Detection of Ozone-Induced Dna Single Strand Breaks in Murine Bronchoalveolar Lavage Cells Acutely Exposed in Vivo

Haney, Joseph T.; Connor, Thomas H.; Li, Li

doi:10.1080/089583799197122

Inorganic Compounds of Carbon, Nitrogen, and Oxygen

Leikauf,

Bein,

Prows

2023

Patty's Toxicology

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This chapter reviews the toxicology of some of the most commonly encountered chemicals in environmental and occupational settings. Although these chemicals are often generated by industrial processes such as combustion, several are generated by natural processes including endogenous production within the body. These substances are basic to the biological process and therefore life itself. Nonetheless, excessive exposures can be life‐threatening and must be controlled. This chapter is modeled after the excellent, previous chapter in this series written by Michael J. Lipsett, Dennis J. Shusterman, and Rodney R. Beard.

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Inorganic Compounds of Carbon, Nitrogen, and Oxygen

Leikauf¹,

Prows²

2001

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This chapter reviews the toxicology of some of the most commonly encountered chemicals in environmental and occupational settings. Although these chemicals are often generated by industrial processes such as combustion, several are generated by natural processes including endogenous production within the body. These substances are basic to the biological process and therefore life itself. Nonetheless, excessive exposures can be life‐threatening and must be controlled. Carbon monoxide (CO) is a colorless, odorless, and nonirritating gas. Because it can disrupt oxygen transport and delivery throughout the body by interfering with oxygen binding, it is classified as a chemical asphyxiant. A product of incomplete combustion, carbon monoxide can be encountered in many occupations and environments. The combination of a lack of warning properties and widespread exposure makes recognition and prevention of CO intoxication a common problem in industrial hygiene. Since the midnineteenth century, combustion technology has improved considerably, but CO remains a persistent threat to health. Carbon monoxide exposure remains a particular concern for firefighters, who often enter enclosed (and therefore poorly ventilated) spaces in structural fires. Lethal CO concentrations can be encountered during the initial “knockdown” (when materials are actively burning) and subsequent “overhaul” (searching for “hot spots” among smoldering materials) phases of firefighting. Unfortunately, the use of respiratory protective gear is often limited to the early phase of firefighting. Exposure assessments during wildlands (outdoor) firefighters, in contrast to urban fires, often report lower CO concentrations. Among smoke inhalation victims (both fatalities and survivors), CO poisoning is the rule rather than the exception. Vehicular CO exposure can involve virtually any work with or near an internal‐combustion engine. Within residential and commercial buildings, combustion appliances are the principal source of CO exposure. Hundreds to thousands of fatal and nonfatal human CO poisonings occur yearly throughout the United States because of improperly functioning (or inadequately vented) water heaters, furnaces, and kerosene space heaters. Poisonings with influenza‐like symptoms (headaches, nausea, and lightheadedness) are often linked to the use of gas stoves and ovens as space heaters during the wintertime. Another source of indoor CO exposure is entrainment of vehicular exhaust through improper placement of building air intakes. The largest source of CO exposure in the United States is tobacco smoke. An unavoidable source of CO exposure is that produced within the body. In erthyrocytes, normal heme turnover yields porphyrin degradation that releases 0.5–1.0 mL of CO per hour in adults. Carbon dioxide (carbonic acid gas, Dry Ice) is normally present in the atmosphere at concentrations of 0.03% above the ocean and from 0.0325 to 0.06% in urban areas. These concentrations are low in comparison to the 3.8% of exhaled human breath, which can be as high as 5.6% CO 2 . Indoor CO 2 concentrations commonly are used as an indicator of the adequacy of ventilation, because CO 2 can be measured quickly and easily. Low concentrations of CO 2 can induce mild discomfort. The American Society of Heating, Refrigerating and Air‐Conditioning Engineers (ASHRAE) has set a standard recommendation of 0.1% (1000 ppm) CO 2 as a criterion of adequate ventilation. This standard relates the ventilation requirement primarily to the population density in the enclosed space. Such estimates are useful for moisture and odor removal and thermal comfort (heating and cooling), but may not provide adequate ventilation when toxic chemicals are present. Carbon dioxide is used in carbonated beverages and is slightly soluble in water (1.79 v/v) at 0°C (1.0 atm), forming a weakly acidic solution of carbonic acid (H 2 CO 3 ). Ammonia reacts with CO 2 under pressure to form ammonium carbamate, then urea, used in fertilizers and plastics. Carbon dioxide is used in blasting coal, as a refrigerant, to promote growth of plants in greenhouses, in fire extinguishers, and in inflating life rafts and life jackets. Dry ice is used for preserving foods and chemicals, especially during transporation. Incidental uses include chilling aluminum rivets and shrinking cylinder liners or bearing inserts. Industrial exposures occur in the manufacture and use of Dry Ice or enclosed spaces where fermentation processes may have depleted the oxygen with formation of CO 2 . This includes mines, tunnels, wells, the holds of ships, tanks, or vats. Because CO 2 is heavier than air, it collects in wells or tanks and will persist unless ventilated. Exposure to CO 2 can occur when fire extinguishers are operated in confined areas. Nitrogen is the main component of the atmosphere, 78.1% (v/v). Industrially, nitrogen is used for the displacement of O 2 or explosive gases from enclosed spaces such as large (fuel tanks) and small (communications cables and material packaging) vessels. Compressed nitrogen is mixed with oxygen, helium, or other gases for deep‐sea diving. Liquefied nitrogen is used in cryogenic metallurgy (to alter the physical characteristics of metals) and in biomedical research (to quick‐freeze and store tissues and microorganisms). Skin contact with liquid nitrogen can cause a serious burn. At high temperatures, nitrogen will combine with O 2 to form nitrogen oxides, with hydrogen to form ammonia, or with carbon (in the presence of bases or barium oxide) to form cyanide. Nitrogen also can form nitrides in the presence of lithium, barium, silicon, calcium, or strontium. Nitrogen can oxidize explosively with ozone. A simple asphyxiant, nitrogen's main toxicity arises from its ability to displace O 2 and generate an atmosphere that does not support the chemical reactions needed for maintenance of life. The displacement of O 2 can be complete or incomplete, leading to varying degrees of hypoxia. Nitric oxide (nitrogen monoxide, mononitrogen monoxide) and nitrogen dioxide [nitrogen peroxide, nitrogen tetroxide (NTO)] are often found in dynamic equilibrium, Historically, these compounds sometimes have been erroneously described as “nitrous fumes.” Nitric oxide and NO 2 occur naturally by bacterial degradation of nitrogenous compounds and to a lesser extent from fires, volcanic action, and fixation by lightning. NO has been the subject of intense and extensive research in a vast array of fields including chemistry, molecular biology, pharmaceuticals, and gene therapy. Formed endogenously, NO has a physiological role in blood‐flow regulation, thrombosis, and neurotransmission, and a pathophysiological role in inflammation, oxidative stress, and host defense. NO is derived from the amino acid L ‐arginine by five‐electron oxidation catalyzed by NO synthetase (requiring reduced pyridine nucleotides, reduced biopteridines, and calmodulin). The by‐product, citrulline, is recycled back to L ‐arginine. In the bloodstream, NO binds primarily hemoglobin, is converted to NO 3 , and is eliminated in the urine with a half‐life of 5–8 h. The main anthropogenic source of NO x emissions in ambient air is the high temperature combustion of fossil fuels in motor vehicles and industry (especially power plants). Nitrogen oxide exposures have occurred in numerous occupational environments, mainly where fossil fuels are combusted. Combustion of fossil fuels in enclosed or poorly ventilated spaces (e.g., mines or skating rinks) may also produce toxic quantities of NO 2 . It is a common contaminant of indoor air whenever natural‐gas stoves and furnaces are employed. In addition, production, transportation, and use of nitric acid can lead to NO x exposure. In agriculture, NO x is a well‐known hazard and produces a condition known as “silo‐filler's disease.” Microbial degradation of stored silage (such as alfalfa or corn) for use as feed for livestock can produce NO 2 from nitrate in a silo or pit. In nonoccupational settings, NO x exposure is usually greater indoors than outside. A colorless gas with a slightly sweet odor and taste, nitrous oxide (nitrogen protoxide, nitrogen oxide, dinitrogen monoxide, hyponitrous acid anhydride, factitious air, laughing gas) is used primarily as an analgesic and anesthetic in surgery and dental procedures. The major toxicological effect associated with N 2 O is the depletion of vitamin B 12 (cyanocobalamin), which is an essential cofactor in mammals for methionine synthetase and methyl malonyl CoA mutase (a mitochondrial enzyme that converts methylmalonic acid to succinic acid). Oxygen is the most prevalent element in the earth's crust, making up 49.2% by weight. It accounts for 20.95% by volume of the earth's atmosphere, and accounts for approximately 65% by weight of the human body. Industrially, O 2 has many uses, but its greatest importance is the dependence of most life forms on O 2 as a source of cellular energy. Because of this absolute requirement, a major use of O 2 is in the clinical treatment of disorders arising from, or resulting in, a lack of O 2 delivery to the cells. Ozone (triatomic oxygen) is a light blue gas with a characteristic odor (reminiscent to some individuals of an electrical discharge such as lightening). Ozone can be found naturally in the troposphere during electrical storms and in the stratosphere. Background levels of ozone in nonurban areas average about 10–20 ppb and are due mainly to intrusion of stratospheric ozone into the lower atmosphere. Occupational exposures can occur when ozone is used in chemical manufacturing (e.g., lipid ozonolysis, bleaching processes, peroxide production) and the disinfection and deodorization of water. It is a unwanted by‐product of photocopying machines, electric‐arc welding, high voltage electrical equipment, X‐ray generators, mercury vapor lamps, linear accelerators, and indoor ultraviolet sources. Because ozone mistakenly has been thought to be therapeutic, ozone generators periodically are marketed as air fresheners for use in commercial operations (restaurants, bars, childcare centers, and bowling lanes) and in the home.

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