Toxicology - deck IV Flashcards
Ptaquiloside is
The carcinogenic glucoside constituent of bracken, a globally ubiquitous fern.
The presence of ptaquiloside and related terpene glycosides in milk, meat and water as well as inhalation of the spores
of bracken of are particular concern from the viewpoints of both human and animal health.
called for further studies on ptaquiloside residues present in foods derived from bracken-fed animals and on the determination of safety intervals for ptaquiloside clearance from tissues and milk.
Saponins are
glycosidic surface active substances (from Latin sapo = soap)
are found in soybeans, sugar beet, peanuts, spinach, broccoli, alfalfa, potato, apples, and in other plants and fruits.
By chemical structure saponins are divided into two large groups
steroidal and triterpenic
Saponins are very toxic substances due to
the surfactant activity, they are able to decompose the cellular
membranes, eliciting blood hemolysis, esp. in the case of cold-blooded animals.
For warm-blooded animals, small perorally administered doses of saponins are generally harmless, since they are decomposed by enteric microflora.
In addition, they are poorly absorbed and their effect is inhibited by blood plasma.
glyzyrrhizin is
a saponin of the roots and rhizomes (rootstalk) of the licorice plant that is in the form of salts.
The medicinal usage of licorice extracts is broad. At the same time, its enteral hydrolysis product glycyrrhetic acid has toxic effects as
well.
e.g. eating way too much licorice candy can result in toxicity
Grayanotoxins have been found in
rhododendron and other plants of family Ericaceae
From the nectar, grayanotoxin passes to honey and may be the causative agent of the honey- or rhododendron intoxication (mad honey disease)
Eating of mushrooms may be connected with various hazards: (3)
- Real mushroom poisoning:
– With persistently toxic mushrooms. Many mushrooms lose their toxicity during processing
– With old mushrooms. Toxic substances are formed during decomposition of the mushrooms. - Poisonings by environmental toxicants, bioaccumulated in mushrooms.
- Allergic-supersensibility reactions against mushroom constituents.
two Really fatally toxic mushrooms of genus Amanita
- green death cap (A. phalloides)
- white death cap (A. virosa)
that contain amatoxins and phallotoxins
Amatoxins are thermostable and insoluble in water; they cannot be destroyed by
boiling, cooking nor by drying of the mushrooms.
Amatoxins are potent poisons, already an acute dose of 0.1 mg/kg bw can be lethal for an adult.
Gyromitrin
Gyromitrin is a volatile and water-soluble toxin that is extracted from the fungus by boiling.
Arsenic is a
metalloid,absolutely necessary for the normal life of some animals such as rats, goats, and young birds.
Elementary arsenic is non-toxic, but derivatives cause disorders of both CNS and PNS and heart functioning, injuries of peripheral blood vessels, upper respiratory tract, liver, skin, GIT, and interfere with chromosomes and the hematopoiesis system.
The most important source of arsenic for humans is food, fish and meat.
Selenium (Se) is a
nonmetallic indispensible chemical element, absolutely necessary for all organisms.
Se is an essential antioxidant that is contained in the active centers of antioxidant enzymes like glutathione peroxidase, and protects cell membranes against the attack of free radicals.
Of all trace elements, Se has one of the narrowest
range between dietary deficiency (< 40 µg/day) and
toxic levels (> 400 µg/day for adults)
Se is also necessary for plants too. Inorganic natural Se is found everywhere in small quantities.
how many proteins that normally contain Se have been found
Thirteen
Up to six of them, including four peroxidases, are parts of the antioxidant system of the cell. This is the reason why Se deficiency significantly reduces the antioxidant
capacity of the cell as well as the efficiency of different parts of immune system of the organism.
The most famous fluorine-containing plastic is chemically extremely resistant…?
polytetrafluoroethylene (PTFE - teflon).
Thermal degradation of PTFE leads to a long list of toxic compounds, including highly corrosive and lethal gases, and PFIB, (perfluoroisobutylene) a chemical warfare agent that is 10 times more lethal than phosgene.
Of foodstuffs, the highest content of Fluorine is in
NaCl
(8.5 mg/kg in average). Normal content of F in solid food is 0,01-0,1 mg/kg.
Most mercury finds itself in the atmosphere as a result of
combustion of fossil fuels, such as coal or petroleum.
Hg is used at the production of chlorine, polymers, and paints.
(Hg) Exists in three different forms:
- Elementary mercury (Hg^0) that is absorbed as vapor and causes damage of the CNS.
- Salts of inorganic mercury (Hg+ and Hg2+) that are poorly absorbed, but the absorbed part is capable of inducing serious renal damage.
- Easily absorbable organic mercury R-Hg+, where R is mainly a methyl, ethyl or phenyl group.
Most dietary mercury intoxications originate from
the Hg-organic fungicides such as dimethylmercury, chloride and phosphate of methylmercury (MeHg).
Being lipid soluble, they absorb easily and bioaccumulate in erythrocytes and in the CNS.
MeHg and even more volatile di-Me-mercury in fish are synthesized by anaerobic micro-organisms from the salts of inorganic mercury deposited in the bottom sediments of various water bodies.
Industrial lead intoxications, connected with mining and melting of lead, became rather frequent during
the industrial revolution at the end of the 19th century.
But were described by Hippokrates already 300 BC.
Among all the metals, lead poisoning is encountered with greatest frequency in certain species of animals and poses a serious concern to animal health.
It is estimated that approximately half of human lead intake is through
food – with around a half originating from plants, where the content of lead is higher.
Plants with a large area of leaves like spinach or cabbage may contain more lead if they are cultivated in the lead emission areas.
When these plants are fed to animals, their organisms absorb little lead, most of lead is excreted with feces. However, some lead gets accumulated in the bones and hair.
Still in some places, existing lead pipelines cause elevated lead concentrations in drinking water.
Metallic lead aand its salts are absorbed slowly and incompletely from the mouth cavity (only 2–20%), remaining part is
excreted with feces.
Acidic diets as well as diets deficient in Ca, Zn, or protein can increase the absorption of lead.
97% of the absorbed lead is transported as a protein-complex into
erythrocytes,
where its half-life is 2–3 weeks.
The concentration of lead in the blood serum is very low.
Lipid-soluble organic lead is remarkably more toxic. For example, triethyl-lead, formed from tetraethyl-lead during combustion of gasoline easily penetrates the skin and reaches the brain which is the first target of lead, particularly in case of small children.
A part of lead is redistributed into the liver and kidneys, and further into
bile and bones. It is possible to see the lead-protein complexes in the kidneys under a light
microscope.
In the bones, lead is deposited in hydroxyapatite, where is determinable by X-rays for centuries. The presence of lead in the bone marrow hinders hematopoiesis.
Lead crosses the placenta and accumulates in the embryo. This results in
Delay of the embryonal nervous system, spontaneous abortion or early birth.
Owing to the immaturity of the blood-brain barrier of newborns, lead is capable of accumulating in their CNS.
. In the case of low concentrations in the blood, lead is excreted actively in ?
and in the case of high concentrations, in ?
bile, and in the case of high concentrations, in the urine.
Some data have been obtained showing that 5% of the lead found in the blood is excreted to the milk.
Lead is capable of influencing the synthesis of porphyrin and subsequently
heme
via enzymes in several steps.
Synthesis of heme proteins such as hemoglobin, myoglobin and CYP can also be inhibited.
the most sensitive measure of an organism’s exposure to lead
is estimated by measuring the concentration of δ-aminolevulinic acid in the blood or urine
Most environmental cadmium (Cd) is of what origin?
Most environmental cadmium (Cd) is of anthropogenic origin, which has reached the athmosphere from Cd smelters and processing or burning of Cd-containing products (plastics, paints, rubber, batteries, domestic waste), and waste waters.
Sources of Cd pollution are also mineral fertilizers and fungicides, and surface as well as tap water.
Tap water can get Cd from water-pipes made from black polyethylene, copper, or galvanized iron.
Since Cd is relatively volatile, it is mainly
an inhalable toxicant.
First accumulates in the lungs, where it is absorbed to the extent of 40%.
The absorbed part is mostly bound to the blood plasma proteins.
Follows accumulation in the liver (τ½ = 5-10 years), in the kidneys (τ½ = 20-30 years), and in the spleen.
Unlike Pb2+ and Hg2+ ions, Cd2+ ions are successfully absorbed by
plants including forage, especially well by root crops like turnips and leaf vegetables like spinach.
In plants, Cd is distributed quite evenly among all tissues.
Cd is well absorbed also by some mushrooms.
Of foodstuffs of animal origin, Cd is mostly
concentrated in
liver, kidneys and milk.
Although Cd accumulates in the soft tissues and
ample experimental results exist of the toxicity of Cd
in animals, under natural conditions, cases of direct toxic or carcinogenic effects of Cd in livestock are uncommon.
The acute toxicity of cadmium that manifests itself in
pulmonary as well as renal or testicular damage,
may lead even to death.
Testicular damage appears within some hours after a single contact with Cd. Results are necrosis, degeneration, and complete loss of spermatozoids.
Cd reduces the bloodflow through the testes and, due to a lack of oxygen and nutritients, ischemic necrosis will develop
Because of a disturbance of Ca metabolism by Cd, what happens?
bones turn fragile (osteomalacia). Later hypertonia, infertility, and chronic pulmonary and renal insufficiency appears.
Targets for the chronic toxicity of Cd are
the lungs and kidneys.
As a result of renal damage, protein and saccharides appear in the urine. Since Cd accumulates in the kidneys in complex with protein metallothionein, the renal damage may appear as a delayed effect after single doses.
Metallothionein (MT) is a
family of cystein-rich low-molecular (MW 500-14000 Da) metal-transporting proteins in the body.
Induction of MT synthesis is recommended for use as a biomarker of response of an organism to the exposure to Cd.
Sources of environmental chromium (Cr) are
combustion of fossil fuels, manufacturing of metals and plastics, galvanization, leather processing, and so forth.
Cr Is poorly absorbed (0.5–2%) and excreted mainly
with feces
The absorbed part is transported into the kidneys as transferrin conjugate and excreted mainly with urine, but also with sweat and bile.
Cr3+ potentiates the effect of insulin, influencing the
metabolism of carbohydrates, lipids and proteins
Cr3+ hinders binding of Fe to
transferrin, influencing the metabolism and
accumulation of Fe.
