TOXICOLOGY The study of chemical or physical agents and their interaction with biologic systems to produce a response in a organism. The dose makes the poison!

TOXICOLOGY DOSE = AMOUNT –Units mg/Kg (per unit weight) mg/cm 2 (per area of skin surface) ppm (per unit volume of air inhaled (gas/vapor)) mg/m3 (for solids inhaled in air)

TOXICOLOGY Types of Exposure –Acute –amount of substance which is capable of causing an immediate reaction (less than 24 hours) –Chronic –small amount which does not cause an immediate reaction but is accumulated in the body to cause a delayed reaction over a longer period of time.

TOXICOLOGY Routes of Exposure oral dermal inhalation injection

TOXICOLOGY Toxicity Tests –goal is to select a test species that is a good model of humans, a response that is not subjective and can be consistently determined, and a test period that is relatively short.

TOXICOLOGY Dose-Response Curve Dose % test organisms responding

TOXICOLOGY DOSE - RESPONSE TERMS –Toxic dose low (TL lo ) = lowest dose introduced by any route (except inhalation) reported to produce any toxic effect in humans or to produce tumorigenic or reproductive effects in animals.

TOXICOLOGY DOSE - RESPONSE TERMS - Toxic Concentration Low (TC lo ) - Lowest concentration of substance in air to which humans or animals have been exposed and has produced any toxic effect

TOXICOLOGY DOSE - RESPONSE TERMS –Lethal Dose low (LD l0 ) Lowest dose of a substance introduced by any route (except inhalation) which has been reported to have caused death in humans or animals.

TOXICOLOGY DOSE - RESPONSE TERMS –Lethal Dose 50 (LD 50 ) - Calculated dose of a substance which is expected to cause death of 50% of the entire defined experimental population.

TOXICOLOGY DOSE - RESPONSE TERMS –Lethal Concentration 50 (LC 50 ) Calculated concentration of a substance in air to which is expected to cause the death of 50% of an entire defined experimental population. (Table 1.)

TOXICOLOGY USING DOSE - RESPONSE INFORMATION Can compare LD 50 of chemicals gives a relative rating of toxicity (Table 2.) Use LD 50 (mg/Kg) and multiply by 70 gives a rough estimate of toxic potential for humans.

TOXICOLOGY DOSE - RESPONSE AND SAFETY FACTORS Percent Response Dose ED50 LD50TLV

TOXICOLOGY FACTORS INFLUENCING TOXICITY –ROUTE OF EXPOSURE Route determines how much is absorbed and which organs are exposed to the highest concentrations.

TOXICOLOGY FACTORS INFLUENCING TOXICITY –GENDER Some substances are more toxic to one gender than another.

TOXICOLOGY FACTORS INFLUENCING TOXICITY –AGE Older people have different blood, hepatic systems, musculature, metabolism, and excretory patterns than younger people. This can influence disposition and toxic effects of chemicals.

TOXICOLOGY FACTORS INFLUENCING TOXICITY –SYNERGISM = 3 –ANTAGONISM = 1/2 –POTENTIATION - Type of Synergism

TOXICOLOGY FACTORS INFLUENCING TOXICITY –GENETICS Not all people are created equal genetically!

TOXICOLOGY FACTORS INFLUENCING TOXICITY –SPECIES VARIATION Physiological differences between species can lead one to over or under estimate toxic effects of a chemical when comparing results from one to another species.

TOXICOLOGY EXPOSURE GUIDELINES ACGIH - American Conference of Governmental Industrial Hygienists Develop and Publish - Threshold Limit Values (TLVs)

TOXICOLOGY TLV - based on the concept that there is a threshold dose or concentration below which there is no adverse effects. - Developed for use in the workplace

TOXICOLOGY TLVs –Refer to airborne concentrations –Represent conditions under which nearly all workers may be repeatedly exposed day after day without adverse effects. –Limited: healthy working age individuals

Toxicology TLV TYPES –TLV-TWA: Time Weighted Average time weighted average concentration for a normal eight-hour work day –TLV-STEL: Short Term Exposure Limit 15 minute time weighted average exposure repeated exposure no more than four times per 8 hour work shift

TOXICOLOGY TLV TYPES –TLV-C: Ceiling Concentration that should not be exceeded, even instantaneously.

TOXICOLOGY EXPOSURE GUIDELINES OSHA - PELs: Permissible Exposure Limits PELs are legally enforceable and apply to all private industries and the Federal government. 29 CFR lists PELs for specific compounds

TOXICOLOGY EXPOSURE TYPES IDLH - Immediately Dangerous to Life and Health –represent maximum concentrations from which one could escape within 30 minutes without any irreversible health effects

TOXICOLOGY BODY RESPONSE TO TOXIC CHEMICALS Respiratory Tract –upper - nasopharyngeal –middle - tracheobronchial –lower - pulmonary acinus

TOXICOLOGY BODY RESPONSE TO TOXIC CHEMICALS Types of inhaled toxicants –Asphyxiants: gases that deprive the body of oxygen Simple asphyxiants (nitrogen, helium, methane) Chemical asphyxiants (cyanide, Carbon Monoxide)

TOXICOLOGY BODY RESPONSE TO TOXIC CHEMICALS Irritants: –chemicals that irritate the air passages, causing constriction of airways and edema (liquid in the lungs) and infection. (ammonia, chlorine, HF, HCl)

TOXICOLOGY BODY RESPONSE TO TOXIC CHEMICALS Necrosis Producers: –chemicals that result in cell death and edema. (ozone, nitrogen dioxide)

TOXICOLOGY BODY RESPONSE TO TOXIC CHEMICALS Fibrosis producers: –chemicals that produce fibrotic tissue which if massive, block airways and decrease lung capacity. (asbestos, silicates, beryllium)

TOXICOLOGY BODY RESPONSE TO TOXIC CHEMICALS Allergens: –chemicals that induce allergic response characterized by bronhoconstriction and pulmonary disease. (isocyanates, sulfur dioxide)

TOXICOLGY BODY RESPONSE TO TOXIC CHEMICALS Carcinogens: –chemicals associated with lung cancer (cigarette smoke, coke emissions, asbestos, arsenic)

TOXICOLOGY BODY RESPONSE TO TOXIC CHEMICALS SKIN –natural barrier: prevents absorption –Sebaceous glands: secrete fatty acids –Melanocytes:protects from UV –Sweat galnds: regulate heat

TOXICOLOGY BODY RESPONSE TO TOXIC CHEMICALS EYES CENTRAL NERVOUS SYSTEM LIVER KIDNEYS BLOOD

TOXICOLOGY TERATOGENS MUTAGENS CARCINOGENS