designs, perceptual function, attention, and intellectual function (Altmann et al., 1995; Cavalleri et al., 1994; Friedman et al., 2020; White et al., 1995). Three epidemiological investigations on neurobehavioral functions among dry cleaning workers (Seeber, 1989; White et al., 1995) or those living near dry cleaning facilities (Altmann et al., 1995) showed disturbances in memory, attention, and reaction time assessments. Residential investigations show similar effects among those living near dry cleaning enterprises with low levels of exposure (Schreiber et al., 2002; Storm et al., 2011). Our findings are consistent with these previously reported cognitive function impairments. Most of these studies were conducted on adults. Our study results complement these findings by showing cognitive function impairments in children exposed to PCE at low levels, which is consistent with a study conducted on children exposed to PCE in community settings (Janulewicz et al., 2008).

We did not observe a difference in PCE concentrations in exhaled breath samples among participants living in the contaminated areas and those not living in any known contaminated areas. However, we were able to find a significant association between exposure and cognitive functions, indicating that the current PCE exposure measure may potentially be correlated with long-term exposure to PCE. Notably, 67 % of our participants have either one or two addresses during their life time. We modeled the number of years living in the contaminated areas as a surrogate for cumulative PCE exposure but did not find any significant associations with neurobehavioral performance outcome measures. This was not fully unanticipated as the number of years living in the contaminated areas may not be a suitable surrogate of cumulative exposure. It is important to note that not all properties within the plumes exhibited vapor intrusion issues. This is likely due to variations in house characteristics, basement types and features, and soil characteristics beneath the properties. Another factor that might contribute to this is the presence of unmeasured indoor sources of PCE in homes.

This study has several limitations that should be considered. Due to the cross-sectional design, we cannot definitively establish a temporal relationship between PCE exposure and neurobehavioral outcomes. Longitudinal epidemiological studies would be valuable in exploring the long-term effects of PCE exposure. There could be potential exposure misclassification due to the single exposure measurement collected in the study. Efforts should be made in future studies to assess variations in the exposure and the association between PCE exposure and its concentrations indoors to better characterize the exposure and its sources and pathways. Relying on caregiver input to acquire some information on exposure and outcomes might have introduced recall bias and impacted the accuracy of data collected, contributing to the uncertainties in the assessment. The self-selected recruitment strategy could lead to selection bias. We did not have an unexposed control group in the study due to the limited time and resources of a pilot study. It would also be challenging to find a completely unexposed population since there are multiple common sources of PCE exposure that are not from environmental contaminations. Additionally, although we inquired about testing schools for PCE indoor air concentrations, this was not conducted in the study. Future studies should consider measuring PCE levels in schools, daycare centers, and other spaces where children spend time to better understand exposure sources and pathways. Finally, the small sample size limits our ability to generalize these results. However, our observation of significant associations in this small sample size warrants further investigation.

The strengths of this study go beyond its design and consistent results. By utilizing a range of assessment tools, such as the NIH Toolbox Cognition Battery, BASC-3, and WRAT-5, we were able to evaluate various aspects of neurobehavioral functioning. This approach provides an understanding of how PCE exposure may impact different domains within neurobehavioral performance in children. The observed pattern of exposure levels leading to more significant effects adds weight to the possibility of a causal association. These findings indicate that although the average scores did not uniformly indicate significant issues, a subset of participants displayed individual scores that warranted in-depth investigation. This study’s findings contribute to the growing body of research demonstrating PCE’s potential hazard to children’s neurobehavioral development, especially for many communities near contaminated sites with PCE and other hazardous chemicals.

The United Nations’ Sustainable Development Goals (SDGs) aim to promote health, well-being, and sustainable living environments globally. Our study aligns with SDG 3 (Good Health and Well-being) Target #9, which focuses on reducing illnesses and deaths caused by hazardous chemicals and pollution, as well as one of the outcome targets of SDG 11 (Sustainable Cities and Communities) that focuses on safe and affordable housing. Our findings highlight the importance of several practical recommendations to improve indoor air quality and reduce exposure to harmful chemicals, as outlined by the National Center for Healthy Housing, Indiana Healthy Homes Alliance, and Improving Kids’ Environment (National Center for Healthy Housing (NCHH), n.d.). These recommendations include encouraging the use of safer cleaning products, limiting dry cleaning, maintaining heating, ventilation, and air conditioning systems with timely air filter replacements, increasing natural ventilation in homes when weather permits to reduce indoor air pollution, and mitigating exposure to PCE and other VOCs from dry-cleaned items by airing them out before bringing them indoors.

The findings of this study emphasize the need for continued monitoring and regulation of PCE exposure, especially in community and residential settings. By emphasizing the strengths and avoiding the limitations of the study, future research can better explore the underlying mechanisms and long-term effects of low-level PCE exposure. These recommendations will help improve public health strategies, ensuring safer living environments for children, particularly in communities near contaminated sites.

This study showed associations between PCE exposure in children and lower scores in various areas of cognitive functioning, including memory, attention, problem-solving abilities, and adaptive functioning. Specifically, it identified that PCE in exhaled breath was linked to impairments in working memory, episodic memory, processing speed, and executive function-cognitive flexibility. These associations were observed at relatively low levels of PCE exposure, compared to higher levels typically observed in occupational settings and residential areas near dry cleaning facilities, which suggests that even seemingly low levels of PCE exposure have a measurable impact on neurobehavioral performance among children. This is potentially generalizable to the greater population, as many similar communities face the challenge of widespread PCE exposure. Further research is needed to confirm these findings, explore the underlying mechanisms, and investigate the long-term effects of PCE exposure at low community exposure levels.