Sensitive to Sensitivity 2002 Alaska Governor

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Sensitive to Sensitivity 2002 Alaska Governors
Safety and Health Conference

• Dr. Robert A. Perkins, PE, CIH
• Civil and Environmental Engineering
• University of Alaska Fairbanks
• 19 March 2002

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• http//www.faculty.uaf.edu
• Perkins
• Presentations

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Topics

• Overview of Sensitivity
• Chemical Sensitivity
• Toxicology of Sensitivity
• Multiple Chemical Sensitivity
• Workplace Stress
• Conclusion

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Types of Sensitivity

• Emotional
• Artistic
• Allergic
• Smells
• Sounds, Music
• Toxicological, Chemical
• sensitive vs. resistant subpopulations

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Factors Affecting

• Heat and Cold
• Physiological
• Hormonal
• Stress
• Fatigue
• Depression

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Laboratory Animals

• Temperature
• affects responses
• many drugs and chemicals
• So does stress
• Today
• Light dark cycles
• Populations in cages

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In General, Sensitivity

• Humans and other mammals are sensitive to various
  factors.
• Sensitivity might vary with exogenous factors
• Endogenous factors
• Might vary with time.

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Chemical Sensitivity

• Irritants vs. Sensitizers
• Primary Irritants
• Affect most people
• Chemical contact dermatitis
• Many agents
• acids, solvents
• dies, insecticides
• soaps

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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

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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

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Air Contaminants

• Irritants
• Asphyxiants
• CNS Depressants

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Irritants

• Upper Respiratory Tract
• Lung
• URT and Lung

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URT Irritants

• Chemical
• Particulates
• Mineral
• Biological
• Coughing, lacrimation, difficulty breathing
• Inflammation of membranes

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Allergens

• Many biological particulates are also allergens
• one or a series of exposures has no apparent
  effect.
• Later a challenge dose provokes the reaction

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Classes of Allergens

• Microorganisms and their toxins
• Arthropod bites or stings
• Allergens and toxins from higher plants
• Protein allergens from vertebrate animals.

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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.

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Toxicology of Hypersensitivity

• Immune system
• Innate or nonspecific
• Adaptive or specific

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Adaptive immunity

• Antigens
• Antibodies
• T cells
• B cells

White Blood Cell (T or B)
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T cells

• Type of white blood cell
• Many different types of T cell
• Some are programmed to attack bodys cells
• infected with a virus
• cancer
• Many types have regulatory functions within the
  immune system

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Antigen

• Causes production of antibodies
• Bacteria
• Bacterial toxins

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Antigenic determinant sites
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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

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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

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Hypersensitivity reactions

• Type I, Anaphylaxis
• IV Cell-mediated (delayed) hypersensitivity

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Type I Hypersensitivity

• Minutes
• May cause systemic disorder or local reaction.
• Location depends on portal of entry or the
  allergen.

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Mechanism
Minutes after antigen finds an antibody bound to
mast cell, chemicals are released
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Local

• Localized swelling skin allergy, hives
• Nasal and conjunctival discharge -allergic
  rhinitis and conjunctivitis
• Hay fever - bronchial asthma
• Allergic gastroenteritis - food allergy

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Systemic

• Usually injected,
• needle or bee sting
• Very serious

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Type IV

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

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Examples

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

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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

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• 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

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Formaldehyde

• Plywood, medium-density fiberboard, and
  particleboard.
• Many industrial products and processes
• Very common chemical

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Formaldehyde Actions

• Both an irritant and a sensitizer
• Primary irritant of skin
• Irritation of mucosal surfaces
• protective responses sneezing, coughing, and
  tearing

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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.

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Summary of Toxicology and IH

• Mechanisms are well-known for some chemicals and
  toxins
• Hypersensitivity (allergy) can be demonstrated in
  laboratory

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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.

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• People often experience odor and irritation as a
  unitary perception

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After Dalton, 2001
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Annoyance

• Annoyance
• not sensory
• or physiological effect
• Psychological discomfort from the presence and
  increasing concentration of an odor.

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Reported Sensory Irritation

• Adaptation
• specific, reversible decreased sensitivity
• common in occupation settings
• Expectation and Perceived Irritation
• subjects told
• industrial solvent
• natural extract

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• Social cues
• Used actors as other subjects
• Exposed to solvent odor
• Negative cues
• 70 reported irritation
• Positive
• 12
• Neutral
• 34

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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

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MCS
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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

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• 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."

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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.

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• 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).

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• 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.

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MCS is

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

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Severe MCS

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

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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.

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Jackies 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"

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• 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.

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• ..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".

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• 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

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• 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

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• 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!

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• 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!)

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• 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.

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• 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.

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• 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

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• "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

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• 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!!

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• 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!

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Is MCS a disease

• Four aspects of a disease
• Etiology (cause)
• Pathogenesis (natural history)
• Morphologic changes (cells or tissues)
• Functional derangement (clinical significance)

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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.

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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.

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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.

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Neurologic Mechanisms Including Altered Sense of
Smell

• Neural stimulation is defined as the
  "progressive 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 rose-scented alcohol
  and an unpleasant-smelling pyradine no
  differences were found between the MCS subjects,
  controls, and asthma patients.

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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.

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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.

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MCS Summary, Perkins

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

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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.

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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.

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• 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

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Digression on Causation

• Colleague in next office
• Laugh give me headache

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Workplace stress
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"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

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• 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.

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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

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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
  

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• 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.

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ACGIH

• Considering role of physical stress
• heat, cold,
• Adjusting TLVs

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Industrial Hygienists Role

• Bad IH
• Good IH

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  Summary

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