2 EXECUTIVE SUMMARY

EPA received a petition (#9 E 6029) 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 co ncentrated 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 exposur e 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 Administr ation (OSHA) Permissible Exposure Limit (PEL) for nitric acid as well as the American Conference of Governmental Industrial Hygienists (ACGIH) Threshold Lim it Value (TLV) for nitric acid is 2 ppm (5 mg/m 3 ).

While there are no data on the toxicity of dil ute forms of nitric acid following oral exposure, the toxicity of dilute nitric acid would be expected to be comparable to the toxicity of th e NO3

- anion known as nitrate.

The following summary of the toxicity of nitr a te chemicals are reproduced from th e 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 Nit rate and Nitrite, and Cyanobacterial Peptide Toxins (2010) and the World Health Organization (WHO) are reproduced and referenced in this assessment.

So dium nitrate is of low oral acute toxicity (toxicity category III

- IV) in rodents and rabbits.
Acute dat a 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/ carcino genicity 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. S igns 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 sodiu m nitrate alone was administered in the3 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, t here 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 r eproductive 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 ea ch species (41 mg/kg/day in mice and hamsters and 66 mg/kg/day in rats and rabbits).

Neuro toxicity studies for sodium nitrates were not available for review. However, t here was no evidence of potential neur otoxicity in any of the submitted studies. Ther efore, sodium
nitrates are not expected to be neur otoxic

.

Immunotoxicity studies for sodium nitrates were not available for review. However, t here was no evidence of potential immunotoxicity in any of the submitted studies. Therefore, sodium
nitrates ar e 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 A ssociation 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 m g/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.
The refore, the chronic reference dose established at 1.6 mg/kg/day was based on the

con centration 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 excrete d 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/v 50 je 0 6.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 datab ase for sodium
nitrates . The refore, nitric acid is not expected to pose an acute risk.

No residue data were prov ided for sodium nitrate s. In the absence of actua l 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 sens itive population (infants); the chronic dietary expo sure of nitric acid is
5.63 % of the cPAD for the U.S. adult population and 2 4 % of the cPAD for children 1

- 2 years old (the most sensitive population).

Short

- term aggregate exposure takes into accoun t 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, ni tric 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 as sessment 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 ex pected 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 so dium
nitra te 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)

. Th is MCLG is established by EPA’s Office of Water un der the Safe Drinking Water Act and represent a
determination of safe levels of th is 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 co ncentrations 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 aggre gate exposure to nitric acid . Therefore, the establishment of an exemption
from tolerance under 40 CFR 180.9 4 0 (a) for residues of nitric acid when used in food contact surface sanitizing solutions applied in public eating places, dairy processing equipme nt, and
food

- processing equipment and utensils at no more than 1000 ppm ( 0. 1% by weight ) in the end

product formulation can be considered safe under section 408 of the FFDCA.

1

. BACKGROUND

On July 1

, 1999

, Ecolab Inc. submitted a petition ( 9E6029) reques ting an amendment to 40 CFR 180 by establishing an exemption from the requirement of a tolerance for residues of nitric5 acid (CAS Reg. No

. 7697

- 37

- 2)

, when used as an inert ingredient, at a concentration not exceed

100 0 ppm in food contact surface sanitizi ng solutions. EPA published the NOF for this petition in the Federal Register on April 7 , 200 0 (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 CF R 178.1010(b)(43) and (c)(19). Sodium nitrates are approved as a direct and indirect fo od additive, food contact surface sanitizer, oxidizing component of explosives and blasting agents.

Since e xposure to various nitrate chemicals are more likely than exposure to a st rong acid
such as nitric acid ; nitrate chemicals are discussed. Sodium ni trate 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 f rom the Reassessment of the Exemptions from the Re quirement 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 Pep tide Toxins (2010) and the World Health Organization (WHO) is reproduced and referenced in this assessment.

2. Inert Ingredient Profile

Some of the physical a nd chemical characteristics of nitric acid and s odium nitrate along
with its structure and nom enclature, 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 L iquid Melting Point (°C) 31 Boiling Point (°C) 250

Dens ity ( g/cm3 ) 1.5129 Vapor Pressure ( mm Hg ) 48
Partition Coefficient ( Log

- 0.216 P) Water Solubility I nfinite Other Solubility Specific Gravity 1.14 Henry's Law Constant

Table 1b

. Physical and Chemical Properties of Sodium nitrate

Paramete r 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 Coefficie nt (Log P) - 0 .79

Water Solubility 81.5 g/100 mL at 1 5 C Other Solubility Specific Gravity 2.26 Henry's Law Constant

3

. Hazard A ssessment

The following studies were reproduced and referenced from the Reassessment of the Exemptions from the Re quirement 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 Pep tide Toxins (2010) and the World Health Organization (WHO)

.

Toxicity Studies with Sodium Nitrate

Table A.1.1 Ac ute Toxicity Profile of S odium N itrate

Guideline No. Study Type Reference Results Toxicity Category7 Table A.1.1 Ac ute Toxicity Profile of S odium N itrate

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 Acu te 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 ( 1 0/sex/do se) 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 25 00 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 cont inued 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 2 500 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 w ere killed 20 weeks later. Tumo r incidences8 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 f or 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 alo ne 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 spo ntaneous tumours of the urinary bladder were reported in historical

contro ls 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 tr eated 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 con taining 0, 2.5 or 5.0% (equivalent to 3125 or 6250 mg/kg/day ) sodium
nitrate for 2 years. No significant differences in f ood intake, body weight or tumo r incidence s were observed between untreated control and treated animals (Sugiyama et al., 1979).

Repro duction T oxicity Study

- Rabbit9 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). Thre e 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 Administra tion 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 (hamste r) 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 nitrate

nitrogen) ranged from 0.6

- 66 mg/kg/day for mice, from 0.3

- 41 mg/kg/day for rats, f rom 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, liv e 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

- nitroge n/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

. T he 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

. I n

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 nitra te

- 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. T he nitrate concentration s 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 (appro ximately 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%) te sted for bacterial contamination.10 T he 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 cas es (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 provi ded ( 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 syn thesis 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 e ndogenous 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/je cmono/v 50 je 0 6.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 sa liva 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 th us 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 oxygenati on 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 nitrate

containing 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 (range

finding 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 = 2 500 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

Carc inogenicity

- 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 LOA EL 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 st atistically

.

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 R eproductive/developmental NOAEL= 41 mg nitrate

nitrogen/kg/day

.

Reproductive/development
al studies

- mice

- gavage 0.6

- 66 mg/kg/day Reprod uctive/developmental NOAEL= 66 mg nitrate

nitrogen/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 R eproductive/developmental NOAEL= 41 mg nitrate

nitrogen/kg/day

.

Reproductive/development
al studies

- hamsters

- gavage 0.4

- 66 mg/ kg/day Reproductive/developmental NOAEL= 66 mg nitrate

nitrogen/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 e xcess 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

Fac tors RfD, PAD,
LOC for Risk

Assessment Study and Toxicological Effects

Chronic dietary (All populations) NOAEL = 1.6 mg/kg/day

UF A = 1 x UF H = 1 x

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 short

term (1 to 30 days) NOAEL = 1.6 mg/kg/day

UF A = 1x

UF H = 1x

FQPA SF = 1x LOC for MOE =

1 APHA Human Epidemiolog ical 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
intermediate

- term (1 to 6 months) NOAEL = 1.6 mg/kg/day

UF A = 1x

UF H = 1x

FQPA SF = 1x LOC for MO E =

1 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)

Dermal short

- term (1 to 30 days) NOAEL = 1.6mg/kg/day (dermal absorption rate =

10 0 %)

U F A = 1x

UF H = 1 x FQPA SF = 1x LOC for MOE =

1 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)

Dermal intermediate

term (1 to 6 months) NOAEL = 1.6mg/kg/day (dermal absorption rate =

10 0 %)

UF A = 1x

UF H = 1x LOC for MOE =

1 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)13 FQPA SF = 1x

I nhalation short

- term (1 to 30 days) NOAEL= 1.6 mg/kg/day (inhalation absorption rate = 100%)

UF A = 1x

UF H = 1x FQPA SF = 1x LOC for MOE =

1 APHA Human Epidemiological Survey LOAEL = 1.8

- 3.2 mg/kg/day based on early clinical signs of methemoglobinemia in e xcess of 10% (0

- 3 months old infants formula)

Inhalation (1 to 6 months) NOAEL= 1.6 mg/kg/day (inhalation absorption rate = 100%)

UF A = 1x

UF H = 1x FQPA SF = 1x LOC for MOE =

1 APHA Human Epidemiological Survey LOAEL = 1.8

- 3.2 mg/kg/day based on early cl inical 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.

UF A = extrapolation from anim al to human (interspecies). UF H = 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 dos e. 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.

M ethemoglobinemia was observed in i nfants 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

t enfold (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 differe nt 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 safe ty factor when reliable data available to EPA support the choice of a
different factor.

2. Prenatal and postnatal sensitivity

.

There is no conce rn for fetal susceptibility. There were no treatment related effects observed
in the 2

- generation reproduc tion 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 i n these any of these studies. Therefore, there ar e 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 follow ing 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 sensi tive 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 i ndication 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 developm ental 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 epidemiol ogical 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 nitr ic 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 s anitizing 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 chemic al 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 compou nds 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
resi dues 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 rel ated to the amount of residues that can be transferred to foods as a result of use15 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 asse ssment 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 co nsumes , 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 c ontact 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. The refore, 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 Wate r has established a Maximum Contaminant Level Goal (MCLG) for nitrates of 10 ppm (4.5 mg/kg/day)

. Th is MCLG is established by EPA’s Office of Water under the Safe Drinking Water Act and represent a
determination of safe levels of th is 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 “resident ial exposure” is used in this document to refer to non

- occupational, non

dietary 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 ing redient 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 Determina tion 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 factor s ( 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 a pplicable UFs is not exceeded.

1. Acute risk

. There was no hazard attributable to a single exp osure 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 expos ure will
utilize 24 % of the cPAD for children 1

- 2 years old , the population group receiving the greatest exposure. There are no re sidential 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 take s 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 po se 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 ex posure 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 re voke 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 cumulat ive 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 tox icity 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

. Enviro n mental 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 h ave 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

. Ecotoxic i ty

The i nformation utilized for ecotoxicity was repro d uced 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 (nomi nal) 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 a vailable data, members of the nitrate category are not considered toxic to aquatic organisms.18 9

. Enviro n mental Justice

Potential areas of environmental justice concerns, to the extent possible, were considered in this human health risk assessment, in ac cordance 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/jus tice/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

cou ntry. 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 produ cts 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.

1 0 . Risk Characterization

EPA received a petition (#9 E 6029) 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

res ponse 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 Lim it Value (TLV) for nitric acid is 2 ppm (5 mg/m 3 ).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 th e 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

M onographs 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.

So dium 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. S igns 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 carc inogenic 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 inadequat e 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 teste d. 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).

Neuro toxicity studies for sodium nitrates were not available for review. However, t here was no evidence of potential neur otoxicity in any of the submitted studies. Therefore, sodium
nitrates are not expected to be neur otoxic

.

Immunotoxicity studies for sodium nitrates were not available for review. However, t here was no evidence of potent ial 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 a ssociated with exposure to nitrate in drinking water. The American Public Health Association conducted a survey to identify clinical cases of20 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.
There fore, 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 ca n 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
htt p //www.inchem.org / documents/jecfa/jecmono/v 50 je 0 6.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 datab ase for sodium
nitrates . The refore, nitric acid is not expected to pose an acute ri sk.

No residue data were prov ided for sodium nitrate s. 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 expo sure of nitric acid is
5.63 % of the cPAD for the U.S. adult population and 2 4 % of the cPAD for children 1

- 2 years old (t he 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

- te rm 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 backgrou nd 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 (methemoglobinem ia) 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 so dium
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 nitrate s of 10 ppm (4.5 mg/kg/day)

. Th is MCLG is established by EPA’s Office of Water under the Safe Drinking Water Act and represent a
determination of safe levels of th is chemical in drinking water, based solely on possible health risks and exposure. Use of s odium 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 n o 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 180.9 4 0 (a) for residues of nitric acid when used in food contact
surf ace 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 end

product 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, Matsuo ka 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; (100 0 ppm)

CF 1 Conversion Factor 1 g/1000 mg

CF 2 Conversion Factor 1 mg/1000 μg

RS Residual solution 1 mg/cm 2 , ( worst

- case assumption)

SA Treated surface area
which comes into contact
with food Cm 2 ; assumed to be 2000 cm 2 for

count er tops and cutting boards;
assumed to be 4000 cm 2 for food
utensils

F % fraction of the inert (migration factor) No units; assume 10 0 %

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

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

DDD Daily Dietary Dose =EDI*C F2/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= 100 0 ug/g*1ug/1000g*4,000 cm2* 1.0 = 40 0 0 ug/ day
Adult DDD = 40 0 0 ug/g* ( 1ug/1000g/70 kg ) = . 06 mg /kg /day
Child DDD = 40 0 0 ug/g* ( 1ug/1000g/15 kg ) = . 26 mg/kg/day

Counter Tops and Cutting Board D isinfectant Uses:

EDI= 100 0 ug/g*1ug/1000g*2,000 cm2* 1.0 = 20 0 0 ug/ day
Adult DDD = 20 0 0 ug/g* ( 1ug/1000g/70 kg ) = . 0 3 mg/kg/day
Child DDD = 20 0 0 ug/g* ( 1ug/1000g/15 kg ) = . 13 mg/kg/day

Total dietary exposure due to food contact surface sanitizing solution:

A dult = . 0 6 ug/kg + . 0 3 = . 0 9 mg/kg/day
Child = . 26 ug/kg + . 1 3 = . 39 mg/kg/day