Toxicology - deck VI Flashcards
DES
Diethylstilbestrol (DES) is a synthetic estrogen.
was used during the 1950s and later to accelerate the weight gain of bovines and sheep.
When this hormone was given to pregnant women to avoid miscarriages, both the teratogenic and carcinogenic side effect of DES appeared.
The use of DES and zeranol as growth stimulators is prohibited in the EU.
Zeranol is an
estrogenic hormone obtained from mycotoxin zearalenone, is highly hepatotoxic and produces hematological alterations at high doses.
The use of DES and zeranol as growth stimulators is prohibited in the EU.
Veterinary drugs - coccidiostatics or anticoccidials are added to
feed to combat with coccidioses caused by enteric
protozoan parasites (Coccidia).
At risk are poultry and rabbits.
Residues of coccidiostatics have been discovered in hen eggs.
monensin, narasin, salinomycin, and other polyether ionophorous antibiotics are used for treatment of
coccidioses
the most common coccidiostatic
Polyether calcium ionophore lasalocid is the most common coccidiostatic, has attracted special attention, esp. in the UK.
In 2003, over 12% of the eggs tested for antibiotics in the UK were contaminated with this toxic antibiotic.
Some of the eggs were found to have much higher levels of
lasalocid than ever recorded before in the UK.
In the last years, there have been an increasing number of incidences of lasalocid residues found in eggs.
A broader survey of spread of coccidiostatic residues in eggs in eight different European countries revealed that about ?% of the samples analysed contained one or more of the nine
anticoccidials in concentrations ranging from 0.1 to 63 µg/kg.
A broader survey of spread of coccidiostatic residues in eggs in eight different European countries revealed that about 36% of the samples analysed contained one or more of the nine anticoccidials in concentrations ranging from 0.1 to 63 µg/kg.
Salinomycin and lasalocid accounted for more than 60% of all positive samples.
It is hypothesized that there may be a potential link between Sudden Adult Death Syndrome via cardiac failure and the consumption of
lasalocid residues in food, particularly in eggs, although there is no clear scientific evidence.
lasalocid is cocciostatic drug used in farm animals
In the EU, food raw material of animal origin is analysed for
anthelmintics like (2)
ivermectin, levamisole, and others according to a respective national monitoring program.
the most toxic anthelmintic
Special attention is paid to ivermectin (IM), the most toxic anthelmintic.
It is available in a variety of formulations, used for treatment of dogs (LD50 = 80 mg/kg), cats, horses, cattle, sheep, and swine.
The avermectins are
neurotoxins, which have been successfully used in the treatment of helmintic parasitic infections of terrestrial
farm animals and also of river blindness (disease caused by infection with the parasitic worm in humans.
The use of β-agonists as
growth stimulators is prohibited in the EU countries.
Clenbuterol is allowed to be used to treat diseases of respiratory organs as well as birth complications.
Acute clenbuterol toxicity resembles that of other β2-adrenergic agonists.
Thyreostatics do what
reduce (or stabilize) the production of thyroid hormones
The thiourea derivatives used for this purpose are carcinogenic. The use of thyreostatics is either completely prohibited or allowed only for some medicinal purposes in the EU.
The purpose of primary food processing is
increasing of safety, quality and palatability as well as simplification of the end-processing of food.
Novel technologies for food processing are: (3)
Novel technologies are, for example, UV-radiation, use of pulsatory electric field and high-pressure pasteurization.
New food additives and packaging materials are being implemented.
During both primary and secondary processing an endless number of different physico-chemical processes may occur that result in:
- Partial or complete degradation or removal of nutrients and other components that may reduce food quality and digestibility.
- Formation of a myriad of new substances, so-called neoformed compounds, from the food itself, including potentially toxic ones.
During processing, various chemical compounds are formed that often
strengthen or weaken (antagonize) the effects of each other.
Furthermore, most of them are unknown for us.
What is Maillard reaction?
Non-enzymatic browning
During thermal processing of foods (drying, roasting, cooking) multistep chemical reactions between amino acids and reducing saccharides (aldoses and ketoses) can occur.
The Maillard reaction is a chemical reaction between amino acids and reducing sugars that gives browned food its distinctive flavor.
acrylamide or propenic acid amide has been
widely used during decades in various spheres of life, mostly (99.9%) for manufacturing of gelly polyacrylamide (PAA).
PAA, which by itself is of low toxicity to mammals, is used in purification of wastewaters, in
manufacturing of paper and cellulose, in the cosmetic industry for shampoos and perfumes, as a soil conditioner in the agriculture, and in chemical laboratories for preparation of analysis gels.
Acrylamide has not been shown to cause cancer in
humans
It was concluded that the although risk of AcA neurotoxicity is negligible, the additional cancer risk may be higher but further studies are needed for confirmation.
Acrylamide is rapidly absorbed by
all possible routes, and, due to high solubility in water, distributed all over the organism including milk and placenta.
AcA can be regarded as one of the most
important …?
acrylamide
as one of the most important heat-induced contaminants occurring in the bread and bakery products.
AcA is formed during
frying, roasting, and baking and is not
typically found in boiled or microwaved foods.
The highest levels are in fried potato products, bread and bakery wares, and coffee.
(acrylamide)
what? ranks alongside smoking as a major cause of cancer, WHO says
Processed meat ranks alongside smoking as a major cause of cancer, WHO says
pyrolysis
anaerobic decomposition occurring during
incomplete combustion of organic materials, such as wood, coal, or oil, large amounts of various Polycyclic aromatic hydrocarbons are formed.
Food can be polluted with PAH either through
athmospheric sediments in gardens or industrial areas, drying of cereal grains by direct contact with combustion gases, at smoking or barbecueing of meat and fish food at open
horizontal coals, at roasting of coffee beans, preparing mate etc.
(Polycyclic aromatic hydrocarbons)
Cooking meat at high temperatures and for a long time produces
heterocyclic aromatic amines (HAA)
Heterocyclic aromatic amines are predominantly formed at temperatures of
120-250 °C, their formation is inhibited by plant
antioxidants.
3 Saturated fatty acids
myristic, stearic and palmitic acids
what type fo fatty acid is oleic acid
Monounsaturated
Fatty acids can be in organisms and foods as (2)
- in free form
- as derivatives, for example esters
PUFAs
Polyunsaturated fatty acids
Polyunsaturated fatty acids are, during storage (even at subzero temperatures) and/or thermal processing subjected to three alterations:
autooxidation, thermal oxidation, and thermal polymerisation.
Autooxidation of PUFAs proceeds at temperatures below
100°C
- either enzymatically in participation of lipoxygenases, cyclooxygenases and CYP; or
- by a free radical- or a singlet oxygen-mediated mechanism.
hydroperoxides, epoxides, and other primary (per)oxidation products are called
called oxylipins
Oxylipins can further decompose into toxic secondary oxidation products, such as
alkanes, aldehydes (malonic aldehyde, hydroxynonenal) and ketones, characterized by an unpleasant smell of a spoiled product.
CLA is
conjugated linoleic acid
milk, beaf, safflower oil
anticarcinogen,
antioxidant
Oxylipins are ubiquitous in
all aerobic organisms
In relation to the organism, OL are divided into endogenous and exogenous.
Exogenous oxylipins are consumed with food, particularly with
meat
Oxylipins as amphiphilic substances easily cross
biomembranes and, hence, are easily absorbed from GIT and distributed over all tissues and cells.
Among the oxylipins are highly toxic linoleic acid oxylipins called
Leukotoxin diols
Cellular enrichment with linoleic acid amplifies
PCB-induced disruption (synergism!)
The severe toxicity of PCBs in the presence of linoleic acid may be in part due to the generation
of epoxides and, particularly, their diol metabolites (LTX-diols) of linoleic acid that can
mediate in part the amplified cytotoxicity of the combination of linoleic acid and PCBs to
endothelial cells.
Oxylipins, the primary oxidation products of
PUFAs can decompose into secondary oxidation
products – aldehydes (incl. dialdehydes), ketones,
short fatty acids.
Oxidation products of cholesterol as a causing factor of
atherosclerosis
Free radicals, formed during oxidation of dietary
unsaturated fatty acids oxidize cholesterol into
various
oxy-, keto-, and epoxy-cholesterols.
Several oxidation products of cholesterol have
revealed proatherogenic activity in the
composition of low density lipoproteins (LDL).
There is a hypothesis that just oxidized cholesterol assimilated from food is the source of
oxidized lipoproteins in blood,
adverse for health of blood vessels.
TFA
Trans fatty acids (TFA)
A trans double bond is a special type of double bond in which the functional groups of the atoms that share the double bond are on the opposite sides of the molecule.
The primary dietary TFAs are
vaccenic acid as the major ruminant TFA, and elaidic acid, the main TFA isomer in industrial hydrogenation.
The TFA content of industrially hydrogenated fats varies widely and may reach ?% of the total
fatty acid content, whereas the TFA content of beef and dairy products is considerably lower
and accounts only for ?–?% of the fatty acid content.
The TFA content of industrially hydrogenated fats varies widely and may reach 60% of the total
fatty acid content, whereas the TFA content of beef and dairy products is considerably lower
and accounts only for 2–5% of the fatty acid content.
Well-known postulate is that lowering LDL cholesterol will reduce the risk of
CHD.
* TFAs, contrarywise, increase LDL and decrease HDL resulting in a worse LDL/HDL ratio…
The main dietary sources of trans fatty acids are
cakes, cookies, crackers, margarine, fried potatoes, potato chips, popcorn etc.
To meet the recommended dietary intake for fat i.e. amount corresponding to what% of
total calories, most dietary fats should come from sources of what two types of fatty acids.
To meet the recommended dietary intake for fat i.e. amount corresponding to 20 to 35% of
total calories, most dietary fats should come from sources of polyunsaturated and
monounsaturated fatty acids.
TFAs can only be formed under heating of the oil at
high temperatures or reusing the oil many
times.
60-90% of food-borne (acute) intoxications are caused by
pathogenic bacteria.
exotoxins, excreted by bacteria into the environment; are produced mainly by
Gram-positive bacteria. These are mostly very toxic antigenous proteins, becoming activated after a certain latency period.
By far the most dangerous bacterial intoxication is
botulism, caused by globular thermolabile proteinous neurotoxin of Clostridium botulinum, a thermostable spore-forming Gram-positive anaerobic bacillus.
Antibotulinum antitoxin (monoclonal antibodies) exists.
The spores of Clostridium botulinum are very persistent, but the toxin is destroyed at
85 °C within 5 min. Is stable in acidic stomach.
Botulinum toxin is a mixture of seven
neurotoxic proteins that irreversibly block motor nerve terminal at the myoneural junction, preventing releasing of acetylcholinesterase (AChE). The process results in the paralysis of the victim.
Death through the respiratory failure.
Intoxications can also be caused by other Gram-positive bacteria like (3)
- Campylobacter „twisted bacterium“ (Campylobacter jejuni),
- Listeria (Listeria monocytogenes), and
- Helicobacter (Helicobacter hepaticus, pylori)…
Thermophilic campylobacter is a leading causative factor of
bacterial enteritis (campylobacteriosis)
in humans. Optimal growth temperature 42°C, sensitive to drying and freezing.
listeriosis overall mortality rate
high – 20-30%
Endotoxins are produced mainly by
Gram-negative bacteria
are complex formations: polysaccharides + lipids, strongly attached to the bacterial cell wall. Relatively thermostable and have latency period.
what two bacterial species cause major
part of the food poisonings in the USA.
Salmonellas, over thousand species. Together with Campylobacteria
The most severe salmonelloses are caused by (2)
S. enteritidis and S. typhimurium.
Biogenic vasoactive amines are (3)
histamine
cadaverine
putrescine
and other similar amines formed during processing and storage of the food.
Histamine poisoning occurs, if: (3)
- The regulation mechanism of histamine formation in the body becomes defective.
- Too much of histamine metabolism inhibitors (drugs, ethanol etc.) have been administered.
- Too much histamine has been ingested with food.
vasoactive amine cadaverine is formed from
lysine
vasoactive amine putrescine is formed from
ornithine
vasoactive amine tryptamine is formed from
tryptophan
Histamine-rich foods such as
cheese, sausages, sauerkraut, tuna, tomatoes, and alcoholic beverages may contain histamine up to 500 mg/kg.
Scombroid fish poisoning
involves Histamine and probably other vasoactive amines emerging after eating of either rotten or bacterially contaminated fish.
Fish may have retained its initial look and smell.
Intoxication develops rapidly – practically immediately or during half an hour, lasts usually for 3 h, but may last for several days.
In the histidine-rich fish, the histamine synthesis from histidine starts immediately after
death even earlier than postmortem proteolysis will release additional histidine.
In the case of some fishing techniques, a fish will die before it has been pulled out of water.
Therefore, the concentration of
biogenic vasoactive amines may greatly increase without an appearance of any of the organoleptic indicators of the putrefaction.
Putrefaction and bacterial production of ammonia as well as biogenic amines occur especially fast at elevated temperatures, but when a sufficient bacterial population has formed,
the process will continue, although much slower, even at temperatures below 0 °C.
urocanic acid syntesized from
histidine by bacteria.
participates in the development of scombroid fish poisoning
None of the convenient food processing methods including freezing, canning, or smoking is capable of decomposing the substance or substances causing
scombroid intoxication.
It is much easier to avoid the formation of these agents in fish by cooling as fast as possible, recommendably below 10°C, a storage lasting for more than 4 h must be carried out at 0°C or
lower temperatures.
Nitrates and nitrites are “two-faced“ substances, being simultaneosly
both food natural components
and additives.
Nitrate ions (NO3-) originate in food from two main sources
- From garden vegetables containing nitrates as normal physiological constituents.
- From food additives.
Nitrates are not considered to be
hazardous to humans in the actually consumed doses.
Problematic is that nitrates are converted into nitrites by mammal microbial systems.
Nitrite ions are acutely
toxic, their LD50 for humans is 22 mg/kg bw, the allowable highest concentration in meat products is 200 ppm, and the ADI value is 0.135 mg/kg.
The reduction of nitrates to nitrites already starts in the
mouth, where 8% of food nitrates are reduced by oral bacteria. This process is facilitated by nitrate ions returning to the mouth from the intestines by blood and saliva.
Nitrites oxidize hemoglobin to
methemoglobin that is not capable of binding oxygen.
When the methemoglobin concentration in the blood increases to a very high level,
anoxia may appear in the tissues.
Nitrites, both those added to meat before canning and those formed during improper storage
of nitrate-rich food commodities, and those that are formed in the mouth from nitrates, produce
N-nitrosamines and N-nitrosamides
in favorable conditions like acidic environment of stomach, or cooking of proteinaceous foods by reaction with secondary amines or amides.
Nitroso-compounds formed are efficient
mutagens and rodent carcinogens.
what is a surprising fact about nitrite?
nitrite actually has health benefits
* Regulates blood pressure
* Prevents injury from heart attack
* Prevents brain damage following a stroke
* Prevents preeclampsia in pregnant women
* Promotes wound heeling
* Promotes successful organ transplantation
* Treats sickle cell anemia
* Prevents gastric ulcer
Food contact materials (FCM) are
all materials and articles intended to come into contact with food, such as packaging and containers, kitchen equipment, cutlery and dishes such as bottles, cans, cartons, knives, forks, cups and plates.
The safety of food contact materials must be evaluated as chemicals can migrate from the
materials into food.
Food contact materials cannot – under normal and foreseeable conditions of use – transfer their constituents into foodstuffs in quantities, which could: (3)
- Endanger human health
- Cause an unacceptable change in the composition of the foodstuffs or
- Cause deterioration in the organoleptic characteristics thereof.
Bisphenol A is an
endocrine disruptor which can mimic estrogen estradiol and bind to and activate the same estrogen receptor as the natural hormone and cause versatile negative health effects in animal studies.
Early developmental stages are the period of greatest sensitivity to its effects, and studies
have linked prenatal exposure to later physical and neurological difficulties.
Bisphenol A can be detected in what percent of the U.S. population?
can be detected in 90 percent of the U.S. population.
US FDA has lately banned the use of BPA in infant formula packaging.
Food is main source of BPA for consumers, thermal paper also potentially significant.
Bisphenol A is mainly used in combination with
other chemicals to manufacture plastics and resins.
For example, BPA is used in polycarbonate, a high performance transparent, rigid plastic.
Polycarbonate is used to
make food containers, such as returnable beverage bottles, infant feeding (baby) bottles, tableware (plates and mugs) and storage containers.
Residues of BPA are also present in
epoxy resins used to make protective coatings and linings for food and beverage cans and vats.
EFSA
European Food Safety Authority
EFSA’s experts concluded that BPA
poses no health risk to consumers of any age group
(including unborn children, infants and adolescents) at current exposure levels.
But EFSA still recommended tolerable daily intake (TDI) to be lowered 10 times from its previous level of 50 µg/kg bw/ day to 5 µg/kg bw/day.
The Authority also noted that uncertainties remained over a number of other health hazards considered as less likely.
Phthalates are
synthetic substances that are used as incorporated into other plastic materials.
Almost 90% is used as plastisizer (softener) in flexible polyvinyl (PVC) products such as plastic bags, food packaging materials and storage tanks, soft toys, intravenous tubes etc
Main contact of humans with phthalates is via
food.
Most phthalates, particularly of higher alcohols are lipid-soluble and hence able to concentrate in foodstuffs like butter, margarine or cheese and accumulate in adipose tissues of humans and water organisms.
Lower phthalates do not concentrate in the food chain
Two major phthalates of higher alcohols that are used as plastisizers in PVC products are
(2-ethylhexyl) phthalate (DEHP)
& diisononylphthalate (DINP)
Residues of DEHP and DINP have been discovered in
fish, water, sediments, they can also bioaccumulate.
Chronic exposure of fish to phthalates may have adverse effects on the health of the humans
eating the fish.
Human exposure to the residues of phthalates may also take place by
drinking water,
the dust of floor covering materials (PVC - infant bronchoconstriction),
foodstuffs packaged into PVC-materials, and
blood transfusion when phthalate-containing PVC-bags are used for donor blood collection.
