Sensitive to Sensitivity2002 Alaska Governor’s Safety and Health Conference Dr. Robert A. Perkins, PE, CIH Civil and Environmental Engineering University of Alaska Fairbanks 19 March 2002
http://www.faculty.uaf.edu • Perkins • “Presentations”
Topics • Overview of Sensitivity • Chemical Sensitivity • Toxicology of Sensitivity • Multiple Chemical Sensitivity • Workplace Stress • Conclusion
Types of “Sensitivity” • Emotional • Artistic • Allergic • Smells • Sounds, Music • Toxicological, Chemical • sensitive vs. resistant subpopulations
Factors Affecting • Heat and Cold • Physiological • Hormonal • Stress • Fatigue • Depression
Laboratory Animals • Temperature • affects responses • many drugs and chemicals • So does stress • Today • Light dark cycles • Populations in cages
In General, Sensitivity: • Humans and other mammals are sensitive to various factors. • Sensitivity might vary with exogenous factors • Endogenous factors • Might vary with time.
Chemical Sensitivity • Irritants vs. Sensitizers • Primary Irritants • Affect most people • Chemical contact dermatitis • Many agents • acids, solvents • dies, insecticides • soaps
Sensitizers, Dermatitis • Initial contact may not produce dermatitis • Dermatitis develops later • very low, non-irritating concentrations • previously could have been handled without any problem. • Hereditary Allergy (Atopy) • hives • latex
Irritant vs. Sensitizer (Allergen) • Irritant affects all or almost all, • Allergen affects few. • except very potent sensitizers, poison oak oleoresin, epoxy resin and components. • Allergy sometimes called hypersensitivity. • Patch testing
Air Contaminants • Irritants • Asphyxiants • CNS Depressants
Irritants • Upper Respiratory Tract • Lung • URT and Lung
URT Irritants • Chemical • Particulates • Mineral • Biological • Coughing, lacrimation, difficulty breathing • Inflammation of membranes
Allergens • Many biological particulates are also allergens • one or a series of exposures has no apparent effect. • Later a “challenge dose” provokes the reaction
Classes of Allergens • Microorganisms and their toxins; • Arthropod bites or stings; • Allergens and toxins from higher plants; • Protein allergens from vertebrate animals.
Summary • A sensitizer (or allergen) is not the same as an irritant. • May be difficult to distinguish • Many substances are both • Small doses of irritant may not effect many people • Many allergens • many people are sensitive to chemicals while others are not affected.
Toxicology of Hypersensitivity • Immune system • Innate or nonspecific • Adaptive or specific
Adaptive immunity • Antigens • Antibodies • T cells • B cells White Blood Cell (T or B)
T cells • Type of white blood cell • Many different types of T cell • Some are programmed to attack body’s cells • infected with a virus • cancer • Many types have regulatory functions within the immune system
Antigen • Causes production of antibodies • Bacteria • Bacterial toxins
Antigen • Must have at least 2 determinant sites for antibody generation • One determinant site (a partial antigen or hapten) can bind chemically to a carrier molecule that has one determinant site of its own. • Important for drug and chemical allergies
Antibodies • Thousands of genetically different B cells, each produces its own specific type of antibody. • Once activated, replicates and releases many copies of the same antibody. • Antibodies attach to the antigen • other enzymes attach the antigen
Hypersensitivity reactions • Type I, Anaphylaxis • IV Cell-mediated (delayed) hypersensitivity
Type I Hypersensitivity • Minutes • May cause systemic disorder or local reaction. • Location depends on portal of entry or the allergen.
Mechanism Minutes after antigen finds an antibody bound to mast cell, chemicals are released
Local • Localized swelling skin allergy, hives • Nasal and conjunctival discharge -allergic rhinitis and conjunctivitis • Hay fever - bronchial asthma • Allergic gastroenteritis - food allergy
Systemic • Usually injected, • needle or bee sting • Very serious
Type IV • Delayed hypersensitivity • Involves T cells • Tuberculin reaction is example
Examples • TDI • Formaldehyde
TDI • Toluene diisocyanate • A small molecule that acts as hapten • combines with native proteins • new compound that is recognized as foreign • Future exposures result in allergic reaction • especially broncoconstriction
Only 5% to 10% of exposed have this reaction. • But these develop at very low doses. • TLV, 0.005ppm • 0.02 STEL • In some individuals airways seem to become hyper-reactive to many agents • smoke and other air pollutants
Formaldehyde • Plywood, medium-density fiberboard, and particleboard. • Many industrial products and processes • Very common chemical
Exposure Low Range, PPM High Range, PPM Outdoor, country 0.01 Outdoor, city 0.09 0.15 Mobile home, current 0.05 0.60 Mobile home, pre-1980 0.10 0.80 Room, 2d hand smoke 0.23 0.27 ACGIH, TLV, ceiling 0.30 OSHA, 8 hr average 0.75 Eye irritation reported 1.0 OSHA, ceiling 2.0 Broncoconstriction 2.0 Typical strong discomfort 4.0 5.0 Sever eye, difficult breathing 10 20
Formaldehyde Actions • Both an irritant and a sensitizer • Primary irritant of skin • Irritation of mucosal surfaces • protective responses: sneezing, coughing, and tearing
Sensitizer • Rare to find antibodies • Bronchial provocation tests for asthma • 12 of 230 who were suspected responded • 3 of 15 another test • Type I exists in some individuals • Type IV on skin.
Summary of Toxicology and IH • Mechanisms are well-known for some chemicals and toxins • Hypersensitivity (allergy) can be demonstrated in laboratory
Annoying Smells • URT Irritation • Odor • Travel to the brain via different nerves. • Both activated by a single stimulus to the nose, so are often confused.
Annoyance • Annoyance • not sensory • or physiological effect • Psychological discomfort from the presence and increasing concentration of an odor.
Reported Sensory Irritation • Adaptation • specific, reversible decreased sensitivity • common in occupation settings • Expectation and Perceived Irritation • subjects told • “industrial solvent” • “natural extract”
Social cues • Used actors as “other subjects” • Exposed to solvent odor • Negative cues • 70% reported irritation • Positive • 12% • Neutral • 34%
Summary • “The frequent lack of correspondence between exposure concentration, objective signs of exposure-related symptoms, and adverse reports has led to problems setting occupation exposure limits.” • Dalton, 2001
Multiple Chemical Sensitivity • Multiple chemical sensitivities is an acquired disorder characterized by recurrent symptoms, referable to multiple organ systems, occurring in response to demonstrable exposure to many chemically unrelated compounds at doses far below those established in the general population to cause harmful effects. No single widely accepted test of physiologic function can be shown to correlate with symptoms. [Cullen]
Element Ontario(1985) Cullen(1987) Ashford & Miller(1991) AAEM(1992) NRC(1992) AOEC(1992) Nethercottet al.(1993) IPCS(1996) Multiple environmental causes X X X X X X X Time (chronicity) X X X X X X Multiorgan symptoms X X X X X X Symptoms at very low levels X X X X X X Symptoms affected by presence/absence of exposure X X X X Exclusion of other etiologies X X X X Symptoms acquired X X X Demonstrable exposure X
Kurt (1995) in his research. He defined MCS as "[a] symptom complex triggered by odor or a perceived exposure; occurring at exposure levels below those of allergic sensitivity or irritation; analogous to the symptoms of panic disorder as defined by (DSM-III-R); lacking objective clinical pathologic criteria; and responsive to panic disorder management."