Gregory M. Zarus

The prevalence of plastics in the environment raises concerns about their complex and poorly understood effects on human health. Research continues to uncover more sources of exposure and wider ranges of plastics within the body. Adverse health effects have been observed in animals, but their relevance to humans remains unclear. To address the growing need for reliable toxicity assessment resources and tools to aid in the synthesis of findings and the identification of data gaps and needs, we have developed a data visualization tool to provide streamlined access to the evaluated data on the chemical impacts of plastics on human health. The Plastics-Related Toxicology Profiles Tool uses Tableau Public to organize the extracted chemical-specific information from ATSDR Toxicological Profiles, the United Nations Environmental Program’s 2023 Chemicals in Plastics Technical Report, and a literature review of relevant research in Google Scholar and PubMed. The tool organizes extracted data from 98 ATSDR Toxicological Profiles representing over 476 substances related to plastics production in 16 tabulated health outcome categories associated with plastics exposure. The chemicals are organized into four categories based on their role in plastics manufacturing. The top four health endpoints impacted by all listed substance profiles are respiratory, neurologic, hepatic, and developmental effects. More than 30% of the substance profiles affected these systems as well as other non-cancer endpoints involving the immunological, renal, and reproductive systems, as well as increased cancer risk in respiratory and hepatic systems. Most monomers negatively impact development and the respiratory system, and most metal additives affect the respiratory system. We explain how this data visualization tool combined with ATSDR’s framework for assessing health impacts from multiple chemicals could be applied to identify the target organs impacted by components of the common plastic polyvinyl chloride. Hazard quotients and index show low toxicity and health risk of components in the cured product. This data provide a valuable resource for prioritizing health risk assessments. Use of this interactive tool can enhance the ability of public health professionals to navigate the expanding literature, synthesize findings, and identify future health risk assessment and research priorities.

Plastics are an integral part of modern life and are essential to agriculture and food packaging. “Plastics” refers to an immense number of materials that are created from different polymers and an estimated 13,000 chemical additives. While the presence of plastics in the environment has been a concern for decades, their breakdown products, micro- and nanoplastics (MNPs), are an emerging human health and environmental concern. Recent studies on microplastic contamination in our air, water, land, food, and bodies provide the data needed to begin evaluating the resultant health effects and creating exposure reduction strategies. In this work, we utilize a mixtures hazard index (HI) method to identify harmful additives found within plastics identified in agricultural products. We illustrate the relative potency of a few toxic substances within microplastics such as DEHP, which is possibly 2,000 times more toxic than available potential substitutes. Additionally, we demonstrate that a few toxic additives can result in an elevated hazard index for the amount of microplastics detected in crops. Thus, the hazard index method can be applied to aid in the development of a new generation of plastics with lower toxic potential.

Parkinson’s disease (PD) is a complex neurodegenerative disorder influenced by age, genetic predispositions, and environmental exposures, with a growing global incidence. This review aims to summarize findings from ATSDR Toxicological Profiles, EPA Risk Assessments, and other sources of peer-reviewed literature to examine the potential associations between PD and select metals, pesticides, and chlorinated organic compounds. Additionally, it explores using computational toxicology methods to elucidate the interactions between specific chemicals, associated genes, and their possible roles in PD. A total of 29 substances were identified to be neurotoxic with direct or probable association with PD. Risk of disease onset or symptom exacerbation of PD has been linked to exposures to neurodegenerative metals, pesticides, chlorinated organic compounds, and other environmental toxicants, alongside intrinsic factors such as genetic predisposition and aging. Supporting evidence from neurotoxicological studies directly or possibly associated with PD are summarized in referenced toxicological profiles and EPA risk assessments. Genotoxic endpoints evaluated in exposure-induced neurodegeneration including oxidative stress, DNA strand breaks, mitochondrial dysfunction, impaired DNA repair, and telomere alterations may play a critical role in linking environmental exposures to PD pathogenesis. Although these endpoints represent imperative data gaps between environmental and genetic risk factors for PD, isolating individual substances may not be necessary for prevention, as many co-occur at contaminated sites or within certain occupations. Further research is needed to clarify causal relationships between environmental exposure and genotoxic endpoints seen in neurodegenerative processes that can also be seen in PD for consideration in the development of preventive and therapeutic strategies.

Individuals across their lifespan may experience hearing loss from medications or chemicals, prompting concern about ototoxic environmental exposures. This study applies computational modeling as a screening-level hazard identification and chemical prioritization approach and is not intended to constitute a human health risk assessment or to estimate exposure- or dose-dependent ototoxic risk. We evaluated in silico drug-induced ototoxicity models on 80 environmental chemicals, excluding 4 with known ototoxicity, and analyzed 76 chemicals using fingerprinting, similarity assessment, and machine learning classification. We compared predicted environmental ototoxicants with ototoxic drugs, paired select polychlorinated biphenyls with the antineoplastic drug mitotane, and used PCB 177 as a case study to construct an ototoxicity pathway. A systems biology framework predicted and compared molecular targets of mitotane and PCB 177 to generate a network-level mechanism. The consensus model (accuracy 0.95 test; 0.90 validation) identified 18 of 76 chemicals as potential ototoxicants within acceptable confidence ranges. Mitotane and PCB 177 were both predicted to disrupt thyroid-stimulating hormone receptor signaling, suggesting thyroid-mediated pathways may contribute to auditory harm; additional targets included AhR, transthyretin, and PXR. Findings indicate overlapping mechanisms involving metabolic, cellular, and inflammatory processes. This work shows that integrated computational modeling can support virtual screening and prioritization for chemical and drug ototoxicity risk assessment.

Over 292 million tons of municipal solid waste (MSW) are generated annually in the United States, with more than half disposed of in landfills. Municipal solid waste landfills (MSWLFs) are stationary sources of air pollution and potential health risks for nearby communities. The Agency for Toxic Substances and Disease Registry (ATSDR) has completed over 300 public health assessments (PHAs) and related investigations at MSWLFs and open dumps since the 1980s. This paper reviews the ATSDR’s evaluations of air pathway concerns at 125 MSWLF sites assessed between 1988 and early 2025, with many being evaluated during the 1990s. Most sites were located in the Midwest and Northeast, and only 25% remained active. The ATSDR found no air-related public health hazard at 86% of sites. At sites where hazards were identified, common issues included elevated outdoor or indoor toxicants (e.g., hydrogen sulfide, benzene, trichloroethylene, and mercury) and unsafe methane accumulations. Contributing factors included older site designs, inadequate gas-collection, subsurface fires, and distance from nearby residences. Corrective actions effectively reduced exposures at the affected sites. Results suggest that well-located and maintained landfills minimize public health hazards, while aging or poorly managed sites pose risks. Continued monitoring and research are warranted as waste management shifts toward reducing, reusing, recycling, composting, and energy-recovery technologies to improve efficiency, advance technologies, and address systemic public health challenges.

Hearing loss (HL) causes numerous challenges for individuals. N,N-diethyl-meta-toluamide (DEET) is a common ingredient in insect repellants and some sunscreens. M-(diethylcarbamoyl) benzoic acid (DCBA) is a DEET metabolite measured in the urine of National Health and Nutrition Examination Survey participants. This study examines potential associations between HL and urinary DCBA in U.S. adults. Speech-frequency hearing loss (SFHL) was defined as an average hearing threshold above 25 dB across four frequencies (0.5, 1, 2, and 4 kHz). In comparison, high-frequency hearing loss (HFHL) was based on the average threshold above 25 dB at three higher frequencies (3, 4, and 6 kHz) in the better hearing ear. Hearing loss severity was categorized as normal (≤25 dB), mild (26–40 dB), and moderate or worse (≥41 dB). Higher DCBA exposure was significantly associated with increased odds of high-frequency hearing loss (HFHL). Participants in the highest exposure quartile had greater odds of HFHL (aOR = 2.34; 95% CI: 1.14–4.81), with a dose–response trend (p < 0.05) confirmed in sensitivity analyses controlling for chronic conditions and inflammation. Multinomial models further showed elevated odds of both slight/mild (aOR = 2.15; 95% CI: 1.05–4.42) and moderate/worse HFHL (aOR = 2.84; 95% CI: 1.10–7.37), supporting the robustness of the association. To our knowledge, this is the first report of HL being associated with a DEET metabolite in a nationally representative cross-sectional sample.

Metal exposure is a potential risk factor for amyotrophic lateral sclerosis (ALS). Increasing evidence suggests that elevated levels of DNA damage are present in both familial (fALS) and sporadic (sALS) forms of ALS, characterized by the selective loss of motor neurons in the brain, brainstem, and spinal cord. However, identifying and differentiating initial biomarkers of DNA damage response (DDR) in both forms of ALS remains unclear. The toxicological profiles from the Agency for Toxic Substances and Disease Registry (ATSDR) and our previous studies have demonstrated the influence of metal exposure-induced genotoxicity and neurodegeneration. A comprehensive overview of the ATSDR’s toxicological profiles and the available literature identified 15 metals (aluminum (Al), arsenic (As), cadmium (Cd), chromium (Cr), cobalt (Co), copper (Cu), iron (Fe), lead (Pb), manganese (Mn), mercury (Hg), nickel (Ni), selenium (Se), uranium (U), vanadium (V), and zinc (Zn)) showing exposure-induced genotoxicity indicators associated with ALS pathogenesis. Genetic factors including mutations seen in ALS types and with concomitant metal exposure were distinguished, showing that heavy metal exposure can exacerbate the downstream effect of existing genetic mutations in fALS and may contribute to motor neuron degeneration in sALS. Substantial evidence associates heavy metal exposure to genotoxic endpoints in both forms of ALS; however, a data gap has been observed for several of these endpoints. This review aims to (1) provide a comprehensive overview of metal exposure-induced genotoxicity in ALS patients and experimental models, and its potential role in disease risk, (2) summarize the evidence for DNA damage and associated biomarkers in ALS pathogenesis, (3) discuss possible mechanisms for metal exposure-induced genotoxic contributions to ALS pathogenesis, and (4) explore the potential distinction of genotoxic biomarkers in both forms of ALS. Our findings support the association between metal exposure and ALS, highlighting under or unexplored genotoxic endpoints, signaling key data gaps. Given the high prevalence of sALS and studies showing associations with environmental exposures, understanding the mechanisms and identifying early biomarkers is vital for developing preventative therapies and early interventions. Limitations include variability in exposure assessment and the complexity of gene–environment interactions. Studies focusing on longitudinal exposure assessments, mechanistic studies, and biomarker identification to inform preventative and therapeutic strategies for ALS is warranted.

Telomere length (TL) predicts the onset of replicative senescence, and its shortening is a limiter on the number of divisions individual somatic cells can perform. Metal-induced genotoxic events are discussed in Agency for Toxic Substances and Disease Registry’s (ATSDR) toxicological profiles. In vivo and in vitro toxicological studies suggest the correlation between toxic metals and TL. However, the correlation between TL and exposure to toxic metals in human populations is unclear despite decades of observational research. We conducted a literature search within the ATSDR toxicological profiles and PubMed database for peer-reviewed articles as of 04/2023 discussing TL and metal exposure in human populations. Through review of the 272 publications meeting these criteria, we identified 25 observational studies that considered the correlation between TL and exposure to some or all of six metals: cadmium (Cd), arsenic (As), nickel (Ni), selenium (Se), lead (Pb), and cesium (Cs). Because reported effect sizes were often not comparable across studies, we performed a sign test based on the reported significance for each metal–TL correlation. We found that Cd was consistently significantly correlated with shorter telomeres (p = 0.016). However, no consistent linear relationship was observed between TL and any of the other metals considered. Exploring this association can enhance our understanding of how metal exposure may influence TL dysfunction. Our findings suggest that Cd exposure contributes to shorter TL, which may affect the DNA damage response (DDR) resulting in numerous chronic health conditions. Further, we highlight inconsistencies in findings on the correlation between metal exposure and TL across different populations and exposure levels. This suggests that correlations between some metals and TL may vary across populations, and that correlations may change at different exposure levels. Also, our findings suggest the need for further research on the potential for nonlinear relationships and non-additive effects of co-exposure to multiple hazardous metals, which could explain the inconsistencies observed across studies. The inconsistent incidences of metal–TL correlations justify additional exploration into the complex interaction between metals and TL.

Ototoxicity refers to the adverse effects of substances on auditory or vestibular functions. This study examines the evidence of ototoxicity’s association with exposure to common environmental pollutants, as documented in toxicological profiles by the Agency for Toxic Substances and Disease Registry. Our aim was to evaluate whether the evidence supports modifying the charting of ototoxic effects in the summary tables of these toxicological profiles and providing a guide for scientists to access these data. Health outcomes of interest included hearing loss, vestibular effects, cochlear lesions, tonal alterations, cellular damage, and ototoxicity-related outcomes (neurological, nephrotoxic, hepatic, and developmental effects). We obtained ototoxicity information for 62 substances. Hearing-related effects were reported, along with neurological effects. Overall, 26 profiles reported strong evidence of ototoxicity, including 13 substances previously designated as ototoxic by other health and safety agencies. Commonly studied outcomes included hearing loss, damage to ear anatomy, and auditory dysfunction. Vestibular dysfunction and tinnitus are rarely studied. Our findings highlight the lack of conclusive evidence of ototoxic properties for many substances, especially for pesticides and herbicides. This review supports charting the evidence of ototoxicity separately in toxicological profiles’ summary tables. Improving the communication of ototoxicity-related health effects might impact their recognition and prompt further research. A stronger evidence base could support improved prevention efforts in terms of serious health outcomes.