Respiratory Carcinogens

Much of the research into cancer of the respiratory system has been devoted to identifying lung carcinogens. Several chemical mixtures are known to 

Workers in aluminum production, coal gasification, coke production, iron and steel foundries, tar distillation, shale oil extraction, wood impregnation, roofing, road paving, carbon black production, carbon electrode production, chimney sweeping, and calcium carbide production are all exposed to PAHs and are known to have increased rates of lung cancer relative to the general population. I89 90  

Metal machinists, printing press operators, and cotton and jute spinning workers are also at higher risk for lung cancer than the general population. 91 These workers use mineral oils that are complex mixtures of aliphatic and aromatic hydrocarbons. The oils are formulated into end products containing a variety of additives and contaminants. These include nitrosamines, chlorinated hydrocarbons, sulfur, amines, and formaldehyde. 

Workers who process uranium and those employed in atomic power laboratories also are at increased risk for lung cancerJ92-93 These workers are typically exposed to complex mixtures of chemicals and radiation. 

The complexities of the mixtures just described make it difficult to ascribe the increased lung cancer rates to any particular chemical or mixture. All the above exposures are to mixtures of lipophiles and hydrophiles, which have been shown to be associated with unexplained cancer clusters J94l 

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Cigarette smoking is responsible for about 80% of lung cancer cases. Other risk factors include exposure to respiratory carcinogens (e.g., asbestos, benzene), genetic risk factors, and history of other lung diseases (e.g., tuberculosis, pulmonary fibrosis). 

For highly reactive compounds that can readily hydrolyze upon contact with aqueous solutions, volatility can be an important factor. For example, bis(chloromethyl) ether, one of the most potent human respiratory carcinogens, can only be shown to be carcinogenic in animal tests by the inhalational route (Figure 14.3). The chemical readily hydrolyzes when dissolved in aqueous solution. Other notable examples include acylating agents and isocyanates. 

Hoffmann D, Hoffmann I. 1993. Tobacco smoke as a respiratory carcinogen. In Hirsch A, Goldberg M, Martin J-P, et al., eds. Prevention of respiratory diseases. New York, NY Marcel Dekker, Inc., 497-532. 

Hoffmann, D. and E.L. Wynder Environmental respiratory carcinogens in Chemical carcinogens,... 

Nesnow, S., L.L. Triplett, and T.J. Slaga Studies on the tumor initiating, tumor promoting, and tumor co-initiat-ing properties of respiratory carcinogens Carcinogenesis 2716. 

Methanol is not classified as carcinogenic, but can be acutely toxic if ingested 100—250 mL may be fatal or result in blindness. The principal physiological effect is acidosis resulting from oxidation of methanol to formic acid. Methanol is a general irritant to the skin and mucous membranes. Prolonged skin contact with methanol vapor or Hquid can cause dermatitis. Methanol vapor can cause eye and respiratory tract irritation, nausea, headaches, and dizziness. 

Propylene oxide is a primary irritant, a mild protoplasmic poison, and a mild depressant of the central nervous system. Skin contact, even in dilute solution (1%), may cause irritation to the eyes, respiratory tract, and lungs. Propylene oxide is a suspected carcinogen in animals. The LC q (lowest lethal concentration by inhalation in tats) is 4000 mg/kg body weight. The LD q (oral) is 930 mg/kg. The LD q (dermal) is 1500 mg/kg. The TWA (8-h exposure) is 100 ppm and the STEP (15-min exposure) is 150 ppm. 

Succinic anhydride is extremely irritating to the eyes. It causes skin, mucous membranes, and respiratory tract irritation. It may be a sensiti2er. There is no evidence of carcinogenic activity in male or female tats given 50 or 100 mg/kg succinic anhydride (186) the Ames test is negative (187). LD q in rat 1510 mg/kg. There ate no estabflshed exposure limits for ACGIH TLV or TWA. 

Exposure effects Inhalation (general) Respiratory irritation Ingestion Skin/eye irritation Skin and respiratory sensitization Mutagenicity Teratogenicity Carcinogenicity ... 

Carcinogens Cancer-producing agents Skin Respiratory Bladder/urinary tract Liver Nasal Bone marrow Coal tar pitch dust crude anthracene dust mineral oil mist arsenic. Asbestos polycyclic aromatic hydrocarbons nickel ore arsenic bis-(chloromethyl) ether mustard gas. p-naphthylamine benzidine 4-am i nodi pheny lam ine. Vinyl chloride monomer. Mustard gas nickel ore. Benzene. 

Nickel carbonyl Carbonylation of acetylene and alcohols to produce acrylic and methacrylic acids Acute respiratory failure carcinogenic... 

Ethylene oxide <-18 CH, CH, 7 o 429 3.0-100 0.9 1.5 11 Colourless gas at room temperature Irritant to eyes and respiratory tract, and an experimental carcinogen Polymerizes uncontrollably with immense explosive force on contact with certain chemicals (e.g. ammonia)... 

Formaldehyde has been rated as a possible carcinogen by the United States Occupational Safety and Health Act (OSHA) rules and should be handled with due caution. It is also a strong lacrymator and choking respiratory irritant. It irritates the skin, eyes, and mucous membranes [76]. Since it is used for tanning leather, it is obvious that fonnaldehyde has a high potential for reactions with proteins. Formaldehyde gas is flammable and most formalin solutions contain significant amounts of methanol, which is also volatile, toxic, and flammable. 

However, for some type of adverse effects, such as genotoxicity, carcinogenicity, and respiratory sensitization, it may not be possible from present knowledge to define this threshold of activity, so we may conclude that any level of exposure might carry some finite risk. In this case, OELs should be established at levels sufficiently low to avoid risks these are called pragmatic OELs. 

If tlie pollutant causes iui acute non carcinogenic risk, tlie inaximuin one hour concentration is used for C, and tlie acute reference exposure limit is used for tlie REL. Likewise, if tlie pollutant causes a clironic non carcinogenic risk, tlie one year average concentration is used, as is tlie clironic reference exposure limit. In tliis procedure, a Iiazard index is calculated for each pollutant separately, and tlien tlie indices are summed for each toxicological endpoint (i.e., tlie respiratory system, tlie central nervous system, etc.). Finally, tlie total hazard index is tlien compared to a value wliich is considered significant. 

Warning 4,4 -Tetramethyldiaminodiphenylmethane is thought to be carcinogenic [4]. Therefore, the dipping solution should be used if possible (gloves ). It is only in this way that it is possible to guarantee that the spray vapors do not come into contact with the skin or respiratory tract. 

Caution o-Tolidine is very toxic and possibly carcinogenic For this reason the dipping method should be preferred. This is the only way to ensure that the spray mist does not reach the respiratory tract or skin. 

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