Organic substances poisoning –
alcohols, ethylene glycol,
phthalates, musk compounds
Lecture No. 5
Copyright © Mgr. Zuzana Široká, PhD.
Alcohols
Ethanol
- Poisoning by pure alcohol not very common in animals
- Possible ingestion of fermented fruits or of dough
containing yeasts, less from cosmetic products
- Rapidly absorbed, interaction with many
neurotransmiters and other systems (influences GABA
and NMDA receptors, dissolves lipids in membranes)
- First excitation, then depression of CNS, causes
hypoglycaemia, disturbs thermoregulation, blocks
production of adiuretin
- Its metabolite acetaldehyde is also toxic (alcohol
dehydrogenase)
- In 1 ‰ – excitation of CNS, muscle incoordination, diuresis
= dehydration, thirst (due to the lack of antidiuretic hormone
- hangover)
In 2 ‰ – strong inebriety, inability to move exactly
In 3-4 ‰ – coma, decrease of temperature (vasodilatation of
skin capillaries), blood pressure, respiration, metab. acidosis
- Chronic intake: gastritis (increased secretion of digestive
juices, vasoconstriction in GIT), stomach ulcers, steatosis
and cirrhosis of liver, polyneuritis, worse immune
reactions, deficit of thiamine (feeding with waste from
brewery etc.)
- Treatment: symptomatic - liquids, glucose, correction of
acid-base balance, monitoring of heart function and
respiration. In chronic poisoning supplementation of
thiamine. Activated charcoal is not effective. It is possible
to perform haemodialysis.
Methanol
- Colourless liquid
- Used as a solvent, antifreeze, fuel, released
from sweetening agent called aspartam
- Absorbed after ingestion, inhalation, via skin
- In an organism converted to formaldehyde and formic
acid – by alcohol dehydrogenase, much faster then
ethanol. These products toxic (bind to Fe3+ in breathing
enzymes), not methanol!
- Formic acid degraded to CO2 and H2O, but folic acid is
necessary for this process – after a short time – depletion
of folic acid
- Low activity of enzymes necessary for the conversion to
CO2 in humans (poisonings on the CR, Poland, India),
apes, pigs (LD 1,5 ml/kg). Other species less sensitive (e.g.
Dog 5-11 ml/kg).
- In sensitive species very slowly excreted – acummulation
- First nausea, vomiting, headache, dizziness, other
symptoms after a several hours’ latency
- Atrophy of optic nerve – blindness, decreased heart
function, incoordination, cyanosis, seizures, death
- Emetics, ethanol!!! – is first metabolised and methanol can
be excreted unchanged (especially by lungs), bicarbonates
to control acidosis, haemodialysis. Activated charcoal
ineffective
Ethylene glycol – winter poisoning
- Colourless, odourless, syrupy
liquid with a sweet taste
- Coolant or antifreeze in automobiles
and personal computers, important
in the plastics industry for the
manufacture of polyester fibers and
resins, in cosmetics and cleaning
products etc.
- Rapid absorption (even after
inhalation, quick metabolism, acute
poisonings
- In an organism converted to oxalic
acid, which is nephrotoxic
- LD dog 4,4 ml/kg, cat 0,9 ml/kg
- Symptoms of ethylene glycol poisoning usually
follow a three-step progression
Stage 1: neurological symptoms, dizziness,
headaches, confusion. Over time, the body
metabolizes ethylene glycol into other toxins first it is metabolized to glycolaldehyde, which
is then oxidized to glycolic acid, glyoxylic acid,
and finally oxalic acid
Stage 2: is a result of accumulation of these
metabolites - tachycardia, hypertension,
hyperventilation and metabolic acidosis
Stage 3: kidney injury leading to acute kidney
failure - oxalic acid reacts with calcium and
forms calcium oxalate crystals in the kidney –
usually death, oxalates in kidney is typical
pathological sign. Uremia, vomiting, oral
ulceration, seizures, death.
• - The antidotes for ethylene glycol poisoning are ethanol
or fomepizole, efficient in first 4 hours, later not.
ethanol (usually given i.v. as a 5 or 10% solution in
5% dextrose) - competition with ethylene glycol for the
enzyme alcohol dehydrogenase - decreases the
formation of toxic metabolites
fomepizole (4-methylpyrazole) – inhibition of
alcohol dehydrogenase –
blockage of the formation of
the toxic metabolites
- Haemodialysis can also be
used to enhance the removal of
unmetabolized ethylene glycol,
as well as its metabolites from
the body
Propylene glycol
- Replaces ethylene glycol
- Antifreeze, solvent, in cosmetics, pharmaceuticals,
food additive
- A bit less toxic than ethylene glycol (LD for dog 9
ml/kg)
- After ingestion changed to lactate, makes acidosis.
In horses and cats moreover causes damage to
erythrocytes and formation of Heinz bodies
(anaemia).
- Depression, ataxia, tremors,
circulatory collapse
Phthalates
• Salts of phthalic acid
• Used as plasticizers in polyvinyl chloride industry in toys, nail polish, fishing lures, adhesives, caulk,
paint pigments
• Easily released from plastic toys or from containers
to food (mainly in higher temperature), no covalent
bond with plastic, some of them volatile
• Have xenoestrogenic (antiandrogenic) and
•
carcinogenic effect (only animals),
•
lipophilic, found mainly in soil or
water and sediments
food chain
• Absorbed orally and via skin
• Degradation in an organism – no
oxidation/reduction, only conjugation
• 80 % excreted in urine and bile, rest
accumulated in fatty tissue
• Acute toxicity: tiredness, blurred vision,
lacrimation
Chronic toxicity: damage of liver, kidneys,
increased pigmentation, disturbances of
reproduction, risk of allergies in children,
increased risk of diabetes development
Bisphenol A (BPA)
- Plasticizer – no colour, to make bottles, CDs and
DVDs, coating in waterpipes, cans etc.
- Now banned in baby products
- Endocrine disruptor:
- binds to estrogen receptor
- problem with brain development in fetuses
- increased risk of obesity
- disruption of thyroid function
- possible carcinogen
Musk compounds
• Nitro and polycyclic musks –
frequently used as fragrance
ingredients in personal care
products
• Found in humans and aquatic organisms
• Inhibit the activity of multidrug efflux transporters
responsible for multixenobiotic resistance (MXR) xenobiotics are able to enter the cell (transporter
proteins responsible for MXR include P-glycoprotein,
multidrug-resistance protein and other members of the
ATP-binding cassette family of transport proteins )
• Low binding affinity to estrogen receptors – also weak
xenoestrogens
• More info:
http://en.wikipedia.org/wiki/Effects_of_alcohol_
on_the_body
• http://www.methanol.org/
• http://www.methanol.com.au/_aboutmethanol.asp
• http://www.jtbaker.com/msds/englishhtml/E5125
.htm
• http://www.epa.gov/ttn/atw/hlthef/ethy-gly.html
• http://www.phthalates.com/
• http://www.phthalates.org/index.asp
• http://findarticles.com/p/articles/mi_m0CYP/is_1
_113/ai_n15625807