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)