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Industrial Toxicology. Industrial Hygiene IENG 431 Dr. Carter J. Kerk Industrial Engineering Department SD School of Mines Spring 2009. Assignment. Read Plog , Chapter 6 HW6

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industrial toxicology

Industrial Toxicology

Industrial Hygiene

IENG 431

Dr. Carter J. Kerk

Industrial Engineering Department

SD School of Mines

Spring 2009

  • Read Plog, Chapter 6
  • HW6
    • Find a chemical/product from where you live or nearby. Obtain an MSDS off the Internet. Write a 1-2 page evaluation of the product. Include discussion of how it might enter the body thru the 4 routes, handling requirements, and brief discussion of safe handling and use
    • Due Date?
  • Color ACB Plates: 98, 104, 106, 108, 110, 112
  • Toxicity: The ability of a substance to cause harm or adversely affect an organism
  • Toxicology: The science and study of harmful chemical interactions on living tissue
occupational toxicology
Occupational Toxicology
  • Workplace exposure to chemicals
  • You or someone you know has probably experienced an episode of toxicology
    • Injury or death due to:
      • Smoke inhalation
      • Confined space incident
      • Ingestion or absorption of a chemical
the dose response relationship
The Dose-Response Relationship
  • A time of exposure (dose) to a chemical, drug, or toxic substance, will cause an effect (response) on the exposed organism
  • If the amount or intensity of the dose increases, there will be a proportional increase in the response
  • Dose: The amount of a substance administered (or absorbed), usually expressed in milligrams of substance per kilogram of the exposed organism (mg/kg)
  • Response: The effect(s) of a substance; may be positive or negative
acute and chronic terminology exposure as well as response
Acute and Chronic Terminology: Exposure as well as Response
  • We previously discussed acute and chronic exposure
  • Acute exposure: short time / high concentration
  • Chronic exposure: long-term, low concentration
  • Acute response: rash, watering eyes, cough from brief exposure to ammonia
  • Chronic response: emphysema from years of cigarette smoking
possible response levels
Possible Response Levels
  • No response: at low dosage levels there may be no response at all
  • Threshold dose: the lowest level of dosage at which a response is manifested
    • NOAEL: no observed adverse effect level
    • NEL: no effect level
  • Above threshold dose: response can be positive up to a point and then could become toxic to the organism
  • Different people or organisms will exhibit a variety of responses
indicators of relative toxicity
Indicators of Relative Toxicity
  • Toxicity: ability of a substance to cause harm or have an adverse affect
  • How much harm?
  • What aspect of the population?
  • Notation:
    • LD, lethal dose
    • LC, lethal concentration
    • ED, effective dose
    • EC, effective concentration
ld 50 a measure of relative toxicity
LD50 – a measure of relative toxicity
  • Most common toxicity notation
  • Determined in the lab and based on an acute exposure to adult test animal
  • Lethal dose that produces death in 50% of the exposed population
  • LD50, 35 mg/kg, oral, rat
    • 35 mg of dose per kg of rat’s body weight, when administered orally, produces death in 50% of exposed population
  • Comparing the LD50 between two substances gives the relative toxicity between the two substances
how can we interpret animal test
How can we interpret animal test?
  • Animal tests can give an indication of relative toxicity which can be extrapolated to humans
  • Problems
    • Toxicity variance between organisms
    • Animal doses (strength or time) may be higher than realistic human exposures
    • On a body weight basis, humans are usually more susceptible to toxic effects, sometimes by a factor of ten
    • Therefore, human interpretation requires use of a safety factor
epidemiological studies
Epidemiological Studies
  • Prospective epidemiological study
    • Take a cohort (or group of individuals) with a common exposure
    • Follow through time to see if they develop disease
  • Retrospective epidemiological study
    • Take a cohort with a disease and trace back through time to see if there is a common exposure
  • These are difficult with many confounding factors, but are quite valuable
latency period
Latency Period
  • Long delay between exposure and disease
  • Some diseases may not develop for many years
    • Lung cancer may occur as much as 30 years after exposure to asbestos
  • This makes animal studies and epidemiological studies even more difficult, but also very valuable
toxicity data limitations
Toxicity data limitations
  • Although there is considerable toxicity data available, for most chemicals it is still limited
  • Less than 10% of the thousands of chemicals have regulatory or recommended standards for safe exposure
routes of exposure
Routes of Exposure
  • Inhalation
  • Ingestion
  • Absorption through the skin
  • Less common
    • Injection
    • Absorption through eyes and ear canals
  • Most common route of entry into body
  • Therefore our area of highest concern
  • Lungs are designed for efficient gas exchange between the air and bloodstream
  • Lungs have up to 1000 square feet of exchange area (about 32 feet by 32 feet)
  • Normal day’s breathing volume: 8 cu ft
  • Therefore great potential for toxins to enter bloodstream
  • ACB Respiratory System: 91, 96
skin absorption 2 nd most important route
Skin Absorption (2nd most important route)
  • Skin surface area is about 20 square feet (4.5 ft by 4.5 ft)
    • Compare to 1000 sq ft for lungs
  • Materials can be absorbed into blood stream just below the skin surface or toxins can be stored in fat deposits
  • Obviously workers can easily expose their hands into solvents, oils, chemicals, etc., plus these materials can be sprayed or rubbed on other parts of the body
  • Many chemicals are either soluble in water or in oil (fat, lipid)
    • The skin easily absorbs lipid-soluble materials
      • Solvents
    • Water-soluble materials are not easily absorbed
      • Lipid layer on skin provides a barrier
  • ACB Skin: 161
ingestion 3 rd most important route
Ingestion (3rd most important route)
  • Ingestion is not usually intentional
  • Unintentional ingestion
    • Failure to wash hands and face before meals
    • Eating/drinking in areas where airborne hazards exist
    • Lighting cigarettes with dirty hands
    • Application of cosmetics
    • Use of chewing tobacco or gum in contaminated areas
  • The digestive tract is moist and designed for efficient absorption
  • Surface area of intestines is greatly increased by small projections (villi)
    • Thin surfaces, highly vascularized
    • Materials easily transferred to bloodstream
  • ACB Digestive System: 98, 104
  • Less common
  • Possible hazards
    • Outdoor work, construction sites, hazardous waste sites, plants, animals, reptiles, insects, abrasions, puncture wounds, cuts, needle sticks
absorption into eyes and ears
Absorption into eyes and ears
  • Much less common but possible
  • Moist surfaces
distribution of toxins
Distribution of Toxins
  • Once toxins are in the body, there are several mechanism of movement and action
  • Inhalation
    • Toxics may enter bloodstream
    • Toxics may irritate or scar lung tissues directly
  • Skin Absorption
    • Toxics may enter bloodstream
    • Toxics may irritate, corrode or burn skin directly
once absorbed into the body toxins can move to other tissues and organs through various ways
Once absorbed into the body, toxins can move to other tissues and organs through various ways:
  • Filtration
    • Toxins move through membrane pores
  • Diffusion
    • Movement from higher concentration to lower concentration
  • Active transport
    • Movement across a membrane otherwise impermeable by a transport mechanism
      • Chemical reaction or carrier molecule, requires energy
  • Phagocytosis
    • Toxins “eat” or engulf other cells or by use of white blood cells
biotransformation excretion of toxins
Biotransformation & Excretion of Toxins
  • Water soluble substances: easily to eliminate
  • Lipid soluble substances are difficult to eliminate
  • Biotransformation: process by which materials are chemically altered to make them easier to eliminate (as in lipid soluble substances)
  • Biotransformation and excretion through the liver
  • Filtration and excretion through the kidneys
  • Therefore, liver and kidneys are useful in eliminating toxins from the body, but on the other hand become target organs of toxins because of their nature
  • Important in metabolism, energy storage, protein synthesis
  • Receives blood from digestive tract and works to concentrate, transform, and excrete substance (both good and bad [toxins])
  • Thus produces bile (enriched) which is returned to the intestines
  • ACB Digestive System: 106
hepatoxic effects
Hepatoxic Effects
  • Hepatoxic = “liver toxins”
  • Necrosis = cell death
  • Steatosis = intercellular fat accumulation, fatty liver
  • Cholestasis = interference with the production of bile and biliary excretion
  • Immune cell infiltrate = presence of abnormally high numbers of immune cells
  • Neoplasia = cancer
  • Cirrhosis = fibrosis, collagen fibers deposited throughout liver
    • Causes: chronic alcoholism, hepatitis
    • Collagen
      • interferes with normal function and the internal architecture
      • a protein-based connective tissue that is not normally present in the liver
      • Normally found as a component of tendons, ligaments, and bones
  • Receive 25% of cardiac output for filtration
  • Primarily for elimination of water soluble molecules
  • Large molecules (proteins) and lipid soluble materials are reabsorbed through the tubules of the nephron
    • Nephron = functional unit of the kidney (see next slide
  • Materials pass by filtration, diffusion, active transport
  • ACB Urinary System: 108, 110-112
classes of toxins and toxic responses
Classes of Toxins and Toxic Responses
  • Irritants and Sensitizers
  • Systemic Toxins
  • Neurotoxins
  • Reproductive Toxins
  • Carcinogens
  • Localized, some physical damage
  • To skin, eyes, respiratory system
  • Corrosion – most severe response
    • Ulceration, tissue damage, usually permanent
    • E.g., chemical burns from acids and bases
  • Acute irritations
    • Redness, inflammation, usually reversible
  • Substances that stimulate a response from the immune system, usually the second exposure
    • Triggering exposure can be extremely low dose
  • Immune system – recognize and reject foreign objects in the body, including infectious disease and hazardous materials
  • Allergic reaction releases antibodies to attack
  • Reaction ranges from skin rash to anaphylactic shock (life threatening)
systemic toxins
Systemic Toxins
  • Toxins that affect target organs
    • Vinyl chloride – liver (cancer)
    • Cadmium – kidney
    • Benzene – blood marrow (leukemia)
  • Toxicity mechanism is often related to the normal function of the target organ
  • Compounds that negatively affect the nervous system
  • Response can be mild to severe
    • Effects can impact thinking ability, motor control, regulation of breathing and heartbeat
  • Central Nervous System [CNS] (brain, spinal cord)
    • Coordination, emotion, speech, memory
  • Peripheral Nervous System [PNS] (all but brain, spinal cord)
    • Sensory info (touch, heat/cold, proprioception, pain)
    • Motor impulses (movement)
  • Autonomic Nervous System [ANS]
    • heart rate, breathing, organ control, reflexes
  • Neurotoxins can produce neuropathy – a toxic effect characterized by progressive decline and death of nerves
reproductive toxins
Reproductive Toxins
  • Substances that affect the reproductive process
  • May affect males, females, or both
  • Lead
    • Males – decreased numbers of sperm or defective sperm
    • Pregnant Females – can cause deformities in developing fetus, especially fetus’ developing nervous system
  • Teratogens (Greek: monster) – toxins that cause abnormal development or birth defects
thalidomide a teratogen
Thalidomide (a teratogen)
  • Originally prescribed as a sedative and specifically advertised for safe use by pregnant women
  • Thousands of babies were born between 1959 and 1962 with severe deformities (no legs, arms, deformed ears, etc.)
  • Popular use in Europe and Canada
  • Use in US was delayed for FDA studies which later proved its danger
des diethyl stilbestrol
DES (Diethyl stilbestrol)
  • Another teratogen
  • Synthetic hormone (estrogen)
  • Approved in 1941 for use in women as an aid in the prevention of miscarriage
  • Finally discontinued in 1972
  • Linked to development of cancer and other abnormalities of their children
  • Toxins that cause cancer
  • Occupational carcinogens consist of a variety of chemical and physical agents including
    • organic and inorganic solvents
    • heavy metals
    • solid materials (asbestos fibers)
    • “natural” substances – hormones, nitrosamine
    • Materials that suppress the immune system
federal regulations
Federal Regulations

OSHAct (1970)

TSCA (1976)


  • Within DOL (Department of Labor)
  • Regulatory Authority
  • Sets PELs for >4000 specific chemicals
    • Many based on ACGIH TLVs (App B)
  • Hazard Communication Standard
    • 29 CFR 1910.1200
tsca 1976
TSCA (1976)
  • Toxic Substances Control Act
  • Administered by EPA
  • Covers almost all chemicals manufactured in the US (>83,000)
  • Requires manufacturers to develop adequate data on health and environmental effects
  • EPA can ban or restrict us of these chemicals
  • National Institute for Occupational Safety & Health
    • Under CDC (Centers for Disease Control) within HHS (Department of Health & Human Services)
  • Publishes Criteria Documents
  • American Conference of Governmental Industrial Hygienists
  • TLVs – Threshold Limit Values (App B)
  • What is a TWA?
  • What is a Ceiling Value?
  • See Figure 6-4
  • Nims DK. Basics of Industrial Hygiene. John Wiley & Sons, Inc., 1999.
  • Read Plog, Chapter 6
  • HW6
    • Find a chemical/product from where you live or nearby. Obtain an MSDS off the Internet. Write a 1-2 page evaluation of the product. Include discussion of how it might enter the body thru the 4 routes, handling requirements, and brief discussion of safe handling and use
    • Due Date?
  • Color ACB Plates: 98, 104, 106, 108, 110, 112