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
Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.
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.
As preservatives-antibacterial, antifungal, or antioxidant
To change physical characteristics, taste, color, odor
3.Chemicals in work placeInorganics-metals and flurides, CO, etc.Organic compounds-aliphatic hydrocarbons (hexene)
aromatic hydrocarbons (eg. benzene, toluene)
4. Drugs of abuseCNS depressants-ethanol,secobarbitalCNS stimulants-cocaine, methamphatamine,
The danger to the individual depends on :
the nature of the toxic response
the dose necessary to produce the toxic response
the relationship between the therapeutic dose and the toxic dose
eg, anticancer drugs are carcinogens
Chloroquinol-SMON-subacute myelo-optic neuropathy
Methyldopa, chloropromazine, methotrexate
In general, toxic side effects are not common and may occur only in susceptible individuals or populations.
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
Allergic reactions and contact dermatitis
Bromate, cold-wave neutralizer
Thioglycolates and tioglycerol-cold-wave lotion and depilatories
Sodium hydroxide-hair straighteners
Descriptive Toxicology: The science of toxicity testing to provide information for safety
evaluation and regulatory requirements.
Mechanistic Toxicology: Identification and understanding cellular, biochemical and
molecular basis by which chemicals exert toxic effects.
Regulatory Toxicology: Determination of risk based on descriptive and mechanistic
studies, 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.
Occupational Toxicology: Combines occupational medicine and occupational hygeine.
Environmental Toxicology: Integrates toxicology with sub-disciplines such as ecology,
wildlife and aquatic biology, environmental chemistry.
1. Analytic toxicology
2. Toxicity testing
3. Toxicologic pathology
4. Structure-activity study
5. Biomathematics and statistics
C. Applied Toxicology
1. Clinical toxicology
2. Veterinary toxicology
3. Forensic toxicology
4. Environmental toxicology
5. Industrial 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
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
The commonly used time unit is one day and thus, the usual dosage unit is mg/kg/day.
Environmental exposure units are expressed as the amount of a xenobiotic in a unit of the media. mg/liter (mg/l) for liquids
mg/gram (mg/g) for solids
mg/cubic meter (mg/m3) for airOther commonly used dose units for substances in media are parts per million (ppm), parts per billion (ppb) and parts per trillion (ppt).
Fractionatinga total dose usually decreases the probability that the total dose will cause toxicity. The reason for this is that the body often can repair the effect of each subtoxic dose if sufficient time passes before receiving the next dose. In such a case, the total dose, harmful if received all at once, is non-toxic when administered over a period of time. For example, 30 mg of strychnine swallowed at one time could be fatal to an adult whereas 3 mg of strychnine swallowed each day for ten days would not be fatal.
long latent period at lower doses-carcinogen
very low dose-no effect
chronic use-deleterious effects on the gastric mucosa
fatal dose 0.2-0.5 g/kg
dietary essentials eg. Iron, copper, magnesium, cobalt, manganese, and zinc
toxic at higher dose
"All substances are poisons; there is none which is not a poison. The right dose differentiates a poison and a remedy.“
establishes causality that the chemical has in fact induced the observed effects
establishes the lowest dose where an induced effect occurs - the threshold effect
determines the rate at which injury builds up - the slope for the dose response.
Individual, or graded, dose-response relationship
results from an alteration of a specific biochemical process
Quantal dose-response relationship
in a population-”all or none”
determination of the LD50
LD (lethal dose)50-the dose required to kill 50% of a population of an organism under stated conditions
NED for 50% response is 0
NED for 84.1% response is 1
Probit (probability unit)=NED+5
The LD50 tests have become controversial among toxicologists, animal welfare organizations, legislators and the public primarily due to the ethics of using a large number of animals and evaluating only mortality.
NOAEL-no observed adverse effect level
Chronic Continuous dosing for up to 6 months to 2 years
• Acute effects do not predict chronic effects
• Doses causing chronic effects may not cause acute or sub-acute effects
• Chronic effects of a chemical exposure may manifest themselves as a common disease and go unnoticed
• mechanisms by which chemicals cause cell injury and cell death
• the mode of action of specific organic and inorganic chemicals
• how to interpret results of in vitro tests for the evaluation of in vivo toxicity
• How multiple chemical exposures and other stressors can alter toxicity
• the importance of dose in determining adverse effects
• what factors influence the target organ dose of a chemical
• mechanisms by which chemicals affect specific organ system functions