Health Effects of Naphthalene Exposure: A Systematic Evidence Map and Analysis of Potential Considerations for Dose–Response Evaluation

Abstract

BACKGROUND: Naphthalene is a polycyclic aromatic hydrocarbon that has been associated with health effects, including cancer. As the state of the science on naphthalene toxicity continues to evolve, updated toxicity reference value(s) may be required to support human health risk assessment. OBJECTIVES: We present a systematic evidence map of studies that could be used to derive toxicity reference value(s) for naphthalene. METHODS: Human and animal health effect studies and physiologically based pharmacokinetic (PBPK) models were identified from a literature search based on populations, exposures, comparators, and outcomes (PECO) criteria. Human and animal studies meeting PECO criteria were refined to a smaller subset considered most informative for deriving chronic reference value(s), which are preferred for assessing risk to the general public. This subset was evaluated for risk of bias and sensitivity, and the suitability of each study for dose-response analysis was qualitatively assessed. Lowest observed adverse effect levels (LOAELs) were extracted and summarized. Other potentially relevant studies (e.g., mechanistic and toxicokinetic studies) were tracked as supplemental information but not evaluated further. Existing reference values for naphthalene are also summarized. RESULTS: We identified 26 epidemiology studies and 16 animal studies that were considered most informative for further analysis. Eleven PBPK models were identified. The available epidemiology studies generally had significant risk of bias and/or sensitivity concerns and were mostly found to have low suitability for dose-response analysis due to the nature of the exposure measurements. The animal studies had fewer risk of bias and sensitivity concerns and were mostly found to be suitable for dose-response analysis. CONCLUSION: Although both epidemiological and animal studies of naphthalene provide weight of evidence for hazard identification, the available animal studies appear more suitable for reference value derivation. PBPK models and mechanistic and toxicokinetic data can be applied to extrapolate these animal data to humans, considering mode of action and interspecies metabolic differences.

Systematic Evidence Map for Over One Hundred and Fifty Per- and Polyfluoroalkyl Substances (PFAS)

“…Key study evaluation considerations included potential sources of bias (factors affecting the magnitude or direction of an effect in a systematic way) and insensitivity (factors limiting detection of a true effect). Core and prompting questions used to guide the judgment for each domain are described in more detail in the IRIS Handbook 22 and have been described in several other published publications, including Yost et al., 24 , 47 Radke et al., 25 , 49 and Dishaw et al. 48 After a consensus rating was reached, the reviewers considered the identified strengths and limitations to reach an overall study confidence rating of High, Medium, Low, or Uninformative for each health outcome ( Figure 1 ).…”

Disposable Polypropylene Face Masks: A Potential Source of Micro/Nanoparticles and Organic Contaminates in Humans

“…Dibutyl phthalate has been recognized as a class 1B reproductive toxicant in the REACH authorization list, , and 1-methylnaphthalene has been reported as a neurotoxicant and lung carcinogen . Naphthalene and benzophenone classes are potential carcinogens due to radical formation after being transformed in humans …”

“…75 Naphthalene and benzophenone classes are potential carcinogens due to radical formation after being transformed in humans. 76 While most of the identified chemicals have not been quantified, we conducted a preliminary health risk assessment by taking the three quantified phenols as examples. If we assume two masks are consumed daily, the bioaccessibilities of the three phenols are all 100%, and the average body weight for an adult is 60 kg, a daily exposure at 60−350 ng kg −1 day −1 can be obtained.…”

Increased breath naphthalene in children with asthma and wheeze of the All Age Asthma Cohort (ALLIANCE)

“…It is a natural constituent in coal tar and oil, and a ubiquitous pollutant in the environment [27]. Large amounts are produced worldwide [30], primarily as an intermediate for other chemicals and airborne emissions originate from incomplete combustion, e.g. in traffic exhaust, during burning of biomass, or tobacco smoke [27].…”