Toxins Associated with Energy Production & Utilization: Naphthalene
Chemical Structure
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Napthalene Poster Final Hollie Migdol

Published on: Mar 3, 2016

Transcripts - Napthalene Poster Final Hollie Migdol

  • 1. Toxins Associated with Energy Production & Utilization: Naphthalene Abstract Introduction Chemical Structure Hollie Migdol, Antonio Machado Department of Environmental & Occupational Health, California State University, Northridge Environmental Fate & Transport Regulations Routes of Exposure Mechanisms of ToxicityToxicological Endpoints Metabolism of Naphthalene Association with Energy Production Naphthalene exposure can be produced by: • Coal tar • Petroleum refining • Burning coal or oil Naphthalene is produced commercially from either coal tar or petroleum. Naphthalene also occurs naturally in fossil fuels such as petroleum and coal, and are produced when organic materials (e.g., fossil fuels, wood, tobacco) are burned.2 • Hydraulic fracturing The EPA is currently conducting a study to determine the impacts on ground water and drinking water from fracking. There are 11 variations of chemicals containing naphthalene that are used in the fracturing. Naphthalene is mainly used as a gelling agent and non ionic surfactant.7 Naphthalene p450 o mEH OH OH = o o OH SG OH o OH OH There are 3 possible routes of exposure to Naphthalene: • Skin absorption- Contact with contaminated soil or water can induce this route of exposure and naphthalene will be absorbed into the blood stream. • Ingestion – Contaminated food can be consumed or accidentally ingested due to the inhalation of. The intestine wall will absorb the compounds through passive diffusion and then will be transported to the liver for further metabolism through the portal vein. • Inhalation- Molecules of naphthalene in the air can be inhaled through the mouth and nose. An inhaled substance may be eliminated from the lung by mucociliary or cough clearance to the gastrointestinal tract, by passive or active absorption into the capillary blood network, or by metabolism in the mucus or lung tissue.16 The general population is exposed to naphthalene mainly by inhalation of ambient and indoor air. Exposure to naphthalene may occur from ingestion of drinking water and/or food, but these exposures are expected to be much less than inhalation exposures for the general population.2 Air Majority of naphthalene entering the environment is through releases from combustion. About 10% of the naphthalene released in the environment is related to coal production and distillation. 92.2% of the naphthalene released into the environment is released into the air. Naphthalene in the atmosphere can be transferred to soil and surface water through deposition, 2-3% of the naphthalene in the air is transmitted to other environmental media.2 Naphthalene is removed from the air through reaction with photochemically produced hydroxyl radicals.2 The half-life of Naphthalene undergoing this reaction is less than one day. Naphthalene reacts with ozone, nitrate radicals and N2O5 while in the atmosphere.1 Soil The biodegradation half-life of Naphthalene in the soil at the depths of 3.3m-12.5m ranges from 18-480 days.6 This is dependent on the the microbial count and oxygen content of the soil. The higher the microbial count in the soil results in a lower biodegradation half-life and the lower the oxygen content of the soil results in the higher biodegradation half-life. The lowest microbial counts are found in finer soils.6 Water About 5% of all Naphthalene entering the environment is released into the water. Some naphthalene (about 60%) from these sources is discharged into surface waters and the remainder is distributed to POTWs. It is likely that volatilization will be an important route of naphthalene loss from water. The half-life of naphthalene in the Rhine River was 2.3 days, based on monitoring data.2 The mean concentration of naphthalene found in the water samples taken from 31 freshwater and estuarine sites adjacent to, nearby, or downstream from potential pollutant sources in Florida was 33 mg/L.12 Naphthalene is rarely detected in drinking water. Chronic Exposure: Hemolytic anemia: Hemolytic anemia is the most frequently reported manifestation of naphthalene exposure in humans.2 Naphthalene exposure may be an important cause of G-6-PD-deficiency-related acute hemolysis.15 Jaundice: Jaundice has been reported in infants and adults after exposure to naphthalene.11 However, the jaundice is a consequence of hemolysis rather than a direct effect of naphthalene on the liver.2 Cataracts: In humans, cataract formation has been associated with exposure to naphthalene.2 Cataracts occurred in 8 of 21 workers employed for 5 years in a dye- producing plant where naphthalene was used.10 • Naphthalene has been reported to induce oxidative stress, resulting in lipid peroxidation and DNA damage in a cultured macrophage cell line, J774A.1.3 • DNA single-strand breaks are caused by naphthalene in hepatic tissues.18 • CPY1A2 was identified as the most effective isoform for naphthalene metabolism. Other p450 enzymes involved are CYP3A4, 2E1, and 2A6. Although CYP3A4 showed generally lower metabolic activity toward naphthalene than CYP1A2. In regards to the secondary metabolism of naphthalene the primary metabolites were analyzed for metabolism by P450 isozymes. CYP1A2 and 2D6, and CYP2A6 and 3A4 were identified as the most efficient isoforms for metabolizing 1-naphthol and dihydrodiol, respectively.5 • Another study used mice with no CYP2F2 showing that CYP2F2 plays a significant role in naphthalene induced lung toxicity but not naphthalene induced nasal toxicity. The loss of CYP2A5 expression led to decreases in the rates of naphthalene metabolic activation by olfactory mucosa microsomes. CYP2A5 plays a role in bioactivation and toxicity of naphthalene in the olfactory mucosa but not in the lung.9 • Naphthalene causes severe dose- and site-selective injury to mouse nonciliated bronchiolar (Clara) epithelial cells. Toxicity is characterized by exfoliation of injured Clara cells into the airway lumen 24 h after exposure. early stages of injury include smooth ER swelling and bleb formation which precede increases in cell membrane permeability after acute naphthalene injury to bronchiolar Clara cells in vivo.17 p450 Excretion Chemical Name Cancer Potency (mg/kg-day)-1 No Significant Risk Level (μg/day) Naphthalene13 0.12 5.8C10H8 Agency2 Regulated Value2 ACGIH TLV(8-hr TWA): 10ppm STEL: 15ppm EPA Air emissions: none allowed Drinking water: DWEL 0.7 mg/L Reportable quantities (Hazardous Waste): 100 lbs. RfD (oral): 2.0 x10-2 mg/kg/day RfD(inhalation):3.0x10-3 mg/m3 NIOSH REL (10-hr TWA): 10ppm STEL: 15ppm IDLH: 250 ppm OSHA PEL (8-hr TWA): 10ppm Acute Exposure: Naphthalene inhalation in humans causes headache, confusion, eye irritation, nausea, and profuse perspiration with vomiting, inflammation of the optic nerve, bloody urine, and edema. Naphthalene ingestion has resulted in abdominal pain, nausea, vomiting, diarrhea, darkening of the urine, irritation of the bladder, and hypothermia.8 Guanine Adduct14 Adenine Adduct14 University of Missouri. 2010. Using Pesticides Safely in the Home and Garden. Available: [accessed 17 December 2013]. Nature. 2003. Nature Reviews- Drug Discovery. Available: [accessed 17 December 2013]. University of Minnesota Amplatz Children's Hospital. 2011. When Your Child Has Hemolytic Anemia. Available: Article/40319 [accessed 17 December 2013]. 1. Atkinson R, Arey J, Zielinska B, Aschmann SM. 1987. Kinetics and Products of the Gas-Phase Reactions of OH Radicals and N2O5 with Naphthalene and Biphenyl. Environ Sci Technol; doi:10.1021/es50001a017 [accessed 17 December 2013]. 2. ATSDR (Agency for Toxic Substances and Disease Registry). 2005. Toxicological Profile for Naphthalene, 1-methylnaphthalene, and 2-methylnaphthalene. Atlanta, GA:U.S. Dept. of Health and Human Services. Available: [accessed 17 December 2013]. 3. Bagchi M, Bagchi D, Balmoori J, Ye X, Stohs SJ. 1998. Naphthalene-Induced Oxidative Stress and DNA Damage in Cultured Macrophage J774A.1 Cells. Free Radical Biology and Medicine 25:137-143. [accessed 17 December 2013]. 4. CALEPA (California Environmental Protection Agency). 2005. No Significant Risk Level (NSRL) for the Proposition 65 Carcinogen Naphthalene. Sacramento, CA:Office of Environmental Health Hazard Assessment. Available: [accessed 17 December 2013] 5. Cho TM, Rose RL, Hodgson E. 2006. In Vitro Metabolism of Naphthalene by Human Liver Microsomal Cytochrome p450 Enzymes. The American Society for Pharmacology and Experimental Therapeutics 34:176-183. [accessed 17 December 2013]. 6. Durant ND, Wilson LP, Bouwer EJ. 1994. Screening for natural subsurface biotransformation of polycyclic aromatic hydrocarbons at a former manufactured gas plant. In: Bioremediation of chlorinated and polycyclic aromatic hydrocarbon compounds (Hinchee RE, Leeson A, Semprini L, et al., eds). Boca Raton: CRC Press, Inc., 457-461. [accessed 17 December 2013]. 7. EPA(Environmental Protection Agency). 2011. Toxicological Review of Naphthalene (CAS No. 91-20-3). Washington, D.C.:U.S. Environmental Protection Agency. Available: [accessed 17 December 2013]. 8. EPA(Environmental Protection Agency). 1998. Plan to Study the Potential Impacts of Hydraulic Fracturing on Drinking Water Resources. Washington, D.C.:Office of Research and Development. Available: [accessed 17 December 2013]. 9. Hu J, Sheng L, Li L, Zhou X, Xie F, D’Agostino J, Li Y, Ding X. 2013. Essential Role of Cytochome p450 Enzyme CYP2A5 in Olfactory Mucosal Toxicity of Naphthalene. American Society for Pharmacology and Experimental Therapeutics; doi: 10.1124/dmd.113.054429 [accessed 17 December 2013]. 10. IARC (International Agency for Research on Cancer). 2002. Some Traditional Herbal Medicines, Some Mycotoxins, Naphthalene and Styrene IARC Monogr Eval Carcinog Risk Hum 82:367–418. [accessed 17 December 2013]. 11. Linick M. 1983. Illness associated with exposure to naphthalene in mothballs—Indiana. MMWR Morbid Mortal Wkly Rep 1983;32:34–35. [accessed 17 December 2013]. 12. Miles CJ, Delfino JJ. 1999. Priority pollutant polycyclic aromatic hydrocarbons in Florida sediments. Bull Environ Contam Toxicol 63:226-234. [accessed 17 December 2013]. 13. NTP. 2000. Toxicology and Carcinogenesis Studies of Naphthalene ((CAS NO. 91-20-3) in F344/N Rats (Inhalation Studies).TR 500. Research Triangle Park, NC:National Toxicology Program. [accessed 17 December 2013]. 14. Saeed M, Higginbotham S, Gaikwad N, et al. 2009. Depurinating naphthalene–DNA adducts in mouse skin related to cancer initiation. Free Radical Biology and Medicine 47:1075-1081. [accessed 17 December 2013]. 15. Sanctucci K, Shah, B. 2000. Association of Naphthalene with Acute Hemolytic Anemia. Academic Emergency Medicine; doi: 10.1111/j.1553-2712.2000.tb01889.x. [accessed 17 December 2013]. 16. Smyth, HDC, Anthony JH. 2011. Pulmonary Drug Metabolism, Clearance, and Absorption. In: Controlled Pulmonary Drug Delivery (Olsson, B eds). New York:Springer, 21-50. [accessed 17 December 2013]. 17. Van Winkle LS, Johnson ZA, Nishio SJ, Brown CD, Plopper CG. 1999. Early events in naphthalene-induced acute Clara cell toxicity: comparison of membrane permeability and ultrastructure. Am J Respir Cell Mol Biol 21:44–53. [accessed 17 December 2013]. 18. Vuchetich PJ, Bagchi D, Bagchi M, Bagchi EA, Hassoun L, Stohs SJ. 1996. Naphthalene-induced oxidative stress in rats and the protective effects of vitamin E succinate. Free Radical Biology and Medicine 21:577-590. [accessed 17 December 2013]. References Conclusion Naphthalene is a common toxin associated with energy production and utilization. This poster is a review of scientific journals and their data pertaining to Naphthalene studies. It follows the pathway of Naphthalene starting from its presence in the environment followed by the possible exposure routes by humans. The research continues to describe the metabolism inside the body, toxicological endpoints, mechanisms of toxicity, current regulations, and the association of Naphthalene with energy production. The main question to be addressed involves determining the mechanism of toxicity with in the body of humans and whether or not Naphthalene has the potential to cause cancer within humans. A current major concern in energy production is the outcome of using toxic chemicals in the process of Hydraulic Fracturing and how they will affect the ground water. This allows for potential exposure to these chemicals for the populations in the areas where Hydraulic Fracturing occurs. The toxicological endpoints of Naphthalene exposure and the mechanisms of toxicity need to be studied further. Although there are no studies that have been able to prove carcinogenesis in humans following Naphthalene exposure, there is clear evidence of carcinogenesis within rat studies. There is also clear evidence that Naphthalene has detrimental effects on DNA and can induce oxidative stress. DNA disruptions and oxidative stress are often associated as contributors to carcinogenesis. With the data collected in this assignment it is safe to assume that Naphthalene exposure will probably cause cancer in humans. Cancer: Naphthalene is possibly carcinogenic to humans (Group 2B).10 The ATSDR reviewed 45 studies and of these studies, 10 found evidence of chromosomal aberrations, gene mutations, recombination abnormalities, or DNA fragmentation. The National Toxicology Program conducted a 2-year study on rats involving the inhalation of naphthalene and determined “clear evidence of carcinogenic activity” based on increased incidences of respiratory epithelial adenoma and olfactory epithelial neuroblastoma of the nose.13 Naphthalene is a polyaromatic hydrocarbon (PAH) made up of two benzene rings attached to one another. PAHs are released into the environment through domestic and industrial incomplete combustion processes. There are some PAHs that are known human carcinogens and many that are possible human carcinogens but require further investigation. Naphthalene is a white solid substance that easily evaporates. It is also known by the names of white tar, tar camphor, mothballs and moth flakes. Its primary uses in the United States is in the production of plastics, dyes, resins, lubricants and fuels. Naphthalene is also used as a pesticide. It naturally occurs in the environment in fossil fuels such as petroleum and coal. Naphthalene is released into the environment through the burning of wood and tobacco products. Majority of the Naphthalene entering the environment is through the air. Following exposure, Naphthalene is metabolically activated by p450 enzymes and undergoes phase I and phase II metabolism. The parent molecule itself does not cause injury to the body but the metabolites that are created during the detoxification process by the body. Further studies are required to determine the process of carcinogenesis for Naphthalene . National Genetics and Genomics Education Centre. 2013. Rosalind Franklin celebrated in a Google doodle. Available: [accessed 17 December 2013]. League of Women Voters of the City of New York. 2012. What is Hydraulic Fracturing. Available: [accessed 17 December 2013]. University of Maryland Medical Center. 2011. Cataracts. Available: [accessed 17 December 2013].

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