INTRODUCTION TO

VETERINARY
TOXICOLOGY

Team Teaching
Division of Pharmacology and Toxicology
SVMBS IPB

2023 Lantana merah (toksik)

References

◼ Veterinary Toxicology → D. J. Humpreys. 1997. Baillerie

Tindal.
◼ Basic Toxicology → Toksikologi Dasar. Frank. C. Lu →
Edi Nugroho 1995.
◼ Ilmu Forensik dan Toksikologi → P. V. Chandra. 1995.
◼ Poisoning and Over Doses → Ken. R. Olson. 1992.
◼ Veterinary Toxicology → Clarke and Clarke. 1996.
◼ Veterinary Toxicology → Gardner and Gardner. 1982.
◼ Toxicology → Casarett and Doull’s. 2002. 2003 (Essential)
◼ Modern Toxicology → Hodgson and Levi. 2000.
TOXICOLOGY- Introduction (1)

◼ The science of poison and intoxication.

◼ Poison = venom = toxicant = toxic agent → xenobiotic

“Small amounts/concentrations of chemical substances that

enter the body in regardless method can cause physicochemical
disturbances/abnormalities (illness/death is not due to
a decrease in physical strength)”
(2)
◼ Poisoning = intoxication
◼ Disorder (abnormalities) manifestations of the
harmful effects of poison are abnormality on:
❑ behavior
❑ production/reproduction capacity
❑ health
❑ fetal developmental disorders
❑ cancer development
❑ death.
(3)
Veterinary Toxicology
A scientific study about the
◼ Origin and characteristics of the poison

◼ Exposure mode

◼ Poisoning diagnosis

◼ Poisoning therapy in animals

◼ Veterinary education for poisoning prevention

DOSAGE (1)
◼ 1564 Paracelsus
“Dosis Sola Facit Venenum”

◼ Toxicity → Dosage
❑ Extremely toxic

❑ Highly toxic

❑ Moderately toxic

❑ Slightly toxic

❑ Practically non toxic

❑ Relatively harmless
DOSAGE (2)
FACTORS AFFECTING
the ACTIVITY of POISONS
1. Dosage --> animal size
2. Species
3. Age
4. Gender
5. Physic-chemical properties of the poison
6. Animal health/general condition
(lactation period, gestation)
7. How to administer (poison's routes of entry)
SEVERAL CAUSES
of POISONING
1. Deliberately (with intent)
2. Unintentional (accident, human negligence)
3. Poisoning due to “occupation"
(Occupational Intoxication)
CLASSIFICATION
CLASSIFICATION OF POISONS CAN BE BASED ON:

1. The affected organs (liver, kidney, etc.)

2. Toxic effects (irritant, corrosive, convulsant, etc.)
3. The chemical forms (acid, organic, or base)
4. Origin (animal/venom, plant/phytotoxin, fungus, bacteria)
5. Usage (pesticide, antimicrobial)
6. Analytical behavior (metallic, anionic, volatile)
7. Combination of the above aspects
TYPES OF POISONING
1. Acute
a single contact with a high dose of poison,
immediate symptoms (<7 days)
2. Subacute
a low dose poison causes symptoms in 7-30 days
3. Sub chronic
a low dose of repeated exposure, symptoms manifested in 1-3 mo
4. Chronic
a low dose of repeated exposure, symptoms manifested in >3 mo
5. Other form → sensitizing, teratogenic, carcinogenic.
TOXICOKINETICS- LADME
◼ Liberation
◼ Absorption ➔ Poison reaction
❑ Local/ remote local
❑ Oral (solid, liquid)
❑ Dermal/contact ❑ Systemic

❑ Inhalation (gas/volatile) ❑ General → Poison effect : 1. Reversible

❑ Parenteral (SC, IM, IP, IV) 2. Irreversible

◼ Distribution → accumulation
❑ Depend on the poison's affinity to organs, ex: deposited in
particular tissues
 Poison

Enter the Body

by
Oral Topical Inhalation Parenteral

Absorption bloodstream
Distribution → tissues → Organs

METABOLISME

Toxicity Deposit Excretion

TOXICOKINETICS
◼ Metabolism
The process of changing biochemical substances that enter the body into
other substances (metabolites), facilitate "easy excretion"
Step 1 (oxidation) → Reduction/step II → conjugation
◼ There are 2 types of metabolism
❑ Biotransformation
Metabolic processes that actually produce some more-harmful
metabolites, for example:
- parathion → para-oxon
- fluoroacetate → fluorocitrate
❑ Detoxication
The process of changing chemical substances from toxic → non-toxic
substances.
TOKSIKOKINETIKA
◼ Excretion
Via :
❑ feces

❑ Sweat

❑ Urine

❑ Saliva

❑ Milk

❑ Respiration (?)
THE MODE of ACTION of POISON

◼ Different for each type, but generally damage cell

function / structure → disrupt metabolism, replication,
or cell death
◼ Damage can extend to tissues, organs or organ systems
◼ Ex. Affecting/inhibiting the action of certain enzymes:
- E. Aconitase by fluorocitrate
- E. Acetyl choline esterase by organophosphor
- E. Cytochrome oxidase by HCN
POISONING DIAGNOSES
◼ Anamneses
◼ Clinical symptoms
◼ Pathology-anatomical findings
◼ Surrounding condition
◼ Laboratory analytical results
With/without pathognomonic symptoms: "usually" there are
certain signs:
- Smell of breath → alcohol, cresol, garlic → phosphorus
- Urine:
1. Green (Phenol)
2. Red (Phenothiazine)
3. Blue (Methylene blue)
CLINICAL SYMPTOMS OF POISON (1)

◼ Stomach ache → Acid Base

◼ Anemia → Cu, Ca, Pb
◼ Blindness → Benzoate (Paint), Molybdad-Lamb
◼ Coma → Depressant
◼ Constipation → Pb, Phenothiazine – Horse
◼ Convulsions → Cu (Sheep), Benzoic acid (paint)
◼ Cyanosis → ATU, Pesticides (organophosphorus,
organochlorine)
◼ Depression/weakness → Zinc phosphite, Fluoro acetate
◼ Diarrhea → Acids, Bases, CCl4
◼ Pupil dilation → Barbiturates, Strychnine
 CLINICAL SYMPTOMS OF POISON (2)

◼ Dyspnea → HCN, organophosphorus

◼ Excitement → Benzoic acid (Paint), Caffeine
◼ Hematuria → Anticoagulant, Hg
◼ Muscle tremor → Carbamate, Kerosene, Phenol
◼ Paralysis → CO (Pia), Cu (Sheep)
◼ Salivation → Benzoic acid (Paint), NaCl (Pig)
◼ Vomit → Acid/alkali, Enterotoxin
◼ Surrounding environment → medicine/pesticide/factory
◼ Anatomical pathological symptoms → yellowing of the skin
Liver toxins, phosphorus
POISONING CONTROL

◼ Treatment should be done as soon as possible

◼ Treat the “patient” not the poison
◼ Principle:
- Stop further contact with the poison
- Stop further absorption.
- Perform "symptomatic" treatment
- Provide "non-specific & supportive treatment"
- Give specific antidote (if poison is known)
 ANTIDOTA

◼ Atropine sulphate → Organophosphorus 0.1 mg/kg BB - Antu

◼ Dimercaprol (BAL) → Arsenic 3 Mg/kg BB, IM
◼ Pilocarpine → Atropine
◼ Bemegrid. Na → Barbiturate 20 Mg/kg BB, IV
◼ Pentobarbitone Na → Caffeine, Strychnine
◼ Methylene Blue → Chlorate 1-2 Mg/kg BB, IV 1%
◼ Sodium calcium edetate (EDTA)
◼ Sodium sulphate → Cu 0.5-2 g
◼ Nalorphine → Narcotic analgesic
ANTIDOTA (2)

1. Physical (mechanics) → powdered glass poisoning → food

Albumin → mucous layer → Tannins/charcoal
2. Chemical → Strong acid Weak base
Lime Oxalates acid
KMNO4 → Phosphate, Quinine, HCN
3. Universal → R/ Activated charcoal 2 bag
Tannic acid 1 bag
Mg oxide 1 bag
4. Physiologic → Physostigmine Atropine
LABORATORY ANALYSIS

➔ Materials for laboratory examinations must be EXACT

in:

◼ Quantity → minimum
◼ Time → immediately
◼ Method:
collection, storage, treatment during shipment, and
selected examination methods
Examination

◼ Ante-mortem (while alive), sampling:

❑ Blood
❑ Urine
❑ Vomit
❑ Feces
❑ Food waste, medicine and others

◼ Post mortem → pathology-anatomy

Organ sampling : liver, lung, kidney, brain, carcass, stomach,
intestine (+ contents), skin, bone
◼ Histopathology
◼ Chemical analysis
SAMPLES SHIPMENT (1)
◼ Enforcing the diagnosis of poisoning → ascertaining the
“chemical (compound)” causing the poisoning
◼ The right laboratory (want and can), for example:
❑ BPPH (Balai Penyidikan Penyakit Hewan/
Animal Disease Investigation Center)
❑ Balitvet (Balai Penelitian Veteriner/
Veterinary Research Center)
❑ Faculty of Veterinary Med → Toxicology
❑ Forensic Lab :
a. Police
b. General Hospital
c. Animal Hospital
SAMPLES SHIPMENT (2)

◼ Legal (legal) aspects → related people/lab workers

→“expert witnesses”
◼ Must be with the right amount of materials, sufficient quantities,
and inspection/analysis methods with the right methods and tools
◼ Time and method of sending material samples (specimens) for
examination in the laboratory
◼ Each type of material is placed in a separate container, do not
mix.
◼ Container requirements: 1. sturdy (not easily damaged / leaking)
2. Does not react with ingredients
3. Clean, closed (sterile)
4. Preferable transparent (glass)
SAMPLES SHIPMENT (3)

◼ Each ingredient must be labelled:

- the name of the material/organ
- type/species of animal, sex, age, number
- date, owner, origin
◼ Label material: must be sturdy, not easily
damaged, and the writing use unchangeable ink
◼ Specimens should not be given any preservatives
except for histopathological examination.
SAMPLES SHIPMENT (4)

◼ Along with the specimen, attached with a “statement

letter" from the veterinarian or animal owner explaining:
❑ clinical symptoms (visible)
❑ other necessary information (previous treatment, actions, or
information of animal's surroundings)
❑ suspicion of toxic substances, for example suspected Hg poisoning
(don't just mention metal poisoning)

◼ Avoid damage by shipping specimens as quickly as

possible
◼ Send ingredients in refrigerated containers (ice/ice flask,
dry ice)
 Toksikologi Toksikologi
Klinik Pangan

1. Kedokteran Makanan
2. Ked. Hewan

Kimia Analitik Kimia Limbah

Ekologi Higiene Perusahaan

Toksikologi Lingkungan Toksikologi Industri

TOKSIKOLOGI

Kimia Lingkungan Kimia Analitik

BIOKIMIA
FISIOLOGI FARMAKOLOGI
ANATOMI PATOLOGI BIOLOGI
Regulatory Toxicology
“LD 50 measurement MLD 50 LD 100”

◼ Related to the law :

❑ Environmental Protection Agency (EPA)

❑ Food and Drug Administration (FDA-USA)

❑ WHO and FAO

❑ Occupational Safety & Health Administration

Regulatory Toxicology
“LD 50 measurement MLD 50 LD 100”

◼ Terms :
1. No Observed Adverse Effect Level → NOAEL
2. Acceptable Daily intake → ADI

ADI = NOAEL (mg/Kg Body Weight/Day)

100
◼ NOAEL = amount or concentration of a chemical
found in the body (by research) does not have an
adverse effect on life.
Thank you
 Inhalation
Toxicology
Toxicology in Drug Development