Top Gene Interactions
- Metabolism: PAH metabolism occurs in all tissues, usually by cytochrome P-450 and its associated enzymes. PAHs are metabolized into reactive intermediates, which include epoxide intermediates, dihydrodiols, phenols, quinones, and their various combinations. The phenols, quinones, and dihydrodiols can be conjugated to glucuronides and sulfate esters; and the quinones can form glutathione conjugates. (L10)
- Uses/Sources: Industrially, naphthalene is used in the production of phthalic anhydride, as a solvent for chemical reactions, as a wetting agent and as a fumigant. Naphthalene is produced industrially via coal tar and naturally with trace amounts of naphthalene being produced by black walnuts, magnolias and specific types of deer.
- Health Effects: Inhalation of naphthalene vapor has been associated with headaches, nausea, vomiting and dizziness. Hemolysis, the abnormal breakdown of red blood cells, may occur following ingestion or sufficient dermal exposure to either naphthalene or to naphthalene-treated fabric. In humans, cataracts and other ocular injury have been reported following acute and chronic occupational exposure to naphthalene. Additional signs of toxicity in children include convulsions and coma. Infants may develop encephalopathy and kernicterus, a form of brain damage, due to the presence of increased levels of methemoglobin, hemoglobin, and bilirubin in their plasma. Naphthalene appears to be mildly carcinogenic. Rats exposed to naphthalene vapors at 10, 30, or 60 ppm for 6 hours a day, five days a week for two years developed respiratory epithelial adenomas and olfactory epithelial neuroblastomas.
- Symptoms: Symptoms of hemolytic anemia include fatigue, lack of appetite, restlessness, and pale skin. Exposure to large amounts of naphthalene may cause confusion, nausea, vomiting, diarrhea, blood in the urine, and jaundice (yellow coloration of the skin).
- Treatment: There is no known antidote for PAHs. Exposure is usually handled with symptomatic treatment. (L10)
- Route of Exposure: Oral (L10); inhalation (L10)
- Carcinogenicity: 2B, possibly carcinogenic to humans. (L135)
- Toxicity: LD50: 490 mg/kg (Oral, Rat) (T29) LD50: >20 g/kg (Dermal, Rabbit) (T29) LD50: 150 mg/kg (Intraperitoneal, Mouse) (T14) LD50: 969 mg/kg (Subcutaneous, Mouse) (T14) LD50: 100 mg/kg (Intravenous, Mouse) (T14)
Mechanism of Action
|Target Name||Mechanism of Action||References|
Cellular tumor antigen p53
Peroxisome proliferator-activated receptor alpha
Cytochrome P450 1A2
Cytochrome P450 1B1
Melanocyte-stimulating hormone receptor
Melanocortin receptor 3
Melanocortin receptor 4
Melanocortin receptor 5
|DNA||The reactive metabolites of PAHs (epoxide intermediates, dihydrodiols, phenols, quinones, and their various combinations) covalently bind to DNA and other cellular macromolecules, initiating mutagenesis and carcinogenesis. (L10, L23, A27, A32)||
Aryl hydrocarbon receptor
|Many PAH's induce the expression of cytochrome P450 enzymes, especially CYP1A1, CYP1A2, and CYP1B1, by binding to the aryl hydrocarbon receptor or glycine N-methyltransferase protein. These enzymes metabolize PAH's into their toxic intermediates. The reactive metabolites of PAHs (epoxide intermediates, dihydrodiols, phenols, quinones, and their various combinations) covalently bind to DNA and other cellular macromolecules, initiating mutagenesis and carcinogenesis. (L10, L23, A27, A32)||