6.1: Intro To Toxicology Flashcards by Margaux Amaro

deals with the effects of chemicals found in the workplace

Occupational Toxicology

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Oversees workplace safety and health regulation

Occupational Safety and Health Administration (OSHA)

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standards for specific materials of particularly serious toxicity

Permissible Exposure Limits (PELs)

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Regulatory limits set by OSHA

Permissible Exposure Limits (PELs)

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represent the airborne concentrations of substances that workers can be exposed to on a daily basis without adverse health effects

threshold limit values (TLVs)

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deals with the deleterious impact of chemical pollutants
in the environment, on living organisms

Ecotoxicology

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ability of chemical agent to cause injury/disease in a given situation or setting

Hazard

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expected frequency of the of the occurrence of an undesirable effect arising from exposure to a chemical or physical agent

Risk

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Routes of Exposure

Inhalational > Transdermal Route > Oral

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Water and Soil pollutants are absorbed through?

inhalational, ingestion or transdermal

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An exposure to a toxic substance that is absorbed by the target human or animal results in a

dose

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single exposure or multiple exposure over a brief period of time (e.g. accidental discharge)

Acute Exposure

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single or multiple exposure over a longer period of time (e.g. repetitive handling of chemical)

Chronic Exposure

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What are the Environmental Considerations?

• Degradability, bioaccumulation, transport and
biomagnification

• Poorly degraded chemicals (by abiotic or biotic pathways)
exhibit environmental persistence and can accumulate.

• Persistent organic pollutants (POPs), polychlorinated
biphenyls, dioxins and furans

• Methyl mercury discharges -> neurotoxic

• Lipophilic substances: organochlorine pesticides
bioaccumulate in body fat -> endocrine disruption,
neurological disorders, and carcinogenesis

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[ T or F ]

Poorly degraded chemicals do not exhibit environmental persistence and can’t accumulate

FALSE. they exhibit and can accumulate

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concentrates the chemical in organisms higher on the food chain.

Biomagnification

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True or False:

The pollutants that have the widest environmental impact are poorly degradable; are relatively mobile in air, water, and soil; exhibit bioaccumulation; and also exhibit biomagnification.

Chrew

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• Colorless, tasteless, odorless and non-irritating gas

Carbon Monoxide (CO)

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[T or F]

Carbon Monoxide has teratogenic potential

True that

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What is the Mechanism of Action

• CO combines tightly but reversibly with the oxygen-binding site of hemoglobin (Hb)

• Carboxyhemoglobin

• CO affinity 220x oxygen

• Reduced oxygen transfer to the tissues

• Organs with the highest oxygen demand are most seriously affected (Brain, Heart and Kidneys)

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Clinical Effects of Carbon Monoxide

Symptoms of hypoxia
Psychomotor impairment
Headache and tightness in the temporal area
Confusion and loss of visual acuity
Tachycardia, tachypnea, syncope, and coma
Deep coma, convulsions, shock and respiratory failure

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Carbon Monoxide is aggravated by:

Heavy labor
High Altitude
High Ambient Temperature
Smoking exposure
Cardiorespiratory diseases

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Treatment for Carbon Monoxide

• First step: Remove from source

• Oxygen is the specific antagonist for CO

• High concentrations of oxygen for a short amount of time only

• Hypothermic therapy

• Neuropsychological and motor dysfunction persists
for a long time after treatment

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It is a colorless irritant gas and is generated primarily by the combustion of sulfur- containing fossil fuel

Sulfur Dioxide (SO2)

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The principal source of urban SO2 are:

* Burning of coal * Domestic heating * High-sulfur transportation * Coal-fired power plants

Mechanism of Action [Sulfur Dioxide (SO2)]

* **High solubility of SO2** in moist membranes forms sulfurous acid. * Severe irritant on the eyes, mucous membranes, respiratory tract and skin * **90%** of inhaled form is absorbed in the Upper Respiratory tract causing **Acute Irritant Asthma** * The phenomenon of adapting to **irritating concentrations** has been reported in workers

Clinical Effects and Treatment [ Sulfur Dioxide (SO2) ]

* Eye, nose and throat irritation, **reflex bronchoconstriction** and increased bronchial secretions * **Bronchial Asthma** * **Delayed-onset pulmonary edema** * Treatment: supportive, non-specific

# Identify the air pollutant: * **Brownish** irritant gas associated with fires * Farmers exposed to **fresh silage** * Miners exposed to **diesel equipment** * **Automobile** and **truck traffic emissions**

Nitrogen Oxides (NO2)

What is the Mechanism of Action of Nitrogen Oxides (NO2)?

* Relatively insoluble **deep lung irritant** * Inhalation damages the lung infrastructure that **produces the surfactant** necessary to allow smooth and low-effort lung alveolar expansion

Clinical Effects and Treatment [ Nitrogen Oxides (NO2) ]

* **Silo-Filler’s Disease, Non-allergic Asthma, ”Twitchy-airway disease”** * Acute: Irritation of eyes and nose, cough, mucoid or frothy sputum production, dyspnea and chest pain; Pulmonary edema, fibrotic destruction of terminal bronchioles * Chronic: Emphysematous changes * Treatment: Supportive, non-specific

• Bluish irritant gas naturally found in the earth’s atmosphere • Burning of fossil fuel • Emitted from power plants, motor vehicles and other sources of high heat compounds • high-voltage electrical equipment and air and water purification systems • agriculture

Ozone (O3) and Other Oxides

Mechanism of Action [Ozone (O3) and Other Oxides ]

* Irritant of **mucous membranes** * Produces **upper respiratory tract irritation** to **deep lung irritation** with **pulmonary edema** * Formation of **reactive free radicals**

Clinical Effects and Treatment [ Ozone (O3) and Other Oxides ]

* Shallow, rapid breathing and decrease in pulmonary compliance * Acute: Irritation and dryness to throat, changes to visual acuity, substernal pain and dyspnea, **ARDS** *Chronic: Chronic Bronchitis, Bronchiolitis, Emphysema *Treatment: Supportive, non-specific

What are the 2 solvents?

* Halogenated Aliphatic Hydrocarbons * Aromatic Hydrocarbons

• Halohydrocarbons • found in industrial solvents, degreasing agents and cleaning agents • Carbon tetrachloride, trichloroethylene, chloroform, tetrachloroethylene and 1,1,1-trichloroethane • Most are classified as known or probable human carcinogens • Freon, a fluorinated aliphatic, causes severe damage in the ozone • layer in the trophosphere

Halogenated Aliphatic Hydrocarbons

Clinical Effects [Halogenated Aliphatic Hydrocarbons]

* **Human Carcinogens** - some are associated with renal, prostate and testicular cancer * CNS depression, kidney injury, liver injury, cardiotoxicity, arrythmia * Chronic Exposure in the Workplace: **Impaired memory, peripheral neuropathy** * Treatment: Supportive, non-specific

What are the three types of Aromatic Hydrocarbons

• Benzene • Toluene • Xylene

It is component of gasoline

Benzene

What is the Acute Exposure of Benzene?

* CNS Depression * Nausea * Euphoria * Locomotor Problems * Coma * Vertigo, Drowsiness and headaches

What are the Chronic Exposure of Benzene?

**Bone Marrow Injury** | Aplastic Anemia, Leukopenia, Pancytopenia, Thrombocytopenia

Treatment [ BENZENE ]

Supportive, non-specific

• Methylbenzene • paint thinners, nail polish remover, glues, and correction fluid; explosives • No myelotoxic properties • CNS depressant, skin and eye irritant, fetotoxic • Associated with rapid loss of consciousness, severe fatigue, ataxia

Toluene

# Identify this **aromatic hydrocarbons** * dimethylbenzene * Colorless, **sweet-smelling agent** * Substitute for benzene in solvent degreasing operations * No myelotoxic properties * CNS depressant, skin irritant

Xylene

Different types of Pesticides

* Organochlorine Pesticides * Organophosphorus Pesticides * Carbamate Pesticides * Botanical Pesticides

# Identify the pesticide: * **Aryl, carbocyclic or heterocyclic compounds** with chlorine substituents * Known **endocrine disruptors** in humans and animals * **DDT** – domestic mosquito elimination in malaria-infested regions of Africa * **Long-term effects** poorly understood

Organochlorine Pesticides

Four classes of Organochlorine Pesticides

* DDT (chlorphenothane) and analogs * Benzenehexachlorides * Cyclodienes * Toxaphenes

Mechanism of Action and Clinical Effects [Organochlorine Pesticides]

* MOA: interfere with **inactivation of the sodium channel** in excitable membranes and cause **rapid repetitive firing** in most neurons; calcium ion transport is inhibited * DDT – **Tremor** is the first manifestation * Carcinogenic potential but more long-term studies are required

# Identify this pesticide: * Used against **large variety of pests** * **Direct contact** or via **plant systemic** * Based on warfare chemicals like **sarin, soman and tabun** * Absorbed via the skin, respiratory and GI tract * In the environment, not considered a persistent pesticide

Organophosphorus Pesticides

Mechanism of Action and Clinical Effects [Organophosphorus Pesticides]

* MOA: inhibition of **acetylcholinesterase** through phosphorylation of the esteratic state * **M-U-D-D-L-E-S** * If not reversed, patients will develop **neuromuscular transmission failure** – cardiorespiratory failure, weakness of respiratory muscles and death * Specific treatment and useful antagonists are available (i.e. physostigmine, pralidoximine)

What are the 4 Environmental Pollutants

• Polychlorinated and Polybrominated Biphenyls • Perfluorinated Compounds • Endocrine Disruptors • Asbestos

• Highly halogenated biphenyl compounds • Used for insulation, fire retardancy • Mass production resulted in enormous environmental problems • Very toxic and now banned for use • Food is the major source of PCB Residues in humans • Potent endocrine disruptors; associated with reproductive and teratogenic effects on animal studies • Persists in the environment

Polychlorinated and Polybrominated Biphenyls

• Coolant materials in air-conditioning systems • Used as oxygen-carrying materials in clinical studies • Used as heat-, stain-, and stick-resistant coatings for cookware, fabrics and other materials (i.e. Teflon) • Had deleterious effect in the ozone layer of the atmosphere • Persistent environmental chemical

Perfluorinated Compounds (PFCs)

• Ingested and inhaled by humans • Human half-life is 3 years • Potent endocrine disruptor • Long-term adverse effect on reproductive function, cellular proliferation and other cellular homeostatic mechanisms • Associated with proliferation of breast cancer cells; renal, ovarian,prostate and Non-Hodgkin’s lymphoma • Associated with cholesterol and uric acid abnormalities • Polymer Fume Fever

Perfluorinated Compounds (PFCs)

• Mimic, enhance or inhibit a hormonal action • Estrogen-like or antiandrogenic effects; some affect thyroid functions • Includes plant constituents like phytoestrogens, mycoestrogens • Synthetic forms are industrial chemicals, persistent organochlorine agents (DDT), PCBs and brominated flame retardants • Increasing concerns mainly due to bioaccumulation, toxicity and increasing contamination in the environment

Endocrine Disruptors

• Widely used in industry for over 100 years • Causes progressive fibrotic lung diseases (asbestosis), lung cancer, mesothelioma • Synergistic effect with cigarette smoking and exposure to radon daughters • Mechanism for cancer is not well-defined

Asbestos

# Identify this metal: * Light alkaline metal * Used in ceramics and alloys; computers; dental equipment; devices that requires hardening like missile ceramic nose cones and heat shield tiles in space vehicles * **Inhalational** route * **Human carcinogen (class 1)** * Acute Beryllium Disease and Chronic Beryllium Disease * **rogressive pulmonary fibrosis**

Beryllium (Be)

• Transition metal • Found in nickel cadmium batteries, pigments, low-melting point eutectic materials; in solder; in television phospors; and in plating operations; semiconductors and plastics • Inhaled and ingested • Cadmium Fume Fever • Chronic exposure may lead to progressive pulmonary fibrosis, renal failure • Human Carcinogen (Class 1)

Cadmium (Cd)

* Any material, natural or manufactured, bearing a size of at least one dimension that lies between 1 to 100 nm in size * Gold, silver, cadmium, ceramic, aluminum oxide nanowears, carbon, silicon, and germanium nanotubes, zinc oxide nanocrystal, gold nanowafers, and copper oxide nanocubes * Toxicology profile is fairly novel * The increasing production led to environmental contamination

Nanomaterials

* Inhalational, oral, dermal, parenteral are the routes of exposure * toxicity may be both similar and different from the larger, bulk materials * Can cross cellular membranes, penetrate nuclear material and genetic information * Silica – kidney toxicity * Zinc oxide – hepatocellular damage * Multiwalled carbon nanotubes – cytotoxic in humans * Titanium dioxide – toxic to lungs and other organs

Nanomaterials

Hierarchy of Controls

* elimination * substitution * engineering controls * administrative controls *PPE [ESEAP]

Likelihood that a hazard will cause harm

Risk

Byproduct of incomplete combustion

Carbon Monoxide (CO)