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Flashcards in Toxicology Deck (17)
1

carbon monoxide

Air Pollutant
Asphyxiant (along with cyanide)

Part of EPA six criteria for Air Quality
- CO, SO2, NO2, Ozone, PM, Lead

Source:
- Vehicles>>>>fire

Acute Respiratory Health Effects

2

Sulfur Dioxide (SO2)

Source: Fossil Fuel, mostly coal

Environmental Problems: Acid rain, pH change in soil, metal leaching

Health effects:
- Water soluble so damages upper airways
- STRONG association with ASTHMA

Concentration and Effect:
3 ppm: easily detected odor
10 ppm: URI
20 ppm: Irritating toeyes
50-100ppm: max. tolerable

Symptoms:
- Acute:
- Irritation, cough, burning, lacrimation, difficulty
swallowing
- Vomiting, diarrhea, abdominal pain, fever, headache,
vertigo, agitation, tremor, convulsion, pulmonary edema
- Toxicity most severe in patients with lung problems:
asthma, emphysema, bronchitis

- Long term:
- Aggravation of chronic cardiopulmonary disease
(asthma, chronic obstruction, coronary artery disease)
- Children: reduced lung function, increased upper
respiratory infections

Pathophysiology:
- SO2 + moisture in airways= SULFUROUS ACID
- Irritation

3

Nitrogen Oxides

Source:
- Power Plants
- Cars

Major source of Ozone
Not very water soluble
- penetrates deep into lungs

Potent respiratory tract toxin
- Clinical Features
- Bronchitis, pneumonia, hemorrhagic pulmonary
edema, alveolar damage

- Pathophysiology
- May cause lipid peroxidation, decreased ciliary
movement, bronchoconstriction, enzyme inhibition

Toxicity:
- Decomposes in alveoli to nitrous acid (NHO2),
nitric acid (HNO3), and NO (vasodilator) on contact
with moisture

4

Ozone

O3

Bluish gas, no or slightly pungent odor

5

Ethanol

EtOH
Produced by yeast

Many Therapeutic Uses

1 unit = 10ml EtOH = 8g EtOh

Absorption:
- Rapid
- Food decreases rate in SI

Transport:
- To liver

Distribution:
- Vd correlates with total body water (40 L)
- Conc. depends on water conc.
- Found in lipids also (brain)

BAC
- Grams of EtOH/100ml blood
- 1 drink results in .03%
- Elimination is 1/2 drink per hour

Metabolism:
- Mostly by ADH in LIVER, stomach
- Aspirin inhibits ADH availability in stomach, and women have less ADH in stomach

ADH follows zero order (saturation kinetics)
- Average rate is 6-8 g EtOH/hr (3/4-1 drink)

Pharmacology
- CNS: Depressant
- Facilitates GABA
- Inhibits NMDA glutamate receptors

- Respiratory: Little effecct until high lvls (depress brainstem drive)

CV: Vasodilation (hypothermia), Increase HDL and decrease LDL (french paradox)

Renal:
- Increase urine flow: diuresis by two mechanisms, volume effect and inhibition of ADH

Sexual Function:
- Frontal lobe dis-inhibitor
- Depressant
- Gonadal toxin

GI:
- Low dose stim appetite
- High dose depress appetite (due to high calories)

Liver:
- Stimulate cytochrome p450
- Produce ROS
- Toxicity
- Fatty liver, toxic hepatitis, cirrhosis

Acute Alcohol Poisoning
- Relaxed-- Euphoric-- Excited-- confused--stupor--COMA--DEATH

Acute may cause HYPOGLYCEMIA due to inhibiting GLUCONEOGENESIS

Chronic Alcohol Abuse:
- Loss of appetite
- Vitamin and nutrient deficiencies
Ketotic (Wernicke- Korsakoff syndrome)
- Stomach ailments, ulcers and diarrhea
- Cardiomyopathy
- Coagulation defects
- Sexual impotence

6

Isopropanol

Alcohol of Therapeutic use

Characteristics
- Burning, bitter taste
- 2nd most ingested alcohol

Source:
- Rubbing alcohol (70%)
- Windshield wiper fluid (50-85%)
- Antifreeze (40-55%)
- Window Cleaner (0-25%)

Kinetics
- Rapid, complete uptake from GI tract
- Metabolism to acetone
- Slow elimination in kidneys (20-50%)
- Lungs acetone breath

Toxicity
Twice as potent CNS depressant as EtOH

7

Methanol

CH3OH

Characteristics

8

Ethylene Glycol

Characteristics

9

Arsenic

Metal
AsIII most toxic

Bioaccumulate: NO
- Half Life: 3 days
- Major route of exposure: lung, GI

Major target organ
- Short Term:
- Liver
- Kidney
- Heart
- Lung
-Long term:
- Hair, nails, skin (KERATIN), binds to sulfhydryl groups in hair and nails

Major source
- Pesticide, Medicine (chemo), Glassware paint
- FOOD/Water
- Occupational inhalation

2nd most common Heavy-Metal induced Death in USA (CHILDREN)

Pathophysiol
- Inh. mito enzymes (lower ATP, higher ROS
- Inh. SH enzymes

Symptoms:
- 70-180 mg: LETHAL
- Nausea, GI discomfort, Gastric bleeding, vomiting
- Hepatosplenomegaly
- Cardiac arrhythmia, vasodilation
- Constriction of throat, difficulty swallowing
- Shock, hypoxic convulsion, coma, death

Treatment:
- Fluid replacement, BP support (dopamine)
- Chelation

Current EPA Acceptable LVL:
- 10 mcg/L= 1/5000 cancer

10

Cadmium

Metal

Bioaccumulate: YES!!!
- Half life 10-30 years

Major target organ
- Lung: COPD, bronchitis, emphysema
- CV: Systolic HTN
- BONE: Itai-Itai (osteomalancia, Ca metabolism disrupted by vit D metabolism decrease in kidneys
- Cancer

KIDNEY!!!!!, renal tubular disease, proteinuria, Fanconi's syndrome in 50% of patients with 300 mcg/g kidney


Major source
- FOOD: plants uptake from soil, shellfish, meats (liver, kidney)
- SMOKING 1mgCD/year
- Normal daily intake: 10-40 mcg/day

Pathophysiol
- GI absorption: 5-8 %
- RESPIRATORY: 15-30%
- Transport:
- Blood
- Liver
- Kidneys
BODY BURDEN MOSTLY IN KIDNEYS

11

Lead

Metal

Bioaccumulate: YES
- Oral uptake: 5-15 adult (41% child)
- RETENTION: (5% adults)(32% children)
- Inhalation is very efficient at absorption/retention

Major target organ
- CNS
- Bone
- GI
- LOWERS IQ
- Blood

Major source
- FOOD
- ENVIRONMENT: paint/lead dust
- Recreational shooting (blood Pb level >30%)
- 3 million tons of lead applied to older occupied housing
- Crawling children are exposed to lead from dust and peeling paint
- 1 million children at risk of lead poisoning (blood level >10 mcg/dl)

Pathophysiol
- >90 percent of lead sequestered in blood
- Storage
- 95% adults skeleton
- 70% children skeleton
- Soft Tissue
- 5% adult skeleton
- 30% children

Excretion in breast milk puts baby at risk

Crosses placenta so places the Fetus at risk also

Binds sulfhydryl groups

Disrupts mito function and interferes with oxphos

Neurotoxicity: Disrupts Ca dependent intracellular messengers and brain protein kinase C

Stimulates formation of inclusion bodies containing lead-protein

Higher intake in children, higher blood levels, higher risk for CNS toxicity

12

Mercury

Metal

Bioaccumulate: YES
- T1/2: 70 days

Major target organ
- CNS
- Kidney
- CV health damage
- Prenatal: retardation, blindness, cerebral palsy-like syndromes (fetal Minamata disease)

Major source
- Natural but exposed due to coal burning, (2-3x increase of atmospheric Hg)
- Biomagnification: Incremental increase in conc. of a contaminant at each level of the food chain
- Do not eat, shark, swordfish, king mackerel, or tilefish

Pathophysiol
- Organic (alklmercury) most toxic over inorganic
- Body burden: 15-35 g (50g)
- Daily intake 3-7 mg/kg

Dentistry: Amalgam contains mercury and is controversial for use

13

Dimercaprol

Chelator

14

Penicillamine

Chelator

15

Cyclodienes

POPs:
Dieldrin
Chlordane
Toxaphene

POPs are

16

Polychlorinated Biphenyls

POPS

PCBs

Use

17

Polybrominated diphenyl ethers

POPs

PBDEs

In rodents