PRINCIPLES OF TOXICOLOGY...a discussion of the fundamental means by which toxicological properties are determined.

DEFINITIONS l Toxicology n Science that studies the harmful or toxic properties of substances

TOXICITY vs HAZARD [an important distinction] l Toxicity n The ability of a substance to have an adverse effect on the health or well-being of a human –The toxicity of a chemical depends on the degree of exposure and absorption l Hazard n The probability that the concentration will occur at that site in the body

Toxicity vs. Hazard l Two chemicals can possess the same degree of toxicity, but present different degrees of hazard. n Ex. Odorless and non-irritating vs. pungent odor l The chemical with warning properties may present a lesser degree of hazard.

TOXICOLOGY l Early interest was in “how to poison” l In 1800’s, tests to identify poisons were developed (i.e., forensic medicine) l Only in 20th century has toxicology been applied to defining safe work conditions

TOXICOLOGY IS MULTIDISCIPLINARY l CHEMISTRY l BIOCHEMISTRY l PHYSIOLOGY l PATHOLOGY l IMMUNOLOGY l PHYSICS l ENGINEERING l STATISTICS

ROUTES OF EXPOSURE l Inhalation l Ingestion l Skin contact l Injection

EFFECTS OF EXPOSURE l ACUTE - a “one-time” event n rapid absorption of material n exposure sudden & severe n critical period for death/survival l CHRONIC - small doses over long time n rate of intake > rate of elimination n material remains in tissue; injures

Comparison of Chemical Exposures [Industrial vs Non-Industrial] l Route of Exposure inhalation ingestion skin absorption l Type of Contact acute chronic l Number of Agents l Other Aspects

TYPES OF TOXIC EFFECT l mortality l pathological change l growth rate change l physiological injury l biochemical change l behavioral effects l reproductive system damage l mutagenic, etc.

Toxic Effect by Target Organ l irritant l asphyxiant l anesthetic l hepatotoxic l nephrotoxic l neurotoxic l pulmonary

Factors Influencing Intensity of Toxic Action l route of entry l rate of exposure l age of host l prior exposure l environment l host factors gender, genetics l other factors

Dose-Response Relationship l Correlation between the amount of exposure and the resulting effect

Lethal Dose/Lethal Concentration l LD 50 - Dose required to kill 50% of population l LC 50 – Concentration required to kill 50% of population

How is toxicological data obtained? l animal toxicological studies l accidental human overexposures l controlled exposures of human volunteers l epidemiological studies descriptive retrospective (conventional) prospective (cutting edge)

Sources of Toxicological Information l Material Safety Data Sheet n Identity n Hazardous Ingredients/Identify Information n Physical/Chemical Characteristics n Fire and Explosion Hazard Data n Reactivity Data n Health Hazard Data n Precautions for Safe Handling and Use n Control Measures

Information Resources l l