The onset of human degenerative diseases in humans, including type 2 diabetes, cardiovascular disease, neurological disorders, neurodevelopmental disease and neurodegenerative disease has been shown to be related to exposures to persistent organic pollutants, including polychlorinated biphenyls, chlorinated pesticides, polybrominated diphenyl ethers and others, as well as to polynuclear aromatic hydrocarbons, phthalates, bisphenol-A and other aromatic lipophilic species. The onset of these diseases has also been related to exposures to transition metal ions. A physiochemical mechanism for the onset of degenerative environmental disease dependent upon exposure to a combination of lipophilic aromatic hydrocarbons and transition metal ions is proposed here. The findings reported here also, for the first time, explain why aromatic hydrocarbons exhibit greater toxicity than aliphatic hydrocarbons of equal carbon numbers.
If the inline PDF is not rendering correctly, you can download the PDF file here.
Adlard PA Bush AI. (2006). Metals and Alzheimer’s disease. J Alzheimers Dis10(2–3): 145–63.
Anfinsen CB. (1973). Principles that govern the folding of protein chains. Science181: 223–30.
Bai YN Yang AM Pu HQ He J Cheng N Zheng TZ et al. (2014). Nickel-exposed workers in China: a cohort study. Biomed Environ Sci27(3): 208–11.
Barbier O Jacquillet G Tauc M Cougnon M Poujeol. (2005). Effect of heavy metals on and handling by the kidney. Nephron Physiol99(4): 105–10.
Beckerson P Wilson MT Svistunenko DA Reeder BJ. (2015). Cytoglobin ligand regulated by changing haem-coordination in response to intramolecular disulfide bond formation and lipid interaction. Biochem J. 465(1): 127–37.
Boggs JM. (1987). Lipid intermolecular hydrogen bonding: influence on structural organization and membrane function. Biochim Biophys Acta906(3): 353–404.
Bostrom CE Gerde P Hanberg A Jernstrom B Johansson C Kyrklund T et al. (2002). Cancer risk assessment indicators and guidelines for polycyclic aromatic hydrocarbons in the ambient air. Environ Health Perspect110(Suppl 3): 451–88.
Bowman AB Kwakye GF Hernandez EH Aschner M. (2011). Role of manganese in neurodegenerative disease. J Trace Elem Med Biol25(4): 191–203.
Bushnik T Haines D Levallois P Levesque P Levesque J Van Ostdam J Viau C. (2010). Lead and bisphenol A concentrations in the Canadian population. Health Rep21(3): 7–14.
Calderon-Garciduenas L Solt AC Henriquez-Roldan C Torres-Jardon R Nuse B Herritt L et al. (2008). Long-term air pollution exposure is associated with neuroinflammation an altered innate immune response disruption of the blood-brain barrier ultrafine particulate deposition and accumulation of amyloid beta-42 and alpha-synuclein in children and young adults. Toxicol Pathol36: 289–310.
Chen YW Yang CY Huang CR Hung DZ Leung YM Liu SH. (2009). Heavy metals islet function and diabetes development. Islets1(3): 169–76.
Chen P Parmalee N Aschner M. (2014). Genetic factors and manganese-induced neurotoxicity. Frontiers in Genet5: Article 265.
Cornell BA Separovic F. (1983). Membrane thickness and acyl chain length. Biochim Biophys Acta733(1): 189–93.
deKroon AIPM Rijken PJ De Smet CH. (2013). Checks and balances in membrane phospholipid class and acyl chain homeostasis the yeast perspective. Progress in Lipid Res52(2013): 374–94.
Endo S Eshcer BI Goss KU. (2011). Capacities of membrane lipids to accumulate neutral organic chemicals. Environ Sci Technol45: 5912–21.
Evans DR Fackler NLP Xie Z Rickard CEF Boyd PDW Reed CA. (1999). piarene/cation structure and bonding. Solvation versus ligand binding in iron(III) tetraphenylporphyrin complexes of benzene toluene p-xylene and (60)Fullerene. J Am Chem Soc121: 8466–74.
Fukushima T Tan X Luo Y Wang P Song J Kanda H et al. (2014). Correlations among heavy metals in blood and urine and their relationships to depressive symptoms in Parkinson’s disease patients. Fukushima J Med Sci60(2): 1–8.
Gauthier PT Norwood WP Prepas EE Pyle GG. (2014). Metal-PAH mixtures in the aquatic environment: A review of co-toxic mechanisms leading to more-than-additive outcomes. Aquatic Toxicol154: 253–69.
Gupta A. (1999). Functional impairment of blood-brain barrier following pesticide exposure during early development of rats. Human Experiment Toxicol18(3): 174–79.
Holthuis JCM Menon AK. (2014). Lipid landscapes and pipelines in membrane homeostasis. Nature510: 48–57.
Hsu PC Liu CC Chen LY Guo YL. (1997). Lead exposure causes generation of reactive oxygen species and functional impairment in rat sperm. Toxicology122(1–2): 133–43.
Jarup L. (2003). Hazards of heavy metal contamination. Br Med Bull68: 167–82.
KitagawaS Li H Sato S. (1997). Skin permeation of parabens in excised guinea pig dorsal skin its modification by penetration enhancers and their relationship with n-octanol/water partition coefficients. Chem Pharm Bull (Tokyo)45(8): 1354–57.
Korchowiec B Corvis Y Viitala T Feidt C Guiavarch Y Corbier D Rogalska E. (2008). Interfacial aproach to polyaromatic hydrocarbon toxicity: phosphoglyceride and cholesteral monolayer response to phenanthrene anthracene pyrene chrysene and benzo(a)(yrene. J Phys Chem112: 13518–31.
Kumudini N Uma A Devi YP Naushad S Mridula R Borgohain R Kutala VK. (2014). Association of Parkinson’s disease with altered serum levels of lead and transition metals among South Indian subjects. Indian J Biochem Biophys51(2): 121–26.
Kuo CC Moon K Thayer KA Navas-Acien A. (2013). Environmental chemicals and type 2 diabetes: an updated systematic review of epidemiologic evidence. Curr Diab Rep13(6): 831–49.
Lee AG. (2003). Lipid-protein interactions in biological membranes: a structural perspective. Biochim Biophys Acta1612(1): 1–40.
Lee AG. (2004). How lipids affect the activities of integral membrane proteins. Biochim Biophys Acta1666(1–2): 62–87.
Librando V Sarpietro MG Castelli F. (2003). Role of lipophilic medium in the absorption of polycyclic aromatic compounds by biomembranes. Environ Toxicol Pharmacol14(1–2): 25–32.
Liland NS Simonsen AC Duelund L Torstensen BE Berntssen MHG Mouritsen OG. (2014). Polyaromatic hydrocarbons do not disturb liquid-liquid phase coexistence but increase the fluidity of model membranes. Chem Phys Lip184C: 18–24.
Lipinski B. (2010). Prostate cancer vaccines fibrin and selenium: a conceptual review. Open Prost Cancer J3: 69–73.
Lipinski B. (2011). Hydroxyl radical and its scavengers in health and disease. Oxid Med Cell Longev2011: Article ID 809696 9 p.
Lipinski B Pretorieus E. (2012). Novel pathway of iron-induced blood coagulation: implications for diabetes mellitus and its complications. Pols Arch Med Wewn122(3): 115–22.
Lipinski B Pretorius E. (2013). Iron-induced fibrin in cardiovascular disease. Curr Neurovasc Res10: 269–74.
Lipinski B Pretorius E. (2013a). The role of iron-induced fibrin in the pathogenesis of Alzheimer’s disease and the protective role of magnesium. Frontiers Human Neurosci7(Article 735): 1–11.
Lipinski B. (2014). Cancer wars: significance of protein unfolding in cancer and its inhibition with natural amphiphilic substances. Frontiers in Oncology4: 183.
Lipinski B. (2014a). Can selenite be an ultimate inhibitor of Ebola and other viral infections? Br. J Med and Medical Res6(3): 319–24.
Lodish H Berk A Kaiser CA Krieger M. (2007). Molecular cell biology New York: W.H. Freeman.
Manganaro AM. (1997). Review of transmucosal drug delivery. Mil Med162: 27–30.
Martinez-Finley EJ Gavin CE Aschner M Gunter TE. (2013). Manganese neurotoxicity and the role of reactive oxygen species. Free Radic Biol Med62: 65–75.
Mates JM Segura JA Alonso FJ Marquez J. (2010). Roles of dioxins and heavy metals in cancer and neurological diseases using ROS-mediated mechanisms. Free Rad Biol Med49(9): 1328–41.
McIntosh TJ Simon SA MacDonald RC. (1980). The organization of n-alkanes in lipid bilayers. Biochim Biosphys Acta597(3): 445–63.
Murray CJL Vos T Lozano R Naghavi M Flaxman AD et al. (2012). Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet380(7): 2197–2223.
OSHA. (2006). United States Department of Labor Occupational Safety and Health Administration Washington DC. OSHA 1910.100 table Z-1 and OSHA 1910.1028. www.osha.gov/law-regs.html (Accessed October 9 2014).
Padilla MA Elobeid M Ruden DM Allison DB. (2010). An examination of the association of selected toxic metals with total and central obesity indices: NHANES 99-02. Int J Environ Res Public Health7: 3332–47.
Pardridge WM. (2012). Drug transport across the blood-brain barrier. J Cereb Blood Flow Metab32(11): 1959–72.
Park HJ Kim JY Kim J Lee JH Hahn JS Gu MB Yoon J. (2009). Silver-ion mediated reactive oxygen species generation affecting bactericidal activity. Water Res43(4): 1027–32.
Patel MM Goyal BR Bhadada SV Bhatt JS Amin AF. (2009). Getting into the brain: approaches to enhance brain drug delivery. CNS Drugs23(1): 35–58.
Perbellini L Brugnone F Caretta D Maranelli G. (1985). Partition coefficients of some industrial aliphatic hydrocarbons (C5–C7) in blood and human tissues. Br J Ind Med42: 162–67.
Pretorius E Lipinski B. (2013). Differences in morphology of fibrin clot induced with thrombin and ferric ions and its pathophysiological consequences. Heart Lung Circulation22: 447–49
Qiu C Cheng S Xia Y Peng B Tang Q Tu B. Effects of subchronic benzo(a) pyrene exposure on neurotransmitter receptor gene expression in the rat hippocampus related with spatial learning and memory change. Toxicology289(2–3): 83–90.
Rana SV. (2014). Perspectives in endocrine toxicity of heavy metals--a review. Biol Trace Elem Res160(1): 1–14.
Rani A Kumar A Lal A Pant M. (2014). Cellular mechanisms of cadmium-induced toxicity: a review. Int J Environ Health Res24(4): 378–99.
Retzinger GS DeAngelis AP Patuto SJ. (1998). Adsorption of fibrinogen to droplets of liquid hydrophobic phases. Arterioscler Thromb Vasc Biol18: 1948–57.
Rossignol DA Genuis SJ Frye RE. (2014). Environmental toxicants and autism spectrum disorders: a systematic review. Transl Psychiatry4: e360.
Sato A Nakajima T. (1987). Pharmacokinetics of organic solvent vapors in relation to their toxicity. Scand J Work Environ Health13: 81–93.
Schwingshacki L Hoffmann G. (2014). Adherence to Mediterranean diet and risk of cancer: a systematic review and meta-analysis of observational studies. Int J Cancer135(8): 1884–97.
Scinicariello F Buser MC. (2014). Urinary polycyclic aromatic hydrocarbons and childhood obesity: NHANES (2001–2006). Environ Health Perspect122(3): 299–303.
Seelbach M Chen L Powell A Choi YJ Zhang B Hennig B Toborek M. (2010). Polychlorinate biphenyls disrupt blood-brain barrier integrity and promote brain metastasis formation. Environ Health Perspect118(4): 479–84.
Sharma B Singh S Siddiqi NJ. (2014). Biomedical implications of heavy metals induced imbalances in redox systems. Biomed Res Int2014: Article ID 640754 26 p.
Sikkema J de Bont JAM Poolman B. (1994). Interactions of cyclic hydrocarbons with biological membranes. J Biol Chem269(11): 8022–28.
Sikkema J de Bont JAM Poolman B. (1995). Mechanisms of membrane toxicity of hydrocarbons. Microbiol Rev59(2): 201–22.
Smith AQ Campbell JL Keys DA Fisher JW. (2005). Rat tissue and blood partition coefficients for n-alkanes (C8–C12). Int J Toxicol24(1): 35–41.
Sprague BL Trentham-Dietz A Hedman CJ Wang J Hemming JD Hampton JM et al. (2013). Circulating serum xenoestrogens and mammographic breast density. Breast Cancer Res15(3): R45.
Tchounwou PB Yedjou CG Patlolla AK Sutton DJ. (2012). HEavy metal toxicity and the environment. EXS101: 133–64.
Valko M Morris H Cronin MT. (2005). Metals toxicity and oxidative stress. Curr Med Chem12(10): 1161–1208.
Vizcaya D Rivera M Lavoue J Siemaitycki J. (2014). Lung cancer and exposure to benzene toluene and xylene: results from two case-control studies in Montreal. Occup Environ Med71(Suppl 1): A91.
Wang BJ Sheu HM Guo YL Lee YH Lai CS Pan MH Wang YJ. (2010). Hexavalent chromium induced ROS formation Akt NF-kappaB and Mapk activation and TNF-alpha and IL-1 production in keratinocytes. Toxicol Lett198(2): 216–24.
Wang W Lampi MA Huang XD Gerhardt K Dixon DG Greenberg BM. (2009). Assessment of mixture toxicity of copper cadmium and phenathrenequinone to the marine bacterium Vibrio fishcheri. Environ Toxicol24(2): 166–7.
Xu H Finkelstein DI Adlard PA. (2014). Interactions of metals and Apolipoprotein E in Alzheimer’s disease. Front Aging Neurosci6: 121.
Xu J Zhou Q Liu G Tan Y Cai L. (2013). Analysis of serum and urinal copper and zinc in Chinese northeast population with the prediabetes or diabetes with and without complications. Oxid Med Cell Longev2013: 635214.
Zeliger HI. (2003). Toxic effects of chemical mixtures. Arch Environ Health58(1): 23–29.
Zeliger HI. (2011). Human toxicology of chemical mixtures 2nd ed. Elsevier London.
Zeliger HI Pan Y Rea WJ. (2012). Predicting co-morbidities in chemically sensitive individuals from exhaled breath analysis. Interdiscip Toxicol5(3): 123–126.
Zeliger HI. (2013). Lipophilic chemical exposure as a cause of type 2 diabetes (T2D). Rev Environ Health28(1): 9–20.
Zeliger HI. (2013a). Lipophilic chemical exposure as a cause of cardiovascular disease. Interdiscip Toxicol6(2): 55–62.
Zeliger HI. (2013b). Lipophilic chemical exposure as a cause of neurological impairments neurodevelopmental disorders and neurodegenerative diseases. Interdiscip Toxicol6(3): 103–10.
Zeliger HI. (2014). Co-morbidities of environmental diseases: a common cause. Interdiscip Toxicol7(3): 171–22.