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Sensitive to Sensitivity 2002 Alaska Governor’s Safety and Health Conference Dr. Robert A. Perkins, Sensitive to Sensitivity 2002 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” • http: //www. faculty. uaf. edu • Perkins – “Presentations”

Topics • • • Overview of Sensitivity Chemical Sensitivity Toxicology of Sensitivity Multiple Chemical 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 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 Factors Affecting • • • Heat and Cold Physiological Hormonal Stress Fatigue Depression

Laboratory Animals • Temperature – affects responses – many drugs and chemicals • So 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. • 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 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 – 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 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 Air Contaminants • Irritants • Asphyxiants • CNS Depressants

Irritants • Upper Respiratory Tract • Lung • URT and Lung Irritants • Upper Respiratory Tract • Lung • URT and Lung

URT Irritants • Chemical • Particulates – Mineral – Biological • Coughing, lacrimation, difficulty 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 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 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. • 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 Toxicology of Hypersensitivity • Immune system – Innate or nonspecific – Adaptive or specific

Adaptive immunity • • Antigens Antibodies T cells B cells White Blood Cell (T 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 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 • Bacterial toxins Antigen • Causes production of antibodies • Bacterial toxins

Antigenic determinant sites Antigenic determinant sites

Antigen • Must have at least 2 determinant sites for antibody generation • One 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 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 Hypersensitivity reactions • Type I, Anaphylaxis • IV Cell-mediated (delayed) hypersensitivity

Type I Hypersensitivity • Minutes • May cause systemic disorder or local reaction. • 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 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 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 Systemic • Usually injected, – needle or bee sting • Very serious

Type IV • Delayed hypersensitivity • Involves T cells • Tuberculin reaction is example Type IV • Delayed hypersensitivity • Involves T cells • Tuberculin reaction is example

Examples • TDI (elicits a Type I response) • Formaldehyde (both Type I and Examples • TDI (elicits a Type I response) • Formaldehyde (both Type I and Type IV)

TDI • Toluene diisocyanate • A small molecule that acts as hapten – combines 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 • Only 5% to 10% of exposed have this reaction. – But these develop at very low doses. • TLV, 0. 005 ppm – 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 • Formaldehyde • Plywood, medium-density fiberboard, and particleboard. • Many industrial products and processes • Very common chemical

Exposure Low Range, PPM Outdoor, country High Range, PPM 0. 01 Outdoor, city 0. Exposure Low Range, PPM Outdoor, country High Range, PPM 0. 01 Outdoor, city 0. 09 0. 15 Mobile home, current 0. 05 0. 60 Mobile home, pre-1980 0. 10 0. 80 Room, 2 d 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 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 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 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. 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.

 • People often experience odor and irritation as a unitary perception • People often experience odor and irritation as a unitary perception

After Dalton, 2001 After Dalton, 2001

Annoyance • Annoyance – not sensory – or physiological effect • Psychological discomfort from 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 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 • 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 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

MCS MCS

Multiple Chemical Sensitivity • Multiple chemical sensitivities is an acquired disorder characterized by recurrent 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 Ontari o (1985) Cullen (1987) Ashfor d & Miller (1991) AAEM (1992) Multiple Element Ontari o (1985) Cullen (1987) Ashfor d & Miller (1991) AAEM (1992) Multiple environmental causes X X Time (chronicity) X X X Multiorgan symptoms X X X Symptoms at very low levels X X Symptoms affected by presence/ absence of exposure X Exclusion of other etiologies X Symptoms acquired X Demonstrable exposure X AOEC (1992) Netherc ott et al. (1993) IPCS (1996) X X X X X NRC (1992) X X X

 • Kurt (1995) in his research. He defined MCS as • 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. "

History • 1979: U. S. District Court for the District of Hawaii rules MCS History • 1979: U. S. District Court for the District of Hawaii rules MCS disabling and orders the Department of Health, Education, and Welfare to provide Social Security disability benefits to an individual (Slocum vs. Califano). • 1984: A California bill to require research on MCS is passed by both houses of state legislature, but is opposed by California Medical Association and vetoed by Gov. Deukmajian.

 • 1985: • 1985: "Report of the Ad Hoc Committee on Environmental Hypersensitivity Disorders" prepared by the Ontario Ministry of Health, Canada, calls for research on MCS and assistance for MCS patients. • 1986: Oregon Court of Appeals orders workers' compensation benefits for furniture store employee on basis of MCS (Robinson vs. Saif Corp. ). • 1987: California Court of Appeals awards workers' compensation benefits to employee who was found to have MCS resulting from long-term exposure to polychlorinated biphenyls (Kyles vs. Workers' Compensation Appeals Board).

 • 1989: Ohio Court of Appeals reinstates an order of the Ohio Civil • 1989: Ohio Court of Appeals reinstates an order of the Ohio Civil Rights Commission finding unlawful employment discrimination for dismissal of an employee with MCS (Kent State University vs. Ohio Civil Rights Commission). • 1990: Pennsylvania Human Relations Commission orders a landlord of an MCS patient to take measures to accommodate her, including reduction in the use of pesticides (Atkinson vs. Lincoln Realty). • 1992: Department of Housing and Urban Development recognizes MCS as a disability requiring reasonable accommodations under the Fair Housing Act Amendments and the Rehabilitation Act of 1973.

MCS is • Controversial, chronic, polysymptomatic condition. • Patients report illness from exposure to MCS is • Controversial, chronic, polysymptomatic condition. • Patients report illness from exposure to low levels of many different environmental chemicals: – drugs, food

Severe MCS • Severe, daily multisystem symptoms • Occupationally and socially disabling • Preponderantly Severe MCS • Severe, daily multisystem symptoms • Occupationally and socially disabling • Preponderantly middle-aged, white women with above-average education.

Other conditions with core MCS symptoms • • • Chronic fatigue syndrome Fibromyalgia Persian Other conditions with core MCS symptoms • • • Chronic fatigue syndrome Fibromyalgia Persian Gulf Syndrome Solvent-exposed workers Chemical odor intolerance – unpleasant reaction to odor – multiple nonspecific symptoms – no distinct relationship to toxicology property of any particular chemical.

Jackie’s Story • Had happy life • “Almost overnight becoming so weak, dizzy, exhausted, Jackie’s Story • Had happy life • “Almost overnight becoming so weak, dizzy, exhausted, and "spacy" that you couldn't function any more. Imagine sleeping for 10 to 12 hours a night and waking up every morning feeling just as exhausted as when you went to bed. “ • sent to a psychiatrist because your doctor thinks you're just "depressed" and need to "snap out of it"

 • Quit job • “. . too weak to hold your head up • Quit job • “. . too weak to hold your head up for more than a few minutes at a time. Imagine having to resort to using a wheelchair for going shopping, etc. , because you were so dizzy and had such balance problems that it made it difficult to walk. ”

 • “. . diagnosed in 1991 with • “. . diagnosed in 1991 with "Chronic Fatigue Syndrome" (CFS) by a reputable Infectious Disease Specialist in Gainesville, Florida. He said there was basically no treatment for CFS and that I would just have to learn to rest and not try to push myself anymore. Following this advice, I suffered for 4 more years with no improvement in my symptoms - I could barely remember what it felt like to feel "good".

 • “Finally, in September 1995, I read a book called • “Finally, in September 1995, I read a book called "Tired or Toxic? " by Sherry Rogers - which has totally changed my life! In the pages of this book, I found that every one of my bizarre symptoms could be caused by exposure to toxic chemicals in my environment. I learned that our bodies can only handle so many toxins before our immune systems will "overload" and not be able to process them any more”

 • “I realized that my • “I realized that my "chemical poisoning" began when I spent over 10 years living in mobile homes. Mobile homes are made of lots of particleboard, glued wallpapers, synthetic carpets, etc. - all of which outgas formaldehyde. Formaldehyde is very toxic and causes many of the symptoms I experienced: dizziness, spaciness, etc. It also weakens the immune system, making you more vulnerable to other toxic chemicals “

 • Formaldehyde is in MANY things these days. It's in most cosmetics - • Formaldehyde is in MANY things these days. It's in most cosmetics - including BABY SHAMPOO and BABY LOTION. Look for "Quaternium-15" on the label - that's formaldehyde in disguise. It's also in the clothes you wear - if they're permanent press or polyester. It's in your polyester/cotton bed sheets. It's even in a lot of the food you eat. And, yes - formaldehyde is the stuff they embalm people with. At this rate, we won't need to be embalmed by the time we die!

 • As a child, I was constantly exposed to the cigarette smoke. I • As a child, I was constantly exposed to the cigarette smoke. I also had many "silver" fillings placed in my mouth, which I now know are made of about 50% MERCURY! Mercury is even more toxic than ARSENIC and yet it's placed in our mouths because it's cheap and easy to use! This mercury leaks out of the fillings and can slowly cause health problems, similar to the way arsenic poisoning happens slowly over time. (NOTE: I recently underwent amalgam removals and hope this will also help improve my health!)

 • Then in 1987, when Gorden and I got engaged, my doctor prescribed • Then in 1987, when Gorden and I got engaged, my doctor prescribed birth control pills for me. I now know that birth control pills also weaken the immune system - especially the ones with high amounts of estrogen. They also lead to candida overgrowth (yeast infections). The candida further weakens the immune system and also releases toxins into the bloodstream. I had immediate reactions to the birth control pills - they totally "confused" my hormonal system.

 • In 1989, I started working in a • In 1989, I started working in a "sick building". It was a new building with all new carpeting, new paint, new partitions, new furniture, etc. I now know that all these things outgas MANY toxic chemicals. Since my immune system was already weakened, this was too much for it to handle.

 • In 1993 we started spraying our house with Dursban to get rid • In 1993 we started spraying our house with Dursban to get rid of fleas. We had no idea this pesticide was as toxic and dangerous as it is! I couldn't tell at the time how much it was affecting my health because I already had such severe symptoms. Looking back, I now see that many "new" symptoms began right around the time we started using the Dursban

 • • "CFS" was something I had no idea how to treat - it left me a "victim". "MCS" on the other hand, gives me many things I can do to help myself get well. Recovering from this illness involves: cleaning up your environment, avoiding toxic chemicals as much as possible, eating as many organic foods as possible (almost all regular foods are loaded with pesticides), taking nutritional supplements, using "neutralizing" allergy shots, and many other things. The first thing we did was to find an "Environmental Medicine Specialist" here in Florida

 • While we were there, we stayed at a place called • While we were there, we stayed at a place called "The Natural Place". It's run by a couple with MCS, and it's totally non-toxic! They allow NO scented products, cigarette smoking, or pesticides on the premises. They have all 100% cotton beds and bedding, no carpeting, solid wood cabinets, etc. , and provide air filters for each unit. The most interesting thing happened while we stayed there: MY SYMPTOMS GREATLY IMPROVED!!

 • We are so thankful for this. Now my goal is to help • We are so thankful for this. Now my goal is to help other sufferers who think they have "CFS" or "Fibromyalgia" to "make the connection" and get better too - as well as to help to educate others about the health risks of using certain products so they can learn to protect themselves. I hope my story has given you hope and encouragement if you are sick, and enlightenment if you are still healthy!

Is MCS a “disease” • 1. 2. 3. 4. Four aspects of a disease Is MCS a “disease” • 1. 2. 3. 4. Four aspects of a disease Etiology (cause) Pathogenesis (natural history) Morphologic changes (cells or tissues) Functional derangement (clinical significance)

The Interagency Workgroup on Multiple Chemical Sensitivity • No single accepted case definition of The Interagency Workgroup on Multiple Chemical Sensitivity • No single accepted case definition of MCS has been established; proposed definitions all differ in key criteria, and some definitions suggest a broad spectrum of possible symptoms. The validated epidemiologic data required to clarify the natural history, etiology, and diagnosis of MCS are not available.

Immune Mechanisms • The role of the immune system in MCS is difficult to Immune Mechanisms • The role of the immune system in MCS is difficult to assess from many of the published reports because the laboratory methods are inadequately documented or, in some cases, clearly deficient.

Inflammation • Inflammation has been suggested as being causally related to MCS as a Inflammation • Inflammation has been suggested as being causally related to MCS as a result of the initiation of mediators released from cell membranes by the action of free radicals produced from toxic chemical exposures. • There is no convincing evidence that such mediators are involved with MCS although the hypothesis has not been adequately tested.

Neurologic Mechanisms Including Altered Sense of Smell • Neural stimulation is defined as the Neurologic Mechanisms Including Altered Sense of Smell • Neural stimulation is defined as the "[p]rogressive amplification of responsivity by the passage of time and repeated, intermittent exposures" • In a study of odor responsivity among persons diagnosed with MCS, …tested 31 subjects to assess odor detection thresholds to rosescented alcohol and an unpleasant-smelling pyradine; no differences were found between the MCS subjects, controls, and asthma patients.

Psychological Mechanisms • Psychiatric factors have been seen as the cause of MCS, an Psychological Mechanisms • Psychiatric factors have been seen as the cause of MCS, an effect of having MCS, a predisposing factor in the development of MCS, and a co-morbid occurrence with MCS. • Some believe that, if present, psychiatric symptoms are a secondary accompaniment to a chronic disease process and some believe that MCS is primarily the symptomatic manifestation of a psychiatric disorder.

Bottom Line, ASTDR • Definitive data that would confirm or refute hypothesized mechanisms for Bottom Line, ASTDR • Definitive data that would confirm or refute hypothesized mechanisms for MCS are generally lacking • Investigators have used different definitions of MCS and because MCS classification in studies is based on self-reporting, it is difficult to compare patient groups used in various studies to each other or to evaluate the application of theories to the patient groups.

MCS Summary, Perkins • No agreement among the medical establishment and scientists regarding: • MCS Summary, Perkins • No agreement among the medical establishment and scientists regarding: • What MCS is • What might cause it

How about Neurasthenia • Vague shifting symptoms related to multiple organ systems have been How about Neurasthenia • Vague shifting symptoms related to multiple organ systems have been reported for many years. • 1880, Beard • Thought related to “stresses of modern civilization. ”

Autointoxication • 1900, explains multiple symptoms in otherwise normal individuals. – tiredness, lack of Autointoxication • 1900, explains multiple symptoms in otherwise normal individuals. – tiredness, lack of energy and well-being • Visceroptosis – falling down of intestines • 1918, Chronic intestinal stasis – intestines produced toxins faster than liver could detoxify – Removed colon or kinks in intestines.

 • The only thing that distinguishes environmental illness or MCS from all other • The only thing that distinguishes environmental illness or MCS from all other patients with this pattern of symptoms is the attribution of symptoms to environmental and/or chemical exposures • Critical Reviews in Toxicology

Digression on Causation • Colleague in next office • Laugh give me headache Digression on Causation • Colleague in next office • Laugh give me headache

Workplace stress Workplace stress

"Workplace stress" • The harmful physical and emotional responses that can happen when there is a conflict between job demands on the employee and the amount of control an employee has over meeting these demands. In general, the combination of high demands in a job and a low amount of control over the situation can lead to stress

 • According to the NIOSH view, exposure to stressful working conditions (called job • According to the NIOSH view, exposure to stressful working conditions (called job stressors) can have a direct influence on worker safety and health. • Individual and other situational factors can intervene to strengthen or weaken this influence.

Stress can cause • increased blood pressure • increased metabolism (e. g. , faster Stress can cause • increased blood pressure • increased metabolism (e. g. , faster heartbeat, faster respiration) • decrease in protein synthesis, intestinal movement (digestion), immune and allergic response systems • increased cholesterol and fatty acids in blood for energy production systems • localized inflammation (redness, swelling, heat and pain) • faster blood clotting

How do I know if someone is (or if I am) having trouble coping How do I know if someone is (or if I am) having trouble coping with stress? • Physical: headaches, grinding teeth, clenched jaws, chest pain, shortness of breath, pounding heart, high blood pressure, muscle aches, indigestion, constipation or diarrhea, increased perspiration, fatigue, insomnia, frequent illness

 • Psychosocial: anxiety, irritability, sadness, defensiveness, anger, mood swings, hypersensitivity, apathy, depression, slowed • Psychosocial: anxiety, irritability, sadness, defensiveness, anger, mood swings, hypersensitivity, apathy, depression, slowed thinking or racing thoughts; feelings of helplessness, hopelessness, or of being trapped • Behavioural: overeating or loss of appetite, impatience, quickness to argue, procrastination, increased use of alcohol or drugs, increased smoking, withdrawal or isolation from others, neglect of responsibility, poor job performance, poor personal hygiene, change in religious practices, change in close family relationships.

ACGIH • Considering role of physical stress – heat, cold, • Adjusting TLV’s ACGIH • Considering role of physical stress – heat, cold, • Adjusting TLV’s

Industrial Hygienists Role • Bad IH • Good IH Industrial Hygienists Role • Bad IH • Good IH

 Summary • Low exposure doses may cause problems for sensitive individuals • Well Summary • Low exposure doses may cause problems for sensitive individuals • Well below TLV • No scientific evidence for MCS • Workplace stress can increase problems • IH’s must consider their role in stress.