What is toxicology?

toxic compounds

physical agents

toxicology …………

• Is the study of the harmful effects of chemicals and physical agents on living organisms

• Examines adverse effects ranging from acute to long-term

• Is used to assess the probability of hazards caused by adverse effects

• Is used to predict effects on individuals, populations and ecosystems

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These adverse effects may occur in many forms, ranging from immediate death to subtle changes not realized until months or years later. 

They may occur at various levels within the body, such as an organ, a type of cell, or a specific biochemical.

Sources of toxic compoundsSynthetic organic compound1. Air, water, and food pollutants

Air-CO, oxides of nitrogen, oxides of sulfur, hydrocarbons and particulatesWater-agricultural chemicals including pesticides, herbicides, fugicides, nematocides, rodenticides, fertilizer

Halogenated hydrocarbons- chloroform, dichloroethane, tetrachloride

Clorinated aromatics-PCB, TCDDDetergents-alkyl benzene sulfonates

2. Chemical additives in food

As preservatives-antibacterial, antifungal, or antioxidant

To change physical characteristics, taste, color, odor

.

3.Chemicals in work place Inorganics-metals and flurides, CO, etc. Organic compounds-aliphatic hydrocarbons (hexene)

aromatic hydrocarbons (eg. benzene, toluene)halogenated hydrocarbonsalcoholsestersorganometallicsamino compounds

4. Drugs of abuseCNS depressants-ethanol,secobarbitalCNS stimulants-cocaine, methamphatamine,

nicotine, caffeineOpioids-heroin, morphineHallucinogens-PCP, LSD,THC

5.Therapeutic drugs The danger to the individual depends on :

the nature of the toxic responsethe dose necessary to produce the toxic responsethe relationship between the therapeutic dose and

the toxic doseeg, anticancer drugs are carcinogens

Diethylstilbestrol (DES)Thalidomide

Chloroquinol-SMON-subacute myelo-optic neuropathy

Methyldopa, chloropromazine, methotrexateIn general, toxic side effects are not common and

may occur only in susceptible individuals or populations.

6. Pesticides

7. Solvents

8. Polycyclic aromatic hydrocarbons (PAH)多環芳香

Incomplete combustion of organic materials, in smoke from wood, coal, oil, tobacco, in tar and broiled foods

Carcinogens

9. Cosmetics

Allergic reactions and contact dermatitis

Bromate, cold-wave neutralizer

Thioglycolates and tioglycerol-cold-wave lotion and depilatories

Sodium hydroxide-hair straighteners

Naturally occurring toxins1. Mycotoxins2. Microbial toxins3. Plant toxins4. Animal toxins

"Toxin"=refers to toxic substances that are produced naturally

"Toxicant"=substance that is produced by anthropogenic origin

  

An interdisciplinary field…………Descriptive Toxicology: The science of toxicity testing to provide information for safetyevaluation and regulatory requirements.

Mechanistic Toxicology: Identification and understanding cellular, biochemical andmolecular basis by which chemicals exert toxic effects.

Regulatory Toxicology: Determination of risk based on descriptive and mechanisticstudies, and developing safety regulations.

Clinical Toxicology: Diagnosis and treatment of poisoning; evaluation of methods of detection and intoxication, mechanism of action in humans (human tox, pharmaceutical tox) and animals (veterinary tox). Integrates toxicology, clinical medicine, clinical biochemistry/pharmacology.毒藥物防治諮詢 http://www.pcc.vghtpe.gov.tw/index.asp

Occupational Toxicology: Combines occupational medicine and occupational hygeine.

Environmental Toxicology: Integrates toxicology with sub-disciplines such as ecology,wildlife and aquatic biology, environmental chemistry.

 The scope of toxicity A.Mechanisms of Toxic Action

1. Biochemical toxicology

2. Behavioral toxicology-behavior is the final integrated expression of nervous function

3. Nutritional toxicology-the effects of diet

4. Carcinogenesis-cell growth

5. Teratogenesis-developmental process

6. Mutagenesis-genetic material

7. Organ toxicity-organ function

B. Measurement of toxicants and toxicity

1. Analytic toxicology

2. Toxicity testing

3. Toxicologic pathology

4. Structure-activity study

5. Biomathematics and statistics

6. Epidemiology

C. Applied Toxicology

1. Clinical toxicology

2. Veterinary toxicology

3. Forensic toxicology

4. Environmental toxicology

5. Industrial toxicology

B. Measurement of toxicants and toxicity

1. Analytic toxicology

2. Toxicity testing

3. Toxicologic pathology

4. Structure-activity study

5. Biomathematics and statistics

6. Epidemiology

C. Applied Toxicology

1. Clinical toxicology

2. Veterinary toxicology

3. Forensic toxicology

4. Environmental toxicology

5. Industrial toxicology

 D. Chemical use classes

1. Agricuture chemicals

2. Clinical drugs

3. Drugs of abuse

4. Food additives

5. Industrial chemicals

6. Naturally occurring substances- phytotoxin, mycotoxin, inorganic minerals

7. Combustion products

 E. Regulatory Toxicology

1. Legal aspects-formulation of

laws and regulations and their

enforcement

2. Risk assessment-

the definition of risks, potential

risks and risk- benefit equations

F. Development of antidotes

 

VSC/BMB497A 8

Xenobiotic

O

O

O

O O

OMe

Target OrganismCommunity/Population

Ecosystem

Absorption

Target Tissue

Target Cell

Exposure

Distribution

Metabolism

Classical

Toxicology

Xenobiotic

O

O

O

O O

OMe

MembraneTransport

OrganismToxicity

TissueToxicity

Reg

ulat

ory

Tox

icol

ogy

Excretion

Epidemiology/Environmental Toxicology

TargetMolecule

Cellular andMolecular Events

CellularToxicity

Mol

ecul

aran

d C

ellu

lar

Tox

icol

ogy

Genetic SusceptibilityBiomarkers

Risk assessment

Mechanismsand treatmentof toxicity

Risk characterization

Biology

Response

Metabolism

Toxic Effects

1. Immediate effect and delayed effect

CO, cyanide

2. Local effect and systemic effect

target organ

3. Reversible and irreversible effect

4. Anaphylactic reaction (allergic reaction)

5. Idiosyncratic reaction 特異體質反應

DoseDose by definition is the amount of a substance administered at one time.

However, other parameters are needed to characterize the exposure to xenobiotics.  The most important are the number of doses, frequency, and total time period of the treatment.For example:

650 mg Tylenol as a single dose

500 mg Penicillin every 8 hours for 10 days

10 mg DDT per day for 90 days