Historical Background of Toxicology & Environmental Health

Flashcards covering the historical background of toxicology, key figures, environmental regulations, waste management, chemical fate and transport, metabolism, excretion, and carcinogenesis from ERHS 446 lecture notes.

Dioscorides

Greek physician (50–90 AD) who was the first to classify poisons into Plant, Animal, and Mineral categories.

Paracelsus

Known as the 'Father of Toxicology' (1493–1541), he coined the term 'toxicins' and established principles such as 'the dose makes the poison'.

Toxicins

Specific chemical agents responsible for toxic effects within a substance, a term coined by Paracelsus.

Dose-Response Relationship (Paracelsus)

The principle that the dose determines whether a substance acts as a poison or a therapeutic agent.

Ramazzini

Author of 'Discourse on the Diseases of Workers' (1700), linking occupational exposures to disease; considered the 'Father of Occupational Medicine'.

Percival Pott

Identified the first evidence of chemical-induced cancer in 1775, linking scrotal cancer in chimney sweeps to PAHs.

FDA (Food and Drug Administration)

Established in 1938 after the sulfanilamide disaster, it regulates food additives, cosmetics, medical devices, and drugs.

FIFRA (Federal Insecticide, Fungicide, and Rodenticide Act)

A 1947 act requiring pesticides to be proven safe before registration and use.

Love Canal

A notorious chemical waste dump from the 1940s–70s that led to widespread illness and major environmental cleanup efforts.

EPA (Environmental Protection Agency)

Formed in 1970 to protect human health and the environment, enforcing acts such as the Clean Air Act and Clean Water Act.

OSHA (Occupational Safety and Health Administration)

Established in 1970 to ensure safe and healthful working conditions by setting and enforcing standards.

ATSDR (Agency for Toxic Substances and Disease Registry)

Formed in 1980, it focuses on public health functions related to hazardous waste cleanup sites.

Toxicology

The science that studies the adverse effects of chemicals on living organisms.

Dose

The amount of a substance an organism is exposed to, typically relative to body weight (e.g., mg/kg).

Risk

The probability that exposure to a chemical will cause harm, dependent on hazard (inherent toxicity) and exposure (dose, duration, frequency).

Orfila

Known as the 'Father of Forensic Toxicology' (1815), he developed chemical testing methods for poisons like the Marsh Test for arsenic.

Thalidomide

A morning sickness drug from the 1960s that caused severe birth defects and highlighted the need for comprehensive drug testing, especially during pregnancy.

Rachel Carson

Author of 'Silent Spring' (1962), which raised public alarm about the dangers of pesticides, especially DDT.

Environmental Justice (EJ)

The fair treatment and meaningful involvement of all people regardless of race, income, or background with respect to environmental laws, regulations, and policies.

Hawk’s Nest Tunnel Disaster

A 1930s case where silica dust exposure led to silicosis and hundreds of deaths, disproportionately affecting African American workers who received lower compensation.

Organochlorine Pesticides (e.g., DDT)

Pesticides that disrupt sodium ion channels in insects and were banned in most countries due to their persistence and toxicity.

Organophosphate Pesticides

Pesticides that block cholinesterase, harming the nervous systems of both insects and humans.

PCBs (Polychlorinated Biphenyls)

Man-made chemicals used in electrical and plastic industries, known to be carcinogenic and damaging to immune, reproductive, nervous, and endocrine systems.

Clean Air Act (CAA)

A 1970 U.S. law that regulates air pollutants, with the EPA setting National Ambient Air Quality Standards (NAAQS) for criteria pollutants.

Clean Water Act (CWA)

A 1972 U.S. law controlling discharges into surface waters and aiming to make them 'fishable and swimmable'.

Safe Drinking Water Act (SDWA)

A 1974 U.S. law regulating public water systems and requiring the EPA to set Maximum Contaminant Levels (MCLs) for drinking water contaminants.

TSCA (Toxic Substances Control Act)

A 1976 U.S. law (amended in 2016 by LCSA) regulating industrial chemicals not covered by other statutes, historically criticized for its limited testing requirements.

RCRA (Resource Conservation and Recovery Act)

A 1976 U.S. law that mandates 'cradle-to-grave' tracking and proper disposal of hazardous waste, also regulating municipal solid waste.

CERCLA (Comprehensive Environmental Response, Compensation, and Liability Act) / Superfund

A 1980 U.S. law dedicated to the cleanup of contaminated sites, establishing liability for polluters and funding emergency responses.

Basel Convention

A 1989 international treaty regulating the cross-border movement of hazardous waste to prevent its dumping in less industrialized nations.

Waste Management Hierarchy

A framework prioritizing waste strategies: avoidance/reduction (best), followed by recycling/reuse, and then proper handling/disposal.

Fate (of contaminants)

The ultimate disposition or end result of contaminants after release, including movement, degradation, transformation, and accumulation.

Transport (of contaminants)

How contaminants move between different environmental media, such as air, soil, water, and biota.

Bioaccumulation

The buildup of a chemical within a single organism over time, leading to higher concentrations in older individuals.

Biomagnification

The increasing concentration of a chemical in organisms at higher trophic levels (up the food chain).

Persistent Organic Pollutants (POPs)

Chemicals that resist degradation in the environment and human body, such as PBDEs, PFOS, PFOA, BPA, phthalates, atrazine, and PCBs.

Antagonistic Interaction

A toxicant interaction where chemicals reduce each other’s effects (e.g., 2 + 4 = 1).

Additive Interaction

A toxicant interaction where the effects of multiple chemicals sum together (e.g., 2 + 2 = 4).

Synergistic Interaction

A toxicant interaction where chemicals multiply each other’s effects (e.g., 2 + 2 = 10).

Potentiation

A toxicant interaction where a non-toxic chemical increases the toxicity of another substance (e.g., 2 + 0 = 10).

Acute Exposure

A single or short-term contact with a toxicant, often leading to immediate health effects.

Chronic Exposure

Repeated low-dose contact with a toxicant over a long period, potentially leading to cumulative, long-term health effects.

Hormesis

A biphasic dose-response relationship where low doses of a substance may have beneficial or stimulatory effects, while high doses are inhibitory or toxic.

NOAEL (No Observed Adverse Effect Level)

The highest experimental dose of a substance at which no adverse effect is observed.

LOAEL (Lowest Observed Adverse Effect Level)

The lowest experimental dose of a substance at which an adverse effect is observed.

LD50 (Lethal Dose 50%)

The dose of a substance that is lethal to 50% of the tested population.

Therapeutic Index (TI)

A measure of drug safety, calculated as the ratio of TD50 (toxic dose) to ED50 (effective dose); a larger TI indicates a safer drug.

ADME

An acronym representing the four main processes of pharmacokinetics and toxicokinetics: Absorption, Distribution, Metabolism, and Excretion.

First-pass Effect

The metabolism of a toxicant by the liver before it reaches systemic circulation, reducing its bioavailability.

Blood-Brain Barrier (BBB)

A protective barrier of specialized endothelial cells in brain capillaries that restricts the passage of many polar molecules and toxicants into the brain.

Biotransformation (Metabolism)

The biochemical modification of a xenobiotic/toxicant by living organisms, typically converting lipid-soluble compounds into water-soluble metabolites for excretion.

Phase I Metabolism (Functionalization)

The first phase of biotransformation involving reactions like oxidation, reduction, and hydrolysis, which introduce or modify functional groups to make compounds more polar, sometimes leading to bioactivation.

Cytochrome P450 (CYP450)

A superfamily of enzymes primarily involved in Phase I metabolism, critical for metabolizing numerous endogenous and exogenous compounds, including toxicants and drugs.

Phase II Metabolism (Conjugation)

The second phase of biotransformation where hydrophilic groups are attached to metabolites from Phase I, further increasing their polarity and facilitating excretion.

Glutathione Conjugation

A Phase II metabolic pathway mediated by Glutathione-S-transferase (GST), critical for detoxifying electrophilic carbons and epoxides, and important in preventing acetaminophen hepatotoxicity.

Liver Zonation

The functional and metabolic differences across the liver lobule, with Zone 1 (periportal) having high oxygen and metabolic activity, and Zone 3 (centrilobular) being enriched in CYP450 enzymes and more susceptible to toxic injury.

Clearance (CL)

The volume of blood or plasma completely cleared of a chemical per unit of time, reflecting the efficiency of its elimination from the body.

Carcinogenesis

The multi-stage process of cancer development, typically involving initiation, promotion, and progression.

Mutagenicity

The ability of a chemical or physical agent to cause a permanent, heritable change in the genetic material (DNA or chromosomes).

Genotoxic

Describes substances that directly cause damage to DNA or chromosomes.

Initiation (Carcinogenesis)

The rapid, irreversible mutational event caused by an initiator (chemical or physical agent) that alters the DNA of a cell.

Promotion (Carcinogenesis)

The selective expansion of initiated cells into preneoplastic lesions, requiring repeated or continuous exposure to a promoter, and is typically reversible until a certain threshold.

Progression (Carcinogenesis)

The irreversible stage of carcinogenesis where preneoplastic lesions develop into malignant neoplasms (cancer), acquiring additional DNA/chromosomal damage.

DNA Adducts

Covalent attachments of a chemical to DNA, which can disrupt normal DNA function and are a major risk factor for cancer if not repaired.

p53

A tumor suppressor gene that plays a critical role in DNA repair and preventing uncontrolled cell growth by inducing apoptosis or cell cycle arrest in response to DNA damage.

Ames Test

A widely used in vitro screening test that evaluates the mutagenicity of a chemical by assessing its ability to cause mutations in histidine-deficient Salmonella bacteria.

IARC Group 1 Carcinogen

A classification by the International Agency for Research on Cancer indicating that an agent is 'carcinogenic to humans' based on sufficient evidence (e.g., tobacco, benzene, asbestos).