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pharm
5/5

poppenga

note: 4 oz of baking chocolate will 
kill (can kill) a brittany spaniel

editorial note re: household hazard 
handout: lots of the information came from a specific text and tx 
information should be looked at - p 15, the last typewritten page of that 
handout, talks about chocolate intoxication - the last sentence there - 
emetics are contraindicated if animal has hyperreflexia or seizures *even 
if* you use the listed drugs to control the seizures. this is not written 
correctly in the handout.

review is friday at noon til 2.

today: the 
final lecture from dr p.
we will go over environmental toxicants. 


petroleum hydrocarbons
dioxins (TCDD)
polychlorinated biphenyls (PCBs)

Organochlorine insecticides (not used anymore,not made...but are 
environmentally persistent)
mercury (kind of a global environmental 
toxicant affecting a few spp)

Petroleum hydrocarbons:

1. crude oil: a) 
sweet and b) sour crudes [gasoline, naphtha, and kerosene] concentrations 
of these are higher in sweet than sour crudes

2. refined petroleum 
products: soups of hydrocarbons - aliphatic (long and short chain 
C-C-C.... methane, propane, butane, etc), chlorinated aliphatic [CCl4, 
trichloroethylene, other solvents], and aromatics [benzene, toluene]

these are complex mixtures.

crude oils can be classified by oil field, 
or oil well - each field has different components.

wrt animal exposures 
- these occur under different scenarios. in oil producing states, grazing 
animals may encounter oil fields; wildlife species may encounter spilled 
oil, other environmental contamination can occur. keep in mind 
compositoin of oil products changes as it "weathers" - the weathering 
process involves the loss of volatile components like short chain 
aliphatics, and concentration of non volatile products. this can affect 
wildlife depending when they are exposed - within first 48 hrs of spill, 
or much later. one problem with oil spills is that oil isn't diluted by 
water. 
also animals can be exposed in home, via commercial or home use. 
also kerosene is sometimes deliberately given to ruminants for some 
reason.

most of these things are highly lipophilic, good GI absorbance, 
good transcutaneous absorption, also through lungs. aspiration/inhalation 
pneumonia can occur. 

MOTA of Petroleum hydrocarbons: as expected with 
diverse chemicals, effects are diverse
direct irritation - most HCs are. 
low viscosity refined products may cause pulmonary damage via aspiration 
- these are gasoline, kerosene, other low viscosity high volatility 
products. aspirated more readily than say motor oil, other high viscosity 
products. these materials in ruminants will cause fairly severe bloating. 
disrupts microflora. in monogastrics, vomiting is common - problem w/low 
viscosity products - increased hazard of aspiration.
aromatics like 
benzene - bone marrow depression.
polyaromatics like naphthalene - PAHs - 
hemolytic anemia and avian embryotoxicity (trans egg).
they affect avian 
repro perhaps via alternations in normal hormonal cycles - they interrupt 
normal estrogen and prolactin cycling and result in failure to incubate 
eggs. also act as chronic stressor to all wildlife exposed. may depress 
immune system.

wrt toxicity:

crude oils: sweet are more toxic than 
sour, probably due to increased low viscosity/volatile product component

see handout for toxic doses

refined products: variable since composition 
is variable.
short chain aliphatics - butane, propane, methane, not that 
toxic
long chain aliphatics - gasoline, kerosene - risk of aspiration 
pneumonia. if you aspirate only 1 mL into trachea, can cause severe 
pneumonia leading to death. 
petroleum distillates often used as vehicles 
for insecticides - 10 mL orally will be toxic to adult human of average 
size. 

clinical signs: variable

crude oil: 
ruminants = bloat (cattle 
like to eat crude oil); 
monogastrics = emesis; 
CNS: ataxia, muscle 
tremors, confusion - some of these hydrocarbons are neurotoxic, some are 
severe CNS depressants; 
respiratory: aspiration pneumonia - acute, 
hemorrhagic, necrotic

[mineral oil: nontoxic, highly viscous, highly 
refined]

refined products: 
CNS: depression, ataxia, coma
chlorinated 
hydrocarbons: (trichloroethylene, CCl4) cardiac arrhythmias, liver damage 
- esp with CCl4!
respiratory: pneumonia

dx:

signs in wildlife - oil 
exposed wildlife - primary adverse effect on birds and some sea mammals 
is loss of insulating properties of feathers and fur, early hypothermia - 
chilling, loss of buoyancy, loss of condition if lives over 24 hrs, 
mammals may be beached. early death in birds esp is due to hypothermia. 
birds stop eating. preening results in ingestion.
lethargy, dermatitis, 
conjunctivitis, respiratory distress/pneumonia, dehydration, anemia, 
diarrhea, disorientation, pneumonia.
in sea otters - pulmonary emphysema 
is a common sequela - pretty unique to them.

those who work at tristate 
bird research and rescue -they are world renowned for their ability to 
work with oiled birds. 

lab dx - it may be possible to pick up some 
components of the stuff in tissue, like liver, but largely tissue 
analysis isn't done. with aromatics you may see pancytopenia, generally 
we see elevated liver enzymes in many of these animals. on necropsy, you 
may see material in GI tract. crude oil exposure is seen on birds often, 
that's easy. sometimes if you mix GI tract contents with water will see 
oily stuff float to top. pulmonary lesions are dramatic, usually 
ventrally located with congestion, consolidation, and abscesses depending 
on length of survival. nonspecific liver changes - fatty change, 
necrosis; maybe some renal tubular changes.

tx: emesis or gastric lavage 
is contraindicated due to potential for pneumonia - only exception is if 
the petroleum distillates are a vehicle for a very toxic insecticide - 
youmight have to induce vomiting since insecticide exposure is a greater 
risk than the pneumonia risk. AC not a good adsorbent for HCs. so 
symptomatic and supportive care is pretty much it.

if dermal exposure 
isn't critical for survival, eg cattle exposed to crude oil, not much you 
can do.

for wildlife, remove oil from fur and feathers to prevent 
hypothermia. provide warmth. fluid, nutritional support critical. dawn 
dishwashing detergent is good to emulsify oil and rinses off pretty well. 
free up nares from contamination, flush out eyes well. support in form of 
heat, fluids and nutrition is critical.

controversy: is it worth the 
resources to decontaminate exposed marine mammals and birds? it is very 
expensive. for every sea otter returned to the wild after the Valdez 
incident, it cost $60,000!!! wow. 

main points wrt petroleum HCs:

-they 
are complex mixtures
-livestock losses: cattle in oil producing states

-wildlife exposure - with valdez we lost 100,000 to 300,000 birds, many 
of which were scavenged by predators which then were sickened as well.

-multiple systemic effects, dependent on concentrations of specific 
chemicals in the mixture.

again: AC isn't a good adsorbent for the 
petroleum HCs. it won't hurt, though. also if you have an exposure where 
a more active insecticide is part of the product, go ahead and give it 
for that, it will help with that. 

Dioxins: not that these are a huge 
problem you will encounter often, not that there are many acute deaths, 
but youare probably familiar with the term dioxin and we'll go over it.


protypical compound: TCDD - aka 2,3,7,8 tetrachlorodibenzodioxin. one of 
most toxic chemicals known to man. we have found ONE naturally occuring 
dioxin, we think.

polychlorinated dibenzodioxins in general - there are 
about 75 isomers. chemical structure important wrt toxicity. two benzene 
rings connected with two C-O-C bonds; off the rings you have Cl atoms in 
various configurations. you can have different combinations of Cl 
attachments to different positions. TCDD is most toxic. it's a flat, 
planar molecule. 

source: well, Agent Orange was used in SE Asia as a 
defoliant, and in manufacturing this some contamination of the stuff with 
dioxin occured. also, a wood preservative used a lot sometimes is 
contaminated with dioxins, and other processes involveing chlorination 
(as for bleaching of wood pulp for paper) can form dioxins. these are the 
most toxic chemicals known, but we aren't really exposed.

but it is so 
toxic, and effects can be so subtle, it is a concern. 
most of the 
dioxins are extremely long lived and persistent in environment, very very 
lipophilic, reside in fat depots for a long time, resist normal 
metabolism. exposures have occured in several situations - you may know 
of Times Beach, MO - the EPA's infamous superfund site - dioxin 
contaminated waste oil was applied to the street to control dust - the US 
had to buy the whole town. 
use of herbicides - many people in SE asia 
were exposed to contaminants in AO.
poultry feed - clays from a specific 
mining site in the south added to poultry feed for anti-caking property, 
and FDA tested some chickens and found dioxin in them, traced it back to 
this clay - contained dioxin. big economic loss. 

lots of work wrt MOTA 
of dioxins. 
-binds a receptor complex in cytosol of hepatocyte (Ah-R 
[the aromatic hydrocarbon receptor] + ARNT [aromatic receptor nuclear 
transporter])
-receptor + dioxin is transferred into the nucleus
-binds 
to DNA sites called dioxin responsive elements, leading to 
transcriptional activation and enzyme induction. 
so that's fairly 
complex and specific. b/c you transcript proteins and enzymes, multiple 
biological functions are affected -
adrenal, thyroid, thymic, and immune 
functions are all affected. thymic involution occurs, causing loss of 
humoral immunity. also dioxins teratogenic in lab animals. 
species 
specific difference in susceptibility - humans very sensitive - probably 
related to binding affinity for the receptor - higher in some spp than 
others. that's why humans are more sensitive. some lab animals are 
relatively resistant. 

toxicity - structure is important, can affect 
toxicity. planar configuration is important. these things affect affinity 
for receptor. this is a cumulative toxin - so lipophilic and stable it 
accumulates in the body over time. wrt toxicity, we're talking micrograms 
per kg per day as toxic dose. not much is needed.

dx- 
signs include 
wasting, immunosuppression, it's a chronic thing, happens over time; 
porphyria, photosensitivity, anemia, thrombocytopenia; 
"chick edema 
disease" - embryo and chick mortality, growth retardation, developmental 
abnormalities like bill deformities, clubfeet, eye abnormalities, 
defective feathering; also edema, liver enlargement. seen in poultry and 
some wild birds.

specific dx - difficult. some labs can take tissue 
samples and measure presence of dioxins in those samples - a bit easier 
with improved analytical techniques. 
necropsy - no characteristic 
lesions, except w/chick edema syndrome. hard to pin down.

main points: 
persistent environmental hazard, very very toxic, humans more senstive 
than many animals, and they are cumulative toxins, and they cause complex 
pathophysiologic effects due to multiple protein or enzyme induction. 
phew.

Polychlorinated biphenyls - PCBs. kind of related to dioxins. 
there are 209 congeners possible, mixtures of specific PCPs. basically 
two phenyl rings attached without the O bonds, and Cl hanging off the 
rings. you can get rotation around the central C-C bond. can be planar or 
rotated.
these are lipophilic and environmentally persistent, like 
dioxins. they are chemically inert, so not metabolized well, like 
dioxins. this was actually one of the useful things about PCBs years ago. 
these are no longer manufactured but are used as insulators in older 
electrical transformers.
residues in food products are of primary 
concern. exposure of food producing animals is important. the other 
problem with PCBs is probably exposure of some wildlife animals to high 
concentrations; probably if most of us had a fat biopsy taken it wouldn't 
be hard to find some PCBs. fairly ubiquitous.
not currently mfrd, but if 
a line transformer explodes there can be a lot of contamination spread 
around. also contaminated oil, a number of silos were contaminated with 
sealant, so there is contaminated feed.

 "Yusho disease" in humans - 
historically, interest derived from an outbreak in Japan where people 
were exposed to high levels from contaminated rice oil. 
signs in 
handout. 

MOTA: like dioxin, bind Ah receptor in cytosol of hepatocyte; 
coplanar PCBs most potent ligands and have the same effects as dioxin. 
nonplanar PCBs are less toxic. probably 10-12 of the 209 PCBs are 
coplanar and most toxic.

toxicity: not acutely toxic to speak of; toxic 
dose measured in grams/kg for acute toxicity. this is unlike dioxins. 
these things do persist in the body, though, and over time changes occur 
associated with the receptor binding, enzyme induction, protein 
production. signs the same as for dioxin.

dx - concern is mostly about 
food animals, residues in products intended for human. easily detectable 
in tissues.

that's it!
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sweeney

Dr. Poppenga found errors 
in the problem answers he gave us. be advised. replace 0.0025 with 0.025 
and replace 1.3 with 0.77

ok. anyway.

IMD announcement - exams not 
graded yet.
we will get them later this week.

sweeney story - corduroy 
pillows - they're making headlines. ha.

ok, so this hour we're going 
over a few cases of large animal intoxications.

1. late spring, you go 
to farm with 3 horses, small pasture. all three horses are salivating. 
lots of slobbering. major reason for this in lg animals is usually 
inability to swallow, not hypersalivation. causes of dysphagia = 
botulism, choke, esophageal obstruction, rabies, etc. so you examine 
horse, it seems normal. no obstruction. but lots of saliva coming out of 
mouth. ideas? clover. red clover. makes horses salivate b/c it has a 
fungus - which makes a toxin called "slobber factor" or slaframene (sp?). 
it just makes them slobber, not really a problem.

2. another call to see 
a pet goat. this goat has some carpal swelling. usually in pen but just 
got out of pen. also vomiting. it ate some rhododendron while out of the 
pen. azalea, mt laurel, and rhododendron contain andromedatoxin which 
causes GI upset, vomiting. one of the few things that will make a goat 
vomit. in really severe cases, may also cause CNS signs eg seizures, 
ataxia. most often just depression, vomiting. tx: laxatives, charcoal? 
well, not really effective. ideally, do rumenotomy, get the stuff out of 
the rumen, wash it out. gastric lavage in goat isn't really possible, 
partially chewed leaves do not go through stomach tube anyway.

3. pony 
head pressing against wall - showing neuro signs. on farm in maryland 
where they have some horses and ponies on a 40 acre pasture. this is late 
december, early january. one horse died 3-4 days ago with no signs in 
advance, just found it dead. this pony got sick 3-4 days later. pony is 
showing signs of cerebral disease - the part that controls behavior, 
locomotion. is headpressing, blind (has pupillary light reflex but no 
menace reflex, so must have occipital cortex lesion), developed seizures 
and became recumbent. what's going on? ddx lead intoxication if this were 
a cow (in horses, tends to be more a peripheral neuropathy), rabies, EHV1 
(normally causes more of a myelitis but rarely affects brain), brain 
tumor, abscess; toxin? pony is turned out on pasture but in winter also 
gets hay, and ear corn from the dairy farm down the road. fumonisin - 
moldy corn disease. the fungus that infects the corn is fusarium, which 
makes fumonisins, which cause liquefactive necrosis of white matter of 
brain. antidote? nope. can try supportive care, DMSO, steroids, try to 
releive brain edema -but recovery is rare, euthanasia is usual. 
confirmation - feed analysis. 

4. amish dairy farm. they are having an 
unusual problem. 35-40 milking cows there, and all those are healthy, but 
the heifers are having trouble. the heifers are out on pasture and it is 
a dry summer. farmer calls you and asks you to come out - heifers are 
breathing heavy. you get out there - ddx? respiratory disease, pneumonia, 
shipping fever/pasteurella, atypical pneumonia associated with tryptophan 
but this isn't a lush pasture....hmm. you examine the cows and they are 
breathing rapidly. necks extended. lungs sound ok though. mms are pale. 
HR rapid. a couple of them have some SQ swellings. one has blood dripping 
from it where a bug just bit it. so...anemia? blood dripping from bite 
wound---> clotting defect? what causes clotting factor deficiency? 
warfarin? unlikely in cattle. moldy sweet clover - production of 
dicoumarol, vit K inhibition, clotting deficit, anemia. PT/PTT = dx. on 
these cows, PT/PTT are norml. thrombocytopenia? we learned of a disease 
causing this...BVD = most common cause of bovine thrombocytopenia in 
recent years. that may be #1 ddx. look for scleral hemorrhages - 
characteristic of thrombocytopenia. but these animals are afebrile, well 
vaccinated. what toxin causes thrombocytopenia? same plant that causes 
neuro signs in horses....brackenfern! brackenfern toxicity is rare - has 
to eat a lot of it to show signs. but animals that are deprived of other 
feed due to drought may eat it. causes bone marrow suppression in cattle 
- why? causes poliomalacia in horses. why aren't megakaryocytes making 
platelets in cattle that eat brackenfern?  he didn't say

5. farm in NJ - 
some horses that were not doing well. this horse losing wt x 1 month; 
acting funny x 1 day; yawning, seeming depressed, and today is standing 
wtih head down, unaware of surroundings, vague CNS signs. another horse 
on farm also losing wt. no cns signs but skin problem - area on nose of 
excoriations, sloughed skin. ddx cns - rabies, other, moldy corn; ddx 
skin - lesion confined to central nose so?? looks like sunburn.  
photosensitization. there are two types of this - primary and secondary. 
in secondary photosensitization, plants they eat are green, and normally 
the phytoerythrins, the photoactive chemicals, are detoxified by the 
liver and never get into skin. but if animal has liver failure, liver 
disease, these photoreactive things aren't detoxified, they enter 
peripheral circulation, enter skin, and react with sun to release energy 
producing a burn. usually in nonpigmented areas like on this horse. what 
causes CNS signs and photosensitization? liver disease. 
hepatoencephalopathy in first horse. so what causes liver failure in 
horses? CCl4, but why would a horse be near that? dewormers like 
thiobendazole in large doses could do this. sometimes you have horse 
trainers feed arsenic to stimulate the appetite (?); but we are thinking 
plants, here. on west coast - oregon, CA, tansy ragwort, synechio. 
puralizadine alkaloids (??) = toxin. these horses were on hay cubes sent 
here from CA - causes chronic liver damage. detect on biopsy. no specific 
antidote. to use up hay - feed it to sheep - sheep tolerate these toxins 
at much higher doses.

6. cow with red nose. in medsurg we learned about 
a disease called rednose - what was that? IBR. but those animals have 
vesicles in the mucosal area of the nares. this looks more like sunburn 
on the very distal area of nose. the outside of the udder is also burned. 
palpating some white areas on dorsum reveals leathery areas getting ready 
to slough. another case of photsensitization. liver is ok. what is it? 
primary photosensitization. this occurs when a normal animal ingests 
certain plants which contain photoreactive chemicals not normally 
metabolized by the liver. st. john's wort. yellow, daisy like flowers.


7. broodmares - mid autumn - horses in paddocks. this horse got acutely 
ill. depressed, dark red/brown urine. PE - normal temp, rapid HR, 
dehydrated, depressed, lying down, mms congested with brownish yellowish 
discoloration. icteric sclera. three things cause red urine - hemoglobin 
in urine, red cells in urine, (hemoglobinuria, or hematuria), or 
myoglobinuria. what causes these things? how do you know what it is? spin 
it down. if cells separate out, it has red cells in it. this urine stayed 
pigmented. ok, it's Hb or Mb in there. how to tell apart? 
spectrophotometer (ha ha). but renal threshold for Mb is very very low. 
if Mb is released into plasma it will exceed renal threshold and appear 
in urine at concentration so low you don't detect it in plasma. but with 
Hb you will also have pink plasma. spin down some blood. this horse had 
pink plasma. so it has hemoglobinuria. so horse has intravascular 
hemolysis. why? could be RBC parasite. could be red maple intoxication. 
EIA can cause intra or extravascular hemolysis. could be iatrogenic - one 
commonly used drug, DMSO, causes IV hemolysis when given IV. or if you 
give hypotonic fluids can cause it. another thing we saw though is that 
when we drew blood, the blood was brownish. not normal red color. 
chocolatey brown color. well, that's methemoglobin. what produces 
methemoglobinemia? red maple intoxication. 

these leaves have three main 
lobes. horses eat wilted leaves from fallen branches to get sick, not 
fresh leaves. causes oxidative insult to heme portoin of molecule. 
sometimes see heinz bodies - those plus metHb are diagnostic.

tx - 
nonspecific therapy - vit C, other antioxidants, try to prevent further 
insult. fluids, to prevent hemoglobinuric nephropathy, renal failure. 
specific antidote - not really. new methylene blue not effective in 
horses. maybe transfusion. supportive care. 

8. dead cow? looks dead to 
me. cow lying on its side. at NBC they say, where there's livestock, 
there's deadstock. this is an example of deadstock. every farmer loses a 
cow now and then, but there are three dead cows on this field. there were 
really 7 out of 10 dead on the rest of the field. they were normal last 
time they were seen (within 23 hrs). they were suddenly found dead. 
farmer has lightning strike insurance and he wants you to dx that. on 
necropsy from lightning you might see external burns, you might see a 
small gall bladder b/c animal ate right up to time of death. these 
animals have no burns. they are all scattered all over the farm, not all 
near one tree. so what else causes sudden death? anthrax. toxin. beef 
animals fed big round bales of hay may get nitrate intoxication and die 
suddenly. that's what these animals had. field test for nitrate - what is 
fluid of choice to test? aqueous humor - mix that with diphenylamine and 
it should turn blue. that's one thing to try anyway. some plants 
concentrate nitrates - johnson grass in the south, pigweed. 

9. sheep 
with icteric skin. pet 3 yr old ewe in westchester, never been bred, only 
sheep on farm, eats hay and grain in winter. became acutely anorexic and 
got severe icterus and skin necrosis in nonfleeced area. urine is red. 
she has hemoglobinuria. why? copper toxicity. probably that is th most 
common cause of hemolysis in sheep. sheep very sensitive to copper. dx - 
check grain. anything to ask the owners? are they feeding horse rations 
or cattle rations or sheep rations? they don't know the difference - were 
using cattle rations that included a copper supplement. this pet sheep 
was affected - sometimes whole flocks are affected. molybdenum 
deficiency, recall, also can result in copper toxicity. confirm dx with 
blood copper level but that may cycle, b/c signs are acute but 
intoxication is chronic - copper builds up in liver then is acutely 
released. px is poor but we tx some animals - how? chelation therapy - 
penicillamine. that will chelate copper, increase excretion of copper 
into urine. also can give molybdenum and oral sodium sulfate to inhibit 
copper absorption. also fluids, etc. may recover from acute episode, then 
get stressed and release more copper and have another acute episode and 
die from that. frustrating to tx. for commercial flock, don't usually 
treat affecteds, but change rations and tx flock with molybdenum. other 
copper sources - foot baths (copper sulfate shouldn't be used in sheep).



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