Page 2 of 25

as histopathological lesions in the nasal turbinates were observed. In a 7

- repeat dose oral feeding study in rats, no systemic toxicity was observed at doses up to 1805 mg/kg/day . No effects were seen for parental toxicity, offspring/developmental toxicity or reproductive performance in a combined reproductive/developmental toxic ity screening test at doses up to 1000 mg/kg/day. In one developmental toxicity study in rats, no parental systemic or developmental toxicity was observed at doses up to 400 mg/kg/day. Available prenatal developmental toxicity data showed

some evidence of slight maternal toxicity but no developmental effects. Methane sulfonic

acid was not mutagenic and did not induce chromosomal aberrations. There are no metabolism, chronic toxicity or carcinogenicity studies available on methane sulfonic acid. However, based on the lack of systemic toxicity at 1000 mg/kg/day and above in a combined reproductive/developmental screening study and 7

- day dietary study, and the lack of mutagenicity concern, there are low concerns for cancer.

A lthough neurotoxicity studie s have not been submitted for methane sulfonic acid there is no evidence of neurotoxicity in any study in the toxicity database including a combined reproductive/developmental toxicity screening test and prenatal developmental toxicity studies

.

The inhal ation toxicity NOAEL was taken from the repeat

- dose inhalation study discussed

earlier. There were no treatment related macroscopic findings in the treated animals. Microscopic findings believed attributable to the test material included mucosal necrosis

, suppurative inflammation and/or nasal exudate in males and females in the 0.23 and 0.74 mg/L groups. The NOAEL was determined to be 0. 74 mg/L (

~ 191 mg/kg/day).

The dermal toxicity NOAEL is selected from a n oral developmental toxicity study with the

ass umption of 100% dermal absorption

. Based on the results of this study, the dermal toxicity

NOAEL was 400 mg/kg/day

.

The o ral toxicity NOAEL is taken from the developmental toxicity study with female Sprague

Dawley rats where the NOAEL was identified as 400 mg/kg/day . This dose is used for the dietary exposure assessment.

Based upon the requested use patterns, humans may be exposed to methane sulfonic acid via diets, dermal and inhalation . Dietary exposure may occur as a result of residues transf erred from

treated food contact areas and eating meat from treated animals . Dietary exposure may occur as a result of residues remaining in treated food/dairy processing equipment or systems. Dermal and inhalation exposures may occur as a result of the u se of sanitizing solutions which contain

methane sulfonic acid . Exposures from the use of sanitizing solutions may be “occupational” exposures or “residential” exposures. Occupational exposures are those that result from persons who use/apply sanitizing solutions during the course of normal work related activities such as cleaning/disinfecting food contact preparation surfaces and food or dairy processing machinery or systems. “Residential” dermal and inhalation exposure may occur when individuals use

cl eaning solutions that contain methane sulfonic acid

.

The proposed use on animals at 3 % concentration is for use in a disinfectant teat wash for dairy cattle, goats or sheep. This could result in dietary exposure. However, the Agency believes that

use a s a disinfectant teat wash would contribute negligible amounts of methane sulfonic acid toPage 3 of 25

food/dairy processing. The current Agency assessments of dietary exposure are believed to be conservative (protective) enough to negate any health concerns as a res ult of that use pattern. Margins of Exposure for residential exposures (including aggregate exposure) and for occupational exposures are greater than 100 which do not exceed the Agency’s level of concern.

Discussion of environmental fate and effects is taken from EPA (2008). The conclusions in the earlier evaluation is not expected to have changed and thus are relied upon herein. The relative distributions of chemicals released into the environment can be estimated using the Level III Fugacity Model. This model (Table 6 ) shows that methane sulfonic acid will partition primarily to soil and water, with a higher affinity to soil, and a negligible portion to air and sediment.

Methane sulfonic acid is a strong acid with pKa of

- 1.92. This value indicates that methane

sulfonic acid will exist as an anion in moist soils and water. Methane sulfonic acid is minimally

volatile from water since anions do not volatilize. Methane sulfonic acid is highly mobile in soi l

with a Log Koc of 0.0 and biodegradation occu rs rapidly ; 100% of theoretical biochemical oxygen demand in 28 days using an activated sludge inoculum. If released to the atmosphere,

methane sulfonic acid will degrade by reaction with photochemically produced hydroxyl radicals

with an estimated half

- l ife of approximately 58 days. Methane sulfonic acid is expected to have low persistence and low bioaccumulation potential.

Based upon the findings presented earlier in the human health and risk assessment and the findings regarding environmental fate an d effects, the Agency approves of the requested uses of

methane sulfonic acid . As such, methane sulfonic acid may be formulated into products for use as an acid cleaner in pesticide formulations with a limit not to exceed 3 % final end use

concentration w hen used on animals [as a disinfectant teat wash for dairy cattle, goats or sheep];

and not to exceed 0.5 % (5,000 ppm in end

- use dilution solution) when used in antimicrobial

formulations for food

- contact surface sanitizing in public eating places, dairy

- p rocessing equipment, and food

- processing equipment and utensils.

II. INTRODUCTION

On 30 May 2014, the U.S. Environmental Protection Agency (EPA or “the Agency”) received a request (Petition No. IN

- 10720) from the firm Lewis & Harrison (122 C Street, N. W., Suite 505, Washington, DC 20001) on behalf of the BASF Corporation (100 Park Avenue, Florham Park, NJ 07932) to approve an exemption from the requirement of a tolerance under 40 CFR § 180.930 and § 180.940(a) for methane sulfonic acid (CAS Reg. No. 75

- 75

- 2) as an inert ingredient used as an acid cleaner in pesticide formulations

. The petition proposes that methane sulfonic acid “may be formulated into products for use as an acid cleaner in pesticide formulations with a limit

of 3 % when used on animal s [as a disinfectant teat wash in dairy cattle, goats or sheep] ; and

0.5 % (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

process ing equipment and utensils.” Based on the foregoing statement, the Agency utilizes 5,000 ppm as the maximum permissible end

- use concentration.

The Agency has pr eviously reviewed and approved the non

- food use of methane sulfonic acid (EPA, 2009) . Some o f the information contained in the Agency’s 2009 assessment is usedPage 4 of 25

within the current document. Further, some information contained in Petition No. IN

- 10720 is

also used in this document.

Methane sulfonic acid is marketed worldwide by BASF in various grades up to a very pure electronics grade. The registrant has verified that the maximum concentration of methane

sulfonic acid for use in a formulation is 15% (email, J. Delahay (BASF) to K. Samak (EPA), dated 10/26/2009). Typically, most formulations w ill contain < 5% methane sulfonic acid

. It is a strong organic acid and is readily biodegradable, ultimately forming sulfate and carbon

dioxide. M ethane sulfonic acid has many uses, including; metal finishing, electropolishing, lead

recovery , and the pro posed use as a cleaner in non

- food contact regulated formulations

.

III. PHYSICAL/CHEMICAL PROPERTIES (EPA, 2009)

The Agency’s H igh P roduction V olume S creening website, lists the physical properties of

methane sulfonic acid (CAS No. 75

- 75

- 2). Methane sulfonic acid is a liquid at room

temperature.

Table 1. Physical and Chemical Properties of Methanesulfonic Acid

Parameter Value MRID

or Source

Structure O ||

O=S

- OH |

CH 3 HPV, 2008

CAS Reg. No. 75

- 75

- 2 HPV, 2008 Molecular Weight 96.10 HPV, 2008

Common Names Methanesulfonic Acid HPV, 2008 Physical State Liquid at room temperature HPV, 2008 Density ( kg/m 3 ) 1481 @ 18°C Melting Point (°C) 19 (measured) HPV, 2008 Boiling Point (°C) 167 at 10 Hg; Decomposition at 225 (measured) HPV, 2008

Flash Po int (°C) 189 HPV, 2008 Water Solubility (g/L at 20°C) 1000 1 × 106 mg/L; miscible2 (measured) HPV, 2008

Vapor Pressure (mm Hg at 20°C) 9.75 × 10

- 3 (measured)

4.28 × 10

- 4 mm Hg at 25°C2 HPV, 2008

Partition Coefficient (log Kow)

- 4.98 (estimated) HPV, 20 08 Photodegradation Half

- life = 39 days HPV, 2008 Stability in Water (Hydrolysis)(t 1/2 ) Not expected to undergo hydrolysis in the

environment HPV, 2008

Biodegradation at 28 days (%) 100 HPV, 2008Page 5 of 25

IV TOXICOLOGICAL PROFILE

Acute Oral Toxicity ( EPA. 2009). (1) Male and female Sprague

- Dawley rats were administered methane sulfonic acid via oral gavage at 300, 500 or 750 mg/kg. Most clinical abnormalities were observed in two animals that

died and those that survived to day 14 and included saliva tion, decreased activity, wobbly gait, breathing abnormalities, apparent hypothermia, decreased/no defecation, feces small in size, urine stain, hunched posture, unkempt appearance, rough hair coat, piloerection, extremities pale in color, dehydration, ema ciation, distended abdomen, decreased food consumption and dark

material around the facial area. B ody weight loss was noted for one 300 mg/kg

- bw male, one 500 mg/kg

- bw male, two 500 mg/kg females and one 750 mg/kg male during the study day 0

- 7

interval. Body weight loss was noted for one 300 mg/kg male and one 750 mg/kg male during the study day 7

- 14 interval. Gross internal findings observed in the animals that died included distension/abnormal content/reddened mucosa in the digestive tract, dark red/mo ttled lungs,

blackish

- purple spleens, dark red lymph nodes, stained glandular mucosa in the stomach and body fat depletion/ discoloration/adhesions in the abdominal cavity.

LD 50 (male) > 750 mg/kg

LD 50 (female) < 500 mg/kg

LD 50 (combined) = 649 mg/kg

(2) Male and female Sprague

- Dawley rats were administered methane sulfonic acid via oral gavage at 500, 1000 or 1500 mg/kg. Clinical abnormalities observed during the study included salivation, breathing abnormalities, wobbly gait, decreased activity, decreas ed defecation, rough haircoat, urine/fecal stain and dark material around the facial area. Body weight loss was noted for one 1000 mg/kg male and one 1000 mg/kg female during the study day 0

- 7 interval and for one 300 mg/kg male and one 1000 mg/kg male du ring the study day 7

- 14 interval. In animals that died, gross pathologic f indings included dark red foci on the liver, blackish

- purple spleens and abnormal content, reddened/thickened mucosa and discoloration in the digestive tract.

LD 50 (male) < 1000 mg/ kg

LD 50 (female) < 1500 mg/kg

LD 50 (combined) = 1157.5 mg/kg

(3) Male Wistar rats were given methane sulfonic acid via oral gavage at 0.25, 0.5 or 1.0 mL/kg (or 2000, 4000, or 8000 mg/kg). All rats died by day 5. Sluggishness and unsteady gait were

seen at all doses. At 1.0 mL/kg, deep breathing was immediately observed. Findings at necropsy included: livers mottled and burned, stomach burned, pylorus hemorrhaged and gas filled, intestines hemorrhaged and gas filled, kidneys mottled and slightly congest ed.

LD 50 > 0.25 mL/kg equivalent to 2000 mg/kg

Acute Dermal Toxicity (EPA. 2009) (1) New Zealand White rabbits (10) were treated with 1000 mg/kg of methane sulfonic acid for 24 hours and observed for 14 days. Instances of few feces were the only abnorm al physical 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.

LD 50 > 1000 mg/kgPage 6 of 25

(2) Six albino New Zealand White rabbits were treated with 200 or 20 00 mg/kg of methane

sulfonic acid for 24 hours. At the end of the exposure period, no systemic toxicity was observed. Two rabbits at 2000 mg/kg died 28 hours after contact and an additional rabbit was euthanized 3 days after treatment for humane reasons. The 2000 mg/kg dermal exposure is highly toxic (severe skin injuries causing death) whereas the 200 mg/kg exposure induces minor skin lesions (erythema and acid burns). LD 50 > 200 < 2000 mg/kg

Acute Inhalation Toxicity (MRID 49396007 ) Twenty mice (strai n not specified) received a one

- time whole

- body exposure for one hour in a saturated (with methanesulfonic acid) atmosphere estimated to be 0.05 mg/L. No discernable effects were seen during the one

- hour test or during the 7

- day observation period.

Ski n Irritation (MRID 49396007) A skin irritation study was conducted with the mouse (strain not known). T he distal 4 cm of four

anesthetized mice were immersed in undiluted methane sulfonic acid for one hour then plu n ged

into a saturated solution of sodium bicarbonate for 30 seconds

. The tail of each mouse was white when exposure was terminated and the appendages fell off within one or two days. Methane

sulfonic acid was determined to be corrosive to the skin.

Eye Irritation (MRID 49396007) One eye each of two rabbits (strain not specified) received a single dose of 1.0 ml undiluted

methane sulfonic acid . There was immediate vocalization as a result of the pain. The reaction involved all ocular tissues and occurred immediately. The conjunctiva became completely necrotic without evident swelling. The iris was dilated with ragged edges and failed to react t o light. The cornea opacified completely within 24 hours. Methane sulfonic acid is extremely corrosive to the eye.

Sensitization (MRID 4939600 7) A skin sensitization test was conducted on Hartley Guinea pigs (10/sex/dose) using the Buehler derived test method. There were 5 (male and female) control animals. From a pilot study

undiluted methane sulfonic acid at 70% produced grades of 2,1 and ± with edema, blanching and scabbing on two sites. At 50, 25, 10, 5, 2.5 and 1.0% there were grades of ± and 0.5 % produced grades of ± and 0. The 50% concentration was chosen for the study. On day 1 0.3 ml of the test substance was applied to the left sh oulder. On day 7, the same region received a second dose. On day 14, the treated site received and 3 rd and final dose . All applications lasted approximately 6 hours. For the challenge, on day 28 all animals received 0.3 ml of test substance at 25%

conc entration on their left flank. The challenge duration was 24 hours. There was no positive control. Twenty guinea pigs were induced by 50% methane sulfonic acid 70% solution (i.e. 35%

methane sulfonic acid ) and challenged by 25% methane sulfonic acid 70 % solution (i.e., 17.5 %

methane sulfonic acid ). None of the test animals responded with a skin grade that would have been suggestive of sensitization.Page 7 of 25

Repeat

- Dose Toxicity (MRID 49396007)

Inhalation

A four

- week inhalation repeat dose toxicity stud y was conducted using “albino rats”. Fifteen male and 15 female per dose group were exposed 6hr/day 5day/week for 4 weeks. Doses were 0.026, 0.073 and 0.242 mg/L aerosol. During the study, 4, 1, 1 and 5 animals in the control, low dose, mid

- and high

- dos es were found dead. The deaths were attributed to the confinement in the

restraint tubes and none were attributable to exposure to the test article. Exposure related clinical signs included rales in the high

- dose group and an increased incidence of yello w matting on various body surfaces in the mid

- dose and high

- dose groups (males and females). No significant findings were noted during the recovery period. There was a transient reduction in body weight gain in the high

- dose males during the first week. The high dose groups had slightly decreased food consumption during the entire exposure period. There were no adverse effects noted in hematology, biochemistry, urinalysis or organ weights. Test article related microscopic findings

were observed in the nasal turbinates of the high dose group that were found dead and in all treated groups at study week 4 and 6 evaluations. After the 2

- week recovery period there seemed at least partial recovery from the irritative effects of the test material. Since this is a localized effect, it was not considered as systemic toxicity . Therefore the NOAEL was 0.242 mg/L, the highest dose tested. The LOAEL was not established in this study.

Sprague

- Dawley rats were exposed to 0, 0.026, 0.082, 0.23 and 0.74 mg/L in a 5 day repeat inhalation toxicity study (five males, 5 females per dose groups + control group). Exposures

were nose

- only for 6 hr/day. Two and three test article related deaths occurred in the 0.23 and 0.74 mg/L groups. All other survived to schedule d necr opsy. There were test article related rales in the 0.23 and 0.74 mg/L groups. Mean body weight loss and or reduced mean body weight gain were noted in males and females in the 0.74 mg/L group during day 0

- 1 through2

- 3. Mean body weights were generally r educed in males and females in the group through the entire study. Food consumption was reduced through the entire study in males and females of the 0.74 dose group. Organ weigh t s were unaffected by exposure to the test material. There were no

treatment related macroscopic findings in the treated animals. Microscopic findings believed attributable to the test material included mucosal necrosis, suppurative inflammation and/or nasal exudate in males and females in the 0.23 and 0.74 mg/L groups. Since th is is a localized effect, it was not considered as systemic toxicity. The NOAEL was determined to be 0. 74 mg/L ( 191 mg/kg/day ) under the conditions of this study.

Feeding Studies

A 7

- day repeat dose feeding study was conducted with Wistar rats. Five male and female rats per dose were given 0, 51, 185, 420 and 1805 mg/kg / day in males and 0, 55, 201, 551 and 2122 mg/kg/day for females. There was a concurrent, untreated control group. Methane sulfonic acid

was administered in the feed ad libitum. There we re no treatment related deaths during the study. There were no changes in food consumption, body weight change, liver and kidney weight as a result of exposure from the food. The NOAEL was determined to be 1805 and 2122 mg/kg/day for males and females re spectively.

In Vitro Genotoxicity (MRID 49396007) (1) A reverse gene mutation assay was conducted using Salmonella typhimurium test strains TA 1535, TA 1537, TA1538, TA98 and TA100. Test concentrations were 100, 500, 1000, 2500 andPage 8 of 25

5000 μ g/plate and 500 0 and 10000 μ g /plate on TA98 and TA100. The test was conducted with

and without metabolic activation. Methane sulfonic acid induced marked toxicity on two test

strains TA98 and TA100 at 1000 μ /plate with and without metabolic activation. It was observed that the S9 mix preparation precipitated at those two concentrations. Without metabolic

activation at 5000 μ g/plate a moderate toxic effect was noted on TA100 whereas on TA98 a decrease of the revertant colonies number with a sparse background was noted. Methanesulfonic acid with or without metabolic activation did not induce any increase of revertant colonies per plate at any dosage.

(2) In another reverse gene mutation assay, Salmonella typhimurium strains TA98, TA100, TA1535, TA1537 and TA1538 were tested with and without metabolic activation with concentrations of 10, 32, 100, 316 and 1000 μ g/plate . There were no increases in reversion to prototrophy in any of bacterial strains, either with or without metabolic activation. Inhibition of growth, o bserved as thinning of the background lawn of non revertant cells and reduction in colony numbers occurred in all strains with exposure to 1000 μ /plate which was determined to be the cytotoxic concentration.

(3) In a third reverse gene mutation assay, S almonella typhimurium strains TA100 and 1535

were tested with concentrations of methane sulfonic acid of 384.4 1to 12300 μ /plate with and without metabolic activation. There were three replicates per dose. Metabolic activation was

from S9

- mix from Spragu e Dawley rats treated with Aroclor 1254 with distilled water as the

vehicle. The test was negative for test related revertant colonies.

(4) A micronucleus assay was conducted using CD

- 1 mice. In a preliminary study a single oral gavage dose of 0, 125 , 250, 500, 1000 and 2500 mg/kg. Subsequently, male and female mice were given a single dose of methane sulfonic acid of 20, 100 or 500 mg/kg. In all cases m ethane

sulfonic acid was dose d orally in distilled water. Concurrent vehicle and positive contro l groups of mice were similarly dosed with distilled water or chlorambucil (30 mg/kg) respectively. Fi ve males and five females from each group were sacrificed at 24 after treatment. Additional lots of five males and five females were given methane sulfo nic acid at 0, 20, 100 or 500 mg/kg or the

vehicle control and were sacrificed at 48 and 72 hours after treatment. Bone marrow smears on glass slides were stained and prepared for examination. At least 2000 erythrocytes per animal was taken for the presen ce of micronuclei. In the range finding study one female died approximately 30 seconds post

- dose at 2500 mg/kg. One male was sacrificed in extremis approximately 30 minutes post

- dose. Signs included hunched posture, piloerection, slow labored breathing and inability to move. At the 1000 mg/kg dose, one male was found dead at about 2 hours post

- dose. The remaining male and both females were killed in extremis approximately 21 hours post

- dose. All other animals survived to schedule sacrifice. Piloerect ion was noted in all

animals in the 2 4 hour period following dosing at 500 mg/kg. No adverse reactions to treatment were recorded for any other group of animals dosed with methane sulfonic acid.

In the main study two males dose d at 500 mg/kg were found dea d approximately 212 hours post

dose. One animal exhibiting piloerection, severe rales and loss of facial hair was killed approximately 48 hour post

- dose. All surviving males in the 500 mg/kg groups showed pilo

erection. One male and one female showed rales

. All other animals remained unsymptomatic.Page 9 of 25

No significant variation in treated animals was reported in terms of micronucleated erythrocytes per animal. The chlorambucil group exhibited a significant increase of micronucleated polychromatic erythro cytes. No indication of bone marrow toxicity as evidence b y depression o f bone marrow proliferation was noted in any group treated with methanesulfonic acid.

Reproductive Toxicity (EPA. 2009) In a combined reproductive/developmental toxicity screenin g test, Sprague

- Dawley rats were

administered methane sulfonic acid daily via gavage at 250, 500, or 1000 mg/kg/day

. Males were dosed four weeks prior to mating, two weeks during the mating period and until sacrifice. Females were dosed four weeks prior to mating, two weeks during the mating period, through gestation (3 weeks), lactation until day 4 post

- partum (pp) and until sacrifice (day 5 pp). No mortality was seen. Clinical signs in males included ptyalism (excessive salivation) at 1000 mg/kg/day

. There were no treatment

- related effects on body weights, organ weight changes or histopathology. Methane sulfonic acid did not affect male and female reproductive performance or the progeny of the parental rats up to 1000 mg/kg/day. NOAEL (parental/reprod uctive /offspring toxicity) = 1000 mg/kg/day (based on no effects at highest dose tested)

Developmental Toxicity (EPA. 2009) (1) Female rats (25/dose ; strain: Sprague

- Dawley ) were given daily oral gavage doses of

methane sulfonic acid at 0, 25, 100 or 40 0 mg/kg / day from gestation day 6 through 15 (GD 6

- 15). Based on the results of this study, the NOAEL was determined to be 400 mg/kg/day for maternal toxicity and developmental toxicity. NOAEL (maternal and developmental toxicity) = 400 mg/kg/day (based on no effects at highest dose tested)

(2) Female rats (8/dose ; strain: Sprague

- Dawley ) were given daily oral gavage doses of the test substance at 0, 25, 50, 100, 200 or 300 mg/kg/day from GD 5 through 15. Treatment

- related clinical signs included rales, labored respiration and gasping in the 100, 200 and 300 mg/kg/day

groups. Findings of red material around the nose and/or mouth in the 100, 200 and 300 mg/kg/day groups often correlated with occurrences of the aforementioned respiratory

abnormalities. S light mean body weight losses and reduction in food consumption occurred in the 100, 200 and 300 mg/kg/day groups during GD 6

- 9 when evaluated on a group mean basis. Food consumption was slightly reduced in the 100, 200 and 300 mg/kg/day groups during GD 6

- 9 when the group means were compared with the control group mean. Thi s reduced food consumption seemed to be the result of a localized gastro

- intestinal effect due to the dosage concentration to these groups and the corrosive nature of the test article. No effects on any other parameters were reported in the dams. No developmental toxicity was observed at dose levels up to 300 mg/kg/day. LOAEL (maternal toxicity) = 100 mg/kg/day (based on slight changes in body weight and food consumption) NOAEL (matern al toxicity) = 50 mg/kg/day

Sub chronic toxicity No sub chronic toxicity studies are available on methane sulfonic acid.Page 10 of 25

Chronic toxicity and carcinogenicity No chronic or carcinogenicity studies are available on methane sulfonic acid

.

Neurotoxi city Although neurotoxicity studies have not been submitted for methane sulfonic acid , there is no evidence of neurotoxicity in any study in the toxicity database. No treatment

- related effects were seen for parental toxicity or reproductive performance in a combined reproductive/developmental toxicity screening test at the highest dose tested (1000 mg/kg/day ). Available prenatal developmental toxicity data showed no clinical sign of neurotoxicity at the highest dose tested (400 mg/kg/day ). In another dev elopmental toxicity study, t reatment

- related clinical signs included rales, labored respiration and gasping at 100, 200 and 300 mg/kg/day , but

the se signs were considered secondary to corrosive nature of the chemical and not a neurotoxicity trigger Based o n the above weight of evidence, methane sulfonic acid is not expected to be neurotoxic.

V. Toxicity Endpoint Selection

The inhalation toxicity NOAEL was taken from the 5 day repeat dose inhalation toxicity study where Sprague

- Dawley rats were exposed to 0, 0.026, 0.082, 0.23 and 0.74 mg/L. There were no treatment related macroscopic findings in the treated animals. Microscopic findings believed attributable to the test material included mucosal necrosis, suppurative inflammation and/or nasal

exudate in males and females in the 0.23 and 0.74 mg/L groups. The NOAEL was determined to be 0.74 mg/L ( 191 mg/kg/day ) under the conditions of this study.

The inhalation NOAEL was converted to mg/kg/day using the convention described by Whalen in 2001 (Whalen, J. 2001. Policy: inhalation Toxicity Study Waivers for Active Ingredients and

Formulations” Internal memorandum unpublished to OPP Toxicology Reviewers 12 SEPT 2001, Health Effects Division/Office of Pesticide Programs.)

Inhalation Mg/L → Oral mg/kg/day = Rat

Mg/L * A * MV * D = mg/kg/day

BW

A The inhalation:oral absorption ratio. In the absence of oral and inhalation absorption data, the ratio is assumed to be 1.

MV minute volume (L/min) (0.17 L/M average volume for Sprague

- Dawley r ats)

D Duration of daily exposure (minutes/day)(360 min/day = number of minutes in six hour

exposure BW Body weight = 0.236 kg (avg. weight for male and female Sprague

- Dawley rats.

0

. 74 mg/L * 1 * 0.17 L/min * 360 min/day = 191 mg/kg/day

.

0.236 kgPage 11 of 25

The dermal toxicity NOAEL is selected from a developmental toxicity study (EPA, 2009).

Female Sprague

- Dawley rats (25/dose ; strain ) were given daily oral gavage doses of methane

sulfonic acid at 0, 25, 100 or 400 mg/kg/d ay from gestation day 6 through 15 (GD 6

- 15). Based on the results of this study, the NOAEL was determined to be 400 mg/kg/day for maternal toxicity and developmental toxicity. NOAEL (maternal and developmental toxicity) = 400 mg/kg/day (based on no eff ects at highest dose tested)

.

The oral toxicity NOAEL is taken from the developmental toxicity study (EPA, 2009) with

female Sprague

- Dawley rats where the NOAEL was identified as 400 mg/kg/day . This dose is

used for the d ietary exposure assessment.

VI

. EXPOSURE

Based upon the requested use patterns, there are a number of ways by which humans may be exposed to methane sulfonic acid . Dietary exposure may occur as a result of residues transferred from treated food contact areas. Dietary exposure may occur as a result of residues remaining in treated food/dairy processing equipment or systems. Dermal and inhalation exposures may occur as a result of the use of sanitizing solutions which contain methane sulfonic acid

. Exposures from the use of sanitiz ing solutions may be “occupational” exposures or “residential” exposures. Occupational exposures are those that result from persons who use/apply sanitizing solutions during the course of normal work related activities such as cleaning/disinfecting food

c ontact preparation surfaces and food or dairy processing machinery or systems. “Residential” dermal and inhalation exposure may occur when individuals use cleaning solutions that contain

methane sulfonic acid

.

The proposed use on animals at 3 % concentra tion is for use in a disinfectant teat wash for dairy cattle, goats or sheep. This could result in dietary exposure. The use as a disinfectant teat wash

contributes small amounts of methane sulfonic acid to food from meat and dairy products ( inert

dietar y assessment attached)

.

Dietary Exposure/Risk Characterization

To assess dietary exposure resulting from residues on food contact surface areas, the Agency uses the Food and Drug Administration (FDA) Food Contact Surface Sanitizing Solution Dietary

E xposure Assessment Model (FDA/CFSAN OPA: Chemistry Guidance

– Sanitizing Solution version 1.1; January 1993; Office of Premarket Approval now Office of Food Additive Safety). The model is presented in the attachment. The model was run using the maximum c oncentration expected for methane sulfonic acid (5000 ppm) and adjusted for body weight according to current OPP policy. The results are summarized as follows:

EDI = (1 mg/cm 2 )(5000 ug methane sulfonic acid /1000 mg)(4000 cm 2 food contact surface area /pe rson/day )(100%
transfer rate of sanitizer to food) = 20,000 μ g/person/day = 20 mg/person/day

Mg/kg/day

Adult 20 mg/day ÷ 80 kg bw = 0.25 mg/kg/day

Child 20 mg/day ÷ 1 5 kg bw = 1. 3 mg/kg/day

Margin of Exposure (MOE) = NOAEL ( 400 mg/kg/day )/ExposurePage 12 of 25

Adu lt 400 mg/kg/day /0.25 mg/kg/day = 1,600

Child 400 mg/kg/day / 1.3 mg/kg/day = 310

Dietary Exposure from Clean

- In

- Place (CIP)

The assessment of dietary exposure as a result of food handling/processing machinery that is

cleaned

- in

- place. The sanitizing so lution is pumped through the plumbing of the machinery and not followed by a rinse with potable water. The algorithm, f ood mass to surface ratios and consumption levels of various foods are taken from Shamim (2006; MRID 49396009)

.

Table 2.0 Food Mass to Surface Ratios and Consumption Levels

Food Food Mass to Surface Ratio

Gram/cm 2 Food Consumption

Gram/person/day

Milk 6.6 124 Mayonnaise 64 9

Beer 150 182 Beverage Other 150 240

The algorithm used to calculate dietary exposure is:

The above assump tions and the following equations were used to calculate EDI and Dietary Daily Dose (DDD):

EDI Estimated Daily Intake (mg/p/day) = AR x RS x DIR x methane sulfonic acid

- 1 x F x 10

- 6 x CMF

DDD D ietary D aily D ose (mg/kg/day) = AR x RS x DIR x methane sulfonic acid ACID

- 1 x F x 10

- 6 x CMF/BW

Where:

AR = Application rate of sanitizer (ppm)

RS = Residual solution (mg/cm 2 )

M SA = Mass

- surface area ratio (the treated surface that comes into contact with food) (g/cm 2 )

DIR = Daily intake rate of food i n a given day (g/p/day)

F = Fraction of the pesticide transferred or migrated to food (unitless) (100%)

BW = Body weight (kg)

CMF = Calorie intake modification factor (100% adults; 64.4% Children) Example of adult consuming milk: 5,000 ( ppm ) * 1 mg * 12 4 g * ( 6.6 g )

- 1 * 1 * 10

- 6 * 1 (adult) = 0.094 m g /p/day

cm 2 p erson/day cm 2

0.09 4 m g /p/day ÷ 80 kg bw = 1.17

- 3 mg/kg/day 0.094 mg/p/day ÷ 15 kg bw * 0.644 calorie intake modificatio n factor = 4.04

- 3 mg/kg/dayPage 13 of 25

Table 3.0 Estimated Daily Intake from Clean

- In

- Place (Adult and Toddler)

Food Adult 80 kg bw Toddler *

1 5 kg bw
mg/kg/day

Milk 1.17

- 3 4.0 4

- 3

Eggs/Mayonnaise 8.8

- 6 3.01

- 5

Beer 7.58

- 5 N/A Beverages, Other 1

- 4 3.43

- 4

TOTAL 0.00135 0.00441

* Toddler includes 64.4% calorie intake modification from adult value = CMF

Estimated Dietary Exposure.

Estimated dietary exposures that might result from residues from treated dairy cattle, sheep or

go ats are estimated using the Agency’s dietary exposure model. Estimated residues are calculated for meat and dairy products. Results from the inert dietary exposure model (copy attached) indicate that the total daily exposure to the total U.S. population is 0.006755 mg/kg/day ( 0.2 % of the chronic reference dose). The most highly exposed subpopulation is for children 1

- 2 years of age and the estimated total daily exposure is 0.029442 mg/kg/day ( 0.7 % of the chronic reference dose)

.

Residential (Non

- Occup ational) Exposure/Risk Characterization

A final end

- use dilution of methane sulfonic acid is stated to be 5000 ppm or 0.5 % (5000/1000000) * 100% = 0.5. Rates of application are based upon the assumption of 0.5 %

methane sulfonic acid in final end

- use dilu tion.

Assessment of residential (non

- occupational) exposure and risk is done using techniques taken

from the “ Amine Oxide 900439, (C10

- 16); C10

- C18

- Alkyldimethylamine oxides; Human Health Risk Assessment and Ecological Effects Assessment to Support Propos ed Exemption from the Requirement of a Tolerance When Used as Inert Ingredients in Pesticide Formulations. ” (Memorandum, 22 SEPT 09 L. Austin to P. Shah).

The following key assumptions were used in this assessment:

 For the mopping scenario, the CMA de rmal and inhalation unit exposure values for ungloved mopping were used (71.6 mg/lb inert. and 2.38 mg/lb inert, respectively). These values are based on data collected from six replicates mopping floors and receiving exposure via contact with the mop or with the bucket.

 For the wiping scenario, the CMA dermal and inhalation unit exposure values for ungloved wiping were used (2,870 mg/lb inert and 67.3 mg/lb inert, respectively). These values are based on data collected from six replicates (dental technic ians) who used a finger pump sprayer to apply the product and then wiped the surfaces with a paper towel.Page 14 of 25 1 gallon formulated pesticide solution*(8.34 lbs/gallon)*( 0. 5) % methane sulfonic acid )*(2 oz/ 128 oz dilution factor) =

0.00 065 lbs methane sulfonic acid in formulated pesticide solutions per day

0.13 gallon formulated pesticide solution*(8.34 lbs/gallon)*( 0.5) % methane sulfonic acid = 0.0 054 lbs methane sul fonic

acid in formulated pesticide solutions per day

0.094 gallon formulated pesticide solution*(8.34 lbs/gallon)*(4% amine oxide) = 0.0 039 lbs methane sulfonic acid in formulated pesticide solutions per day  For aerosol spray, trigger pump and air deodorization scenarios, the PHED dermal and inhalation unit exposure values are 220 mg/lb inert and 2.4 mg/lb inert, respectively. The values are based on homeowners applying an aerosol insecticide to baseboards in kitchens and are representative of a handler wearing short pants and a short sleeve shirt, with no gloves.

The quantities handled/treated were estim ated based on information from various sources and assumptions.

 For the mopping scenarios, it was assumed that 1 gallon of diluted solution is used. HED assumes that cleaning products are assumed to have the same density as water (8.34 lbs/gallon). Whi le typical product concentrate directions indicate that 1 oz concentrated product per 1 gallon of water should be used, HED followed the AD SOP and assumed a dilution factor of 2 oz concentrated product/128 oz (1 gallon) of water for the residential

handle r risk assessment to represent heavy

- duty cleaning formulations. This is comparable to the one quarter cup of cleaner diluted in one gallon of water as stated in AD’s SOP. Based on information from RD, the Agency assumed that the maximum percentage by we ight in indoor products would be 0.5 % methane sulfonic acid

.

 For the wiping and trigger pump spray scenarios, it was assumed that 0.5 liter (0.13 gal) of ready

- to

- use (RTU) solution is used. For anti

- microbial products, 0.5 % methane

sulfonic acid in pro duct is assumed.

 For the aerosol foam spray , it is assumed that one can of product is used. For the aerosol spray/trigger pump, it is assumed that a 12 oz net weight product is used (0.094 gallons).

0.5 % methane sulfonic acid amine oxide inert in anti microbial product assumed.

Dermal and inhalation absorption are assumed to be 100 %.

HED believes the duration of exposure for most homeowner applications of indoor cleaning products is believed to be best represented by the short

- term duration (1 to 30 days) because the different scenarios (i.e. methods of application) are assumed to be episodic, not daily. In addition, homeowners are assumed to use different cleaning products with varying active and inert ingredients.

Risk SummaryPage 15 of 25

For all residenti al handler scenarios, risk estimates are not of concern (i.e., MOEs are all greater than 100)

. A summary of the results are provided below in Tables 4.0 , below.

The Agency believes that the handler scenarios assessed represent worse

- case exposures and r isks resulting from use of indoor cleaning products containing methane sulfonic acid

in residential environments.

Table 4.0 Estimated Residential “Handler” Exposures and Risks

Exposure

Scenario (Formulation/ Application) Application

Rate 1 (lb

inert/ gal lon) Quantity

Handled/

Treated per day 2 Dermal

Unit Exposure (mg/lb inert) 3 Inhalation

Unit Exposure (mg/ lb inert) 3 Dermal

Dose (mg/kg /day) 4 Inhalation

Dose (mg/kg/ day) 5 Baseline

Dermal

MOE 6 Baseline

Inhalation

MOE 7

Indoor hard surface, Mopping (ST) (C MA data) 0.00 06 5

lb/gal 1 gallon 71.6 2.38 0.000 58 0.00018 690,000 1M

Indoor hard surface, Wiping (ST) (CMA data) 0. 005 4

lb/gal 0.13

gallons 2870 67.3 0.0 25 0.0 0059 16000 324,000

Indoor hard surface, Aerosol spray (ST) (PHED data) 0. 0039

lb/gal 0.094

gal lons (12 oz) 220 2.4 0.00 1 0.00 00 1 400,000 19 M

1 Application rates are based on maximum applicat ion rates of products containing methane sulfonic multiplied by 0.5 % to

convert from product application rate to inert application rate.

2 Per AD (Revised Res idential SOPs 2001) i ndoor house

- hold products are assumed to be used at 1 gallon of solution for the mopping scenario , 0.5 L (0.13 gallon) of solution for the wiping scenario, and a 12 oz (0.094 gallon) can of trigger pump

3 Unit Exposure data sources are identified in the exposure scenario column. All exposure scenarios assess exposure reflecting applicators wearing short

- sleeved shirts and shorts and no respiratory protection.

4 Daily Dermal Dose = (Dermal Unit Exposure (mg inert /lb inert handled ) * Ap p lication Rate (lb /gal) * Quantity handled (gallons/day) )/ Body Weight ( 8 0 kg)

5 Daily Inhalation Dose = (Inhalation Unit Exposure (mg inert / lb inert) * Application Rate (lb /gal ) * Quantity handled ( gallons/day )) / Body Weight ( 8 0 kg)

6 Dermal MOE = PoD (NOAEL of 4 00 mg/kg/day)/ Daily dermal dose (mg/kg/day)

7 Inhalation MOE = PoD (NOAEL of 191 mg/kg/day) / Daily inhalation dose (mg/kg/day)

Occupational Exposure

Estimates of occupational exposures and risks were conducted using standard procedur e developed by the Science Advisory Committee for Exposure (ExpoSAC)/Health Effects Division/Office of Pesticide Programs/EPA. The algorithm to estimate exposure is:

UE * AR * Units ÷ BW where

UE = Unit Exposures (mg/lb inert handled) AR = Rate of Applic ation (lb inert/gal) (0.5% * 8.34 lb/gal = 0.0417 lb inert/gal) Units Treated = Quantity Handled (applied)/day (in this case gallons) BW = Body Weight (80 kg assumed for average adult in U.S.) Absorption via the dermal and inhalation route of exposure is a ssumed to be 100% therefore there is no correction for absorption factors.Page 16 of 25 Table 5.0 Occupational Exposures and Risks From Using Products Containing methane sulfonic acid

Method of Application Dermal

Unit Exposure mg/lb

handled Inhalat ion

Unit Exposure mg/lb

handled Application

Rate

lb M ethane

sulfonic

acid /gal Quantity

Handled/ Treated per day (gallons) Dermal

Dose mg/kg/day Inhalatio n

Dose mg/kg/day Dermal

MOE Inhalation MOE

Brush 220 0.28

0.0415

lb M ethane

sulfonic

acid / gallon 0.26 0.0297 3.8

- 5 13,500 5M

Foam 220 1.3 0.26 0.0297 1.8

- 4 13,500 1M

Immersion 11 1.89 10 0.057 9.8

- 3 7020 20,000
Trigger Pump Spray 220 0.681 0.26 0.0297 9.2

- 5 13,500 2.1M

Low

pressure handwand

(clean) 220 1.3 2 0.23 1.4

- 5 1740 1.4M

High

pressur e

spray (sanitize) 11 0.12

40 0.23 2.5

- 9 1740 7.6 10

Sponge/mes h wipe (clean) 2870 67.3 0.26 0.39 9.1

- 3 1025 21,000

Cleaning in Place (CIP) (clean and sanitize) 0.135 0.00361 10,000 0.7 0.019 571 10,000

1 Dermal Unit Exposures are taken from Leighto n (2005).

2 Inhalation Unit Exposures are taken from Smegal et al. (2006).

3 Application rate based upon use

- solution concentration of 5000 ppm methane sulfonic acid

. 4 Quantity handled per day taken from Smegal et al. (2006).

5 Daily dermal and inhalation dos e described above

6 Dermal and inhalation Margin of Exposure (MOE) = Toxicological No Observed Adverse Effect Level (NOAEL) ( mg/kg/day ) ÷ Daily dermal or inhalation dose ( mg/kg/day ).Page 17 of 25

VII. AGGREGATE RISK

In addition to consideration of single, acute exp osures, the Agency also considers the possibility of aggregate exposures. Aggregate exposure refers to the sum(s) of individual exposures that might occur within a limited time frame. Aggregate exposure assessments are conducted for

non

- occupationally ex posed individuals i.e., for adults and toddlers (residents). In this case aggregate exposures consider oral (dietary) exposure that might result from residues in meat or dairy products from cattle, sheep or goats that were subjected to a disinfectant teat wash, from residues from treated food handling surfaces and from non

- occupational uses such as hard surface cleaning/wiping. Exposures from hard surface cleaning/wiping does not apply to

toddlers.

For adults the Agency uses the highest residential appl icator exposure ( indoor hard surface cleaning using hand wiping ), dietary exposure from treated dairy animals as estimated by using

the dietary exposure model (results attached) and from estimated post

- application exposure s estimated by the FDA Food Surfac e Model . For toddlers, the Agency combines estimated exposures from the FDA model and the inert dietary exposure model.

Results from the inert dietary exposure model indicate that the total daily exposure to the total U.S. population is 0.006755 mg/kg/da y ( 0.2 % of the chronic reference dose). The most highly exposed subpopulation are children 1

- 2 years of age and the estimated total daily exposure is

0.029442 mg/kg/day ( 0.7 % of the chronic reference dose)

.

Table 6.0 Estimated Aggregate Non

- Occupationa l Exposure

Source Adult mg/kg/day Toddler

mg/kg/day

FDA Food Surface Model 0.25 1.3 Daily intake from Clean in Place 0.00135 0.00441 Dietary exposures

- meat and dairy products from cattle, sheep and

goats 0.006755 0.029442

Non

- Occupational Use from Hard surface wiping 0.025 N/A

TOTAL 0.2 83 1.3

Margin of Exposure = NOAEL mg/kg/day ÷ Exposure (daily dose) mg/kg/day

400 mg/kg/day

/ 0.2 83 = 1 680 (adult)

400 mg/kg/day/1.3 mg/kg/day = 3 07

.

The chronic RfD (cPAD) is 4.0 mg/kg/day . The total aggregate dose for non

- occupational exposure occupies 0.0 7 % of the cPAD and therefore does not exceed the Agency’s level of

concern.Page 18 of 25

IX. ENVIRONMENTAL FATE & EFFECTS

Discussion of environmental fate and effects is taken fr om EPA (2008). The conclusions in the earlier evaluation is not expected to have changed and thus are relied upon herein. The relative distributions of chemicals released into the environment can be estimated using the Level III Fugacity Model. This mod el (Table 6 ) shows that methane sulfonic acid will partition primarily to soil and water, with a higher affinity to soil, and a negligible portion to air and sediment. (HPV, 2008)

Table 7 . Level III Fugacity Estimated

Fugacity Level III Methanesulfonic Acid Air (%) <1 Water (%) 40.7 Soil (%) 59.2 Sediment (%) < 1

Methane sulfonic acid is a strong acid with pKa of

- 1.92. This value indicates that methane

sulfonic acid will exist as an anion in moist soils and water. Methane sulfonic acid is minimal ly

volatile from water since anions do not volatilize. Methane sulfonic acid is highly mobile in soi l

with a Log Koc of 0.0 and biodegradation occurs rapidly ; 100% of theoretical biochemical oxygen demand in 28 days using an activated sludge inoculum. If released to the atmosphere,

methane sulfonic acid will degrade by reaction with photochemically produced hydroxyl radicals

with an estimated half

- life of approximately 58 days. Methane sulfonic acid is expected to have low persistence and low bioaccumulat ion potential. (HPV, 2008)

The evaluation of available aquatic toxicity data for fish, aquatic invertebrates and aquatic plants indicates that the potential acute hazard of methane sulfonic acid to fish and aquatic plants is low and to aquatic invertebra tes is moderate based on the following studies; in acute toxicity studies with water fleas ( D aphnia magna ) the 48

- hr EC 50 was 260 mg ai/L, with an NOEC of 120 mg/L; the 96

- hr LC 50 in rainbow trout ( Oncorhynchus mykiss ) was 73 mg ai/L with an NOEC of 56 mg/ L; the NOEC 96

- hr LC 50 in fresh water green algae ( Selenastrum capricornutum ) was 5.8 mg/L; and the 72

- hour EC50 (biomass) ( Pseudokirchneriella subcapitata) was 14 mg /L (HPV, 2008).

Of all the organic sulfonic acids, methane sulfonic acid has the lowest b iochemical oxygen

demand. It is readily biodegradable, ultimately forming sulfate and carbon dioxide; and is not expected to bioaccumulate. Methane sulfonic acid dissolves easily in water and can therefore be extracted from the organic phase with only a small amount of water. This allows the acid to be readily recycled (BASF, 2008).

Based on the these studies and the biodegradability of methane sulfonic acid to form sulfate and carbon dioxide, effects of concern to non

- target aquatic organisms resultin g from the use of this substance as an inert ingredient are not anticipated in the environment.Page 19 of 25

X. DETERMINATION OF SAFETY

Section 408(b)(2)(c) of FFDCA provides that EPA shall apply an additional tenfold (10X) margin of safety for infants and child ren in the case of threshold effects to account for prenatal and postnatal toxicity and the completeness of the database on toxicity and exposure unless EPA determines based on reliable data that a different margin of safety

will be safe for infants and ch ildren. This additional margin of safety is commonly referred to as the FQPA safety factor (SF). In applying this provision, EPA either retains the default value of 10X, or uses a different additional safety factor when reliable data available to EPA suppo rt the choice of a different factor.

Based on lack of any systemic toxicity and the irritating property of the chemical which precluded testing at a higher doses, EPA has concluded that there are no toxicological endpoints of concern for the U.S. popula tion, including infants and children, and has conducted a qua ntitative assessment. As part of its qualitative assessment, the Agency did not use safety factors for assessing risk, and no additional safety factor is needed for assessing risk to infants and children.

Taking into consideration the available information, EPA concludes that the additional 1X FQPA safety factor will be retained.

XI. ENVIRONMENTAL JUSTICE

Potential areas of environmental justice concerns, to the extent possible, were considered in this human health risk assessment, in accordance with U.S. Executive Order 12898, "Federal Actions to Address Environmental Justice in Minority Populations and Low

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

As a part of every pesticide risk assessment, OPP considers a large variety of consumer subgroups according to well

- established procedures. In line with OPP policy, HED estimates

ri sks 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 pa tterns 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, se ason of the year, ethnic group, and region of the country. Additionally, OPP is able to assess dietary exposure to smaller, specialized subgroups and exposure assessments are performed when conditions or circumstances warrant. Whenever appropriate, non

- d ietary 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 evaluated. Further considerations are currently in developme nt 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.Page 20 of 25

XII. HUMAN STU DIES

This assessment does not rely on any studies in which human subjects were intentionally exposed to a pesticide.

XIII

. I NTERNATIONAL LIMITS: None

XIV. RISK CHARACTERIZATION

Methane sulfonic acid has moderate acute oral toxicity to rats, an d moderate acute dermal toxicity to rabbits. Methane sulfonic acid is corrosive to mouse skin, extremely corrosive to the eye, but showed no evidence of dermal sensitization. Following repeated nose

- only

inhalation exposures in rats to low concentrations , clear evidence of portal

- of

- entry effects, such as histopathological lesions in the nasal turbinates were observed. In a 7

- repeat dose oral feeding study in rats, no systemic toxicity was observed at doses up to 1805 mg/kg/day . No effects were

seen for parental toxicity, offspring/developmental toxicity or reproductive performance in a combined reproductive/developmental toxicity screening test at doses up to 1000 mg/kg/day. In one developmental toxicity study in rats, no parental systemic or developmen tal toxicity was observed at doses up to 400 mg/kg/day. Available prenatal developmental toxicity data showed some evidence of slight maternal toxicity but no developmental effects. Methane sulfonic

acid was not mutagenic and did not induce chromosomal ab errations. There are no metabolism, chronic toxicity or carcinogenicity studies available on methane sulfonic acid. However, based on the lack of systemic toxicity at 1000 mg/kg/day and above in a combined reproductive/developmental screening study and 7

- day dietary study, and the lack of mutagenicity concern, there are low concerns for cancer.

A lthough neurotoxicity studies have not been submitted for methane sulfonic acid there is no evidence of neurotoxicity in any study in the toxicity database in cluding a combined reproductive/developmental toxicity screening test and prenatal developmental toxicity studies.

The inhalation toxicity NOAEL was taken from the repeat

- dose inhalation study discussed

earlier. There were no treatment related macroscopi c findings in the treated animals. Microscopic findings believed attributable to the test material included mucosal necrosis, suppurative inflammation and/or nasal exudate in males and females in the 0.23 and 0.74 mg/L groups. The NOAEL was determined to be 0. 74 mg/L ( 191 mg/kg/day).

The dermal toxicity NOAEL is selected from a developmental toxicity study. Based on the results of this study, the NOAEL was determined to be 400 mg/kg/day for maternal toxicity and developmental toxicity. NOAEL (materna l and developmental toxicity) = 400 mg/kg/day (based on no effects at highest dose tested)

.

The oral toxicity NOAEL is taken from the developmental toxicity study with female Sprague

Dawley rats where the NOAEL was identified as 400 mg/kg/day . This dose is used for the inert dietary exposure assessment.

Based upon the requested use patterns, humans may be exposed to methane sulfonic acid

. Dietary exposure may occur as a result of residues transferred from treated food contact areas.Page 21 of 25

Dietary exposure may occur as a result of residues remaining in treated food/dairy processing equipment or systems. Dermal and inhalation exposures may occur as a result of the use of sanitizing solutions which contain methane sulfonic acid . Exposures from the use of sa nitizing solutions may be “occupational” exposures or “residential” exposures. Occupational exposures are those that result from persons who use/apply sanitizing solutions during the course of normal work related activities such as cleaning/disinfecting f ood contact preparation surfaces and food or dairy processing machinery or systems. “Residential” dermal and inhalation exposure may occur when individuals use cleaning solutions that contain methane sulfonic acid

.

The proposed use on animals at 3 % conc entration is for use in a disinfectant teat wash for dairy cattle, goats or sheep. This could result in dietary exposure. The current Agency assessments of dietary exposure are believed to be conservative (protective) enough to negate any health

concerns as a result of that use pattern. It is not further considered in a quantitative sense.

Margins of Exposure for residential exposures (including aggregate exposure) and for occupational exposures are greater than 100 which do not exceed the Agency’s leve l of concern.

Discussion of environmental fate and effects is taken from EPA (2008). The conclusions in the earlier evaluation is not expected to have changed and thus are relied upon herein. The relative

distributions of chemicals released into the env ironment can be estimated using the Level III Fugacity Model. This model (Table 6 ) shows that methane sulfonic acid will partition primarily to soil and water, with a higher affinity to soil, and a negligible portion to air and sediment.

Methane sulfonic acid is a strong acid with pKa of

- 1.92. This value indicates that methane

sulfonic acid will exist as an anion in moist soils and water. M ethane sulfonic acid is minimally

volatile from water since anions do not volatilize. M ethane sulfonic acid is high ly mobile in soi l

with a Log Koc of 0.0 and biodegradation occurs rapidly ; 100% of theoretical biochemical oxygen demand in 28 days using an activated sludge inoculum. If released to the atmosphere,

methane sulfonic acid will degrade by reaction with phot ochemically produced hydroxyl radicals

with an estimated half

- life of approximately 58 days. M ethane sulfonic acid is expected to have low persistence and low bioaccumulation potential.

Based upon the findings presented earlier in the human health and r isk assessment and the findings regarding environmental fate and effects, the Agency approves of the requested uses of

methane sulfonic acid . As such, methane sulfonic acid may be formulated into products for use as an acid cleaner in pesticide formulatio ns with a limit not to exceed 3 % final end use

concentration when used on animals [as a disinfectant teat wash for dairy cattle, goats or sheep];

and not to exceed 0.5 % (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.Page 22 of 25 REFERENCES

EPA. 2009. United States Environmental Protection Agency. Decision Document for Inert Approval: Methane sul fonic acid (CAS No. 75

- 75

- 2)

– Non

- Food Use

. 791198.DEC1.doc.

MRID 49396007. 2014. MRID 49396007 cites “Except from IUCLID Data Set for
Methansulfonic Acid; OPPT # 201

- 16750B; Received at OPPT NCIC on 25 Sept. 2008.

Extracted from Final HPV Asses sment Report on Methanesulfonic Acid CAS NO. 75

- 75

- 2 Submitted by: Arkema Inc. 20 MAY 2008. http://www.epa.gov/chemmrtk/pubs/summaries/methanes/c1424rt3.pdf

Shamim, A. N. 2006. “Dietary Risk Assessment for Alkyl Dimethyl Benzyl Ammonium

Chloride (ADBAC) for Reregistration El i gibility Decision (RED) Process” EPA

interoffice memorandum to Jacqueline Campbell

- McFarlane . 27 July 2006.

Smegal, D., T. Milano, R. Quic k, R. Petrie, C. Walls, N. Shamim, and K. Leifer. “ Alkylbenzene Sulfonates (ABS) Risk Assessment for the Reregistration Eligibility Decision (RED) Document”, PC Codes: 079010, 190116 and 098002(active); 790102, 790116, 790101 (inert) Case No. 4006. DP Barcode: D330338. Unpublished memorandum. Health

Effects Division/OPP.Page 23 of 25 ATTACHMENT



### FDA Food Contact Surface Sanitizing Solution Dietary Exposure

Assessment Model
(FDA/CFSAN OPA: Chemistry Guidance

– Sanitizing Solutions “Sanitizing Solutions:

Chem istry Guidelines for Food Additive Petitions” version 1.1; January 1993; Office of Premarket Approval now Office of Food Additive Safety).

EDI (mg/day) = (1 mg/cm 2 )(ug chemical/1000 mg)(4000 cm 2 /person/day) = μg/person/day/1000 mg/μg

EDI (mg/day) = (1 mg/cm 2 ) (ppm inert; in this case expressed as 5000 ug methane sulfonic acid /1000 mg)(4000

cm 2 /person/day = 20, 000 ug/person/day = 20 mg/person/day

DDD (mg/kg/day) =

Adult 20 mg/day ÷ 80 kg bw = 0.25 mg/kg/day

Child 20 mg/day ÷ 11 kg bw = 1.3 mg/kg /day

Margin of Exposure (MOE) = NOAEL ( 400 mg/kg/day )/Exposure

Adult 400 mg/kg/day /0.25 mg/kg/day = 1600

Child 400 mg/kg/day / 1.3 mg/kg/day = 310

It is assumed that 100% of the residue is transferred to the exposed individual

Where:

AR = Applica tion rate (ppm)

RS = Residual solution (mg/cm 2 )

SA = Surface area of the treated surface which comes into contact with food (cm 2 )

BW = Body weight (kg)

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

Input Parameters for Food Contact Surface Sanitizing Solution Dietary Exposure

Assessment

Parameter Value

Rationale

Residual Solution on

Surface 1 mg/cm 2 FDA assumpti on

Area of Treated Surface 4,000 cm 2 FDA assumption for food

utensils/surfaces

concentration in diluted

solution 5000 ppm Diluted Solution concentration, based on maximum concentration (expressed in ppm).

Fraction Transferred 100% US EPA Antimic robials Div. SOP for Residential Exposure 3.1.1Page 24 of 25

Body Weight (kg) Average adult =

Child = 80

1 5 EPA (2011) Hot sheet 31

US EPA Ver. 3.16, 03

- 08

- d

DEEM

- FCID Chronic analysis for INERTS NHANES 2003

- 2008 2

- day

Residue file name: J: \ INERTS_57ACTIVE_BeefGoatSheepMilk.R08 Adjustment factor #2 NOT used. Analysis Date 06

- 04

- 2015/07:56:39 Residue file dated: 06

- 04

- 2015/07:55:52

R eference dose (RfD, Chronic) = 4 mg/kg/day COMMENT 1: Inert 57 active ingredients + MMP

====================================================================

===========

Total exposure by population subgroup

------------------------------ -------------------------------------------------

Total Exposure

----------------------------------- Population mg/kg Percent of Subgroup body wt/day Rfd

-------------------------------------- ------------- ---------------- Total US Population 0.006755 0.2% Hispanic 0.007980 0.2%

Non

- Hisp

- White 0.006625 0.2%

Non

- Hisp

- Black 0.006040 0.2%

Non

- Hisp

- Other 0.006985 0.2% Nursing Infants 0.002362 0.1%

Non

- Nursing Infants 0.009925 0.2%

Female 13+ PREG 0.005348 0.1%

Children 1

- 6 0.022188 0.6%

Children 7

- 12 0.010994 0.3%

Male 13

- 19 0.007426 0.2%

Female 13

- 19/NP 0.005218 0.1%

Male 20+ 0.005144 0.1%

Female 20+/NP 0.003992 0.1%

Seniors 55+ 0.004110 0.1%

All Infants 0.007591 0.2%

Female 13

- 50 0.004410 0.1%

Children 1

- 2 0.029442 0.7%

Children 3

- 5 0.018965 0.5%

Children 6

- 12 0.011748 0.3%

Youth 13

- 19 0.006306 0.2%

Adults 20

- 49 0.004880 0.1%

Adults 50

- 99 0.004108 0.1%

Femal e 13

- 49 0.004436 0.1%Page 25 of 25

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