Transcript Sensitive to Sensitivity

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”
Topics
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Overview of Sensitivity
Chemical Sensitivity
Toxicology of Sensitivity
Multiple Chemical Sensitivity
Workplace Stress
Conclusion
Types of “Sensitivity”
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Emotional
Artistic
Allergic
Smells
Sounds, Music
Toxicological, Chemical
– sensitive vs. resistant subpopulations
Factors Affecting
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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
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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
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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
Antigenic determinant sites
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 (elicits a Type I response)
• Formaldehyde (both Type I and Type IV)
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
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, 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
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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
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Odor
4
Irritation
2
Concentration
19
16
13
10
7
4
0
1
Perceived Intensity
Psychophysical Relationships,
Weak Irritant
After Dalton, 2001
10
8
6
Odor
4
Irritation
2
Concentration
19
16
13
10
7
4
0
1
Perceived Intensity
Psychophysical Relationships,
Stronger Irritant
Annoyance
• Annoyance
– not sensory
– or physiological effect
• Psychological discomfort from the presence
and increasing concentration of an odor.
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8
Odor
6
Irritation
4
Annoyance
2
Concentration
19
16
13
10
7
4
0
1
Perceived Intensity
Psychophysical Relationships,
Negative response to odor property
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
MCS
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 environmental causes
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Time (chronicity)
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Multiorgan symptoms
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Symptoms at very low levels
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Symptoms affected by presence/
absence of exposure
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Exclusion of other etiologies
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Symptoms acquired
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Demonstrable exposure
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NRC
(1992)
AOEC
(1992)
Netherc
ott
et al.
(1993)
IPCS
(1996)
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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."
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: "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
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 middle-aged, white women
with above-average education.
Other conditions with core MCS
symptoms
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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 handle.
• 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
"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 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”
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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 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
deficient.
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
"[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 unpleasantsmelling 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
civilization.”
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
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
influence.
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.
ACGIH
• Considering role of physical stress
– heat, cold,
• Adjusting TLV’s
Industrial Hygienists Role
• Bad IH
• Good IH
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.