Sensitive to Sensitivity neurasthenia

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					  Sensitive to Sensitivity
2002 Alaska Governor’s Safety and Health

     Dr. Robert A. Perkins, PE, CIH
  Civil and Environmental Engineering
     University of Alaska Fairbanks
             19 March 2002
• Perkins
  – “Presentations”
•   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
• 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
• Upper Respiratory Tract
• Lung
• URT and Lung
                 URT Irritants
• Chemical
• Particulates
  – Mineral
  – Biological
• Coughing, lacrimation, difficulty breathing
• Inflammation of membranes
• Many biological particulates are also
  – one or a series of exposures has no apparent
  – 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.
• 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
• 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
  – infected with a virus
  – cancer
• Many types have regulatory functions
  within the immune system
• Causes production of antibodies
• Bacteria
• Bacterial toxins
Antigenic determinant sites
• 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
  – Important for drug and chemical allergies
• Thousands of genetically different B cells,
  each produces its own specific type of
• 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
• Location depends on portal of entry or the

Minutes after antigen finds an antibody bound to
mast cell, chemicals are released
• Localized swelling skin allergy, hives
• Nasal and conjunctival discharge -allergic
  rhinitis and conjunctivitis
• Hay fever - bronchial asthma
• Allergic gastroenteritis - food allergy
• Usually injected,
  – needle or bee sting
• Very serious
                Type IV
• Delayed hypersensitivity
• Involves T cells
• Tuberculin reaction is example
• Formaldehyde
• 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
  – 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
• Plywood, medium-density fiberboard, and
• 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
• 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.
• People often experience odor and irritation
  as a unitary perception
                           Psychophysical Relationships,
                                  Weak Irritant
Perceived Intensity

                       6                                          Odor
                       4                                          Irritation






                                   Concentration       After Dalton, 2001
                               Psychophysical Relationships,
                                     Stronger Irritant
Perceived Intensity

                       6                                       Odor
                       4                                       Irritation






                                    Concentration      19
• Annoyance
  – not sensory
  – or physiological effect
• Psychological discomfort from the presence
  and increasing concentration of an odor.
                        Psychophysical Relationships,
                      Negative response to odor property
Perceived Intensity

    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%
• “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                          Ontari   Cullen   Ashfor    AAEM      NRC     AOEC     Netherc    IPCS
                                    o     (1987)      d      (1992)   (1992)   (1992)     ott     (1996)
                                 (1985)              &                                   et al.
                                                    Miller                              (1993)

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/     X                 X                  X                 X
absence of exposure

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."

• 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: "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 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
• Patients report illness from exposure to low
  levels of many different environmental
  – drugs, food
             Severe MCS
• Severe, daily multisystem symptoms
• Occupationally and socially disabling
• Preponderantly middle-aged, white women
  with above-average education.
    Other conditions with core MCS
•   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, 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 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 "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
  "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 "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 - 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 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 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 "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
• 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
• "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
  "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:
• 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
           Is MCS a “disease”
•    Four aspects of a disease
1.   Etiology (cause)
2.   Pathogenesis (natural history)
3.   Morphologic changes (cells or tissues)
4.   Functional derangement (clinical
    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 assess from many of the
  published reports because the
  laboratory methods are inadequately
  documented or, in some cases, clearly
• 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
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 rose-scented 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 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 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:
• What MCS is
• What might cause it
     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
• 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
   – Removed colon or kinks in intestines.
• 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
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
  stressors) can have a direct influence on
  worker safety and health.
• Individual and other situational factors can
  intervene to strengthen or weaken this
           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 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 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.
• Considering role of physical stress
  – heat, cold,
• Adjusting TLV’s
    Industrial Hygienists Role
• Bad IH
• Good IH
• 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.

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