Toxicology Exam I Material (Insecticides & Rodenticides) Flashcards
Is Rotenone more toxic via ingestion, inhalation, or cutaneous exposure?
inhalation
With regard to pyrethrins, what type of exposure is most common?
Dermal
Ingestion and Inhlation are possible
What is the mechanism of action (MOA) of Chlorinated Hydrocarbons?
Interferes with Na+ channels, causing CNS stimulation
Why is 2-PAM contraindicated with Carbaryl?
It can potentially increase the carbamylation process, further potentiating toxicity
T/F: Tachycardia is a clinical sign associated with muscarinic stimulation
False
It’s not.
T/F: Organophosphates that require desulfuration will be less toxic to young patients
True
What does DUMBELS stand for?
- Diarrhea
- Urination
- Miosis
- Bronchospasm/Bronchoconstriction/Bradycardia
- Emesis
- Lacrimation
- Salivation
T/F: Organophosphates and Carbamates undergo storage activation
False
Carbamates do not undergo storage activation
A toxicant that is metabolized by oxidative enzymes has a faster rate of metabolism in:
Cattle
What is the specific treatment for organophosphate toxicity?
2-PAM
“Cholinesterase reactivating oxime”
T/F: Some carbamates undergo “lethal synthesis”
False
Which of the following toxins acts mainly as an alpha-2 agonist?
- Amitraz
- DEET
- Couphos
- Pyrethrins
Amitraz
What is the difference between 1st and 2nd generation pyrethrins?
Addition of α-cyano moeity
- 1st gen (Type I) do not contain α-cyano moeity
- 2nd gen (Type II) do contain α-cyano moeity, which increases their insecticidal potency
Which tissues are best for postmortem diagnosis of pyrethrin toxicity?
liver and brain
What chemical property of Chlorinated Hydrocarbons is responsible for bioaccumulation in the food chain?
Chlorinated Hydrocarbons are highly lipophilic
Which of the following insecticide toxicants would you expect to have the longest half-life?
- Organophosphates
- Carbamates
- Chlorinated Hydrocarbons
- Pyrethrins
Chlorinated Hydrocarbons
T/F: If there is a strong response to low dose atropine (0.02mg/kg) during an atropine response test, it is less likely that the patient has organophosphate toxicity
True
The atropine dose for treatment of organophosphates is about 10x the dose given during the atropine response test. So if the patient responds to such a low dose, it’s probably not OP toxicity
T/F: Pyrethrins are generally not very toxic to mammals, but very toxic to birds and fish
True
Which of the following is consistent with Cholecalciferol Toxicity?
- Increased Ca, Decreased Phosphate, and Increased PTH
- Decreased Ca, Decreased Phosphate, and Increased PTH
- Increased Ca, Decreased Phosphate, and decreased PTH
- Increased Ca, Increased Phosphate, and decreased PTH
Increased Ca, Increased Phosphate, and decreased PTH
T/F: Pyrethrins are extracted from the tears of migrating antarctic buffalo that left their family to find a better life for their children
False
- Close though!*
- Pyrethrins are extracts of pyrethrum flowers (Crysanthemums)*
Would you expect to see CNS stimulation or CNS depression with D-Limonene toxicity?
CNS depression
T/F: Some organophosphates undergo “lethal synthesis”
True
T/F: For laboratory diagnosis of organophosphate toxicity, <50% acetylcholinesterase activity is considered diagnostic
False
<50% activity is considered suspicious.
<25% activity is considered diagnostic
T/F: Chlorinated Hydrocarbons generally degrade relatively quickly in the environment
False
Soil half-life reportedly between 2-15 years
T/F: 2-PAM is not reliably effective for treatment of carbamates
True
Reversible binding reduces benefit
Why is piperonyl butoxide or MGK-264 added to pyrethrins?
Inhibits pyrethrin metabolism in insects
(but potentially increases toxicity in mammals)
T/F: Cats are more sensitive to D-Limonene than dogs
True
What is the best tissue to sample post-mortem for diagnosis of Rotenone toxicity?
liver
Which of the following toxins are dogs more sensitive to than cats?
- Bromethalin
- Rotenone
- Strychnine
- Amitraz
Strychnine
What are the specific lesions associated with organophosphates?
No specific lesions
Which of the following has direct acetylcholinesterase activity?
- Dichlorvos
- Diazinon
- Fenthion
- Parathion
Dichlorvos
What is the mechanism of action (MOA) of D-Limonene?
Unknown
However, it is suspected that it may act through central and peripheral vasodilation due to an undetermined neuronal mechanism
What are the two most common signs of Rotenone toxicity?
Respiratory depression and convulsions
What is the main clinical sign of Chlorinated Hydrocarbon toxicity?
CNS Stimulation
What is the mechanism of action (MOA) of carbamates?
Reversible inhibition of cholinesterases
Acetylcholinesterase can hydrolyze carbamates, but at a slower rate than Ach
Why do you want to avoid hypothermia when treating small patients who have had topical pyrethrin exposure?
Hypothermia may further alter Na+ channel kinetics
The dose that will produce alterations (hematologic, biochemical, pathologic, or clinical), and administering twice this dose will result in lethality is called:
Toxic Dose High (TDH)
What is the mechanism of action for organophosphates?
Irreversible inhibition of cholinesterases
This will increase acetylcholine at all cholinergic sites
What species is most sensitive to Chlorinated Hydrocarbons?
Cats
All animals are susceptible (nonspecific) but cats are the most sensitive
What is the main storage tissue for Chlorinated Hydrocarbons?
FAT
What condition in canine patients is commonly treated with o,p-DDD?
Pituitary dependent hyperadrenocorticism (Cushing’s Syndrome)
What is the mechanism of action (MOA) of pyrethrins?
Delay closure of Na+ channels in the axonal membrane of the insect

This leads to knockdown effect, which is rapid paralysis caused by inhibition of neurons (the insect is immobile, but not dead yet
T/F: Chlorinated Hydrocarbons (DDT, for instance) are highly lipophilic and excreted in the bile. This suggests that they likely undergo enterohepatic recirculation
True
T/F: Organophosphates become more toxic after being stored for a long period of time
True
If sealed and stored for 1-2 years, will become more toxic
Which drug would you use in pyrethrin toxicity to control severe muscle tremors?
Methocarbamol
If you have a patient on phenobarbital and they are exposed to an organophosphate that requires desulfuration, will the organophosphate be more or less toxic?
More toxic
Phenobarbital is an enzyme inducer. Organophosphates that require desulfuration will be activated by liver metabolism (“Lethal Synthesis”), so they will be more toxic if enzyme inducers are present
What is the cause of death in high exposure to organophosphates?
Respiratory failure
What is the mechanism of action (MOA) of Rotenone?
Blocks oxidative phosphorylation, preventing NADH from being oxidized to NAD, thus interfering with production of ATP
Affects cell respiration (crosses cell membranes)
Which of the following is the best treatment for a dog that is hemorrhaging from Brodifacoum toxicosis?
- Vitamin K1 PO
- Vitamin K3 PO
- FFP
- Vitamin K1 SC
FFP
Fresh Frozen Plasma
How are animals most commonly exposed to organophosphates?
Orally (contaminated feed)
Exposure may also occur dermally (when used as a dip or spray) or via inhalation (aerosol spray)
T/F: Atropine is used to treat muscarinic and neuromuscular signs associated with organophosphate toxicity
False
Atropine does not treat the neuromuscular problems; just the muscarinic signs
T/F: Alkalinization of the stomach increases absorption of Nicotine
True
In the case of toxicity, this would be a bad thing. So for instance, you would not want to give your patient with Nicotine toxicity an antacid because it will enhance the absorption
What is the mechanism of action (MOA) of Nicotine?
- At low doses mimics Ach and stimulates post-synaptic nicotinic receptors (CNS, ganglia, NM junctions)
- Stimulates CRTZ (chemoreceptor trigger zone - may see vomiting)
- At high doses stimulation will be followed by blockage (persistent depolarization)
What drug is useful for controlling the parasympathetic effects of Nicotine toxicity?
Atropine
What is the mechanism of action (MOA) of Amitraz?
alpha-2 agonist in the CNS
- Weak alpha-1 agonist activity
- Weak monoamine oxidase (MAO) inhibitor
What is the most common clinical sign associated with Amitraz toxicity?
Transient Sedation
May last 24-72 hours
Why is hyperglycemia often seen associated with Amitraz toxicity?
alpha-2 inhibition of insulin
Name two antidotes for Amitraz toxicity. Which one is considered the better option?
Yohimbine and Atipamezole
Atipamezole is considered the better option because it has fewer cardiorespiratory effects than yohimbine
If chelation therapy is recommended for a toxicant when levels reach 5mg%, will a blood level of 900mcg/dL require therapy?
No
5mg% = 5000 mcg/dL
Therefore, 900 mcg/dL is not high enough to require therapy

Which three insecticides that we covered in class are CNS depressants?
Amitraz, Ivermectin, D-limonene
*Financial AID can be depressing*
DEET concentration of ____ppm is considered diagnostic for DEET toxicity
20 ppm
What is the most common source of Naphthalene toxicity?
Ingestion of mothballs

What is the mechanism of action (MOA) for Naphthalene?
Causes oxidative damage to RBCs –> methemoglobinemia
Will not be able to bind O2, and will also alter O2 binding at other heme sites, leading to tissue hypoxia
T/F: The amount of poison that under a specific set of conditions will result in detrimental biologic changes is known as LD50
False
The amount of poison that under a specific set of conditions will result in detrimental biologic changes is called _toxicity_
Which of the following toxins works though its inhibition of oxidative phosphorylation in the TCA cycle?
- Rotenone
- Methoxychlor
- Naphthalene
- Cholecalciferol
Rotenone

A compound that has a LD50 of 100mg/kg is considered:
- Practically nontoxic
- Slightly toxic
- Highly toxic
- Moderately toxic
- Extremely toxic
Moderately toxic
T/F: Atropine is effective in treating muscle fasciculations as a result of organophosphate toxicity
False
The effect of a toxicant produced by daily exposure for 30 days or less is decscribed as:
subacute toxicosis
A compound that has LD50 of 200 mcg/kg is considered:
extremely toxic!
The first clinical signs in organophosphate poisoning are mainly due to:
muscarinic stimulation
2-PAM antagonizes the toxic effects of organophosphates by:
reactivation of acetylcholinesterase
T/F: As a rule of thumb, 100g/ton of a toxicant in a feed is pretty much equivalent to 110ppm of the toxicant in the feed
True
The “knockdown” effect is used to describe the action of what insecticide?
Pyrethrins
The preferred medication for initial control of seizures in a dog with an unknown toxicant would be:
Diazepam
What animals are most susceptible to Ivermectin toxicity?
dogs and small birds
Collie breeds are especially susceptible
If you wanted to use Ivomec® extra-label and you know that toxicity can be seen at doses as low as 300mcg for a 1 kg kitten, how many milliliters of undiluted (1%) Ivomec® would that be?
0.03 mL

T/F: Ivermectin is well distributed throughout the body and crosses the BBB
False
Ivermectin is well distributed throughout the body, but does not cross the BBB. It is kept out of the CNS by p-glycoprotein efflux pump
What is the mechanism of action (MOA) of Ivermectin?
GABAA agonist
Binding to glycine and voltage-gated chloride channels also occurs in overdose situations. At low concentrations, it may reduce GABA and cause excitatory signs (reversed as concentrations increase)
Does D-Limonene cause CNS depression or CNS stimulation?
CNS depression
What drug is used to treat muscle fasciculations associated with organophosphate toxicity?
2-PAM
Which of the following should NOT be used in the treatment of organophosphate poisoning in dogs?
- acepromazine
- atropine
- activated charcoal
- diphenhdramine
- diazepam
acepromazine
In a chemical analysis, the result is expressed as 67 µg/g. What is the equivalent to this value in %?
0.0067%
1 µg/g = 0.0001%
Fun fact, right? Wrong - That fact isn’t even a little bit fun.
The effect of a toxicant produced by daily exposure for 30 days or less is decscribed as:
subacute toxicosis
The dose which will produce alterations (hematologic, biochemical, pathologic, or clinical) and administering twice this dose will result in lethality is called:
toxic dose high (TDH)
In a chemical analysis, the result is expressed as 9 µg/g. This is equivalent to what value in %?
0.0009%
1 µg/g = 0.0001%
The relative toxicity of drug A is 35 mg/kg. How would this drug be classified?
Highly toxic
T/F: Emesis is recommended for patients with CNS signs as a result of Tea Tree Oil toxicity
False
Emesis is not recommended due to risk of aspiration
When would you expect onset of clinical signs of tea tree oil (TTO) toxicity?
2-12 hours
1 kg = ____ lb
1 kg = 2.2 lbs
100 g/ton = _____ ppm
100 g/ton = ~110 ppm
1 µg/g = _____%
1 µg/g = 0.0001%
1 gal = _____ ounces
1 gal = 128 ounces
1 ppm = _____ mg/L
1 ppm = 1 mg/L
0.1 mg% = _____ ppm
0.1 mg% = 1 ppm
If a dog ingests a rat that recently feasted on a pile of warfarin, what is that an example of?
Relay Toxicosis (2o toxicosis)
What species is most susceptible to anticoagulant rodenticide toxicity?
Dogs
Order of sensitivity: Pigs > dogs & cats > ruminants > horses & chickens

Which one has a longer half-life: Warfarin or Brodifacoum?
Brodifacoum
- t1/2 of Brodifacoum: 6 days
- t1/2 of Warfarin: 19 hours
What is the general mechanism of action (MOA) of anticoagulant rodenticides?
Inhibit Vitamin K epoxide reductase
(Vitamin K epoxide reductase is the enzyme that converts Vit K epoxide to reduced form). This inhibition leads to depletion of reduced Vit K and reduced activation of clotting factors II, VII, IX, and X.
When would we expect to see onset of clinical signs with anticoagulant rodenticide toxicity?
1-5 days
T/F: Animals with anticoagulant rodenticide toxicity may die without external evidence of bleeding
True
Name the lesions associated with anticoagulant rodenticide toxicity:
Intrapulmonary, intrathoracic/abdominal hemorrhage, petechiation, ecchymosis
Of the following coagulation parameters, which will become abnormal first with anticoagulant rodenticide toxicity?
- Activated clotting time (ACT)
- Prothrombin time (PT)
- Activated partial thromboplastin time (aPTT)
- Proteins induced by vitamin K antagonists (PIVKA)
PIVKA
Proteins induced by vitamin K antagonists (PIVKA)
What Vitamin K-dependent clotting factor has the shortest half-life?
Factor VII
For clotting factor tests associated with anticoagulant rodenticide toxicity, PIVKA will be prolonged 1st. However, because PIVKA blows, we’ll look at PT. Because PT tests Factor VII, it should be the next one to go down.
T/F: Vitamin K3 is the treatment of choice for anticoagulant rodenticide toxicity
False
Vitamin K3 is not effective and has stupid side effects. Use Vitamin K1
T/F: Phytonadione is the treatment of choice for anticoagulant rodenticide toxicity
True
Phytonadione is Vitamin K1 (oral route is recommended)
T/F: Vitamin K1 should always be given IV
False
Vitamin K1 should pretty much always be given orally. If given IV there is a high risk of anaphylaxis
T/F: Response to Vitamin K1 may be reduced in liver failure
True
What would your duration of Vitamin K treatment be for Warfarin?
~1 week
What would your duration of Vitamin K treatment be for Brodifacoum?
~4 weeks
If anticoagulant rodenticide intoxication is suspected but you do not know what specific rodenticide was ingested, how long should you treat with Vitamin K1?
4 weeks (28 days)
T/F: Nursing animals can be exposed to cholecalciferol rodenticides through the milk
True
What is the general mechanism of action (MOA) of cholecalciferol rodenticides?
Causes hypercalcemia and hyperphosphatemia
- Increased serum calcium due to increased GI absorption and decreased renal excretion of Ca++
- Deposition of calcium in soft tissues such as kidney tubules, cardiac and lung tissues, vascular walls, and stomach
- Leads to tissue damage, increased capillary permeability and hemorrhage, renal ischemia
- Increased renal loss of sodium and potassium (competition with calcium for reabsorption)
When do you expect onset of clinical signs associated with cholecalciferol rodenticides?
24-36 hours
If a patient presents with hypercalcemia and significantly elevated parathyroid hormone (PTH) level, would cholecalciferol rodenticide be on the top of your differential list?
No
- The top differential would be hyperparathyroidism*
- Cholecalciferol rodenticide toxicity results in hypercalcemia, hyperphosphatemia, and decreased PTH*
T/F: Bromethalin is effective against warfarin resistant rodents
True
T/F: Guinea pigs are resistant to Bromethalin
True
Guinea pigs lack the correct metabolic enzymes for Bromethalin

T/F: Bromethalin undergoes “lethal synthesis”
True
Metabolized by N-demethylation in the liver to the metabolite desmethylbromethalin (more toxic)
T/F: Bromethalin does not undergo hepatic recirculation
False
It does.
What is the mechanism of action (MOA) for Bromethalin?
Uncoupling of oxidative phosphorylation
Basically this will alter ATP production, resulting in a lack of cellular energy, resulting in cell death
What are the ‘primary targets’ for Bromethalin?
brain and spinal cord
Are acute or delayed clinical signs typically associated with Bromethalin toxicity?
Delayed (subacute)
Acute signs are more rare and usually only occur with supralethal doses
A dog showing signs of anorexia, vomiting blood, cardiac arrhythmias, polyuria and polydipsia is MOST likely intoxicated with what rodenticide?
Cholecalciferol
Which of the following is an indicator of much poorer prognosis in cases of cholecalciferol rodenticide poisoning?
- GI bleeding
- PU/PD
- Anorexia
- Lethargy
GI Bleeding
T/F: Anticoagulant rodenticides inhibit production of precursor proteins of clotting factors II, VII, IX, and X
False
Anticoagulant rodenticides inhibit _activation_ of precursor proteins of clotting factors II, VII, IX, and X
List the species sensitivity to anticoagulant rodenticides in decreasing order:
pigs > dogs & cats > ruminants > horses > chickens