Chapter 24: Toxic Effects of Solvents

Organic Solvents

Used to dissolve, dilute, or disperse materials insoluble in water.

Petroleum Refinement

Most organic solvents are refined from petroleum.

Lipophilicity

Increases with more carbon and/or halogen atoms in organic solvents.

Volatility of Organic Solvents

Decreases as lipophilicity increases.

Classification of Solvents

Based on molecular structure or functional group.

Determinants of Solvent Toxicity

Include number of carbon atoms, degree of saturation, molecular structure, and functional groups.

Mixed Solvent Toxicity

Toxic effects may be additive; solvents may interact synergistically or antagonistically.

Factors Affecting Health Impact of Solvents

Include toxicity, exposure rate, amount, duration, individual susceptibility, and chemical interactions.

Household Exposure to Solvents

Can occur from inhalation, dermal absorption, and ingestion.

Occupational Exposure to Solvents

Occurs during production, processing, storage, transport, and evaporation processes.

Environmental Exposure to Solvents

Frequently found in air and groundwater, usually at low parts per billion concentrations.

Alveoli

Location in the lungs where inhaled VOCs are absorbed into the blood.

Hydrophilic Solvents in Blood

Dissolve better in blood compared to lipophilic solvents.

First-Pass Elimination

Process where solvents are removed by exhalation during pulmonary circulation.

GI Tract Absorption of Solvents

Solvents are well absorbed; peak blood levels occur within minutes.

Stratum Corneum

Skin's outer layer through which lipophilic solvents penetrate.

Trichloroethylene (TCE)

A solvent commonly found at hazardous waste sites, linked to cancer incidence.

TCE Metabolism

Primarily metabolized in the liver, with toxicities mediated by metabolites.

Methylene Chloride (MC)

A widespread solvent used in various industrial processes and known for respiratory exposure.

MC Absorption

Inhaled MC reaches steady blood concentration within 1-2 hours.

Methylene Chloride Metabolism

Occurs via P450 oxidation and glutathione transferase pathways.

Chloroform

Used in refrigerant production; a probable human carcinogen damaging liver and kidney.

Chloroform in Drinking Water

Occurs as a by-product of water chlorination, often found in low ppb levels.

Carbon Tetrachloride (CCl4)

A previously common solvent, now restricted due to toxicity and environmental concerns.

CCl4 Metabolism

Bioactivation leading to lipid peroxidation, affecting calcium homeostasis.

Benzene

A solvent primarily derived from petroleum; a known carcinogen associated with leukemia.

Benzene Sources of Exposure

Includes gasoline emissions, cigarette smoke, and auto exhaust.

Adverse Effects of Benzene Exposure

Includes hematopoietic toxicity leading to blood cell damage.

Benzene Metabolism

Leads to toxic metabolites contributing to myelotoxicity.

Toluene

Found in paints and fuels; inhalation is the primary exposure route.

Toluene Toxicity Symptoms

Range from dizziness to unconsciousness and respiratory depression.

Solvent Abuse

Inhalation of volatile substances for psychoactive effects, particularly among adolescents.

Styrene

Primarily used in polystyrene manufacture; metabolized to reactive oxides.

Automotive Gasoline Composition

A complex mixture of hydrocarbons with variable toxicity profiles.

Ethanol

Most widely consumed solvent, causing metabolic and absorption differences.

Ethanol Metabolism

Includes oxidation by ADH to acetaldehyde and contributions by CYP2E1 and catalase.

Gender Differences in Ethanol Response

Women generally exhibit higher sensitivity and mortality from alcohol.

Methanol Toxicity

Associated with serious health effects, especially ocular damage from formate.

Methanol Treatment Protocol

Involves sodium bicarbonate, ethanol, or fomepizole to inhibit metabolism.

Ethylene Glycol (EG)

Used in antifreeze and other products; rapidly absorbed and metabolized.

Ethylene Glycol Toxicity Stages

Progresses through intoxication, cardiopulmonary effects, and renal toxicity.

Ethylene Glycol Treatment Goals

Correct acidosis, inhibit metabolism, and remove EG via hemodialysis.

Diethylene Glycol (DEG) Usage

Used in industrial applications, with a lethal dose historically leading to fatalities.

Acute Methanol Poisoning Symptoms

Includes coma, acidosis, and ocular toxicity appearing after a latent period.

Formate's Role in Methanol Toxicity

Inhibits mitochondrial enzymes, leading to vision damage.

Renal Injury Prevention in Ethylene Glycol Poisoning

Ethanol or fomepizole are administered to mitigate kidney damage from metabolism.