2

Table of Contents

EXECUTIVE SUMMARY

................................ ................................ ................................ ... 3

I. BACKGROUND

................................ ................................ ................................ ................... 6

II. INERT INGREDIENT PROFILE

................................ ................................ ......................... 6

A. Summary of Uses

................................ ................................ ................................ ....... 6

B. Physical Chemical Properties

................................ ................................ .................... 7

III. HUMAN HEALTH ASSESSMENT

................................ ................................ ..................... 8

A. Summary of Toxicity Data

................................ ................................ ......................... 8

B. Toxicity Endpoint Selection

................................ ................................ .................... 12

C. Special Considerations for Infants and Children

................................ ..................... 13

IV. EXPOSURE ASSESSMENT

................................ ................................ .............................. 13

A. Dietary Exposure:

................................ ................................ ................................ .... 13
i. Acute exposure

................................ ................................ ................................ ..... 16
ii. Chronic exposure

................................ ................................ ................................ . 16

iii. Can cer exposure

................................ ................................ ................................ . 16
iv. Dietary exposure from drinking water

................................ ................................ 16

B. Residential (Non

- Occupational) Exposure:

................................ ............................. 16

i. From non

- dietary exposure.

................................ ................................ .................. 16

V. AGGREGATE RISK ASSESSMENT

................................ ................................ ................ 16

i. Acute Dietary Risk.

................................ ................................ ............................... 16
ii. Chronic Dietary Risk.

................................ ................................ .......................... 17
iii. Aggregate Cancer Risk for U.S. Population.

................................ ...................... 17

iv. Short

- term Aggregate Risk.

................................ ................................ ................ 17

v. Intermediate

- Term Aggregate Risk.

................................ ................................ .... 17

VI. OCCUPATIONAL EXPOSURE/RISK PATHWAY

................................ .......................... 17

VII. CUMULATIVE EXPSOURE

................................ ................................ ............................. 17

VIII. ENVIRONMENTAL JUSTICE STATEMENT

................................ ................................ .. 18

IX. ENVIRONMENTAL FATE CONSIDERATIONS

................................ ............................ 18

X. ECOTOXICITY

................................ ................................ ................................ ................... 19

XI. RISK CHARACTERIZATION

................................ ................................ ........................... 19

REFERENCES

................................ ................................ ................................ ................................ 21

APPENDIX

................................ ................................ ................................ ................................ ...... 223

EXECUTIVE SUMMARY

Exponent on behalf of Ecolab, Inc. (370 N. Wabasha Street, St. Paul, MN 55102) is requesting that EPA expand the current sodium bisulfate tolerance exemption. Sodium bisulfate also referred to as sodium acid sulfate (CAS Reg. No. 7681

- 38

- 1) has an existing inert ingredient

tole rance exemption listed in 40 CFR 180.920 for pre

- harvest use. Ecolab requested that EPA expand the tolerance exemption to include use as an inert ingredient in antimicrobial formulations in accordance with 40 CFR 180.940(a), which includes use on food con tact surfaces in public eating places, dairy processing equipment, and food processing equipment and utensils at no more than 2000 ppm in formulation

.

Sodium bisulfate has a long history of use in pesticides as an antimicrobial disinfectant active ingred ient, in pre

- harvest pesticide formulations as an inert ingredient and in food applications as a food additive, pH control, and a leavening agent in cake mixes. All of these uses involve direct exposure and ingestion by humans. EPA re

- registered sodium bis ulfate for indoor antimicrobial residential use as a toilet bowl cleaner to control household and odor causing bacteria, Staphylococcus spp . (EPA, 1993). In 1993, sodium bisulfate was granted a exemption from the requirement of a tolerance when used as an acidifying/buffering agent in pesticide formulations to growing crops in accordance with 40 CFR 180.1001(d), which was re vised in 2004

to 40 CFR 180.920.

Sodium bisulfate when used as a general acidifier or general food additive was a subject of

Generall y Recognized as Safe (GRAS) notification for which the Food and Drug Administration (FDA) found no objections with. T he subject meets the FDA definition of a natural product (FDA 1998)

. The Joint FAO/WHO Expert Committee on Food Additives ( JECFA ) ( J ECFA, 2000, 2010a) has approved the use of sodium bisulfate as a food additive (an acidifier) in a broad range of beverage, confectionary, and general food uses at levels ranging from 500 to 4000 mg/kg. JECFA assigned an acceptable daily intake ( ADI ) of “n ot specified” because the parent sulfate anion is a natural constituent of food and a product of sulfur metabolism.

Sodium bisulfate readily dissociates to the bilsulfate anion and the sodium cation. Bisulfate/sulfate anion is a naturally

- occurring cons tituent in many food substances a s well as an

essential component in a large number of mammalian (human) metaboli c processes. The

bisulfate/sulfate anion is present in all human tissue, with blood plasma sulfate concentrations of 2

- 3 mmol/L . Since the bis ulfate anion is converted to sulfate in aqueous solution, toxicology studies for sodium sulfate are generally considered as relevant for sodium bisulfate.

The information presented in this document is summarized from the EPA Reregistration Eligibility Do cument, Mineral Acids dated September 1993, Joint FAO/WHO Expert Committ ee on Food Additives (JECFA) 2010 , United Nation Envionment Programme (UNEP) SIDS Initial Assessment Report on sodium sulfate (2005) , Institute of Medicine of the National Academies (2 005) Dietary Reference Intakes for Water, Potassium, Sodium, Chloride, and Sulfate and Food and Drug Administration (FDA) Generally Recognized as Safe (GRAS) Notice 1998 and Letter

2011.4 The acute oral toxicity of sodium bisulfate is low (Toxicity categ ory III). The acute oral

LD 50 in male rats was 2800 mg/kg. It was minimally irritating to the rabbit’s skin (Toxicity category IV) and mildly irritating to the eyes (Toxicity category III) . An acute inhalation study was

available with sodium sulfate. In halation toxicity was not observed at 0.01 mg/l (the only dose tested). No dermal toxicity or dermal sanitization studies were available in the database.

Due to the data for sodium bisulfate

, both human metabolic processes and toxicity data for

sodium sulfate were used for the risk characterization . Both sodium bisulfate and sodium sulfate readily undergo hydrolysis and dissociate to sodium ion s and sulfate ion s in the body

. Although

there are n o subchronic oral toxicity studies were available in the da tabase for sodium bis ulfate,

studies are available for sodium sulfate

.

No mutagenicity or genotoxicity studies were available in the database.

No carcinogenicity studies were available in the database. National Toxicology Program (NTP), International Agency for Research on Cancer (IARC), and Occupational Safety & Health Administration (OSHA) have not listed sodium bisulfate as a carcinogen. A DEREK analysis was performed on sodium bisulfate and no struc tural alerts were detected.

In two teratogenicity studies in mice, sodium sulfate wa s administered via subcutaneous injection and gavage at doses of 60 and 2800 mg/kg bw, respectively. Neither maternal nor developmental toxicity was observed ≤ 2800 mg/kg bw. This exceeds the limit dose of 1,000 mg/kg/day.

No immunotoxicity or neurotoxicity studies were available in the database.

Sodium bisulfate metabolism is essentially that of sodium cation and sulfate anion. W hen sodium bisulfate is added to food products containing water or after ingestion of sodium bisulfate it ionizes to sodium ions, hydrogen ions and sulfate ions. Following ingestion, sulfate anions are predominantly not absorbed from the gastrointestinal t ract and are excreted unchanged in urine.
However, t he sulfate anion is normal constituent in the body, predominantly resulting from the body’s metabolism of sulfur

- containing food sources such as foods containing the essential amino acids cysteine and me thionine. Sulfate anions are a vital component in a number of human biosynthetic pathways such as cartilage production and the formation of pancreatic digestive

enzymes

.

Based on the metabolism of sodium bisulfate to sulfate and sodium ions, both of whi ch are essential components in the human metabolic processes, there is a lack of toxicological concern. Additionally, t here is no indication of toxicity at the limit dose and a toxicological endpoint of concern for risk assessment purposes was not identifi ed. Since no endpoint of concern was identified for the acute and chronic dietary exposure assessment and short and intermediate dermal and inhalation exposure, a quantitative risk assessment for sodium bisulfate is not necessary.

The Agency believes t hat amending the tolerance exemption to include 40 CFR § 180.940(a) will not significantly/measurably increase occupational exposure. The change in use pattern would be expanded to include food contact surfaces such as tableware, utensils, dairies and5

bev erage and food processing plants. In view of the regulatory history of sodium bisulfate , i.e., approved use under 40 CFR §180.9 2 0 and no new toxicological information to indicate otherwise, it is not necessary to quantitatively assess occupational exposur e.

Based on the e c otoxicity data available on sodium sulfate , sodium bisulfate is not expected

to be toxic to aquatic and sediment dwelling organisms. Toxicity to terrestrial plants is also expected to be low.

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.

Taking into consideration all available information on sodium bisulfate, EPA concludes that there is a reasonable certainty that no harm to any population subgroup will result from aggregate exposure to sodium bisul fate when considering occupation, dietary exposure and all other nonoccupational sources of pesticide exposure for which there is reliable information. Therefore, the establishment of an exemption from tolerance under 40 CFR 180.940(a) for residues

of sodi um bisulfate (CAS Reg. No. 7681

- 38

- 1) when used as a pesticide inert ingredient at no more than 2000 ppm in antimicrobial formulations on food

- contact surfaces in public eating places, dairy processing equipment, food processing equipment and utensils can be considered assessed as safe under section 408(q) of the FFDCA.6

I. BACKGROUND

Exponent on behalf of Ecolab, Inc. (370 N. Wabasha Street, St. Paul, MN 55102) is requesting that EPA expand the current sodium bisulfate tolerance exemption. Sodium bisulfate also referred to as sodium acid sulfate (CAS Reg. No. 7681

- 38

- 1) is already approved for inert ingredient tolerance exemption listed in 40 CFR 180.920 for pre

- harvest use. Ecolab request that EPA expand it to include use as an inert ingredient at no more than 2000 ppm in antimicrobial formulations in accordance with 40 CFR 180.940(a), which includes use on food contact surfaces in public eating places, d airy processing equipment, and food processing equipment and utensils.

The information presented in this document is summarized primarily from the EPA Reregistration Eligibility Document, Mineral Acids dated September 1993, Joint FAO/WHO Expert Committee on Food Additives (JECFA) 2010, United Nation Envionment Programme (UNEP) SIDS Initial Assessment Report on sodium sulfate (2005) and Food and Drug Administration (FDA) Generally Recognized as Safe (GRAS) Notice 1998 and Letter 2011.

Sodium bisulfate ha s a long history of use in pesticides as an antimicrobial disinfectant active ingredient, as a pre

- harvest pesticide inert formulation ingredient and in food applications as a food additive, pH control, and a leavening agent in cake mixes. All of these use s involve direct exposure and ingestion by humans. EPA re

- registered sodium bisulfate for indoor antimicrobial residential use as a toilet bowl cleaner to control household and odor causing bacteria, Staphylococcus spp. (EPA, 1993). In 1993, sodium bisulfa te was granted a exemption from the requirement of a tolerance when used as an acidifying/buffering agent in pesticide formulations to growing crops in accordance with 40 CFR 180.1001(d), which was revised in 2004 to 40 CFR

180.920.

USDA also cleared the use of sodium bisulfate as a cooling and retort water treatment agent to inhibit corrosion on the exteriors of canned goods. Sodium bisulfate is also used in the poultry industry and dairies, to acidify animal waste for the reduction of ammonia emission a nd as a browning inhibitor for granny smith apple slices while reducing microbial growth (Fan et al., 2009). Sodium bisulfate is Generally Recognized as Safe (GRAS) by FDA (1998) and meets the FDA definition of a natural product. JECFA (FECFA, 2000, 2010a) has approved the use of sodium bisulfate as a food additive (an acidifier) in a broad range of beverage, confectionary, and general food uses at levels ranging from 500 to 4000 mg/kg. JECFA assigned an ADI of “not specified” because the parent sulfate ani on is a natural constituent of food and a product of sulfur

metabolism.

II. INERT INGREDIENT PROFILE

A. Summary of Uses

In accordance with 40 CFR 180.920, sodium bisulfate is currently exempt from the requirement of a tolerance when used as an acidifying/buffering agent in pesticide formulations applied to growing crops. EPA has re

- registered sodium bisulfate in solid and liquid (solutions), for indoor antimicrobial residential use as a toilet bowl cleaner to control

household a nd odor causing bacteria, Staphylococcus spp . EPA (1993) specified the rate of7 application as 30,400 ppm up to 49, 248 ppm a.i. by weight. Sodium bisulfate is used as a

food additive with FDA (1998 approv ing sodium bisulfate as a Generally Recognized As Safe (GRAS) food additive with sulfate salts cited safe in 21 CFR 184.111; 184.1230; 184.1643; and 186.1797.

JECFA (2010b) has established an ADI for sodium bisulfate of “not specified”. The term ADI “not specified” is established by JECFA to indicate a food component of very low toxicity and hazard to human health. JECFA (2010) report ed that: “Sodium hydrogen

sulfate [sodium bisulfate] is typically added to beverages, confectionery, fillings, syrups, processed cheeses, salad dressings, sauces, jams and j ellies, and processed vegetable products at levels ranging from 500 to 4000 mg/kg for beverages

. S odium hydrogen sulfate is generally used in non

- citrus

- flavoured soft drinks, tea, and chocolate

- flavoured

and coffee

- flavoured drinks, as it does not impart a sour or citric taste, as do other

acidifiers.”

B. Physical Chemical Properties
Some of the physical and chemical characteristics of sodium bisulfate , along with its structure and nomenclature, are found in Table 1.

Table 1. Physical and Chemical Properties of Sodium Bisulfate

Parameter Value Source

Structure ChemIDplus

CAS # 7681

- 38

- 1 Molecular Weight (g/mol) 120.06 Sigma

- Aldrich MSDS

Common Names Acid Sulfate, Sodium Pyrosulfate, Sodium Hydrogen Sulfate Sigma

- Aldrich MSDS

Physical State Powder Sigma

- Aldrich MSDS Melting Point (°C) 315 Chemicalbook Boiling Point (°C) @ 19 hPa N/A Density (g/cm 3 @ 20°C) 2.1 Chemicalbook Vapor Pressure (mmHg @

25°C) N/A

Partition Coefficient (Log P) N/A

Water Solubility ( g/L) 120.06 g/L at 20°C (Completely soluble) Sigma

- Aldrich MSDS8 pH 1.0 Sigma

- Aldrich MSDS Henry's Law Constant N/A EPI Suite 4.0 (registrant)

III. HUMAN HEALTH ASSESSMENT

A. Summary of Toxicity Data

Sodium bisulfate readily dissociates into the sodium cation and the bilsulfate anion. The

b isulfate/sulfate anion is a naturally

- occurring constituent in many food substances and a mammalian (human) metabolite therefore the existing toxicology database is limited. Since the bisulfate anion is converted to sulfate in solution, toxic ology studies for sodium sulfate are generally considered as also being relevant to the toxicity of sodium bisulfate.

Acute Oral Toxicity In an acute oral toxicity study, five Sprague

- Dawley rats/sex/dose (except for 3000 mg/kg females: 10 rats), were administered by gavage, a single dose of 1750 ( f emale only), 2000, 2250, 2500, 3000 and 3500 (male only) mg/kg of body weight of sodium bisulfate. Control rats were similarly dosed with deionize d water. Surviving animals were killed after 14 days. Clinical signs (dose not specified) included weight loss, dehydration, scruffy coats, lethargy and death. Necropsy showed gross abnormalities observed in the animals that died included mottled red lungs and livers mottled with pale areas. Several of these animals were also observed to have either lesions on their stomachs or stomachs ruptured with contents emptied into the peritoneal cavity. The LD 50 (M ale ) was 2800 (2393

- 3276) mg/kg. The study failed to establish a dose response for the females. (CAL DPR, 2002) (WHO 2010a)

Dermal Toxicity

No studies available in the database.

Inhalation Toxicity

The United Nations Environmental Programme (UNEP) in a 2005 SIDS Document on

sodium sulfate references an inhalation study with an aerosol showed no adverse effects at 10 mg/m 3 or 0.01 mg/L, however the typical limit concentration testing is 2 mg/L.

Primary Eye Irritation In a study using sodium sulfate was performed on rabbits with endpoint determination

ba sed on the DRAIZE scoring system. Sodium sulfate had no adverse effect on the iris and cornea. The substance was instilled into the conjunctival sac of the eye. The positive effects were primarily based on the conjunctvea (redness) observed in the test. Th e effects were reversible within 7 days. It is considered as mildly irritating to the eyes (Bayer, 1991 unpublished) (UNEP 1995)

.

Primary Skin Irritation A 0.5 g portion of sodium bisulfate (moistened with deionized water) was applied to two sites, one i ntact and one abraded, on the back of each rabbit (sex not specified) , applied9 under two layer thick cotton gauze patches measuring one inch square. The entire trunks of the animals were wrapped in a non

- occlusive manner for twenty

- four hours. Observations

showed that the intact sites had an e rythema score of 1 in 3/6 rabbits at 24 hours with clearing by 72 hours. Edema score of 1 was seen in 2/6 rabbits at 24 hours and cleared by

72 hours. It is minimally irritating to the skin of rabbits.

Dermal Sensitiz ation

No studies available in the database.

The results of the available acute toxicity s tudies are summarized in Table 2

. Acute Toxicity

Table 2 . Acute Toxicity Profile of Sodium Bisulfate

Study Type Results Toxicity Category MRIDs # /Reference

Acute Oral

- rat LD 50 (male) = 2800 mg/kg

bw

LD 50 (female) = N/A (sodium bisulfate) III CAL DPR 2002

WHO 2010a

Acute Dermal

- N/A N/A N/A N/A

Acute Inhalation

- N/A LD 50 > 0.01 mg/L

(sodium sulfate) N/A UNEP SIDS Sodium

Sulfate 2005 Primary Eye

Irritation

- rabbit Slightly irritating clearing

within 7 days (sodium sulfate) III UNEP SIDS Sodium

Sulfate 2005

Primary Skin

Irritation

- rabbit Minimal irritation clearing

by 72 hours (sodium bisulfate) IV CAL DPR 2002

Dermal Sensitization N/A N/A N/A

Subchronic Toxicity

- No subchronic studies were available in the database for sodium bisulfate

. However there

are studies available for sodium sulfate.

According to the OECD SIDS 2005 assessment on sodium sulfate, 5 male S prague

- D awley rats were given 0.84% of s o d i um sulfate in diet (320

- 400 mg/kg/day) for 27 and 44 weeks. There was no mortality, tumors, body weight change or significant changes in food and/or water consumption. The NOAEL was ~320

- 400 mg/kg/day. (Blunck & Crowther 1975) (UNEP 2005)

In 30

- day oral toxicity study cited in the OECD SIDS 2005 assessment on sodium sulfate, 24 male Sprague

- dawley rats were given in diet 0.0, 0.125, 0.250, 0.5, 1 and 2% sodium sulfate (estimated 125, 250, 500, 1000 and 2000 mg/kg /day) for 4 weeks. No changes in food and water consumption, body weight gain, food conversion efficiency, urine production or diarrhea. Blood hemoglobin, white blood count, serum alkaline phosphatase,10 inorganic phosphate and gross organ pathology were als o unaffected. The NOAEL was 2000 mg/kg/day

. The LOAEL was not observed in this study (Moinuddinand Wing

- Tsit Lee) (UNEP 2005)

Chronic Oral Toxicity

- No chronic studies were available in the database for sodium bisulfate

.

Mutagenicity and Genotoxicity No mutagenicity or genotoxicity studies were available in the database for sodium bisulfate. However there is one study available for sodium sulfate. In a study cited in OECD SIDS 2005 on sodium sulfate. Sodium sulfate showed no effect

in the Ames test usi ng various strains of S. typhimurium (TA1535, TA1537, TA100, TA98)

both with and without S9 activation in a GLP standardized test.

Carcinogenicity No carcinogenicity studies were available in the database. National Toxicology Program (NTP), Internationa l Agency for Research on Cancer (IARC), and Occupational Safety & Health Administration (OSHA) has not listed sodium bisulfate as a carcinogen. Also a DEREK analysis was run on sodium bisulfate and no structural alerts for carcinogenicity

were detected. See the Appendix for the full DEREK report.

Teratogenicity Sodium sulfate was included in a test of a method for rapid assessment of teratogenicity. Pregnant ICR/SIM mice were given a saturated aqueous solution of sodium sulfate orally by gavage to delive r a dose of 2800 mg/kg bw per day on days 8

- 12 of gestation. No maternal deaths occurred and the average maternal weight gain during the treatment period

was no t significantly different from that of water

- treated controls. Twenty

- four litters were

delivere d alive, and none were resorbed. The mean numbers of neonates delivered alive and dead in each litter and the survival of neonates on day 3 were not statistically significantly different from those of controls. Neonatal body weights on days 1 and 3 and

bod y

- weight gain were recorded. Only body weight on day 1 was statistically significantly greater than that of controls. The maternal and developmental NOAEL = 2800 mg/kg bw, the only dose tested. The maternal and developmental LOAEL was not established (Se i denberg et al., 1986) from WHO (2000)

.

No reproductive studies were available in the database for sodium bisulfate

.

Immunotoxicity

No i mmunotoxicity studies were available in the database for sodium bisulfate

.

Neurotoxicity

No neurotoxicity studies were available in the database sodium bisulfate

.

Metabolism and Pharmacokinetics11 Sodium bisulfate mammalian metabolism is essentially that of the sodium cation and sulfate anion. As previously noted, when sodium bisulfate is added to food products containing water or after ingestion of sodium bisulfate it ionizes to sodium ions, hydrogen

ions and sulfate ions.

Following ingestion, sulfate anions are predominan tly not absorbed from the gastrointestinal tract and are excreted unchanged in urine. However, the sulfate anion is a normal constituent in the body, predominantly resulting from the body’s metabolism of

sulfur

- containing food sources such as foods contai ning the essential amino acids cysteine and methionine. Sulfate anions are vital component s in a number of human biosynthetic pathways such as cartilage production and the formation of pancreatic digestive enzymes

. Additionally , the sulfate anion is also an important conjugate in the Phase II conjugation/ elimination of oxidized (OH) aromatic ring metabolites and for hydroxyl steroid hormones, such as estrogen, where it acts as a transport agent to target organ tissue receptors.

The following paragraph wa s taken from Institute of Medicine of the National Academies “Dietary Reference Intakes for Water, Potassium, Sodium, Chloride, and Sulfate.” (2005) :

“The nutrient is required by the body for synthesis of 3’

- phosphoadenosine

- 5’

- phosphosulfate (PAPS), whi ch in turn is used for synthesis of many important sulfur

- containing compounds such as chondroitin sulfate and cerebroside sulfate. While substantial levels of sulfate are found in foods and various sources of drinking water, the major source of inorganic sulfate for humans is from body protein turnover of the sulfur amino acids, methionine and cysteine. Dietary inorganic sulfate in food and water, together with sulfate derived from methionine and cysteine found in dietary protein, as well as the cysteine c omponent of glutathione, provide sulfate for use in PAPS biosynthesis. Sulfate requirements are thus met when intakes include recommended levels of sulfur amino acids. For this reason, neither an Estimated Average Requirement (and thus a Recommended

Dietar y Allowance) nor an Adequate Intake of sulfate is established.”

Table 3 . Toxicology Profile for Sodium Bisulfate

Guideline No./ Study Type Doses

Levels MRID No.

(year)/References Results

27 and 44 week oral toxicity

– rats (diet) 0.84% in

diet (320

- 400 mg/kg/day) (sodium sulfate) Blunch and

Crowther 1975 (UNEP 2005) NOAEL ~320

- 400 mg/kg/day

No mortality, tumors, changes in body weight, or food/water consumption.12

Table 3 . Toxicology Profile for Sodium Bisulfate

Guideline No./ Study Type Doses

Levels MRID No.

(year)/References Results

4 week oral toxicity

– rats (diet) 0.0, 0.01,

0.125, 0.250, 0.5,

1 and 2% (estimat ed

2000 mg/kg/day) (sodium sulfate) Moinuddinand

Wing

- Tsit Lee (UNEP 2005) NOAEL 2000 mg/kg/day

No changes in food/water consumption, body weight gain, food conversion efficiency, urine production or diarrhea. Also no changes in blood hemoglobin, white bl ood count, serum alkaline phosphatase, inorganic phosphate or gross organ pathology.

Developmental Toxicity

- rats 2800

mg/kg bw/day (sodium sulfate) Seidengerb et al.

1986 D evelopmental NOAEL = 2800 mg/kg bw

.

D evelopmental LOAEL was not established

.

Ames Test

– S. typhimurium 312

- 5000

μg with

and

without

activation Bayer AG 1988

(UNEP 2005) Negative

B. Toxicity Endpoint Selection
Sodium bisulfate readily dissociates to the bilsulfate anion and the sodium cation.

Bisulfate/sulfate anion is a naturally

- occurring constituent in many food substances as well as an essential component in a large number of mammalian (human) metabolic processes.

T he sulfate anion is a normal constituent in the body, predominantly resulting from the body’s metabolism of sulfur

- containing food sources such as foods containing the essential amino acids cysteine and methionine. Sulfate anions are vital component s in a number of human biosynthetic pathways such as cartilage production and the formation of pancreatic diges tive enzymes . Additionally, the sulfate anion is also an important conjugate in the Phase II conjugation/ elimination of oxidized (OH) aromatic ring metabolites and for hydroxyl steroid hormones. The available toxicity studies indicate that sodium bisulfa te has a very low overall toxicity. A developmental toxicity study showed neither maternal nor developmental effects at 2800 mg/kg/day which is above the limit dose of 1000 mg/kg/day. Since signs of toxicity were not observed at the limit dose and sodium and

bi sulfate ions are present ubiquitously in the human body, an endpoint of concern for risk assessment purposes was not identified. Therefore, since no endpoint of concern was identified for the acute and chronic dietary exposure assessment and short a nd intermediate dermal and inhalation exposure, a quantitative risk assessment for sodium bisulfate is not

necessary.13 C. Special Considerations for Infants and Children
FFDCA, as amended by FQPA, directs the Agency to use an additional 10X safety factor (SF ), to account for potential pre

- and postnatal toxicity and completeness of the data with respect to exposure and toxicity to infants and children. FQPA authorizes the Agency to modify the 10X FQPA SF only if reliable data demonstrate that the resulting le vel of exposure would be safe for infants and children. There was no hazard identified in a repeat dose rat developmental toxicity study at or above the limit dose of 1,000 mg/kg/day to either parental animals or their offspring. There is no concern for neu rotoxicity, immunotoxicity or carcinogenicity for sodium bisulfate. There is no evidence to suggest susceptibility in infants and children. Since s odium and sulfate ions are found naturally in the human body as an essential component of human biosynthetic processes, endpoints to quantitatively assess dietary risk were not selected. EPA has low concentrations and no residual uncertainties with regard to pre

- or postnatal toxicity from sodium bisulfate exposures. Since a qualitative assessment was conducted f or potential human health exposure to copper, the 10X FQPA SF was not retained.

IV. EXPOSURE ASSESSMENT

A. Dietary Exposure:

In evaluating dietary exposure to the sodium bisulfate, EPA considered exposure under the petitioned for exemptions from the requireme nt of a tolerance. EPA assessed dietary exposures

from sodium bisulfate in food as follows:

In conducting the dietary exposure assessment using the Dietary Exposure Evaluation

Model DEEM

- FCID TM , Version 3.16 , EPA used food consumption information from the U.S. Department of Agriculture’s National Health and Nutrition Examination Survey, What We Eat In America, (NHANES/WWEIA). This dietary survey was conducted from 2003 to

2008 . As to residue levels in food, n o residue data were submitted for sodium bisulfate. In the absence of specific residue data, EPA has developed an approach which uses surrogate information to derive upper bound exposure estimates for the subject inert ingredient. Upper bound exposure es timates are based on the highest tolerance for a given commodity from a list of high

- use insecticides, herbicides, and fungicides. A complete description of the general approach taken to assess inert ingredient risks in the absence of residue data is

cont ained in the memorandum entitled “Alkyl Amines Polyalkoxylates (Cluster 4): Acute and Chronic Aggregate (Food and Drinking Water) Dietary Exposure and Risk Assessments for the Inerts.” (D361707, S. Piper, 2/25/09) and can be found at http://www.regulations.gov in docket ID number EPA

- HQ

- OPP

- 2008

- 0738.

In the dietary exposure assessment, the Agency assumed that the residue level of the inert ingredient would be no higher than the highest tolerance for a given commo dity. Implicit in this assumption is that there would be similar rates of degradation (if any) between the active and inert ingredient and that the concentration of inert ingredient in the scenarios14 leading to these highest of tolerances would be no highe r than the concentration of the active ingredient.

The Agency believes the assumptions used to estimate dietary exposures lead to an extremely conservative assessment of dietary risk due to a series of compounded conservatisms. First, assuming that t he level of residue for an inert ingredient is equal to the level of residue for the active ingredient will overstate exposure. The concentration of active ingredients in agricultural products is generally at least 50 percent of the product and

often can be much higher. Further, pesticide products rarely have a single inert ingredient; rather there is generally a combination of different inert ingredients used which additionally reduces the concentration of any single inert ingredient in the pesticide pro duct in relation to that of the active ingredient

.

Second, the conservatism of this methodology is compounded by EPA’s decision to assume that, for each commodity, the active ingredient which will serve as a guide to the potential level of inert ingredient residues is the active ingredient with the highest tolerance level. This assumption overstates residue values because it would be highly unlikely, given the high number of inert ingredients, that a single inert ingredient or class of ingredients would be present at the level of the active ingredient in t he highest tolerance for every commodity. Finally, a third compounding conservatism is EPA’s assumption that all foods contain the inert ingredient at the highest tolerance level. In other words, EPA assumed 100 percent of

all foods are treated with the inert ingredient at the rate and manner necessary to produce the highest residue legally possible for an active ingredient. In summary, EPA chose a very conservative method for estimating what level of inert residue could be on food, and then

use this met hodology to choose the highest possible residue that could be found on food

and assumed that all food contained this residue. No consideration was given to potential degradation between harvest and consumption even though monitoring data shows that

tolera nce level residues are typically one to two orders of magnitude higher than actual

residues in food when distributed in commerce.

Accordingly, although sufficient information to quantify actual residue levels in food is not available, the compounding of these conservative assumptions will lead to a significant exaggeration of actual exposures. EPA does not believe that this approach underestimates exposure in the absence of residue data.

The dietary assessment for food contact sanitizer solutions calculated the Daily Dietary Dose (DDD) and the Estimated Daily Intake (EDI). The assessment considered: application rates, residual solution or quantity of solution remaining on the treated surface without rinsing with potable water, surface area of the treated surface which comes into contact with food, pesticide migration fraction, and body weight. These assumptions are based on FDA guidelines (FDA, 2003).

FDA Food Contact Surface Sanitizing Solution Dietary Exposure Assessment Model

EDI (mg/p/day) = AR x RS x SA x F x 10

- 6 (1)

DDD (mg/kg/day) = AR x RS x SA x F x 10

- 6 /BW (2)15 Where:

AR = Application rate (ppm)

RS = Residual solution (mg/cm 2 )

SA = Surface area of the treated surface which comes into contact with

food (cm 2 )

F = Fraction of the pesticide transferred or migrated to food ( unit less )

BW = Body weight (kg)

The input parameters listed in Table 4 below and equations 1 and 2 above are used to calculate EDI, DDD and %PAD for the three population subgroups (adult male s, adult females, and infants /children)

.

Table 4 : Input Parameters for Food Contact Surface Sanitizing Solution Dietary Exposure

Assessment

Parameter Value

Rationale

Residual Solution on

Surface 1 mg/cm 2 FDA assumption

Area of Treated

Surface 4,000 cm 2 FDA assumption for food

utensils/surfaces

concentration in

diluted solution 500 ppm Diluted Solution concentration,

based on maximum concentration (expressed in ppm).

Fraction Transferred 100% FDA assumption

Body Weight (kg)

Adult man = Adult woman =

Child = 70

60

15 EPA, 1997

EDI (mg/p/day) = AR x RS x SA x F x 10

- 6
500 ppm * 1 mg/cm 2 * 4000 cm 2 * 100% * 10

- 6 = 20 mg/p/day

DDD (mg/kg/day) = AR x RS x SA x F x 10

- 6 /BW therefore, for adult males 20 mg/p/day/70 kg bw /p = 0.28 mg/kg/day for adult female 20 mg/p/day/60 kg bw/p = 0.33 mg/kg/day for 3 year old child 20 mg/p/day/15 kg bw/p = 1.33 mg/kg/day

In estimating total dietary (food and drinking water) exposures, the exposures estimated using the FDA model for components of food contact sanitizing solutions and the estimated dietary16

exposures (food and drinking water) resulting from the use of the ine rt ingredient in pesticide formulations are combined. The exposure estimates for the inert ingredient in pesticide formulations were derived using the Agency’s DEEM

- FCID model for chronic dietary exposures.

i. Acute exposure . No adverse effects attri butable to a single exposure of sodium bisulfate were seen in the toxicity databases. Therefore, acute dietary exposure assessment for

sodium bisulfate is not required.

ii. Chronic exposure

. No adverse effects attributable to chronic exposure of sodium bisulfate were seen in the toxicity database and sodium bisulfate is a normal body

constituent . Therefore, a chronic dietary exposure assessment for sodium bisulfate is not required.

iii. Cancer exposure

. T he National Toxicology Program (NTP), International Agency for Research on Cancer (IARC), and Occupational Safety & Health Administration (OSHA) ha ve not listed sodium bisulfate as a carcinogen. Sodium bisulfate is not mutagenic in the Ames test

. A DEREK

anal ysis was run on sodium bisulfate and no structural alerts for carcinogenicity were detected. Therefore, based on the lack of concern for carcinogenicity of sodium bisulfate a cancer dietary exposure assessment is not necessary to assess cancer risk.

iv. D ietary exposure from drinking water

. No adverse effects attributable to acute or chronic exposure of sodium bisulfate were seen in the toxicity database and sodium bisulfate is a normal body constituent. Therefore, a dietary exposure assessment f rom drinki ng water for sodium bisulfate is not required.

B. Residential (Non

- Occupational) Exposure:

i

. From non

- dietary exposure. The term ‘‘residential exposure’’ is used in this document

to refer to non

- occupational, non

- dietary exposure (e.g., for lawn and garden pest control, indoor pest control, termiticides, and flea and tick control on pets). In the case of sodium

bisulfate , the request is for use as an inert ingredient in antimicrobial formulations for use on food contact surfaces. Sodium bisulfate may also be used in products that are registered for specific uses that may result in residential exposure. However, based on the lack of toxicity, an exposure assessment from “residential exposures” was not performed.

V. AGGREGATE RISK ASSESSMENT

i. Acute Dietary Risk.
An acute aggregate risk assessment takes into account exposure estimates from acute dietary consumption of food and drinking water using the exposure assumptions discussed in section IV for acute exposure. However there was no hazard attributable to a single exposure seen in the toxicity database fo r sodium bisulfate; therefore there is no concern17 for an acute diet ary risk and an acute aggregate risk assessment was not conducted for

sodium bisulfate

.

ii. Chronic Dietary Risk.
A chronic aggregate risk assessment takes into account exposure estimates from chronic dietary consumption of food and drinking water using t he exposure assumptions discussed in section IV from chronic exposure. However because no toxicological endpoint of

concern was identified for chronic dietary exposure, there is no concern for a chronic dietary risk and a chronic aggregate risk assessment was not conducted for sodium

bisulfate.

iii. Aggregate Cancer Risk for U.S. Population.
The Agency has not identified any concerns for carcinogenicity relating to sodium bisulfate; therefore, a n aggregate cancer risk assessment was not conducted for sodi um bisulfate.

iv. Short

- term Aggregate Risk

. Short

- term aggregate exposure takes into account short

- term residential exposure plus chronic exposure to food and water (considered to be a background exposure level). Sodium bisulfate could be as an inert ing redient in pesticide products that could result in

short

- term residential exposure. However, since there are no toxi cological endpoints of concern for residential exposure or food and water, EPA has concluded that the combi ned

short

- term aggregate risk assessment is not required

.

v. Intermediate

- Term Aggregate 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). Sodium bisulfate is not expected to be used as an inert ingredient in pesticide products that could result in intermediate

- term residential exposure. S ince there are also no toxicological endpoints of concern for residential exposure or food and water, EPA has

co ncluded that the combined intermediate

- term aggregate risk assessment is not required.

VI. O CCUPATIONAL EXPOSURE/RISK PATHWAY

The Agency believes that amending the tolerance exemption to include 40 CFR § 180.940(a) will not significantly/measurably increase occupational exposure. The change in use pattern would be expanded to include food contact surfaces such as tableware, uten sils, dairies and beverage and food processing plants. In view of the regulatory history of sodium bisulfate , i.e., approved use under 40 CFR §180.9 2 0 and no new toxicological information to indicate otherwise, it is not necessary to quantitatively assess occupational exposure.

VII. C UMULATIVE EXPSOURE18 Cumulative effects from substances with a common mechanism of toxicity . Section 408(b)(2)(D)(v) of FFDCA requires that, when considering whether to establish, modify, or revoke a tolerance, the Agency consider “available information” concerning the cumulative effects of a particular pesticide's residues and “other substances that have a common mechanism of toxicity.”

EPA has not found sodium bisulfate to share a common mechanism of toxicity wi th any

o ther substances, and that sodium bisulfate do es not appear to produce a toxic metabolite produced by other substances. For the purposes of this tolerance action, therefore, EPA has assumed that

sodium bisulfate does not 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 EPA's website at http://www.epa.gov/pesticides/cumulative

.

VIII. E NVIRO NMENTAL JUSTICE STATEMENT

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, R D 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 CSFII and are used in pesticide risk assessments for all registered food uses of a pesticide. These

data are a nalyzed 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 o r 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 post

- application are evaluate d. 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 pa tterns among specific subgroups

IX. E NVIRONMENTAL FATE CONSIDERATIONS

The environmental fate and risk inf ormation available for sodium sulfate reported by UNEP (2005) states:

“In water sodium sulfate completely dissociates into sodium and sulfate ions. The ions cannot hydrolyze. In anaerobic environments sulfate is biologically reduced to (hydrogen)19 sulphide by sulfate reducing bacteria, or incorporated into living organisms as a source of sulphur, and thereby included in the sulphur cycle. Sodium sulfate is not reactive in aqueous solution at room temperature. Sodium sulfate will completely dissolve, ionize and distribute across the entire planetary “aquasphere”. Some sulfates may eventually be deposited, the majority of sulfates participate in the sulphur cycle in which natural and

industrial sodium sulfates are not distinguishable

. ”

X. E COTOXICITY

The environmental fate and risk inf ormation available for sodium sulf ate reporte d by UNEP (2005) states:

“ The BCF of sodium sulfate is very low and therefore significant bioconcentration is not expected. Sodium and sulfate ions are essential to all living organisms and their intracellular and extracellular concentrations are actively regulated. However, some plants (e.g. corn and Kochia Scoparia ), are capable of accumulating sulfate to concentrations that are potentially toxic to ruminants. Algae were shown to be the most sensitive to sodium

sulfate with an EC 50 120h

– 1,900 g/l. For invertebrates, ( Daphnia magna ), the EC 50 48h = 4,580 mg/l and fish appeared to be the least sensitive with a LC 50 96h

– 7,960 mg/l for Pimephales promelas . Activated sludge showed a very low sensitivity to sodium sulfate. There was no effect up to 8 g/l. S odium sulfate is not very toxic to terrestrial plants. Picea

banksiana was the most sensitive species, an effect was seen at 1.4 g/l. Sediment dwelling organisms were not very sensitive either, with an LC 50 96h = 600 mg/l for Trycorythus sp

. Overall, it can be concluded that sodium sulfate has no acute adverse effect on aquatic and sediment dwelling organisms. Toxicity to terrestrial plants is also low.”

XI. R ISK CHARACTERIZATION

Sodium bisulfate metabolism is essentially that of sodium cation and sulfate anion. When sodium bisulfate is added to food products containing water or after ingestion of sodium bisulfate it ionizes to sodium ions, hydrogen ions and sulfate ions. Following ingestion, sulfate anions are predominantly not absorbed from the gastroint estinal tract and are excreted unchanged in urine. However, the sulfate anion is normal constituent in the body, predominantly resulting from the body’s metabolism of sulfur containing food sources such as foods containing the essential amino acids cystei ne and methionine. Sulfate anions are a vital component in a number of human biosynthetic pathways such as cartilage production and the formation of pancreatic digestive

enzymes

.

Since there is no indication of toxicity at the limit dose a toxicological endpoint of concern for risk assessment purposes was not identified. Since no endpoint of concern was identified for the acute and chronic dietary exposure assessment and short and intermediate dermal and inhalation exposure, a quantitative risk assessme nt for sodium bisulfate is not necessary.20 The Agency believes that amending the tolerance exemption to include 40 CFR § 180.940(a) will not significantly/measurably increase occupational exposure. The change in use pattern would be expanded to include food contact surfaces such as tableware, uten sils, dairies and beverage and food processing plants. In view of the regulatory history of sodium bisulfate , i.e., approved use under 40 CFR §180.9 2 0 and no new toxicological information to indicate otherwise, it is not necessary to quantitatively assess occupational exposure.

Taking into consideration all available information on sodium bisulfate, EPA concludes that there is a reasonable certainty that no harm to any population subgroup will result from aggregate exposure to sodium bisulfate when consi dering occupation, dietary exposure and all other nonoccupational sources of pesticide exposure for which there is reliable information. Therefore, the establishment of an exemption from tolerance under 40 CFR 180.940(a) for residues of sodium bisulfate (C AS Reg. No. 7681

- 38

- 1) when used as a pesticide inert ingredient at no more than 2000 ppm in antimicrobial formulations on food

- contact surfaces in public eating places, dairy processing equipment, food processing equipment and utensils can be considered

a ssessed as safe under section 408(q) of the FFDCA.21

REFERENCES

Alan M. Rulis, FDA Director Office of Premarket Approval, Letter to Ms. Betty J. Pendleton

Jones

- Hamilton Co., dated June 5, 1998, GRAS Notice No. GRN 000003, Docket No. 98S

- 0104

California Environmental protection Agency Department of Pesticide Regulation Medical Toxicology Branch Summary of Toxicology Data Sodium Bisulfate, 2002. Chemical Code # 905,

Tolerance #50263.

Fan X, Sokorai KJ, L iao CH, Cooke P, Zhang HQ., 2009 . Antibrow n ing and antimicrobial properties of sodium acid sulfate in apple slices. J Food Sci.; 74: 485

- 92.

FDA. 2003. “Sanitizing Solutions: Chemistry Guidelines for Food Additive Petitions.” http://www.cfsan.fda.gov/~dms/opa

- cg3a.html. Last access ed June 9, 2003.

Institute of Medicine of the National Academies, Dietary Reference Intakes for Water, Potassium, Sodium, Chloride, and Sulfate. The National Academies Press (2005)

Stephen Mixon, Director of Operations, Advanced Food Technologies, LLC., Letter to Antonia Mattia Office of Food Additive Safety, FDA dated October 12, 2011, “GRAS Notification for sulfuric acid and sodium sulfate blend used as an antimicrobial in meat and poultry processing.”

UNEP 1995 SIDS Sodium Sulfate US EPA Registration Eligibility Document, 1993. Mineral Acids Case 6064.

World Health Organization (WHO) Food Additives Series: 44 Safety Evaluation of Certain Food Additives And Contaminants, 2000.

World Health Organization (WHO) Food Additives Series: 62 Safety Evaluation of Certain Food Additives And Contaminants, 2010a. Pages 237

- 247.

WHO Technical Report Series 956 71 st Report of the Joint FAO/WHO Expert Committee on Food Additives, 2010b Page 43

- 46.22

APPENDIX



## Derek Nexus Report

Author

HED Report date

18 September 2013 13:27:47

Prediction date 18 September 2013 13:27:11 Program version Derek Nexus: 3.0.1, Nexus: 1.5.0 Compound name

Structure

- 2 Species bacterium, mammal Endpoints alpha

- 2

- mu

- Globulin nephropathy, Anaphylaxis, Bladder urothelial hyperplasia, Carcinogenicity, Cardiotoxicity, Cerebral oedema, Chloracne, Cholinesterase inhibition, Chromosome damage in vitro, Chromosome damage in vivo, Cumulative effect on white cell count and immunology, Cyanide

- type effects, Developmental toxicity, Genotoxicity in vitro, Genotoxicity in vivo, Hepatotoxicity, HERG channel inhibition in vitro, High acute toxicity, Irritation (of the eye), Irritation (of the gastrointestinal tract), Irritation (of the respiratory tract), Irritation (of the sk in), Lachrymation, Methaemoglobinaemia, Mutagenicity in vitro, Mutagenicity in vivo, Nephrotoxicity, Neurotoxicity, Occupational asthma, Ocular toxicity, Oestrogenicity, Peroxisome proliferation, Phospholipidosis, Photo

- induced chromosome damage in vitro, Photoallergenicity, Photocarcinogenicity, Photogenotoxicity in vitro, Photogenotoxicity in vivo, Photomutagenicity in vitro, Phototoxicity, Pulmonary toxicity, Rapid prototypes: adrenal gland toxicity, Rapid prototypes: bladder disorders, Rapid prototypes: blood in urine, Rapid prototypes: bone marrow toxicity, Rapid prototypes: bradycardia, Rapid prototypes: cardiotoxicity, Rapid prototypes: chromosome damage in vitro, Rapid prototypes: hepatotoxicity, Rapid prototypes: kidney disorders, Rapid prototypes: mitochondrial dysfunction, Rapid prototypes: nephrotoxicity, Rapid prototypes: splenotoxicity, Rapid prototypes: testicular toxicity, Rapid prototypes: thyroid toxicity, Respiratory sensitisation, Skin sensitisation, Teratogenicity, Testicular toxicity, Th yroid toxicity, Uncoupler of oxidative phosphorylation Superendpoints Carcinogenicity (SUPER), Chromosome damage (SUPER), Genotoxicity (SUPER), Hepatotoxicity (SUPER), HERG channel inhibition (SUPER), Irritation (SUPER), Miscellaneous endpoints (SUPER), Mutagenicity (SUPER), Ocular toxicity (SUPER), Rapid prototypes: adrenal gland toxicity (SUPER), Rapid prototypes: bladder disorders (SU PER), Rapid prototypes: blood in urine (SUPER), Rapid prototypes: bone marrow toxicity (SUPER), Rapid prototypes: bradycardia (SUPER), Rapid prototypes: cardiotoxicity (SUPER), Rapid prototypes: chromosome damage in vitro (SUPER), Rapid prototypes: hepatot oxicity (SUPER), Rapid prototypes: kidney disorders (SUPER), Rapid prototypes: mitochondrial dysfunction (SUPER), Rapid prototypes: nephrotoxicity (SUPER), Rapid prototypes: splenotoxicity (SUPER), Rapid prototypes: testicular toxicity (SUPER), Rapid proto types: thyroid toxicity (SUPER),23 Reproductive toxicity (SUPER), Respiratory sensitisation (SUPER), Skin sensitisation (SUPER), Thyroid toxicity (SUPER)

Constraints

Perceive tautomers true

Perceive mixtures true

Perceive alerts without rules false Average molecular mass 120.06 (Lhasa Limited, version 1.0)

Exact molecular mass 119.9493 (Lhasa Limited, version 1.0) Log Kp

- 4.99 (Potts & Guy, version 1.0 (LogP: BioByte Corp., version 5.3; Average Molecular Mass: Lhasa Limited, version 1.0)) Log P

- 2.17 (BioByte Corp., version 5.3)



### Submitted compound



### Predictions

Derek KB 2012 1.0
KnowledgeBase name

Derek KB 2012 1.0 KnowledgeBase version

1.0 KnowledgeBase last modified

29 November 2012 11:56:30 KnowledgeBase location C:/Program Files/Lhasa Limited/Lhasa Knowledge Suite

- Nexus 1.5/KnowledgeBases/org.lhasalimited.pluto.knowledge.derek_1.0.724

KnowledgeBase certified by Lhasa Limited, Leeds, Yorkshire, UK Nothing to report



### Reasoning glossary:

Certain