Who Is at Most Risk of Adverse Health Effects from Overexposure to Nitrates and Nitrites?
Course: WB 2342
CE Original Date: December 5, 2013
CE Renewal Date: December 5, 2015
CE Expiration Date: December 5, 2017
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Infants less than 4 months of age are most at risk of adverse health effects from over exposure to nitrates and nitrites through ingestion of formula diluted with nitrate contaminated water [EPA 2007; WHO 2011a; WHO 2011b].
Although there is no nutritional indication to add complementary foods to the diet of a healthy term infant before 4 to 6 months of age, the American Academy of Pediatrics suggests that home-prepared infant foods from vegetables (i.e. spinach, beets, green beans, squash, carrots) should be avoided until infants are 3 months or older [Greer and Shannon 2005].
Gastroenteritis with vomiting and diarrhea can exacerbate nitrite formation in infants and has been reported to be a major contributor to methemoglobinemia risk in infants independent of nitrate/nitrite ingestion [Lebby et al. 1993; Gebara and Goetting 1994; Avery 1999; Nelson and Hostetler 2003; DeBaun et al. 2011].
In addition, the pregnant woman and her fetus might be more sensitive to toxicity from nitrites or nitrates at or near the 30th week of pregnancy [Gitto et al. 2002; Gordon 2012].
Individuals with glucose-6-phsphate dehydrogenase (G6PD) deficiency may have greater susceptibility to the oxidizing effects of methemoglobinemia inducers.
Infants younger than 4 months of age who are fed formula diluted with water from untested rural domestic wells are especially prone to developing health effects from nitrate exposure [EPA 2007; WHO 2011a; WHO 2011b; Dusdieker and Dungy 1996]. They are more susceptible to developing methemoglobinemia for a number of reasons including:
Infant gut pH
Impaired reduction of MetHb
Infection and inflammatory reactions can increase endogenous synthesis of nitrate in both infants and adults [NRC 1995; Nelson and Hostetler 2003].
These factors combine to place young infants with diarrhea, who are fed formula diluted with nitrate contaminated well water, at the greatest risk for toxicity [Johnson and Kross 1990; Zeman et al. 2002; EPA 2007; WHO 2011a, 2011b].
The pregnant woman and her fetus represent another high-risk group.
Pregnancy is a high oxygen demand physiologic state. Due to the increased intake and utilization of oxygen, increased levels of oxidative stress are reasonably expected. The hematologic changes of pregnancy include a 40-50% increasing blood volume (plasma greater than RBC mass) expansion peaking at around 30 weeks [Gordon 2012]. With plasma volume increasing more than the RBC mass, the maternal hematocrit falls resulting in a "physiologic anemia of pregnancy" reaching a peak at 30 to 34 weeks [Gordon 2012].
Due to oxidative stress, methemoglobin is continually produced within red blood cells, but its levels are kept low (0.5% to 2.5% of total hemoglobin) by enzymatic pathways that work to reduce methemoglobin. Conditions such as pregnancy with its high oxygen demand and increased levels of oxidative stress may overwhelm the body's ability to reconvert methemoglobin back to hemoglobin, resulting in increased methemoglobin levels [Gitto et al. 2002].
Exposure to nitrates also increases oxidative stress and depletes antioxidant reserves. Thus, pregnant women may be more sensitive to the induction of clinical methemoglobinemia by nitrites or nitrates at or near the 30th week of pregnancy when oxidative stress peaks.
Reproductive outcome studies performed at sites with high nitrate levels in the water supply provide some evidence of maternal transfer of nitrate and nitrite [Manassaram et al. 2006; Tabacova et al. 1997 and 1998; Croen et al. 2001].
An increased risk of developing methemoglobinemia from exposure to oxidizing agents has been reported in individuals with coexisting
Genetic factors may increase the risk of drug induced methemoglobinemia and hemolytic anemia [McDonagh et al. 2013].
Recreational drug users are at increased exposure risk, especially users of volatile nitrite inhalers and drugs like cocaine. Cocaine can be adulterated with a variety of substances including phenacetin and local anesthetics like benzocaine [Hunter et al 2011; Flomenbaum et al. 2006] (see Table 2).
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