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Health Effects of Naphthalene Exposure: A systematic Evidence Map and Analysis of Potential Considerations for Dose-Response Evaluation
Citation:
Yost, E., A. Galizia, D. Kapraun, A. Persad, Suryanarayana Vulimiri, M. Angrish, J. Lee, AND I. Druwe. Health Effects of Naphthalene Exposure: A systematic Evidence Map and Analysis of Potential Considerations for Dose-Response Evaluation. ENVIRONMENTAL HEALTH PERSPECTIVES. National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, NC, (076002):1-30, (2021). https://doi.org/10.1289/EHP7381
Impact/Purpose:
This journal article presents an evidence map for naphthalene that highlights the studies that could be used to derive or revise a reference value.
Description:
Background: Naphthalene is a naturally occurring polycyclic aromatic hydrocarbon that is also manufactured for use in consumer products such as moth repellents and has been associated with a variety of health effects including cancer. As the state of the science on naphthalene toxicity continues to evolve, updated toxicity reference value(s) for naphthalene may be required to support human health risk assessment. Objectives: This scoping report presents a systematic evidence map of studies informative of the health effects of naphthalene exposure, focusing on human and experimental animal studies that could potentially be used to derive updated reference value(s) for human health risk assessment. We qualitatively analyzed the suitability of the available human and animal datasets for dose-response analysis and assessed the availability of physiologically-based toxicokinetic (PBTK) models, toxicokinetic data, and mechanistic data that can be used to inform dose extrapolation. Methods: A literature search was conducted in four online scientific databases (PubMed, Web of Science, Toxline, and Toxic Substances Control Act Test Submissions) and augmented by review of regulatory sources as well as forward and backward searches. Human and animal health effect studies and PBTK models were identified based on defined PECO (Population, Exposure, Comparator, Outcome) criteria. Other potentially relevant studies (e.g. mechanistic and toxicokinetic studies) were also identified as supplemental information. Human and animal studies that met PECO criteria were refined to a smaller subset that evaluated major outcomes associated with naphthalene exposure (respiratory, hematological, immune, reproductive, developmental, ocular, and cancer) and that used exposure designs that were considered most informative for further analysis. These studies were evaluated for reporting quality, risk of bias, and sensitivity using a domain-based approach and were rated as high confidence, medium confidence, low confidence, or uninformative. The suitability of each study for dose-response analysis was then qualitatively assessed based on study design and exposure characteristics. The lowest-observed-adverse-effect levels (LOAELs) in the animal studies were extracted and summarized. Results: The literature search and screen identified 32 epidemiology studies and 62 animal toxicology studies that met PECO criteria, which were refined to 24 epidemiology studies and 15 animal studies that were considered most informative for further analysis. Ten PBTK models and 664 studies with potentially relevant supplemental information were also identified, including 405 studies with mechanistic data and 235 studies with toxicokinetic data. The available epidemiology studies generally had risk of bias and/or sensitivity concerns and were rated medium confidence, low confidence, or uninformative, whereas the available animal studies had fewer concerns and were generally rated high or medium confidence. Looking across health outcomes, the available epidemiology studies were found to have low suitability for dose-response analysis due to the nature of the exposure measurements, whereas there were animal studies available for each outcome that were considered suitable for dose-response analysis. Conclusion: Although both epidemiological and experimental animal studies of naphthalene provide weight of evidence for hazard identification, the available animal studies appear to be more suitable for reference value derivation. PBTK models and the available mechanistic and toxicokinetic data can be applied to extrapolate these animal data to humans, considering mode of action and interspecies metabolic differences.
URLs/Downloads:
DOI: Health Effects of Naphthalene Exposure: A systematic Evidence Map and Analysis of Potential Considerations for Dose-Response Evaluation