Toxicology Test 3

Front 1

What are pesticides? benefits? risks? What is it regulated by?

Back 1

-chemicals used to destroy undesireable pests or plants
-improved crop yield and eradication of vector borne diseases
-human fatalities and long term toxicity
-environmental contamination
-biomagnification (lipid solubility)
-translocation by vaporization, drift, water supply
-federal insectiside, fungicidal, rodenticide act
-nemanticides, plant growth regulators defoliants, desiccants addes in 1951 and 1961
-administrative authority turned over to EPA in 1972

Front 2

What can exposure to pesticides may result in?

Back 2

-neurotoxicity
-reproductive effects including endocrine systems (endocrine disruptors)
-teratogenic effects
-carcinogenic and oncogenic effects
-mutagenic effects
-hematological effects including anemia
-immunological effects including suppression and activation
-transgenerational effects

Front 3

What are insecticides?

Back 3

-essentially chemicals attacking the neurotransmitter receptors, ion channels, and related enzymes in insects
-nicotinic receptors aree also present in humans, insecticides cause toxcitiy in humans

Front 4

What are organochlorines as insecticides? Acute and chronic effects?

Back 4

-low volatility, chemically stable, lipid soluble, slow rate of biotransformation and degradation
-estrogenic and enzyme-nducing effects interfere directly or indirectly with fertility and reproduction
-acute toxicity associated with CNS disturbances
-chronic toxicity manifests as hepatic hypertrophy, centrilobular necrosis, hepatic tumors
-toxicity involves CNS and PNS hypersensitivity due to prolonged negative afterpotential
-chlornated cyclodiene, benzene, cyclohexane, inseticide toxicity characterized by CNS hypersensitvity
-high lipid solubility, slow metabolism promotees extensivee and prolonged stoage of insecticides

Front 5

What are proposed sites of action of DDT (insecticide)?

Back 5

-reducing potassium transport through pores
-inactivating sodium channel closure
-inhibiting sodium-potassium and calcium-magnesium ATPases
-calmodulin-calcium bid=dning with release of neeurotransmitter

Front 6

What are proposed sites of action of cyclodiene-type insecticide?

Back 6

-chlorine ion transport by nhibiting GABA receptors on the chloride channel as well as inhibition of Ca, Mg-ATPase

Front 7

What are anticholinerative insecticides? symtoms ot toxicity? Delayed toxicity?

Back 7

-organophosphorus esters (parathion,paraoxon) and carbamate esters
-symptoms of poisons are due to cholinestrase inhibition
-muscarinic symtpoms: tightness in chest, wheezing, saliva
-nicotinic symtoms:involuntary twitching, hypertension
CNS symptoms: anxiety, restlessness, insomnia
-death due to asphyxia scondary to respiratory failure
-delayed neurotoxicity: seen with organophosphorus esters but not carbamate esters

Front 8

Where do organophosphorus and carbamate esters bind to as in active site of enzyme?

Back 8

-hydroxyl group

Front 9

What are pyrethroid insecticides?

Back 9

-compounds extracted from pyrethrum or chrysanthemum floweres
-rapid paralytic action on flying insects despite low toxicity in insects and mammals due to efficient metabolism

Front 10

What are possible sites of action for pyrethroid insecticides?

Back 10

-GABA inhibitor which also innhbiits chlorine intake
-Ca/MG ATPase for efflux of calcium

Front 11

How do you classify herbicides?

Back 11

-by application time and method (preplanting, preemergent, postemergent)
-mechanism of toxicity (selectve, contact, translocated)

Front 12

What is the mechanism of action of Ureas, 1,3,5-triazines, etc.?

Back 12

-inhibiton of photosynthesis by disryption of light reactions and blockade of electron transport

Front 13

What is the mechanism of action of dinitrophenols and halophenols?

Back 13

-inhibition of respiration by blockade of electron transfer from NADH or blocking thee coupling of electron transfer to ADP to for ATP

Front 14

What is the mechanism of action of aryloxyalkylcarboxylic acids and benzoic acids?

Back 14

-growth stimulents
-auxins

Front 15

What is the mechanism of action of alkyl N-arylcarbamates?

Back 15

-inhibitors of cell and nucleus division

Front 16

What is the mechanism of action of chloracetamide, o-substituted diphenyl ethers and hydrazines as an herbicide?

Back 16

-inhibition of carotenoid synthesis
-protective pigments in chloroplasts to prevent chlorophyll from being destroyed by oxidative reactions

Front 17

What is the mechanism of action of S-alkyl dialkylcarbamodithioates and aliphatic chlorocarboxylic acids as an herbicide?

Back 17

-inhibiton of lipid synthesis

Front 18

What are chlorophenoxy compounds as herbicides?

Back 18

-auxins- stimulate growth in plants
-TCDD (dioxin)- carcinogenic,teratogenic and immunosuppresant for humans
-agent orange: combination of n-butyl esters of 2,4-D and 2,4,5-T contaminated with TCDD

Front 19

What are biochemical effects of TCDD on humans?

Back 19

-enzyme induction--> altered metabolism
-modulation of hormones and receptors--> altered homeostasis
-modulation of growth factors and receptors--> altered growth and differentiation

Front 20

What is the molecular mechanism of action of dioxin-like chemicals to activate AhR-dependent gene expression?

Back 20

-enters cell and binds to AhR gene expressing compound, which is also bound to protein hsp90
-the proteins undergo tranformation and the chemical is translocated into the nucleus and binds to DRE's, ARNT's
-once expressing P4501A1, mRNA expresses new polypeptides which leades to toxicity

Front 21

What are bipyridals as herbicides (paraquat, diquat)?

Back 21

-pulmonary toxicants
-conduct lipid peroxidation

Front 22

What are the various properties of solvents?

Back 22

-exposure
-frequency of exposure
-toxicity

Front 23

How is exposure a property of solvents?

Back 23

-volatile solvents present as vapors (route of entry via respiratory system and penetration into systemic circulation via diffusion)
-partition coefficient affects toxicity onset time
-percutanous route of entry includes local irritation and affects integrity of skin barrier

Front 24

How is frequency of exposure a property of solvents?

Back 24

-consumer vs occupational exposure
-standarization includes threshold limit value, time-weighted average, and short term exposure limit
-regulation is by OSHA and NIOSH

Front 25

How is toxicity a property of solvents?

Back 25

-involves central nervous system
-disorieentation progression to loss of consciousness
-respiratory or cardiovascular collaspe
-physical interaction between solvent and cells of CNS
-organ specific toxicities of some solvents due to repeateed exposure to tolereable lvls of solvents
-can cause metabolic bioactivation (species difference in p450 enzymes)
-based on saturation kinetics (partition coefficient and lipphilicity)

Front 26

How is benzene a toxic solvent?

Back 26

-sources include steel production, fuel, and solvent for rubber and inks, also starting material for chemical synthesis
-acute toxicity includes CNS depression leading to unconsciousness and death
-has hematopoietic toxicity including aplastic anemia and acute myelogenous leukemia
-caused by benzene metabolites

Front 27

What detox pathway can help against benzene toxicity?

Back 27

-glutathione

Front 28

How is chloraform and carbon tetrachloride toxic solvents?

Back 28

-reversible hepatoxicity
-nephrotoxicity
-forms free radicals for lipid peroxidation and covalent binding

Front 29

How is ethyl alcohol a toxic solvent?

Back 29

-TLV= 1000ppm
-legal intoxication= .8mg/100mL
-metabolism will reduce blood alcohol by 15-20 % per hour
-general anethetic and nutrient for CNS
-can cause fetal alcohol syndrome (mental deficency and microcephaly)
-alcohol metabolism by alcohol dehydrogenase, aldehyde dehydrogenase, and cytochrome P450

Front 30

How is methanol a toxic solvent?

Back 30

-retinal toxicant causing reversible or permanent blindness
-methanol becomes formaldehyde, then formic acid then CO2 during metabolism by catalase peroxidative and alcohol dehydrogenase pathway

Front 31

How is ethylene glycol and propylene glycol toxic solvents?

Back 31

-ethylene glycol is antifreeze
-metabolized by alcohol dehydrogenase then aldehyde oxidase to beocme oxalic acid
-proylene glycol is additive in food and cosmetics
-metabolized by same enzymes to become pyruvic acid
-used in lacquers, varnishes, resins, printing ink,, textiledyes, and gasoline additives
-can cause reproductive toxicity

Front 32

What is the molecular pathway of Rhodanese activity with cyanide?

Back 32

-thiosulfate group reacts with thiol group on cysteine-247 to form a disulfide
-it then reacts with cyanide to produce thiocyanide then converts back to normal thiol

Front 33

How is rhodanese enzyme activity important?

Back 33

-important in the contamination of cyanide since thiocyanate formed is relatively harmless
-the use of thiosulfate solution as an antidote for cyanide poisoning is based on the activation of this enzymatic cycle

Front 34

What is the route of metals in the environment for potential toxicity?

Back 34

-metal emission goes to either the atmosphere and/or with fallout/washout goes to terrestial systems (with runoff/irrigation), lakes/rivers (with flow), yo estuaries (with mixing), to oceans
-from there to sediments and specimens

Front 35

What are the various areas of exposure for metal toxicity?

Back 35

-metals from the air can get into the respiratory tract
-metals in food, water, and drugs can get into the GI-tract
-metals can also get on the skin
-eventually circulates around the blood and passes through the kidneys and liver
-then gets excreted by sweat, hair, urine, and feces

Front 36

What is cellular uptake of metals?

Back 36

-soluble metal compounds taken through cellular ion channels and transporters
-particulate metal compounds taken in by phagocytosis
-metal compound may be reduced and bind to proteins inside cells
-mechanism of toxicity depends on metal species

Front 37

What does metal toxicity depend on?

Back 37

-length of exposure time
-concentration
-and type of metal species

Front 38

What is the biological half-life of metals?

Back 38

-short (arsenic)
-long (cadmium)
-due to specific tissue retention

Front 39

What does cellular target of metals depend on?

Back 39

-metal species and lipid solubility

Front 40

What are indicator tissues for recent exposures? long term?

Back 40

-blood, urine (except for cadmium)
-hair

Front 41

What factors influence toxicity of metals?

Back 41

-interactions with essential metals
-formation of metal-protein complexes
-age and stage of development
-lifestyle factors
-chemical form or speciation
-immune status of host

Front 42

What metals are carcinogenic for humans?

Back 42

-arsenic
-beryllium
-cadmium
-hexavalent chromium
-nickle compounds

Front 43

What metals are carcinogenic to animals?

Back 43

-arsenic
-beryllium
-cadmium
-hexavalent chromium
-dextran
-inorganic lead
-inorganic mercury chloride
-metallic and compound nickel

Front 44

What are metals in carcinogenesis? What are various mechanisms?

Back 44

-metals act as carcinogens or co-carcinogns involving:
-interferance with cellular redox systems and oxidative stress
-inhibiton of DNA repair causing mutations
-deacetylation leading to gene activation and methylation leading to gene silencing
-deregulation of cellular prolifereation control by induction of proto-oncogens, inactivating p53 and apotosis signals
-can bind directly to DNA (Chromium)
-cna have specific interactions with proteins

Front 45

What metals can cause chelation?

Back 45

-natural chelators:
-metallothionine by cadmium, insulin by zinc, hemoglobin by iron, mRNA by Mn, antibiotics by magnesium, and enymes by sulfhydral groups
-EDTA: Ca++ form not Na+
-BAL and derivatives
-microbial products: penicillamine and desferrioxamine
-dithiocarbamates for Nickel or cadmium

Front 46

What is lead toxicity? neurological? peripheral? hematological? Renal? cardiovascular? endocrine? carcingenicity?

Back 46

-neurological: cognitive, IQ, neurodevelopment, neurotransmitter release, disrupts tight junctions, replaces calcium, affects Na-K-ATPases
-peripheral neuropathy by demyelation and schwann cell degeneration
-hematological: anemia, erythrocyte maturation and shortened lifespan and impaired heme synthesis by inhibiton of porphyrin incorportation
-renal effects: inhibit proximal tubule function
-cardiovascular: hypertension
-endocrine effect: affects male reproduction
-carcinogenicity: shown in animal models but not in humans

Front 47

What is mercury toxicity?

Back 47

-target organ depends on chemical species:
-inorganic salts go to kidney
-organic salts go to CNS
-vapor goes to CNS
-has high affinity for thiol group in enymes
-can cause parethesia, ataxia, dysarthria, deafness and death

Front 48

What is cadmium toxicity?

Back 48

-important contaminant in environment (industry and seafood)
-may be inhaled through some cigarettes
-calcium or iron deficiency enhances cadmium absorption
-competes for zinc uptake
-retained in body (bone) for a long time (bone pain and fragility)
-major acute target is kidney
-complexes with metallomethionine (produced in the liver)
-teratogenic and carcinogenic (testicular, prostate)

Front 49

What is arsenic toxicity?

Back 49

-a classic poison, many chemical forms used in pesticides, etc.
-a concern in drinking water as mineral water of volcanic source
-target tissues include GI, skin, neurotoxicity (central and peripheral), and respiratory system
-carcinogenic (skin, lung) and teratogenic
-high affinity for thiol group
-use BAL treatment as antidote

Front 50

What is beryllium toxicity?

Back 50

-important industrial metal (alloy, ceramic)
-tissue target is lung (berylliosis and cancer)
-immune toxicity includes contact dermatitis and delayed hypersensitivity

Front 51

What is chromium toxicity?

Back 51

-multiple valence forms
-cofactor for insulin
-glucose tolereace factor
-renal toxicity and cancer for respiratory tract

Front 52

What is nickel toxicity?

Back 52

-deficency causes anemia (iron absorption)
-immunogenic (contact dermatitis from jewlery and causes lung and nasal cancers)

Front 53

What is cobalt toxicity?

Back 53

-essential component in vitamin B12
-causes cardiomyopathy and polycythemia

Front 54

What is copper toxicity?

Back 54

-cofactor in many enzymes such as SOD, cytochome oxidas, and catalase
-can casue abnormal organ development

Front 55

What is iron toxicity?

Back 55

-in hemeglobin
-excessive uptake may occur in use eof iron pots, frequent blood transfusion
-results in accumulation of iron storage sites (ferritin and heemosiderin)
-deficency causes increase in transferrin

Front 56

What is manganese toxicity?

Back 56

-cofactor in enzymes and RNA
-inhalation of Mn causes pneumonitis and CNS damage (parkinsons?)

Front 57

What is selenium toxicity?

Back 57

-cofactor for enzymes such as glutathione peroxidase
-excess produces CNS toxicity

Front 58

What is atrophy?

Back 58

-decrease in cell size or number in a tissue, organ, or part

Front 59

What is hypertrophy?

Back 59

-increase in cell size, both physiologic and pathologic

Front 60

What is hyperplasia?

Back 60

-increase in cell number, both physiologic and pathogenic

Front 61

What is metaplasia?

Back 61

-change in cell phenotype, more often pathogenic

Front 62

What is dysplasia?

Back 62

-failure to differentiate completely and normally, usually pathologic

Front 63

What is anaplasia?

Back 63

-failure to differentiate (to an adult phenotype), a criterion of malignant neoplasm

Front 64

What is neoplasm?

Back 64

-tissue (mass) resulting from abnormal cell growth, tumor in lay term

Front 65

What is neoplasia?

Back 65

-the process of neoplastic growth

Front 66

What is benign neoplasm?

Back 66

-a neoplasm growing localy

Front 67

What is malignant neoplasm (cancer)?

Back 67

-a neoplasm that invadees and/or metastasizes

Front 68

What is invasion?

Back 68

-growth into surrounding tissues, traversing normal tissue boundary

Front 69

What s metastasis?

Back 69

-growth of cancer cells at a second, separate sites, involving spreading by the circulation

Front 70

How do you diagnose neoplasms?

Back 70

-gross examination: lumps, bumps, ulcer...
-imaging: x-ray, CT scan, ultrasound, MRI, PET
-blood sampling: PSA, TNF...
-histological examination by brush cytology, needle biopsy and incisional and dissectional biopsy

Front 71

What is the pathology of neoplasm?

Back 71

-each type of neoplasm has a characteristic behavior with some variation
can be benign or malignant

Front 72

What is the nomenclature of neoplasms?

Back 72

-indicating cell origin and suggesting malignancy
-benign ends in -oma: adenoma,fibroma...
-malignnat ends in carcinoma ot sarcoma: adenocarcinoma,, leimyosarcoma...
-exceptions include melanoma, glioma, and astrocytoma

Front 73

What is a carcnoma?

Back 73

-tumors derived from epithelial cells including squamous cell carcinoma, adenocarcinoma (gladular), urothelial carcinoma
-most common cancer type and reprsnts 80-90% of all cancer cases

Front 74

What is lymphoma/leukemia?

Back 74

-cancers of bone marrow derived cells (lymphoma) or white blood cells (leukemia)

Front 75

What is sarcoma?

Back 75

-tumors derived from mesenchyma tissues such as muscle bone, cartilage, fat, and fibroblast

Front 76

What is differentiation of tumors?

Back 76

-refers to extent to which tumor cells resemble comparable normal cells, both morphologically and functionally
-benign tumors are generally well differentiated
-malignant tumors range from well differentiated to anaplastic
-have cellular and nuclear pleomorphism
-high nuclear to cytoplasmic ratio
-hyperchromatic straining
-more mitoitc cells
-tumor giants cells

Front 77

What is the rate of growth of tumors?

Back 77

-most benign tumors grow slowly whereas most cancers grow rapidly
-tumor growth rates are correlated with their level of differentiation
-with significant variations dependent upon body hormone lvls, tissue blood supply, and many unknown factors

Front 78

What is local invasion of tumors?

Back 78

-nearly all benign tumors grow as cohesive and expandive masses that remain localized to their site of origin
-most benign tumors are encapsulated ina rim of compressed connective tissue, calleed fibrous capsule, that separates them from the host tissue
-growth of cancers is accompanied by progressive infiltration, invasion, and destruction of the surrounding tissue
-most cancers are poorly demarcated from the surrounding normal tissue

Front 79

What is metastasis of tumors?

Back 79

-tumor implants discontinuous with primary tumor
-only malignant tumors do this
-some exceptions are gliomas and basal cell carcinomas
-conducts direct seeding of body cavities and surface
-goes to lymphatic channels
-goes to blood vessels

Front 80

What is the pathway of tumor metastasis?

Back 80

-primary tumor formation
-localized invasion
-intravasation
-transport through circulation
-arrest in microvessels of various organs
-extravasation
-formation of micrometastasis
-colonization-formation of macrometastasis

Front 81

What is grade and stage of tumors?

Back 81

-grade indicates degree of tumor cell differentiation
-stage indicates extent of invasion adn metastasis

Front 82

What are the vasrious grades of tumor differentiation?

Back 82

-grade 1- well differnetiated
grade 2-moderatly
grade 3- poorly
grade 4- anaplastic

Front 83

How do you make Paraffin-embedded sections for histological slides?

Back 83

-tissue sampling
-fixation
-tissue processng (dehydration in alcohol, clearing with
xylene, and embedding in paraffin)
-sectioning
-staining

Front 84

How do you make frozen sections for histological slides?

Back 84

-Tissue sampling
-Tissue processing
(embedding in OCT medium)
-Sectioning
-staining

Front 85

How do you do Hematoxylin and eosin (H & E) staining?

Back 85

-Most common staining to show cellular components
• Hematoxylin, being a basic dye, has high affinity for the
nucleic acids of the cell nucleus and stain the nucleus in blue.
• Eosin is an acidic dye with affinity for cytoplasmic components
(mainly proteins) and stain the cytoplasma in pink.

Front 86

What is the epithelium?

Back 86

Derived from ectoderm, endoderm, or mesoderm
• Avascular cellular layer lining free spaces (lung, digestive tract)
• Responsible for more than 80% cancer incidences
• Classification based on architecture or relationship to other epithelial cells
-includes a single or stratefied epithelium

Front 87

How do you classify epithelium?

Back 87

-squamous
-cuboidal
-columnar
-transitional

Front 88

What are Collective (mesenchymal) Tissues?

Back 88

• Connecting and anchoring tissues; providing support, strength,
insulation and protection to other tissues and organs of the body.
• Derived from mesoderm.
• Producing extracellular matrix including various fibrous proteins
(fibronectin, collagen etc.)
-fibroblasts and adipose tissues

Front 89

What is hypertrophy?

Back 89

1.Increase in cell size, resulting in an increase in the
size of the organ, both physiologic and pathologic.
2.Generally involving non-dividing cells such as skeletal
and cardiac muscle cells.
3.Reversible

Front 90

What is hyperplasia?

Back 90

1.Increase in cell number, resulting in an increase in
the size of the organ, both physiologic and pathologic.
2.Generally involving dividing cells and often occurring
with hypertrophy.
3.Reversible

Front 91

What is metaplasia?

Back 91

• A reversible change in which
one adult cell type is replaced
by another type.
• The most common epithelial
metaplasia: columnar to
squamous.

Front 92

What is dysplasia?

Back 92

failure to differentiate completely
and normally , usually pathologic.

Front 93

What is anaplasia?

Back 93

failure to differentiate (to an adult
phentype), a criterion of malignant neoplasm.