Nitrogen dioxide poisoning

Did You Know?

• Nitrogen dioxide is about 1.5 times heavier than air and during silage storage remains in the silage material.
• Silo-filler's disease is a consequence of exposure to nitrogen dioxide poisoning by farmers dealing with silos; food grains such as corn and millet produce nitrogen dioxide within hours due to anaerobic fermentation.
• Nitrogen dioxide poisoning may alter macrophage activity and immune function, and overexposure may lead to methemoglobinemia.

Signs and symptoms

Nitrogen dioxide poisoning is dangerous to all living things, similar to chlorine or carbon monoxide poisoning. The gas is easily taken in through the lungs, and inhaling it can cause heart failure and sometimes death in severe cases. Tolerance varies by individual and ethnicity, and can be changed by factors like metabolic rate, barometric pressure, and blood disorders, but major exposure can lead to fatal heart failure and a shorter lifespan. High-level exposure inflames the mucous membranes and both the upper and lower respiratory tracts. Symptoms are non-specific and overlap with ammonia, chlorine, or carbon monoxide poisoning, as well as pneumonia or viral infections. Common signs include rhinitis, wheezing, coughing, conjunctivitis, headache, throat irritation, and trouble breathing, which may worsen into nasal fissures, ulcers, or perforation. The patient looks ill, with low blood oxygen and shallow, rapid breaths. Supportive therapy involves removing the person from further exposure. Systemic effects include fever and loss of appetite. Chest X-rays and electrocardiography can show diffuse, bilateral lung infiltrates. No specific lab test exists, but arterial blood gas, methemoglobin, complete blood count, glucose, lactate, and blood smear tests may help. Testing urine or tissue for nitrogen dioxide does not confirm the diagnosis. Chronic poisoning can develop days or weeks after the exposure limit is greatly exceeded, mainly affecting the respiratory tract.

Epidemiology

The EPA has regulations for monitoring nitrogen dioxide levels. Historically, some US states including Chicago, the Northeast corridor, and Los Angeles have had high levels. In 2006, the WHO estimated over 2 million deaths annually from air pollution, with nitrogen dioxide as one of the pollutants; over 50% of the disease from these pollutants occurs in developing countries. An EPA survey suggests 16% of US housing units are sited near an airport, highway, or railroad, exposing approximately 48 million people. A WHO feasibility study reported that daily deaths of 1 to 2% are attributed to ozone exposure above 47.3 ppb, 3 to 5% above 75.7 ppb, and 5 to 9% above 114 ppb. Silo filler's disease is pervasive during harvest seasons. In May 2015, the National Green Tribunal directed Delhi and other Indian states to ban diesel vehicles over 10 years old to reduce emissions. In 2008, the UK Committee on the Medical Effects of Air Pollutants reported air pollution causes about 29,000 deaths in the UK. The WHO urban air quality database estimated Delhi's mean annual PM10 in 2010 as 286 μg/m3 and London as 23 μg/m3; in 2014, Delhi's annual mean PM2.5 in 2013 was 156 μg/m3, while London had 8 μg/m3 in 2010. London's nitrogen dioxide breached the EU standard; in 2013 the annual mean was 58 μg/m3 against a threshold of 40 μg/m3. In March 2015, Brussels took the UK to court for breaching emissions limits at its Aberthaw power station in Wales, which operated under a permit allowing 1200 mg/Nm3, more than twice the 5 mg/Nm3 limit.

Biochemical effects

Chronic exposure to high levels of nitrogen dioxide results in allosteric inhibition of glutathione peroxidase and glutathione S-transferase, enzymes in the mucous membrane antioxidant defense system. This generates free radicals that cause lipid peroxidation in the mucous membrane, leading to oxidative stress. The oxidative stress causes dissociation of the GSTp-JNK complex, oligomerization of GSTP, and induction of the JNK pathway, resulting in apoptosis or inflammation of bronchioles and pulmonary alveoli. In the bloodstream, nitrogen dioxide poisoning irreversibly inhibits erythrocyte membrane acetylcholinesterase, which may lead to muscular paralysis, convulsions, bronchoconstriction, and death by asphyxiation. It also decreases glucose-6-phosphate dehydrogenase, predisposing to hemolysis. Acute and chronic exposure reduces glutathione reductase, an enzyme critical for maintaining the reducing environment of the cell.

Reproductive effects

Exposure to nitrogen dioxide inhibits the production of Sertoli cells in the male reproductive system, retarding sperm cell production. In females, nitrogen dioxide poisoning disrupts the balance of reactive oxygen species, leading to oxidative stress that affects the female reproductive lifespan. This oxidative stress can cause ovulation-induced DNA damage to the ovarian epithelium and is linked to free-radical-induced birth defects, abortions, hydatidiform moles, pre-eclampsia, and endometriosis. Oxidative stress also causes defective placentation, potentially leading to placental hypoxia and reperfusion injury, which may result in endothelial cell dysfunction. Increased oxidative stress from nitrogen dioxide poisoning may lead to ovarian epithelium inflammation and, in severe cases, cancer.