Week 11 Notes - Chemical Pollution 2 PDF

Asbestos- Silicate fibers  naturally occurring fibrous silicate mineral;  malleable, thermal and electrical insulator, highly fire-resistant: o candle wicks that never burned-up  Exposure o Occupational- ship yard workers in World War II. o Environmental...

Asbestos- Silicate fibers  naturally occurring fibrous silicate mineral;  malleable, thermal and electrical insulator, highly fire-resistant: o candle wicks that never burned-up  Exposure o Occupational- ship yard workers in World War II. o Environmental- in walls of buildings as a fire retardant  Clinic: o PMF with asbestos or ferruginous bodies o Pleural thickening and plaques o Bronchogenic carcinoma o Mesothelioma Beryllium  Exposure is occupational in the nuclear and aerospace industries  Acute berylliosis due to exposure to single high dose level (above 100 μg/m3: severe cough, rhinitis, pharyngitis, dyspnea, anorexia &weight loss, increased fatigue, dermatitis)  Chronic berylliosis due to chronic low level exposure → non caseous granulomas Metals and toxic chemical Elements [MN] They cannot be destroyed therefore they may bio-accumulate They interact with many, many, many other substances and in multiple ways One (limited) beneficial effects doesn’t exclude toxicity Lead poisoning  readily absorbed metal that binds to sulfhydryl groups  Half-life in blood ~ 40 days, in bones & teeth: decades; intermediate: brain, spleen, liver, kidney  Sources of exposure o Occupational: paint, gasoline, ammunition, wheel weights, fishing weights o Incidental - especially a problem for children (smoke and chewing on lead painted toys) o through contaminated air (dust), food, and water, and through skin.  Pathology: o Replaces other metals in proteins (enzymes), especially iron in hemoglobin synthesis o interferes with calcium metabolism, o can pas BBB ← Ca-ATPase pump.  neurotoxic, especially blocking NMDA glutamate receptors  Effects o Anemia with basophilic stippling of RBCs o Renal tubular acidosis (Fanconi's syndrome) Dr M Hossu Notes 175  o Intestinal colic (Painter's colic) o Adults get a peripheral neuropathy o Children get an encephalopathy o Lead line on the gingival margin Mercury  heavy metal that causes formation of disulphide bonds in proteins and displaces Selenium  irreversible inhibition of seleno-enzymes, (e.g. thioredoxin reductase) that restore antioxidant molecules (Vit C & E), back into their reduced forms, enabling them to counteract oxidative stress → organs with highest Oxygen consump on affected first = Brain  used as antiseptic, cosmetic, tonic (!)  Sources- world wide environmental contaminant, particularly in fish  Effects o Acute poisoning - produces acute tubular necrosis and acute renal failure. Inhalation of mercury vapor or ingestion of pesticides containing mercury o Chronic poisoning o Cerebral and cerebellar atrophy with dementia, emotional instability (The mad hatter), failure of co-ordination and visual and auditory disturbances. o Produces cerebral palsy and mental retardation in children. Arsenic Group V element - metalloid  Widely used historically as a poison  as treatment of leukemia, psoriasis, and chronic bronchial asthma; organic arsenic antibiotics for spirochetal and protozoal disease.  also in semiconductors, insecticide, herbicide, wood preservative, antimicrobials and growth promoter used in animal and poultry feeds (as organic arsenicals https://www.atsdr.cdc.gov/toxprofiles/tp2-c5.pdf)  Organic arsenic is less harmful than inorganic arsenic. Sources / exposure  Arsenic contamination of ground water is found in many countries throughout the world, including the US. o Well water is more contaminated than regulated city water  Seafood is a common source of (the less toxic) organic arsenic.  The arsenic reported in 2012 in fruit juice (apples) and rice by Consumer Reports was primarily inorganic arsenic  Rice cooking method: Menon M, Dong W, Chen X, Hufton J, Rhodes EJ. Improved rice cooking approach to maximize arsenic removal while preserving nutrient elements. Sci Total Environ. 2021 Feb 10;755(Pt 2):143341 Mechanisms:  Allosteric inhibition pyruvate dehydrogenase Dr M Hossu Notes 176  o essential metabolic enzyme: oxidation of pyruvate to acetyl-CoA by NAD+. → disrupted energy homeostasis o → severe lactic acidosis and apoptosis  prevents use of thiamine → clinical aspect resembling thiamine deficiency.  Stimulates the production of hydrogen peroxide (H2O2)  Alters voltage-gated potassium channels o = especially inorganic arsenic trioxide found in ground water o → disruption of cellular electrolytic function resulting in neurological disturbances, prolonged QT interval→ life-threatening arrhythmia, high blood pressure, central nervous system dysfunction, anemia, neutropenia, and death.  Acute poisoning produces death within a few hours preceded by severe abdominal pain, tubular necrosis, arrhythmia.  Chronic poisoning produces arsenical keratosis of the skin, carcinoma of the skin, nails show transverse lines (Mee's lines); demyelinating peripheral neuropathy; lung and bladder cancer Resources  Arsenic on CDC: https://www.atsdr.cdc.gov/toxprofiles/tp2-c5.pdf  Nigra et all. The effect of the Environmental Protection Agency maximum contaminant level on arsenic exposure in the USA from 2003 to 2014: an analysis of the National Health and Nutrition Examination Survey (NHANES). Lancet Public Health. 2017 Nov;2(11):e513-e521 [www.ncbi.nlm.nih.gov/pmc/articles/PMC5729579/]  The World Health Organization recommends limiting arsenic concentrations in water to 10 μg/L, although this is often an unattainable goal due to the difficult nature of removing arsenic from water sources. Fluoride Mechanism:  has the highest electronegativity and the second highest electron affinity, making it highly reactive with metals and H  The most favorable metal reactions with fluoride are aluminum, calcium, and magnesium,  the most stable compounds are aluminum, iron, and beryllium;  biological significant CaF2 and MgF2 are highly insoluble and precipitate Sources  also be found in 296 different species of minerals  Free fluoride is present in the ocean at 1.2–1.4 ppm (mg/L)  groundwater, particularly in volcanic or mountainous areas, can contain as much as 50 mg/L  makes up about 1.5–3% of the final phosphate fertilizers  emitted as fumes upon coal combustion  fluoride-accumulating plants: tomato, spinach, grapes, tea, and elderberry. Dr M Hossu Notes 177  Effects  Replaces Ca in bone and teeth making them harder but more rigid, brittle, and porous  Cavity prevention: o Strengthen enamel AFTER its formation; acts from outside of the tooth: i.e. saliva or mouth content. o Mild toxic for mouth bacteria o Fluorosilicic acid (H2SiF6) is the most commonly used additive for water fluoridation in the United States as is an inexpensive by-product of phosphate fertilizer manufacture o ameloblasts: growth-inhibition at low concentration →ER stress and caspase- mediated DNA fragmentation; o children exposed during enamel production (before 8-12 yoa) → dental fluorosis!!! o Dental plaque is the cause of cavities o microbial imbalance, sucrose (sugar), acid pH, long term adherence to the teeth  toxicity: Gurth et all Toxicity of fluoride: critical evaluation of evidence for human developmental neurotoxicity in epidemiological studies, animal experiments and in vitro analyses. Arch Toxicol. 2020 May;94(5):1375-1415: o the inhibition of proteins (metal- enzymes -lipase since 1889!) 30–50% of proteins require metal), organelle disruption, altered pH, and electrolyte imbalance o cell proliferation may be stimulated at concentrations in the micromolar range o triggers oxidative stress, cell cycle arrest, and apoptosis. o Increases generation of superoxide anions; o Induces mitochondrial toxicity: decreased activity of mitochondrial enzymes, decreased mitochondrial protein expression, damage of respiratory chain, ER disorder of calcium regulation, → ↓ATP, accumulation of ROS, opening of the transition pore&release of cytochrome c from mitochondria → apoptosis; o Inhibit cell migration, e.g., of embryonic neurons and sperm; o increases expression of inflammatory factors, such as NF-kappaB and IL-8 Resources  Wei et all. Effect of Fluoride on Cytotoxicity Involved in Mitochondrial Dysfunction: A Review of Mechanism. Front Vet Sci. 2022 Apr 19;9:850771  Kubota et all. Fluoride induces endoplasmic reticulum stress in ameloblasts responsible for dental enamel formation. J Biol Chem. 2005 Jun 17;280(24):23194-202  Kashbour W, Gupta P, Worthington HV, Boyers D. Pit and fissure sealants versus fluoride varnishes for preventing dental decay in the permanent teeth of children and adolescents. Cochrane Database Syst Rev. 2020 Nov 4;11(11) Dr M Hossu Notes 178