Introduction Flashcards
Deals with the undesirable effects of chemicals on living systems, from individual cells to complex ecosystems.
TOXICOLOGY
Predict outcomes of exposure in human and animal populations.
TOXICOLOGY
Study adverse effects of xenobiotics on living organisms.
TOXICOLOGY
Study of adverse effects of chemical, physical, or biological agents on humans, animals, and the environment.
TOXICOLOGY
These were very popular for hunting animals (and sometimes fellow humans).
Arrow and dart poisons
the term “toxicology” is derived from _______, a Greek word which when translated reads, “__________________”.
toxicon, poison into which arrowheads are dipped
Ordeal poison
Physostigmine (Physostigma venenosum) or “Calabar bean” & Amygdalin from peach pits.
Common arrow poison
- Cardiotoxic plants: Strophanthin, aconitine, and Helleborus
- Snake/Toad venom
40-80 AD
Greek Physician who classify poisons into 3 groups: Animal, vegetable and mineral (De Materia Medica)
DIOSCORIDES
204-135 BC
Greek Physician who began experimenting animal poison using condemned criminals
NICANDER
370-286 BC
Early treatise on plant poisons (De Historia Plantarum)
THEOPHRASTUS
1198
Treatise on Poisons and their Antidote (Insects, snakes and mad dogs.)
MAIMONIDES (Moses ben Maimon)
1493 – 1541
* Studied Dose-response relationship.
* First scientific approach in toxicology.
* “The dose makes the poison”
PARACELSUS
1787 – 1853
* Father of modern toxicology.
* Advocate practice of autopsy.
* Published “Traite des Poisons” – foundation of forensic toxicology
Mathieu Joseph Bonaventure Orfila
12th Century BC.
An Indian collection that contains religious, knowledge and praises. Some contents describe plant poisons.
RIG VEDA
470 – 399 BC
Executed by the administration of hemlock (Conium maculatum).
SOCRATES
The tale leads to the use of the word “Mithridates” as an antidote or protective mixture.
THE TALE OF KING MITHRIDATES VI
138 to 78 BC
Issued “Lex Cornelia” – law against poisoning. Became a regulatory statute directed at careless dispensers of drugs
SULLA
1480
Warned of the toxicity of Hg and Pb from goldsmithing
ELLENBOG
1556
Published short treatise on mining disease (Miner’s sickness) other were published by Paracelsus.
AGRICOLA
1770
Published “Discourse on the Diseases of Workers”– discussed occupation ranging from miners to potters.
RAMAZZINI
1775
Recognition of the role of soot in scrotal cancer among chimney sweeps.
POTT
1797 – 1882
Published a simplified English version of “A Treatise on Poisons”.
COSTILL
1848
First published work on clinical toxicology “Practical Treatise on Poisons”
CHRISTISON
1850-1929
Published early work on the toxicity of narcotics, mathanol, glycerol and chloroform
LEWIN
Focus of the Study
- Mechanism
- Symptoms
- Detection
- Treatment
- Mechanism: How toxicity occurs
- Symptoms: What are the clinical manifestations?
- Detection: Confirmatory test and identification
- Treatment: Antidote and management
The incidence of poisoning in ______ is among the highest in the world
India (50,000/yr)
CAUSES OF POISONING
- industrial
- accidental
- deliberate
COMMON AGENTS THAT CAUSES TOXICITY
- Pesticides: organophosphates
- Sedatives: BZD, barbiturates
- Chemicals: corrosives (acids and bases)
- Alcohols: ethanol and methanol
- Plant toxins: datura, oleander, Strychnos, Castors
- Households: cleaning agents
PHYSIOLOGY AND PHARMACOLOGY
By using toxic agents to understand the medicinal and the physiologic phenomena.
IMPORTANCE AND CONTRIBUTION
Ex. Use of muscarine and nicotine (Cholinomimetic drugs)
IDENTIFICATION AND QUANTITATION
Hazards resulting from occupational exposure to chemicals and the public aspects of chemicals in air, water, food, drugs and other parts of the environment
IMPORTANCE AND CONTRIBUTION
Lead containing paints or gasoline fume inhalation
DISCOVERY AND DEVELOPMENT
Contribution in new formulation, development and innovation. Participation in the discovery of new drug and pesticides.
IMPORTANCE AND CONTRIBUTION
clinical trials
STANDARDIZATION AND REGULATION
Participate in developmental standard designed to protect human health and environment from adverse effects of chemicals.
IMPORTANCE AND CONTRIBUTION
AREAS IN TOXICOLOGY
- mechanistic toxicology
- regulatory toxicology
- risk assessment
- descriptive toxicology
Concerned with the mechanism by which chemicals exert their toxic effects on living organisms.
MECHANISTIC TOXICOLOGY
AREAS IN TOXICOLOGY
Often lead to the development of sensitive predictive test useful in risk assessment, design and production of safer alternative chemical and rational therapy for chemical poisoning and treatment of disease
MECHANISTIC TOXICOLOGY
AREAS IN TOXICOLOGY
- Toxicity testing
- Provides necessary information for safety evaluation and regulatory requirements.
DESCRIPTIVE TOXICOLOGY
AREAS IN TOXICOLOGY
- Concerned with the responsibility of deciding on the basis of data provided by the descriptive toxicologist if a drug or other chemical posses a sufficiently low risk to be marketed for stated purpose
- Concentration based standard of “safe” exposure
REGULATORY TOXICOLOGY
AREAS IN TOXICOLOGY
Concerned with the medico legal aspects of the harmful effects of chemicals on humans
FORENSIC TOXICOLOGY
SPECIALIZED AREAS OF TOXICOLOGY
Aids in establishing the cause of death and in criminal investigation.
FORENSIC TOXICOLOGY
SPECIALIZED AREAS OF TOXICOLOGY
Within the realm of medical science concerned with disease caused by, or uniquely associated with toxic substances
CLINICAL TOXICOLOGY
SPECIALIZED AREAS OF TOXICOLOGY
Involved in emergency medicine and poison management
CLINICAL TOXICOLOGY
SPECIALIZED AREAS OF TOXICOLOGY
Develop treatment emergency poison antidotes regimens for ameliorating poisoning and xenobiotic injury.
CLINICAL TOXICOLOGY
SPECIALIZED AREAS OF TOXICOLOGY
Focuses on the impacts of chemical pollutants found in the environment biological organisms
ENVIRONMENTAL TOXICOLOGY
SPECIALIZED AREAS OF TOXICOLOGY
Studies chemicals that are contaminants of water, soil or air food
ENVIRONMENTAL TOXICOLOGY
SPECIALIZED AREAS OF TOXICOLOGY
Also associated with the studies of chemical effects on animals
ENVIRONMENTAL TOXICOLOGY
SPECIALIZED AREAS OF TOXICOLOGY
Deals with the chemicals found in the workplace
OCCUPATIONAL TOXICOLOGY
SPECIALIZED AREAS OF TOXICOLOGY
Protects workers from toxic substances and makes their work environment safe
OCCUPATIONAL TOXICOLOGY
SPECIALIZED AREAS OF TOXICOLOGY
Identify the agents of concern, define conditions leading to their use, and prevent the absorption of harmful amounts
OCCUPATIONAL TOXICOLOGY
SPECIALIZED AREAS OF TOXICOLOGY
It is the application of new and modern methods of technologies for early detection of toxicants in the field setting or practice area.
APPLIED TOXICOLOGY
SPECIALIZED AREAS OF TOXICOLOGY
Study of adverse effects on the developing organism
Ex. Teratology
DEVELOPMENTAL TOXICOLOGY
SPECIALIZED AREAS OF TOXICOLOGY
Focuses on the study of the occurrence of adverse effects on the male and female reproductive system.
REPRODUCTIVE TOXICOLOGY
SPECIALIZED AREAS OF TOXICOLOGY
- Every known chemical has the potential to produce injury if it is present in sufficient amount.
- For a given chemical, each of the various effects that may occur in a given organism will have their own dose-response relationship
LETHAL DOSE 50 (LD50)
GENERAL CHARACTERISTIC OF TOXIC RESPONSE
Generally refers to toxic substances that are produced by biological system such as plants, animals or bacteria
Toxin
Toxic substances produces by or a by-product of human activities.
Toxicant
SPECTRUM OF UNDESIRED EFFECTS
- Allergic reactions/Sensitization
- Idiosyncratic reaction
- Immediate vs. delayed toxicity
- Reversible vs. irreversible effects
- Local vs. systemic toxicity
- Interaction of chemicals
Occur in hypersensitive individuals or after sensitization in allergic or sensitized persons.
e.g. Reaction ranges from skin irritation to anaphylactic shock
ALLERGIC REACTION
Occur in individuals who have genetic polymorphism that lead to structural changes in biomolecules, making them very sensitive to chemicals.
IDIOSYNCRACTIC REACTION
Most chemicals exert their effects soon after exposure.
IMMEDIATE TOXICITY
Others may be delayed for days to years (cancer)
DELAYED TOXICITY
Depends on tissue’s ability to regenerate itself at a variety of levels: molecular, cellular and tissue
Liver vs. CNS
REVERSIBLE VS. IRREVERSIBLE
Corrosives and irritants act locally, little goes systemic.
e.g. Eyes and skin
LOCAL
Systemic effects in sensitive (not always highest concentration) tissues.
e.g. CNS, circulatory and blood, visceral organs
SYSTEMIC
Combined effect is the same as the sum of effects when given alone
Ex. CNS depressants + Alcohol | Amphetamine + caffeine
ADDITIVE
CHEMICAL INTERACTION
combined effects are much greater than the sum of effects when given alone
Ex. CCl4 and EtOH | Pyrethroids and piperonyl butoxide (PBO)
SYNERGISTIC
CHEMICAL INTERACTION
Note: Pyrethroids and piperonyl butoxide(PBO) - a pesticide synergist (knock-down effect)
Exposure to a chemical with no toxicity increases the toxicity of another compound
Ex. CCl4 and isopropanol
POTENTIATION
CHEMICAL INTERACTION
Co-administration of two chemicals interferes with the toxicity of both or one of them.
Ex. Antidotal therapies
ANTAGONISM
CHEMICAL INTERACTION
Chemicals counterbalance each other by exerting opposite physiological function
Ex. Convulsions treated with benzodiazepines
FUNCTIONAL
TYPES OF ANTAGONISM
Chemical reaction between two compounds leads to less of the toxic compound
Ex. Chelators and metals
CHEMICAL (or inactivation)
TYPES OF ANTAGONISM
An antitoxin active against the venom of a snake, spider, or other venomous animal or insect.
ex. of chemical antagonism
Antivenins
Disposition of toxic chemical is changed so that concentration and/or duration is diminished.
Ex. Ipecac, charcoal, pH alteration, metabolism, induction or inhibition
DISPOSITIONAL
TYPES OF ANTAGONISM
Chemicals compete for the same receptor, decreasing effective binding of toxic compound.
Ex. Naloxone and morphine
RECEPTOR
TYPES OF ANTAGONISM
Tamoxifen and estradiol – antagonist of the estrogen receptor in breast tissue
A state of decreased responsiveness due to a prior exposure to the same or a structurally similar chemical in an individual
TOLERANCE
A decreased amount of chemical reaches the site where the effect is produced
DISPOSITIONAL TOLERANCE
TYPES OF TOLERANCE
Same amount of chemical reaches the site, but target receptor response decreased
RECEPTOR TOLERANCE
TYPES OF TOLERANCE
A selective process (evolution) by which sensitive individuals do not survive and only those with a genetic trait that accommodates the chemical survive.
RESISTANCE
A prompt and marked disturbance of function or death within a short time.
ACUTE POISONING
TYPES OF POISONING
that are caused by:
* Taking a strong poison
* Excessive single dose of a drug
* Several small doses but frequent administration of a drug
ACUTE POISONING
TYPES OF POISONING
Marked by a gradual deterioration of function of tissues and may not result in death
CHRONIC POISONING
TYPES OF POISONING
due to:
* Taking several small doses of drugs at long intervals
* Taking only toxic doses of the drug
CHRONIC POISONING
TYPES OF POISONING
<24 hrs, generally a single dose
ACUTE
DURATION OF EXPOSURE
Usually dietary
REPEATED
DURATION OF EXPOSURE
Repeated exposure for a month or less
SUBACUTE
DURATION OF EXPOSURE
Repeated exposure for 1-3 months
SUBCHRONIC
DURATION OF EXPOSURE
Exposure > 3 months
CHRONIC
DURATION OF EXPOSURE
Benzene:
Acute Exposure: ?
Chronic Exposure: ?
Acute Exposure: CNS Narcosis
Chronic Exposure: Bone marrow damage and leukemia
DIFFERENT OUTCOMES OF EXPOSURES
Cigarette smoke
Acute Exposure: ?
Chronic Exposure: ?
Acute Exposure: CNS Stimulation
Chronic Exposure: Pharyngeal, laryngeal, mouth, lung, esophageal, pancreas, bladder cancer and emphysema
DIFFERENT OUTCOMES OF EXPOSURES
- Contributed by circumstances or deduced from occurrences and facts
- Not strong evidence
Ex. various Motives for poisoning, purchasing the poison keeping the materials used, etc.
CIRCUMSTANTIAL OR MORAL EVIDENCE
EVIDENCE OF POISONING
- Includes symptoms observed during poisoning.
- This is not conclusive though some disease may be present and similar symptoms may be observed as those of poisoning
Ex. Arsenic poisoning is like cholera, alcoholic coma may stimulate diabetic coma
SYMPTOMATIC EVIDENCE
EVIDENCE OF POISONING
- Obtained by chemical analysis of the suspected substance, or the vomitus or secretion of the body.
- This alone is not reliable because the poison may be decomposed or changed or it may have been placed anywhere after death.
CHEMICAL EVIDENCE
EVIDENCE OF POISONING
Evidence from examination of tissues and organs after death
POST – MORTEM EVIDENCE (AUTOPSY)
EVIDENCE OF POISONING
- Obtained by administering the suspected substance to some living animal and noting the effects or symptoms.
- Not very conclusive procedure since tolerance may not be the same as in man.
EXPERIMENTAL EVIDENCE (PHYSIOLOGIC TEST)
EVIDENCE OF POISONING
major route of entry of poison in the industrial settings
Atmospheric (Sulfur oxides, pollutants nitrogen
oxides, carbon monoxide and dioxides)
Inhalation
ROUTES OF EXPOSURE
water and soil pollutants
Ingestion
ROUTES OF EXPOSURE
Broad range effects can be found with many drugs or chemicals with sufficient exposure.
CHEMICAL EXPOSURE
EFFECTS OF CHEMICAL EXPOSURE
- neurotoxicity
- blood and immunity
- reproductive and genetic alterations
- cardiovascular
- respiratory
- nephrotoxicity
- Describes the response of an individual organism to varying doses of chemical
- Often referred to as “Graded” response because the measured effect is continuous over a range of doses
INDIVIDUAL DOSE-RESPONSE RELATIONSHIP
DOSE-RESPONSE RELATIONSHIP
- Characterizes the distribution of responses to different doses in population.
- Population that responds at each dose vs. the log of the dose administered is obtained.
The effective dose (ED50), toxic dose (TD50), and lethal dose (LD50) are extracted from experiments carried out in this manner.
QUANTAL DOSE-RESPONSE RELATIONSHIP
DOSE-RESPONSE RELATIONSHIP
VARIATION IN TOXIC RESPONSES
- Selective toxicity
- Species differences
- Individual differences in response [Genetic polymorphism (aka idiosyncrasy)]