Nitroglycerin

CAS RN:55-63-0

Health Effects

0.2.1 SUMMARY OF EXPOSURE
  • 0.2.1.1 ACUTE EXPOSURE
    • A) USES: Nitroglycerin is an organic nitrate that is used as a vasodilator to treat coronary artery disease and heart failure. It is used therapeutically in forms of tablets (sublingual and extended-release), lingual aerosol, transdermal and intravenously. It is also a high explosive and is used occasionally in the production of explosives, smokeless powders, rocket propellants and in combating oil well fires.
    • B) EPIDEMIOLOGY: Nitroglycerin is a commonly prescribed drug and poisoning is relatively uncommon. Occupational exposure mainly occurs via dermal or inhalational exposure.
    • C) PHARMACOLOGY: Its mechanism of action is stimulation of cGMP production, resulting in vascular smooth muscle relaxation. It relaxes veins at low doses and arteries at high doses.
    • D) TOXICOLOGY: Toxicology is an extension of pharmacologic effects. Nitroglycerin is a nitrate, which can be converted to nitrites in the GI tract leading to oxidation of hemoglobin, methemoglobinemia, which may be more common in infants.
    • E) WITH THERAPEUTIC USE
      • 1) ADVERSE EFFECTS: Headache, dizziness, and mild orthostatic hypotension are common adverse effects associated with nitroglycerin. WITHDRAWAL: Abrupt cessation of medical or occupational exposure may cause angina.
      • 2) INDUSTRIAL EXPOSURE (dermal and inhalation): nausea, vomiting, abdominal cramps, headache, confusion, delirium, bradypnea, bradycardia, paralysis, seizures, cyanosis, methemoglobinemia, circulatory collapse and death.
    • F) WITH POISONING/EXPOSURE
      • 1) MILD TO MODERATE TOXICITY: Headache, flushing and orthostatic hypotension with reflex tachycardia can occur.
      • 2) SEVERE TOXICITY: Severe effects may include profound hypotension with tachycardia. Profound and prolonged hypotension can cause end-organ damage including cardiac ischemia, ischemic stroke, liver injury and renal failure. Fatalities are rare, but may occur after circulatory collapse and respiratory failure.
  • 0.2.1.2 CHRONIC EXPOSURE
    • A) WITH POISONING/EXPOSURE
      • 1) After 2 to 4 days of repeated nitroglycerin exposure, tolerance to the vasodilatory activity occurs. Such tolerance may be quickly lost if exposure ceased. Angina and heart attacks can occur if exposure stops suddenly, and deaths have resulted. Nausea and headache can occur upon rechallenge.
        • a) For certain individuals, however, tolerance does not occur and these workers need to be removed from exposure after a trial period of 2 to 3 weeks.
      • 2) Epidemiological studies suggest that the effects of long-term workplace exposure may not be completely reversed upon termination of exposure. Former workers may be at increased risk for cardiovascular diseases.
        • a) Workers who are continuously exposed to nitroglycerin can become dependent on nitroglycerin to maintain a minimum level of coronary flow. In addition, aging of the blood vessels can occur due to the repeated dilation from continuous exposure.
      • 3) Workers exposed to nitroglycerin have reduced tolerance for alcohol.
      • 4) The pharmacological effects of nitroglycerin persist even when it is no longer detectable in the circulation.
      • 5) Digestive troubles, tremors, neuralgia, severe headache, hallucinations, and skin rashes can occur with chronic nitroglycerin poisoning.
    • B) ANIMAL STUDIES suggest that decreased activity of alcohol dehydrogenase leads to decreased rate of alcohol metabolism.
0.2.3 VITAL SIGNS
  • 0.2.3.1 ACUTE EXPOSURE
    • A) WITH POISONING/EXPOSURE
      • 1) Hypotension is common. Bradycardia may occur in predisposed patients; reflex tachycardia may occur. Death occurs secondary to circulatory collapse or respiratory failure.
0.2.4 HEENT
  • 0.2.4.1 ACUTE EXPOSURE
    • A) WITH POISONING/EXPOSURE
      • 1) LOSS OF VISION: A transient loss of vision reportedly occurred before acute toxic effects from nitroglycerin exposure.
      • 2) Miosis and corneal damage occurred after intravenous exposure.
0.2.5 CARDIOVASCULAR
  • 0.2.5.1 ACUTE EXPOSURE
    • A) WITH POISONING/EXPOSURE
      • 1) Hypotension secondary to peripheral vasodilation is common. Bradycardia may be noted due to a central noradrenergic effect.
  • 0.2.5.2 CHRONIC EXPOSURE
    • A) WITH POISONING/EXPOSURE
      • 1) Myocardial ischemia and infarction secondary to rebound vasospasm have been reported in industrial workers. This most often occurs within 2 to 3 days of cessation of exposure in workers chronically exposed to nitroglycerin.
0.2.6 RESPIRATORY
  • 0.2.6.1 ACUTE EXPOSURE
    • A) WITH POISONING/EXPOSURE
      • 1) Respiratory difficulties and death may result from exposure.
0.2.8 GASTROINTESTINAL
  • 0.2.8.1 ACUTE EXPOSURE
    • A) WITH POISONING/EXPOSURE
      • 1) Nausea, vomiting, colicky pain, and diarrhea may occur following overdose.
0.2.9 HEPATIC
  • 0.2.9.1 ACUTE EXPOSURE
    • A) ANIMAL STUDIES: Hepatocellular carcinoma and cholangiofibrosis developed in rats chronically exposed to nitroglycerin in their diet.
0.2.13 HEMATOLOGIC
  • 0.2.13.1 ACUTE EXPOSURE
    • A) WITH THERAPEUTIC USE
      • 1) Nitroglycerin is converted to nitrites in the body which may result in methemoglobinemia. Hemolysis and fever have been reported in G6PD deficient patients treated with isosorbide dinitrate.
  • 0.2.13.2 CHRONIC EXPOSURE
    • A) WITH THERAPEUTIC USE
      • 1) Nitroglycerin induces Heinz body formation, methemoglobinemia (rarely), and anoxia.
0.2.14 DERMATOLOGIC
  • 0.2.14.1 ACUTE EXPOSURE
    • A) WITH THERAPEUTIC USE
      • 1) Contact dermatitis is rarely reported following administration of the ointment or transdermal delivery formulations. Skin flushing is common.
      • 2) Skin irritation may occur with transdermal products, the effects are rarely severe.
  • 0.2.14.2 CHRONIC EXPOSURE
    • A) WITH POISONING/EXPOSURE
      • 1) Irritant dermatitis can occur. Occasionally, allergic dermatitis has been reported.
    • B) WITH THERAPEUTIC USE
      • 1) Irritant dermatitis can occur. Occasionally, allergic dermatitis has been reported.
0.2.18 PSYCHIATRIC
  • 0.2.18.1 ACUTE EXPOSURE
    • A) WITH THERAPEUTIC USE
      • 1) Initial symptoms may be followed by central nervous system disorders as intense as acute mania. Severe poisoning can result in confusion, pugnaciousness, hallucinations and maniacal manifestations.
0.2.20 REPRODUCTIVE HAZARDS
  • A) ISOSORBIDE DINITRATE, ISOSORBIDE DINITRATE AND HYDRALAZINE COMBINATION, and NITROGLYCERIN (brands, Nitro-Dur(R), Rectiv(TM), and Nitromist(R)) are classified as US FDA Pregnancy Category C. ISOSORBIDE MONONITRATE and the nitroglycerin brand, Nitrostat
  • (R) are classified as Pregnancy Category B. There are no adequate and well-controlled studies of nitroglycerin use in pregnant women. In animal studies, dose-related increases in embryotoxicity (mummified pups) were observed in rabbits administered oral isosorbide dinitrate. Increased occurrences of diaphragmatic hernias with decreased hyoid bone ossification were observed among pups when maternal rats were fed a diet including up to 1% of nitroglycerin; however, the increase was not statistically significant. Developmental abnormalities of the musculoskeletal system have been reported in female rats exposed to intraperitoneal nitroglycerine and fetotoxicity has been reported with high dose dermal exposure to nitroglycerine. Isosorbide mononitrate exposures in pregnant rats resulted in stillbirths, decreased maternal weight gain, decreased motor activity, and impaired lactation.
0.2.21 CARCINOGENICITY
  • 0.2.21.1 IARC CATEGORY
    • A) IARC Carcinogenicity Ratings for CAS55-63-0 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):
      • 1) Not Listed
    • B) IARC Carcinogenicity Ratings for CAS87-33-2 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):
      • 1) Not Listed
    • C) IARC Carcinogenicity Ratings for CAS78-11-5 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):
      • 1) Not Listed
    • D) IARC Carcinogenicity Ratings for CAS7297-25-8 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):
      • 1) Not Listed
  • 0.2.21.2 HUMAN OVERVIEW
    • A) At the time of this review, human carcinogenicity studies have not been conducted.
  • 0.2.21.3 ANIMAL OVERVIEW
    • A) Nitroglycerin is a mutagenic agent and an equivocal tumorigenic agent with experimental tumorigenic data.
0.2.22 GENOTOXICITY
  • A) Nitroglycerin was mutagenic in Ames tests conducted at 2 different laboratories (Prod Info NITRO-DUR
  • (R) transdermal infusion system patch, 2014; Prod Info Nitrostat
  • (R) sublingual tablets, 201
    • 4) and produced mutations in S typhimurium at a dose of 50 microgram per well without metabolic activation and 2500 nanomole per plate with activation (RTECS , 2000).
  • B) There was no evidence of mutagenicity of nitroglycerin in the following tests: in vivo dominant lethal assay (male rats treated with doses up to 363 mg/kg/day), orally (Prod Info NITRO-DUR
  • (R) transdermal infusion system patch, 2014; Prod Info nitroglycerin in 5% dextrose intravenous injection, 2014; Clayton & Clayton, 1993), or in ex vivo cytogenic tests in rat and dog cells (Prod Info NITRO-DUR
  • (R) transdermal infusion system patch, 2014; Prod Info nitroglycerin in 5% dextrose intravenous injection, 2014; Prod Info Nitrostat
  • (R) sublingual tablets, 2014).
  • C) There was no evidence of mutagenicity with isosorbide mononitrate in the following tests: in vitro Salmonella test, in human peripheral lymphocytes, in Chinese hamster cells (V79), or in the in vivo rat micronucleus test (Prod Info monoket
  • (R) oral tablets, 2014).
Find more information on this substance at: Hazardous Substances Data Bank , TOXNET , PubMed