Introduction Flashcards
(99 cards)
1
Q
Deals with the undesirable effects of chemicals on living systems, from individual cells to complex ecosystems.
A
TOXICOLOGY
2
Q
Predict outcomes of exposure in human and animal populations.
A
TOXICOLOGY
3
Q
Study adverse effects of xenobiotics on living organisms.
A
TOXICOLOGY
4
Q
Study of adverse effects of chemical, physical, or biological agents on humans, animals, and the environment.
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TOXICOLOGY
5
Q
These were very popular for hunting animals (and sometimes fellow humans).
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Arrow and dart poisons
6
Q
the term “toxicology” is derived from _______, a Greek word which when translated reads, “__________________”.
A
toxicon, poison into which arrowheads are dipped
7
Q
Ordeal poison
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Physostigmine (Physostigma venenosum) or “Calabar bean” & Amygdalin from peach pits.
8
Q
Common arrow poison
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- Cardiotoxic plants: Strophanthin, aconitine, and Helleborus
- Snake/Toad venom
9
Q
40-80 AD
Greek Physician who classify poisons into 3 groups: Animal, vegetable and mineral (De Materia Medica)
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DIOSCORIDES
10
Q
204-135 BC
Greek Physician who began experimenting animal poison using condemned criminals
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NICANDER
11
Q
370-286 BC
Early treatise on plant poisons (De Historia Plantarum)
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THEOPHRASTUS
12
Q
1198
Treatise on Poisons and their Antidote (Insects, snakes and mad dogs.)
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MAIMONIDES (Moses ben Maimon)
13
Q
1493 – 1541
* Studied Dose-response relationship.
* First scientific approach in toxicology.
* “The dose makes the poison”
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PARACELSUS
14
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1787 – 1853
* Father of modern toxicology.
* Advocate practice of autopsy.
* Published “Traite des Poisons” – foundation of forensic toxicology
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Mathieu Joseph Bonaventure Orfila
15
Q
12th Century BC.
An Indian collection that contains religious, knowledge and praises. Some contents describe plant poisons.
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RIG VEDA
16
Q
470 – 399 BC
Executed by the administration of hemlock (Conium maculatum).
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SOCRATES
17
Q
The tale leads to the use of the word “Mithridates” as an antidote or protective mixture.
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THE TALE OF KING MITHRIDATES VI
18
Q
138 to 78 BC
Issued “Lex Cornelia” – law against poisoning. Became a regulatory statute directed at careless dispensers of drugs
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SULLA
19
Q
1480
Warned of the toxicity of Hg and Pb from goldsmithing
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ELLENBOG
20
Q
1556
Published short treatise on mining disease (Miner’s sickness) other were published by Paracelsus.
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AGRICOLA
21
Q
1770
Published “Discourse on the Diseases of Workers”– discussed occupation ranging from miners to potters.
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RAMAZZINI
22
Q
1775
Recognition of the role of soot in scrotal cancer among chimney sweeps.
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POTT
23
Q
1797 – 1882
Published a simplified English version of “A Treatise on Poisons”.
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COSTILL
24
Q
1848
First published work on clinical toxicology “Practical Treatise on Poisons”
A
CHRISTISON
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1850-1929
Published early work on the toxicity of narcotics, mathanol, glycerol and chloroform
LEWIN
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# Focus of the Study
1. **Mechanism**
2. **Symptoms**
3. **Detection**
4. **Treatment**
1. Mechanism: How toxicity occurs
2. Symptoms: What are the clinical manifestations?
3. Detection: Confirmatory test and identification
4. Treatment: Antidote and management
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The incidence of poisoning in ______ is among the highest in the world
India (50,000/yr)
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CAUSES OF POISONING
* industrial
* accidental
* deliberate
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COMMON AGENTS THAT CAUSES TOXICITY
1. Pesticides: organophosphates
2. Sedatives: BZD, barbiturates
3. Chemicals: corrosives (acids and bases)
4. Alcohols: ethanol and methanol
5. Plant toxins: datura, oleander, Strychnos, Castors
6. Households: cleaning agents
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PHYSIOLOGY AND PHARMACOLOGY
By using toxic agents to understand the medicinal and the physiologic phenomena.
| IMPORTANCE AND CONTRIBUTION
## Footnote
Ex. Use of muscarine and nicotine (Cholinomimetic drugs)
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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
## Footnote
Lead containing paints or gasoline fume inhalation
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DISCOVERY AND DEVELOPMENT
Contribution in new formulation, development and innovation. Participation in the discovery of new drug and pesticides.
| IMPORTANCE AND CONTRIBUTION
## Footnote
clinical trials
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STANDARDIZATION AND REGULATION
Participate in developmental standard designed to protect human health and environment from adverse effects of chemicals.
| IMPORTANCE AND CONTRIBUTION
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AREAS IN TOXICOLOGY
* mechanistic toxicology
* regulatory toxicology
* risk assessment
* descriptive toxicology
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Concerned with the mechanism by which chemicals exert their toxic effects on living organisms.
MECHANISTIC TOXICOLOGY
| AREAS IN TOXICOLOGY
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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
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* Toxicity testing
* Provides necessary information for safety evaluation and regulatory requirements.
DESCRIPTIVE TOXICOLOGY
| AREAS IN TOXICOLOGY
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* 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
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Concerned with the medico legal aspects of the harmful effects of chemicals on humans
FORENSIC TOXICOLOGY
| SPECIALIZED AREAS OF TOXICOLOGY
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Aids in establishing the cause of death and in criminal investigation.
FORENSIC TOXICOLOGY
| SPECIALIZED AREAS OF TOXICOLOGY
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Within the realm of medical science concerned with disease caused by, or uniquely associated with toxic substances
CLINICAL TOXICOLOGY
| SPECIALIZED AREAS OF TOXICOLOGY
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Involved in emergency medicine and poison management
CLINICAL TOXICOLOGY
| SPECIALIZED AREAS OF TOXICOLOGY
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Develop treatment emergency poison antidotes regimens for ameliorating poisoning and xenobiotic injury.
CLINICAL TOXICOLOGY
| SPECIALIZED AREAS OF TOXICOLOGY
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Focuses on the impacts of chemical pollutants found in the environment biological organisms
ENVIRONMENTAL TOXICOLOGY
| SPECIALIZED AREAS OF TOXICOLOGY
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Studies chemicals that are contaminants of water, soil or air food
ENVIRONMENTAL TOXICOLOGY
| SPECIALIZED AREAS OF TOXICOLOGY
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Also associated with the studies of chemical effects on animals
ENVIRONMENTAL TOXICOLOGY
| SPECIALIZED AREAS OF TOXICOLOGY
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Deals with the chemicals found in the workplace
OCCUPATIONAL TOXICOLOGY
| SPECIALIZED AREAS OF TOXICOLOGY
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Protects workers from toxic substances and makes their work environment safe
OCCUPATIONAL TOXICOLOGY
| SPECIALIZED AREAS OF TOXICOLOGY
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Identify the agents of concern, define conditions leading to their use, and prevent the absorption of harmful amounts
OCCUPATIONAL TOXICOLOGY
| SPECIALIZED AREAS OF TOXICOLOGY
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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
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Study of adverse effects on the developing organism
## Footnote
Ex. Teratology
DEVELOPMENTAL TOXICOLOGY
| SPECIALIZED AREAS OF TOXICOLOGY
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Focuses on the study of the occurrence of adverse effects on the male and female reproductive system.
REPRODUCTIVE TOXICOLOGY
| SPECIALIZED AREAS OF TOXICOLOGY
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* 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
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Generally refers to toxic substances that are produced by biological system such as plants, animals or bacteria
Toxin
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Toxic substances produces by or a by-product of human activities.
Toxicant
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SPECTRUM OF UNDESIRED EFFECTS
* Allergic reactions/Sensitization
* Idiosyncratic reaction
* Immediate vs. delayed toxicity
* Reversible vs. irreversible effects
* Local vs. systemic toxicity
* Interaction of chemicals
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Occur in hypersensitive individuals or after sensitization in allergic or sensitized persons.
## Footnote
e.g. Reaction ranges from skin irritation to anaphylactic shock
ALLERGIC REACTION
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Occur in individuals who have genetic polymorphism that lead to structural changes in biomolecules, making them very sensitive to chemicals.
IDIOSYNCRACTIC REACTION
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Most chemicals exert their effects soon after exposure.
IMMEDIATE TOXICITY
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Others may be delayed for days to years (cancer)
DELAYED TOXICITY
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Depends on tissue’s ability to regenerate itself at a variety of levels: molecular, cellular and tissue
## Footnote
Liver vs. CNS
REVERSIBLE VS. IRREVERSIBLE
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Corrosives and irritants act locally, little goes systemic.
## Footnote
e.g. Eyes and skin
LOCAL
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Systemic effects in sensitive (not always highest concentration) tissues.
## Footnote
e.g. CNS, circulatory and blood, visceral organs
SYSTEMIC
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Combined effect is the same as the sum of effects when given alone
## Footnote
Ex. CNS depressants + Alcohol | Amphetamine + caffeine
ADDITIVE
| CHEMICAL INTERACTION
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combined effects are much greater than the sum of effects when given alone
## Footnote
Ex. CCl4 and EtOH | Pyrethroids and piperonyl butoxide (PBO)
SYNERGISTIC
| CHEMICAL INTERACTION
## Footnote
Note: Pyrethroids and piperonyl butoxide(PBO) - a pesticide synergist (knock-down effect)
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Exposure to a chemical with no toxicity increases the toxicity of another compound
## Footnote
Ex. CCl4 and isopropanol
POTENTIATION
| CHEMICAL INTERACTION
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Co-administration of two chemicals interferes with the toxicity of both or one of them.
## Footnote
Ex. Antidotal therapies
ANTAGONISM
| CHEMICAL INTERACTION
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Chemicals counterbalance each other by exerting opposite physiological function
## Footnote
Ex. Convulsions treated with benzodiazepines
FUNCTIONAL
| TYPES OF ANTAGONISM
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Chemical reaction between two compounds leads to less of the toxic compound
## Footnote
Ex. Chelators and metals
CHEMICAL (or inactivation)
| TYPES OF ANTAGONISM
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An antitoxin active against the venom of a snake, spider, or other venomous animal or insect.
| ex. of chemical antagonism
Antivenins
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Disposition of toxic chemical is changed so that concentration and/or duration is diminished.
## Footnote
Ex. Ipecac, charcoal, pH alteration, metabolism, induction or inhibition
DISPOSITIONAL
| TYPES OF ANTAGONISM
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Chemicals compete for the same receptor, decreasing effective binding of toxic compound.
## Footnote
Ex. Naloxone and morphine
RECEPTOR
| TYPES OF ANTAGONISM
## Footnote
Tamoxifen and estradiol – antagonist of the estrogen receptor in breast tissue
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A state of decreased responsiveness due to a prior exposure to the same or a structurally similar chemical in an individual
TOLERANCE
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A decreased amount of chemical reaches the site where the effect is produced
DISPOSITIONAL TOLERANCE
| TYPES OF TOLERANCE
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Same amount of chemical reaches the site, but target receptor response decreased
RECEPTOR TOLERANCE
| TYPES OF TOLERANCE
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A selective process (evolution) by which sensitive individuals do not survive and only those with a genetic trait that accommodates the chemical survive.
RESISTANCE
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A prompt and marked disturbance of function or death within a short time.
ACUTE POISONING
| TYPES OF POISONING
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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
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Marked by a gradual deterioration of function of tissues and may not result in death
CHRONIC POISONING
| TYPES OF POISONING
80
due to:
* Taking several small doses of drugs at long intervals
* Taking only toxic doses of the drug
CHRONIC POISONING
| TYPES OF POISONING
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<24 hrs, generally a single dose
ACUTE
| DURATION OF EXPOSURE
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Usually dietary
REPEATED
| DURATION OF EXPOSURE
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Repeated exposure for a month or less
SUBACUTE
| DURATION OF EXPOSURE
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Repeated exposure for 1-3 months
SUBCHRONIC
| DURATION OF EXPOSURE
85
Exposure > 3 months
CHRONIC
| DURATION OF EXPOSURE
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Benzene:
Acute Exposure: ?
Chronic Exposure: ?
**Acute Exposure**: CNS Narcosis
**Chronic Exposure**: Bone marrow damage and leukemia
| DIFFERENT OUTCOMES OF EXPOSURES
87
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
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* 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
89
* 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
90
* 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
91
Evidence from examination of tissues and organs after death
POST – MORTEM EVIDENCE (AUTOPSY)
| EVIDENCE OF POISONING
92
* 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
93
major route of entry of poison in the industrial settings
| Atmospheric (Sulfur oxides, pollutants nitrogen
oxides, carbon monoxide and dioxides)
Inhalation
| ROUTES OF EXPOSURE
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water and soil pollutants
Ingestion
| ROUTES OF EXPOSURE
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Broad range effects can be found with many drugs or chemicals with sufficient exposure.
CHEMICAL EXPOSURE
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EFFECTS OF CHEMICAL EXPOSURE
* neurotoxicity
* blood and immunity
* reproductive and genetic alterations
* cardiovascular
* respiratory
* nephrotoxicity
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* 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
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* 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
99
VARIATION IN TOXIC RESPONSES
* Selective toxicity
* Species differences
* Individual differences in response [Genetic polymorphism (aka idiosyncrasy)]
