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**EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER**  **EPA Registration**  **Division contact: [**  **P. V. Shah, (703) 308 -**  **1846 ]**  **INSTRUCTIONS: Please utilize this outline in preparing the pesticide petition. In**  **cases where the outline element does not apply, please insert “NA -**  **Remove” and maintain the outline. Please do not change the margins, font, or format in your**  **pesticide petition. Simply replace the instructions that appear in**  **green , i.e., “**  **[ insert**  **company name ]**  **,” with the information specific to your action.** PP IN
- 107 20
. (EPA

–HQ

– OPP

–2014
- 0633 ). The firm L ewis and Harrison, 122 C Street NW., Suite 505, Washington, DC 20001 one behalf of the BASF Corporation 100 Park Ave., Florham Park, NJ 07932 requests to establish an exemption from the requirement of a tolerance for residues of methane sulfonic acid (CAS No. 75
- 75
- 2 ) when used as a pesticide inert ingredient in pesticide formulations under §180.930 and §180.940(a) when used as a acid cleaner in pesticide formulations with a limit of 3% when used on animals; and 15% (5,000 ppm in use

- dilution solution) when used in antimicrobial formulations for food

- contact surface sanitizing in public eating places, dairy

- processing equipment, and food

- processing equipment and utensils . The petitioner believes no analy tical method is needed because r esidue d ata, including an anal yt ical method, is not pertinent or required for this petition since an exemption from tolerance is requested. **Contact: Registration Division/OPP** **.** EPA has determined that the petition contains data or information regarding the elements set forth in section 408 (d)(2) of FDDCA; however, EPA has not full y evaluated the sufficiency

of the submitted d ata at this time or whether the data supports granting of the petition. Additional data may be needed befor e EPA rules on the petition. A. Residue Chemistry Residue data, including an anal yt ical method, is not pertinent or required for this petition since an exemption from tolerance is requested. B. Toxicological Profile An extensive safet y data base has been complied on Methanesulfonic Acid (MSA). The safet y data base includes acute, subchronic, developmental toxicity , and mutagenicity

studies. Data have been submitted as part of the High Production Volume program in EPA’ s Office of Pollution Prevention and Toxics. Those data are summarized below.2 1. Acute toxicity MSA is of low toxicity

via the oral, dermal, and inhalation routes. At high concentrations, MSA can be severel y irritating and corrosive to eyes and skin. MSA is not a dermal sensitizer.

a. Acute oral toxicity The acute oral toxicity

of MSA ranges from 649 mg/kg (>750 mg/kg ♂; 461 mg/kg ♀) for anh ydrous acid to 1,157.5 mg/kg (860.1 mg/kg ♂; 2,407.6 mg/kg ♀) for a 70% solution. >5,000 mg/kg. i. A cute oral toxicity in Sprague Dawley rats: Anhydrous MSA Groups of five rats/sex were exposed b y oral gavage to 300, 500 and 750 mg/kg bw anhy drous (99.6% pure) MSA (Elf Atochem, 1988). Clinical signs included salivation, decreased activity , wobbl y gait , breathing abnormalities, apparent hy pothermia, decreased/no defecation, feces small in size, urine stain, hunched posture, unkempt appearance, rough haircoat, piloerection, extremities pale in color, de hy dration, emaciation, distended abdomen, decreased food consumption and dark material around the facial area. Bod y weight loss was noted for one male at 300 mg/kg bw, two females and one male at 500 mg/kg bw, and one male at 750 mg/kg bw during the study

day 0
- 7. Bod y weight loss was noted for one male ea ch at 300 mg/kg bw and 750 mg/kg bw during the study day 7
- 14. Body

weight gain was noted for all other surviving animals during the test period. Gross pathology findings observed in the animals that died included distension/abnormal content/reddened mucos a in the digestive tract, dark red/mottled lungs, blackish

- purple spleens, dark red ly mph nodes, stained glandular mucosa in the stomach and body fat depletion/discoloration/adhesions in the abdominal cavity . Necrops y findings on stud y day 14 for the anima ls that survived included abnormal content in the digestive tract and thickened mucosa in the stomach. The acute oral LD 50 of anhy drous MSA in the male rat was greater than 750 mg/kg bw and 461 mg/kg bw in the female rat, and 649 mg/kg bw in the sexes comb ined. ii. Acute oral toxicity

in Sprague D awley rats: 70% MSA Groups of five rats/sex were exposed b y oral gavage to 500, 1000, and 1500 mg/kg bw 70% MSA in water (Elf Atochem, 1997a). Clinical signs included salivation, breathing abnormalities, wobbly gait, decreased activity , decreased defecation, rough haircoat, urine/fecal stain and dark material around the facial area. Bod y weight loss was noted for two animals at 1000 mg/kg bw during the stud y da y 0
- 7 and for one animals each at 300 mg/kg bw 1000 mg/kg bw during the stud y da y 7
- 14. Body weight gain was noted for all other surviving animals during the test period. Gross internal findings were observed onl y in the animals that died and included abnormal content and reddened/thickened mucosa and discoloration in the digestive tract, dark3

red foci on the liver and bl ackish

- purple spleens. The acute oral LD 50 of 70% MSA in the male rat was 860 mg/kg bw, 2408 mg/kg bw in the female rat, and 1158 mg/kg bw in the sexes combined. iii. Acute oral toxicity in Wistar r ats: 98% MSA Five male rats were exposed by oral gavage to anhydrous MSA (98% pure) at 0.25, 0.5 ml/kg bw. Three rats were exposed at 1.0 ml/kg bw (Union Carbide, 1975). At all dose levels, rats were sluggish and presented an unsteady gait. In addition, at 1.0 ml/kg bw, deep breathing was immediately obs erved. At 0.25 ml/kg bw, 2/5 rats died. At 0.5 ml/kg bw 5/5 rats died; and at 1.0 ml/kg bw 2/3 rats died. Necrops y findings included livers mottled and burned, stomach burned, pylorus hemorrhaged and gas filled, intestines hemorrhaged, injected and gas fil led, kidney s mottled and slightly congested. The LD 50 was 0.28 ml/kg bw.

b. Acute dermal toxicity. The acute dermal toxicity of MSA ranges from greater than 200 to less than 2,000 mg/kg bw. i. Acute dermal toxicity in New Zealand White rabbit s: 70% MSA In an OECD 402 test, one male New Zealand White rabbit was dosed dermally at 1000 mg/kg bw of 70% MSA in water (Atofina, 2002). Since no irritation was noted, an additional nine animals (4 males and 5 females) were dosed. The test article was kept in contact with the skin for 24 hours. Animals were observed for mortality , toxicity and pharmacological effects, bod y weights recorded and animals were examined for gross pathology . Dermal responses were recorded 24 hours post

- dosing and on day s 7 and 14. All animals survived the treatment. Instances of few feces were the only abnormal signs noted during the observation period. Dermal responses were slight to well

- defined on day 1, absent to severe on day 7 and absent to slight on day 14. Bod y weight changes and necrops y results were normal. The LD 50 was greater than 1000 mg/kg bw. ii. Acute dermal toxicity in albino rabbits: Anhy drous MSD Six albino rabbits were exposed to 200 and 2000 mg/kg bw anh ydrous MSA (purity not specified) under occl usive cover for 24 hours (Pennwalt, 1978). Skin contact with 2000 mg/kg bw caused intense and prolonged pain. The skin was dark grey in appearance and scattered portions were separating from the subcutaneous tissues. Two rabbits died and 1 rabbit was euth anized. There were no mortalities at 200 mg/kg bw. Ery thema was present over the entire trunk of each animal together with numerous small lesions. There were no clinical signs and animals gained weight during the 7

- day

observation period. The LD 50 was greater than 200 and less than 2000 mg/kg bw.4

c. Acute inhalation toxicity. No mortalities have been noted in several tests conducted with rats and mice. Insufficient volatility

of methane sulfonic acid limits the actual exposure and therefore toxicity risks. i. Acute inhalation toxicity in mice: 99% MSA In testing using 99% MS A, 20 mice were exposed to whole body atmospheric. No effects of an y kind were discernible in an y of the 20 mice either during or after exposure for 1 hour to saturated vapor (at 20°C). All showed normal gains in body weight during the subsequent 7

- day ob servation period. d. Acute eye irritation. At high concentrations, MSA can be severel y irritating and corrosive to eyes. i. Acute eye irritation in albino rabbits: 99% MSA In acute ey e irritation testing using rabbits, 0.1 mL of 99% MSA was instilled in the ey es of two animals in a single administration. One of the two animals had a rinse of the treated ey e with flowing water (initiated 20 to 30 seconds after instillation an d continued for one minute). Animals were observed at 10 minutes; 1, 2, 3, 4, 24, 48, and 72 hours; and 4, 5, 6, and 7 day s post - treatment. Each instillation caused excruciating pain. In the unwashed ey e, the reaction involved all ocular tissues and o ccurred immediatel y; the conjunctivae became completely necrotic (white) without evident swelling; the iris was dilated with ragged edges and failed to react to light; and the cornea opacified completel y within 24 hours. In the washed ey e, the reaction di d not differ significantl y from that of unwashed eye. Under the conditions of this test, MSA is extremely corrosive to ey e.
e. Acute skin irritation. At high concentrations, MSA can be severel y irritating and corrosive to skin. i. Acute skin irritation in albino rabbits: 99% MSA In acute skin irritation testing with albino rabbits, six animals were dosed with either 200 or 2,000 mg/kg of 99% MSA utilizing a pre

- fitted impervious sleeve for 24 hours. At the conclusion of the exposure period, the test substance was removed with a saturated solution of sodium bicarbonate and the animals were observed for a period of seven day s.5

For animals treated with 2,000 mg/kg, skin contact caused intense and prolonged pain. At the end of exposure, the skin of each animal was dark gray in appearance and scattered portions were separating from the subcutaneous tissues. Two rabbits died the following night (28 hours after initial contact) and one rabbit was euthanized three day s after treatment for humane reasons. At 200 mg/kg, no mortality was seen in an y test animals. Erythema (score 2) was present over the entire trunk of each animal together with numerous small lesions which resembled acid burns. Animals nevertheless remained as ymptomatic and gained body

weight during the observation period. Under the conditions of this test, dermal exposure to 99% MSA at 2,000 mg/kg is highl y toxic (severe skin injuries causing death), whereas 200 mg/kg exposure induces minor skin lesions (ery thema and acid burns) but no sy stemic toxicity
. ii. Acute skin irritation in mice: 99% MSA In acute skin irritation testing with mice, the tails of four anesthetized mice were immersed in 99% MSA to a depth of 4 cm. One hour later the tissue reaction was terminated b y plunging the appendages into a saturated solution of sodium bicarbonate for a period of 30 seconds. The tail of each mouse was white when exposure was terminated and the appendage fell off in a day or two. Under the conditions of this test, 99% MSA is c orrosive to mouse skin.

f. Skin sensitization MSA is not a dermal sensitizer. i. Skin sensitization in Hartley guinea pig: 70% MSA In sensitization testing using the Buehler method in Hartley guinea pigs, 20 animals per dose were exposed to the test substance for both the induction and challenge test. A control group of five males and five females was similarly dosed with water. The i nduction consisted of a 50% occlusive epicutaneous dose, while the challenge was a 25 % occlusive epicutaneous dose. There were three 6

- hour applications in 14 day s followed b y the challenge exposure over 24 hours. The induction schedule consisted of th e following:

• On day

1, dermal application with 0.3 mLof test substance (treated group) or with the vehicle (control group) on the left shoulder.

• On day

7, the same region received another topical application
• On day

14, this same site was treated b y a last topical application All these applications lasted approximately 6 hours.6

For the challenge dose, on day 28, all the animals received 0.3 ml of the test substance at the concentration of 25% in their right flank. The challenge exposure duration was 24 hours. There was no rechallenge and no positive control. Animals were examined 24 hours after each induction and the challenge application. A preliminary

study was conducted in order to determine the concentrations to be tested in the main study
. The irritation potential of 70% MSA at levels of undiluted, 50%, 25%, 10%, 5%, 2.5%, 1% and 0.5% was evaluated in two groups of four animals each. Four levels of test material were evaluated per animals. Dilutions were obtained with distilled water (w/v). Each application consisted of 0.3 mLof different solutions applied into a 25 mm Hill Top Chamber, which was placed on animals clipped back for 6 hours. The day after, animals were depilated and two hours later, examined for irritation. Another score was performed 40 hours after exposure. RESUL TS OF PILOT STUDY: Undiluted 70% MSA produced grades of 2, 1 and ±, with edema, blanching and scabbing on two sites. Testing at 50%, 25%, 10%, 5%, 2.5% and 1% produced grades of ±, while 0.5% produced grades of ± and 0. Consequently , the 50% concentration was chosen for use at induction for the test group, since it caused no greater than mild to moderate primary irritation. Moreover, the 25% concentration was selected for challenge, because it caused no more than s light irritation. RESUL TS OF DEFINITIVE TEST: None of the test animals responded with a skin grade that would have been suggestive of sensitization. Under the conditions of this test, MSA is not a sensitizer.

2. Genotoxicity No evidence of genotoxicity or chromosomal effects was observed in mutagenicity studies conducted with MSA.

a. Reverse Mutation: 98.8% MSA (anhydrous) and 70% MSA Bacterial reverse mutation assay s (OECD 471) were conducted with anh ydrous MSA (98.8% pur e) (SNEAP, 1990) and 70% in water (Pennwalt, 1989a). No genotoxicity was observed on Salmonella ty phimurium tester strains TA1535, TA1537, TA1538, TA98 and TA100 up to the cy totoxicity threshold of 5000 μg/plate in the presence and absence of metabolic act ivation.

b. Chromosomal Aberration: 70% MSA Groups of five mice/sex were given a single dose of MSA (70% in water) by oral gavage at 20, 100 or 500 mg/kg bw (Pennwalt, 1989b). Concurrent vehicle and7

positive control group of mice were similarly dosed w ith distilled water or chlorambucil, respectively . The test method was comparable to OECD 474. There was no evidence of induced chromosomal or other damage leading to micronucleus formation in poly chromatic ery throcy tes of treated mice 24, 48 or 72 hours a fter oral administration.

3. Reproductive and developmental toxicity. No reproductive or developmental effects were noted in any of the tests conducted.
a. Reproductive toxicity. In an OECD 421 stud y, groups of 12 rats/sex were exposed to MSA (70.5% in water) by oral gavage at doses of 250, 500 and 1000 mg/kg bw/day (Arkema and Chevron Phillips, 2005). Males were exposed 4 weeks before mating, during the mating period (2 weeks) and until sacrifice. Females were exposed 4 weeks before mating, during the mating period (2 weeks), pregnancy (3 weeks), lactation until day 4 postpartum (pp) inclusive, and until sacrifice (day 5 pp). One male animal died at 1000 mg/kg bw/day on day 33 and one female given 250 mg/kg bw/day was found dead on day

10 post - coitum. There were no test article related clinical signs of toxicity . There were no effects on bod y weights or food consumption. There were no effects on mating index, pre - coital interval, fe rtility index, duration of gestation, delivery data or postnatal and neonatal losses. There were no effects on the mean number of liveborn pups per litter. Minor differences, considered to be of no toxicological significance, were observed in the weights o f testes and epididy mides between treated and control males. Macroscopic post

- mortem examination revealed no treatment

- related effects. No microscopic treatment

- related changes were observed for testicular staging or for the ovaries, including semi

- quantit ative evaluation of the morphological characteristics of ovarian ph ys iology . The no observed effect level (NOEL) for parental toxicity and for toxic effect on reproductive performance and on progeny is 1000 mg/kg bw/day
. b. Developmental toxicity. i. OEC D 414 Oral rangefinding study in female rats: 70.15% MSA A range finding stud y was conducted according to OECD 414 (Elf Atochem, 1996d). Groups of 8 female rats were exposed by oral gavage to doses of MSA (70.15% in water) of 0 (control), 25, 50, 100, 200 and 300 mg/kg bw/d on gestation days 5

- 15. Treatment
- related clinical signs observed consisted of rales, labored respiration and gasping in the 100, 200 and 300 mg/kg bw/d groups. Findings of red material around the nose and/or mouth in the 100, 200 an d 300 mg/kg/d groups often correlated with occurrences of the aforementioned respiratory abnormalities. These findings appeared to be a function of the dosage concentration; rather the dosage level, as they were observed with similar frequency in the 100, 200 and 300 mg/kg/d groups, each of8

which received the test article at a concentration of 50 mg/ml. There were no deaths. Slight mean bod y weight losses and reduction in food consumption occurred in the 100, 200 and 300 mg/kg bw/day groups during gestation day s 6
- 9 when evaluated on a group mean basis. However, several animals in these groups experienced large, transient body

weight losses and corresponding large decreases in food consumption on one or more occasions during the first day s of the dosing peri od. Mean body weights, gravid uterine weights, net bod y weights and net bod y weight gains were unaffected b y treatment at all dose levels. No treatment related internal necropsy findings were observed at any dose level. And no effects were observed at any dose level on intrauterine growth and survival. No external developmental variations of malformations were observed in an y of the foetuses in the treated groups. ii. OECD 414 Oral definitive study in female rats: 70.15% MSA In an OECD 414 stud y, gr oups of 25 female rats were exposed to MSA (70.15% in water) b y oral gavage at doses of 0 (control), 25, 100 and 400 mg/kg bw from gestation day

6 through 15 (Elf Atochem, 1996c). There were no test article related clinical signs and no deaths. There were no effects on body weight or food consumption. At necropsy , intrauterine growth and survival were unaffected by test article administration at all dose levels. There were no test article related fetal malformations or developmental variations. A dose level of 400 mg/kg bw/day was considered to be the no observable adverse effect level (NOAEL) for maternal toxicity and developmental toxicity
.

iii. OECD 421 Oral study in rats: 70.5% MSA In an OECD 421 stud y, groups of 12 rats/sex were exposed to MSA (70.5% in water) by oral gavage at doses of 250, 500 and 1000 mg/kg bw/day (Arkema and Chevron Phillips, 2005). Males were exposed 4 weeks before mating, during the mating period (2 weeks) and until sacrifice. Females were exposed 4 weeks before mating, during the mating period (2 weeks), pregnancy (3 weeks), lactation until day 4 postpartum (pp) inclusive, and until sacrifice (day 5 pp). There were no effects on postnatal and neonatal losses; the mean number of liveborn pups per litter; pup mortality or clinical signs; pup body

weight; or pup sex ratio. The NOELfor developmental effects was 1000 mg/kg bw/day
. 4. Subchronic toxicity
a. Subchronic oral toxicity. i. 7

- day dietary exposure in rats: 98% MSA (anhydrous) Five rats/sex were exposed to concentrations of MSA (98% anhy drous) in the diet of 0.043%, 0.159%, 0.382% and 1.635% (males) and 0.045%, 0.183%, 0.479% and9

1.80% (females) for seven day s (Union Carbide Corporation, 1975). These concentrations were equivalent to 0, 51, 185, 420, 1805 mg/kg bw/d (males) and 0, 55, 201, 551, 2122 mg/kg bw/d (females). There were no deaths, no effects on body weights or organ weights. The NOAEL was 1805 mg/kg/day for males and 2122 mg/kg/day

for fem ales. b. Subchronic dermal toxicity. There are no available subchronic dermal toxicity studies for MSA.
c. Subchronic inhalation toxicity. i. 5

- day nose

- only inhalation in rats: 69.9% MSA Five rats/sex were exposed by nose - onl y inhalation to MSA (69.9% aqueous solution) at concentrations of 0 (control) 0.026, 0.082, 0.23 and 0.74 mg/L for 6 hours/day for 5 day s (Elf Atochem, 1996a). There were 2 and 3 deaths in the 0.23 and 0.74 mg/L groups , respectively . Rales were the onl y clinical sign observed in the 0.23 and 0.74 mg/L groups. Mean bod y weights and food consumption were generall y reduced in males and females in the 0.74 mg/L group throughout the study . There were no effects on organ weights and no gross findings at necropsy . Microscopic findings in the nasal cavities included mucosal necrosis, suppurative inflammation and/or nasal exudate in males and females in the 0.23 and 0.74 mg/L groups. The NOEL for s ys temic toxicity was found to be 0.082 mg/L.

ii. 28
- day nose - onl y inhalation in rats: 69.9% MSA Fifteen rats/sex were exposed by nose - onl y inhalation to MSA (69.9% aqueous solution) at concentrations of 0 (control) 0.026, 0.073 and 0.242 mg/L for 6 hours/day for 5 day s/week for four weeks (Elf Atochem, 1996b). There was a two

- week recovery period following the 4

- week exposure period. During the exposure phase of the study , 4, 1, 1 and 5 animals in the control, low

- , mid

- and high

- exposure groups, respectivel y, were found dead. Th ese deaths were not considered test article related. Clinical signs were reported only during the exposure period and consisted of rales and an increased incidence of yellow matting on various body surfaces in the high

exposure group animals. Matting was a lso observed in the mid

- exposure group males. A transient reduction in mean body weight gain during the first week of exposure and slightly

decreased food consumption throughout the exposure period were noted for the high

- exposure group males. There were no effects on hematology , urinaly sis, or organ weights. There was a statistically significant increase in blood urea nitrogen and aspartate aminotransferase in the high

- exposure group males and females, respectivel y, at the study week 4 evaluations, but re turned to levels comparable to the control group after the two

- week recovery period. There were no test article related gross findings in the animals that were found dead during the stud y and no gross findings in animals at the end of the study . Test artic le

- related microscopic findings were observed in the nasal turbinates of the high

- exposure group10

rats that were found dead and in all treated groups at the study week 4 and 6 evaluations. The severit y of some of the findings observed after the two

- week rec overy period suggested at least partial recovery from the irritative effects of the test article. Based on the compound

- induced lesions observed in the nasal turbinates, the no observed effect level (NOEL) for local irritation was considered to be less than 0.026 mg/L. The NOEL for sy stemic toxicity was considered to be 0.026 mg/L. 5. Chronic toxicity. There are no chronic/oncogencity studies available on MSA. However, chronic studies should not be required for MSA since MSA is not a mutagen, reproducti ve toxin or endocrine disruptor. There is nothing to indicate that MSA will have an y adverse chronic effects on humans or the environment.

6. Animal metabolism. There are no animal metabolism data available on MSA. However, animal metabolism data shou ld not be required for MSA since MSA is not a mutagen, reproductive toxin or endocrine disruptor. There is nothing to indicate that MSA will have an y adverse chronic effects on humans or the environment.

7. Metabolite toxicology
. There are no metabolites of toxicological concern.

8. Endocrine disruption
. There is no information or evidence to indicate that MSA is an endocrine disruptor. C. Aggregate Exposure 1. Dietary exposure. Dietary (food and drinking water) and r esidential (dermal and inhalation) exposures are possible from the use of MSA as an inert ingredient in antimicrobial formulations. MSA has been demonstrated to be readily biodegradable, which reduces the likelihood of residues on food. For the same reason , no significant contributions to drinking water are expected from the use of MSA as inert ingredients in pesticide products. MSA has low toxicity and exposure to residues above toxicity levels of concern are not anticipated. A quantitative dietary

ris k assessment for the MSA is not necessary since there are no toxicity endpoints of concern that are associated with dietary ingestion of the MSA. Nonetheless, a quantitative risk assessment has been conducted using the sy stemtic NOEL from the reproduction study . Specificall y, a Reference Dose (RfD) of 1011

mg/kg/day

was calculated based on a NOEL of 1,000 mg/kg/day in the OECD 421 study in rats using a 10x uncertaint y factor for inter

- and intra

- species extrapolation. The chronic Population Adjusted Dose (cP AD) is also 10 mg/kg/day . No additional uncertaint y factor was added to the cPAD calculation as the reproductive and developmental toxicity

studies do not indicate any additional susceptibility for infants and children. The chronic dietary

exposure due to MSA use as an inert ingredient in disinfectants (sanitizer) used on food

- contact surfaces was assessed. This assessment calculated the Daily Dietary Dose (DDD) and the Estimated Daily I ntake (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). The EDI calculations presented in this assessment assume that food can contact either 2,000 cm 2 or 4,000 cm 2 (50% and 100% of the FDA worst

- case scenario) of treated surfaces, and that 10% of the material would migrate to food. The 10% migration rate is based on Agency

Residential Standard Operation Procedures. These daily estimates were conservatively

used to assess chronic dietary risks ( i.e. , percent chronic population adjusted dose or %cPAD). Assuming a level of 5,000 ppm of MSA in the use dilution solution, the following EDI is calculated: EDI : 100% FDA Worst Case EDI = 1 mg/solution x 5,000 μ g x 4,000 cm 2 x 10% = 2,000 μ g/person/day

cm 2 1,000 mg person/day 

### OR 2.0 mg/person/day

EDI : 50% FDA Worst Case EDI = 1 mg/solution x 5,000 μ g x 2 ,000 cm 2 x 10% = 1,000 μ g/person/day

cm 2 1,000 mg person/day 

### OR 1.0 mg/person/day The above calculation is for use of the substance in products that are used in public

eating facilities, which is worst

- case. Use in food

- processing plants would yield dramaticall y lower exposures.12

Assuming bod y weights for men (70 kg), women (60 kg), and infants and children (15 kg), the following percent DDD values are calculated: DDD: 100% FDA Worst Case

• Male: 2.0 mg/person/day ÷ 70 kg/person = 0.029 mg/kg/day

• Female: 2.0 mg/person/day ÷ 60 kg/person = 0.033 mg/kg/day

• In fants/Children: 2.0 mg/person/day ÷ 15 kg/person = 0.13 mg/kg/day DDD: 50% FDA Worst Case

• Male: 1.0 mg/person/day ÷ 70 kg/person = 0.014 mg/kg/day

• Female: 1.0 mg/person/day ÷ 60 kg/person = 0.017 mg/kg/day

• In fants/Children: 1.0 mg/person/day ÷ 15 kg/person = 0.067 mg/kg/day Based on the calculated DDDs and the cPAD value of 10 mg/kg/day , the following percent cPAD estimates are derived: % cPAD: 100% FDA Worst Case

• Male: 0.029 mg/kg/day ÷ 10 mg/kg/day

= 0.29% cPAD
• Female: 0.033 mg/kg/day ÷ 10 mg/kg/day

= 0.33% cPAD
• In fants/Children: 0.13 mg/kg/day ÷ 10 mg/kg/day

= 1.3% cPAD % cPAD: 50% FDA Worst Case

• Ma le: 0.014 mg/kg/day ÷ 10 mg/kg/day = 0.14% cPad

• Female: 0.017 mg/kg/day ÷ 10 mg/kg/day

= 0.17% cPad

• In fants/Children: 0.067 mg/kg/day ÷ 10 mg/kg/day

= 0.67% cPad MSA may

contain the impurity , methy l methane sulfonate (MMS), which is of toxicological concern. BASF has measured levels of 480 and 530 ppb in separate batches of 70% MSA, resulting in a mean value of 505 ppb. Corrected for purit y, this value is estimated at 721.4 ppb. Because MMS is a known mutagen and a potential carcinoge n we need to estimate the upper bound cancer risk from this dietary exposure. FDA regulations state that a substance with a TD 50 of 6.25 mg/kg bw/day will result in a one in a million risk level with a dietary exposure of 1.5 μ g/person/day 1 . Based on this benchmark, we can use the lowest statistically significant TD 50 for MMS of 31.6 mg/kg bw/day2 to estimate the upper bound cancer risk from MMS exposure resulting from the use of MSA as an acid excipient in a sanitizing solution at a level of 1,000 ppm for the most vulnerable population, infants and children:
1. 21 CFR 170.39. We have used an FDA benchmark to simplify calculations. EPA risk estimates would not be significantly different. 2. Gold, L.S., T.H. Slone, N.B. Manley, G.B. Garfinkel, L. Rohr b ach and B.N. Ames (1997). Carcinogenic Potency Database, Handbook of Carcinogenic Potency and Genotoxicity Databases (L.S. Gold & E. Zeiger, eds.) 1

- 605.13

0.13 mg/kg bw/day

x 721.4 ppb MMS in MSA = 9.38 x 10 - 8 mg/kg bw/day MMS exposure
9.38 X 10 - 8 mg /kg bw

/day x 15 kg bw/person x 1.0 x 10 - 6 x 6.25 mg/kg bw/day = 1.9 x 10 - 10 0.0015 mg/person/day 31.6 mg/kg bw/day The above estimated risk for a c hild is far smaller than what would ordinarily be considered negligible.
i. Food. Food contact exposures are well below 100% of the cPAD, and are therefore below EPA’s established level of concern for all U.S. subpopulations. The combined exposure for males, females, and infants and children is < 1% of the cPAD, even for the 100% worst case scenario. ii. Drinking water. Drinking water exposure is highly unlikel y from the use of MSA as an inert ingredient in antimicrobial pesticide products. Moreover, MSA are readil y biodegradable according to OECD criteria, which reduce the likelihood of residues on food. Exposures to res idues above toxicity levels of concern are not anticipated. D. Cumulative Effects MSA does not share a common mechanism of toxicity with an y other pesticide active and/or inert ingredient. E. Safety Determination The proposed use of MSA will not inc rease the current exposure due to other non

pesticide exposures. The food

- contact sanitizer use for all population subgroups combined is <1% of the cPAD.

1. U.S. population. The % cPAD calculated for males (0.14

- 0.29%) and females (0.17

- 0.33%) is well below the level of concern. Based on these conservative exposure estimates, there is a reasonable certainty

that no harm will result to the U.S. population from the aggregate exposure to MSA. 2. Infants and children
. FFDCA Section 408 requires an additional tenfold margin of safety for the protection14

of infants and children in case of threshold effects to account for prenatal and postnatal toxicity , and an inadequate toxicity database. Where an adequate and reliable database is available and there is a lack of evidence for increased susceptibility , the FQPA safet y factor may be reduced or removed. An evaluation of susceptibility and uncertainty

issues associated with MSA has been performed, and EPA has previously re duced the FQPA safet y factor from the default 10x to 1x for the following reasons:

• The availability

of a substantial and scientificall y sound mammalian toxicology database that includes acute, repeat dose, reproduction, developmental, and endocrine data for MSA;

• OECD testing indicating that there was no evidence of developmental toxicity or malformations in the developing offspring;

• There is no evidence to suggest that MSA would have an adverse effect on the reproductive organs;

• MSA does not belong t o a class of chemicals known or suspected of having adverse effects on the estrogen receptor or endocrine system. MSA has been evaluated in acute, repeated dose, developmental, and chronic toxicity studies capable of detecting effects on endocrine mediated events and have not demonstrated an y endocrine

- related effects. The % cPAD calculated for infants and children (0.67

- 1.3%) is well below the level of concern. Based on these conservative exposure estimates, there is a reasonable certaint y that no harm will result to infants and children from the aggregate exposure to MSA.
F. International Tolerances There are no CODEX MRL s established for MSA.