Dose Effect and Confounding Factors

Flashcards covering the principles of toxicology, dose-response relationships, individual susceptibility factors, and biomarkers based on the lecture notes.

Principles of Toxicology

The three core principles are: i) Dose-Response, ii) $hazard \times exposure = risk$, and iii) individual sensitivity.

Routes of Exposure/Pathway

The methods by which a toxin enters a receptor, including Ingestion, Injection, Dermal, Inhalation, and through Mucous Membranes.

Paracelsus's Dictum

The statement from Paracelsus ($1493$-$1541$) that 'All substances are poisons; there is none which is not a poison. The right dose differentiates a poison from a remedy.'

Chronic Dose Duration

Exposure to a substance that occurs over a long period of time.

Acute Dose Duration

Short-term exposure to a substance.

Systemic Effects

Toxic effects that can include Endocrine Disruption, Genotoxicity, Neurotoxicity, and metabolic toxicity among others.

ADME

An acronym for the toxicological processes of Absorption, Distribution, Metabolism, and Excretion.

Exposure Dose

The dose of a toxin present in the environment.

Absorbed Dose

The proportion of the exposure dose that actually enters the living organism.

Toxic Dose ($TD$)

The dose that causes adverse or harmful effects, often expressed as $TD_{0}$, $TD_{10}$, $TD_{50}$, etc.

Threshold Dose

The dose at which a toxic effect is first observed.

Lethal Dose ($LD_{50}$)

A statistically derived dose that is lethal to $50\%$ of the tested group.

Monotonicity

Refers to dose-response curves where the slope never reverses from positive to negative or vice versa; they may be linear or nonlinear.

Nonmonotonicity

Refers to dose-response curves where the slope changes sign, including 'U-shaped' or 'inverted-U-shaped' relationships.

Internal Dose

The amount of toxicant absorbed that is available to cause harm.

Target Organ Dose

The amount of a substance that reaches the specific site where adverse effects occur, also known as the biologically effective dose.

Stratum Corneum

A natural barrier in the skin containing keratin (a chemically resistant protein filament) which reduces the ability of skin to absorb toxicants.

Blood Brain Barrier

A barrier that prevents proteins and other large molecules from entering brain cells; it is less effective in infants.

Endocrine Disrupting Chemical (EDC)

An exogenous substance that causes adverse health effects in an intact organism or its progeny subsequent to changes in the endocrine system.

Bisphenol A (BPA)

A chemical used in polycarbonate plastics and epoxy resins that acts as an endocrine disruptor with concern for effects on the brain, behavior, and prostate gland in fetuses and infants.

Atrazine

A herbicide used in the US (banned in the EU) that can alter the sex of frogs and is suspected of impacting birth weights and defects in humans.

Alcohol Dehydrogenase

An enzyme whose levels are lower in females and barely detectable in infants, affecting their ability to detoxify alcohol.

G6PD Deficiency

An X-linked condition resulting in reduced levels of $NADPH$ and glutathione, leading to increased susceptibility to drug-induced haemolytic anaemias.

Polynuclear Aromatic Hydrocarbons (PAHs)

Common air and water pollutants, such as Benzo[a]pyrene, that require metabolism into diol epoxides to become potent carcinogens.

Bay Theory

A theory predicting that an epoxide in the bay region of a PAH will be highly reactive and mutagenic.

DNA Adducts

Markers formed when reactive metabolites bind covalently to DNA, used in research to determine PAH-induced carcinogenesis risk.

Biomarker of Exposure

A chemical, metabolite, or interaction product measured in biological fluid that reflects an individual's internal dose.

Biomarker of Effect

A measurable biochemical, physiological, or behavioural change associated with toxin exposure, such as 8-hydroxyl deoxyguanine in urine for oxidative stress.

Hazard

The potential for a substance to cause an adverse or harmful effect.

Risk

A measure of the likelihood of the occurrence of a particular adverse effect, often calculated as $probability \times magnitude$.

Precautionary Principle

The approach that cautionary measures should be taken when an activity threatens harm to health or the environment, even if cause-and-effect relationships are not fully scientifically established.