Plasticizer Exposure and Its Consequences on Health

Wider research context: Industrial plasticizers are ubiquitous in modern society, utilized in products ranging from food packaging to medical supplies. Despite their widespread use, the health implications of chronic plasticizer exposure in humans remain inadequately understood. These substances potentially interfere and disrupt various biological processes, including immune activity, gut microbiota balance, endocrinological function, and neurophysiological health. Current epidemiological or exposure studies were able to pinpoint clinical associations with plasticizer exposures, but conclusive mechanistic human in vivo data are missing.

Research questions: The PEACH study is designed to fill critical gaps in the understanding of the biological implications of plasticizer exposure. The investigators aim to analyse the pharmacokinetics of plasticizers in different patient cohorts and elucidate their bioaccumulation, distribution, and metabolism. Thereby, the interplay between plasticizer exposure and metabolism, gut microbiota composition and immune cell functionality will be explored. Furthermore, the impact of plasticizer exposure on neurotransmitter physiology will be elucidated.

Approach: The study employs a comprehensive methodology that integrates the findings from clinical cohorts, systems biology approaches, and in vitro models. Three distinct work packages will examine pharmacokinetic properties via mass spectrometry, study immunological effects through advanced sequencing technologies & phenotypization, and investigate pharmacodynamic interactions with neurotransmitter transporters using human in-vitro assays. Longitudinal sampling from acute and chronic exposure cohorts will offer an evolving perspective on effects of plasticizer exposure.

Level of originality: The PEACH study introduces groundbreaking methodologies and scope to the investigation of plasticizer exposure. It aims to support the scientific community with first human in-vivo pharmacokinetic models for these compounds while utilizing high-throughput techniques for pharmacodynamic assessment, marking a notable advancement in the field.

TDTM:

• Inclusion: Adult, homozygous ß-Thalassemia Major, transfusion dependency.
• Exclusion: Plastic implants, chronic infectious disease, pregnancy.

Thalassemia Intermedia/Minor:

• Inclusion: Adult, homozygous/heterozygous ß-Thalassemia Intermedia/Minor
• Exclusion: Plastic implants, chronic infectious disease, pregnancy, transfusion dependency

Healthy adults:

• Inclusion: Adult
• Exclusion: Chronic disease, plastic implants, infectious disease, pregnancy, anemia, medication-, drug-, or alcohol-abuse

Glioma patients:

• Inclusion: Adult, high/low-grade glioma, tumor larger then 3cm, resection with access to the ventricular system
• Exclusion: Large intraventricular hemorrhage, plastic implants, infectious disease

ICU patients:

• Inclusion: Adult, brain hemorrhage, external CSF drain from ventricle
• Exclusion: intraventricular hemorrhage, plastic implants, ECMO, hemodialysis, infectious disease

Patients undergoing diagnostic lumbar-puncture:

• Inclusion: Adult, diagnostic CSF sampling, outpatient setting
• Exclusion: Ventricular hemorrhage, plastic implants, infectious disease