Exploring Hematologic Effects of Microplastics: Urinary Mono-n-butyl Phthalate and Blood Cell Counts

Introduction: Microplastic exposure is an emerging global health concern, implicated in inflammation, oxidative stress, and endocrine disruption. As microplastics degrade, they release associated chemicals, including phthalates. Mono-n-butyl phthalate (MBP), is a human biomarker for phthalate and indirectly microplastic exposure. While MBP is a known endocrine disruptor linked to reproductive, metabolic, and neurodevelopmental issues, its specific impact on human hematopoiesis remains understudied. Broader phthalate research suggests potential disruption of bone marrow function and hematopoiesis, through altered antioxidant enzyme activity, increased hemoglobin oxidation, and reduced hematopoietic stem cell expansion. This study addresses a critical knowledge gap by investigating the association between environmental microplastic exposure, as indicated by urinary creatinine-normalized MBP (CnMBP) levels, and hematologic parameters in a nationally representative population. Our objective was to evaluate the relationship between urinary CnMBP levels, hemoglobin and platelet counts. Methods: Participants from the National Health and Nutrition Examination Survey (1999-2018) were included. Blood hemoglobin levels and platelet counts were determined using Coulter HMX Hematology Analyzer. Urinary CnMBP levels were measured using HPLC separation and tandem mass spectrometry. Survey-weighted linear and logistic regression models were used without and with adjusting for age, gender, race, body mass index, hypertension, diabetes mellitus, CKD, and family income. To assess levels of anemia and thrombocytosis, parameters of hemoglobin level <12.0 g/dL in women and <13.0 g/dL in men and platelet count above 450 × 10⁹/L were utilized, respectively, in accordance with World Health Organization (WHO) parameters. Results: Of 20,616 participants, Mean (SD) age was 35.2 (23.3) years, hemoglobin 14 (1.49) g/dL, platelet count 270 (71) 109/L. Participants in the highest CnMBP quartile, compared to the lowest, had 0.63 g/dL lower hemoglobin ( –0.63 g/dL, p<0.001). Other quartiles also revealed significantly lower hemoglobin levels (Q2: –0.09 g/dL, p=0.034; Q3: –0.33 g/dL, p<0.001). Participants in the highest exposure quartile also had a 43% higher odds of anemia (OR = 1.44, 95% CI: 1.12–1.84, p=0.004). Upon examining platelet counts, participants in higher CnMBP quartiles had progressive increases in their platelet counts (Q2: 7.5 ×10⁹/L, p<0.001; Q3: 16.5 ×10⁹/L, p<0.001; Q4: 18.3 ×10⁹/L, p<0.001). No significant increase in thrombocytosis was noted (Q2: OR 0.74, 95% CI: 0.38–1.45, p=0.38; Q3: OR 1.03, 95% CI: 0.63–1.68, p=0.92; Q4: OR1.32, 95% CI: 0.80–2.16, p=0.28). All significant results remained significant after adjustment for confounders. Conclusion: Higher CnMBP levels, a microplastics biomarker, were significantly and independently associated with lower hemoglobin and higher platelet levels, translating into an increased probability of anemia, though not thrombocytosis. These observations align with evidence suggesting microplastics and associated chemicals disrupt biological systems, including inducing oxidative stress and altering blood cell function. Given microplastics' pervasive presence, these results highlight a novel and critical public health concern. Further mechanistic research is warranted to clarify how MBP influences hematopoiesis and assess clinical implications for populations with chronic microplastic exposure. This study enhances understanding of microplastics' systemic effects and emphasizes the urgent need for exposure mitigation and hematologic health protection.