Heavy Metals, Microplastics & Endocrine Disruptors (PFAS, BPA) — References

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• Parent Topic: Heavy Metals, Microplastics & Endocrine Disruptors (PFAS, BPA)
• Reference Hub: 04 - Longevity & Environment References MOC

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Primary Literature Dossier

1. Gasiorowski et al. (2022) — Effect of Plasma and Blood Donations on Levels of PFAS in Humans: A Randomized Clinical Trial

• Citation: Gasiorowski R, Forbes MK, Silver G, Krastev Y, Kerr B,omelchenko T, Lewis J, Taylor MP. Effect of Plasma and Blood Donations on Levels of Perfluoroalkyl and Polyfluoroalkyl Substances in Firefighters in Australia: A Randomized Clinical Trial. JAMA Network Open. 2022 Apr 1;5(4):e226257.
• Identifiers: PMID: 35394514 (PubMed · Europe PMC) | DOI: 10.1001/jamanetworkopen.2022.6257 (DOI · SciDB · Scholar)
• Study Design & Sample Size: 52-week open-label, parallel-group randomized clinical trial ($n=285$ Australian firefighters with baseline serum PFOS $\ge 5\text{ ng/mL}$ randomized 1:1:1 to plasma donation every 6 weeks [up to 9 donations], whole blood donation every 12 weeks [up to 5 donations], or observation control).
• Key Quantitative Outcomes:
  • Compared to observation (where PFAS levels remained unchanged), regular plasma donations reduced mean serum PFOS by $-2.9\text{ ng/mL}$ ($95\%\text{ CI}:-3.6\text{ to }-2.3\text{ ng/mL},p<0.001$, a ~30% reduction) and significantly reduced PFHxS by $-1.1\text{ ng/mL}$ ($p<0.001$).
  • Whole blood donations every 12 weeks also significantly reduced serum PFOS by $-1.1\text{ ng/mL}$ ($95\%\text{ CI}:-1.5\text{ to }-0.7\text{ ng/mL},p<0.001$), providing the first Level-1 human RCT intervention proven to accelerate clearance of bioaccumulated PFAS.

2. Marfella et al. (2024) — Microplastics and Nanoplastics in Human Atheromas and Cardiovascular Events

• Citation: Marfella R, Prattichizzo F, Sardu C, Fulgenzi G, Graciotti L, Spadoni T, D’Onofrio N, Scisciola L, La Grotta R, Frigé C, Pellegrini V, Municinò M, Siniscalchi M, Spinetti F, Vigliotti G, Vecchione C, Carrizzo A, Accarino G, Squillante A, Spaziano G, Mirra D, Esposito R, Altieri S, Falco G, Fenti A, Galoppo S, Lettieri S, Monda M, Messina G, Ceriello A, Giugliano G, Iovino P, Balestrieri ML, Cacciapuoti F, Montone RA, Bonomo L, Crea F, Paolisso G. Microplastics and Nanoplastics in Atheromas and Cardiovascular Events. New England Journal of Medicine. 2024 Mar 7;390(10):900-910.
• Identifiers: PMID: 38446676 (PubMed · Europe PMC) | DOI: 10.1056/NEJMoa2309822 (DOI · SciDB · Scholar)
• Study Design & Sample Size: Prospective multicenter observational cohort study ($n=304$ patients undergoing carotid endarterectomy for asymptomatic carotid artery disease; excised plaque specimens analyzed via pyrolysis–gas chromatography–mass spectrometry [Py-GC/MS], stable isotope analysis, and transmission electron microscopy, with $n=257$ followed for a mean of $33.7\text{ months}$).
• Key Quantitative Outcomes:
  • Polyethylene (PE) was detected inside the carotid artery plaque of 150 patients ($58.4\%$) (mean concentration $21.8\pm 24.5\mu \text{g/mg}$ of plaque), and polyvinyl chloride (PVC) in 31 patients ($12.1\%$), with electron microscopy revealing jagged foreign nanoplastic particles ($<200\text{ nm}$) embedded inside plaque macrophages alongside markedly elevated plaque $\text{IL-18}$, $\text{IL-1}\beta$, $\text{IL-6}$, and $\text{TNF-}\alpha$.
  • Patients whose plaques contained micro/nanoplastics had a 4.53-fold higher risk of composite myocardial infarction, stroke, or all-cause death (multivariable-adjusted $\text{HR }4.53,95\%\text{ CI}:2.00\text{–}10.27,p<0.001$).

3. Lanphear et al. (2018) — Low-Level Lead Exposure and Cardiovascular and All-Cause Mortality in US Adults

• Citation: Lanphear BP, Rauch S, Auinger P, Allen RW, Hornung RW. Low-level lead exposure and mortality in US adults: a population-based cohort study. The Lancet Public Health. 2018 Apr;3(4):e177-e184.
• Identifiers: PMID: 29544878 (PubMed · Europe PMC) | DOI: 10.1016/S2468-2667(18)30025-2 (DOI · SciDB · Scholar)
• Study Design & Sample Size: Nationally representative prospective cohort study (NHANES III, $n=14,289$ US adults aged $\ge 20\text{ years}$ with baseline venous blood lead measurements followed for a median of $19.3\text{ years}$).
• Key Quantitative Outcomes:
  • An increase in blood lead concentration from the 10th percentile ($1.0\mu \text{g/dL}$) to the 90th percentile ($6.7\mu \text{g/dL}$) was associated with a 37% increase in all-cause mortality ($\text{HR }1.37,95\%\text{ CI}:1.17\text{–}1.60$), a 70% increase in cardiovascular disease mortality ($\text{HR }1.70,95\%\text{ CI}:1.30\text{–}2.22$), and a 108% increase in ischemic heart disease mortality ($\text{HR }2.08,95\%\text{ CI}:1.52\text{–}2.85$).
  • Even when restricted to adults with blood lead $<5\mu \text{g/dL}$ (previously deemed “normal”), cardiovascular mortality remained significantly elevated ($\text{HR }1.95$).

4. Genuis et al. (2011 / 2012) — Human Excretion of Bisphenol A, Phthalates, and Heavy Metals: Blood, Urine, and Sweat (BUS) Study

• Citation: Genuis SJ, Beesoon S, Birkholz D, Lobo RA. Human excretion of bisphenol A: blood, urine, and sweat (BUS) study. Journal of Environmental and Public Health. 2012;2012:185731. (Companion Heavy Metal BUS Study: Archives of Environmental Contamination and Toxicology. 2011 Nov;61(3):344-357; PMID 21057782 (PubMed)).
• Identifiers: PMID: 22253637 (PubMed · Europe PMC) (10.1155/2012/185731 (DOI · SciDB)) & PMID: 21057782 (PubMed · Europe PMC) (10.1007/s00244-010-9611-5 (DOI · SciDB))
• Study Design & Sample Size: Paired biomonitoring study ($n=20$ adult subjects providing simultaneous matched blood, urine, and sauna-induced sweat samples analyzed by GC-MS and ICP-MS).
• Key Quantitative Outcomes:
  • Bisphenol A (BPA) was identified in 80% ($16/20$) of induced sweat samples, including in numerous individuals who had zero detectable BPA in their serum or urine.
  • Mono(2-ethylhexyl) phthalate (MEHP) concentration in sweat was more than 2-fold higher than in urine, and Cadmium ($\text{Cd}$), Lead ($\text{Pb}$), and Arsenic ($\text{As}$) were robustly concentrated in sweat relative to plasma.