1
Q
Define environmental toxicology
A
Multidisciplinary study of how chemicals affect organismal health and the environment
2
Q
Define ecotoxicology
A
Study of harmful effects of chemicals and pollutants on ecosystems
3
Q
What is the key difference between environmental toxicology and ecotoxicology
A
Ecotoxicology is broad scale - population to biosphere level
Environmental toxicology is individual level - cellular and individual levels
4
Q
Direct v indirect toxicology
A
Direct - toxic agent acts directly on the organisms
Indirect - results from the influence or changes in the environment - ex. species A eats species B but species B dies out due to pollution resulting in no food for species A
5
Q
What is the dose response relationship
A
all substances are poisonous in the correct dose - toxic effects are always dose or concentration dependent
6
Q
3 main principles of toxicology
A
- Experimentation is essential in examining the response to chemicals
- Need to distinguish between theraputic and toxic effects of chemicals
- properties are usually only distinguishable by dose
7
Q
What is NOEC
A
No observed effects concentration - safe level
8
Q
What is LOEC
A
Lowest observed effects concentration - first evidence of toxicity
9
Q
What is the mathematical formula for determining the maximum acceptable toxic concentration?
A
MATC = (NOEC + LOEC)/2
- used to determine threshold
10
Q
What is LD50 and LC 50?
A
dose or concentration that causes 50% mortality under a defined test condition - usually expressed as a function of time
11
Q
What is EC50?
A
Concentration that elicits 50% of an expected effect / response under a defined test condition
12
Q
What is IC50?
A
Concentration that reduces the normal response of a perameter by 50% - usually used in biomedicine - ex. lowering an immune response
13
Q
What might the dose response curve look like for carcinogenic or non threshold chemicals?
A
straight line - toxic at every dose
14
Q
What might the dose response curve look like for micronutrients?
A
U shaped curve - have optimal concentration range
15
Q
What are acute toxicity tests?
A
- short term exposure to high dose in a single species
- 48 -96 hour tests
- adjusted for species lifespan
- common endpoint is mortality
16
Q
Three kinds of acute aquatic tests?
A
- static - no water changes or filtering
- static renewal - partial water changes
- flow through - allows for continuous exposure to new toxin - allows isolation from excrement or other debris - best test but really expensive
17
Q
What are chronic toxicity tests?
A
- long term exposure to low or sub lethal doses in a single species
- 21 days to several years depending on organism / study design
- common endpoint - effects on growth or reproductive fitness
- several other endpoints in higher vertebrates - endocrine malfunction
18
Q
What is the acute to chronic ratio? ACR?
A
= Acute LC50 / MATC
- used to gauge concentration of a toxicant taht may cause chronic toxicity to exposed organisms
- most chemicals will have acute toxicity data but not chronic data - so used as a best estimate since chronic studies are rare
19
Q
What are microcosms and mesocosms?
A
studies using two or more species or more than one toxicant
- more environmentally realistic
- allows to study interspecific and community level interactions
- similar to a trophic transfer system
- microcosm is at a microscopic scale
20
Q
Why are field studies critical for environmental impact assessment?
A
environmental or field studies are more valuable for impact assessment because it was done in an actual environment - variable test conditions
21
Q
Common organism used for terrestrial vertebrate toxicity tests?
A
Rodents - lab mice
22
Q
What is high abundance of a species an indicator of?
A
High tolerance to environmental conditions
23
Q
Two common organisms used in soil toxicity testing
A
earthworms and springtails
24
Q
3 common organisms used in aquatic toxicity testing
A
- fish ie. zebrafish
- daphnia
- algae
these three fill different trophic levels in an ecosystem
25
4 key characteristics for selecting test organisms
- should be sensitive to a wide range of toxicants - because then its applicable to a wide range of species - if regulations are made based on a "weak" species
- should be widely available through lab culture or collections from field
- should be successfully maintained in the laboratory environment and be available in sufficient quantities
- the genetic composition and history of the culture should be known
26
3 possible outcomes of a mixture of two different toxicants?
- additive
- synergistic (multiplicative or compounding)
- antagonistic
27
What is toxicokinetics?
- absorption and uptake processes
- internal handling and metabolism
- excretion
28
Inputs/ outputs for a toxicant
- input in food and water
- output in loss from gills, skin, urine and feces
- output in biotransformation - not applicable to metal element toxicants
- bioaccumulation is input - output
29
What is growth dilution?
the concentration of a contaminant can decreae in a growing organism - this is not a component of elimination
- rate of tissue growth during adolescence is greater than pollutant uptake
30
What is bioconcentration?
- the uptake of dissolved phase of a toxicant to achieve total body concentrations that exceed the dissolved phase of water
- term limited to use in aquatic toxicology
- basically concentration of contaminant in the biological tissue is greater than the dissolved concentration in water
31
Define biomagnification
- increasing concentration of a toxicant from lower to higher trophic levels - ie. up the foodchain
- not all contaminants but specific biocontaminants
- usually compounds that cannot be broken down / are not water soluble - lipid soluble will retain stuff for a long time
- for metals like mercury - mercury is a foreign element to the body, unlike copper, we do not have the physiological mechanisms to get rid of mercury, whereas we could get rid of other elements in higher than average quanities as they are also used by the body so there is a pathway to degrade them
32
Define xenobiotic compound
Matter not normally part of an organisms environment. if the compound causes damage, then it is a poison or toxic contaminant
- can be found in any region
33
Two main types of molecules - properties and uptake types
Lipophilic / non polar / neutral - simple diffusion is most common mechanism of transport and uptake - can pass directly thru membrane cuz nonpolar and lipophilic - requires a gradient for movement by diffusion
Hydrophilic / polar / electrically charged - requires facilitated diffusion as hydophobic polar compounds cannot just cross the plasma membrane - will diffuse but needs specific ion channels to do so
* generally voltage gated ion channels are used for positive cations but transport for negative species will often be through specific channels
34
How do foreign metal species like Cd2+ and Pb2+ make it into the body?
Calcium 2+ analogs - same charge so will use Ca2+ voltage gated ion channels to bypass bodies defenses
35
What forms are metalloids often found as in the environment?
Negative oxyanionic forms
36
Are some molecules able to transport outside of the cell membranes?
- paracellular pathway - movement between gap junctions
37
What is endocytosis and when does it happen?
- infolding of the cell membrane engulfing a molecule and releasing it on the inside of the cell membrane
- happens with large molecules
38
4 parts of partitioning in toxixokinetics ADME
Absorption
Distribution
Metabolism
Excretion
39
After a toxin is taken up in th e blood, where can it go to be metabolized or stored?
Liver, adipose tissue, bones, kidneys, one way transport to brain / CNS
- largest quanitity will accumulate in the liver
- lipophilic molecules will be accumulated and stored in adipose tissue
- metal ions will end up in the skeleton
-
40
Three entry points for toxicants and resulting uptake locations
Ingestion - GI tract
Dermal contact - absorbed into the skin
Inhalation - lungs
41
The chemical properties will affect where it is ultimately stored and metabolized within the body - True or False?
True
42
Which form of metals are bioavailable and highly toxic?
The free ionic form - Pb2+ - requires mediators - proteins / peptides - that bind to the free ionic form of the metal upon entry to ensure it is not in free ionic form - will then go on to be detoxified / metabolized
43
Two kinds of biotransformation of organic compounds (ie lipid compounds) during metabolism of toxicants + what is biotransformation
- either undergoes phase I then phase II metabolism before elimination or only phase I metabolism then elimination
- biotransformation is turning a lipid / lipophilic molecule into a polar , water soluble one that can be excreted thru the body in urine
- some metabolites require two steps to be water soluble enough to leave the body
44
4 major routes for excretion?
Urine
Bile
Feces
Lungs (?)
45
Phase II biotransformation reactions are known as _______ reactions
conjugation reactions
46
5 major classes of organic pollutants
- polycyclic aromatic hydrocarbons (PAHs)
- polychlorinated biphenyls (PCBs)
- chlorinated phenols, dioxins and dibenzofurans - halogenated hydrocarbons
- Peticides - organophosphates / organochlorines
- Aromatic herbicides
47
3 Major classes of inorganic pollutants
- metals and metalloids - Cd, Pb, Cu, Ni, Zn, Hg
- nonmetallic inorganics - chlorine and ammonia
- inorganic gasses - CO2, CO, SO2
- organometallics - methylmercury
- nutrients - NO3 PO4
- radionuclides - Uranium
48
Define bioavaliability
the extent to which a contaminant in a source is free for uptake
49
3 main factors and three subfactors (for each main factor) affecting bioavailability and bioaccumulation
- Chemical properties - lipophilicity, persistence, toxicity
- Biological factors - metabolism, excretion rate, feeding habits
- Environmental conditions - temperature, presence of other substances, pH levels
50
Why does the bioavailability of a substance matter?
because if the substance cannot be uptaken into biological systems then it is not relevant
51
5 processes that determine the amount of substance available for biological uptake?
- degradation, volatilization, leaching, sequestering, lipophlicity
52
What are the octanol water partition coefficients and the octanol air partition coefficient?
Kow - concentration of substance in octanol phase / concentration in aqueous phase - expressed as a log value ranges from -3 to +7
- high Kow means more lipophilic, more bioavailable and less water soluble
Koa - concentration in octanol phase / concentration in atmospheric phase - expressed as a log value ranges from 0.3 - 12 - similar to the Kow
- high Koa means more lipophilic and less volatile
- also known as the index of lipophilicity - which calculation depends on context
53
why does bioavailability only increase with lipophilicty to a point?
increases as long as molecules stay within 10 - 15nm, main process for absorbing lipophilic molecules is simple diffusion, when size gets too big has to switch to endocytosis which is slower
54
What are biotic factors affecting toxicity? (4)
Age -We are the most susceptible to toxins when young and old
Sex - specific differences in metabolism and therefore toxicity - also estrogen and androgen mimics
Genetics - some species are resistant to toxic agents - eg mosquitoes to DDT
Physiological condition
- amount of adipose tissue - resovoir for lipophilic toxicants
- impairment of liver / kidney functions
- altered physiology due to various other environmental stressors
55
Two general properties of metals?
- Metals can neither be created or destroyed
---- problematic environmental contaminants
---- however chemical form of the metal can be altered
- Metals are naturally occurring
---- anthropogenic activities increase metal bioavailability because metals are moved from biologically inaccessible to accessible compartments in the biospheres OR the form of the metal is changed to more bioavailable or toxic forms
56
Difference between class A and class B metals?
Class A have high affinity to oxygen - and oxygen functional groups like carbonyls / phosphates
Class B have high affinity to sulfur (and nitrogen)
57
Why are class B metals generally more toxic than class A metals?
Since class B metals have high affininty for binding to sulfur and nitrogen (amino groups) will have high affinity to bind with proteins / amino acids which has a drastic effect on the body
58
What is hardness of water
hardness is the amount of calcium / magnesium concentration in the water. Divalent cations
-
59
What determines alkalinity?
carbonate, bicarbonate and hydroxyl content
60
For metal salt species which is better to solubilize the metal ? acidic or basic?
acidic will make the salt more soluble - resulting in more metal in free ionic form
alkaline range makes metal salt less soluble with less free metal ions in the solution
61
Is alkaline or acidic water better for avoiding free metal cations?
Alkaline is better, as HCO3- and OH- contribute to inorganic complexation meaning that the metal ions will get tied up with them and therefore not bioavailable and less toxic
- alkaline water implies that carb, bicarb and OH- are already present
62
WOuld metals be more bioavailable / toxic or less bioavailable / toxic in seawater relative to freshwater
Metals are less bioavailable / toxic in seawater as Na Cl allow for inorganic complexation and increase the hardness / alkalinty of the water
63
When we talk about metal uptake from soil, where are the metals actually coming from?
The metals are in the pore water in between soil particles
64
3 cellular mechanisms for detoxifying metal ions?
MT - metallothioneins - metal binding protein that will complex with the metal
GSH - glutathione - does same thing, also has lots of cysteine
MRG - metal rich granules - will envelop metal grains in vacuoles and excrete
65
4 main modes of toxic action by metals?
- alteration of subcellular and membrane bound enzyme/protein activities
- binding to the active site of an enzyme
- displaces essential metals from certain proteins and replacing with bad metal
- generation of ROS
66
What are metalloenzymes?
enzymes with metal essential to its structure / as a cofactor
- carbonic anhydrase which maintains pH in the blood
67
Which metals accelerate ROS generation?
Fe, Cu, Cr
- Cd, Hg depletes ROS removing proteins in the cell and allows ROS to do more damage
68
What are the three main ROS?
O2- (w/ extra unpaired e-)
OH (w/ extra unpaired e-)
H2O2
69
Two types of mechanisms that enable ROS damage?
REDOX metals - cause oxidative stress by increasing the amount of free radicals directly by engaging in electron trasnfer reactions with them
NON REDOX - metals cause oxidative stress will disable ROS scavenging proteins (by interfering with sulfur) - will increase amount of ROS by decreasing the amount of ROS scavenging proteins
70
Natural sources of Cadmium?
Rocks and soils
- by product of lead / zinc mining
- nickle cadmium batteries
- electroplating and galvanizing
- cigarette smoke
71
Where is Cd2+ stored in the body?
Major sequestration occurs primarily in the kidney and the liver but mainly the kidney
- high biological residence time - 10-33 yrs in humans
72
effects of Cd on the body?
- disrupts calcium regulation in animal systems
- loss of calcium from aquatic organisms
- deposition in the bones causing osteoporosis
- immunosupression
- lung issues
- kidney damage
- Cd will bind to SH proteins with high affinity causing enzyme dysfunction and depletion of metal chelating and ROS scavenging proteins
73
Major effects of selenium poisoning?
Disproportionately toxic to egg laying organisms
- developmental malformations
- damage to liver, kidney and heart
- reproductive failure
- neurotoxicity
74
4 main classes of hydrocarbons and halogenated hydrocarbons
Polyaromatic hydrocarbons (PAHs)
- hundreds of different forms
Polychlorinated / Polybrominated biphenyls (PCB / PBB)
Dibenzodioxins and dibenzofurans
- polychlorinated dibenzodioxins (PCDDs)
- polychlorinated dibenzofurans (PCDFs)
75
What generates PAHs?
Combustion of organic compounds
76
Two sources of PAHs?
pyrogenic - fire created through organic combustion reactions
petrogenic - fuel / oil related
77
How does the amount of rings in a PAH affect its properties
MOre rings means - more in solid/ particle phase, higher binding affinity to organic C, less solubility, more lipophilicity, higher molecular weight, less volatility
78
3 points about PAH chemistry / kinetics?
Lipophilic - highly bioaccumulative
Rapidly metabolized and excreted by higher vertebrates
- crustaceans cannot metabolize PAH therefore they accumulate high levels
Transported in the atmosphere but more of a local problem in cities since they can easily be broken down - due to volatility
Prone to photodegredation - mainly for the unsubstituted ones
79
Two classes of PCBs?
Coplanar vs non coplanar
- coplanar PCBs are more toxic (but not more lipophilic) than non coplanar - acts as an aryl hydrocarbon receptor agonist and will bind instead of the correct cofactor
80
Why can 12 specific coplanar PCBs bind to the aryl hydrocarbon receptor?
they are monoortho substituted PCB, all have 0-1 Cl at ortho position
81
Which PCBs are going to be found in the gasseous phase?
Low to medium degrees of chlorination
82
Which PCBs biomagnify more?
Ones with higher degrees of chlorination
83
What is the most toxic synthetic compound?
Polychlorinated dibenzodioxin
- specifically 2,3,7,8- Tetrachloro-dibenzo-p-dioxin
- used as a reference for the toxicity of other dioxin compounds - highly lipophilic so highly bioaccumulative
- by the toxic equivalence factor - 1 - TCDD is most toxic
84
Why is benzoapyrene bad?
Metabolic activity can cause epoxylation forming an epoxide which can bind to the DNA forming a DNA adduct which can lead to mutations / cancer
- when reduced can also form ROS and cause further oxidative stress
85
What is TEQ?
the sum of (the concentrations of all individual dioxin like compounds multiplied by their toxic equivalency factor)
- it is very rare for toxicity to be caused by only a single dioxin like compound
86
What is the major agent for dioxin like compound exposure?
Consumed through diet
- mainly in beef and dairy - which are high in fat so it makes sense they would retain high amount of dioxins which are lipophilic
87
Chronic effects of dioxin like compounds?
- can activate oncogenes which can lead to abberant tissue growth and cancer
- immunosuppression/ reproductive impairment
- endocrine disruption
- blue sac disease in developing fish embryo
88
What is blue sac disease?
yolk sac in developing fish embyro weakens and body fluid will leak into the yolk sac
89
The octanol-water partition coefficient (Kow) is the ratio of the
concentration of a chemical in octanol and water at equilibrium.
It is commonly used to determine the ___________________ of
a pollutant.
lipophilicity
90
In a contaminated area, the total body burden of DDT in rainbow
trout and ospreys is 2ppm and 25ppm, respectively. This
difference in concentration of DDT between the two species is
due to the _____________________ effect of DDT
Biomagnification / bioaccumulation
91
Osteoporosis is a documented effect of chronic exposure to
__________ in mammals including humans
Cadmium
92
3 Major factors influencing metal bioavailability and toxicity in water?
- hardness
- pH / alkalinity
- concentration of organic and inorganic ligands in water
93
How does the presence of ligands in water affect metal bioavailability?
Will complex with free metal cations reducing the amount of cations and therefore toxicity
94
How does hardness affect metal bioavailability?
Hardness caused by Ca2+ will compete for ligands / binding sites with other 2+ metal cations, thereby reducing the number of bad metals that are actually taken up
95
What is bioaccumulation?
available portion of a compound that is taken up by biological organisms
= uptake - elimination
96
What is bioconcentration?
uptake of a contaminant that the concentration in the body exceeds the concentration in the water
97
What is xenobiotic activation?
The metabolite of a compound is more toxic than the parent compound - can happen with benzopyrene - phase 1 metabolism forms epoxide, which can create DNA adducts or free radicals
TOX 301
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