week 9- environment Flashcards

(62 cards)

1
Q

• Common wastewater contaminants:

A

o antibiotics, perfumes, detergents, drugs, steroids, disinfectants, etc.
o surface water and ground water
o runoff from large areas → concentrated
o potential risks to human health if → drinking water

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2
Q

• toxicants: sources, transport/transform, removal, effects:

A

o S: industry, transportation, sewage plants, agriculture, fire
o T: sun, winds, clouds
o R: rain or dry deposition
o E: drinking water, human health, ground water, agriculture, smog, soils

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3
Q

• Airborne toxicants:

A

o Volatile chemicals travel far in winds
o Polychlorinated Biphenyl: similar to dioxin. Industry. carcinogenic, neurotoxin, endocrine disruptor
o PCBs: carried 1000s miles to arctic, found in polar bears and seals
o At low latitude, pollutant evaporation > deposition
o high: deposition > evaporation

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4
Q

• persistence:

A

o Some chemicals more stable, persist longer in environment
o DDT and PCBs are persistent
o Bt toxin in GM crops is not persistent
o Temp, moisture, sun, etc, affect rate of degradation
o Most toxicants degrade into simpler breakdown products
o Some of these are also toxic
o (DDT breaks down to DDE, also toxic)

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5
Q

• Bioaccumulation:

A

o Poisons accumulate in tissues
o body may excrete, degrade, or store toxicants
o Fat-soluble ones are stored.
o DDT is persistent and fat soluble → builds up in tissues
o → can move up the food chain

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6
Q

• Biomagnification:

A

o Poisons move up the food chain
o At each trophic level, chemical concentration ↑= biomagnification.
o DDT conc ↑ from plankton to fish to fish-eating birds

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7
Q

• Dose-response analysis:

A

o to determine toxicity by measuring response to different doses
o Lab animals used →Mice and rats breed quickly
o relevant to humans dt shared mammal physiology
o plotted on dose-response curve

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8
Q

• dose-response curve:

A

o threshold= dose at which response begins
o LD50= dose lethal to 50% of test animals
o Allow to predict effects of higher doses
o Extrapolation: predict how will affect humans at various conc
o usu response ↑ w dose
o OR: curve may not be linear
o endocrine disruption: may ↓

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9
Q

• endocrine disruption:

A

o Some chemicals in vivo “mimic” hormones
o Can bind → inappropriate response
o Normal: hormone system works w tiny conc
o → so it can respond to tiny conc of toxicants

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10
Q

• Signal words:

A

o relative acute toxicity of pesticide seen on label
o The (toxicologically) appropriate signal word MUST appear on every pesticide label
o The three possible signal words are:
o 3 words: danger, warning, caution, (notice?), (poison)

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11
Q

• CAUTION:

A
o	lowest toxicity 
o	All pesticides w LD50 > 500 mg/kg must display 
o	2 groups:
o	 “Relatively nontoxic” (>5000)
o	“slightly toxic” (500 – 5000)
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12
Q

• WARNING:

A

o intermediate toxicity
o All pesticides w LD50 50-500 mg/kg must display
o = “moderately toxic”

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13
Q

• DANGER, POISON:

A

o highest toxicity
o All pesticides w LD50 ↓ 50 mg/kg must display
o = “highly toxic”
o POISON= same thing, Legally defined term
o Label must have both “DANGER” and “POISON”
o also skull and crossbones icon

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14
Q

• factors affecting toxicity:

A

o Sensitivity to toxicant can vary w sex, age, weight, etc
o Babies, older, poor health → more sensitive
o acute = high exposure in short period of time
o chronic = lower amounts over long period of time

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15
Q

• synergistic effects:

A

o Substances can interact when combined
o → mb effects greater than sum of their individual effects
o Challenge: no way to test all possible combinations!
o → environment has complex mixtures of many toxicants

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16
Q

• Exposure:

A
o	route (site) helps determine dose: diff routes → diff rates of absorption
o	Ex: Dermal (skin), Inhalation (lung), Oral ingestion (GI), Injection
o	route important if there are tissue-specific toxic responses → local or systemic
o	Time: how long exposed
o	Duration and freq contribute to dose, both may alter toxic effects
o	Acute =  usu single exposure
o	Chronic = mult exposures over time (frequency)
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17
Q

• Transport and storage of toxins on body:

A

o T: Lymphatics, blood; usu via blood protein that binds toxicant, eg a lipoprotein
o S: Liver, Lungs, Kidneys, Bone, Adipose (fat)
o mb stored in one reservoir, later transported elsewhere
o Storage site may or may not be site of toxic effect
o Pb stored in bone, but toxic to liver
o DDT stored in fat but toxic via prolonged gradual release

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18
Q

• Detoxification in vivo:

A
o	Some chem transformed/metabolized to aid excretion
o	Detox → less toxic metabolic product
o	Kidney → urine
o	Liver → feces, bile
o	Lung → expired air
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19
Q

• Types of toxicants:

A

o Carcinogens → CA
o Mutagens → mutations in DNA
o Teratogens → birth defects
o Allergens → unnecessary immune response
o Neurotoxins: damage nervous system
o Endocrine disruptors: interfere w hormones

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20
Q

• Environmental toxicity assessment:

A

o Toxin exposure hx most important factor to determine appropriate testing
o Detailed chronological hx, determine jobs, hobbies, geographical areas
o Acute & Chronic:
o In utero
o Childhood: vaccines, meds, food, water, air, environment, hobbies
o Dental: Hg, Ni
o Workplace: sick-buildings, agriculture, industry, military
o Age of house: Pb paint phased out 1978 (now only 0.06% Pb allowed)

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21
Q

• Heavy metal toxicity:

A

o Pb, Hg, Cd, As, Mn, Ni → Inorganic and Organic salts
o Heavy metals = protoplasmic poisons
o Impair cell fxn
o Astringent, corrosive, caustic to skin
o Lethal to microorganisms
o Accumulate in body on chronic exposure
o Damage liver, kidney, bone marrow, GI mucosa, neurons, skin
o not immediately recognized dt wide range of non-specific sxs

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22
Q

• mecanisms of heavy metal toxicity:

A
o	usu mult
o	inhibit/potentiate Enzyme/cofactor 
o	Disrupt membrane, transport processes
o	Disrupt mitochondrial fxn → fatigue
o	↓ neuronal fxn & nerve conduction
o	Ability to bind to -SH groups on proteins & amino acids
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23
Q

• Lab tests for heavy metals:

A
o	Hair
o	Serum
o	RBC analysis
o	Urine challenge: DMPS, DMSA
o	Blood chem, CBC, CC, CMP
o	Genetic: detox, cord blood, placenta
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24
Q

• Blood tests for heavy metals:

A

o Best for short-term acute exposure
o Metals cleared rapidly from blood, accum in storage depots
o T1/2 blood (days): long term deposition
o Pb 30-60 d: bone 25 yr
o Cd up to 120 d: liver & kidney 10-20 yr
o Hg 60-70 d: organic forms lipid soluble  adipose, PNS, CNS for yrs
o As 2-12 hrs: liver, kidney, muscle, skin, brain
o Mn 10-42 d: bone and brain
o Ni 24 hrs: lungs, thyroid, adrenals

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25
• Serum “normal” levels heavy metals:
``` o As: 0.0 – 62 g/L o Cd: 0.0-5.0 g/L o Pb: kids ↓ 5 g/dl, adults ↓25 o Mn: 4.2 –16.5 g/L (whole blood), 0.0-7.8 (serum) o Hg: 0-60 g/L o Ni: 0.6-7.5 g/L ```
26
• Hair test for heavy metals:
o 1979 EPA: “hair is representative tissue for biological monitoring of most toxic metals” o 2001 JAMA: UNRELIABLE o Best as screening test (but not for Pb in kids) o (+) MUST confirm w blood or provocative urine testing o CDC, for kid Pb poisoning: 57% sens, 18% false (-) o High inter-lab variability
27
• Impaired Hg excretion:
o Collected first hair cuts in fully immunized infants o 94 autistic kids, 45 controls o Average Hair Mercury: 0.25mcg/g in autistic kids o 4.90mcg/g in controls o Autistic kids ↑ prenatal Hg exposure o Autistic kids have inherent problem excreting heavy metals → large risk toxicity w very small exposures
28
• Genetic findings in autism:
o MTHFR, ADA: ↓ glutathione o GST M1-null: ↑ susc Hg and xenobiotic toxicity, ↑ body burden Hg o ALAD: ↑ susc Pb toxicity; ↑ body burden Pb o PON-1: ↑ susc pesticide toxicity o HLA-DR4: ↑ allergy and intolerance to heavy metals
29
• Urine tests for heavy metals:
o Best test for chronic toxicity (most cases) o Random: indication of “ambient” levels o Provocative challenge test: o best estimate of body burden o no good test for accurate total body heavy metal burden
30
• chelating agents:
o for reduction of body burdens of toxic metals. o DMPS, DMSA, D-Penicillamine, EDTA o chemically bind w (chelate) metals, minerals, chem toxins o actually encircles a mineral or metal ion, excrete via urine and feces
31
• Desirable Attributes for Chelating Agents:
``` o Gain access to the metals o Tightly bind and control metals o Not injure recipient o Accelerate mobilization/ removal of metals o Cheap o Easy to administer ```
32
• Chelating agent effectiveness, depends on:
o 1) affinity of chelator for the metal o 2) distribution of chelator to parts of body where metal is o 3) ability of chelator to mobilize metal from body once chelate is formed
33
• DMPS, DMSA affinities for metals:
o DMPS: Hg, Pb, Ag, Cd, Ni, As, An, Cu, Mo, Zn, Mn | o DMSA: Pb, Cd, Hg, Ag, Ni, As, Mo, Cu, Zn, Mn, Fe, Tin
34
• FDA-approved chelating agent:
o Ca-Na2-EDTA: 1950s o DMSA: for Pb poisoning in kids, 1990 o DMPS: NOT FDA approved (Informed consent required!!)
35
• Ca-Na2-EDTA:
o Oral: only ~ 5-10% absorbed. Not appropriate for challenge test o Suppositories: Not optimal for challenge testing; effective for long-term detox of Pb o Urine levels (↑) after IV EDTA: o Pb 147x, Zn 32x, Mn 15x, Fe, Cd 7x, An 4x
36
• DMPS:
o 2-3-dimercapto-1-propane sulfonate o Official drug in Soviet Union since 1958, registered w German health authorities (Dimaval) o T1/2 oral ∼ 9 hr (~ 50 % absorbed ) o T1/2 IV ↓1 hr o Minor penetration into RBCs o Principal route of excretion is renal o CMP, CBC, CCLR (renal creatinine clearance) required before administration o Affinity for Hg o Don’t use if sensitive to sulfur compounds
37
• DMPS Urine Provocative Challenge Test
o Baseline 24 Hr urine tested for toxic elements o Provoked 6-hr urine tested o 250 mg (50 mg/ml) DMPS given by IV push o Dental techs: 5 ug Hg/ 6 hr (before) → 424 (after) o Dentists: 3, 162 o Controls: 1, 27
38
• DMSA:
o 2-3-Dimercaptosuccinic Acid (Dithiol/dimercapto cousin to BAL) o Least toxic of this class o Synthesized 1940’s by British chemist L.N. Owen o Extensively investigated by the Chinese o Oral (peds rectal), Water soluble, active in extracellular space o CMP, CBC, CCLR required first o Determine sensitivity to sulfur drugs
39
• DMSA elimination:
o Absorption rapid but variable ~25-49% o Rapid hepatic metabolism. ~90% cysteine disulfides, ~10% unchanged o ~75% renal elimination in 24 hr (↓2 d half life) o ~40-80% fecal elimination
40
• DMSA application:
o Affinity: highest → Pb, Hg, As, Cd, Ni → lowest o Urine Provocative Challenge Test o FDA to tx Pb poisoning in kids o Dose: 30 mg/Kg/d divided in three doses (10 mg/Kg po TID) o Duration: per blood levels or clinical judgment. Many protocols exist
41
• DMSA potential side effects:
o Transient ↑ liver enzymes o Thrombocytosis o Nausea o Reversible neutropenia, dose dependent
42
• Sources of Pb:
``` o Lead Paint o Dust, Soil o Water (Pb pipes) o Industry o Hobbies o Traditional Ethnic Remedies o Gasoline (tetraethyl Pb): rid of Pb gas → ↓ blood Pb levels ```
43
• NOEL:
o No observable effect level o no toxic threshold for Pb o =no measurable level of Pb in body below which no harm occurs
44
• Pb absorption:
o Orally consumed Pb abs in place of Ca o Kids: 30-50% of Pb o Adults: 5-10% of Pb o ↑ during Pg o crosses placenta & BBB o BBB not complete until 6 mos → absorbed by CNS of fetus, infant o ↑Abs 5-10x in infants and young kids than adults
45
• Pb toxicity:
o Ssx: Irritability, anorexia, malaise, HA, constipation, abd pain “lead colic”, renal toxicity o “Acute lead encephalopathy” dt very high exposures = cerebral edema, ↑intracranial pressure → death o ↓: IQ, nerve conduction, Vit D metabolism, Hb synthesis
46
• Mechanisms of Pb toxicity:
o Pb binds enzymes w functional sulfhydryl groups → deactivates → impair oxidative balance o Inhibits: porphobilinogen synthetase, globin synthesis → coproporphyrin and ALA spill into urine o Anemia: usu micro/hypo, basophilic stippling, mb ↑ serum Fe
47
• Blood test for Pb:
o #1 for screening recent Pb exposure  EDTA tube o “Normal” for kids is ↓5 g/dl, adults ↓ 25 o If ↑, must report to Oregon Health Division o 10-70: provide care o > 70: hospitalize, chelation therapy
48
• Pb test sources:
o Whole blood: conc 75x > serum or plasma, highest correlation with toxicity. preferred test to detect Pb exposure o Hair: in apparent steady-state lead balance, correlates w blood Pb. Normal ↓5 μg/g. > 25 = severe Pb exposure o Urine: ↑ w Pb poisoning, but urinary elimination occurs for many d after a single exposure
49
• Pesticides:
o chems used to kill or control insects, weeds, fungi, rodents, microbes o = Insecticides, herbicides, fungicides, rodenticides, etc. o sprays, liquids, powders, granules, baits, foggers (total release aerosols) o Humans exposed w manufacture, mixing, applications of pesticides o Inhalation, Ingestion, Eye & skin contact
50
• types of pesticides:
o insecticides: Cholinesterase Inhibitors (Organophosphates and Carbamates), Organochlorines, Pyrethroids o herbicides: glyphosphate, Cholinesterase Inhibitors
51
• cholinesterase inhibitors:
o Organophosphates (OPs) & carbamates (CMs): o Cholinomimetic: inhibit ACh-esterase enzyme o ACh builds up in synapses, overexcites nervous system o → rapid twitching of some muscles, paralyzed breathing, convulsions, death (extreme) o Ops in chem warfare, nerve agents: Tabun, Sarin, Soman, VX o Ssx: SLUDGE: salivation, sweating, lacrimation, urination, diarrhea, gastric motility, emesis
52
• Physiology of CIs:
o Act in mins-hrs, depends on exposure level o inhibit either plasma pseudocholinesterase or RBC cholinesterase o Pseudo ↓ more rapidly, but recover more quickly than RBC cholinesterase o ↓ Pseudo: Hepatitis, cirrhosis, malnutrition, chronic alcoholism, OCPs o ↓ RBC cholinesterase: Hemolytic anemia
53
• Tests for CI exposure:
o Do both: plasma and whole blood o Baseline when worker not exposed for at least 30 d o RBC (true) cholinesterase, whole blood; identical to acetyl cholinesterase found in synapses; better reflection; CNS gray matter o Plasma (pseudo) cholinesterase; not identical; easy to assay; CNS white matter o 15-25% ↓ CI: slight poisoning o 25-35%: mod o 35-50%: severe
54
• Orgnochlorines:
o DDT, DDE, insecticides o Dichloro-diphenyl-trichloroethane o Moderately toxic, DDT banned in US in 1972, unless public health emergency (eg malaria outbreak) o 2004- banned world wide for agriculture (but India, N Korea, other) o used mainly to control mosquito-borne malaria
55
• toxicity of DDT:
o DDT → soil, runoff, streams, fish →concentrate in predatory animals o Acute: (low-mod exposure) N/D, ↑ LFTs, irritation (eyes, nose, throat), disturbed gait, malaise, excitability; (high) tremors, convulsions o Chronic: assoc maternal DDT blood levels & miscarriage; Blood & breast milk can be analyzed for DDT & DDE
56
• DDT storage in body:
o Metabolites readily stored in adipose o DDE: fat bx, metabolite implicated in breast CA, Liver CA death o DDE= 1,1-dichloro-2,2-bis(p-dichlorodiphenyl)ethylene o DDD =1,1-dichloro-2,2-bis(p-chlorophenyl)ethane
57
• Organochlroine testing:
o Fat, blood, urine, semen, breast milk o blood and urine: easy, may show low, mod, hi exposure o can’t show exact amount of exposure, or predict chance of health effects
58
• glyphosate:
o =”Roundup” (Monsanto) o =Broad spectrum herbicide to kill crop weeds o Non-selective, kills all plants: grasses, broad leaf, woody plants o extremely difficult to measure in environmental samples o “Roundup Ready” crops engineered to withstand exposure to glyphosate o allows herbicide applications after crop emergence, killing weeds but not crops (ex: soybeans)
59
• glyphosate toxicity:
o Acute toxicity is very low o Acute Oral LD50 = 4,300 mg/kg o Other toxins in Roundup: various surfactants (polyoxyethyleneamines, POEAs) o POEAs =serious irritants of respiratory tract, eyes, skin, contaminated w dioxane, a suspected carcinogen
60
• 24-hr urine glyphosate:
o to monitor exposure o farmers: 233 parts per billion (ppb) the day it was used o Non-hodgkins lymphoma pts 2.3x likely to have had contact with glyphosate
61
• Chlorophenoxy herbicides:
o “Agent orange” = 50-50 mix of two chemicals (2,4,D & 2,4,5,T) o was mixed w kerosene or diesel fuel & dispersed by aircraft spraying o 19 million gallons used in S Vietnam in Vietnam War o contaminated with TCDD, or dioxin → health concerns o Now banned o Brand= “Crossbow” (2,4-d)
62
• Chlorophenoxy herbicides toxicity:
o Acute exposure: stomach pains, V/D o Chronic: Carcinogen, may cause reproductive problems o Monitor exposure: GLCT of blood, urine, ASAP bc excreted in 24-72 hrs