Micro- and nanoplastics (MNPs) are abundant in the environment, with traffic-related tyre-wear contributing substantially to atmospheric levels. MNPs have been detected in human tissues, however, their health effects remain poorly known. Therefore, we assessed immunological and respiratory health changes associated with short-term exposure to traffic-related MNPs in healthy, young adults. In a semi-controlled study design, 23 healthy subjects participated in four-hour exposure sessions at three different sites: a highway, a stop-and-go high-traffic location and an urban park. Directly before and after, and the following morning, we collected venous blood samples to assess changes in total and differential white blood cell (WBC) counts. Before and directly after each visit we measured lung function and respiratory symptoms. During each exposure session, atmospheric synthetic and natural rubber particles were collected and measured using pyrolysis gas-chromatography coupled to mass-spectrometry, within particles smaller than 10 µm (PM10). Additionally, traffic-related combustion and brake wear-related pollutants were measured including PM10, ultrafine particles, black carbon, trace metals and polycyclic aromatic hydrocarbons. Mixed model analyses were used to assess changes in WBC counts and lung function from baseline to post-exposure (pairwise differences), adjusting for time-varying and subject-dependent covariates. We observed significant associations between an interquartile range increase in multiple tyre-wear rubber markers and a 7.1–9.3 % elevation in monocytes in blood obtained immediately after exposure. Moreover, in blood obtained the following morning, these associations not only persisted but increased for monocytes (9.3–17.7 %) and were additionally found for neutrophils (7.4–14.0 %). The associations remained consistent after adjusting for other traffic-related air pollutants. Null associations were found with lung function and symptoms. Short-term exposure to traffic-related MNPs was associated with an increase in total and differential WBCs. Associations might be indicative of pro-inflammatory effects in healthy people, which could lead to clinically relevant responses in vulnerable populations. © 2025 The Author(s)

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