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INTERESTING TOXICOLOGY
CASES
Bruce J. Kelman, PhD, DABT, ATS, Registered Toxicologist (UK and EUROPEAN Registries)
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Outline Causation analysis performed by toxicologists
Difference between differential diagnosis and differential etiology
Forensic case 1 (Air traffic control tower)
Forensic case 2 (Coaxial cable-induced illness)
Construction defect (Seattle Public Schools)
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TOXICOLOGIST Causation paradigm
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Did exposure to a chemical cause this injury?
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Toxicologist causation
Was chemical present?
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Toxicologist causation
Can chemical cause the effect (at any dose)?
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Toxicologist causation
Was exposure sufficiently large and long to cause the effect?
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Toxicologist causation
Did effects occur within an appropriate time frame of exposure?
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Toxicologist causation
What are alternative causes of the effect?
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Was chemical present?
Can chemical cause the effect (at any dose)?
Was exposure sufficiently large and long to cause the effect?
Did effects occur within an appropriate time frame of exposure?
What are alternative causes of the effect?
Specific causation evaluation
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PHYSICIANS
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Differential diagnosis/etiology Differential diagnosis
Identifies a set of diseases or illnesses responsible for the patient’s symptoms
Part of (but different than) causation
Differential etiology
Identifies causal factors involved in an individual’s disease or illness
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Federal Judicial Center. Reference Manual on Scientific Evidence, Third Edition. 2011.
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Symptom presentation
Evaluate patient/signs
Conduct and interpret diagnostic testing
Set of diseases considered
Rule out diseases or injuries
Differential diagnosis/etiology
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Differential Diagnosis
Differential Etiology
Toxicology Causation
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INTERESTING TOXICOLOGY CASES
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Interesting cases to be shared today
Forensic cases (2)
Seattle Public Schools construction defect
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Air Traffic Control Tower Case #1
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Case #1: Air Traffic Control Tower
Air traffic controller claimed injury from exposure to vapor from HVAC cleaner
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Exposure claim
Vapors drawn into HVAC system and distributed to area where the subject worked
Subject smelled a slight pungent orange/lemon-type scented odor for ~10 min before leaving area
Reported nausea, dizziness, facial and hand numbness immediately following exposure
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Health claims
difficulty sleeping
fatigue
memory & concentration difficulties
lightheadedness
dizziness
headaches
disorientation
delayed speech/word finding
stuttering
↑ sensitivity to smells
metallic dysgeusia
facial numbness
tongue numbness
jaw paralysis
extremity numbness
↓ left-side corneal reflex
palpitations
hyperventilation
↑ blood pressure
breathing difficulty with chest tightness
nausea
chills
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Medical records Day Subjective
complaints Objective Findings Diagnosis/Plan
0 Dizziness Face & hand numbness
Unremarkable Dx: “Chemical inhalation” “…the condition found was caused or aggravated by the employment activity described.”
5 Metallic taste Intermittent dizziness Somewhat weak and wobbly Slight numbness below left eye
Persistent normal objective findings Unremarkable neurological exam [except ↓sensation in left trigeminal area, a subjective determination]
Dx: “Trichloroethylene exposure” Causation: “It appears this is consistent with trichloroethylene exposure, which is industrial.”
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Medical records Day Subjective
complaints Objective Findings Diagnosis/Plan
132 Short term memory issue Lack of concentration Lack of energy Difficulty sleeping
Neuropsychological evaluation
“Based on my testing, it appears that there is some legitimate organic deficiency, but at the very high end of the cognitive spectrum. However, the very fact that she sees herself as any less competent than she is accustomed to being produces a tremendous secondary shock which exacerbates the reality of her situation.” Psychotherapy
246 Slight numbness around left eye, left side of tongue and lips
Unremarkable, except: Well-healed, multiple surgical scars above left wrist from prior surgery Slight subjective sensation in lateral 2 fingers
“Adequate evidence does not presently exist to support the conclusion of direct work related causation.” “There is no subjective finding to substantiate this diagnosis [trigeminal neurologic related to TCE exposure].”
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Medical records Day Subjective
complaints Objective Findings Diagnosis/Plan
568 Cognitive, concentration and memory Sx. Occasional minor back pain flares. Numbness of face and tongue.
Unremarkable, except: Decreased sensation to touch of left mid face.
“…her symptoms in the short period of time after the incident were more consistent with anxiety and hyperventilation.” “There is a distinctly functional (psychologically mediated, hypersomatic) flavor to her clinical presentation. Her current presentation of persistent cognitive symptoms is not related to any organic effects of the events and has no toxic basis.”
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Was chemical present?
Can chemical cause the effect (at any dose)?
Was exposure sufficiently large and long to cause the effect?
Did effects occur within an appropriate time frame of exposure?
What are alternative causes of the effect?
Specific causation evaluation (toxicology)
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Was the chemical present?
Trichloroethylene (CAS #79-01-6)
Limonene
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Is the chemical capable of producing claimed health effects?
difficulty sleeping
fatigue
memory & concentration difficulties
lightheadedness
dizziness
headaches
disorientation
delayed speech/word finding
stuttering
↑ sensitivity to smells
metallic dysgeusia
facial numbness
tongue numbness
jaw paralysis
extremity numbness
↓ left-side corneal reflex
palpitations
hyperventilation
↑ blood pressure
breathing difficulty with chest tightness
nausea
chills
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green bullet indicates symptoms consistent with acute inhalation TCE-exposure (ATSDR, 2007).
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Was exposure sufficient to cause claimed health effects?
Exposure assessment:
Model upper limit of exposure using output of aerosolized cleaner (measured mass difference per 3 sec)
Upper limit of exposure in office was 5.3 ppm
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Was exposure sufficient to cause claimed health effects?
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Did effects occur within an appropriate time frame?
Symptoms started after reading MSDS
Symptoms were progressively worse over time
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Alternative explanations
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Day Subjective complaints
Objective Findings Diagnosis/Plan
132 Short term memory issue Lack of concentration Lack of energy Difficulty sleeping
Neuropsychological evaluation
“Based on my testing, it appears that there is some legitimate organic deficiency, but at the very high end of the cognitive spectrum. However, the very fact that she sees herself as any less competent than she is accustomed to being produces a tremendous secondary shock which exacerbates the reality of her situation.” Psychotherapy
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Alternative explanations
Idiopathic environmental intolerances (IEI)
an acquired disorder characterized by recurrent nonspecific symptoms that occur in response to exposure to many, often odorous, chemically unrelated compounds at doses well below the levels shown to cause harmful effects
General consensus by the scientific community*: the toxigenic theory of IEI is unproved and unsubstantiated and more likely to be psychogenic in origin
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* American Academy of Allergy Asthma and Immunology; American College of Occupational and Environmental Medicine; American College of Physicians American Medical Association; World Health Organization
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Coaxial Cable-Induced Illness Case #2
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Case #2: Coaxial Cable-Induced Illness
• Two telecommunication workers
running cable claimed injury from chemicals off-gassing from coaxial cable
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Exposure claim • A “smell” emanated from new cable they were installing
in an office building
• Telecommunication workers claimed exposure to and injury from compounds off-gassing from the cable
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Health claims – Employee #1
Respiratory tract effects Nasal irritation, congestion; runny
nose; sinus congestion; sneezing Throat soreness, tightness, irritation Hoarseness Chest congestion & tightness Cough and sputum Breathing difficulty Shortness of breathing from physical
exertion
Neurological effects Headache, disorientation,
concentration difficulty, weakness, fatigue, deterioration of speech pattern
Ocular effects Dryness, irritation, redness, soreness
Other symptoms Flu-, cold-, or arthritis-like Loss of appetite Loss of thyroid organ Nausea when exposed to other solvents Stiffness and achiness of muscles
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Health claims – Employee #2
Respiratory tract effects Nasal burning, irritation Throat soreness Hoarseness Chest tightness Cough Breathing difficulty Shortness of breathing from physical
exertion
Ocular effects Burning, dryness, irritation, watering
Other symptoms Allergy to plastic Itchiness on the hand Nausea
Symptoms reoccur Upon exposure to new plastics,
cleansers, and bleach
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Medical records – Employee #1 Day Subjective complaints Objective Findings Diagnosis/Plan
0 No medical visits
58 Sore throat; Cough; Labored breathing; Distorted vision
Exam unremarkable except mild inflamed nasal mucosa and some mild cobble-stoning in the oropharynx
Dx: allergic reaction
80 Chest tightness Pulse oximeter room air 98%; Chest x-ray: no significant infiltrate or masses in the lung fields
Dx: Chemical substance; Exposure to fumes, gases and vapor
86 Chest tightness; Nasal congestion
Unremarkable spirometry Impression: Irritant-induced reactive airway disease and irritant induced rhinitis.
142 Sore throat Exam unremarkable except pharynx mildly injected
Pharyngitis. “…there is a possibility that the gastroesophageal reflux may be playing a part in this…”
219 Enlarged and tender thyroid; Elevated TSH; Positive TPO antibody
Impression: Subacute thyroiditis; Possible Hashimoto thyroiditis
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Medical visits - Employee #1
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Medical records – Employee #2 Day Subjective complaints Objective Findings Diagnosis/Plan
0 No medical visits
36 Shortness of breath; Burning of eyes and nasal mucosa; Headache
Exam unremarkable No dx made. Patient wants to go home and rest
59 Breathing difficulty; Burning of eyes
Exam unremarkable Dx: Probable irritation of eyes and throat, secondary to exposure to fumes
80 Cough; Voice change; Eye irritation; Heaviness in chest
Exam unremarkable Dx: Exposure to phosphate ester plasticizers compound; Upper airway irritation
86 Exam and PFT unremarkable Impression: Irritant-induced reactive airway disease
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Medical visits - Employee #2
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Was chemical present?
Can chemical cause the effect (at any dose)?
Was exposure sufficiently large and long to cause the effect?
Did effects occur within an appropriate time frame of exposure?
What are alternative causes of the effect?
Specific causation evaluation (toxicology)
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Was the chemical present?
When retained:
Cable composition known; coated with Phenol Doverphos 8
Triphenyl phosphite Phosphorous acid, diisodecyl phenyl ester Phosphorous acid, isodecyl diphenyl ester
Emission characteristics unknown
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Was the chemical present?
Testing (GC/MS)
Doverphos 8: No (constituents not detected )
Phenol: Yes (detected)
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Is the chemical capable of producing claimed health effects?
DOVERPHOS 8 CONSTITUENTS PHENOL
No toxicological and epidemiological studies showed inhalation exposure to the coating in an occupational environment can cause the claimed health effects.
Irritant effects to mucous membranes noted in animal studies.
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Health claims consisted of symptoms but no significant signs.
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Was exposure sufficient to cause claimed health effects?
Doverphos 8 constituents
Not detected in emissions testing of cable No scientific literature reported coating material exposures
at toxic doses to animals or humans All chemical constituents of coating material were
minimally toxic and unlikely to cause any long-term effects Evaporation rate close to that of corn oil (i.e., very slow)
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Was exposure sufficient to cause claimed health effects?
Phenol
GC/MS analysis measured emission rate from cable
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Estimated phenol concentration in room containing 1000 linear feet of cable (with no ventilation)
After 8 hour of emission 0.02 mg/m3
After 2 weeks of emission 1.3 mg/m3
OSHA 8-hr PEL 19 mg/m3
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Did effects occur within an appropriate time frame?
Onset of symptoms not documented or reported to have occurred within 24 hours after onset of exposure
Symptoms were reported to get progressively worse over time
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Alternative explanations
Documented presence of preexisting and/or unrelated medical disorders Hashimoto’s thyroiditis Fuch’s dystrophy
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Differential Diagnosis
Differential Etiology
Remember
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School Smell Case #3:
Construction defect
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Case #3: School Smell
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Exposure Students and staff complain of “strong odor” of
unknown source
Odor complaints occurred
when HVAC was not running on 100% fresh air, 24 hr/day, or when HVAC shut down for maintenance
Complaints became more frequent with time
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Health claims Staff and students complained of
red, itchy eyes rashes on face, arms sore throat difficulty breathing headache fatigue reproductive problems
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Site inspection and beyond A noticeable, irritating odor was present
Industrial hygienists Confirmed odor was strongest at concrete/carpet interface Collected samples
Comfort parameters: all within normal ranges EPA TO-17: no remarkable measurements
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Site inspection and beyond (cont.) Materials scientists
Collected carpet samples to confirm source of emissions Identified carpet interactions with damp, alkaline concrete
Literature searches PubMed: no reported effects Material science publications: cases of nasal and ocular
effects in building occupants to methyl- hexanols
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What was the chemical in question?
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Sjoberg, A. (2001) Secondary emissions from concrete floors with bonded flooring materials: effects of alkaline hydrolysis and stored decomposition products. Doctor of Philosophy Thesis
Wet & alkaline concrete can react with applied adhesive to release VOCs
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Emission of 5-methyl-1-hexanol measured in a chamber test
0
2,000
4,000
6,000
8,000
10,000
12,000
14,000
Carpet Mastic (Adhesive)
Concrete (Fresh)
Concrete (Bakeout 48h @ 80F )
Concrete (Bakeout 7d @ 80F)
5-m
ethy
l-1-h
exan
ol (
ng)*
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*Amount collected in 6L of nitrogen (0.2L/min flow rate)
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Solution to the construction defect Removed carpet
Bead blasted concrete
Applied correct concrete sealant
Installed new carpet
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End of story
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0
1000
2000
3000
4000
5000
6000
7000
8000
9000
AS
FO
UN
D
AFT
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SE
ALI
NG
NEW
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3 D
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ON
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Hex
anol
s (µ
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Room 299 Room 148
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Remember Sometimes complex medical complaints require help
outside of the biomedical community
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Veritox Inc. 18372 Redmond Way Redmond, WA 98052 425-556-5555 | 425-556-5556 (fax)
www.veritox.com
Bruce J. Kelman, PhD, DABT, ATS, Registered Toxicologist (UK and EUROPEAN Registries)
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