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Volume 14
Issue 6
10.3390/toxics14060517
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Article

Neonatal Exposure to Di(2-ethylhexyl) Phthalate Is Associated with Lung Injury in a Rat Model of Chronic Lung Disease of Prematurity

by
Shahana Perveen
1,2,3,4,*,
Li Lou
1,4,
Sohini Alim
1,4,
Abigail Akselrod
1,4,
Chunfang Zhao
1,4,
Namita Sen
1,4,
Clifford S. Deutschman
1,3,4 and
Annemarie Stroustrup
1,2,3,5,6
1
Northwell Health, New Hyde Park, NY 11040, USA
2
Division of Neonatology, Cohen Children’s Medical Center, New Hyde Park, NY 11040, USA
3
Department of Pediatrics, Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY 11549, USA
4
Institute for Molecular Medicine, Feinstein Institutes for Medical Research, Manhasset, NY 11030, USA
5
Department of Occupational Medicine, Epidemiology & Prevention, Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY 11549, USA
6
Institute for Health System Science, Feinstein Institutes for Medical Research, Manhasset, NY 11030, USA
*
Author to whom correspondence should be addressed.
Toxics 2026, 14(6), 517; https://doi.org/10.3390/toxics14060517 (registering DOI)
Submission received: 10 May 2026 / Revised: 5 June 2026 / Accepted: 10 June 2026 / Published: 12 June 2026
(This article belongs to the Special Issue Phthalates: Environmental Distribution, Human Exposure, and Health Risks)
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Abstract

Chronic lung disease of prematurity (CLD) is a common complication of preterm birth with a complex pathology. Recent epidemiologic studies have identified a link between neonatal exposure to di(2-ethylhexyl) phthalate (DEHP), frequently used in medical equipment, and the development of CLD. We hypothesize that DEHP exposure in the early neonatal period contributes to lung injury in newborn rats. Newborn rat pups were raised in one of the following environments: room air (RA), RA + DEHP, hyperoxia (60% oxygen), and hyperoxia + DEHP. Ambient DEHP was inhaled at a dose of 25 mg/m3 for 6 h daily for 14 days. Lung tissue and blood samples were collected on the 14th day of life. Independent exposure to DEHP and hyperoxia resulted in thicker pulmonary septal walls, fewer alveoli, increased pulmonary polymorphonuclear leukocytes and myeloperoxidase (MPO) activity and decreased expression of CD31 on endothelial cells in lung tissue. Additionally, DEHP-exposed rats showed higher serum malondialdehyde (MDA) levels and reduced vascular endothelial growth factor (VEGF) mRNA and protein levels compared to controls. Our experiments demonstrate that inhaled DEHP, with or without hyperoxia, resulted in a similar pattern of morphological lung injury and inflammation characteristic of CLD, suggesting an association with CLD of prematurity.
Keywords: phthalates; environmental toxin; bronchopulmonary dysplasia; chronic lung disease; lung injury; prematurity; animal model phthalates; environmental toxin; bronchopulmonary dysplasia; chronic lung disease; lung injury; prematurity; animal model
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MDPI and ACS Style

Perveen, S.; Lou, L.; Alim, S.; Akselrod, A.; Zhao, C.; Sen, N.; Deutschman, C.S.; Stroustrup, A. Neonatal Exposure to Di(2-ethylhexyl) Phthalate Is Associated with Lung Injury in a Rat Model of Chronic Lung Disease of Prematurity. Toxics 2026, 14, 517. https://doi.org/10.3390/toxics14060517

AMA Style

Perveen S, Lou L, Alim S, Akselrod A, Zhao C, Sen N, Deutschman CS, Stroustrup A. Neonatal Exposure to Di(2-ethylhexyl) Phthalate Is Associated with Lung Injury in a Rat Model of Chronic Lung Disease of Prematurity. Toxics. 2026; 14(6):517. https://doi.org/10.3390/toxics14060517

Chicago/Turabian Style

Perveen, Shahana, Li Lou, Sohini Alim, Abigail Akselrod, Chunfang Zhao, Namita Sen, Clifford S. Deutschman, and Annemarie Stroustrup. 2026. "Neonatal Exposure to Di(2-ethylhexyl) Phthalate Is Associated with Lung Injury in a Rat Model of Chronic Lung Disease of Prematurity" Toxics 14, no. 6: 517. https://doi.org/10.3390/toxics14060517

APA Style

Perveen, S., Lou, L., Alim, S., Akselrod, A., Zhao, C., Sen, N., Deutschman, C. S., & Stroustrup, A. (2026). Neonatal Exposure to Di(2-ethylhexyl) Phthalate Is Associated with Lung Injury in a Rat Model of Chronic Lung Disease of Prematurity. Toxics, 14(6), 517. https://doi.org/10.3390/toxics14060517

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