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Introduction to Toxicology: Understanding Dose-Response Relationships

Explore the world of toxicology, focusing on dose-response relationships and factors influencing toxicity in organisms. Learn about exposure types, testing methods, and guidelines in this comprehensive overview.

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Introduction to Toxicology: Understanding Dose-Response Relationships

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  1. 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!

  2. TOXICOLOGY • DOSE = AMOUNT • Units • mg/Kg (per unit weight) • mg/cm2 (per area of skin surface) • ppm (per unit volume of air inhaled (gas/vapor)) • mg/m3 (for solids inhaled in air)

  3. 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.

  4. TOXICOLOGY • Routes of Exposure • oral • dermal • inhalation • injection

  5. 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.

  6. TOXICOLOGY • Dose-Response Curve % test organisms responding Dose

  7. TOXICOLOGY • DOSE - RESPONSE TERMS • Toxic dose low (TLlo) = 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.

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

  9. TOXICOLOGY • DOSE - RESPONSE TERMS • Lethal Dose low (LDl0) Lowest dose of a substance introduced by any route (except inhalation) which has been reported to have caused death in humans or animals.

  10. TOXICOLOGY • DOSE - RESPONSE TERMS • Lethal Dose 50 (LD50) - Calculated dose of a substance which is expected to cause death of 50% of the entire defined experimental population.

  11. TOXICOLOGY • DOSE - RESPONSE TERMS • Lethal Concentration 50 (LC50) 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.)

  12. TOXICOLOGY USING DOSE - RESPONSE INFORMATION • Can compare LD50 of chemicals gives a relative rating of toxicity (Table 2.) • Use LD50 (mg/Kg) and multiply by 70 gives a rough estimate of toxic potential for humans.

  13. TOXICOLOGY DOSE - RESPONSE AND SAFETY FACTORS TLV LD50 ED50 Percent Response Dose

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

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

  16. 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.

  17. TOXICOLOGY • FACTORS INFLUENCING TOXICITY • SYNERGISM - 1 + 1 = 3 • ANTAGONISM - 1 + 1 = 1/2 • POTENTIATION - Type of Synergism

  18. TOXICOLOGY • FACTORS INFLUENCING TOXICITY • GENETICS Not all people are created equal genetically!

  19. 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.

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

  21. 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

  22. 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

  23. 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

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

  25. TOXICOLOGY EXPOSURE GUIDELINES • OSHA - PELs: Permissible Exposure Limits • PELs are legally enforceable and apply to all private industries and the Federal government. • 29 CFR 1910.1000 lists PELs for specific compounds

  26. 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

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

  28. 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)

  29. 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)

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

  31. 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)

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

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

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

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

  36. TOXICOLOGY • TERATOGENS • MUTAGENS • CARCINOGENS

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