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Food Toxicology -TOX30306 > Week 2 + Week 3 - Vet medecines + combination toxicology + Natural toxins > Flashcards

Week 2 + Week 3 - Vet medecines + combination toxicology + Natural toxins Flashcards

1
Q

What are the two groups for the classification of vet medical products in europe

A

1- Substances with anabolic effect - unauthorised 2- vet drugs contaminants

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2
Q

What is the organisation that regulates the use of new drugs

A

European Medicines Agency (EMA)

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3
Q

What are the two criteria set by EMA for the use of new drugs

A

1- efficacy should be demonstrated 2- application should not result in residues with adverse effects on the health of the consumers

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4
Q

What is the MRL ?

A

it is the maximum residue level (MRL) that is allowed as a residue in a food product obtained from an animal that has received medical vet txt. It is based on the ADI but its exceedance doesn’t necessarly indicate a health concern

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5
Q

T or F : the exceedance of the MRL is a concern for the health of humans

A

false, depends on the ADI set of the residue

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6
Q

T or F : the risk assessment for the vet drugs residues is the same as for the other chemicals like additives

A

true, but also the antimicrobial effects (toxic to gut flora) needs to be access

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7
Q

How is the MRL calculated ?

A

based on a regular diet of the animal product and the ADI of each of the residues. we use the ADI and then you will set estimated levels of food you would take of the animal products and then from that you set the MRI depending on the amount of food estimated.

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8
Q

T or F : the MRL are set by EFSA

A

false, they are set according to the procedures laid down in the regulation EC and the commission regulation EU

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9
Q

What is the withdrawal period

A

the minimum time between the last treatment and the slaughter of the animal or collection of milk or eggs for human consumption to be able for the residue levels to be under the MRL. This period is also set by the european medicin agency

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10
Q

how si the withdrawal period calculated ?

A

using the 95% confidence interval line

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11
Q

The estimation of the withdrawal period can be done with ____

A

Population based kinetic modeling (PBK modeling) : it predicts and measure the concentration of the drug in the tissues/muscles depending on the numebr of txt.

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12
Q

How does the monitoring of medecines occurs in the EU?

A

There is a plan for the monitoring for specific groups of residues only. The member states must submit each year the national monitorign plans to the commission and the european commission will ask EFSA to prepare an annual report of the results of residue monitoring in live animals and animal products in member states

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13
Q

EFSA will work with _____ for the monitoring of residues

A

reference laboratories. For example WUR is a reference laboratory for the monitoring of growth promoters

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14
Q

What are the different types of unauthorised substances or substances having an anabolic effect

A
  1. Stilbenes and derivatives
  2. Antithyroid agents
  3. steroids
  4. resorcyclic acid lactones
  5. beta-agonists
  6. prohibited substance
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15
Q

What are the veterinary drugs and contaminants that are allowed and monitered

A
  1. Antibacterial substances
  2. other veterinary substances
  3. other substances and contaminants
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16
Q

Stilbenes and its derivative is an atagonist for the _____ and so used as a ____ in cattle

A

agonist of the oestrogen receptor and used as a growth promoter. So here the MRL is 0 since it is a prohibited substance but 0.005% of analysed sample contains it.

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17
Q

Thyrostatic compounds may be used to ___ .An example of anthyroid agent is ___

A

increase weight due to water retention by inhibition of the thyroid hormones, so their use is prohibited (MRL = 0).
antithyroid agent example : thiouracil

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18
Q

What is the molecular action of thiouracil ?

A

it will inhibit the thyroid peroxidase enzyme important for the oxidation of iodide to iodine (so not thyroid hormone produced)

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19
Q

T or F : Thiouracil residue levels may be due to high levels of cruciferous vegetables in feed.

A

true because it is produced from the glucosinolates of cruciferous vegetables by the microbiota

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20
Q

What is the mode of action of nandrolone ?

A

it is an activator of the androgen receptor (anabolic steroid) and so it is a growth promoter (development of muscles) and so MRL is 0.

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21
Q

An example of resorcyclic lactone is ____ and it activates the ___

A

zeranol
estrogen receptor.

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22
Q

An example of beta agonist is ___

A

clenbuterol

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23
Q

What is the use of clenbuterol ?

A

illegally : agonism of the beta receptor and so more smooth muscle relaxation and increased muscle to fat ratio
legally : use to trat diseases of the respiratory organs

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24
Q

Chloramphenicol is a compound occuring as a toxin produced by ____ in the feed and it is also ___

A

produced by bacteria - streptomyces venezuelae

genotoxic, so MRL = 0.
it is used for the eye infections in animals

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25
What is the effect of chloramphenicol in humans at high dose
1. genotoxic -- carcinogenicity data not available 2. aplastic anemia -- dammage of the bone marrow
26
\_\_\_\_ were widely used in the past for pig and chickens but its mutagenic and carcinogenic potential has made this substance become illegal for use
Nitrofurans. The metabolite AOZ created from furalozidone is mutagenic
27
What are the three tpyes of antibacterial monitored
1. antibiotics 2. sulphonamides 3. quinolones
28
T or F : over from 2014 to 2017 the % of non-compliant sample did not change much
true, this means that the monitoring and the illegal/contamination is consistent (0.3%-0.4%)
29
T or F: The use of genotoxic chemicals (e.g. nitrofuransand nitroimidazoles) is forbidden
true, only cloromphinicol at low dose in the eyes can be used
30
Response-addition is used when two compounds have \_\_\_\_\_
dissimilar action
31
Dose-addition is used when two compounds have \_\_\_\_\_
similar mode of action
32
What are the possible combination effects ?
1. dissimilar action : response-addition 2. similar action : dose-addition 3. interactions
33
What are the two types of mixtures in general ?
``` Complex mixture (more than 10 chemicals) Simple mixture (less than 10 chemicals) ```
34
Liquid smoke, cigarettes, petroleum extracts are examples of ___ mixture
complex
35
What is the RA approach for the complex mixtures ?
RA based on mixture as a whole -- whole mixture approach
36
For simple mixtures, the RA is based on \_\_\_
based on the individual components, if known the possible combination effects can be taken into acocunt
37
T or F : the combination effect of mixture of components having different mode of action is known as the dose-addition
false, the dose can't be added for the components since they do not have the same mode of action
38
In the case of mixture of compounds having the same mode of action, the effect of the combination is equal as the sum of\_\_\_\_
as the sum of the effect of the compounds in the mixture (response addition)
39
What does happen in the case of the response addition mixture if each chemicals are present at doses below the ADI/TDI ?
no adverse effects of the mixture is expected
40
T or F : in the response-addition, chemicals do not influence each other’s action
true
41
this graph is :
response addition since the addition of the components is the same as the highest component
42
what is the risk of this mixture if each compound have a different mode of action?
0 risk since it is response addition and each compounds are below the ADI/TDI
43
Does this mixture has a mixture effect ?
no because onl one component is above threshold, the others are considered to be 0.
44
In the case the compounds in a mixture have the same mode of action, the mixture is called :
dose-addition mixture
45
T or F : in the case of dose-addition, the response is equal to the higest response
false, the respone is the sum of all the individual doses
46
Which mixture is this : Even if each chemical is present at doses below ADI/TDI, adverse effects may be induced.
dose-addition
47
What is the RA approach use for mixtures with the same mode of action?
1- common mechanism group (CMG) 2- cumulative assessment group (CAG)
48
T or F : in somecases notexact samemechanisms/modes of action, e.g. chemicals that cause toxicity to specific organ maybe grouped together without knowlegdeon exact modes of action
true, then the common mechanism group approach is used
49
What mixture type is this graph
dose addition because all the compounds are below threshold but together they are above the threshold
50
What are some example of dose-addition mixtures (3)
1. Dioxins and PCBs : activate aryl hydrocarbon receptor (AhR) 2. Organophosphates : inhibits acetylcholinesterase (AChE) 3. Marine biotoxins (saxotoxins)
51
For the dose-addition, the magnitude of response can be predicted by \_\_\_\_
expressing the dose of each chemical normalized on the basis of potency to a single reference compound.
52
What is the relative potency factor (RPF) ?
Its the potency of chemical congener as a relative potency compared to the index chemical
53
What is the index chemical ?
Usually a potent congener (not necessarrily the most potent) of a chemical group for which adequate data are available for the risk assessment (hazard characterization). The index chemical will have a relative potency of 1.
54
Interactions of 2 components of the mixture can occur at the level of ___ and \_\_\_
kinetics and dynamics
55
How does dioxins and / PCBS are evaluated for their risk
using the toxic equivalency factor (TEF)
56
What are the criteria for compounds to be in the group of dioxins and dl-PCBs and to evaluated by the TEF
●Structural similarity to PCDDs and PCDFs ●Bind the AhR ●Elicit AhR-mediated biochemical and toxic responses ●Be persistant and accumulate in the food chain
57
How are determined the relative potency factors ?
based on their relative potency (dose-response curve)
58
How are toxic equvalency factors are determined?
based on the in vivo data. For example for dioxins/dl-pcbs it is based on the CYP1A induction
59
What is the formula for calculating the TEQ?
TEQ= TEF \* dose
60
What is the common mechanism of organophosphate pesticides (OPs)
inhibition of the AChE
61
T or F : the toxic equivalent dose (calculating by adding the TEQ of each comppounds in the mixture) can be compared with the ADI and ARfD of the index chemical
true
62
What is the common mechanism of per and polyafluoroalkyl substances (PFAS)
they all cause similar liver toxicity and so the mixture approach is used even if we don't know hte exact mechanism.
63
What are the RPF number based on for PAF
ebased ont he liver weight increase in male rats
64
what are the two types of interactions for mixture of compounds interacting together
1. toxicodynamics interactions 2. toxicokinetics interactions
65
Toxicokinetics interactions occurs when a compounds affects :
1. uptake of another 2. biotransformation of another (competition for enzymes / enzyme induction) 3. the excretion / clearance of another
66
if a compound affects the uptake of another, biotransformation of another (competition for enzymes / enzyme induction) or the excretion / clearance of another we can say the compounds are having a _____ interaction
toxicokinetic
67
Grapefruit juice and furanocoumarin is an example of ____ interactions
toxicokinetics since grapefruit inhibits the CYP3A4 and so reduces the clearance of felopidine (furanocoumarins)
68
pyrrolizidine alkaloids and DDT are examples of ____ interactions
toxicoinektics : pyrrolizidine alkoids in the plants is more toxic when there is DDT because DDT induces the enzyme and the toxicicity of the plants alkaloids is due to the metabolite of the enzyme
69
Toxicodynamics interactions are expected when :
●two or more chemicals act on different enzymes in an important cell signaling pathway ●two or more components act on different elements of cellular protection mechanisms or cellular repair mechanisms
70
in the case of pyrollizidine alkaloids, the toxicity is based on the ___ toxicity data
riddelliine
71
\_\_\_ are anti-nutritional factors (ANF) found in beans (soybeans, kidney beans)
lectins
72
What is the mode of action of lectins
Trypsin inhibitor (interfere with protein-digestion by serine proteases). Tbey are heat labile
73
What is the source of solanins and their mode of action
sources : flowers, leaves and stems of potatoes , peel potatoes Mode of action : overstimulation of the ACh receptor by inhibiting the acetylcholinesterase
74
T or F : solanine are reduced by the cooking
false, they are neither water soluble neither heat labile
75
Glycoalkaloind occuring in potatoes :
solanin
76
T or F : since the MOS is lower than 100, the solanine levels is a concern
true, but the peeling reduces 30-80% of the solanine levels
77
What are the various famine foods we saw in class
1. cyanogenic glycosides 2. Lathyrogens
78
What is the source of cyanogenic glycosides and the mode of action and deases associated with chronic consomption
* *source** : cassava that has not been properly cooked / fermented will keep their cyanide moiety (C=N) and will be released in the GIT * *mode of action** : inhibition of the cytochrome c oxidase (ATP production) or formation of thiocyanate (inhibits ioide uptake by thyroid) * *disease** : konzo paralytic disease or goitre
79
T or F : cooking of cyanogenic glycoside is sufficient for removing the cyanide moeity
false, cooking only is not sufifcient since cyanogenic glycosides are heat stable., it also needs soaking / fermenting for the enzymatic release of the HCN moiety.
80
T or F : the metabolites of cyanogenic glycosides are not toxic
false, one of the metabolite formed for the excretion through urine is Thiocyanate and it inhibits the iodine uptake and can lead to groite
81
what is the processing done in order to remove the cyanogenic glycosides
1. soaking / fermenting for the enzymatic release HCN 2. cooking or drying for the evaporation of the HCN If the two steps are not done then cyanide will be found in the gut and absrobed
82
What is another product other than cassava (linamarin) that contains cyanogenic glycosides
bitter almonds contains amygdalin
83
Cassava contains the toxic cyanogenic glycoside called ____ and almonds contains the toxic cyanogenic glycoside called \_\_\_
cassava : linamarin almonds : amygdalin
84
T or F : linamarin exposition is a concern while amygdalin is not
true, since linamarin from cassava exposure is over the ARfD of cyanide (20 µg/kg bw/day
85
T or F : cyanide of a concern for the acute effect
true
86
T or F : some apricot kernels are very concerning because one kernel contains the ARfD
true, the amount of kernel that can be consumed in adults without exceeding the ARfD is 0.37
87
\_\_\_\_ is a toxic amino acid (structure analog) found in pea like plants
lathyrogen
88
Why is lathyrogen a problem in drought/flooding prone coutries like bangladesh, ethiopia, india and nepal?
because lathyrogen is found in pea crops which give high yields under extreme conditions
89
What is the mechanism of action of lathyrogen ?
it is a sturcture analogue of an a.a and so the proteins will replace the essential a.a by this toxic analog)
90
what is the condition associated with the consumption of grass peas (lathyrogen)
neurolathyrism because it contains ODAP (which is a type of lathyrogen) that is similar to glutamate and so the toxic effect will be muscle weakness / stiffness an paralysis of the leg muscles
91
Consumption of grass pea (lathyrus sativus) is associated with the condition ____ while the consumption of sweet pea (lathyrus odoratus)
grass pea : neurolathyrism sweet pea : osteolathyrism
92
What is the mode of action of sweet pea lathyrogens (lathyrus odoratus)
the main compond is beta-aminopropionitrile (BAPN) and this compounds inhibits the cross connections between the collagen and elastin = weakens the connective tissues and leads to osteolathyrism
93
What is the mode of action of fava glycosides À?
forms oxidative prone molecules in the body --\> reduced expression of glucose-6-phhosphate dehydrogenase (G6PD) reduced the levels of glutathione --\> oxidative stress --\> hemoysis
94
what si the condition associated with fava glycosides consumption in certain sensitive individuals
hydrolysis will yield compounds that will induce hemolytic disorder is a certain suseptible population
95
what is the source of fava glycosides ?
beans - fava beans
96
Where does the G6PD deficiency happens more ?
in regions affected by malaria
97
t or f : Phytotoxinsin foods are generally recognized as safe at normal dietary intake
true, the situation of toxicological concerns are famine, impropee prepations, supplement and sensitive individuals or over consumption of natural foods (teas)
98
Toxins from marine algae are called \_\_\_\_
Fycotoxins
99
what are the three types of toxins from animal products we have seen in class ?
1. Bacterial toxins 2. Fycotoxins (from marine algea) 3. Animal toxins (TTD and scombrotoxins)
100
What is the mechanism of action of botulinum toxin
inhibits the release of acetylcholine by presynpatic membrane at the junction of muscles by cleaving the SNARE proteins important for membrane fusion (paralysis of respiratory muscles first)
101
What are the common food sources of botulinum toxin ?
red sausages - justifies the use of sodium nitrate honey
102
T or F : Many natural toxins in animals products are a result of contamination, for example with toxin producing bacteria or algae
true
103
The toxin responsible for paralytic shellfish poisoning is \_\_\_
saxitoxin
104
What is the mode of action of saxitoxin (paralytic shellfish poisoning)
blocking the sodium channels.
105
What are the symptoms of intakes of saxitoxin?
nausea, vomiting, diarrhoea, numbness, confusion, coordination problems
106
The toxin responsible for neurotoxic shellfish poisoning is \_\_\_
brevetoxin
107
The toxin responsible for ciguatera fish poisoning is \_\_\_
ciguatoxin
108
What are the symptoms of brevetoxin posoning (neurotoxic shellfish poisoning)
nausea, vomiting, diarrhoea, numbness, tingling lips, coordination problems, confusion. Contrary to paralytic shelffish poisoning there is no paralysis, respiratory distress / death
109
What is the mode of action of brevetoxin ?
activation of the sodium channel, no proper neurons signalign
110
What is the mode of action of ciguatera fish poison (ciguatoxin)
activation of the sodium channel (increased permeability)
111
What are the symptoms of cciguatera fish poisoning ? (CFP)
Very similar to neurotoxic shellfish poisoning : nausea, vomiting, diarrhoea, numbness, tingling lips, coordination problems, confusion. Contrary to paralytic shelffish poisoning there is no paralysis, respiratory distress / death
112
The toxin responsible for amnesic shellfish poisoning is \_\_\_
domoic acid
113
what is the mode of action of domoic acid (amnesic shellfish poisoning)
domoic acid as a structure similar to glutamate and so lead to neurotoxicity by overstimulation of glutamate neurons (high intracellular calcium and neuronal death concentrated in the hippocampus)
114
The toxin responsible for diarrhetic shellfish poisoning is \_\_\_
okadaic acid
115
what is the mode of action of diarrhetic shellfish poisoning (DSP)
inhibitio of ser/thr protein phosphatase : so you can't remove the phosphorylation of proteins and so you affect the activity and the ions channels in the ephithelial cells in the gastro intestinal tract = increased loss of fluids
116
how are shellfish poison detected ?
1. in vivo - mouse bioassay - before 2015 2. in vitro - electrical activity neurons 3. in vitro - neuro 2a assay
117
What is the multi-electrode array platform assay ?
assay done to record the presence of shellfish poisons or other marine biotoxins by recording the neuronal activity (inhibition / activation). it is a very sensitive method
118
What is the neuro 2a cytotoxicity assay (MTT assay)
another very sensitive assay in which the you test the lethal dose to 50% of hepathic cells and express as the EC50)
119
what is the mode of action of tetrodotoxin (TTX)
inhibition of the sodium channels and so lead to paralysis : death in 6-24 hours. The symptoms are similar to saxitoxin and it is death by paralysis of respiratory muscles
120
T or F : TTX is no concern in europe
false, in NL the levels detected were not close to the lethal dose nevertheless TTX was detected in shellfish at levels over the acute reference dose
121
what is the toxin in the case of scrombotoxins ?
scrombotoxins are histamine formed by decarboxylation by bacteria on histidine rich fish like tuna, mackerel, bonito, sardines. This results in allergic reaction to the histamine level
122
what are the symptoms of scromboid poisoning ?
Immune/allergy-like responses - Redness - Swelling - Heat - Pain - Loss of function
123

Food Toxicology -TOX30306 (9 decks)

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