Respiratory Toxicology – 06/06/05
An Introduction To Respiratory Toxicology
A Small Dose of ™ Respiratory Tox
Respiratory Toxicology – 06/06/05 A Small Dose of Toxicology
Functional Anatomy - Upper
Upper Respiratory Passages – Nose Mouth Throat Vocal cords
Respiratory Toxicology – 06/06/05 A Small Dose of Toxicology
Functional Anatomy - Middle
Middle Respiratory Passages Trachea Bronchi Bronchioles
Bronchioles narrow in Asthma Bronchitis Emphysema
Respiratory Toxicology – 06/06/05 A Small Dose of Toxicology
Tracheobronchial region
16 generations of conducting airways Trachea: 2.5 cm2 cross-sectional area
bronchi bronchioles:180 cm2 cross-sectional
area, 65,000 (216) airwaysLined with ciliated epithelial cells and thin
mucus layer, the ‘mucociliary escalator’ for clearance of particles
Smooth muscles regulate airflow
Respiratory Toxicology – 06/06/05 A Small Dose of Toxicology
Gas Exchange
Pulmonary region: Alveoli Alveolar ducts Respiratory bronchioles
Respiratory Toxicology – 06/06/05 A Small Dose of Toxicology
Asthma Bronchi
Respiratory Toxicology – 06/06/05 A Small Dose of Toxicology
Respiratory Function
Primary • Gas exchange - oxygen, carbon
dioxide, water vapor
Secondary• Communication • Biotransformation of pollutants• Defense against infection and
entry of airborne toxicants
Respiratory Toxicology – 06/06/05 A Small Dose of Toxicology
Lung Facts
Major route of entry• surface area = 50-100 m2
Barrier thickness = 1 µmAffected by hazardous materials &Chemicals (solvents and particles)
Respiratory Toxicology – 06/06/05 A Small Dose of Toxicology
Oxygen Uptake
70 kg person at rest, the flow rate of air in and out is 7.5 L/min, or 450 L/hour; the flow rate of oxygen into the blood is 21.5 g/hour
During 30 minutes of exercise, the flow rate of air is 45 L/min, and amount of oxygen taken in is 85.7 g.
24 hours – 15,000 L
Respiratory Toxicology – 06/06/05 A Small Dose of Toxicology
Dust Inhalation
Dust particle (PM10) concentration is 100 µg/m3, then the mass inhaled is 1.5 mg dust/day/70 kg body weight.
[100 µg/m3 x 15 m3 /day = 1.5 mg dust]
Dust mag 12,000 NASA
Respiratory Toxicology – 06/06/05 A Small Dose of Toxicology
Ozone Inhalation
Ozone concentration is 0.1 ppm. Rate of ventilation is 10 L/min (light exercise) over 3 hrs.
The mass inhaled and deposited on the respiratory surfaces is 0.36 mg/day.
(0.1 ppm ozone = 0.2 mg/m3) [0.2 mg/ m3 x 180 min x .010 m3/min = 0.36 mg]
Respiratory Toxicology – 06/06/05 A Small Dose of Toxicology
Tidal Volume (VT): Volume of air inhaled/exhaled during one breath
Vital Capacity (VC): Largest possible tidal volume (with maximal effort)
Functional Residual Capacity (FRC): Volume of air in lungs after normal expiration
Residual Volume (RV): Volume of air that can’t be expelled, even with maximal effort
Total Lung Capacity (TLC): Vital Capacity + Residual Volume
Lung Volumes and Capacities
Respiratory Toxicology – 06/06/05 A Small Dose of Toxicology
Lung Volumes and Capacities
TidalVolume
FunctionalResidual Capacity
ResidualVolume
VitalCapacity
TotalLung
Capacity
Reference: Adapted from Gordon and Amdur , 1991
Respiratory Toxicology – 06/06/05 A Small Dose of Toxicology
Environmental Effects
Asthma - pollen, irritant chemicals Chronic Bronchitis - cigarette smoke Retarded Growth of the Respiratory
System in Children - ozone, oxides of nitrogen
Elevated Frequency of Respiratory Infections - ozone, particulate matter
Respiratory Toxicology – 06/06/05 A Small Dose of Toxicology
Occupational Disease
Pneumoconioses - dust in the lungs, fibrosis (scarring, stiffening) generally present
Coal workers (CWP) - simple or progressive Silicosis - is associated with tuberculosis,
cancer Shaver’s disease - bauxite Berylliosis – beryllium; immune system Siderosis - iron; often considered benign Stannosis - tin Asbestosis - is associated with cancer
Respiratory Toxicology – 06/06/05 A Small Dose of Toxicology
Occupational Disease
Industrial Bronchitis - chemical irritants Byssinosis - cotton processing Endotoxin in bacterial contaminant
suspected Hypersensitivity pneumonitis - mold, fungi
Respiratory Toxicology – 06/06/05 A Small Dose of Toxicology
Occupational Disease - Cancer
Bronchogenic cancer: initial site in airway; asbestos, ionizing radiation, coke oven emissions, nickel carbonyl; strong synergism between asbestos and tobacco smoke
Mesothelioma: initial site is in visceral pleura (outer lining of lungs); few causes other than asbestos
Respiratory Toxicology – 06/06/05 A Small Dose of Toxicology
Occupational Asthma
One of the most common occupational respiratory diseases
Caused by an agent encountered in the workplace
More than 200 known etiologic agents Temporal limitation of airflow Non-specific bronchial hyperresponsiveness First described in about 460 B.C. by
Hippocrates, in fishermen, farmers, woodworkers, and others
Respiratory Toxicology – 06/06/05 A Small Dose of Toxicology
Occupational Asthma
Allergic response, may be delayed Wheeze, cough, shortness of breath Agents: animal dander, colophony,
isocyanates, grain and wood dusts, anhydrides and phthalates, platinum compounds
Respiratory Toxicology – 06/06/05 A Small Dose of Toxicology
Occupational Asthma: Contributing Factors
OccupationalAsthma
HostFactors
ExposureFactors
Climate/Geography
Factors
IndustryFactors
JobFactors
Adapted from Brooks, 1992
Respiratory Toxicology – 06/06/05 A Small Dose of Toxicology
Occupational Asthma: Examples
Industry/Occupation Agent(s)Milling/Baking Flour, insects, mite debrisAgriculture Animal antigens, dustsHealth care Latex, formaldehydeGrain handler Grain, insect debris, dustLaboratory worker Animal antigensLumber and woodworking Wood dusts (plicatic acid)Paper product manufacture Natural gluesAirplane/sporting manufacture Epoxy resinsPainting Isocyanates, chromium (VI)Plastics industry Isocyanates, anhydridesMetals Industry Stainless/galvanized steel,
chromium (VI)
Respiratory Toxicology – 06/06/05 A Small Dose of Toxicology
Bronchihal Asthma
Bronchial hyperresponsiveness: exaggerated bronchoconstriction in response to various stimuli Reduced expiratory airflow Dyspnea: shortness of breath Wheezing Airway inflammation Mucus hypersecretion
Various triggers: IgE mediated: dust, pollens, other allergens Non-IgE mediated: infection, exercise, air
pollutants
Respiratory Toxicology – 06/06/05 A Small Dose of Toxicology
Respiratory Hazards- Agriculture
Dusts Occupational asthma and bronchitis: grains, hay,
pollen, animal dander, feces, bacterial antigens and toxins, insect and mite antigens
Fibrosis: silica Chemicals
Occupational asthma and bronchitis: pesticides (carbamates and organophosphates), fertilizers, antibiotics in animal feed
Toxic gases Bronchitis, cough, shortness of breath, pulmonary
edema: H2S, NH3, CH4 (from decomposition of urine),
Asphyxiation: CO (from gasoline powered machines)
Respiratory Toxicology – 06/06/05 A Small Dose of Toxicology
Respiratory Hazards- Industrial
Smelters Fibrosis: aluminum Squamous cell carcinoma: Nickel
Foundries Occupational asthma: metals Bronchitis: Iron oxides Fibrosis: Iron oxides
Welding Occupational asthma: metals (nickel),amines,
chromic acid, ozone (during gas shielded arc welding)
Bronchitis: Iron oxides Emphysema: cadmium oxide, ozone Fibrosis: Iron oxides
Respiratory Toxicology – 06/06/05 A Small Dose of Toxicology
Gas or Vapor Exposure
Irritants Cause mucus membrane inflammation Examples: Ammonia, sulfur dioxide
Asphyxiants Limit O2 supply to the body Examples -
Simple: Nitrogen, methane Chemical: carbon monoxide, hydrogen
cyanide
Respiratory Toxicology – 06/06/05 A Small Dose of Toxicology
1275 - Ether discovered by Spanish chemist Raymundus Lullius and called “sweet vitriol”
1500s - Paracelsus experimented (enjoyed?) with the effects of ether
1842 – First used in surgery by Crawford Williamson Long, MD, of Jefferson, Georgia, U.S.
1846 - Dr. William T.G. Morton a dentist, anaesthetized a patient for surgery at the Massachusetts General Hospital
1929 – discovery of cyclopropane
1956 – discovery of halothane in England
Historical Events - Anesthetics
Respiratory Toxicology – 06/06/05 A Small Dose of Toxicology
First Operation with Ether
Robert Hinckley's (1880’s)"The First Operation with Ether"
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Chloroform – one of the earliest anesthetic agents – discontinued early 1900’s because of liver toxicity
Chloroform (CHCl3)
CH
Cl
Cl
Cl
Respiratory Toxicology – 06/06/05 A Small Dose of Toxicology
• Cyclopropane
• Enflurane
• Halothane
• Methoxyflurane
• Diethy ether
Anesthetic Agents
Respiratory Toxicology – 06/06/05 A Small Dose of Toxicology
Products – Mostly Solvents
• Gasoline• Diesel Fuel• Charcoal lighter fluid• Lantern fuel• Grease• Lubricating oils• Degreasing agents• Paint stripers• Paint thinner• Turpentine• Nail polish remover
Respiratory Toxicology – 06/06/05 A Small Dose of Toxicology
Products – Partly Solvents
• Glues• Adhesives• Oil based paints• Furniture polishes• Floor polishes and waxes• Spot removers• Metal and wood cleaners• White out• Computer disk cleaner• Varnishes and shellacs• Wood and concrete stains
Respiratory Toxicology – 06/06/05 A Small Dose of Toxicology
Exposure
Lungs – Quick to brain Skin – Slow, irritant Oral – e.g. alcohol
Respiratory Toxicology – 06/06/05 A Small Dose of Toxicology
Obvious (high exposure)Death, loss of consciousness, paralysis, convulsion, disorientation, euphoria, giddiness, confusion.
SubtleImpaired performance, depression, apathy, fatigue,
Acute Adverse Effects
Respiratory Toxicology – 06/06/05 A Small Dose of Toxicology
Motor – fatigue, tremor, incoordination Sensory – visual, auditory Cognitive – short and long term memory,
intellectual ability Mood – depression, apathy, irritability,
depression
CNS Effects
Respiratory Toxicology – 06/06/05 A Small Dose of Toxicology
ObviousCancer, reproductive effects, liver and kidney damage, developmental effects, visual system damage
SubtleImpaired performance, impaired memory, depression, reduced intellectual ability
Chronic Adverse Effects
Respiratory Toxicology – 06/06/05 A Small Dose of Toxicology
Chronic Obstructive Pulmonary Disease (C.O.P.D.)
Bronchitis-bronchiolitis
CC O PO P DD
Emphysema
Adapted from Robbins and Kumar, 1987
Chronic airflow limitationresistance to expiratory flow
-inflammation-secretions
-alveolar enlargement -damage to alveolar septa
Respiratory Toxicology – 06/06/05 A Small Dose of Toxicology
• TLV – Threshold Limit Value
• STEL – Short Term Exposure Limits (15 minute exposure)
• TWA – Time Waited Average (acceptable for 8 hr day, 40 hr week)
• TLV-C – Threshold Limit Value-C (ceiling not to be exceeded)
Regulatory Status
Respiratory Toxicology – 06/06/05 A Small Dose of Toxicology
A Small Dose of ™ Resp Tox
Respiratory Toxicology – 06/06/05 A Small Dose of Toxicology
Additional Information
Web Sites• American Lung Association – National -
http://www.lungusa.org/
• United Nations Office for Drug Control and Crime Prevention (UN ODCCP) – Access: http://www.undcp.org/odccp/index.html
• U.S. Department of Labor – Occupational Safety & Health Administration (OSHA) – Access: http://www.osha.gov/SLTC/respiratoryprotection/index.html - Information on respiratory protection.
Respiratory Toxicology – 06/06/05 A Small Dose of Toxicology
Authorship Information
For Additional Information ContactSteven G. Gilbert, PhD, DABT
E-mail: [email protected]: www.asmalldoseof.org
This presentation is supplement to “A Small Dose of Toxicology”