Should veterinarians consider acrylamide that potentially occurs in starch-rich foodstuffs as a neurotoxin in dogs?

Abstract

Three clinically healthy Labrador puppies developed ataxia, hypermetria and convulsions shortly after eating the burnt crust of maize porridge. Two of the puppies died. Acrylamide toxicity was considered based on the history of all 3 puppies developing nervous signs after being exposed to a starch-based foodstuff that was subjected to high temperature during preparation. Acrylamide-induced neurotoxicity is thought to partially result from a distal axonopathy.

Full text

Clinical communication — Kliniese mededeling
Should veterinarians consider acrylamide that potentially occurs in
starch-rich foodstuffs as a neurotoxin in dogs?
L Le Roux-Pullena* and D Lessingb
INTRODUCTION
The presence of acrylamide, a poten-
tially toxic substance, was only discov-
ered in starch-rich foodstuffs as recently
as 2002. The synthesis of acrylamide in
starch-containing foods such as potatoes,
cereals and bread is dependent on expo-
sure to high temperatures10. The risk this
compound poses to the consumer at the
concentrations that occur in regularly
consumed foodstuffs is still being debated,
but prompted the European Chemical
Agency to add acrylamide to the list of
substances of very high concern in 20104.
The acrylamide monomer is a potent
neurotoxin that has been known for over
50 years. Numerous toxicity trials have
been conducted in mammals, including
dogs.
The acrylamide monomer is a white,
odourless, crystalline solid at room tem-
perature and is used to produce non-toxic
poly-acrylamide polymers. These poly-
mers have multiple industrial uses,
among others in wastewater treatment
and the textile industry2.
The toxic effect and subsequent clinical
manifestation depend on the degree of
exposure to acrylamide. The clinical
neurological signs are attributed to a
distal axonopathy, otherwise known as a
‘dying-back’ neuropathy9,11,13.
Clinical signs reported in humans after
acute acrylamide exposure include sweat-
ing, nausea, myalgia, speech disorders,
numbness and weakened extremeties2.
To the authors’ knowledge there are no
previous cases documented of dogs that
incidentally developed acrylamide neu-
ropathythroughtheirdailydiet,butsome
of the trials during which acrylamide
has been intentionally administered to
domestic animals are discussed. The effects
of acrylamide administration in dogs
were found to be similar than those
observed in other species12.
CASE HISTORY
A Labrador bitch and her 3, 2-month-
old puppies, all clinically healthy and in
good physical condition, were fed
maize porridge that was badly burnt. A
day after exposure the owner reported
that 1 of the puppies suffered a seizure
and died. Soon afterwards another
puppy started walking in an abnormal
manner, vomited and had convulsions,
but 24 to 48 hours after the 1st signs were
noted, the puppy recovered. When the
3rd puppy started showing similar signs,
the owner consulted a private veterinary
practitioner.
On clinical examination the puppy
was ataxic and displayed hypermetria.
No other neurological signs were seen,
although a full neurological examination
was not done. The puppy was in good
bodily condition. The temperature, pulse,
respiratory parameters and mucous
membrane colour were within normal
limits. There was no oculonasal discharge
or diarrhoea present. A blood smear
showed no abnormalities and was nega-
tive for Babesia spp. parasites.
The veterinarian administered water-
soluble vitamins (Vitamin B Co, Oberon
Pharma), dexamethasone (Dexafort,
Intervet Schering-Plough Animal Health)
and intravenous fluid therapy. The
puppy was hospitalized for observation.
Despite sustained treatment the puppy’s
condition deteriorated. He developed
tetraparesis and died 3 days later.
On post mortem examination a hard,
black, thin, oval object 3 cm in diameter
was found in the stomach. No other
macroscopic lesions were noticed. The
foreign object was identified as burnt
porridge, which the owner fed to the
puppy a few days earlier. The dam and
litter had been fed porridge before and
could have been exposed to burnt rem-
nants on previous occasions.
DISCUSSION
All the puppies in this litter exhibited
similar neurological signs in a short
period , and either intoxication or the
involvement of an infectious agent were
considered as the most likely differential
diagnoses for their ailment.
There was no history of exposure to any
exogenous neurotoxins. The clinical signs
that typically accompany frequently seen
organic and inorganic intoxications in
dogs (including methaldehyde, strych-
nine and tremogenic mycotoxins) were
absent3. The typical haematological
pathology seen in lead poisoning was not
present on the blood smear. The puppies’
daily diet included a good commercial
puppy feed, making a thiamine deficiency
unlikely. The involvement of neurotropic
infectious agents causing diffuse neuro-
logical signs were ruled out as unlikely
based on history and clinical examina-
tion.Thefollowingagentswereexcluded:
•Toxocara canis: although ascarid toxaemia
is a likely diagnosis in this case, none of
the puppies showed any other signs of
worm infestation prior to eating the
burnt maize porridge, no worms were
present in the puppy on which a post
mortem was performed, and the dam
wasdewormed shortly before whelping.
0038-2809 Jl S.Afr.vet.Ass. (2011) 82(2): 129–130 129
aDepartment of Paraclinical Sciences, Faculty of Veteri-
nary Science, University of Pretoria, Private Bag X04,
Onderstepoort, 0110 South Africa.
bFrankfort Dierekliniek, PO Box 215, Showgrounds,
Frankfort, 9830 South Africa.
*Author for correspondence.
E-mail: lerica.leroux@up.ac.za
Received: March 2011. Accepted: June 2011.
ABSTRACT
Three clinically healthy Labrador puppies developed ataxia, hypermetria and convulsions
shortly after eating the burnt crust of maize porridge. Two of the puppies died. Acrylamide
toxicity was considered based on the history of all 3 puppies developing nervous signs after
being exposed to a starch-based foodstuff that was subjected to high temperature during
preparation. Acrylamide-induced neurotoxicity is thought to partially result from a distal
axonopathy.
Keywords: acrylamide, ataxia, convulsions, distal axonopathy, high temperature,
hypermetria, starch.
Le Roux-Pullen L, Lessing D Should veterinarians consider acrylamide that potentially
occurs in starch-rich foodstuffs as a neurotoxin in dogs? Journal of the South African Veteri-
nary Association (2011) 82(2): 129–130 (En.). Department of Paraclinical Sciences, Faculty of
Veterinary Science, University of Pretoria, Private Bag X04, Onderstepoort, 0110 South
Africa

•Neospora caninum: neither the dam nor
the puppies had any exposure to bovine
placental tissue, neosporosis has never
been diagnosed in cattle of the sur-
rounding farming community, and the
dam had whelped and raised normal
puppies before.
•Toxoplasma gondii: this parasite is more
commonly seen in immunosuppressed
animals and less likely in dogs, and the
more commonly seen respiratory and
gastrointestinal signs accompanying
toxoplamosis were not observed in
these puppies. The classic neurological
sign of hyperextended pelvic limbs seen
in young animals suffering from toxo-
plamosis or neosporosis were absent in
all 3 puppies3.
•Distemper virus: although the puppies
had not yet received their 1st inocula-
tion prior to the development of clinical
signs,thedamwasfullyvaccinated,and
the clinical signs that typically precede
neurological signs in puppies infected
with distemper virus after birth were
not present3.
It is nevertheless a limitation of this
report that no tests were done to confirm
the absence of the abovementioned
differential diagnoses.
Acrylamide toxicity
Acrylamide is well absorbed by most
routes, but exposure usually occurs
through oral intake or contact with the
skin. The monomer is distributed widely
throughout the body and metabolized by
the liver to non-toxic metabolites, which
are mainly excreted in the urine9. Studies
have demonstrated rapid and large-scale
absorption in dogs after oral intake of
acrylamide6. The resulting neuropathy
and the severity of the syndrome that
follows intoxication are dependent on the
magnitude of the dose, the rate of admin-
istration and the period of exposure to the
toxin11. The peripheral (motor and sensory)
and central nervous systems are affected,
but the latter seems to require higher
doses of toxin. The neuropathy is widely
accepted to be an example of a central–
peripheral distal axonopathy13. This is
defined as a process whereby the distal
portion of the longest peripheral axons is
affected 1st, but after continuous expo-
sure the distal segments of corticospinal,
spinocerebellar and dorsal column axons
also become involved. Ataxia resulting
from cerebellar dysfunction follows
owing to afferent and efferent cerebellar-
and Purkinje fibre degeneration1,11. More
recent studies suggest that terminal
degeneration might be the primary site of
pathology and precedes axonopathy8.
With high-level acute acrylamide expo-
sure, however, the clinical picture is
typically an encephalopathy with accom-
panying ataxia and seizures, followed by
a peripheral neuropathy. Widespread
autonomic dysfunction can occur11.
Acrylamide also has an effect on calmo-
dulin (CaM) concentration and protein
kinase C (PKC) activity, offering a
hypothesis that this may be another
mechanism whereby acrylamide induces
neuropathy14.
Earlier studies in cats revealed severe
tonic-clonic convulsions and other signs
of a diffuse central nervous excitation
when lethal doses (100 mg/kg adult
feline) of acrylamide monomer were
administered intravenously. Administra-
tion of sublethal doses induced ataxia and
tremors7. When adult male Beagle dogs
and miniature pigs were fed 1 mg acryla-
mide/kg/day in the diet for 3–4 weeks no
neurotoxic signs were elicited, but acryl-
amide was present in muscle tissue
collected at post mortem examination.
Although the nervous system is the
primary target for the acrylamide mono-
mer, less than 1 % of the substance was
detected in the brain. Neuropathy was
observed in the dogs and pigs when the
acrylamide was administered at 5 mg/kg/
day for an extended period of 30 to
60 days6. Chronic exposure in dogs leads
to the typical progressive sensorimotor
peripheral neuropathy, including toe
cuffing and ataxia and weakness, with a
unique association to megaoesophagus
due to vagal nerve axonopathy12. When
sublethal doses of acrylamide are discon-
tinued, the neuropathy that developed
may resolve slowly. More severe deficits
like spasticity and cerebellar ataxia are
likely to remain1,9.
The most prominent histological finding
in acrylamide neuropathy is degeneration
of peripheral nerves2. Chemical analysis
of tissue samples, for example muscle,
could aid in the diagnosis of acrylamide
poisoning. In addition to neuropathy,
carcinogenicity, mutagenicity and repro-
ductive toxicity have also been demon-
strated in rats2, 13.
The LD50 in rats is 100–150 mg/kg13. The
LD50 incats and monkeyswasdetermined
to range between 100 and 200 mg/kg after
a single dose2.
Quantitative food surveys done in the
UK in recent years revealed that cereal
can contain up to 57 mg/kg acrylamide
and a kilogram of potatoes up to 112 mg5.
Levels appear to rise as food is heated for
longer periods of time. To the authors’
knowledge there are no figures available
for the levels of acrylamide that can be
present in maize porridge exposed to
hightemperaturesforaprolongedperiod.
Despite strong circumstantial evidence,
it is a limitation of this report that tissue
sampling for histopathology or determin-
ing tissue levels of acrylamide were not
done in order to confirm the suspected
acrylamide toxicity.
CONCLUSION
Porridge prepared from maize meal is a
staple diet for people in South Africa and
the burnt remnants are often fed to
household pets. The possibility of acryla-
mide toxicity occurring in these animals,
in particular immature animals, deserves
consideration and should not be ignored
when neurological cases are seen. Further
studies are needed to quantify the risk
acrylamide in foodstuffs poses to dogs.
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