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Post-Midterm: Survey of Environmental Toxicology > Applied Human Toxicology > Flashcards

Applied Human Toxicology Flashcards

1
Q

Animals - Why are they different?

A
  1. Animals are inbred, genetically identical
  2. Doses can be higher than humans
  3. Can easily study cellular effects, pathology
  4. Can evaluate large numbers of animals
  5. Results more defined and interpretable
  6. Fewer confounding factors
    - Lifestyle, complex exposures, genetics
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2
Q

Differences with humans?

A
  1. Wide genetic variation
  2. Exposures lower, less defined, often mixed**
  3. Life style variables
    - Exercise, smoking, alcohol, diet, etc)
  4. Lack of inbred control groups
  5. Limited acceptable protocols
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3
Q

Animal Tox Methods?

A 
Route of exposure
 Type of exposure
In vivo - Expose animal**
 Evaluate whole animal response
 Evaluate cellular changes
In vitro - Cellular effects**
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4
Q

Routes of exposure - Animals?

A 
Injection, IP and IM
 Oral gavage
 Inhalation
 Dermal
 Food
 Drinking water
Injection and oral gavage relevant for humans**
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5
Q

Types of exposure - Animals?

A 
Acute - irritant to eye, skin, sensitization
 Acute - LD 50
 Subacute - range-finding, days
 Subchronic - days to weeks
 Chronic - months to years
Acute, subacute relate to humans**
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6
Q

In vivo animal testing?

A

Expose and Evaluate Whole Animal End Points
Pathology End Points
Other Cellular End Points

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7
Q

In vitro animal testing?

A

Cellular Level Studies

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8
Q

Human Subject Committees

A
  1. Must have lay representation**
  2. Informed consent
  3. Medical monitoring of project
  4. Selection criteria of exposed and controls
  5. Communicate results to subject and doctor
  6. Deals with real and perceived issues impacting the subject
  7. Who gets the results?
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9
Q

Ethics of Human Exposure

Studies

A
  1. Should humans be exposed to toxics?
     What about children?
  2. What are health effects of exposure?
  3. Are there hyper-responsive subjects?
  4. Response plan for possible acute effects?
  5. What legal protection does researcher have?
  6. Are alternatives available?
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10
Q

Routes of exposure - Humans?

A 
1. Inhalation - common in workplace
 Nasopharyngeal
 Tracheobronchial
 Pulmonary - Alveoli
2. Percutaneous - occup and environmental
 Stratum corneum
 Epidermis, dermis
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11
Q

Oral Ingestion - Humans

A 
What
 Foods & water
How
 Hand to mouth contact (demonstrate)
 Special problems with children
Mechanism
 Solubility and pH dependent
 Remember Henderson-Hasselbalch equation?
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12
Q

Types of human studies?

A
  • Case reports
  • Controlled laboratory testing or challenge tests
  • Workplace exposure studies
  • Epidemiology studies
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13
Q

Case Reports

A
  1. Usually involve one patient
  2. Lack of information on exposure
  3. Many confounding factors
  4. Not research but anecdotal
  5. Not generalizeable
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14
Q

Controlled Laboratory Exposure

A
  1. Need controls and exposed subjects
  2. Expensive, small number of subjects
  3. Low level exposures - uncertain effects
  4. Limited to acute or short-term exposures
  5. Do not reflect “real world” exposures
  6. Analysis and reporting differences from
    different studies
    - Meta analysis
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15
Q

Other issues in human studies?

A
  1. Workload impacts inhalation exposure
  2. Route of exposure often mixed
  3. Clothing and temperature impact dermal
    exposure
  4. Difficulties in conducting 8-hr exposures
    - Bathroom and food breaks
    - Specimen collection
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16
Q

Occupational or Environmental

Field Studies- Assessments

A 
 Confounding factors, mixed exposures
 Widely variable exposures during work day
 Combined job and environment exposures
 Second job exposures or hobbies
 No control for life-style variables
 Controls - matched or own control?
17
Q

Epidemiology Studies - Outcomes

What was the cause?

A

 Need large population and controls
 Multiple exposures - work & environmental
 Exposure assessment often lacking
 Genetic predisposition, susceptibility
 Life style variables, the gray zone
 Cannot often isolate the cause to a single agent

18
Q

Epidemiology studies - Examples

A 
Benzene exposure (retrospective)
 Leukemia incidence related to past exposure
 What dose causes leukemia?
Aniline and o-tolidine in tire making
 Excess of bladder cancer
 Biomarkers of aniline and o-tolidine identified
 NIOSH alert
 What was the exposure?
19
Q

Other Types of Exposure Endpoints

A 
Cytogenetic end points in blood
 Chromosomal abberations
 Sister chromatid exchange
 Micronuclei
 Metabolism studies - examples
 Benzene - field
 PAHs - field
 Chlorobenzene - experimental
20
Q

Comparison of human Epi versus animal exposure studies (Table 34-7)

A

Toxicant exposure, species consideration, analytical challenges

21
Q

Examples of Exposure Studies

A 
Incident related studies
 Toxicokinetic studies - examples
       MBOCA - Accident
 Health effects studies -examples
       Arsenical keratosis – field
       Hiroshima studies
In vitro studies in humans
 Lypmocytes, tissue cultures, DNA cross-linking

Post-Midterm: Survey of Environmental Toxicology (10 decks)

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