Chp. 2 Principles of Toxicology

sensitization and hypersensitivity tests

-Guinea pig maximization test -local lymph node assay; mice

chronic tox test

6 month to 2 year exposure; assess both cumulative tox and carcinogenic potential; all animals

descriptive toxicologist

concerned directly with toxicity testing, which provides info for safety evaluation and regulatory requirements

clinical toxicology

concerned with disease caused by or uniquely associated with toxic substances

regulatory toxicologist

decides, on the basis of data provided by descriptive and mechanistic toxicologists, whether a drug or another chemical poses a sufficiently low risk to be marketed for a stated purpose

genetic polymorphisms

may be responsible for idiosyncratic reactions to chemicals and for interindividual differences in toxic responses

sub-acute tox test

mice; repeated dose study used to obtain info on the tox of a substance after repeated administration for 14 days; provides guidance in establishing acceptable doses or exposure limits

inhalation, instillation, and aspiration tox test

one rodent species; respiratory rate is key endpoint

deleterious/adverse/toxic effects

side effects that are deleterious to the well-being of humans

ecotoxicology

specialized area within env tox, focuses specifically on impacts of toxic substances on population dynamics in an ecosystem

developmental toxicology

study of adverse effects on the developing organism that may result from exposure to chemical or physical agents before conception (either parent), during prenatal development, or postnatally until the time of puberty

Teratology

study of defects induced during development between conception and birth

reproductive toxicology

study of the occurrence of adverse effects on the male or female reproductive system that may result from exposure to chemical or physical agents

potentiation

when a substance that does not have a toxic effect originally, is made toxic by the addition of another chemical

functional antagonism

when the 2 chemicals counterbalance by producing opposite effects

dispositional antagonism

when the absorption, biotransformation, distribution, or excretion of the chemical is altered so the concentration and/or duration of chemical at the target organ is diminished

antagonism

when two chemicals administered together interfere with each other's actions or one interferes with the action of the other. four types: functional, chemical, dispositional, and receptor

dermal irritation test

(Draize test); substance is applied and skin irritation is scored; white rabbit

chemical antagonism

(inactivation) is a chemical reaction between the 2 compounds that produces a less toxic product

selective toxicity

a chemical produces injury to one kind of living matter without harming another form of life even though the two may exist in intimate contact

hapten

a chemical that is not sufficiently large enough to be recognized by the immune system as a foreign substance and thus must first combine with an endogenous protein to form an antigen (or immunogen; then capable of eliciting the formation of antibodies)

forensic toxicology

a hybrid of analytic chemistry and fundamental toxicologic principles that focuses primarily on the medicolegal aspects of the harmful effects of chemicals on humans and animals

chemical allergy

an immunologically mediated adverse reaction to a chemical resulting from previous sensitization to that chemical or to a structurally similar one

margin of safety

an indicator of the magnitude of the difference between an estimated "exposed dose" to a human population and the no observable adverse effect level (NOAEL) determined in experimental animals

subchronic exposure

animal experiment: exposure for 1 to 3 months human exposures: occurring repeatedly over several weeks months

chronic exposure

animal experiment: exposure for more than 3 months human exposures: occurring repeatedly for many months or years

subacute exposure

animal experiment: repeated exposure to a chemical for 1 month or less

acute exposure

animal experiments:exposure to a chemical for less than 24 hours human exposures: a single incident or episode

toxicogenomics

defines the interaction between genes and toxicants in toxicity etiology. permits the application of genomic, transcriptomic, proteomic, and metabolic technologies to identify descriptive and mechanistic info that can protect genetically susceptible individuals from harmful env exposures, and to customize drug therapies based on their individual genetic makeup

undesirable/side effects

effects that are not associated with the primary objective of the therapy of a drug

environmental toxicology

focuses on the impacts of chemical pollutants in the env on biological organisms, specifically studying impacts of chemicals on nonhuman organisms such as fish, birds, terrestrial animals, and plants

chemical idiosyncrasy

genetically determined abnormal reactivity to a chemical

sub-chronic tox test

goal to establish LOAEL, NOAEL, identify specific organs affected by the substance after repeated administration for 90 days; rat, dog, and mouse

mechanistic toxicologist

identifies the cellular, biochemical, and molecular mechanisms by which chemicals exert toxic effects on living organisms

ocular irritation test

substance instilled into eye and eyes are examined

toxicant

term used in speaking of toxic substances that are produced by or are a by-product of human activities

dose-response relationship

the characteristics of exposure and the spectrum of effects in a correlative relationship; can be individual (continuous or graded) or quantal (population defined; "all or none")

additive effect

the combined effect of the two chemicals is equal to the sum of the effects of each agent given alone

synergistic effect

the combined effects of two chemicals are much greater than the sum of the effects of each agent given alone

threshold dose

the minimally ED of any chemical that evokes a stated all or none response

target organs

the one or two organs that a chemical usually elicits systemic toxicity in

therapeutic index

the ratio of the dose required to produce a toxic effect and the dose needed to elicit the desired therapeutic response

Toxicology

the study of the adverse effects of chemicals on living organisms

toxin

toxic substances that are produced by biological systems such as plants, animals, fungi, or bacteria

toxicologist

trained to examine the nature of those effects (cellular, biochemical, and molecular mechanisms of actions) and assess the probability of their occurrence

hypersensitivity/allergic reaction/sensitization reaction

used to describe a chemical allergy; once sensitization has occurred, allergic reactions may result from exposure to relatively low doses of chemicals

genotoxicity

used to detect early tumorigenic effects in chronic illnesses; bacteria cultures and mammalian cells

descriptive tox tests

useful in determining the potential toxicity of a substance to humans using laboratory animal model systems; indentifies the tox of a stubstance at an early stage of its product development, marketing, or distribution

acute lethality test

usually the first test performed on a substance; looks for the LD50 or LC50; tabulates deaths in a 14 day period; mouse, rat, or other

receptor antagonism

when 2 chemicals that bind to the same receptor produce less of an effect when given together than the addition of their separate effects or when one chemical antagonizes the effect of the second chemical; these are called blockers