Post on 01-Jan-2016
METALS
Lead, Pb• Unique properties - used since antiquity• Mostly anthropogenic sources
(Greenland snow pack data, 1954)
• Banned as paint additive – Europe 1921– USA 1978
• Sources: smelters, refineries, power plants, incinerators, manufacturing and recycling operations
Exposure to Pb• Pb in air NAAQS level =1.5ug/m3 (quarterly)
– Mostly (90%) from leaded gasoline, until 1978 (400t/day worldwide)
– Industrial emissions• Pb in water Action water level =15ppb (0.015ppm)
– Airborne Pb deposition in water – Water supply pipes– Lead shots in lakes (Whatcom county, WA)
• Pb in food– From water to plants --> animals --> food– Pb-based glaze for pottery– Pica for children - leaded paint flakes
• Pb in soil– From industrial emissions, home paint disposal, gasoline
(~600,000t/year)– Pica for children
Annual US air emissions:1981 56,000t1990 7,100t
Pb Health effects
• Young animals and humans more susceptible
• Aquatic organisms and birds affected (directly or by water acidification)
Human health effects of PbIn blood - 25 days
Half life In soft tissue - 40 daysIn bone - 25 years !
• Accumulates (95% in bone and teeth) - remobilized• Possible human carcinogen (IARC)
(phosphate and acetate forms)
• Systemic poison– Inhibits hematopoiesis - anemia (heme synthesis)– Causes renal tubular dysfunction– Lung function (asthma, bronchitis, tissue damage)– Muscle and joint pains, skeletal growth effects– Immune system damage– Miscarriage, stillbirth
Action blood level =25ug/dl (2.5ug/ml)
Children more vulnerable
• Pb poisoning is the most common and serious environmental disease
• Primary target CNS– Retardation and brain damage– Behavioral changes– Cognitive development
• Levels dropped since 1974 from 15-18 to 2-3ug/dl - still 2.2% US children are above the 10ug/dl limit
CNS effects from blood level =10ug/dl (1ug/ml) - CDC
Mechanism of action• Binds to -SH groups on enzymes (inactivation)
– adenyl cyclase (ATP to AMP),– aminotransferase (protein metabolism)
• Competition with Ca++ – Mitochondria respiration– Synaptic regulation– Skeletal calcium substitution– tRNA interaction with aminoacids and ribosomes
• Heme synthesis inhibition -aminolevulinic acid dehydratase (Zn++) ( serum ALA levels)– Ferrochelatase (Fe++)
• Nutritional factors affect Pb absorption(Fe deficiency)
Cadmium, Cd• Itai-itai byo disease (Japan 1945)
– Irrigation of rice fields with contaminated water from Zn-Cd-Pb mine
• Bone fractures, deformations, decalcification, pains• Persistent (t1/2=10-25y), one of the most toxic trace
metals• Byproduct of smelting, fossil fuel combustion, phosphate
fertilizers• Used with other metals as anticorrosive, multiple other
uses• Similar to Zn++ (binds proteins), and to Ca++
Exposure to Cd - t1/2 = 7.4-18y
• Air - 25-40% retention– Mostly occupational– Ambient air 1ng/m3 (20-50ng/day)
– Tobacco smoke major inhalation source (1.5-2ug/cig)
• Water (naturally at <10ng/l)
– In salt waters as CdCl2, in fresh waters as CdCO3
• Soil– Deposition from air– Municipal sewage on agricultural soil– Phosphate fertilizers
• Food - 5-10% retention (10-50ng/d to 200-1000ug/d)
– Main source of human exposure (plants bioaccumulate Cd)– Leafy vegetables, grains, cereals– Some seafoods
EPA max 0.01mg/l, (goal 5ug/l)
OSHA air 200ug/m3
Cd Health effects• Known human carcinogen (lung cancer) (air 1ug/m3)
• Accumulation in liver, kidney (t1/2=10-20y), and skeleton over lifetime - Very low excretion (0.005%/day)
• Nephrotoxicity due to Ca++ ion uptake inhibition (free intracellular Cd ions; Metallothionein)
• Mechanisms: Enzyme inhibition, metal co-factor displacement, oxidative damage (lipid peroxidation)
• Antagonist of nutritional metal intake (role of deficiencies in toxicity, protein in diet, vit. C)
• Newborns and children most sensitive
Mercury - Hg• Unique properties and rare on earth crust, but also
ubiquitous • Multiple uses (thermometers, UV light lamps, catalyst, batteries,
electrical apparatus)
• US sources: chloralkali industry and coal fired power plants (40%); also pulp and paper industry, incineration, smelters, gold mining (Amazon)
• Also natural sources (volcano eruptions)• Elemental Hg is oxidized to Hg++ and biotransformed to
organic forms (mostly methyl)• Bioaccumulates in fat tissue - fish intake
Hg Health effects• Brain is target organ: Neurotoxicity, psychomotor
effects, brain damage (fetus)• Poisonings
– Minamata Bay acute toxicity (Japan) (11mg/g)
– Iraq 1971-72, bread - MeHg as fungicide
• Women of childbearing age and children are subpopulations of highest concern
• Enzyme inhibition (-SH binding)• Na+ and K+ membrane permeability• Nephrotoxicity• Se protective?
FDA guideline for fish 0.5ug/gCritical daily dose 300mg
Nickel - Ni
• Occupational toxicity - inhalation - Ni(CO)4
• Water contamination through leakage • Carcinogenic forms - Ni, Ni2S3, NiOx
– DNA and protein crosslinking– Chromosomal aberrations– Oxidative processes
• Competition with essential metals• Skin contact exposure• Crosses the blood-placenta barrier• Mg protective?
OSHA air level 7ug/m3 (occupational)No drinking water safety level
Arsenic -As• Oxides, AsO3, H3AsO3, H3AsO3
• Uses: Insecticides, rodenticides, herbicides, fungicides, preservatives, pigments, vet med.
• Sources: Natural processes, fossil fuel combustion (fly ash particulates), smelting (AsH3)
• Microorganismal oxidation, methylation (organic forms)
• Groundwater and surface water contamination– 350,000 US residents above safe level– Mostly in Asia (India, China), South America (Chile)
• Urban air (0.02ug/m3), soil (0.2-40ug/g)
• Food - fish
EPA safe level 50ug/l (drinking water)
Arsenic Health Effects• Inhalation, ingestion, skin contact
– Liver, kidneys, spleen, intestine (lung), skin, hair, nails
• Toxicity higher for water soluble forms (As3+), metabolic transformation (methylation detox)
• CNS effects (motor activity)• Carcinogen (bladder, kidney, skin, liver, blood, lung and
colon (inorganic forms) (0.35-1.14mg/l)
• Capillary injury - “Blackfoot” (gangrene)• Teratogen• Reacts with -SH: enzyme inhibitor (antidote BAL)• Uncouples oxidative phosphorylation• Oxidative processes (SOD, CAT, GPX, GST inhibition)