Lecture 3 - Toxicology

Question 1

4 primary components of Risk Assessment framework

Answer 1

Hazard Identification, dose response assessment, exposure assessment, risk characterization

toxicology and epidemiology are sources of information for hazard identification and exposure assessment

Question 2

Basic Principles of Toxicology

Answer 2

study of adverse agents on living organisms, especially humans.

toxic substance: agent which provokes an adverse effect

toxicity: potential of agent to cause harm (low toxicity means large quantity required to cause harm)

Paracelcus is the father of modern toxicology “the dose makes the poison”

Question 3

Exposure Routes (Pathways)

Answer 3

inhalation (most significant workplace pathway) - humans breath 15kg/day of air, only small particles reach alveoli, soluble vs insoluble
ingestion: through digestive tract,
dermal: diffusion, direct penetration, invasion
injection (unitentional vs intentional)
transplacental

Question 4

Factors which affect toxicity

Answer 4

route of exposure (how and where it enters), total lifetime dose, chemical makeup and properties, synergistic effects, host factors

Question 5

Fate of toxic substances in the body

Answer 5

absorption: fat soluble substances more easily absorbed through skin, differential absorption among
transport, distribution: via the bloodstream, differential receptivity
digestion metabolism: liver converts compounds to water soluble so they can be excreted. however, this can bioactivate some compounds
storage: fat, bone, kidneys,
excretion: urine, exhalation, perspiration, feces (differential excretion)

Question 6

Exposure. Dose-response

Answer 6

exposure: what is outside the body (conc in air vs air inhaled)
dose: what is inside, weight of toxicant vs weight of person)

latency period: amount of time between exposure and and onset or detection of health effects (also called induction or incubation period)

Question 7

How Toxicity is Assessed

Answer 7

3 tiered approach. prediction/computer modeling, in-vitro (in glass), in vivo (within living)

Question 8

Stages of a Toxic response

Answer 8

exposure, dose, distribution absorption and storage within body, response, excretion from body

Question 9

relationship between route, media, pathway

Answer 9

media is food, route is ingestion, pathway is how contaminants enter the body

Question 10

Classicification of Exposure and Health effects

Answer 10

acute and chronic exposure, acute and chronic health effects. health effects can be localized or systemic

Question 11

Threshold terminology

Answer 11

lowest dose that produces an adverse effect in the most susceptible individual. no-observed-adverse effect level, lowest observed adverse effect level.

LD50, LC50 (old measures, now we have toxic endpoints - carcinogenisis, reproductive toxicity, developmental toxicity, neurotoxicity, immunotoxicity)

Question 12

Conventional Toxicology study types

Answer 12

acute toxicitiy (hours, LD50), information on interactions between multiple agents
chronic toxicity studies: length between sub-chronic and lifetime

Question 13

mechanisms of toxicity

Answer 13

metabolic and cellular poisons, enzyme induction, interference with receptors, oxidative stress and free radicals, effects on signal transduction, adduct formation, genotoxicity, apoptosis, immunotoxicity