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Safety Engineering
-Toxicology-
• Denotes the probability of injury or illness from contact or use
• Industrial Hazards
– Explosivity
– Ignitability
– Reactivity
– Toxicity
Hazardous 2
• Capacity of a substance to produce injury or illness
• Acute Effects
– Short term, appear shortly after exposure. Can be from single exposure
• Chronic Effects
– There is a latency, long period of time before you see effect
Toxic Substance 3
• Chemical Agents (poisons)
• Physical Agents (dusts under 5 m, fibers)
• Biological Agents (pathogens)
Toxic Hazardous Materials 4
• Toxicology is the quantitative and qualitative study of the adverse effects of toxicants on biological organisms.
• Toxicant is a chemical or physical agent that produces adverse effects on biological organisms.
• Poison is a toxicant that cause immediate death or illness when experienced in very small amounts.
Definitions
• How toxicants enter the organism
• How toxicants effect the organism
• How toxicants are eliminated from (leave) the organism
All substances are toxic if taken in the wrong quantities.
Toxic Hazardous Materials 5
So Toxicology is the study of:
• Inhalation (mouth or nose to lungs) then into blood(+*)
• Ingestion (mouth to stomach) then into blood(+)
• Injection (cuts, punctures in skin) into blood
• Dermal absorption (through skin) into blood(+*)
+ Involve membrane transport
* Greatest threats in industry
How toxicants enter organism 6
Routes of Exposure 7
Inhalation (lungs) Most important route if exposed to gases, vapors, mists, aerosols.
– Influenced by respiration rate, concentration, duration.
Key factors for gases and vapors:
• solubility and reactivity
Key factors for aerosols:
• particle size and solubility respirable size: 0.1 m to 10 m
• < 5 m reach alveolar region
Certain Effects of Chemicals on the Lungs
• Irritations – acid mists (HCl)
• Edema – phosgene (COCl2)
• Emphysema – smoke (esp. tobacco)
• Fibrosis – silicon dioxide (SiO2)
• Cancer – asbestos (mesothelioma)
Routes of Exposure 8
Skin absorption
• Depends on site of contact
temperature (vasodilatation)
thickness, blood flow
• Depends on skin condition
integrity; pH
• Time-dependent (duration)
• Properties of the toxin
concentration
reactivity
solubility (in fat/water)
molecular size
Routes of Exposure 9
Ingestion (mouth)
Rare, but contamination can = intake
mucociliary action of respiratory tract
• Stomach Gastrointestinal tract bloodstream
• Absorbed - systemic injury
• Liver, kidney; Detoxification process
Inflammation
cirrhosis - fibrotic liver disease
malignant tumors
• Factors: physical state, duration
Routes of Exposure 10
Injection
Directly into bloodstream “sharps”, needles, broken glassware
skin puncture or injuries
• Bypasses protective mechanisms
• Usually rare in workplace primarily associated with bloodborne pathogens
(biomedical facilitates)
especially hazardous in health care industry
• Carcinogen - causes cancer
• Mutagen - causes chromosome damage
• Reproductive hazard - damage to reproductive system
• Teratogen - causes birth defects
Effects of Toxicants 11
Irreversible Effects
May or may not be reversible
• Dermatotoxic – affects skin
• Hemotoxic – affects blood
• Hepatotoxic – affects liver
• Nephrotoxic – affects kidneys
• Neurotoxic – affects nervous system
• Pulmonotoxic – affects lungs
• Excretion through kidneys, liver and lungs
• Detoxification is the biotransformation of chemicals into something less harmful
• Storage in fatty tissue
Elimination of toxins 12
• Determine toxic effect – local effect, target organ, systemic effect, acute, chronic effects.
• Determine toxic dose – identify the dose that will produce a given toxic effect.
Toxicity Studies 13
Difficulties in Toxicological studies
No ethical way to get human volunteers, hence need to use “model” systems of rats, cats, dogs, rabbits, etc. High doses in animals are needed to predict possible hazard to
humans Specificity of individual response
• Allergy or immunity • Statistical study required • Organism specific response, not applicable to humans • Dosage response • Response time, latency, acute versus chronic • Difficulty in measuring intended variable (lead in liver measured
by lead in blood)
• Run test on “large” population
• Given same dose (usually in dose/body mass)
• Determine the number or fraction of individuals
that have a response
Dose-Response Relationship 14
Basic Concepts
• Dose and response can be measured. • Response magnitude is related to dose. • All toxic interactions follow a dose-response relationship. • With increasing dose, there is an increase in the number
affected and/or an increase in the intensity of the effect
Dose = (Concentration) x (Time)
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average response at a given dose
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20• Repeat tests using different doses
• Find average response to each dose
• Plot Response versus logarithm of dose
• Forms Sigmoid shaped curve
Dose-Response Relationship 15
This relationship is unique for each chemical
Dose units
• Quantity per unit mass (mg/kg)
• Quantity per unit area of skin surface (mg/m2)
EDf – Effective dose for f percent of population. Reversible response
TDf – Toxic dose for f percent of population. Undesirable response that is irreversible
LDf – Lethal dose for f percent of population.
Dose-Response Terms 16
TDlo – Toxic dose low - lowest dose for effect LD10 – Lethal dose 10% - dose that causes death in 10% of the test population LD50 – Lethal dose 50% - dose that causes death in 50% of the test population TClo – Toxic concentration low - used to express toxic concentration via inhalation LC10 – Lethal concentration 10% - dose that causes death in 10% of the test
population –via inhalation LC50 – Lethal concentration 50% - concentration that causes death in 50% of the
test population via inhalation
Lethal dose 17
Agent LD50 (mg/kg)
Ethyl Alcohol 7060
Sodium Chloride 3000
Naphthalene 1760
Ferrous Sulfate 1500
Aspirin 1000
Formaldehyde 800
Ammonia 350
Dextromethorphan Hydrobromide 350
Caffeine 192
Phenobarbital 150
Chlorpheniramine Maleate 118
DDT 100
Strychnine Sulfate 2
Nicotine 1
Dioxin 0.0001
Botulinus Toxin 0.00001
Toxicity Rating (LD50) Dose for 70 kg person • Super Toxic < 5 mg/kg • Extremely Toxic 5 – 50 mg/kg • Very Toxic 50 – 500 mg/kg • Moderately Toxic 0.5 – 5 g/kg • Slightly Toxic 5 – 15 g/kg • Practically Nontoxic >15 g/kg
Target Organs 18
Organs selectively affected by harmful agent:
– Lungs (pneumotoxicity)
– Blood (hematotoxicity)
– Liver (hepatotoxicity)
– Kidneys (nephrotoxicity)
– Nervous system (neurotoxicity)
– Immune system (immunotoxicity)
– Embryos/fetuses (reproductive & developmental toxicity)
Target Organ Effects 19
Toxins Target organ
Signs &
Symptoms Examples
HEPATOTOXIN LIVER JAUNDICE CCl 4
NEPHROTOXINS KIDNEY EDEMA HALOGENATED
HYDROCARBONS
NEUROTOXINS CNS NARCOSIS BEHAVIOR MERCURY
HEMATOPOIETIC SYSTEM HEMOGLOBIN CYANOSIS CO, CS 2
LUNG AGENTS PULMONARY TISSUE COUGH,CHEST
TIGHTNESS SILICA, ASBESTOS
REPRODUCTION TOXIN
REPRODUCTIVE SYSTEM BIRTH DEFECTS LEAD
CUTANEOUS AGENTS SKIN RASHES; IRRITAION KETONE
EYE HAZARDS EYES CONJUCTIVITIS ORGANIC SOLVENTS
Exists in elemental form and in the tri- and pentavalent oxidation states, copper mining & smelting
Toxicity rating: RAs –X < As+5 < As+3 < AsH3
Absorption, distribution and excretion
Variable absorption, soluble salts well absorbed and insoluble salts are poorly absorbed
Distribution: liver and kidney, hair and nails
Excretion
a) Excreted in urine
b) Half-life about 2 days
Biochemical mechanism of toxicity
As+5 reacts with thiols, uncouples energy production
As+3 uncouples oxidative phosphorylation
Toxic Effects 20
Arsenic (in detail)
Arsenic poisoning 1. Early signs and symptoms
Diarrhea
Skin pigmentation
Hyperkeratosis
Edema of lower eyelids, face and ankles
Garlic odor of breath
2. Progression Dermatitis and keratosis of palms, soles – skin cancer
Enlarged liver
Renal injury
Peripheral neuropathy (legs more than arms – contrast to lead)
Encephalopathy
Aplastic anemia, lung & skin cancer
Arsine (AsH3)
1. Gas
2. Hemolysis
Toxic Effects 21
Arsenic (cont.)
Acute cadmium poisoning • Oral – gastrointestinal effects
• Inhalation – local irritation of respiratory tract
Chronic cadmium poisoning • Kidney - Most cadmium sensitive organ
• Lungs After inhalation
Emphysema
• Cardiovascular – hypertension
• Bone
• Testes – sensitive after acute, not after chronic
Toxic Effects 22
Cadmium
Metal fume fever, Cd, An, Mg Batteries, welding, coal & fossil fuel burning
Acute lead poisoning • Rare
Chronic inorganic lead poisoning (plumbism) • Gastrointestinal effects
More common among adults
Referred to as lead colic, often symptoms for which patient seeks relief
Organic lead poisoning • CNS: insomnia, nightmares, irritability, anxiety, anemia, kidney
• Car exhaust is organic
Toxic Effects 23
Lead
CNS: Central Nervous System
Paint (old), plumbers, US moonshine, pottery glazing (old), water pipes (old), was in gasoline, Initially in liver & kidneys
Chronic mercury poisoning • CNS effects:
• Mercury vapor (elemental mercury): largely neuropsychiatric: depression, irritability, shyness, insomnia, emotional instability, forgetfulness, confusion, excessive perspiration, uncontrolled blushing (erethism) and tremors
• Methylmercury Paresthesia (abnormal spontaneous sensation, ex. tingling)
Visual changes (constriction of visual field)
Hearing defects
Dysarthria (speech disorder)
Ataxia (unstable gait, coordination, loss of muscle movement)
Fetus is extremely susceptible
• Inorganic mercury: little known
1. Kidney: target organ of inorganic mercury toxicity
a) Organomercurials-high fetal toxicity
Toxic Effects 24
Mercury
Aluminum
Low toxicity, aluminum hydroxide is antacid
Shaver’s disease – by inhalation in industry – lung fibrosis
Antimony: toxicity similar to arsenic, garlic breath
Beryllium
Mining
Berylliosis / granuloma
Chromium
Necessary for glucose metabolism (trivalent)
Insoluble hexavalent cause lung cancer by inhalation
Toxic Effects 25
Other Metals
Cobalt Essential element in vitamin B12
Polycythemia (increase in RBC)
Goiter
Cardiomyopathy – beer drinkers
Copper Essential element
Wilson’s disease (hereditary, retains copper)
Metal fume fever
Fluoride Reduces dental caries at 0.7-1.2 mg/1 or ppm
Dental fluorosis (discoloration and/or pitting) in children above 2 ppm
Brittle bones at higher concentrations
Discolors leaves
Toxic Effects 26
Other Metals
27
Iron, Fe2O3
Metabolic acidosis – cell death through hemosiderin
Manganese Manganese pneumonitis
CNS: Parkinson’s disease
Nickel Dermatitis (nickel itch, jewelers itch)
Nickel carbonyl (Ni[CO]4) – carcinogenic, highly acutely toxic, pneumonitis leukocytosis, temperature, delirium
Nickel subsulfide – carcinogen in humans (nose)
Toxic Effects 27
Other Metals
Phosphorus Used in matches, rat poisons, fireworks
GI upset – vomitus may be phosphorescent
Liver injury – jaundice
Chronic – necrosis of bone “phossy jaw,”
Selenium Essential (glutathione peroxidase)
Excess in livestock – “blind staggers or alkali disease” characterized by lack of vitality, loss of hair, sterility, atrophy of hooves, lameness and anemia
Excess in humans – discolored/decayed teeth, skin eruptions, GI distress, partial loss of hair and nails, garlic breath
Liver injury
Silver Skin – argyria (blue skin)
Toxic Effects 28
Other Metals
GI - gastrointestinal
Thallium Rodenticides, ant poison (discontinued many countries)
Distributed like potassium, mining
GI irritation – acute
Alopecia
Uranium Kidney injury
Zinc Essential
Acute oral toxicity: vomiting, diarrhea, fever
Inhalation: metal fume fever - fever
Toxic Effects 29
Other Metals
• Acute – CNS depression, defatting skin, myocardium
• Chronic – liver, kidney
• Chlorinated – solvents (CNS/skin/cancer)
CCl4 - carcinogenic, liver, kidney
• Brominated – fumigant, solvents (CNS/skin)
• Fluorinated – refrigerants (ozone layer/myocardium)
Toxic Effects 30
Halogenated Hydrocarbons
- low flammability, excellent solvents
• Benzene – CNS depression, leukemia
• Toluene – CNS depression (glue sniffers)
• Styrene – dermatitis, CNS depression
• Poly-aromatic hydrocarbons – doxin, PCBs, biphenyls – liver/thyroid/skin
• Nitrobenzene – CNS, jaundice (liver effect), methemoglobin - blue lips & fingernails
• Phenol – CNS, liver, kidney, skin effects
(absorbed readily through skin)
Toxic Effects 31
Aromatic Hydrocarbons
32
Methanol – alcohol dehydrogenase- blindness-treat with ethanol
Ethanol – CNS depression, fetal alcohol syndrome, liver cirrhosis
Isopropanol – CNS depression, gastritis
Toxic Effects 32
Aliphatic Alcohols
Ethylene glycol monomethyl ether (EGME) CH3OCH2CH2OH Disrupts sperm development
Developmental toxin – day 7,8-neural tube; day 10-11-digit/paw effects, brain, liver, and kidney
Ethylene glycol monoethyl ether (EGEE) CH3CH2OCH2CH2OH Testicular degeneration
Reproductive/developmental toxins, but less severe
Propylene glycol monomethyl ether (PGME) Not a reproductive/developmental toxin
Toxic Effects 33
Glycol Ethers
• Acetone (dimethyl ketone) – CNS, skin effects
• Methyl ethyl ketone – CNS, skin, reproductive and developmental effects
• Methyl butyl ketone – CNS and peripheral nervous system effects
Toxic Effects 34
Ketones
• Organophosphates – cholinesterase inhibitor; parathion, dursban, dichlorvos,
• Organochlorine – CNS; DDT, aldrin, kepone, mirex
• Carbamates – reversible cholinesterase inhibitor; sevin
• Chlorophenoxy – liver, kidney, CNS; 2,4-D, agent orange, 2,4,5-T
• Pyrethrins – CNS effects; resmethrin
Toxic Effects 35
Pesticides