Toxicology: Arsenic Poisoning

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What are two forms of arsenic?

organic and inorganic (arsenates, arsenites)

What are two distinct clinical syndromes observed with arisen poisoning? ****

What is the mortality for each?
What are the GIT signs for each?
What are the CNS signs for each?

Form Mortality GIT CNS
Organic low none present

Inorganic near 100% severe present

What are sources of arsenic?

- dips, sprays for ectoparasite control

- herbicides

- heart worm medication - thiacetarsamide

- feed additive - arsanilic acid

How are most forms of Ar. absorbed? 2

readily absorbed through the skin or gastrointestinal tract

Where in the body does Ar distribute?

in the energy rich tissues:

liver, kidney and GIT epithelium

Where may one find hi levels after chronic exposure?

the hair and hoof

Describe metabolism of arsenic?

Inorganic forms of arsenic are usually methylated

How is it excreted?

What is the half life?

- in the bile or urine occurs depending upon the form of arsenic

- The half-life is only a few days.

What do inorganic forms cause regarding injury?

- chemical irritation

- tissue degeneration

- destroys epithelium

Describe its MOA?

- a metabolic poison → impaired cellular respiration and uncoupling of oxidative phosphorylation

Where does it cause degenerative changes?

- many organ systems with high-energy requirements

- kidney, liver, brain

What are the syndromes associated with inorganic arsenic?

1. acute

2. subacute

What are characteristics of the acute syndrome with inorganic?

Describe CS? 6

When might death occur?

- high mortality

- sudden onset

- vomiting
abdominal pain
weakness, ataxia
recumbancy
shock
diarrhea

- death within 3 - 4 hours

- Terminal convulsions may be observed.

What are characteristics of the subacute syndrome with inorganic arsenic?

- lower does

- longer duration ranging from 2 - 7 days.

- There are more neurological manifestations present.

What are the GIT signs with subaute inorganic arsenic?

- colic
- vomiting
- diarrhea, salivation
- grinding teeth
- anorexia, thirst

What do animals usually die from in subacute inorganic ar?

dehydration and shock, not CNS sings

What are CNS signs of subabute arsenic inorganic?

- muscle tremors
- incoordination
- clonic convulsions
- hind end paralysis

Describe chronic poisoning with inorganic arsenic?

clinical manifestations are vague

- Unthrifty animals
- poor growth
- indigestion
- reduced milk production
- abortion
- buccal cavity ulceration may be observed.

How is inorganic arsenic Dx?

- Clinical manifestations including GIT and neurological signs may suggest inorganic arsenic poisoning

- Analysis of liver, kidney, hair or food samples may be useful

- A severe gastroenteritis and degenerative changes in most organ systems, may be evident

How is inorganic arsenic tx? 4

When do most die?

- high levels of exposure, most animals die → usually die of shock before can start

- Sodium thiosulfate

- British antiLewisite

- astringents may be helpful

- Fluid therapy for shock is essential

What symptoms are typically present with inorganic arsenic?

gastrointestinal and neurological symptoms

- look at metals that cause simlar effects

What are DDX for inorganic regarding the CNS signs seen>

- lead
- mercury
- salt
- selenium
- chlorinated hydrocarbon insecticides
- organophosphates
- cyanide
- nitrate/nitrite
- blue green algae

What are Ddx for inorganic regarding GIT signs?

- urea
- lead
- selenium
- organophosphate/carbamate **
- chlorinated hydrocarbon insecticides*
- mycotoxins (T - 2 toxin)
- many plants
- herbicides

** no lesions

What other metal toxicities may chronic poisoning be confused with?

Why?

- copper deficiency
- molybdenum toxicity
- selenium
- Fluorosis
- Ergot
- PCB

2. difficult to diagnose without laboratory testing → Vague signs relating to unthrifty animals confused with other metals

Compare the toxicity of organic arsenic forms to inorganic?

What have these forms been used in?

- much less toxic

- Historically, they have been used as feed additives.

What are ex of organic forms of arsenic?

1. arsanilic acid
2. roxarsone
3. nitrophenylarsonic acid

What is often the source of the problem of organic ar poisoning?

Improper feed formulation

Why do these compounds make dx difficult?

How much is eliminated in first 24 hours?

Is food residue a concern?

- rapidly eliminated → make tissue analysis
difficult

- limits food residue concerns

- Approximately 75% of the arsenic is eliminated within 24 hours after exposure is terminated.

What are clinical manifestations dependent on?

level in the feed

How long might it take for syndrome to develop? What does this mean for the animals?

What does this mean for the stages of dz that occurs?

- may take weeks

- gastrointestinal tract is not affected, animals continue to consume feed until the late stages of the disease

When may symptoms of acute poisoning occur?

within a week

What are symptoms of acute poisoning?

Are there GI signs?

- incoordination, ataxia
- paralysis
- blindness

- *not anorexic
- no GIT signs

What signs are seen in chronic poisoning?

what may be the only sign?

- similar signs are seen but to a lesser degree.

- remain alert, but fail to gain weight as expected

How is organic ar poisoning dx?

Why should you interpret tissue analysis with caution?

Will animals recovery?

- EDTA blood

- history of exposure

- clinical manifestations (neurological) will suggest a tentative diagnosis of organic arsenic poisoning

- Feed analysis → recommended

- arsenic is rapidly excreted, tissue analysis should be interpreted with caution.

- The animals will usually make an uneventful recovery if the feed is removed early.

What are DDX for organic arsenic?

Other agents producing a comparable neurological syndrome include:

1. methyl mercury

2. salt

3. 2, 4-D

4. organophosphates

5. TOCP

6. chronic selenium

7. plants - lupines, zygadenus

** see notes for additions**

Can an animal be shipped after it is noted to have organic ar. poisoning?

- yes

- If the poisoning is recognized early, and the feed is withdrawn, the animals recover rapidly and can be shipped in the near future since withdrawal times are very short.

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