2

EXECUTIVE SUMMARY

EPA received a petition (#9E6029) from Ecolab Inc. requesting a tolerance exemption for 

use of nitric acid (CAS Reg No. 7697-37-2) as an inert ingredient in food contact surface 

sanitizing solutions applied in public eating places, dairy processing equipment, and foodprocessing equipment and utensils at a maximum level in the end-use concentration of 1,000 

parts per million (ppm) under 40 CFR Part 180.940 (a). EPA published the notice of filing for 

this petition in the Federal Register on April 7, 2007 (65 FR 18324). No comments were 

received in response to this notice.

Nitric acid is a highly corrosive inorganic acid. In a concentrated form, nitric acid is 

corrosive at the site of contact and does not elicit systemic toxicity. Acute dermal and eye 

exposures to concentrated forms of nitric acid can result in skin burns and irreversible eye 

corrosion. Acute inhalation exposure to nitric acid can result in severe respiratory irritation 

followed by pulmonary edema. Acute ingestion of nitric acid may result in ulceration, 

hemorrhage and perforation of the esophagus and stomach.

The U.S. Occupational Safety and Health Administration (OSHA) Permissible Exposure 

Limit (PEL) for nitric acid as well as the American Conference of Governmental Industrial 

Hygienists (ACGIH) Threshold Limit Value (TLV) for nitric acid is 2 ppm (5 mg/m3

). 

While there are no data on the toxicity of dilute forms of nitric acid following oral exposure, 

the toxicity of dilute nitric acid would be expected to be comparable to the toxicity of the NO3-

anion known as nitrate. 

The following summary of the toxicity of nitrate chemicals are reproduced from the 

Reassessment of the Exemptions from the Requirement of a Tolerance for Ammonium Nitrate, 

Magnesium Nitrate, Sodium Nitrate, and Sodium Nitrite (K. Leifer, EPA 2005), IARC

Monographs on the Evaluation of Carcinogenic Risks to Humans VOLUME 94 Ingested Nitrate 

and Nitrite, and Cyanobacterial Peptide Toxins (2010) and the World Health Organization 

(WHO) are reproduced and referenced in this assessment.

Sodium nitrate is of low oral acute toxicity (toxicity category III-IV) in rodents and rabbits. 

Acute data was not available on the dermal and inhalation routes of exposure, eye and dermal 

irritation, and skin sensitization.

Several studies were available for sodium nitrate. These studies included a 6 week oral 

toxicity range-finding study, chronic/carcinogenicity studies in rodents and a 2-generation 

toxicity study in rabbits. In a 6-week oral toxicity and carcinogenicity studies in F344 rats, 

sodium nitrate was administered in the diet. Signs of toxicity were manifested as decreased body 

weight gain at >5% (approximately 2500 mg/kg/day). In the International Agency For Research 

On Cancer (IARC) Monographs on the Evaluation of Carcinogenic Risks to Humans (Vol 94), 

the carcinogenic potential of sodium nitrate was evaluated in several studies in rodents. In two 

studies in mice, no evidence of carcinogenic activity of sodium nitrate alone was observed in the 

drinking water at concentrations up to approximately 5000 mg/kg/day. In four studies in rats, no 

increased incidence of tumors was observed when sodium nitrate alone was administered in the 
3

drinking water or in the diet at concentrations up to approximately 2500 mg/kg/day. Therefore, 

IARC concluded that there is inadequate evidence in humans for the carcinogenicity of nitrate in 

food or drinking water. Also, there were no treatment related effects observed in the 2-

generation reproduction study in rabbits. The NOAEL in this study was 56.5 mg/kg/day the 

highest dose tested. In addition, the Food and Drug Administration (FDA, 1972a) sponsored 

several reproductive and developmental studies in rodents, hamsters and rabbits treated with 

sodium nitrate. No adverse effects were observed in maternal reproductive parameters nor was 

there fetotoxicity or fetal malformations up to the maximum doses tested in each species (41 

mg/kg/day in mice and hamsters and 66 mg/kg/day in rats and rabbits).

Neurotoxicity studies for sodium nitrates were not available for review. However, there was 

no evidence of potential neurotoxicity in any of the submitted studies. Therefore, sodium

nitrates are not expected to be neurotoxic.

Immunotoxicity studies for sodium nitrates were not available for review. However, there 

was no evidence of potential immunotoxicity in any of the submitted studies. Therefore, sodium

nitrates are not expected to be immunotoxic.

There were three human epidemiological studies available for review. These studies reported 

that cases of infant methemoglobinemia are associated with exposure to nitrate in drinking water. 

The American Public Health Association conducted a survey to identify clinical cases of 

infantile methemoglobinemia that were associated with ingestion of nitrate-contaminated water. 

They concluded that greater incidences of methemoglobinemia were observed in infants 

consuming >1.8 mg/kg/day of sodium nitrate. Methemoglobinemia was not observed in any of 

the studies where infants consumed water containing less than 1.6 mg/kg/day of sodium nitrate. 

Therefore, the chronic reference dose established at 1.6 mg/kg/day was based on the 

concentration of nitrate where methemoglobinemia was not observed in infants, 1.6 mg/kg/day.

Ingested nitrate is rapidly absorbed from the gastrointestinal (GI) tract. It can then be 

detected in blood plasma, saliva and urine. Ingested nitrate is excreted in the urine as urea and 

ammonia. Some of the nitrate is converted to nitrite. According to the World Health 

Organization (WHO Food Additive Series 50 - Nitrate) (see 

http//www.inchem.org/documents/jecfa/jecmono/v50je06.htm). “the formation of nitrite in 

humans is complex, involving uptake of nitrate from food and or water, endogenous synthesis of 

nitrate, secretion of nitrate from blood into saliva, conversion of nitrate to nitrite by bacteria 

present in saliva and reconversion of nitrite to nitrate in blood.”

There was no hazard attributable to a single exposure seen in the toxicity database for sodium 

nitrates. Therefore, nitric acid is not expected to pose an acute risk. 

No residue data were provided for sodium nitrates. In the absence of actual dietary exposure 

data resulting from these uses, the EPA performed a conservative, health protective chronic 

dietary assessment based on conservative, screening level upper-bound estimates of dietary 

exposure to adults and children resulting from dietary food, water and food contact surface 

sanitizing solutions uses. Dietary (food, water, food contact surface sanitizing) exposure does 

not result in chronic dietary risks of concern. Based on the established cRfD (1.6 mg/kg/day) 
4

representing the most sensitive population (infants); the chronic dietary exposure of nitric acid is 

5.63 % of the cPAD for the U.S. adult population and 24 % of the cPAD for children 1-2 years 

old (the most sensitive population). 

Short-term aggregate exposure takes into account short-term residential exposure plus 

chronic exposure resulting from dietary exposure as aforementioned (considered to be a 

background exposure level). Because no short-term adverse effect was identified, nitric acid is 

not expected to pose a short-term risk. 

Intermediate-term aggregate exposure takes into account intermediate-term residential 

exposure plus chronic exposure to food and water (considered to be a background exposure 

level). Because no intermediate-term adverse effect was identified, nitric acid is not expected to 

pose an intermediate-term risk.

Based on the lack of evidence of carcinogenicity in adequate rodent carcinogenicity 

studies, nitric acid is not expected to pose a cancer risk to humans; therefore, a cancer dietary 

exposure assessment was not performed. 

EPA has determined that the FQPA SF can be reduced to 1X since the RfD was derived from 

the NOEL of the critical toxic effect (methemoglobinemia) in the most sensitive human 

population (infants).

Sodium nitrates are not expected to bioaccumulate in soil organisms or aquatic organisms 

due to their high solubility in water and expected low solubility in lipids. Environmental fate 

and ecological effects of concern are not expected from the proposed use pattern of sodium 

nitrate as an inert ingredient in pesticide products.

Under the Safe Drinking Water Act, EPA’s Office of Water has established a Maximum 

Contaminant Level Goal (MCLG) for nitrates of 10 ppm (4.5 mg/kg/day). This MCLG is 

established by EPA’s Office of Water under the Safe Drinking Water Act and represent a 

determination of safe levels of this chemical in drinking water, based solely on possible health 

risks and exposure. Use of sodium nitrate as pesticide inert ingredients would not result in 

drinking water concentrations that would exceed the MCLG. 

Taking into consideration all available information on sodium nitrates, EPA concludes that 

there is a reasonable certainty that no harm will result to the general population or to infants and 

children from aggregate exposure to nitric acid. Therefore, the establishment of an exemption 

from tolerance under 40 CFR 180.940 (a) for residues of nitric acid when used in food contact 

surface sanitizing solutions applied in public eating places, dairy processing equipment, and 

food-processing equipment and utensils at no more than 1000 ppm (0.1% by weight) in the endproduct formulation can be considered safe under section 408 of the FFDCA.

1. BACKGROUND

On July 1, 1999, Ecolab Inc. submitted a petition (9E6029) requesting an amendment to 40 

CFR 180 by establishing an exemption from the requirement of a tolerance for residues of nitric 
5

acid (CAS Reg. No. 7697-37-2), when used as an inert ingredient, at a concentration not exceed 

1000 ppm in food contact surface sanitizing solutions. EPA published the NOF for this petition 

in the Federal Register on April 7, 2000 (65 FR 18324). No comments were received in 

response to this notice. 

There are no existing tolerances or tolerance exemptions for nitric acid.

Nitric acid (21.5%) is approved as an indirect food additive in sanitizing solutions not in 

excess on the minimum amounts required to accomplish the intended technical effect (21 CFR 

178.1010(b)(43) and (c)(19). Sodium nitrates are approved as a direct and indirect food additive, 

food contact surface sanitizer, oxidizing component of explosives and blasting agents.

Since exposure to various nitrate chemicals are more likely than exposure to a strong acid 

such as nitric acid; nitrate chemicals are discussed. Sodium nitrate was reassessed by the Lower 

Risk Pesticide Chemical Focus Group for exemptions from the requirement of a tolerance for 

residues in/on raw agricultural commodities under CFR 180.920 in 2005. It was considered as 

safe under section 408(q) of the FFDCA.

This document provides an assessment of the risk to human health and the environment for 

nitric acid when used as an inert ingredient in food contact surface sanitizing solutions. 

Information utilized from the Reassessment of the Exemptions from the Requirement of a 

Tolerance for Ammonium Nitrate, Magnesium Nitrate, Sodium Nitrate, and Sodium Nitrite (K. 

Leifer, EPA 2005), the IARC Monographs on the Evaluation of Carcinogenic Risks to Humans

VOLUME 94 Ingested Nitrate and Nitrite, and Cyanobacterial Peptide Toxins (2010) and the 

World Health Organization (WHO) is reproduced and referenced in this assessment.

2. Inert Ingredient Profile

Some of the physical and chemical characteristics of nitric acid and sodium nitrate along 

with its structure and nomenclature, are found in Table 1a-b.

Table 1a. Physical and Chemical Properties of Nitric acid

Parameter Value Source

Structure

CAS # 7697-37-2 MSDS

Molecular Weight 63.01

Common Names Nitric acid

Physical State Liquid

Melting Point (°C) 31

Boiling Point (°C) 250

Density (g/cm3) 1.5129

Vapor Pressure (mm Hg) 48

Partition Coefficient (Log -0.21
6

P)

Water Solubility Infinite

Other Solubility

Specific Gravity 1.14

Henry's Law Constant

Table 1b. Physical and Chemical Properties of Sodium nitrate

Parameter Value Source

Structure

CAS # 7631-99-4 MSDS

Molecular Weight 84.99

Common Names Sodium nitrate

Physical State White crystals

Melting Point (°C) 308

Boiling Point (°C) 380

Density (g/cm3) 2.3

Vapor Pressure (mm Hg)

Partition Coefficient (Log 

P) -0.79

Water Solubility 81.5 g/100 mL at 15 C

Other Solubility

Specific Gravity 2.26

Henry's Law Constant

3. Hazard Assessment

The following studies were reproduced and referenced from the Reassessment of the 

Exemptions from the Requirement of a Tolerance for Ammonium Nitrate, Magnesium Nitrate, 

Sodium Nitrate, and Sodium Nitrite (K. Leifer, EPA 2005), the IARC Monographs on the 

Evaluation of Carcinogenic Risks to Humans VOLUME 94 Ingested Nitrate and Nitrite, and

Cyanobacterial Peptide Toxins (2010) and the World Health Organization (WHO).

Toxicity Studies with Sodium Nitrate

Table A.1.1 Acute Toxicity Profile of Sodium Nitrate

Guideline No. Study Type Reference Results

Toxicity 

Category
7

Table A.1.1 Acute Toxicity Profile of Sodium Nitrate

Guideline No. Study Type Reference Results

Toxicity 

Category

Acute Oral - rat Environment Canada;Tech 

Info for Problem Spills: 

Ammonium Nitrate p.59 

(1981) as cited in HSDB

4500 mg/kg/day III

81-1 Acute Oral - mouse Mammalian Toxicity Array 

1982; Corree & Breimer 

1979 as cited in JECFA 

1995

2480-6250

mg/kg/day III-IV

81-1 Acute Oral - rat

4860-9000

mg/kg/day III-IV

81-1 Acute Oral - rabbit

1600 mg/kg/day II

6 week oral-diet-rat

In a range-finding study, Maekawa et al., (1982) conducted a study in which sodium nitrate

was administered in the diet to F344 rats (10/sex/dose) at doses of 0, 1.25, 2.5, 5, 10 and 20% 

(equivalent to 0, 625, 1250, 2500, 5000 or 10 000 mg/kg bw/day). At 20%, all the females and 7 

males died. Bodyweight gain was reduced by greater than 10% in males and females at >10%. 

Also, there was a marked increase in abnormal color of the blood and the spleen due to 

methemoglobin at >10%. 

The ensuing carcinogenicity study was conducted with F344 rats 50 sex/dose at 0, 2.5 or 5% 

(1250 or 2500 mg/kg/day) in the diet for 2 years [equivalent to 0, 1250 or 2500 mg/kg

bw sodium nitrate per day or 0, 910 or 1820 mg/kg bw per day expressed as nitrate ion]. The 

administration of sodium nitrate was stopped at 104 weeks and thereafter tap water and basic diet 

was given in all experimental groups and observation continued until week 123 when all 

survivors were sacrificed. All animals were observed daily and clinical signs, water 

consumption, and mortality were recorded. Body weights were recorded once a week during the 

first 10 weeks of the study then every 2 weeks thereafter. Moribund or dead animals were 

autopsied and examined. Organs and/tissues were prepared for microscopic examination.

Mean body weights were reduced by more than 10% after week 60 in females at 5%. There 

were no treatment related differences observed in clinical signs, mortality rate or water 

consumption or clinical signs when compared to control animals. There was no increase in the 

incidence of tumor formation when compared to controls. The NOAEL was 1250 mg/kg/day 

(2.5%). The LOAEL was 2500 mg/kg/day (5%) based on decrease body weights.

Chronic/Carcinogenicity-Rat

Groups of 15 male and 15 female MRC-derived rats, 8–10 weeks of age, were given

0 or 5 g/L sodium nitrate in the drinking-water for 84 weeks and served as controls in a

study of nitrilotriacetic acid. The animals were killed 20 weeks later. Tumor incidences
8

did not differ between nitrate-treated males and females and the untreated control groups

(Lijinsky et al., 1973a).

Groups of 10 male Sprague-Dawley rats, 2 months of age, received 0 or 4000 mg/L

sodium nitrate in the drinking-water for 14 months. Body weights of the nitrate-treated

group were lower than those of untreated controls. The nitrate-treated rats had a higher

incidence of lung lesions compared with controls (4/4 versus 1/5). The nature of lung

lesions was not described (Chow et al., 1980).

Two groups of locally bred male white rats, weighing 120–140 g [age unspecified],

received daily either a 0.05% solution of N-butyl-N-(4-hydroxybutyl)nitrosamine

(BBNA) in the drinking-water for 30 days alone (18 effective animals) or, after treatment

with BBNA was completed, 4 g/L sodium nitrate also in the drinking-water for 273 days

(34 effective animals). A third group was treated with sodium nitrate alone at the same

dose for 273 days (20 effective animals) and 20 effective animals in the fourth group

served as untreated controls. All surviving rats were killed 10 months after the start of the

experiment. Urinary bladders of all animals were examined histologically. BBNA alone

induced urinary bladder carcinoma in one effective animal (5.6%), papillomas in four

animals (22.2%) and papillary and nodular hyperplasia in eight animals (44.4%).

Combined treatment with BBNA and sodium nitrate resulted in the development of

carcinoma in six (17.6%; P < 0.05), papilloma in five (14.7%) and papillary and nodular

hyperplasia of the urothelium in 22 rats (65%). No morphological changes of the

urothelium were observed in males treated with sodium nitrate alone or in control

animals. No spontaneous tumours of the urinary bladder were reported in historical

controls of this strain of animal. (Pliss & Frolov, 1991).

Chronic/Carcinogenicity-Mice

In a study of the effects of concurrent administration of sodium nitrate and piperazine,

one group of 40 male strain A mice, 7–9 weeks of age, was given 12.3 g/L (equivalent to 12300 

ppm, 12300 mg/kg/day) sodium nitrate in the drinking-water for 25 weeks and was killed 13 

weeks later. Controls were untreated. Other groups were fed piperazine (18.75 g/kg) alone in the 

diet or received piperazine and nitrate. The incidence of lung adenomas did not differ statistically 

between the sodium nitrate-treated mice (7/40), untreated controls (12/37), mice fed piperazine

alone (7/33) or mice fed piperazine and treated with nitrate (15/37). The authors noted

that less than 2.5% of the administered nitrate was reduced to nitrite in vivo in mice

(Greenblatt & Mirvish, 1973).

Groups of 10 male and 10 female ICR mice, 8 weeks of age, were fed an

experimental diet containing 0, 2.5 or 5.0% (equivalent to 3125 or 6250 mg/kg/day) sodium 

nitrate for 2 years. No significant differences in food intake, body weight or tumor incidences

were observed between untreated control and treated animals (Sugiyama et al., 1979).

Reproduction Toxicity Study- Rabbit
9

In a two-generation rabbit study, sodium nitrate was given in the water at concentrations of 8, 

250 or 500 mg/l (approximately 0.9, 28.3 and 56.5 mg/kg/day) for a maximum period of 22 

weeks (Kammerer and Pinault, 1998). Three mating dates were scheduled with stock males on 

weeks 4, 11 and 19. Each dam was allowed to raise the second litter. The offspring received the 

same drinking water from post-partum day 18 until 53 (5 weeks). Pups were weighed at birth 

weaning and at the end of the study, until 5 weeks after delivery. The number of pregnancies 

was comparable among all dose groups. There were no adverse effects noted on litter size and 

pup weights. Post-mortem and histological examinations of liver samples did not reveal 

abnormalities or differences between the groups (Reproduced from OECD SIDS Sodium 

Nitrate). The parental and offspring NOAEL was 56.6 mg/kg/day (the highest dose tested). The 

parental and offspring LOAEL was not established.

The Food and Drug Administration sponsored extensive tests of the reproductive and 

developmental effects of NaNO3 and KNO3 in mice, rats, hamsters and rabbits. Groups of 20-26 

mice, rats or hamsters and 10-13 rabbits were treated by gavage on days 6-15 (mice, rats), days 

6-10 (hamster) or days 6-18 (rabbits) of gestation. Fetuses were delivered by Cesarean section 

and examined for visceral and skeletal malformations. Dose levels (expressed as mg nitratenitrogen) ranged from 0.6-66 mg/kg/day for mice, from 0.3-41 mg/kg/day for rats, from 0.4-66 

mg/kg/day for hamsters and from 0.3-41 mg/kg/day for rabbits. No significant effects were 

detected regarding maternal reproductive parameters (percent pregnant, abortion frequency, 

number of litters), fetotoxicity (percent fetal resportions, live fetuses per dam, average fetal 

weight) or fetal malformations up to the maximum doses administered to each species. These 

studies identify a reproductive/developmental NOAEL of 66 mg nitrate-nitrogen/kg/day for mice 

and hamsters and 41 mg nitrate-nitrogen/kg/day for rats and rabbits (FDA, 1972a, b cited in EPA 

IRIS, 1991).

Epidemiological Data 

Donahoe (1949) reported five cases of moderate to severe cyanosis in infants (age 3-8 weeks) 

in Minnesota and Iowa. The water used to feed the infants was from shallow wells and 

contaminated with bacteria in all cases except one case in which the water was not evaluate. In 

two cases nitrate levels were 50 and 177 ppm (12 and 41 mg nitrate nitrogen/L), respectively. 

This corresponds to doses of 8 and 28 mg nitrate-nitrogen/kg/day.

Bosch et al. (1950) evaluated 139 cases of cyanosis due to methemoglobinemia reported by 

physicians in Minnesota. All of the cases were in young children (ages 8 days to 5 months), with 

90% occurring in infants <2 months of age. The nitrate concentrations were measured in the 

wells (a total of 129) used to supply water to the children with methemoglobinemia. All of the 

wells contained >10 mg/L (approximately 4mg/kg/day) nitrate-nitrogen. Two wells (1.5%) 

contained 10- 20 mg/L (approximately 4- 9 mg/kg/day), although the diagnosis of 

methemoglobinemia was considered questionable in both these cases. There were 25 wells 

(19%) that contained 21-50 mg/L (approximately 9- 22 mg/kg/day), 53 (41%) that contained 51-

100 mg/L (approximately 22- 44 mg/kg/day), and 49 (38%) that contained >100 mg/L 

(approximately 44 mg/kg/day) nitrate nitrogen. Nearly all the wells were shallow with 

inadequate protection from surface contamination. Coliform organisms were detected in 45 of 

51 samples (88%) tested for bacterial contamination.
10

The American Public Health Association conducted a survey to identify clinical cases of 

infantile methemoglobinemia that were associated with ingestion of nitrate-contaminated water

(MRID 48802901). A total of 278 cases of methemoglobinemia were reported. Of 214 cases for 

which data were available on nitrate levels in water, methemoglobinemia did not occur in infants 

consuming water containing <10 mg nitrate-nitrogen/L (1.6 mg nitrate-nitrogen/kg/day). There 

were 5 cases (2%) in infants exposed to 11-20 mg nitrate-nitrogen/L (1.8-3.2 mg/kg/day), 36 

cases (17%) in infants exposed to 21-50 mg/L (3.4-8.0 mg/kg/day), and 173 (81%) in infants 

exposed to >50 mg/L (>8 mg/kg/day). Data on the ages of the infants were not provided

(A.P.H.A Committee. (1949-1950)).

Metabolism

The human body actively synthesizes nitrate. Even if all sources of nitrate could be 

eliminated from the human diet, the human body would continue to actively produce nitrate. 

This endogenous nitrate synthesis occurs due to the formation of nitric oxide in the body. The 

nitric oxide is then oxidized to nitrate. In fact, the concentration of nitrate in excreted urine can 

exceed the concentration of ingested nitrate. The endogenous formation of nitrate, which is 

totally independent of dietary sources of nitrate, complicates our understanding of the 

nitrate/nitrite conversions in the body.

Ingested nitrate is rapidly absorbed from the gastrointestinal (GI) tract. It can then be 

detected in blood plasma, saliva and urine. Ingested nitrate is excreted in the urine as urea and 

ammonia. Some of the nitrate is converted to nitrite. According to the World Health 

Organization (WHO Food Additive Series 50 - Nitrate) (see 

http//www.inchem.org/documents/jecfa/jecmono/v50je06.htm). “the formation of nitrite in 

humans is complex, involving uptake of nitrate from food and or water, endogenous synthesis of 

nitrate, secretion of nitrate from blood into saliva, conversion of nitrate to nitrite by bacteria 

present in saliva and reconversion of nitrite to nitrate in blood.”

Nitrate toxicity is due primarily to its conversion to nitrite, which oxidizes the Fe(+2) form of 

iron in hemoglobin to the Fe(+3) state. This compound (methemoglobin) does not bind to 

oxygen, and thus results in reduced oxygen transport from lungs to tissues. Many adults 

routinely have very low concentrations of methemoglobin in their blood, with typical values 

ranging from 0.5 to 2.0%. Methemoglobinemia can lead to cyanosis (insufficient oxygenation of 

the blood characterized by bluish skin and lips) and, ultimately, death. However, 

methemoglobinemia in adults is rare. Reports on cases of methemoglobinemia indicate that 

causation is due to excessive use of nitrate and nitrites in some food items, contamination during 

manufacturing, contaminated hot-water taps, or accidental ingestion. Healthy adults appear to 

metabolize peak blood concentrations of methemoglobin up to 620 mg/kg-bw within a 24 hour 

time-frame. In its deliberations, WHO considered a level of methemoglobin formation of up to 

5% not to be adverse. The population subgroup of most concern for methemoglobinemia is very 

young infants (generally 0 to 3 months) who have been fed formula mixed with nitratecontaining well water.
11

Table A.1.3. Toxicology Profile for Sodium Nitrate

Guideline No./ Study 

Type

MRID No. (year)/ 

Classification /Doses

Results

6 week oral Toxicity 

Study-rat-diet (rangefinding study)

0, 1.25, 2.5, 5, 10 or 20 % 

(0, 625, 1250, 2500, 5000 or 

10 000 mg/kg bw/day)

NOEL= 5 % (approximately 2500 mg/kg/day)

LOEL= 10 % (approximately 5000 mg/kg/day) based on 

decreased bodyweight gain. 

870.4300

Carcinogenicity - F344 

rats-diet

0, 2.5 or 5% (1250 or 2500 

mg/kg/day)

The NOAEL = 1250 mg/kg/day (2.5%). 

The LOAEL = 2500 mg/kg/day (5%) based on decrease 

body weights.

There was no increased incidence in tumor formation.

870.4300

Carcinogenicity - MRC 

rats-drinking water

0 or 5 g/L (0 or 5000 

mg/kg/day)

There was no increased incidence in tumor formation.

870.4300

Carcinogenicity -Sprague 

Dawley rats-drinking water

0 or 4000 mg/L The NOAEL was not established.

The LOAEL = 4000 mg/L based on an increased incidence 

of lung lesions.

Carcinogenicity -White 

rats-drinking water

0 or 4000 mg/L The NOAEL = 4000 mg/L.

The LOAEL was not established.

No spontaneous tumours of the urinary bladder were 

reported

Carcinogenicity -A strain 

mice-drinking water

0 or 12300 mg/kg/day The NOAEL = 12300 mg/L.

The LOAEL was not established.

The incidence of lung adenomas did not differ statistically.

Carcinogenicity -ICR 

mice-drinking water

0, 2.5 or 5.0% (equivalent to 

3125 or 6250 mg/kg/day)

Two generation Toxicity 

Study-Rabbit

8, 250 or 500 mg/l

approximately 0.9, 28.3 and 

56.5 mg/kg/day

Parental and Offspring NOAELs = 56.5 mg/kg/day.

Parental and Offspring LOAELs were not established.

Reproductive/development

al studies-rats-gavage

0.3-41 mg/kg/day Reproductive/developmental NOAEL= 41 mg nitratenitrogen/kg/day.

Reproductive/development

al studies-mice-gavage

0.6-66 mg/kg/day Reproductive/developmental NOAEL= 66 mg nitratenitrogen/kg/day.
12

Table A.1.3. Toxicology Profile for Sodium Nitrate

Guideline No./ Study 

Type

MRID No. (year)/ 

Classification /Doses

Results

Reproductive/development

al studies-rabbits- gavage

0.3-41 mg/kg/day Reproductive/developmental NOAEL= 41 mg nitratenitrogen/kg/day.

Reproductive/development

al studies-hamsters- gavage

0.4-66 mg/kg/day Reproductive/developmental NOAEL= 66 mg nitratenitrogen/kg/day.

APHA Human 

Epidemiological Survey

MRID 48802901 (1949-

1950)

1.6 - 8 mg/kg/day

NOAEL = 1.6 mg/kg/day.

LOAEL = 1.8-3.2 mg/kg/day based on early clinical signs 

of methemoglobinemia in excess of 10% (0-3 months old 

infants formula).

D. Toxicity Endpoint Selection

Table 1.—Summary of Toxicological Doses and Endpoints for Nitric Acid for Use in Human 

Health Risk Assessment

Exposure/Scenario Point of Departure and 

Uncertainty/Safety 

Factors

RfD, PAD, 

LOC for Risk 

Assessment

Study and Toxicological Effects

Chronic dietary 

(All populations)

NOAEL = 1.6 mg/kg/day 

UFA = 1x

UFH = 1x

FQPA SF = 1x

Chronic RfD = 

1.6 mg/kg/day

cPAD = 1.6

mg/kg/day

APHA Human Epidemiological 

Survey

LOAEL = 1.8-3.2 mg/kg/day based on 

early clinical signs of 

methemoglobinemia in excess of 10% 

(0-3 months old infants formula)

Incidental oral shortterm 

(1 to 30 days)

NOAEL = 1.6 mg/kg/day 

UFA = 1x

UFH = 1x

FQPA SF = 1x

LOC for MOE = 

1

APHA Human Epidemiological 

SurveyLOAEL = 1.8-3.2 mg/kg/day 

based on early clinical signs of 

methemoglobinemia in excess of 10% 

(0-3 months old infants formula)

Incidental oral 

intermediate-term 

(1 to 6 months)

NOAEL = 1.6 mg/kg/day 

UFA = 1x

UFH = 1x

FQPA SF = 1x

LOC for MOE = 

1

APHA Human Epidemiological 

SurveyLOAEL = 1.8-3.2 mg/kg/day 

based on early clinical signs of 

methemoglobinemia in excess of 10% 

(0-3 months old infants formula)

Dermal short-term 

(1 to 30 days)

NOAEL = 1.6mg/kg/day 

(dermal absorption rate = 

100%)

UFA = 1x

UFH = 1x

FQPA SF = 1x

LOC for MOE = 

1

APHA Human Epidemiological 

SurveyLOAEL = 1.8-3.2 mg/kg/day 

based on early clinical signs of 

methemoglobinemia in excess of 10% 

(0-3 months old infants formula)

Dermal intermediateterm

(1 to 6 months)

NOAEL = 1.6mg/kg/day 

(dermal absorption rate = 

100%)

UFA = 1x

UFH = 1x

LOC for MOE = 

1

APHA Human Epidemiological 

SurveyLOAEL = 1.8-3.2 mg/kg/day 

based on early clinical signs of 

methemoglobinemia in excess of 10% 

(0-3 months old infants formula)
13

FQPA SF = 1x

Inhalation short-term 

(1 to 30 days)

NOAEL= 1.6 mg/kg/day 

(inhalation absorption rate 

= 100%)

UFA = 1x

UFH = 1x

FQPA SF = 1x

LOC for MOE = 

1

APHA Human Epidemiological 

SurveyLOAEL = 1.8-3.2 mg/kg/day 

based on early clinical signs of 

methemoglobinemia in excess of 10% 

(0-3 months old infants formula)

Inhalation 

(1 to 6 months)

NOAEL= 1.6 mg/kg/day 

(inhalation absorption rate 

= 100%)

UFA = 1x

UFH = 1x

FQPA SF = 1x

LOC for MOE = 

1

APHA Human Epidemiological 

SurveyLOAEL = 1.8-3.2 mg/kg/day 

based on early clinical signs of 

methemoglobinemia in excess of 10% 

(0-3 months old infants formula)

Cancer (Oral, dermal, 

inhalation)

Not likely to be carcinogenic based on the lack of evidence of carcinogenicity in the 

submitted studies.

UFA = extrapolation from animal to human (interspecies). UFH = potential variation in sensitivity among members 

of the human population (intraspecies). FQPA SF = Food Quality Protection Act Safety Factor. PAD = population 

adjusted dose (a = acute, c = chronic). RfD = reference dose. MOE = margin of exposure. LOC = level of concern.

The cRfD was based on a human epidemiological study where methemoglobinemia was not 

observed in infants consuming water containing 1.6 mg/kg/day of sodium nitrate. 

Methemoglobinemia was observed in infants consuming > 1.8 mg/kg/day. Data from this study 

represented the most sensitive endpoint in the most sensitive population.

E. FQPA Safety Factor considerations

1. In general. Section 408(b)(2)(c) of FFDCA provides that EPA shall apply an additional 

tenfold (10X) margin of safety for infants and children in the case of threshold effects to account 

for prenatal and postnatal toxicity and the completeness of the database on toxicity and exposure 

unless EPA determines based on reliable data that a different margin of safety will be safe for 

infants and children. This additional margin of safety is commonly referred to as the FQPA 

safety factor (SF). In applying this provision, EPA either retains the default value of 10X, or uses 

a different additional safety factor when reliable data available to EPA support the choice of a 

different factor.

2. Prenatal and postnatal sensitivity. 

There is no concern for fetal susceptibility. There were no treatment related effects observed 

in the 2-generation reproduction study in rabbits. Also, the Food and Drug Administration 

sponsored several reproductive and developmental studies in rodents, hamsters and rabbits 

treated with sodium nitrate. No adverse effects were observed in maternal reproductive 

parameters nor was there fetotoxicity or fetal malformations up to the maximum doses tested in 

each species (41 mg/kg/day in mice and hamsters and 66 mg/kg/day in rats and rabbits). Fetal 

susceptibility was not observed in these any of these studies. Therefore, there are no concerns 

for residual uncertainties concerning pre- and post-natal toxicity.

3. Conclusion.
14

EPA has determined that reliable data show that it would be safe for infants and children to 

reduce the FQPA SF to 1X. That decision is based on the following findings:

i. The toxicity database for nitric acid is adequate as it is based on the use of sodium 

nitrate data for which there is a robust toxicity database. The NOAEL used for 

risk assessment was derived from the critical toxic effect in the most sensitive 

human subpopulation (infants age 8 days to 5 months).

ii. There is no indication that nitric acid is a neurotoxic chemical and there is no 

need for a developmental neurotoxicity study or additional UFs to account for 

neurotoxicity.

iii. There is no indication that nitric acid is an immunotoxic chemical and there is no 

need additional UFs to account for immunotoxicity.

iv. There is no evidence that nitric acid results in increased susceptibility in in utero 

rodents. Several reproductive and developmental studies in rodents, hamsters and 

rabbits showed no evidence of increased fetal susceptibility at doses as high as 41 

mg/kg/day in mice and hamsters and 66 mg/kg/day in rats and rabbits. Further, 

although effects in infants were found in an epidemiological study, the cRfD (1.6 

mg/kg/day) is based on a clear NOAEL established in in that study.

v. There are no residual uncertainties identified in the exposure databases. EPA 

made conservative (protective) assumptions regarding dietary exposure to nitric 

acid. This assessment will not underestimate the exposure and risks posed by 

nitric acid.

Based on the above weight of evidence EPA concluded that the FQPA factor could be 

reduced.

4. Exposure Assessment

A. Dietary exposure from food contact surface sanitizing uses. 

Sufficient data were provided on the chemical identity of the sodium nitrates; however, 

limited data are available on the metabolism of these compounds. The Agency relied 

collectively on information provided on the representative chemical structures, the submitted 

physicochemical data, and structure-activity relationship information to determine the residues of 

concern for this inert ingredient. The Agency has concluded that a risk assessment based on 

toxicity data for the parent compounds is not likely to underestimate risk. 

In addition, the requested exemption from the requirement of a tolerance for the use of 

sodium nitrates could allow for uses in food contact surface sanitizing solutions in which 

residues of sodium nitrates could migrate to food or otherwise be ingested. In the absence of 

actual dietary exposure data resulting from these uses, the EPA has utilized a conservative, 

health-protective method of estimating dietary intake that is based upon conservative 

assumptions related to the amount of residues that can be transferred to foods as a result of use 
15

on food contact sanitizing products. This methodology has been utilized by the EPA for other 

risk assessments to estimate exposure of antimicrobial pesticides used in food handling settings.

EPA assessed dietary exposures from nitric acid in food as follows:

i. Acute exposure. No adverse effects attributable to a single exposure of nitric acid were 

seen in the toxicity databases. Therefore, an acute dietary exposure assessment for nitric acid is 

not necessary.

ii. Chronic exposure. In conducting the chronic dietary exposure assessment, 

the Agency believes the assumptions used to estimate chronic dietary exposures lead to an 

extremely conservative assessment of chronic dietary risk due to a series of compounded 

conservatisms. 

First, when a surface is treated with a disinfectant, a quantity of the disinfectant remains 

on the surface (Residual Solution). In the absence of any other data, the EPA has used an 

estimated worst-case concentration of 1 mg of solution per square centimeter of treated surface 

area for this quantity.

Second, the conservatism of this methodology is compounded by EPA’s decision to 

assume a worst case scenario that all food that an individual consumes, will come into contact 

with 4,000 cm2 of sanitized non-porous food-contact surfaces. This contact area represents all 

the surface area from silverware, china, and glass used by a person who regularly eats three 

meals per day at an institutional or public facility. The surface area of counter tops that comes in 

contact with food is expected to be smaller than the surface area for food utensils. As a 

conservative estimate, EPA assumed that 2,000 cm2 of treated counter top surface area, comes 

into contact with an individual’s food per day.

Third, EPA assumes that 100% of the material present on food contact surfaces will 

migrate to food.

iii. Cancer. Sodium nitrate did not cause an increase in tumors in rodents at doses up to 

2500 mg/kg/day. Therefore, based on the weight of evidence, nitric acid is not likely to cause 

cancer in humans and a cancer dietary exposure assessment is not necessary to assess cancer risk.

Drinking Water Exposure

Under the Safe Drinking Water Act, EPA’s Office of Water has established a Maximum 

Contaminant Level Goal (MCLG) for nitrates of 10 ppm (4.5 mg/kg/day). This MCLG is 

established by EPA’s Office of Water under the Safe Drinking Water Act and represent a 

determination of safe levels of this chemical in drinking water, based solely on possible health 

risks and exposure. Use of sodium nitrate as pesticide inert ingredients would not result in 

drinking water concentrations that would exceed the MCLG.

Residential Exposure (non-dietary exposure)
16

The term “residential exposure” is used in this document to refer to non-occupational, nondietary exposure (e.g., textiles (clothing and diapers), carpets, swimming pools, and hard surface 

disinfection on walls, floors, tables). 

 Nitric acid is not used as an inert ingredient in pesticide products that are registered for 

specific uses that may result in both indoor and outdoor residential exposures. Therefore, a 

residential exposure and risk assessment was not conducted for nitric acid.

5. Aggregate Risk and Determination of Safety

EPA determines whether acute and chronic pesticide exposures are safe by comparing 

aggregate exposure estimates to the aPAD and cPAD. The aPAD and cPAD represent the 

highest safe exposures, taking into account all appropriate safety factors (SFs). EPA calculates 

the aPAD and cPAD by dividing the POD by all applicable UFs. For linear cancer risks, EPA 

calculates the probability of additional cancer cases given the estimated aggregate exposure. 

Short-, intermediate-, and chronic-term risks are evaluated by comparing the estimated aggregate 

food, water, and residential exposure to the POD to ensure that the MOE called for by the 

product of all applicable UFs is not exceeded.

1. Acute risk. There was no hazard attributable to a single exposure seen in the toxicity 

database for sodium nitrates. No adverse effect resulting from a single oral exposure was 

identified and no acute dietary endpoint was selected. Therefore, nitric acid is not expected to 

pose an acute risk. 

2. Chronic risk. Using the exposure assumptions described in this unit for chronic 

exposure, EPA has concluded that chronic exposure to nitric acid from dietary exposure will 

utilize 24% of the cPAD for children 1-2 years old, the population group receiving the greatest 

exposure. There are no residential uses for nitric acid.

3. Aggregate cancer risk for U.S. population.

The EPA has not identified any concerns for carcinogenicity relating to sodium nitrates. 

4. Short-term risk. Short-term aggregate exposure takes into account short-term 

residential exposure plus chronic exposure through food contact surfaces sanitizing uses

(considered to be a background exposure level).

 Because no short-term adverse effect was identified, nitric acid is not expected to pose a 

short-term risk.

5. Intermediate-term risk. Intermediate-term aggregate exposure takes into account 

intermediate-term residential exposure plus chronic exposure resulting from food contact 

surfaces sanitizing uses (considered to be a background exposure level).

Because no intermediate-term adverse effect was identified, nitric acid is not expected to 

pose an intermediate-term risk.
17

Determination of safety. 

Based on these risk assessments, EPA concludes that there is a reasonable certainty that 

no harm will result to the general population, or to infants and children from aggregate exposure 

to residues of sodium nitrates.

6. Cumulative Exposure:

Section 408(b)(2)(D)(v) of FFDCA requires that, when considering whether to establish, 

modify, or revoke a tolerance, the EPA consider "available information" concerning the 

cumulative effects of a particular pesticide's residues and "other substances that have a common 

mechanism of toxicity." Unlike other pesticides for which EPA has followed a cumulative risk 

approach based on a common mechanism of toxicity, EPA has not made a common mechanism 

of toxicity finding as to sodium nitrates and any other substances and, this material does not 

appear to produce a toxic metabolite produced by other substances. For the purposes of this 

tolerance action, therefore, EPA has not assumed that sodium nitrates have a common 

mechanism of toxicity with other substances. For information regarding EPA's efforts to 

determine which chemicals have a common mechanism of toxicity and to evaluate the 

cumulative effects of such chemicals, see the policy statements released by EPA's Office of 

Pesticide Programs concerning common mechanism determinations and procedures for 

cumulating effects from substances found to have a common mechanism on EPA's website at 

http://www.epa.gov/pesticides/cumulative/.

7. Environmental Fate

Due to their high water solubility and weak retention by soil, sodium nitrates are very 

mobile in soil, moving at approximately the same rate as water, and have a high potential to 

migrate to ground water. Because it does not volatilize, nitrate is likely to remain in water until 

consumed by plants or other organisms. Nitrate degradation is fastest in anaerobic conditions 

(EPA 2002b).

8. Ecotoxicity 

The information utilized for ecotoxicity was reproduced from the OECD SIDS Initial 

Assessment Report For SIAM 25 Nitrates Category.

Aquatic Effects

The 96-hour LC50 values for fish (Lepomis macrochirus and Oncorhynchus mykiss) were 

greater than 100 mg/L (nominal) for all category members. For urea, the 96-hour LC50 was > 

9100 mg/L in Barilius barna. For sodium nitrate and potassium nitrate the 48-hour EC50 values

for Daphnia magna were 490 and 3,581 (analytical not specified) mg/L, respectively. Based on 

the available data, members of the nitrate category are not considered toxic to aquatic organisms.
18

9. Environmental Justice

Potential areas of environmental justice concerns, to the extent possible, were considered in 

this human health risk assessment, in accordance with U.S. Executive Order 12898, "Federal 

Actions to Address Environmental Justice in Minority Populations and Low-Income 

Populations," http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf).

As a part of every pesticide risk assessment, OPP considers a large variety of consumer 

subgroups according to well-established procedures. In line with OPP policy, HED estimates 

risks to population subgroups from pesticide exposures that are based on patterns of that 

subgroup’s food and water consumption, and activities in and around the home that involve 

pesticide use in a residential setting. Extensive data on food consumption patterns are compiled 

by the USDA under the Continuing Survey of Food Intake by Individuals (CSFII) and are used 

in pesticide risk assessments for all registered food uses of a pesticide. These data are analyzed 

and categorized by subgroups based on age, season of the year, ethnic group, and region of the 

country. Additionally, OPP is able to assess dietary exposure to smaller, specialized subgroups 

and exposure assessments are performed when conditions or circumstances warrant. Whenever 

appropriate, non-dietary exposures based on home use of pesticide products and associated risks 

for adult applicators and for toddlers, youths, and adults entering or playing on treated areas 

postapplication are evaluated. Further considerations are currently in development as OPP has 

committed resources and expertise to the development of specialized software and models that 

consider exposure to bystanders and farm workers as well as lifestyle and traditional dietary 

patterns among specific subgroups.

10. Risk Characterization

EPA received a petition (#9E6029) from Ecolab Inc. requesting a tolerance exemption for use of 

nitric acid (CAS Reg No. 7697-37-2) as an inert ingredient in food contact surface sanitizing 

solutions applied in public eating places, dairy processing equipment, and food-processing 

equipment and utensils at a maximum level in the end-use concentration of 1,000 parts per 

million (ppm) under 40 CFR Part 180.940 (a). EPA published the notice of filing for this 

petition in the Federal Register on April 7, 2007 (65 FR 18324). No comments were received in 

response to this notice.

Nitric acid is a highly corrosive inorganic acid. In a concentrated form, nitric acid is 

corrosive at the site of contact and does not elicit systemic toxicity. Acute dermal and eye 

exposures to concentrated forms of nitric acid can result in skin burns and irreversible eye 

corrosion. Acute inhalation exposure to nitric acid can result in severe respiratory irritation 

followed by pulmonary edema. Acute ingestion of nitric acid may result in ulceration, 

hemorrhage and perforation of the esophagus and stomach.

The U.S. Occupational Safety and Health Administration (OSHA) Permissible Exposure 

Limit (PEL) for nitric acid as well as the American Conference of Governmental Industrial 

Hygienists (ACGIH) Threshold Limit Value (TLV) for nitric acid is 2 ppm (5 mg/m3

). 
19

While there are no data on the toxicity of dilute forms of nitric acid following oral exposure, 

the toxicity of dilute nitric acid would be expected to be comparable to the toxicity of the NO3-

anion known as nitrate. 

The following summary of the toxicity of nitrate chemicals are reproduced from the 

Reassessment of the Exemptions from the Requirement of a Tolerance for Ammonium Nitrate, 

Magnesium Nitrate, Sodium Nitrate, and Sodium Nitrite (K. Leifer, EPA 2005), IARC

Monographs on the Evaluation of Carcinogenic Risks to Humans VOLUME 94 Ingested Nitrate 

and Nitrite, and Cyanobacterial Peptide Toxins (2010) and the World Health Organization 

(WHO) are reproduced and referenced in this assessment.

Sodium nitrate is of low oral acute toxicity (toxicity category III-IV) in rodents and rabbits. 

Acute data was not available on the dermal and inhalation routes of exposure, eye and dermal 

irritation, and skin sensitization.

Several studies were available for sodium nitrate. These studies included a 6 week oral 

toxicity range-finding study, chronic/carcinogenicity studies in rodents and a 2-generation 

toxicity study in rabbits. In a 6-week oral toxicity and carcinogenicity studies in F344 rats, 

sodium nitrate was administered in the diet. Signs of toxicity were manifested as decreased body 

weight gain at >5% (approximately 2500 mg/kg/day). In the International Agency For Research 

On Cancer (IARC) Monographs on the Evaluation of Carcinogenic Risks to Humans (Vol 94), 

the carcinogenic potential of sodium nitrate was evaluated in several studies in rodents. In two 

studies in mice, no evidence of carcinogenic activity of sodium nitrate alone was observed in the 

drinking water at concentrations up to approximately 5000 mg/kg/day. In four studies in rats, no 

increased incidence of tumors was observed when sodium nitrate alone was administered in the 

drinking water or in the diet at concentrations up to approximately 2500 mg/kg/day. Therefore, 

IARC concluded that there is inadequate evidence in humans for the carcinogenicity of nitrate in 

food or drinking water. Also, there were no treatment related effects observed in the 2-

generation reproduction study in rabbits. The NOAEL in this study was 56.5 mg/kg/day the 

highest dose tested. In addition, the Food and Drug Administration (FDA, 1972a) sponsored 

several reproductive and developmental studies in rodents, hamsters and rabbits treated with 

sodium nitrate. No adverse effects were observed in maternal reproductive parameters nor was 

there fetotoxicity or fetal malformations up to the maximum doses tested in each species (41 

mg/kg/day in mice and hamsters and 66 mg/kg/day in rats and rabbits).

Neurotoxicity studies for sodium nitrates were not available for review. However, there was 

no evidence of potential neurotoxicity in any of the submitted studies. Therefore, sodium

nitrates are not expected to be neurotoxic.

Immunotoxicity studies for sodium nitrates were not available for review. However, there 

was no evidence of potential immunotoxicity in any of the submitted studies. Therefore, sodium

nitrates are not expected to be immunotoxic.

There were three human epidemiological studies available for review. These studies reported 

that cases of infant methemoglobinemia are associated with exposure to nitrate in drinking water. 

The American Public Health Association conducted a survey to identify clinical cases of 
20

infantile methemoglobinemia that were associated with ingestion of nitrate-contaminated water. 

They concluded that greater incidences of methemoglobinemia were observed in infants 

consuming >1.8 mg/kg/day of sodium nitrate. Methemoglobinemia was not observed in any of 

the studies where infants consumed water containing less than 1.6 mg/kg/day of sodium nitrate. 

Therefore, the chronic reference dose established at 1.6 mg/kg/day was based on the 

concentration of nitrate where methemoglobinemia was not observed in infants, 1.6 mg/kg/day. 

Ingested nitrate is rapidly absorbed from the gastrointestinal (GI) tract. It can then be 

detected in blood plasma, saliva and urine. Ingested nitrate is excreted in the urine as urea and 

ammonia. Some of the nitrate is converted to nitrite. According to the World Health 

Organization (WHO Food Additive Series 50 - Nitrate) (see 

http//www.inchem.org/documents/jecfa/jecmono/v50je06.htm). “the formation of nitrite in 

humans is complex, involving uptake of nitrate from food and or water, endogenous synthesis of 

nitrate, secretion of nitrate from blood into saliva, conversion of nitrate to nitrite by bacteria 

present in saliva and reconversion of nitrite to nitrate in blood.”

There was no hazard attributable to a single exposure seen in the toxicity database for sodium 

nitrates. Therefore, nitric acid is not expected to pose an acute risk. 

No residue data were provided for sodium nitrates. In the absence of actual dietary exposure 

data resulting from these uses, the EPA performed a conservative, health protective chronic 

dietary assessment based on conservative, screening level upper-bound estimates of dietary 

exposure to adults and children resulting from dietary food, water and food contact surface 

sanitizing solutions uses. Dietary (food, water, food contact surface sanitizing) exposure does 

not result in chronic dietary risks of concern. Based on the established cRfD (1.6 mg/kg/day) 

representing the most sensitive population (infants); the chronic dietary exposure of nitric acid is 

5.63 % of the cPAD for the U.S. adult population and 24 % of the cPAD for children 1-2 years 

old (the most sensitive population). 

Short-term aggregate exposure takes into account short-term residential exposure plus 

chronic exposure resulting from dietary exposure as aforementioned (considered to be a 

background exposure level). Because no short-term adverse effect was identified, nitric acid is 

not expected to pose a short-term risk. 

Intermediate-term aggregate exposure takes into account intermediate-term residential 

exposure plus chronic exposure to food and water (considered to be a background exposure 

level). Because no intermediate-term adverse effect was identified, nitric acid is not expected to 

pose an intermediate-term risk.

Based on the lack of evidence of carcinogenicity in adequate rodent carcinogenicity 

studies, nitric acid is not expected to pose a cancer risk to humans; therefore, a cancer dietary 

exposure assessment was not performed. 

EPA has determined that the FQPA SF can be reduced to 1X since the RfD was derived from 

the NOEL of the critical toxic effect (methemoglobinemia) in the most sensitive human 

population (infants).
21

Sodium nitrates are not expected to bioaccumulate in soil organisms or aquatic organisms 

due to their high solubility in water and expected low solubility in lipids. Environmental fate 

and ecological effects of concern are not expected from the proposed use pattern of sodium 

nitrate as an inert ingredient in pesticide products.

Under the Safe Drinking Water Act, EPA’s Office of Water has established a Maximum 

Contaminant Level Goal (MCLG) for nitrates of 10 ppm (4.5 mg/kg/day). This MCLG is 

established by EPA’s Office of Water under the Safe Drinking Water Act and represent a 

determination of safe levels of this chemical in drinking water, based solely on possible health 

risks and exposure. Use of sodium nitrate as pesticide inert ingredients would not result in 

drinking water concentrations that would exceed the MCLG. 

Taking into consideration all available information on sodium nitrates, EPA concludes that 

there is a reasonable certainty that no harm will result to the general population or to infants and 

children from aggregate exposure to nitric acid. Therefore, the establishment of an exemption 

from tolerance under 40 CFR 180.940 (a) for residues of nitric acid when used in food contact 

surface sanitizing solutions applied in public eating places, dairy processing equipment, and 

food-processing equipment and utensils at no more than 1000 ppm (0.1% by weight) in the endproduct formulation can be considered safe under section 408 of the FFDCA.

REFERENCES

Bosch, H.M., A.B. Rosefield, R. Huston, H.R. Shipman and F.L. Woodward. 1950. 

Methemoglobinemia and Minnesota well supplies. J. Am. Water Works Assoc. 42: 161-170.

EPA. 1991. U.S. Environmental Protection Agency. Integrated Risk Information System (IRIS). 

Nitrate (CASRN 14797-55-8). Available: http:/www.epa.gov/NCEA/iris/subst/0076.htm. (used 

to reference FDA animal studies)

EPA. 2005. Reassessment of the Exemptions from the Requirement of a Tolerance for 

Ammonium Nitrate, Magnesium Nitrate, Sodium Nitrate, and Sodium Nitrite. Memorandum 

from K. Leifer to D. Rosenblatt. January 31, 2005.

Donahoe, W.E. 1949. Cyanosis in infants with nitrates in drinking water as cause. Pediatrics. 3: 

308-311. 

Maekawa A, Ogiu T, Onodera H, Furuta K, Matsuoka C, Ohno Y, and Odashima S (1982).

Carcinogenicity Studies of Sodium Nitrite and Sodium Nitrate in F-344 rats. Food Chem. 

Toxicol. 20, 25-33.

MRID 48802901. A.P.H.A Committee. (1949-1950)."Water Supply: Nitrate in Potable Waters 

and Methemoglobinemia" A.P.H.A. Yearbook 40; 5: 110-120 (May). 
22

APPENDIX

Table 2. Summary of Parameters used for Dietary Exposure Estimation for Food Contact 

Surface Sanitizing Uses

Parameter Comment Value/Units

AR Application Rate (.01% = 

maximum % in end use 

formulation)

ppm or μg/g; (1000 ppm)

CF 1 Conversion Factor 1 g/1000 mg

CF 2 Conversion Factor 1 mg/1000 μg

RS Residual solution 1 mg/cm2 , ( worst-case assumption)

SA Treated surface area 

which comes into contact 

with food

Cm2; assumed to be 2000 cm2 for 

counter tops and cutting boards; 

assumed to be 4000 cm2 for food 

utensils

F % fraction of the inert 

(migration factor)

No units; assume 100% 

BW Body Weight Adult: 70 kg; child: 15 kg

EDI Estimated Daily Intake =AR*CF1*RS*SA*F*

DDD Daily Dietary Dose =EDI*CF2/BW

cPAD Chronic Dietary end point =1.6 mg/kg/day

% cPAD Ratio of DDD and cPAD Exposure expressed as % of chronic 

population adjusted dose

EDI = AR*CF1*RS*SA*F

DDD = EDI*CF2/BW

The body weights used for this assessment are: adult = 70 kg, and child (3-yr old toddler)= 15 kg

Food Utensil Sanitizer Exposure:

EDI= 1000 ug/g*1ug/1000g*4,000 cm2*1.0= 4000 ug/day

Adult DDD = 4000 ug/g*(1ug/1000g/70 kg)= .06 mg/kg/day

Child DDD = 4000 ug/g*(1ug/1000g/15 kg)= .26 mg/kg/day

Counter Tops and Cutting Board Disinfectant Uses:

EDI= 1000 ug/g*1ug/1000g*2,000 cm2*1.0= 2000 ug/day

Adult DDD = 2000 ug/g*(1ug/1000g/70 kg)= .03 mg/kg/day

Child DDD = 2000 ug/g*(1ug/1000g/15 kg)= .13 mg/kg/day

Total dietary exposure due to food contact surface sanitizing solution:

Adult = .06 ug/kg + .03 = .09 mg/kg/day

Child = .26 ug/kg + .13 = .39 mg/kg/day