Toxicology Test 1

Front 1

What is a hazard?

Back 1

-ability of chemical to cause injury ina given setting
-inherant toxicity vs amounts of likely exposure

Front 2

What is a risk?

Back 2

-expected frequency of occurance of undesirable effect

Front 3

What is a toxin?

Back 3

-from natural/living sources
-toxicant that has its origin in animal or plant form (venom)

Front 4

What is a toxicant?

Back 4

-chemical entity that acts as a poison (carbon monoxide or radiation)

Front 5

What is a xenobiotic?

Back 5

-source of a chemical from outside the body

Front 6

What is the rate of exposure and how is it affected?

Back 6

-concentration x frequency x duration
-affected by route of contact
-route of transport
-uptake and distribution
-bioavailability
-pattern and/or timing of exposure

Front 7

What is considered waste?

Back 7

-industrial, animal, runoff from fields, deposition/ percolation from ground, or deposit from space/sunlight

Front 8

What are various ways waste cna get into humans?

Back 8

-inhalation (dust, vapors, gases)
-soil ingestion (veggies, animal feed, animals)
-dermal absoprtion (gases, vapors, soil etc.)
consumption (milk, water, fish, animal, veggies)

Front 9

What is acute exposure?

Back 9

-1 time exposure over 24 hrs or less

Front 10

What is chronic exposure?

Back 10

-multiple exposure over time greater than 6 months

Front 11

What does toxicity cause?

Back 11

-death
-loss of viability
-loss of function (metabolize, use ATP, or oxygen)
-inability to grow (can't replicate, may increase body weight)
-over response to stimuli (e.g hypersensitivity through immune system)

Front 12

What is ED50 (LD50)?

Back 12

-defining characteristic in measuring death

Front 13

What is loss of viablity?

Back 13

-loss og function (inability to metabolize at cellular level)
-inability to grow
-timing may change viability
-adaptation affects viability

Front 14

What is tolerance (dispositional vs responsive)?

Back 14

-decrease in responsiveness to toxic effect due to previous exposure

Front 15

What is transient toxicity?

Back 15

-short -term/reversible

Front 16

What is persiostent toxicity?

Back 16

-long-term/irrefversible

Front 17

What is local toxicity?

Back 17

seen at site of first contact (skin, lungs)

Front 18

What is systemic toxicity?

Back 18

-toxin is distributed to different organs

Front 19

What does toxicity measure?

Back 19

-ED50 (LD50)
-viability
-tolerance
-transient vs persistant
-local vs systemic
-cumulative vs latent

Front 20

What is cumulative toxicity?

Back 20

-increase degree of toxic effect due to repeated doses

Front 21

Whata re examples of mechanistic/predictive focus areas of toxicology?

Back 21

-biochemical
-mutagenic
-carcinogenic
-genomic
-physiologic
-apoptotic
-necrotic
-inflammatory

Front 22

What are examples of regulatory focus areas of toxicology?

Back 22

-FDA
-EPA
-OSHA
-DOT

Front 23

Whata re examples of descriptive focus areas of toxicology?

Back 23

-testing, in vivo vs in vitro, humans, ecosystems, "ides" (insectis, herbic), solvents

Front 24

What are examples of risk assement focus areas of toxicology?

Back 24

-hazard identification
-risk characterization
-risk perception, comparative analysis

Front 25

How does i9n vitro toxicity correspond to LD50?

Back 25

-can be indicative of the LD50
-some correspondance b/t the two
-concentratiopn in cell cuture dish is comparable to the toxicity that reaches the cells in the body

Front 26

What are implications for in vitro vs in vivo?

Back 26

-specificity
-sensitivity
-tissue repair, adaptation to injury

Front 27

How is specificity an inplication for in vivo vs in vitro toxicities?

Back 27

-high organ specifity, only affects liver cells and no others
-test in vitro using epithelial cells and find much les toxicity
-in vitro use the same cells to be comparable or in vivo will just have higher toxicity

Front 28

How is sensitivity an implication for in vitro vs in vivo toxicities?

Back 28

-in vivo distributed throughout entire body and cvould be less toxicity than an in vitro
-unless toxicant becomes a toxin with biological metabolism that is not seen in vitro

Front 29

How is tissue repair/ adaptation ot injury an implication of in vivo vs in vitro toxicity?

Back 29

-response to toxicity is the ability to do tissue repair

Front 30

What is the 2 stage model of tissue repair/adaptation to injury?

Back 30

-inflective stage- toxic chemical initiates injury
-progression/regression stage- presence or absence of compensatory processes
-follows a dose response process in tissue

Front 31

What are factors to consider that affect the tissue repair porcess from toxicity?

Back 31

-age
-species/strain
-nutrition/energy
-disease
-newborns have faster repair than adults
-species at same weight can be different
-chemical toxicity cna be decreases if calories are restricted, stunts growth

Front 32

What is the physical state of toxins/toxicants?

Back 32

-gas
-liquid
-dust

Front 33

What is the chemical stability/reactivity of toxins/toxicants?

Back 33

-explosive
-flammable
-oxidizer

Front 34

What are the general chemical structures of toxins/toxicants?

Back 34

-aromatic amines
-halogenateds
-hydrocarbons

Front 35

What is the poison potential?

Back 35

-qualifying for the public

Front 36

What are the biochemical mechanisms of action for toxins/toxicants?

Back 36

-alkylating agents
-sulfhydryl blockers

Front 37

What are various sites of exposure for toxins/ toxicants?

Back 37

-GI tract (ingestion)
-lungs (inhalation)
-skin (topical, percutaneous, dermal)
-suppository

Front 38

How are factors concerning routes of exposure or administration?

Back 38

-affected by "vehicle", puported non-active component, solvent for the chemical
-also by other "formulation" components
-things to stabilize toxicant (antioxidant for something that is an oxidant)
-affected by route (agent detoxified by liver expected to be less toxic when given orally (portal circulation) than by inhalation (systemic circulation)

Front 39

What is the order of speed of toxicity through various routes of administratiuon of toxins/toxicants from most rapid to least rapid?

Back 39

intravenous > inhalation> intraperitoneal> subcutaneous> intramuscular> intradermal> oral> dermal

Front 40

What is acute exposure to toxins?

Back 40

<24 hour exposure via ip, iv, subQ, oral, dermal
-usually single administration

Front 41

What is subacute exposure to toxins?

Back 41

-less than 1 month
-repeated administration

Front 42

What is subchronic exposuyre to toxins?

Back 42

-1-3 months
-repeated administration

Front 43

What is chronic exposure to toxins?

Back 43

-greater than 3 months
-repeated administration

Front 44

How do toxic affects of a single exposure differ from those produced by repeated exposures?

Back 44

-repair processes
-chemical accumulation (concetration) in specific tissues (lipophilic compunds accumulating in fat)
-takes longer for toxin to be eliminated after repeated doses

Front 45

What is inflammation?

Back 45

-local
-release of cytokines causing redness
-also causes fibros- scarring

Front 46

What is necrosis?

Back 46

-cellular death
-membrane damage
-can be diffuse or local

Front 47

What is enzyme inhibition?

Back 47

-blockade of normal pathways
-can cause accumulation of substrate
-deficiency of function
-such as organophopsates, cyanide (inhibits cytochrome)
-tissues become hypoxic

Front 48

What is biochemical uncoupling?

Back 48

-interferance in synthesis of ATP, oxidative phosphorytlation
-such as dinitrophenol (uncouples synth of ATP, releases heat causing hypothermia

Front 49

What is lethal synthesis?

Back 49

xenobiotics that incorporate in biological pathways
-such as flouroacetate (stops TCA cycle)

Front 50

What is lipid peroxidation?

Back 50

-in biological membranes resulting in cell disfunction and death

Front 51

What is covalent binding?

Back 51

-electophilic metabolites

Front 52

What is immune mediated hypersensitivity?

Back 52

-effect at dermal level

Front 53

What is immune suppression?

Back 53

-modulation of the immune system
-increase susceptibility to tumorgenic chemical
-also immune overactivity

Front 54

What is neoplasia?

Back 54

-process of carcinogenesis
-genotoxic event
-mutated cells (intiating and promotion)

Front 55

What is common vs idiosyncrastic?

Back 55

-common is characteristic theme
-idiosyncratic is newly discovered, has specilized routes

Front 56

What is immediate toxicity?

Back 56

-happens within 6 months

Front 57

What is delayed toxicity?

Back 57

-happens many years later

Front 58

What is local vs systemic?

Back 58

-local is specific site
-systemic is multiple organs

Front 59

What is the difference b/t dose and dosage?

Back 59

Dose: amount per unit time or animal

Dosage: amount per unit per 1000 grams

Front 60

Whata re the principles of toxicity testing?

Back 60

-effects produced by a compound in laboratory animals, when properly qualified, are applicable to humans
-exposure of experimental animals to toxic agents in high doses is necessary and valid method of discovering possible hazards in humans (incidence increases with dose or exposure)

Front 61

Whata re problems with toxicity testing?

Back 61

-biological variability
-selective toxicity based on distribution, cytology, biochemistry
-species differences
-experimental confounders (strain, age, weight, etc.)

Front 62

What are rationale for using in vivo test systems?

Back 62

-actions/effects on intact animal and organ-tissue interactions
-either neat chemicals or complete formulated products cna be tested
-concentrated or diluted products or mixutes cna be tested
-yields data relevant to recovery and healing
-required by many agenies/laws
-uses qualitative and quantitative tests
-amenable to modifications
-uses extensive databases
-low cost
-generally conservative and broad in scope
-single or multiple endpoints

Front 63

What is acute lethality?

Back 63

-LD50- 1 or more routes of admin.
-1 or more species

Front 64

How you in vivo test for acute lethality?

Back 64

-find LD50
-using 1 or more routes of administration
-give no food, give single dose for 14 days and look at results

Front 65

How do you in vivo test for skin adn eye irritations?

Back 65

-use draize test
-shave skin 1 in. in diamter, 2 abrased, 1 intact
-llok for erythema, escher, and edema

Front 66

How do you in vivo test for sensitizations?

Back 66

-use guinea pigs: sahve skin--> repeated admin. for 2-3 weeks then stop for 2-3 weeks
-use Draize test using a much less dose

Front 67

How do you test in vivo for subacute toxicity?

Back 67

-mixed with food--> 14 days--> observe #dead
-then conduct clinical chemistry/histology

Front 68

How do you test in vivo for subchronic toxicity?

Back 68

-90 days, most common test
-look for NOAEL, no observed adverse effect lvl
-use 2 species

Front 69

How do you test in vivo for chronic toxicity?

Back 69

-usually done at same time as human studies
-6 months to 2 years
-use 1 or more species with repeated doses

Front 70

How you test toxicity for development and reproduction?

Back 70

-test development of offspring by testing pregnant mother

Front 71

What is the Ames test?

Back 71

-tets for mutations
-place histidine salmonella strain in histidine-free medium and see if they survive

Front 72

What are limitations of in vivo testing?

Back 72

-potential confounding or masking of findings in complex in vivo systems
-technician training and monitoring are critical
-lack of standarization
-large biological variability b/t experimental units
-structural and biochemcial differences make extraolation from animal to human, and vice-versa, problematic
-large, diverse fragmented databases are not readily comparable
-varaible correlation with human results

Front 73

Whata re high thoughput screening of in vitro tests?

Back 73

-mehcanism-based
-defect or disease-based approach

Front 74

How are cell culture models used for in vitro testing?

Back 74

-human vs animal
-cell type specific vs mixed cell

Front 75

What is in situ testing for in vitro testing?

Back 75

-specific parameter
-specific tissue

Front 76

What are example sof preclinical testing?

Back 76

-in vitro testing
-descriptive (in vivo) animal testing

Front 77

What is phase 0 of clinical testing?

Back 77

-micro dosing
-use volunteers (15 ind)
-single sub-therapeutical dose

Front 78

What is phase I of clinical testing?

Back 78

-largeer number of individuals
-get index of tolerability
-side effects?

Front 79

What is phase II of clinical testing?

Back 79

-20-300 individuals (volunteers and patients)
-is drug working?

Front 80

What is phase III of clinical testing?

Back 80

-multicenter trials
-several hundred to thousands

Front 81

What is phase IV of clinical testing?

Back 81

-post marketing
-surveillance
-monitor use of drugs

Front 82

What is toxicokinetics?

Back 82

-like pharmacokinetics
-modeling/mathematical description of time crouse of disposition for xenobiotics, exogenous molecules

Front 83

What processes occur duing toxicokinetics and how is it measured?

Back 83

-absorption-blood (plasma( sampling
-distribution- conc. as a function of time
-biotransformation
-excretion- concentration of tissue

Front 84

What is the apparent volume of distribution? Equation?

Back 84

-apparent space of where a chemical is put, not a real value
-Vd= Doseiv/ Bx AUC (area under curve)
-Vd= doseiv/ Co for 1 compartment

Front 85

What is the equation to measure clearance?

Back 85

-Cl= Doseiv/ AUC (Kel*Vd)
-Cl=VdX B (2 compartments)
-Cl=Vd x Kel (1 compartment)-Cl= (.693 x Vd)/ T1/2

Front 86

What is the classic approach to toxicokinetics?

Back 86

-one or two compartment model, even if no apparent physiologic or anatomical reality

Front 87

What are physiologically based models of toxicodynamics?

Back 87

-seris of mass balance equations to dexcribe functions of organs/tissues, based on physiologic considerations
-has high predictive power
-higher number of compartments

Front 88

What are perfusion-limited compartments?

Back 88

-those in which uptake in an orgam is limited by blood flow to an organ

Front 89

What is diffusion-limited compartments?

Back 89

-those in which uptake is proportional to membrane permeability and total membrane area

Front 90

Whata re the goals of risk assessment?

Back 90

-balance risks and benefits (drugs, pesticides, chemicals)
-set target levels of risk (which is allowable, what is ddesirable..., e.g. food contaminants, water or air pollutants)
-set priorities for program activities (regulatory agencies, manufacturers, environmental/consumer organisations)
-estimate residual risks and extent of risk reduction after steps are taken to reduce risk

Front 91

What risk assessments are involved in lab/field effects?

Back 91

-hazard identfication
-structure-activity
-invitro tests
-animal bioassay
-epidemiology

Front 92

What risk assessment is involved in mechanistic studies?

Back 92

-dose-response assessment
-relationship
-susceptibility

Front 93

What risk assessment ios involved in exposure measures?

Back 93

-exposyre assessment
-types
-levels
-duration

Front 94

What is experimental determination of causality?

Back 94

-causality becomes knowable when scientific experiments demonstrate strong, consistent (repeatable), specific, dose-dependent, coheerent, temporal, anbd predictive manner that a change in stiumulus determines an assymetric, directional change in the effect

Front 95

What is epidermiolofical determination of causality?

Back 95

-if knowledge is robust, causation can be inferred from observational (non-experimental) studies, where allocation of test subjects or items is not under the control of the investigator

Front 96

What are the possible steps for evidence-based determination of risk?

Back 96

-collection and evaulation of relavent data
-collection and evaulation of relevant knowledge
-joining data with knbowledge to generate a conclusion