Introduction to Toxicology

• Toxicology is presented by Dr. Motasem Saidan ([email protected]) from the University of Jordan, Chemical Engineering Department.

Overview of Toxicology

• Toxin refers to a poisonous and unstable compound created by microorganisms, plants, or animals.
• Toxicant refers to chemical agents or physical agents like particulates smaller than 5 µm, noise, and radiation.
• Toxicity is the impact of a specific amount/dosage of a toxin on a living microorganism.
• Toxicology is the study of poison.
• Paracelsus (1493 - 1541) stated that everything is a poison, depending on the dose.

General Concepts of Toxicology

• Hazardous Material: A material with characteristics that intensify toxic action as a solid, liquid, or gas.
  • Ignitability means a substance is flammable or combustible.
  • Reactivity means a substance can react with itself or other materials.
  • Corrosivity means a substance can deteriorate another substance.
  • Toxicity means a substance is harmful to living things in its normal state.
• Everything is toxic depending on the dose.
• The body's acceptance of a substance is affected by:
  • The type of substance
  • The amount absorbed.
  • The period of time over which the substance is absorbed.
  • The exposed person's susceptibility/sensitivity

Toxic Pathways

• Chemical elements can become concentrated through:
  • Biomagnification, where the accumulation of a substance increases in living tissue as it moves through the food chain, like Cadmium and mercury.

Routes of Toxicant Exposure

• Toxicants can enter biological organisms through various routes:
  • Inhalation
  • Ingestion
  • Absorption
  • Injection

Toxic Blood Level

• Toxic blood level varies based on the route of that substance exposure.
• Toxin can enter the brain, respiratory system, heart, liver, stomach and intestine following exposure.

Food Chain Exposure

• Toxic food examples from toxic food chains are show

Measurement of Toxicity

• Toxicity is measured using:
  • Parts Per Million (ppm)
  • Parts Per Billion (ppb)
  • Parts Per Trillion (ppt)
  • Lethal Dose - LD50
  • Lethal Concentration - LC50
  • Threshold Limit Value - TLV
• Parts Per Million (ppm) is measured as one part in one million parts.
• Parts Per Billion (ppb) is measured as one part in one billion parts.
• Parts Per Trillion (ppt) is measured as one part in one trillion parts.
• Lethal Dose (LD50) is the dosage of a substance administered to laboratory animals that results in 50% fatalities and is expressed in milligrams of the substance per kilogram of body weight (mg/kg).
  • LD50 typically refers to dermal dosages.
  • The lethal dose for humans can be estimated by multiplying the LD50 value by a person's weight.
• Lethal Concentration (LC50) is the concentration of a material, expressed as parts per million (ppm) by volume, that kills half of the laboratory animals during the exposure period.
  • LC50 typically refers to airborne dosages.

Threshold Limit Value (TLV)

• TLV is the upper limit of a toxin concentration to which an average healthy person can be repeatedly exposed on an all-day, everyday basis (8 hours/5 days) without adverse health effects and is typically used for workplace exposure determinations.
  • Gaseous substances in the air are expressed in parts per million (ppm).
  • Fumes or mists in the air are expressed in milligrams per cubic meter (mg/m³).
• TLV values are set by the American Conference of Governmental Industrial Hygienists (ACGIH).
• TLV-TWA: Time Weighted Average concentration for an eight-hour workday.
• TLV-STEL: Short Term Exposure Limit, a 15-minute time-weighted average exposure that can be repeated no more than four times per 8-hour work shift.
• TLV-C: Ceiling Concentration that should not be exceeded, even instantaneously.
• Some example TLV values:
  • Acetone: 750 ppm
  • Ammonia: 25 ppm
  • CO: 25 ppm
  • Chlorine: 0.5 ppm
  • Gasoline: 300 ppm
  • Hexane: 50 ppm
  • Phosgene: 0.1 ppm
• For flammables, TLV is ¼ of the lower flammable limit, and some toxicants have zero thresholds.
• Example exposure model showing safe exposure, TLV, LC50, and LD50 for time and dose.

Toxicology Experiment with Rabbits

• Procedure:
  • Start with 50 rabbits and expose each to a fixed concentration of a substance to get a variety of responses.
  • Determine response curve
  • Plot Bar Chart
  • Repeat experiment at different doses
• The form is not very useful, particularly at low doses.
• To improve the usefulness of the data, take the log of the dose, which results in an S-shaped curve that is better at low dose values.
• To convert the data to a linear form, the S-shape can be transformed into a straight line using a mathematical transformation called a probit.
• The determination of relative toxicity can be shown in a graph.
• The causative factor equation is shown.
• Table for probit analysis is shown.
• An example application of this analysis is presented.