6131 LEC - Industrial and Occupational Agents

Chemical agents play a vital role in many industries and are essential in daily life

• Products such as pharmaceuticals, paints, detergents, and polymers all depend on chemicals.

However, despite widespread use, many chemicals pose significant health risks when handled directly, even if they appear harmless. These adverse health effects may not be immediate,

but can develop after prolonged or repeated exposure.

In fact, chemical agents are

the most prevalent occupational hazard, linked to 41% of work-related diseases. These hazards primarily affect the respiratory and skin systems, and can include occupational cancers (Pourbabaki et al., 2025).

GASES

• Nitrogen Dioxide

• Carbon Monoxide

• Cyanide

 NITROGEN DIOXIDE (NO₂)

• chemistry

• Toxic reddish brown gas; 

• highly reactive strong oxidizing agent; 

 NITROGEN DIOXIDE (NO₂)

forms _ upon contact with water in the respiratory tract, leading to pulmonary irritation

nitric acid

 NITROGEN DIOXIDE (NO₂)

• properties

• Dark brown fuming, low solubility gas

• pungent odor

• irritation occurs only slightly above the TLV

 NITROGEN DIOXIDE (NO₂)

• sources

• Emitted from combustion engines, power plants, welding, and agricultural silos

 NITROGEN DIOXIDE (NO₂)

Exposure from

• structural fires

• gas-shielded [MIG (metal inert gas) or TIG (tungsten inert gas)] welding,

• fuming of nitric acid

• Fermentation of corn silage inside a silo (at its greatest concentration during the first few days after a silo is filled)

 NITROGEN DIOXIDE (NO₂)

• uses

• production of nitric acid and explosives

 NITROGEN DIOXIDE (NO₂) is a

•  brownish-colored, acrid-smelling gas.

NITROGEN DIOXIDE (NO₂)

• mechanism of toxicity

• Formed when corn silage ferments inside a silo

• Part of the irritant gasses with low water solubility

• Exposure time tends to be prolonged

• Would be converted into nitric or nitrous acid

NITROGEN DIOXIDE (NO₂)

• Formed when corn silage ferments inside a silo

• Corn silage is a chopped and fermented whole corn plant

• Result of strong high moisture crops under anaerobic conditions in a structure called silo

NITROGEN DIOXIDE (NO₂)

• Part of the irritant gasses with low water solubility

More effects in the lower respiratory tree

NITROGEN DIOXIDE (NO₂)

• Would be converted into nitric or nitrous acid, causing:

• Alveolar damage

• Pneumonititis

• Pulmonary edema

NITROGEN DIOXIDE (NO₂)

Lung Irritation: 

• NO₂ is a relatively insoluble gas, which allows it to act as a deep lung irritant

NITROGEN DIOXIDE (NO₂)

Free Radical and Acid Formation: 

• It causes direct cellular injury through the generation of free radicals and the formation of acids upon contact with lung moisture

NITROGEN DIOXIDE (NO₂)

Lung Surfactant Damage: 

• Inhalation of this gas damages the lung infrastructure responsible for producing the surfactant necessary for smooth alveolar expansion

 

NITROGEN DIOXIDE (NO₂)

Cellular Targets:

• Type I Alveolar Cells are primarily affected by acute low-to-moderate exposure.

• Type II alveolar cells are also damaged at higher exposure levels.

NITROGEN DIOXIDE (NO₂)

Long-Term effects: 

• Severe damage can impair the replacement of Type I cells, leading to progressive fibrosis, bronchial ablation, and alveolar collapse, resulting in permanent restrictive respiratory disease.

NITROGEN DIOXIDE (NO₂)

Methemoglobinemia: 

NO₂ can also oxidize hemoglobin to methemoglobin, which further compromises oxygen delivery

NITROGEN DIOXIDE (NO₂)

• signs and symptoms

• Wheezing and acute lung injury

• Low water solubility

  • Upper airway symptoms = do not immediately occur

  • Lower airway symptoms =pneumonitis and pulmonary edema

• Acutely high concentrations of NO2

  • Upper airway symptoms

    • Rhinorrhea

    • Coughing

    • Dyspnea

    • Stridor

NITROGEN DIOXIDE (NO₂)

• At low levels (< 10 ppm), symptoms are limited to

• mild cough or nausea.

NITROGEN DIOXIDE (NO₂)

• Higher concentrations may cause

• burning eyes and sore throat.

NITROGEN DIOXIDE (NO₂)

• After a delay of up to 24 hours,

• patients may develop severe chemical pneumonitis, progressive hypoxemia, and pulmonary edema.

NITROGEN DIOXIDE (NO₂)

• Some patients may experience an initial improvement

• before developing bronchiolitis obliterans several days later.

NITROGEN DIOXIDE (NO₂)

• treatment and antidotes

• Removal from the source and ventilation with 100% oxygen.

• Supportive care

• No specific antidote

CARBON MONOXIDE  (CO)

• chemisrty

• Colorless, odorless, non-irritating gas that binds hemoglobin with 200–250x the affinity of oxygen, forming carboxyhemoglobin, thereby impairing oxygen delivery to tissues

CARBON MONOXIDE  (CO)

• properties

an ambient air criteria pollutant regulated by the US Environmental Protection Agency

CARBON MONOXIDE  (CO)

• sources

• By-product of incomplete combustion of carbon-based fuels.

CARBON MONOXIDE  (CO)

other sources

• Exposure from indoor use of internal combustion engines, structural fires; 

• automobile exhaust fumes

• faulty or poorly ventilated charcoal, kerosene, or gas stoves; and, 

• to a lesser extent, cigarette smoke and methylene chloride from paint stripper

CARBON MONOXIDE  (CO)

• uses

industrial chemical synthesis

CARBON MONOXIDE  (CO)

• mechanism of toxicity

• Simple and systemic asphyxiant

• Released from house fires, propane heaters, furnaces, grills, electric generators, and motor vehicle exhaust.

• Binds to hemoglobin with a much greater affinity than oxygen, thus creating carboxyhemoglobin (COHgb)

• Impairs tissue oxygenation

CARBON MONOXIDE  (CO)

• simple asphyxiant

• displaces oxygen from the air

CARBON MONOXIDE  (CO)

• systemic asphyxiant

interferes with the oxygen transportation of hemoglobin and blocks the electron transport chain

CARBON MONOXIDE  (CO)

Hemoglobin Binding: 

• CO is a colorless, odorless gas that combines tightly but reversibly with the oxygen-binding sites of hemoglobin. 

• Its affinity for hemoglobin is approximately 220 times greater than that of oxygen

CARBON MONOXIDE  (CO)

Carboxyhemoglobin Formation: 

• This product is physically incapable of transporting oxygen, thereby reducing the blood's oxygen-carrying capacity

CARBON MONOXIDE  (CO)

Oxygen Dissociation Interference (Bohr Effect): 

• The presence of carboxyhemoglobin further interferes with the release of oxygen from remaining oxyhemoglobin through the Bohr effect, drastically reducing oxygen transfer to tissues.

CARBON MONOXIDE  (CO)

Intracellular Inhibition: 

• may directly inhibit cytochrome oxidase, disrupting cellular respiration, and bind to myoglobin, potentially impairing myocardial contractility

CARBON MONOXIDE  (CO)

Target Organs: 

• Organs with the highest oxygen demands, specifically the brain, heart, and kidneys, are the most severely affected.

CARBON MONOXIDE  (CO)

• signs and symptoms: non specific

• nausea, vomiting, dizziness, confusion, fatigue, chest pain, shortness of breath, and loss of consciousness

CARBON MONOXIDE  (CO)

• most common sx

headache

CARBON MONOXIDE  (CO)

• rare sx

cherry red skin (late finding)

CARBON MONOXIDE  (CO)

• COHgb can be detected by:

• Blood test

• Co-oxymeter = non smokers (<1% -3%) and smokers (<10%)

CARBON MONOXIDE  (CO)

• Symptoms of intoxication are most prominent in organs with

• high oxygen demand, specifically the brain and heart.

CARBON MONOXIDE  (CO)

• Severe exposure can lead to

• syncope, coma, convulsions, and impaired thinking.

CARBON MONOXIDE  (CO)

• In patients with coronary disease,

• it may trigger angina or myocardial infarction, and can progress to arrhythmias, hypotension, and death.

CARBON MONOXIDE  (CO)

• Exposure during pregnancy may lead to

• fetal death.

CARBON MONOXIDE  (CO)

• treatment and antidote

• Immediately initiate high-flow O2 via a non-rebreather mask.

• Hyperbaric oxygen therapy

CARBON MONOXIDE  (CO)

• Hyperbaric oxygen therapy

• Exposing the patient to 100% oxygen at 2 to 3 times the normal, atmospheric pressure.

CARBON MONOXIDE  (CO)

• Hyperbaric oxygen therapy: initiate in patients with

• COHgb level = >25%

• COHgb level (pregnant) = 15% (Increased affinity of fetal hemoglobin for CO)

• Loss of consciousness

• Persistent neurological deficit

• CO exposure for >24 hours

CYANIDE (CN)

• chemistry

• Typically encountered as hydrogen cyanide (HCN) or cyanide salts (NaCN, KCN). 

• Inhibits cytochrome c oxidase in the electron transport chain, blocking cellular respiration.

• Highly toxic chemical

CYANIDE (CN)

• sources

• Electroplating, mining, combustion of plastics, cigarette smoke.

• the active ingredient in the suicide pills taken by spies

CYANIDE (CN)

• Released from:

Burning wool, silk, polyurethane, insulation, particleboard, and rubber products

CYANIDE (CN)

• Found in:

•  apricot pits, cassava root and amygdalinis

• laetrile

CYANIDE (CN)

uses

• Used industrially in metallurgy and chemical synthesis. Cyanide derivatives have limited clinical use.

CYANIDE (CN)

• mechanism of toxicity

• May be immediately considered for patients with occupational exposure

• It is an asphyxiant that blocks cytochrome oxidase and impairs aerobic respiration.

Laetrile

= an unapproved remedy for cancer

CYANIDE (CN)

Cellular Asphyxiant: 

• acts as a chemical asphyxiant by binding to the mitochondrial enzyme cytochrome oxidase (specifically cytochrome aa₃)

CYANIDE (CN)

Oxygen Utilization Blockade: 

• This binding prevents cells from utilizing oxygen for aerobic metabolism, leading to rapid cellular dysfunction and death despite adequate blood oxygenation.

CYANIDE (CN)

Rhodanese Detoxification: 

• Humans possess a mitochondrial enzyme called rhodanese, which effectively detoxifies small amounts of cyanide by converting it into relatively nontoxic thiocyanate

CYANIDE (CN)

Mechanism of Lethality: 

• Toxicity occurs when large, rapidly encountered doses of cyanide overwhelm or saturate the rhodanese enzyme, preventing detoxification and leading to lethal effects.

CYANIDE (CN)

• early signs

headache, nausea, vomiting, altered mental status, mydriasis, tachypnea, and hypertension

CYANIDE (CN)

• Later signs =

• hypoxemia, bradypnea, hypotension, chest pain, cardiac collapse, and seizure

CYANIDE (CN)

• Laboratory work will reveal:

• Severe, refractory lactic acidosis (>10) despite resuscitation

• Anion gap acidosis

• Peripheral venous blood has a partial pressure of oxygen (PO2) of >40

PO2

reflects the amount of oxygen gas dissolved in the blood.

Normal PO2 for venous blood =

30 - 40 mmHg

CYANIDE (CN)

Symptoms typically occur immediately and include headache, nausea, dyspnea, and confusion. Following heavy exposure, the condition can progress rapidly to

syncope, seizures, coma, agonal respirations, and cardiovascular collapse.

CYANIDE (CN)

• Symptoms may be delayed if the cyanide is

• ingested as a salt or if food is present in the stomach, which slows absorption.

CYANIDE (CN)

• Long-term ingestion of cyanogenic glycosides is linked to

• complex neurologic diseases.

CYANIDE (CN)

Konzo,

a condition found in cassava-dependent regions of Africa. This chronic disease differs in mechanism from acute poisoning and is etiologically complex

CYANIDE (CN)

• treatment and antidotes

• Amyl nitrate (inhaled) or sodium nitrate (IV)

• hydroxocobalamin

• sodium thiosulfate

• Amyl nitrate (inhaled) or sodium nitrate (IV)

• To induce methemoglobinemia (MetHb) (Fe2+ > Fe3+)

• Cyanide has a greater binding affinity with methemoglobin.

Amyl nitrate (inhaled) or sodium nitrate (IV)

• CONTRAINDICATION:

• Smoke inhalation and carboxyhemoglobin; worsens hypoxemia.

Amyl nitrate (inhaled) or sodium nitrate (IV)

• Side effects of Nitrites (IV) = CAUTION:

• Profound vasodilation

• Hypotension

• Tachycardia

Hydroxocobalamin

• A vitamin B12 precursor; IV.

• Form a complex with cyanide until it can be:

  • Processed by rhodanese

  • Excreted by the kidneys as Vitamin B12

• Does not cause methemoglobinemia and hypotension 

• Safe, fast, and preferred

Hydroxocobalamin

• side effects

• Nausea, vomiting, pruritus, headache, chromaturia, and erythema

• Sodium thiosulfate

• IV

• A sulfur-group-donating substrate

• Does not cause methemoglobinemia

• Rhodanese uses thiosulfate to convert cyanide into thiocyanate.

Sodium thiosulfate

• side effects

• Nausea, vomiting, hypotension

MAJOR TOXIC METALS

• Lead

• Arsenic

• Mercury

• Cadmium

 LEAD (Pb)

• chemistry

• A heavy metal that disrupts enzyme function by mimicking calcium and zinc; 

• affects heme synthesis and nervous system function

 LEAD (Pb)

• properties

Soft, malleable metal that is obtained chiefly by the primary smelting and refining of natural ores or by the widespread practice of recycling and secondary smelting of scrap lead products

 LEAD (Pb)

• sources

• Lead-based paints, batteries, plumbing, contaminated soil, lead figurines, toys, children’s jewelry, nontraditional medicines, ceramics and glazes, and occupational exposure

 LEAD (Pb)

• uses

• Historically used in pipes, gasoline, and paints.

• Used for weights and radiation shielding; 

• lead alloys are used in the manufacture of pipes; 

• cable sheathing; 

• brass, bronze, and steel; 

• ammunition; 

• solder (predominantly electric devices and older automotive radiators); 

• compounds are also added as pigments, stabilizers, or binders in paints, ceramics, glass, and plastic

 LEAD (Pb)

• mechanisms of toxicity: exerts toxicity in these systems

• nervous system, kidneys, bones, heart, skeletal system, and GI tract.

  • Nephrotoxicity: toxic ATN.

 LEAD (Pb)

• major mechanism of toxicity include

• increased generation of reactive oxygen species, leading to cell damage.

 LEAD (Pb)

Ligand Binding: 

• Lead binds to and alters enzymes and macromolecules by interacting with sulfhydryl, phosphate, or carboxyl ligands

 LEAD (Pb)

Heme Synthesis Inhibition: 

• It blocks the incorporation of iron into protoporphyrin IX and inhibits critical enzymes like aminolevulinic acid dehydratase and ferrochelatase, causing anemia

 LEAD (Pb)

Cation Interference: 

• Lead interferes with the action of essential cations, particularly calcium, iron, and zinc.

 LEAD (Pb)

Oxidative Stress and Signaling: 

• It generates oxidative stress, alters gene expression, and disturbs cell signaling.

 LEAD (Pb)

• Extremely high lead levels can

• precipitate seizures.

 LEAD (Pb)

• Acute poisoning:

• GI symptoms (nausea, vomiting, diarrhea, abdominal pain), hemolysis, and renal failure.

 LEAD (Pb)

• Chronic toxicity:

• abdominal pain, constipation, learning disorders, fatigue, anemia, headaches, neuropathies, and wrist drop.

• Developmental delays, learning disabilities, behavioral problems for children

• Burton lines

• Lead lines

 LEAD (Pb)

ACUTE LEAD EXPOSURE: ingestion

• Ingestion of very large (gram) quantities may cause abdominal pain, hemolytic anemia, toxic hepatitis, and encephalopathy.

 LEAD (Pb)

ACUTE LEAD EXPOSURE: inhalation

• Repeated inhalation of leaded gasoline results in ataxia, myoclonic jerking, hyperreflexia, delirium, and convulsions.

 LEAD (Pb)

CHRONIC  LEAD EXPOSURE

• Chronic exposure is more common than acute poisoning and impacts nearly every organ system.

 LEAD (Pb)

Constitutional

• Patients often experience fatigue, malaise, irritability, insomnia, and weight loss. 

• Gastrointestinal symptoms are marked by cramping abdominal pain (lead colic), nausea, and constipation.

 LEAD (Pb)

Central Nervous System: 

• Effects range from impaired concentration and headache to overt encephalopathy (delirium, seizures, coma). 

• In children, chronic low-level exposure leads to decreased intelligence, stunted growth, andimpaired neurobehavioral development.

 LEAD (Pb)

Peripheral & Cardiovascular: 

• Chronic exposure causes peripheral motor neuropathy, classically manifesting as "wrist drop" (extensor muscle weakness). 

• It is also a significant risk factor for hypertension and cardiovascular mortality.

 LEAD (Pb)

Hematologic: 

• Characterized by normochromic or microcytic anemia, often accompanied by basophilic stippling.