Supporting references and summaries are provided in the TEACH database at http://www.epa.gov/teach/

. Last revised 5/22/07: includes research artic les and other information through 2006. Page 1 

# Nitrates and Nitrites

TEACH Chemical Summary

U.S. EPA, Toxicity and Exposure Assessment for Children’s Health This TEACH Chemical Summary is a comp ilation of information de rived primarily from U.S. EPA and ATSDR resources,
and the TEACH Database. The TEACH Databa se contains summaries of research studies pertaining to developmental exposure and/or health effects for each chemical or chemical group. TEACH does not perform any evaluation of the validity or quality of these research studies. Research studies that ar e specific for adults are not included in the TEACH Database, and typically are not described in the TEACH Chemical Summary.



### I. INTRODUCTION

Nitrates and nitrites are chemicals used in fertilizers, in rodenticid es (to kill rodents), and as food preservatives (1-5). Nitrates and nitrites come in va rious forms, but when dried are typically a white or crystalline powder. Nitrate (NO 3 - ) and nitrite (NO 2 - ) are also naturally-occu rring compounds that are a metabolic product of microbial digestion of wastes containing nitrogen, for example, animal feces or nitrogen-based fertilizers (2, 4). Sodium and potassium nitrates are used as fumigants in canisters, which are placed underground in rodent dens and holes, and th en ignited to explode and release gases that kill the rodents (1, 3). Sodium nitrite is a food a dditive that is used as a preservative (4, 5).

Likely exposure pathways for children include inge sting contaminated drinking water, most commonly of concern for private wells (4); a nd foods containing preservatives, par ticularly cured meats such as hot dogs and lunch meats (4-7). Nitrates have also be en detected in fruits and vegetables (6, 8-10).

Exposure to nitrates and nitrites at le vels above health-based risk values (see Section VI in this Chemical Summary) has been reported to have adverse health effects on infants and children. The health effect of
most concern to the U.S. EPA for children is the “blue baby syndrome” (methemoglobinemia) seen most often in infants exposed to nitrate from drinking water used to make formula (11). Infants of ages 0-3 months are at highest risk for blue baby syndrome b ecause their normal intestinal flora contribute to the generation of methemoglobin; older children and adu lts can experience this syndrome, but at higher concentrations of nitrates (2, 4). The blue baby syndrome is named for th e blue coloration of the skin of babies who have high nitrate con centrations in their blood. The ni trate binds to hemoglobin (the compound which carries oxygen in blood to tissues in the body), and results in chemically-altered hemoglobin (methemoglobin) that impairs oxygen deliver y to tissues, resulting in the blue color of the skin (4, 12). The blue coloration can be seen in the lips, nose, and ears in early stages of blue baby syndrome, and extend to peripheral tissues in more severe cases. Reduced oxygenation of the tissues can have numerous adverse implications for the child, th e most severe of which are coma and death (4).

Exposure to higher levels of nitrates or nitrites has been associated with increased incidence of cancer in adults, and possible increased in cidence of brain tumors, leukem ia, and nasopharyngeal (nose and throat) tumors in children in some studies (8, 9, 11, 13-19) but not others (20-29). The U.S. EPA concluded that there was conflicting evidence in the litera ture as to whether e xposures to nitrate or
nitrites are associated with cancer in adults and in children (1, 2).Chemical Summary Form, Nitrates (continued)

Supporting references and summaries are provided in the TEACH database at http://www.epa.gov/teach/

. Last revised 5/22/07: includes research artic les and other information through 2006. Page 2 

### II. EXPOSURE MEDIA AND POTENTIA L FOR CHILDREN’S EXPOSURE 1

Exposure Media Relative Potential for Children’s Exposure 2,3 Basis 4

Diet Higher Use of nitrate fertilizer on crops can result in higher
concentrations in some foods. N itrites and, less often, nitrates are used as preservatives in f oods such as cured meats, for example, bacon and salami. Nitrates have been found in vegetables and some baby f oods that contain vegetables.
Groundwater Medium Nitrates and nitrites in fertilizers readily migrate from fertilized soil to groundwater. Drinking Water Medium For many situations, the potential for children’s exposure from drinking water is medium to lo w. The potential can be higher when private wells become contaminated with nitrates from feed lot and agricultural runoff, and contaminated groundwater. Some geographic ar eas are at higher risk of drinking water contamination of private wells with nitrates.
Sediment Lower Nitrates and nitrites are highly wa ter soluble and therefore less likely to partition to sediment.
Soil Lower Nitrates and nitrites are not retained in soil and quickly partition to any water phase.
Ambient Air Lower Nitrates and nitrites are not volatile and are not generally released into the air. Register ed users of fumigant canisters containing nitrates for killing of rodents follow strict use protocols that limit exposure to fumes from its use.
Indoor Air Lower Nitrates and nitrites are not usuall y released in indoor air. Use
of nitrite or nitrate inhalants from commercial products in the home may be a concern for adolescents.

1 For more information about child-speci fic exposure factors, please refer to the Child-Specific Exposure Factors Handbook ( http://cfpub.epa.gov/ncea/cfm/r ecordisplay.cfm?deid=55145 ).

2 The Relative Potential for Children’s Exposure category reflects a judgment by TEACH Workgroup, U.S. EPA, thatincorporates potential exposure pathways, frequency of exposure, level of exposure, and current state of knowledge. Sitespecific conditions may vary and influence the relative potential for exposure. For more information on how these determinations were made, go to http://www.epa.gov /teach/teachprotocols_chemsumm.html

. 3 Childhood represents a lifestage rather than a subpopulatio n, the distinction being that a subpopulation refers to a portion of the population, whereas a lifestage is inclusive of the entire population.

4 Information described in this column was derived from several resources (e.g., 1-5) including studies listed in the TEACH Database ( http://www.epa.gov/teach ).Chemical Summary Form, Nitrates (continued)

Supporting references and summaries are provided in the TEACH database at http://www.epa.gov/teach/

. Last revised 5/22/07: includes research artic les and other information through 2006. Page 3 

### III. TOXICITY SUMMARY 5, 6

Reduced oxygenation of hemoglobin (methemoglobinemia) has been reported after exposure to nitrateand nitrite-contaminated drinking water; also called the “blue baby syndrome” because of the cyanotic (oxygen-deficient) symptoms that result from the reduced oxygenation of the blood (2, 4). Infants less than 4 months old are the most sensitive popula tion for methemoglobinemia following exposure to nitrates and nitrites, but it doe s occur in older age groups (12, 13, 30-33). Severe methemoglobinemia can lead to coma or death (2, 4).

Other health effects following fetal exposure to elevat ed levels of nitrates in drinking water included intrauterine growth retardation ( 34), increased incidence of Sudden In fant Death Syndrome (SIDS) (35), cardiac defects (36), and increased risk of nervous system defects (37-40).

The U.S. EPA concluded that there was conflicting evid ence in the literature as to whether exposures to
nitrate or nitrites are associated with cancer in adults and in childre n (1, 2). The types of cancers studied included non-Hodgkin’s lymphoma as well as stomach and gastric cancers in adults (11); and brain tumors, leukemia, and nasopharyngeal cancers in children (13-18, 20-25, 28, 29). Maternal (during pregnancy) or child consumption of nitrite-containing meats may be asso ciated with increased incidence of brain tumors in children (for more details, se e Human Exposures and Effects section) (13, 15-17).

A few studies have reported other health effects that are possibly a ssociated with nitrate exposure in children, including increased incidence of childhood diabetes (41), recurr ent diarrhea (42), and recurrent respiratory tract infections (43). Other reported effects of chroni c exposure reported in adults include frequent urination and spleen hemorrhaging (bleedi ng) (2, 4). Acute high dos e ingestion exposure to nitrates can cause abdominal pain, muscle weakness, blood in stools an d urine, fainting, and death (4).

Carcinogenicity Weight-of-Evidence Classification 7 : There is no weight-of-ev idence classification in the U.S. EPA IRIS file available at this time for either nitrates ( http://www.epa.gov/iris/subst/0076.htm ) or nitrites ( http://www.epa.gov/iris/subst/0078.htm ). The World Health Or ganization International Agency for Research on Cancer (IARC) ranked n itrates and nitrites high on the priority list for upcoming review of possible carcinogenic ity of ingested nitrates and nitrites ( http://monographs.iarc.fr/E NG/Meetings/prioritylist.pdf ).

5 Please refer to research article summaries listed in the TE ACH Database for details about study design considerations (e.g., dose, sample size, exposure measurements).

6 This toxicity summary is likel y to include information from workplace or other studies of mature (adult) humans or experimental animals if child-specific information is lacking for the chemical of interest. Summaries of articles focusing solely on adults are not listed in the TEACH Database b ecause the TEACH Database contains summaries of articles pertaining to developing organisms.

7 For recent information pertaining to carcinogen risk assessment during development, consult “Guidelines for Carcinogen Risk Assessment and Supplemental Guidance on Risks from Early Life Exposure” at http://www.epa.gov/cancerguidelines

.Chemical Summary Form, Nitrates (continued)

Supporting references and summaries are provided in the TEACH database at http://www.epa.gov/teach/

. Last revised 5/22/07: includes research artic les and other information through 2006. Page 4 

### IV. EXPOSURE AND TOXICITY ST UDIES FROM THE TEACH DATABASE

This section provides a brief description of human and animal studies listed in the TEACH Database. These descriptions generally include the overall conclusion in each study without evaluation or assessment of scientific merit by TEACH. For more details about doses and exposure levels, query the TEACH Database. Any consideration of adverse events should include an understanding of the relative exposure on a body weight basis. In many cases, exposure levels in animal studies are greater than exposure levels normally encountered by humans.

A

. HUMAN EXPOSURE AND EFFECTS

< Nitrate contamination of drinking water is of special co ncern in agricu ltural areas (4, 12, 30, 44, 45). Nitrate-contaminated drinking water often arises as a result of fertilizers applied to crops, which are
converted to nitrate in th e soil and then seep into groundwater and into private residential wells. Of particular concern is proximity of animal feed lo ts to some groundwater sources of drinking water, which may lead to groundwater contamination with ni trates from run-off from these feed lots (3, 6, 11, 12).

< Nitrates have been measured in foods, and have been detected in vegetables and preserved meats (6- 8, 10, 13, 46, 47), and baby foods (9, 48, 49). Nitrate and nitrite intakes for children in Estonia were
estimated from measures of nitrate and nitrite concentratio ns in meat products (50) and in vegetables (10).

< Nitrates have been detected in breast mil k, and concentrations increased with increasing consumption of nitrates by the mother (51). Nitrates have also been measured in blood and stools of children (46).

< Nitrite exposure of teens from use of nitrite inhalants (e.g., “poppers” also called amyl nitrate, gasoline, shoe polish, halothane, whippets, and spray paints) has been reported in a survey of teens (52) (See Considerations for Decision Making).

< Measurement of methemoglobin con centrations in blood has been used as a biomarker of effect for infants and children (43). Some studies found an association between concentrations of methemoglobin in blood and nitrate exposure ( 33, 53), but other studies did not (45, 54).

< Health effects that were significantly associated with nitrate or nitrit e exposure during pregnancy
include increased incidence of in trauterine growth retardation ( 34), cardiac defects (36), central nervous system defects (37-40), Sudden Infant D eath Syndrome (SIDS) (35), and miscarriage (55).

< The most sensitive health effect endpoint for nitrate exposure is methemoglobinemia in infants, also called “blue baby syndrome”. When humans metaboliz e nitrate, an alternative form of hemoglobin, called methemoglobin, is formed and is detectable in blood. Infants with blue baby syndrome turn blue because their red blood cells, which contain methemoglobin, have a decreased ability to carry oxygen. Blue baby syndrome has been reported following exposure of infants to nitratecontaminated drinking water (12, 30-33) . Infants of ages 0-3 months ar e at higher risk for blue baby syndrome because their normal intestinal flora cont ribute to the generation of methemoglobin; older children and adults can experience this syndrome, but at higher con centrations of nitrates (2, 4).Chemical Summary Form, Nitrates (continued)

Supporting references and summaries are provided in the TEACH database at http://www.epa.gov/teach/

. Last revised 5/22/07: includes research artic les and other information through 2006. Page 5 < The U.S. EPA concluded that there was conflicting ev idence in the literature as to whether exposures
to nitrate or nitrites are associated with cancer in adults and in children (1, 2). Exposures to nitrates or nitrites during pregnancy, and possible associations with incide nce of cancer in children, have been studied. Two studies reported that increased risk of brain tumo rs in children was significantly associated with increased maternal consumpti on of increasing amounts of cured meats (containing nitrates and nitrites) during pregnancy (13, 17).

< Possible associations between childhood nitrat e exposure and cancer have been investigated. Children living in areas with higher nitrate levels in drinking water had higher levels of some forms of chromosomal damage than contro l children living in areas with lowe r nitrate levels (56). In some studies, increased incidence of childhood brain cancer (13, 15-18) and nasopharyngeal cancer (21)
correlated with childhood n itrate exposure in the diet or drin king water, though other studies found
no such correlations for some of the same cancer s (20-27). An association between nitrate exposure
and incidence of childhood leukemias was found in one study (57) but not in two others (28, 29). Living in areas with high nitrate levels in dr inking water during childhood was associated with a higher incidence of testicular cance r (58) or urothelial cancer (a sp ecific cancer of the urogenital tract) (23).

< Effects on other systems in humans have been a ssociated with childhood e xposure to nitrates or nitrites (41-43, 59-62). Exposure of ch ildren to nitrates or nitrites was associated with increased incidence of childhood diabetes in one study (41), but not others (59-61). Single studies have reported associations between children’s exposure to nitrates or nitrites, a nd recurrent respiratory tract infections (43) , increased risk for thyroid disorders duri ng adulthood (59), or recurrent diarrhea (42).

B. EXPERIMENTAL ANIMAL EXPOSURE AND EFFECTS

< Several experimental animal studies of health effects following prenatal exposure to nitrates or nitrites have been reported (all studies summarized here involved exposure via maternal ingestion). Results of studies of teratogenic effects in offs pring following maternal e xposure to nitrates or nitrites during pregnancy were equivocal. For exampl e, adverse effects were observed in offspring following prenatal exposure, includi ng delays in brain developmen t in the hippocampal region (63), decreased fetal weight gain (64, 65), increased feta l mortality (64), and delayed acquisition of certain behaviors (66). However in other studies, prenatal exposure result ed in no observable teratogenic effects following prenatal exposure to nitrate (67, 68) or nitrite (67, 69).

< Effects of prenatal exposure of mice to nitrites on the hematopoietic (blood cell formation) system revealed increased liver hematopoies is in fetuses in one study (70). The liver is a major organ for blood cell development in fetuses. In another study, increased levels of methemoglobin were observed in pregnant mothers but not their fetuse s following prenatal exposure to nitrite (71).Chemical Summary Form, Nitrates (continued)

Supporting references and summaries are provided in the TEACH database at http://www.epa.gov/teach/

. Last revised 5/22/07: includes research artic les and other information through 2006. Page 6 < Prenatal exposure to mixtures of sodium nitrite with other chemicals may ha ve different effects than each chemical alone. For example, sodium nitrite administered together with ethylurea induced malformations in fetuses, including eye, brain, kidney, and skeletal defects; such malformations were not induced by administration of either chemi cal alone in this study (72). Increased incidence of brain tumors was observed in hamster offspring following concurrent matern al exposure to nitrite and ethylurea during pregnancy (73, 74). Nitrite and ethylurea are though t to chemically react in the gastrointestinal tract to form the potent carcinoge n, ethylnitrosourea (73). Female offspring had a higher incidence of tumors than male offspring (74).



### V. CONSIDERATIONS FOR DECISION-MAKERS

T

his section contains information that may be useful to risk assessors, parents, caregivers, physicians, and other decisionmakers who are interested in reducing the exposure and adverse health effects in children for this particular chemical. Information in this section focuses on ways to reduce exposure, assess possible exposure, and, for some chemicals,
administer treatment.

< The most likely exposure pathways for children are ingestion of contaminated drinking water and ingestion of food containing preservatives, su ch as cured meats and hot dogs (2, 4, 5).

< General consumer information on preservatives in food is available from the U.S. FDA (75, 76).

< Some nitrites in household produc ts have been used as inhalant s by adolescents and adults to enhance sexual performance, and are commonly called “poppers” (77). Compounds include amyl, butyl, isobutyl, and cyclohexyl nitrites, and are of ten sold in small brown bottles and labeled as "video head cleaner," "room odorizer," "leather cleaner," or "liquid aroma" (77).

< The U.S. EPA Oral Reference Dose (RfD) and the Maximum Contaminant Level (MCL) for drinking water (see Toxicity Reference Valu es in this document) are set to prevent methemoglobinemia in infants, the most se nsitive health endpoint in children (78).

< The MCL is 1 mg/L for nitrites and 10 mg/L for nitr ates in drinking water. As a potential health effect, the U.S. EPA states that, “Infants below the age of six months w ho drink water containing
nitrate in excess of the MCL coul d become seriously ill and, if untreated, may die” (78). The U.S. EPA makes the same statement for nitrite in water (78).

< Caregivers may consider an alte rnate water supply, e.g. bottled wa ter, where nitrate-contaminated ground water may be impacting drinking water.

< The U.S. EPA regulates public water systems, and does not have the authority to regulate private drinking water wells that serve fewer than 25 people (79). Some states may have rules to protect users of these wells. The U.S. EPA urges owners of private wells to have their well water tested annually and more often if some one in the household is pregnant or nursing. The U.S. EPA urges
owners to test their well wate r for nitrate concentrations and several other contaminants (80).

< Nitrates are not filtered out of drinking water using filtration de vices that utilize only carbon or
activated carbon filtration. Nitrates can be filtered from drinking water using ion exchange, reverse osmosis, or electrolysis methods (81).Chemical Summary Form, Nitrates (continued)

Supporting references and summaries are provided in the TEACH database at http://www.epa.gov/teach/

. Last revised 5/22/07: includes research artic les and other information through 2006. Page 7 < A Nitrate/Nitrite Toxicity Case Study in Environmental Medicine is available from the U.S. Agency for Toxic Substances and Diseases Registry (A TSDR), which provides clinical information for physicians on the diagnosis and treatment of nitrate and nitrite toxicity. Detail s of a case study of a 2 month-old infant with blue baby syndrome is included (4).

< Consult the “Child-Specific Exposure F actors Handbook,” EPA-600-P-00-002B, for factors to assess children’s drinking water consumption rate s (82). An updated External Draft of the 2006 version of this handbook is available (83).



### VI. TOXICITY REFERENCE VALUES

Oral/Ingestion

U.S. EPA Reference Dose (RfD) for Chronic Oral Exposure:

Nitrate, 1.6 mg/kg-day, based on th e critical effect of early clin ical signs of methemoglobinemia in infants (excess of 10%) 0-3 months of age exposed to nitrate in infant formula ( http://www.epa.gov/iris/subst/0076.htm , I.A.I.) (11). Last agency verification date 8/22/90.

Nitrite, 1E-1 (or 0.1) mg/kg-day, based on meth emoglobinemia in infants chronically exposed to nitrite in drinking water ( http://www.epa.gov/iris/subst/0078.htm , I.A.I.) (84). Last agency
verification date 2/26/86.

U.S. EPA Drinking Water Ad visories (4 kg child):

Nitrate, 1 day=10 mg/kg and 10 day=10 mg/kg;

Nitrite, 1 day=1 mg/kg and 10 day=1 mg/kg ( http://www.epa.gov/ost/drinki ng/standards/dwstandards.pdf , p. 9) (85). Last revised Winter,
2006.

U.S. EPA Maximum Contaminant Le vel (MCL) for Drinking Water:

Nitrate, 10 mg/L; nitrite, 1 mg/L.

Both are based on potential health effects of shortness of breath and blue baby syndrome in infants ( http://www.epa.gov/safewater/mcl.html#mcls ) (86). Last revised 7/02.

U.S. EPA Maximum Contamin ant Level Goal (MCLG):

Nitrate, 10 mg/L; nitrite, 1 mg/L.

Both are based on potential health effects of shortness of breath and blue baby syndrome in infants ( http://www.epa.gov/safewater/mcl.html#mcls ) (86). Last revised 7/02.Chemical Summary Form, Nitrates (continued)

Supporting references and summaries are provided in the TEACH database at http://www.epa.gov/teach/

. Last revised 5/22/07: includes research artic les and other information through 2006. Page 8 

### V II. U.S. FEDERAL REGU LATORY INFORMATION

< The reference value, U.S. EPA Drinking Water Advi sory for a 4 kg Child, for both nitrate and nitrite were recently revised. The 1-day and 10-day values for nitrate are both 10 mg/kg, and for nitrite are both 1 mg/kg (see Toxicity Reference Values).

< The U.S. EPA regulates drinking water for public water systems and drinking water wells that serve at least 25 people (79); information is avai lable for owners of private wells (80).

< Nitrite and nitrate are listed as number 216 and 219 respectively out of 275 chemicals on the 2005 Priority List of Hazardous Substances for the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) s ection 104 (i), as amended by the Superfund Amendments and Reauthorization Act (SARA). This is a list in the order of priority of concern of substances most commonly found at sites listed on the National Pr iorities list (NPL ); there are currently 275 substances on this list (87).

< The U.S. EPA requires reporting of quantities of certain chemicals that exceed a defined reportable quantity, and that quantity varies for different chemicals. U nder the Emergency Planning and Community Right-to-Know Act (EPCRA) Section 313 “Toxic Chemicals,” quantities of nitrate compounds (water soluble) or s odium nitrite greater than 25,000 pounds manufactured or processed, or greater than 10,000 pounds otherwis e used, is required; under th e Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) , reporting releases of sodium nitrite of any quantity exceeding 100 pounds is required (88).



### VIII. BACKGROUND ON CHEMICAL

A. CAS Number: Nitrate 14797-55-8; Nitrite 14797-65-0.

B. Physicochemical Properties: Nearly all nitrate and nitrite salts are soluble in water, and occur as a whitish powder when not dissolved in water (5). Go to the National Library of Medicine ChemID Web site ( http://chem.sis.nlm.nih.gov/chemidplus ) and search for nitrate or nitrite.

C. Production: Fertilizers comprise the majority of envi ronmental releases of inorganic sources of nitrates (5). Total U.S. reported releases of nitrate compounds totale d over 291 million pounds in 2005 (89).

D. Uses: Primary sources of organic nitrates in the environment include human sewage and livestock manure (5). Sources of inorganic nitrates in the environment include potassium nitrate and ammonium nitrate, which may leach to ground wa ter and contaminate private reside ntial drinking water wells (3, 5). Potassium nitrates are mainly used as fertilizers and may also be used in heat transfer salts, glass and ceramics, rodenticides, and in matches and firework s (2). Ammonium nitrates are mostly used as fertilizers, but also in explosives and blasting agents (2).Chemical Summary Form, Nitrates (continued)

Supporting references and summaries are provided in the TEACH database at http://www.epa.gov/teach/

. Last revised 5/22/07: includes research artic les and other information through 2006. Page 9 E. Environmental Fate: Nitrates are very mobile in soil and have a high potential to migrate to ground water due to high solubility in water and weak retention by soil ( 3, 5). Nitrates and nitrites do not volatilize and therefore are likely to remain in wate r until consumed by plants or other organisms (3). Ammonium nitrate is taken up by bacteria, and nitrat e degradation is fastest under anaerobic conditions (5). Nitrite is easily oxidized to nitrate, and ni trate is the more predominant compound of the two detected in groundwater (4).

Additional information on nitrates and nitrites is avai lable in the TEACH Databa se and at the following
Web sites: www.epa.gov/iris/subst/0076.htm www.epa.gov/iris/subst/0078.htm www.epa.gov/safewater/dwh/c-ioc/nitrates.htmlChemical Summary Form, Nitrates (continued)

Supporting references and summaries are provided in the TEACH database at http://www.epa.gov/teach/

. Last revised 5/22/07: includes research artic les and other information through 2006. Page 10 

### REFERENCES

1. U.S. Environmental Protection Agency. 1991. "R eregistration Eligibility Decision: Inorganic Nitrate/Nitrite (Sodium a nd Potassium Nitrates)." http://www.epa.gov/oppsrrd1/ REDs/old_reds/4052red.pdf

. 2. U.S. Environmental Protection Agency Ground Water and Drinking Water. 2006. "Consumer
Factsheet on: Nitrates/Nitrites." http://www.epa.gov/safewater/ dwh/c-ioc/nitrates.html

. 3. U.S. Environmental Protection Agency Pestic ides and Toxic Substances. 1991. "R.E.D. Facts: Inorganic Nitrates/Nitrite (Sodi um and Potassium Nitrates)." http://www.epa.gov/oppsrrd1/ REDs/factsheets/4052fact.pdf

. 4. U.S. Agency for Toxic Substances and Diseas es Registry. 2001. "Case St udies in Environmental Medicine: Nitrate/Nitrite Toxicity." http://www.atsdr.cdc.gov/HEC/CSEM /nitrate/docs/nitrate_nitrite.pdf

. 5. World Health Organization. 2006. "International Program on Chemical Safety, Environmental Health Criteria 5: Nitrates, Nitrit es, and N-Nitroso Compounds." http://www.inchem.org/documents/pims/chemical/pimg016.htm

. 6. Laitinen, S., et al. 1993. "Calculated dietary in takes of nitrate and nitrite by young Finns." Food Addit.Contam 10(4):469-477. 7. Reinik, M., et al. 2005. "Nitrites , nitrates and N-nitrosoamines in Estonian cured meat products: intake by Estonian children and adolescen ts." Food Addit.Contam 22(11):1098-1105. 8. Sanchez-Echaniz, J., et al. 2001. "Methemoglobinemia and consumpti on of vegetables in infants." Pediatrics 107(5):1024-1028. 9. Dusdieker, L.B., et al. 1994. "Nitrate in baby foods. Adding to the nitrate mosaic." Arch.Pediatr.Adolesc.Med. 148(5):490-494. 10. Tamme, T., et al. 2006. "Nitrates a nd nitrites in vegetables and ve getable-based products and their intakes by the Estonian population." Food Addit.Contam 23(4):355-361. 11. U.S. Environmental Protection Agency. 1991. "Integra ted Risk Information System (IRIS): Nitrate." http://www.epa.gov/iris/subst/0076.htm

. 12. Knobeloch, L., et al. 2000. "Blue babies and n itrate-contaminated well water." Environ.Health Perspect. 108(7):675-678. 13. Preston-Martin, S., et al. 1996. "M aternal consumption of cured meats and vitamins in relation to pediatric brain tumors." Cancer Epidem iol.Biomarkers Prev. 5(8):599-605. 14. Ward, M.H., et al. 2000. "Dietary exposure to nitr ite and nitrosamines and risk of nasopharyngeal
carcinoma in Taiwan." Int. J.Cancer 86(5):603-609. 15. Pogoda, J.M., and S. Preston-Martin. 2001. "Mater nal cured meat consumption during pregnancy and risk of paediatric brain tumour in offspring: pot entially harmful levels of intake." Public Health Nutr. 4(2):183-189. 16. Sarasua, S., and D.A. Savitz. 1994. "Cured and br oiled meat consumption in relation to childhood cancer: Denver, Colorado (United States). " Cancer Causes Control 5(2):141-148. 17. McCredie, M., et al. 1994. "Anten atal risk factors for malignant brain tumours in New South Wales children." Int.J.Cancer 56(1):6-10. 18. Preston-Martin, S., et al. 1982. "N-Nitroso compounds and childhood brain tumors: a case-control study." Cancer Res. 42(12):5240-5245. 19. Volkmer, B.G., et al. 2005. "Influ ence of nitrate levels in drinki ng water on urological malignancies: a community-based cohort study." BJU.Int 95(7):972-976.Chemical Summary Form, Nitrates (continued)

Supporting references and summaries are provided in the TEACH database at http://www.epa.gov/teach/

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