2 Aluminum sulfate has use as a food additive, a nd is also used in consumer products including cosmetics and pharmaceuticals such as antacids and buffered aspirin.

The toxicology database for alumin um sulfate is complete, Aluminum sulfate has low acute toxicity by the oral route. No dermal or inhalation acute toxicity studies are available for aluminum sulfate. Aluminum sulfate is not a skin irritant, however, it is irritating to the eye. No skin sensitization studies are available Since ingested aluminum sulfate will readily disso ciate in the stomach to aluminum (as will many other aluminum compounds ), toxicology data on aluminum compounds and

aluminum sulfate are considered as part of this assessment. Aluminum compounds have been evaluated by the Agency for Toxi c Substances and Disease Registry (ASTDR, 2008) and as part of the toxicological profile of alumin um, ASTDR notes that “There is a rather extensive database on the oral toxicity of aluminum in an imals. These studies clearly identify the nervous system as the most sensitive target of aluminum toxicity and most of the animal studies have focused on neurotoxicity and neurodevelopmental toxicity. Ot her adverse effects that have b een observed in animals orally exposed to aluminum include impaired erythropoie sis in rats exposed to 230 mg Al/kg/day and higher, erythrocyte damage (as evidenced by decr eases in hemoglobin, hematocrit, and erythrocyte osmotic fragility, and altered erythrocyte morphol ogy) in rats exposed to 230 mg Al/kg/day and higher, increased susceptibility to infection in mouse dams exposed to 155 mg Al/kg/day, delays in pup maturation following exposure of rats to 53 mg Al/kg/day, and decreases in pup body weight gain in rats and mice exposed to 103 mg Al/kg/day a nd higher. . . Oral studies in rats and mice have not found significant histopathological changes in the brain under typical exposure conditions; however, altered myelination was found in the sp inal cord of mouse pups exposed to 330 mg Al/kg/day on gestation day 1 through postnatal day 35. Overt signs of ne urotoxicity are rarely reported at the doses tested in the available animal studies ( ≤ 330mg Al/kg/day for bioavailable aluminum compounds); rather, exposure to these doses is associated with subtle neurological effects detected with neurobehavioral performance tests. Significant alterations in motor function, sensory function, and cognitive function have been detected following exposure to adu lt or weanling rats and mice or following gestation and/or lactation exposure of rats and mice to aluminum lactate, aluminum nitrate, and aluminum chloride. The most consiste ntly affected performance tests were forelimb and/or hindlimb grip strength, spontaneous mo tor activity, thermal sensitivity, and startle responsiveness. Significant impair ments in cognitive function have been observed in some studies, although this has not been found in other studies ev en at higher doses. Adverse neurological effects

have been observed in rats and mice at dos es of 100–200 mg Al/kg/day and neurodevelopmental

effects have been observed in rats an d mice at doses of 103–330 mg Al/kg/day.

. The toxicological data for aluminum is complic ated by the variety of test materials, various species of animals, study durations, study endpoints, experimental designs, and methods of computation of the total dose of aluminum from test material as well as from the diet and water. The majority of the studies were not conducted und er Good Laboratory Practice (GLP) Standards and were not conducted in accordance with any internatio nal testing guideline. The approach used for this analysis was to tabulate the NOAEL/LOAEL evaluati ons for the most relevant published studies but give greater weight and emphasis to the GLP guid eline studies. Using th is approach, the NOAEL from the two generation rat oral reproduction study of 41 mg/kg/bw/day alumin um sulfate (equivalent to 8.06 mg Al/kg bw/day) base d on the decreased body weight from pups and parents and delay in vaginal opening. The similar effect s seen in the two separate tw o generation rat oral reproduction3 studies, both of which were conducted under GLPs and in compliance with OECD 416 guidelines, gives a high level of confidence and certainty in the data. There are no gaps in the database leading to uncertainty in the risk assessment for infants and ch ildren and there are no qua litative differences in sensitivity of offspring and adults. Therefore, the FQPA safety factor can be reduced to 1x.

The chronic dietary exposure fr om food and water to aluminum sulfate is % of the cPAD for the U.S. population (adults) and 6.7% of the cP AD for children 1-2 years old, the most highly exposed population subgroup. There ar e no current residential uses fo r registered pesticide products containing aluminum sulfate as an inert ingredient and the proposed use w ould result in negligible residential exposures to aluminum sulfate, theref ore a residential exposure and risk assessment was not performed.

Ecological effects of concern ar e not expected from the propose d use of aluminum sulfate in antimicrobial pesticide formulations applied to food contact surfaces at a con centration not to exceed 50 ppm in the pesticide formulation.

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 Just ice in Minority Populations an d Low-Income Populations,” http://www.eh.doe.gov/oepa/ guidance/just ice/eo12898.pdf.

EPA has determined that there are no human health risk concerns that would preclude establishing the proposed exemption from the requireme nt of a tolerance for aluminum sulfate under 40 CFR 180.940(a), for use as an inert ingredient in antimicrobial pesticide formulations applied to food-contact surfaces in public eating places, dair y-processing equipment, and food-processing equipment and utensils at a concentration not to exceed 50 parts per million (ppm).

I. BACKGROUND

Ecolab, Inc., submitted a petition to the U.S. Environmental Protection Agency (EPA), pursuant to section 408(d ) of the Federal Food, Drug, and Cosme tic Act (FFDCA), to amend 40 CFR part 180 with respect to establishing an exemption from the requirement of a tolerance for aluminum sulfate (CAS Reg. No. 10043-01-3) under 40 CFR 180.940( a) for use as an inert ingredient in antimicrobial pesticide formulations applied to food-contact surfaces in public eating places, dairyprocessing equipment, and food-processing equipmen t and utensils] at a maximum concentration not to exceed 50 parts per million (ppm).

II. CHEMICAL IDENTITY AND PH YSICAL/CHEMICAL PROPERTIES

Table 1 lists common synonyms a nd other identification information for aluminum sulfate. Table 2 lists important physical and chemi cal properties of aluminum sulfate.4 Table 1. Nomenclature and Structure

Identity Information

Chemical structure:

Chemical formula Al 2 (SO 4 ) 3 Synonyms: Aluminum sulphate; alumin um sulfate anhydrous; sulfuric acid, aluminum salt (3:2)

CAS Registry Number: 10043-01-3
Chemical Family: Inorganic salt

Table 2. Physical and Chemical Properties

Physical Chemical Property Result

Color 1,2,5 White Molecular Weight 342.15 Physical Form 1,2 Solid, white granule or powder chunks

Odor 1,4,5 Odorless pH 5 2 Stability to normal and elevated temperatures, metals, and metal ions 1, 2 Contact with alkalis and wate r-reactive materials causes

exothermic reactions. Storage Stability 1,3 Stable at room temperature in closed containers under normal storage and handling conditions

Corrosion Characteristics 1 Corrosive to steel when wet Melting Point 2,4,5 770 °C/1418 °F (decomposes) Boiling Point 1 117 °C/242 °F Density 1 varies, <98lb/cu ft Flammability 1,5 May burn, will not ignite n-octanol water partition coefficient 6 P = 9.33 X 10 -02
Solubility in water 1,5 Complete, 313 g/L at 0°C, 891 g/L at 100°C Vapor Pressure 2,5 3.35x10 -05 mmHg at 25°C, Essentially zero

1 http://www.deltachemical.c om/PDFS/DeltaAlumSolid.pdf

2 ChemSpider- http://www.chemspider.com/Record View.aspx?rid=c14d2cf7-36b3-42f0-8338-

e16af3fa38ad5 3 Sigma Aldrich MSDS - http://www.sigmaaldrich.com/ catalog/DisplayMSDSContent.do

4 http://www.inchem.org/doc uments/icsc/icsc/eics1191.htm

5 http://www.inchem.org/documen ts/ukpids/ukpids/ukpid34.htm

6 http://sitem.herts.ac.uk/aeru/ footprint/en/Reports/26.htm

III. USE PATTERN

Aluminum sulfate is currently used as an inert ingredient in nonfood and food use pesticide formulations, with food uses being in conformance with an existing exempti on from the requirement

of a tolerance under 40 CFR 180.920 for use as a solid diluent and carrier. An evaluation of existing product registrations that contain al uminum sulfate as an inert ingred ient identify no residential uses and maximum use on growing crops of less than 1% (w /w). The proposed use of aluminum sulfate is as an inert ingredient in f ood-contact surface antimicrobial sanitizing solutions at a maximum concentration not to exceed 50 ppm.

IV. HAZARD CHARACTERIZATION AND DOSE-RESPONSE ASSESSMENT

A. Summary of Toxicological Effects

The toxicology database for alum inum sulfate is complete, Aluminum sulfate is of low acute toxicity by the oral and dermal rout es. No dermal or inhalation acute toxicity studies are available for

aluminum sulfate. Aluminum sulfate is not a skin ir ritant, however, it is severe ly irritating to the eye.

No skin sensitization studies are available Since i ngested aluminum sulfate wi ll readily dissociate in the stomach to aluminum (as will many other al uminum compounds), toxicology data on aluminum compounds and aluminum sulfate are considered as part of this a ssessment. Aluminum compounds have been evaluated by the Agency for Toxic S ubstances and Disease Re gistry (ASTDR, 2008) and as part of the toxicological prof ile of aluminum ASTDR notes that “There is a rather extensive database on the oral toxicity of aluminum in an imals. These studies clearly identify the nervous system as the most sensitive target of aluminum toxi city and most of the animal studies have focused on neurotoxicity and neurodevelopmenta l toxicity. . Other adverse effe cts that have been observed in animals orally exposed to aluminum include impa ired erythropoiesis in rats exposed to 230 mg Al/kg/day and higher, erythrocyte damage (as evid enced by decreases in hemoglobin, hematocrit, and erythrocyte osmotic fragility, a nd altered erythrocyte morphology) in rats exposed to 230 mg Al/kg/day and higher, increased susceptibility to infection in mouse dams exposed to 155 mg Al/kg/day, delays in pup maturation following exposure of rats to 53 mg Al/kg/day, and decreases in pup body weight gain in rats and mice exposed to 103 mg Al/kg/day and higher. . . Oral studies in rats and mice have not found significant histopathol ogical changes in the br ain under typical exposure conditions; however, altered myelination was found in the spinal cord of mouse pups exposed to 330 mg Al/kg/day on gestation day 1 through postnatal day 35. Overt signs of neurotoxicity are rarely reported at the doses tested in the available animal studies ( ≤ 330mg Al/kg/day for bioavailable aluminum compounds); rather, exposure to these doses is associated with subtle neurological effects detected with neurobehavioral performance tests. Significant alterations in motor function, sensory function, and cognitive function have been detected following exposure to adu lt or weanling rats and mice or following gestation and/or lactation exposure of rats and mice to aluminum lactate, aluminum nitrate, and aluminum chloride. The most consiste ntly affected performance tests were forelimb6 and/or hindlimb grip strength, spontaneous mo tor activity, thermal sensitivity, and startle responsiveness. Significant impair ments in cognitive function have been observed in some studies, although this has not been found in other studies ev en at higher doses. Adverse neurological effects

have been observed in rats and mice at dos es of 100–200 mg Al/kg/day and neurodevelopmental

effects have been observed in rats an d mice at doses of 103–330 mg Al/kg/day”

The lowest-observed-adverse-e ffect level (LOAEL) for these effects range from 13–330 mg Al/kg/day with no-observed-adverse-effect leve ls ranging from 5-100 mg Al/kg/day. The ASTDR aluminum toxicity profile notes that “[a]nimal bioassays have found no conclusive evidence for carcinogenicity of aluminum.”

The most sensitive effect iden tified in the toxicology database fo r aluminum sulfate is based on a multi-generational rat reproduction study with a L OAEL of 188 mg/kg/day for aluminum sulfate based on decreased body weights of pups and pare nts and a delay in vaginal opening. The NOAEL for this study is 41 mg/kg/day for aluminum sulf ate (equivalent to 8.06 mg/kg/day of aluminum). A 10 uncertainty factor for inter- and intra-species vari ation and a 1X FQPA Safe ty Factor results in a chronic population adjusted dose (c PAD) of 0.41 mg/kg/day. The use of this endpoint for risk assessment purposes is health-protective of the e ffects of aluminum (such as neurotoxicological effects) observed in studies of other aluminum compounds.

B. Absorption, Distribution, Meta bolism and Elimination (ADME)

Aluminum present in food and drinking water is poorly absorbed through the gastrointestinal tract. Bioavailability in rabbits following a si ngle maximum safe dose was estimated by comparing areas under the plasma concentration-time curves after oral and intravenous dosing (Yokel and McNamara (1988)). The estimated bi oavailability of the water-sol uble compounds aluminum chloride (333 mg Al/kg), aluminum nitrate (934 mg Al/kg), aluminum citrate (1,081 mg Al/kg), and aluminum lactate (2,942 mg Al/kg) in rabbits was 0.57, 1.16, 2.18, and 0.63%, respectively. Aluminum occurs normally in all body tissues of humans (Ganrot 1986). Metabolism of aluminum does not occur (Ganrot 1986). As an element, aluminum is alwa ys found attached to other chemicals, and these affinities can change within the body. In living orga nisms, aluminum is believed to exist in four different forms: as free ions, as low-mol ecular-weight complexes, as physically bound macromolecular complexes, and as covalently bound macromolecular comp lexes (Ganrot 1986). The free ion, Al+3, is easily bound to many substances and st ructures; therefore, its fate is determined by its affinity to each of the ligands an d their relative amounts and metabolism.

The complexes are metabolically active, partic ularly the nonpolar ones. Because aluminum has a very high affinity for proteins, polynucle otides, and glycosaminoglycans, much of the aluminum in the body may exist as physically bound macromolecular complexes with these substances. Metabolically, these macromolecular co mplexes would be expected to be much less active than the smaller, low-molecular-weight comp lexes. Aluminum may also form complexes with macromolecules that are so stable that they ar e essentially irreversible. For example, evidence suggests that the nucleus and chromatin are ofte n sites of aluminum binding in cells (Crapper McLachlan 1989; Dyrssen et al. 198 7; Ganrot 1986; Karlik et al . 1980). Following ingestion in humans, absorbed aluminum from the blood is elim inated in the kidney and excreted in the urine7 (Gorsky et al. 1979; Greger and Baier 1983; Kaehny et al. 1977; Recker et al. 1977; Sutherland and Greger 1998). The unabsorbed aluminum is excreted primarily in the feces.

C. Dermal Absorption

There were no appropriate dermal absorption or toxicity studies available to allow an estimation of the dermal absorption by a route-to -route comparison of toxicity. For the purposes of this risk assessment 100% dermal absorption is assumed.

D. Safety Factor for Infants and Children (FQPA Safety Factor)

The toxicity database is complete, there is no evidence of increased qualitative or quantitative susceptibility in the young, and the endpoint sel ected for risk assessment purposes is protective of any potential neurotoxicologi cal effects. No immunotoxicol ogical effects were observed in the available aluminum database.and exposure es timates are unlikely to underestimate risk; therefore the 10-fold FQPA SafetyFactor can be reduced to 1x.

E. Completeness of the Toxicology Database

The toxicology database for al uminum sulfate is complete and adequate to support risk

assessments.

F. Evidence of Neurotoxicity

While there are no available ne urotoxicity studies on aluminum sulfate, available studies with aluminum compounds with neurotoxicity endpoints demonstrate adverse effects at dose levels ranging from 30-130 mg Al/kg/day and NOAELs for these effects ranging from 25.7 to 75 mg Al/kg/day. The adult neurotoxicity st udy with the NOAEL of 25.7 mg Al/kg/day has a LOAEL of 54.5 mg Al/kg/day base d on reduction in vestibular-ocu lar reflex (Marneli et al. 2006). The lowest LOAEL for an adult neurotox icity study with an aluminum compound is 30 mg Al/kg/day (Bilkei-Gorzo et al. 1993) based on neurobehavioral effects in maze performance, A NOAEL for this study was not reported as do se levels below 30 mg Al/kg/day were not tested. Standard neuropathol ogy and functional observations ba ttery (FOB) evaluations were included in a study on aluminum chloride by Be ekhuijen, 2007 that was conducted in accordance with OECD 422 guidelines and no adverse effect s were reported on those parameters at does levels up to 90 mg Al/kg/day. In a study of deve lopmental neurological effects (Poirier et al. 2011) in which rats were chronically exposed thr oughout all life stages to aluminum citrate via drinking water, a NOAEL of 30 mg Al/kg/day was identifie d with a LOAEL of 100 mg Al/kg/day based on impaired gr ip strength and foot splay.

G. Evidence of Sensitivity/Susceptib ility in the Developing or Young Animal There is no evidence of increased quantitative or qualitative susceptibility of rat fetuses to in

utero exposure to aluminum chloride (Beekhuije n, 2007). In a 12-month neurodevelopmental toxicity study conducted at dos e levels of 0, 30, 100 and 300 mg Al/kg bw/day, rats were administered aluminum salts via drinking wate r throughout all life-stag es. In this robust8 study (Poirer et al. 2011), a NOAEL of 30 mg Al/kg bw/day was identified with a LOAEL of 100 mg Al/kg bw/day. Rats were exposed chronically vi a drinking water to aluminum citrate in utero, during lactation th rough dams, as juveniles and as older adult animals. Motor, sensory, and learning a nd memory tests were conducted according to OECD 426 guidelines for developmental neur otoxicity testing in pups and adults. Neuropathology evaluations on perfusion fixed br ains were evaluated at postnatal days 23, 64, 120 and 364 and no treatment -related effects were reported. Effects on neurobehavioral endpoints (e.g. auditory star tle, motor activity, f unctional observational battery) were noted primarily at the highest dose level which caused severe systemic toxicity including mortality, a lthough there was evidence of increased excitability, and impaired grip strength and foot splay at th e mid dose as well also in the presence of · systemic toxicity. There were no effect s on learning and memory at any dose level

tested based on a Morris water maze test.

H. Residual Uncertainty in the Exposure Database

In conducting the chronic dietary exposure asse ssment for existing food uses of aluminum sulfate. Application of the Dietar y Exposure Evaluation Model DEEM–FCID TM , Version 3.18, EPA used food consumption information from the U.S. Department of Agriculture’s (USDA’s)

2003-2008 National Health and Nutrition Examin ation Survey, What We Eat in America (NHANES/WWEIA). As to residue levels in food, no residue data were submitted for aluminum sulfate. In the absence of specific residue data, EPA has developed an approach which uses surrogate information to derive upper bound exposur e estimates for the subj ect inert ingredient. Upper bound exposure estimates are based on the hi ghest tolerance for a given commodity from a list of high-use insect icides, herbicides, and fungicides. A complete description of the general approach taken to assess inert ingredient risks in the absence of residue da ta is contained in the memorandum entitled “Alkyl Amines Polyalkoxylat es (Cluster 4): Acute and Chronic Aggregate (Food and Drinking Water) Dietary Exposure and Risk Assessments for the Inerts.” (D361707, S. Piper, 2/25/09) and can be found at http ://www.regulations.gov in docket ID number EPAHQ-OPP-2008-0738.

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

The Agency believes the assumptions used to esti mate dietary exposures lead to an extremely conservative assessment of dietary risk due to a series of compounded conservatisms. First, assuming that the level of residue for an inert ingredient is equal to the level of residue for the active ingredient will overstate e xposure. The concentration of active ingredient in agricultural products is generally at least 50 percent of the product and often can be much higher. Further, pesticide products rarely have a single inert ingred ient; rather there is ge nerally a combination of different inert ingredients used which additionally reduces the concentration of any single inert ingredient in the pe sticide product in rela tion to that of the active ingredient.9 Second, the conservatism of this methodology is compounded by EPA’s decision to assume that, for each commodity, the active ingredient which will serve as a guide to the potential level of inert ingredient residues is the active ingr edient with the highest tolerance level. This assumption overstates residue va lues because it would be highl y unlikely, given the high number of inert ingredients, that a single inert ingredient or class of ingredients would be present at the level of the active ingredient in the highest tolerance for every commodity. Finally, a third compounding conservatism is EPA’s assumption that all foods contain the in ert ingredient at the highest tolerance level. In other words, EPA a ssumed 100 percent of all foods are treated with the inert ingredient at the rate and manner ne cessary to produce the hi ghest residue legally possible for an active ingredient. In summar y, EPA chose a very conservative method for estimating what level of inert residue could be on food, then used this methodology to choose the highest possible residue that co uld be found on food and assumed that all food contained this residue. No consideration was gi ven to potential degradation be tween harvest and consumption even though monitoring data shows that tolerance level residues ar e typically one to two orders of magnitude higher than actual residues in food when distributed in commerce.

Based on an evaluation of all registered pest icide products containing aluminum sulfate and registered for use on food, it was determined that the concentration of al uminum sulfate did not exceed 1% by weight. This effective functional use limitation was included in the dietary exposure assessment of aluminum sulfate.

A dietary exposure assessment of proposed use in antimic robial food contact surface sanitizing solutions was also performed in whic h it is conservatively assumed that 100% of the

diet results from food treated with food contact surface sanitizers and that 100% of the sanitizing solution is transferred into food. A highly conservative model based on FDA assumptions regarding transfer of food c ontact sanitizing solution residues to food is utilized. The dietary exposure values derived from both the conserva tive model used to estimate residues from application to growing crops and raw agricultu ral commodities after harvest are then summed with the exposures estimated from the an timicrobial food cont act sanitizer uses.

Accordingly, although sufficient information to quantify actual residue levels in food and drinking water is not available, the compounding of these conservati ve assumptions will lead to a significant exaggeration of act ual exposures. EPA does not believe that this approach underestimates exposure in th e absence of residue data

V. Toxicity Endpoint and Po int of Departure Selections

A. Dose-Response Assessment

Acute Dietary Endpoint No a ppropriate endpoint was identified from any of the studies in the database, including developmenta l toxicity studies in the rat, consequently it was determined that there was no basis for selecting a dose and endpoint for an acute point of departure (POD) for the general population or females 13-49 .10 .

Chronic Dietary Endpoint for the General P opulation A two generati on reproduction study of

aluminum sulfate in rats was cons idered critical in establishing the PoD for chronic dietary risk assessment. The study supports a NOAEL of 41 mg/kg/day and a LOAE L of 188 mg/kd/day for decreased body weight in parents and pups and a dela y in vaginal opening and should be used as the POD for all durations and exposure scenarios. A UF of 100x (10x for interspecies ex trapolation and 10x for intraspecies variation is a pplied to obtain a chr onic reference dose (cRfD) of 0.41 mg/kg/day. The FQPA factor is reduced to 1x. The chronic population adjusted dose (cPAD) is 0.41 mg/kg/day.

Incidental Oral Exposure (Short- and Intermediate -Term. A two generation reproduction study in rats

was considered critical in estab lishing the PoD for incidential oral exposure (all durations). The study supports a NOAEL of 41 mg/kg/day and a LOAEL of 188 mg/kg/day for decreased body weight in parents and pups and a delay in vagi nal opening and should be used as the POD for all durations and exposure scenarios.

Dermal Exposure (Short-, Intermediate-, and Long-Te rm. Due to uncertainties in the dermal toxicity database, an oral toxicity study was selected for this exposure scenario. The same rationale as stated in the incidental oral exposure section is applied to this expos ure scenario. The study supports a NOAEL of 41 mg/kg/day and a LOA EL of 188 mg/kg/day for decreased body weight in parents and pups and a delay in vaginal opening and should be used as the POD for all durations and exposure scenarios. Additionally for risk assessment purposes a default derm al absorption factor of 100% is

used since these assessments for the routes of e xposure are derived from PO D selected from oral

studies

Inhalation Exposure, Short-, Interm ediate- and Long-Term. There were no reliable inhalation studies available in the existing toxicity database, therefore an oral toxici ty study was used for this exposure

scenario . The same rationale as stated in the in cidental oral exposure sec tion is applied to this exposure scenario. The study supports a NOAEL of 41 mg/kg/day and a L OAEL of 188 mg/kg/day for decreased body weight in parents and pups and a de lay in vaginal opening a nd should be used as the POD for all durations and exposure scenarios. Additionally for risk assessment purposes a default inhalation absorption factor of 100% is used since these assessments for the routes of exposure are

derived from POD selected from oral studies.



### Recommendation for Comb ining Routes of Exposu res for Risk Assessment

Since the same studies were used to select endpoints and doses for risk assessment for dietary, dermal and inhalation routes of exposure (all durations), the risks from these exposure routes should be aggregated.



### Cancer Classification and Risk Assessment Recommendation

There are no available carcinoge nicity studies with aluminum sulfate, however, in a cancer study with aluminum potassium sulfate there we re no exposure-related increased incidences of11 tumors, other proliferative lesions ornonneoplastic lesions in 60 male or 60 female B6C3F1 mice that ingested ≤ 979 mg Al/kg/day as aluminum potassium sulfat e in the diet for 20 months (Oneda et al. 1994). The level of aluminum in the base diet was not reported. Based on this information, aluminum sulfate is not expected to be a carcinogen and a cancer aggregate risk assessment is not required

As required by FIFRA and FFDCA, EPA review s numerous studies to assess potential adverse outcomes from exposure to chemicals. Co llectively, these studies in clude acute, subchronic and chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, reproductive, and general or systemic toxicity. These studies include e ndpoints which may be susceptible to endocrine influen ce, including effects on endocrine target organ histopathology, organ weights, estrus cyclicity, sexual maturation, fert ility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard assessme nts, EPA evaluates acute tests and chronic studies that assess growth, developmental an d reproductive effects in different taxonomic groups. As part of its most recent re-registration decision for pendimethalin, EPA reviewed these data and selected the most sensitive endpoints for relevant risk as sessment scenarios from the existing hazard database. However, as required by FFDCA section 408(p), pendimethalin is subject to the endocrine screening part of the Endocrine Di sruptor Screening Program (EDSP).

EPA has developed the EDSP to determine whet her certain substances (including pesticide active and other ingredients) may ha ve an effect in humans or wildlife similar to an effect produced by a “naturally occurring estroge n, or other such endocrine eff ects as the Administrator may designate.” The EDSP employs a two-tiered ap proach to making the statutorily required

determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a chemical substance to interact with the estrog en, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go thr ough Tier 1 screening and are found to have the potentia l to interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA will determine which, if any, of the Tier 2 tests are nece ssary based on the available data. Tier 2 testing is designed to identify any adverse endocrine-relate d effects caused by the substance and establish a dose-response relationship between the dose and the E, A, or T effect.

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between October 2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 chemicals, which contains 58 pest icide active ingredients and 9 inert ingredients. A second list of chemicals identified for EDSP screening was published on June 14, 2013, and includes some pesticides scheduled for registration review and chemicals found in water

. Neither of these lists

should be construed as a list of know n or likely endocrine disruptors.

For further information on the status of the ED SP, the policies and proc edures, the lists of chemicals, future lists, the test guidelines and the Tier 1 screening battery, please visit our website, www.epa.gov/endo/12 Dietary Exposure and Risk Assessment

Dietary Risk Assessment

Since there were no endpoints of concern id entified for acute dietary risk assessments, a acute dietary risk assessment was not performed. A chronic dietary risk assessment was conducted for the existing uses of aluminum su lfate as an inert ingredient in pesticide formulations applied to growing crops or to raw agricultural commodities af ter harvest. The risk assessment considers food consumption from growing crops and raw agricultu ral commodities treated with pesticides that

contain aluminum sulfate as an in ert ingredient. As to residue le vels in food, no residue data were submitted for aluminum sulfate. In the absence of specific residue data, EPA has developed an approach which uses surrogate information to de rive upper bound exposure estimates for the subject inert ingredient. Upper bound exposure estimates ar e based on the highest tolerance for a given commodity from a list of high-use insecticides, herb icides, and fungicides. A complete description of the general approach taken to assess inert ingredient risks in the abse nce of residue data is contained in the memorandum entitled “Alkyl Amines Po lyalkoxylates (Cluster 4): Acute and Chronic Aggregate (Food and Drinking Water) Dietary Expos ure and Risk Assessments for the Inerts.” (D361707, S. Piper, 2/25/09) and can be found at http://www.regulations.gov in docket ID number EPA-HQ-OPP-2008-0738.

In the dietary exposure assessment, the Agency assumed that the residue level of the inert ingredient would be no higher than the highest to lerance for a given commodity. Implicit in this assumption is that there would be similar rates of degradation (if any) between the active and inert ingredient and that the con centration of inert ingredient in the scenarios leading to these highest of tolerances would be no higher than the concentrati on of the active ingredient. Drinking water exposures are based on worst-ca se modeled estimates and are incorporated directly into the DEEM TM model.

Additionally, a dietary exposure assessment of proposed use in antimicrobial food contact surface sanitizing solutions was also performed in which it is conservatively assumed that 100%

of the diet results from food tr eated with food contact surface sa nitizers and that 100% of the sanitizing solution is transfe rred into food. A highly conservative model based on FDA assumptions regarding transfer of food contac t sanitizing solution resi dues to food is utilized. The dietary exposure values derive d from both the conservative m odel used to estimate residues from application to growing crops and raw ag ricultural commodities af ter harvest are then summed with the exposures estimated from th e antimicrobial food c ontact sanitizer uses.

The chronic dietary risk estimate for the highe st exposed population subgroup, children 1-2 years old is 6.7% of the chronic populatio n adjusted dose (cPAD) and for the general U. S. population is

1.6% of the cPAD. EPA is concerned when estim ated dietary risk exceeds 100%. There are no chronic dietary risks of concern (Appendix 1).

Residential (Non-Occupational) Ex posure/Risk Characterization13 There are no proposed new residen tial uses for aluminum sulfate; based on an evaluation of the currently registered products cont aining aluminum sulfate, there are no products with residential uses, therefore a residential exposure assessment and risk assessment was not performed.

Aggregate Exposure/Risk Characterization

In accordance with the FQPA, EPA must consid er and aggregate (add) pesticide exposures and risks from three major sources: food, drinking wa ter, and residential exposures. In an aggregate assessment, exposures from relevant sources are added together and compared to quantitative estimates of hazard (e.g., a NOAEL or PAD), or th e risks themselves can be aggregated. When aggregating exposures and risks fr om various sources, EPA consider s both the route and duration of exposure. For aluminum sulfate pendimethalin, pot ential exposures from food and drinking water from both the existing uses of aluminum sulfat e on growing crops and raw agricultural commodities after harvest, and the proposed us e as an inert ingredient in an timicrobial food contact sanitizing solutions were aggregated.

Acute Aggregate Risk

The aggregate acute risk estimates include expos ure to residues of pendimethalin in food and water, and does not include dermal, inhalation or incidental oral exposure. Since there were no endpoints of concern identified for acute dietary risk assessments, an acute dietary risk assessment was not performed and there no acute aggregate risks of concern.

Short-Term Aggregate Risk

There is potential short-term exposure to pendi methalin via dietary (which is considered background exposure). However sine there are no residential exposure pathways, the short-term aggregate risk would be equivalent to the chronic dietary exposure estimate. Refer to Section xxor the chronic dietary (food and drin king water) exposure assessment. There are no short-term aggregate

risks of concern.

Table Short-Term Aggregate Risk Calc ulations for Aluminum Sulfate

Life stage Short-Term Scenario

NOAEL mg/kg/day LOC 1 Max Allow a Exposure 2 mg/kg/day Avera g e Foo d

and Water Exposure Crop uses (mg/kg/day) Avera g e Foo d

and Water Exposure

Food contact u

use (mg/kg/day) Total Exposure mg/kg/day 4 Aggregate MOE (food, water, and residential) 5

Adult 41 100 0.41 0.003787 0.00286 0.00665 6170

Child 41 100 0.41 0.014125 0.0133 0.0275 1490

1 Intraspecies factor= 10x; Interspecies factor = 3x 2 Maximum Allowable Exposure (mg/kg/day) = NOAEL (10 mg/kg/day)/LOC (100). 3 Child Residential Exposure = [Oral exposure (0.042 mg/kg/day) + Dermal exposure (0.060 mg/kg/day) = 0.102 mg/kg/day (Table 6.1). 4 Total Exposure = (Avg (Food & Water) Exposure + Residential Exposure). 5 Adult Aggregate MOE = [NOAEL (10 mg/kg/day)/ (Total Exposure (0.08 mg/kg/day)]; Child Aggregate MOE= [NOAEL (10 mg/kg/day)/ (Total Exposure (0.107 mg/kg/day)]14 

### Intermediate-Term Aggregate Risk

Intermediate-term exposures to aluminum sulfate ar e not likely because of the intermittent nature of applications by homeowners. Ther efore the intermediate-term ggregat e risk would be equivalent to the chronic dietary exposure estimate. Refer to Section xx for the chronic dietary (food and drinking water) exposure assessment. There are no inte rmediate-term aggregate risks of concern.

Chronic Aggregate Risk

Chronic exposure is not expected for the reside ntial (dermal and inhalatio n) exposure pathways. Therefore, the chronic aggregate risk would be equi valent to the chronic dietary exposure estimate. Refer to Section xx for the chronic dietary (food a nd drinking water) exposure assessment. There are no chronic aggregate risks of concern.

Cancer Aggregate Risk

Based on the lack of concern for carcinogenic ity a cancer aggregate ri sk assessment was not performed.

Cumulative Exposure/Ri sk Characterization

Unlike other pesticides for which EPA has followe d a cumulative risk approach based on a common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as to aluminum sulfate and any other substances and pendimethalin does not appear to produce a toxic metabolite produced by other substances. For the purposes of this tolerance action, therefore, EPA has not

assumed that aluminum sulfate has a common mechanism of toxic ity with other substances. For information regarding EPA’s efforts to determin e which chemicals have a common mechanism of toxicity and to evaluate the cumu lative effects of such chemicals, see the policy statements released by EPA’s Office of Pesticide Programs concer ning common mechanism determinations and procedures for cumulating effects from substa nces found to have a common mechanism on EPA’s

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

.

IX. ENVIRONMENTAL JUSTICE STATEMENT

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

to Address Environmental Just ice in Minority Populations an d Low-Income Populations," http://www.eh.doe.gov/oepa/ guidance/justice/eo12898.pdf

.15 As a part of every pesticide risk assessment , OPP considers a large variety of consumer subgroups according to well-establis hed procedures. In line with O PP policy, RD estimates risks to population subgroups from pesticide exposures that are based on patte rns of that subgroup’s food and water consumption, and activities in and around the hom e that involve pesticid e use in a residential setting. Extensive data on food consumption pa tterns are compiled by th e USDA under CSFII and are used in pesticide risk assessments for all regi stered food uses of a pesticide. These data are analyzed and categorized by subgroups based on age, season of the year, ethnic group, and region of the country. Additionally, OPP is able to assess dietary exposure to smaller, specialized subgroups and exposure assessments are performed when c onditions or circumstances warrant. Whenever appropriate, non-dietary exposures based on home use of pesticide pr oducts and associated risks for adult applicators and for toddlers, youths, and adults entering or pl aying on treated areas postapplication are evaluated. Further considerat ions are currently in development as OPP has committed resources and expertise to the developm ent of specialized software and models that consider exposure to bystanders and farm workers as well as lifestyle and trad itional dietary patterns among specific subgroups

X. ENVIRONMENTAL FATE

Aluminium occurs ubiquitously in the environment in the form of silicates, oxides and hydroxides, combined with other elements such as sodium and fluorine and as complexes with organic matter. It is not found as a free metal because of its re activity. It has only one oxidation state (+3) in nature; therefore, its transport and distribution in the environment depend only upon its coordination chemistry and the chemical-physical ch aracteristics of the local environmental system. At pH values greater than 5.5, na turally occurring aluminium com pounds exist predominantly in an undissolved form such as gibbsite (Al(OH) 3 ) or as aluminosilicates, except in the presence of high amounts of dissolved organic material, which binds with aluminium and can lead to increased

concentrations of dissolved aluminium in streams and lakes. Several factors influence aluminium mobility and subsequent transport within the en vironment. These include chemical speciation, hydrological flow paths, soil-wate r interactions, and the composition of the underlying geological materials. The solubility of aluminium in equilibrium with solid phase Al(OH) 3 is highly dependent on pH and on complexing agents such as fluoride, silicate, phosphate and organic matter. The chemistry of inorganic aluminium in acid so il and stream water can be considered in terms of mineral solubility, ion ex change and water mixing processes.

Upon acidification of soils, aluminium can be re leased into solution for transport to streams. Mobilization of aluminium by acid pr ecipitation results in more aluminium being available for plant uptake.

Transport and Distri bution Across Media

Aluminium occurs ubiquitously in silicates su ch as feldspars and micas, complexed with sodium and fluoride as cryolite, and in bauxite rock composed of hydrous aluminium oxides, aluminium hydroxides, and impurities such as free silica (ATSDR, 1992). Aluminium is not found as a free metal because of its reactivity. It has only on e oxidation state (+3); therefore, its transport and16 distribution in the environment de pend upon its coordination chemistry and the characteristics of the local environmental system. Aluminium partitions between solid and liqui d phases by reacting and complexing with water molecules and electron-rich anions, such as chlo ride, fluoride, sulfate, nitrate, phosphate and negatively charged functiona l groups on humic materials and clay.

At a pH greater than 5.5, na turally occurring aluminium compounds exist predominantly in an undissolved form such as gibbsite (Al(OH) 3 ) or as aluminosilicates, exce pt in the presence of high amounts of dissolved organic material such as fulvic acid, which binds with aluminium and can cause

an increase in dissolved aluminium concentratio ns in streams and lakes (ATSDR, 1992). Several processes influence aluminium mobility and its s ubsequent transport within the environment; these include chemical speciation, hydrologi cal flow paths, other spatial a nd temporal factors related to soil-water interactions, and the composition of the underlying geological materials (Grant et al., 1990). Watersheds with shallow, acidic soils and poorly buffered surface waters mobilize aluminium when exposed to acidic depos ition (Driscoll et al., 1988).

Air

Aluminium enters the atmosphere as a major constituent of a number of atmospheric particulates, such as soil-derived dusts from erosi on and particulates from co al combustion (Grant et al., 1990). Eisenreich (1980) studied the atmospheric loading of aluminium to Lake Michigan, USA. It was found that aluminium was generally associated with large particles (> 2 μm diameter) and that these were deposited near the source.

Freshwater

Dissolved aluminium

In groundwater or surface water systems an equ ilibrium is formed that controls the extent

to which aluminium dissolution can occur. The sol ubility of aluminium in equilibrium with solid phase Al(OH) 3 is highly pH-dependent. Aquo complex Al(H 2 O) 6 3+ predominates at low pH values (e.g., pH < 4), but as the pH of the solution increases (e.g., pH 4-6) and/or the temperature rises, the positive charge of aluminium forces hydrolysis of a water ligand producing the Al(OH)(H 2 O) 5 2+ ion. The degree of hydrolysis increases as the solution pH increases, resulting

in a series of Al-OH co mplexes such as Al(OH) 2+ , Al(OH) 2 + , Al(OH) 4 - (Schecher & Driscoll, 1987).

Aluminium Adsorbed on Particles

The adsorption of aluminium by particles was found to increase with total aluminium, pH and particle concentration. Calc ulations using an adsorption e quation, and taking competition by dissolved humic substances into account, suggest that adsorbed aluminium may commonly account for a significant proportion (> 10%) of tota l monomeric aluminium in such water.

Seawater17 In contrast to fresh water, seawater (salinity > 32%) has a consta nt pH of approximately 8.2. Hydes (1977) found that bottom and suspended clay se diments probably act as a source of dissolved aluminium to seawater. However, removal below predictions of clay solubility is probably the result of biological activity.

Soil

In soil, aluminium is released into solution for trans port to streams upon acidification. The chemistry of inorganic aluminium in acid soil and, in particular, the solubility controls are very similar to those given in secti on 4.1.2 for fresh water (Furrer, 1993). However, the extrapolation of stream water chemistry to soil is difficult because of the complexity of hydrological pathways and chemical reactivity during water mixing (Neal, 1988).

Bioaccumulation

Plants

Plants differ in their ability to take up aluminium; some accumulate aluminium whereas others

are able to immobilize it at the root surface (Roy et al., 1988). Exposure to aluminium in nutrient solution leads to accumulation, especially in the roots (Lee, 1972; Boxman et al., 1991).

Invertebrates

Invertebrates have the ability to up take aluminum to vary ing degrees. Frick & Herrmann (1990) studied the accumulation of alum inium by nymphs of the mayfly ( Heptagenia sulphurea ) exposed to concentrations of 0.2 and 2 mg inorgani c monomeric aluminium/ litre at pH 4.5 for up to 4 weeks. The highest mean concentrations f ound in mayflies were 1.24 and 2.34 mg/g aluminium (dry weight) for the higher treatment groups, whic h did not undergo moulting. The major part of the aluminium was deposited on/in the exuviae of the nymphs, as aluminium determinations revealed a

70% decrease in cont ent after moulting.

Fish

Fish have the ability to up take alumin um to varying degrees depending mostly on the water pH. Other factors such as water temperature and minera ls present may play a derminant role as well. Cleveland et al. (1986) exposed brook trout ( Salvelinus fontinalis ) eggs, larvae and juveniles to 300 μg/litre total aluminium at three pH levels. At 30 days post-ha tch for larvae and for an exposure period of 30 days for juveniles (37 to 67 days), si gnificantly more aluminium was accumulated at pH 5.28 than at either pH 7.24 or 4.44. Aluminium le vels at pH 5.28 were 398 and 112 mg/kg for the larvae and juveniles, respectively. At pH 7.24 re sidues were 12 and 33 mg/ kg, and at pH 4.44, 71 and 17 mg/kg, respectively.

Cleveland et al. (1991) maintained brook trout in water contai ning 200 μg/litre total aluminium at pH values of 5.0, 6.0 and 7.2 for 56 days. Estimated steady state ioconcentration factors for aluminium, which were inversely related to pH, were 215 at pH 5.3, 123 at pH 6.1 and 3618 at pH 7.2. The estimated time to 90% steady state was 1.5 days at pH 5.3, 4.2 days at pH 6.1 and 1.7 days at pH 7.2. Elimination duri ng the 28-day depuration phase was mo re rapid at pH 5.3 than at pH

6.1 or 7.2.

Karlsson-Norrgren et al. (1986b) found that brown trout ( Salmo trutta ) accumulated significantly more aluminium in gill tissue at pH 5.5 than at pH 7.0 (60-160 μg/kg and 10-40 μg/kg dry weight, respectively) when exposed to 200-500 μg total aluminium/litre.

Segner et al. (1988) e xposed young brown trout ( Salmo trutta ) to total aluminium (230 μg/litre) at pH 5.0 in high calcium water at a te mperature of 12°C for 5 days. Whole body aluminium concentrations were 230 mg/kg dry weight in aluminium-expo sed fish, as compared to 75 mg/kg (pH 5.0) and 44 mg/kg (pH 7.2) for fish in aluminium-free water.

Wicklund Glynn et al. (1992) exposed minnows ( Phoxinus phoxinus ) to acidic water (pH 5.0) with and without total aluminium (150 μg/litre) at varying calcium (0, 0.07 and 2 mmol/litre) and humus (5 and 25 Pt) concentrations for 15 days. Alum inium concentrations in the gills were highest in the lower calcium level groups with or without humus. In the absence of calcium the median aluminium level in the gills was 109 mg/kg wet we ight, and at 2 mmol/litre calcium the aluminium level was 50 mg/kg.

Birds

There are bird studies that s how a dose-related and significant increase in aluminum content

of the femur and sternum. Carri ère et al. (1986) fed ring doves ( St reptopelia riso ria) on a diet containing 0.1% aluminium sulfate with reduced calcium and phosphorus ( 0.9% Ca; 0.5% P) for a period of 4 months. Analysis of the tissues of breeding adult doves revealed that there was no accumulation of aluminium in kidney, brain or male femurae; however, the fe murae of female doves showed a significant increase from a mean of 7.42 mg/kg dry weight in controls to 15.87 mg/kg in

treated birds. Juvenile doves fed on diets containing 500, 1000 and 1500 mg/kg aluminium sulfate did not accumulate aluminium in leg and wing bones but did show a si gnificant tendency to

accumulate in the sternum.

Sparling (1991) fed black ducks ( Anas rubripes) and mallard ( Anas platyrhynchos) on a diet containing 200, 1000 or 5000 mg al uminium/kg with varying amount s of calcium (3600 and 15 100 mg/kg) and phosphorus (6200, 13 500 a nd 21 500 mg/kg) for a period of 10 weeks. All of the diets produced a dose-related and significa nt increase in the aluminium content of the femur. Black ducks maintained on normal calcium and phosphorus levels showed femur aluminium concentrations of 5.42, 13.6 and 19.5 mg/kg after 10 weeks at the thr ee dose levels, respectively. Mallard femurs

contained aluminium levels of 9.49, 12.1 and 18 mg/kg, respectively.

Photodegredation, Analytical Method Validation, Hydrol ysis stability in water or Transport/distribution (fugacity model):19 No studies have been found to address Ph otodegredation, Analytical Method Validation, Hydrolysis stability in water or Tran sport/distribution (fugacity model). Aluminum is the most

abundant metal on Earth and constitute s 8.13% of the Earth’s crust (IP CS, 1997). Aluminum is found in many consumer products incl uding antacids, astri ngents, buffered aspirin, food additives, antiperspirants and cosmetic s (ATSDR Aluminum, 2008).

Conclusion

Aluminum background must be accounted for based on its abunda nce in the earth’s crust. Although aluminum is shown to pe rsist in the environment and bioa ccumulate in wildlife the actual exposure to the environment as the result of the pr opose use pattern is expected to be minimal and therefore the proposed aluminum sulfate use as an in ert ingredient is of low concern and risk to the

environment and wildlife.

Table 6. Bioaccumalation

Species Dose Du ration Result (μg/L) Reference Invertebrate Mymphs & mayfly (Heptagen i sulphurea) 0.2 & 2 mg

aluminum/ litre at pH 4. 5 4 weeks 1.24 - 2.34 mg/g

aluminum Frick & Herrma n (1990)

Fish BrookTrout (Salvelinum fontinalis) 300ug/litre

aluminum 30 days 398 &112 mg/kg

for larvae and juveniles, respectively at ph levels 5.28 Cleveland et all. (1986)

Brook Trout (Salvelinum fontinalis) 200ug/litre

aluminum 1.5, 4.2, 6.1, 1.7 days at varying pH levels aluminum

concentration was inversely related to pH Cleveland et all. (19991)

Brown Trout (Salmo trutta)) 200-500

aluminum/

litre n/a Aluminum - gill tissue – inversely related to pH KarlssonNorrgren et al. (1986b)

Brown Trout (Sal m trutta) 230 ug/litre 5 days 230 mg/kg

aluminum Segner et al. (1988))

Minnows (Phoxin u phoxinus) 150 ug/litre 15 days 109 mg/kg

aluminum in gills Wicklund Glynn et al. (1992) Bird Ring doves - adult(Streptopelia risoria) 0.1%

aluminum

sulfate 4 months 15.87 mg/kg in

femurae of

female doves Carriere et al. (1986)

Ring doves – juve n (Streptopelia risori a 0.1%

aluminum

sulfate 4 months Significant

accumulation

in the sternum Carriere et al. (1986)20 Black ducks (Anas rubripes) 200, 1000,

5000

aluminum / kg 10 weeks 5.42, 13.6, 19.5 mg/kg,respectivelyblack duck fem. Sparling (1991)

Mallard ducks (An aplatyrhyNchos) 200, 1000,

5000

aluminum / kg 10 weeks 9.49, 12.1, 18 mg/kg,respectivelyMallard femurs Sparling (1991)

XI. ECOLOGICAL EFFECTS

Biotransformation

Biodegradation and Abiotic Degradation

Elemental aluminium does not degrade in th e environment. In the trivalent oxidation state, it can complex with electron-rich species (ATSDR, 1992).

Inherent Biodegradation:

No studies have been found to address inherent biodegradation. Biodegradation is typically identified for organic compounds and not inorganic salts such as aluminum sulfate.

Aquatic Toxicity

The following table presents eco toxicity data endpoints located in EPA’s ECOTOX database for

aluminum sulfate. These data demo nstrate that aluminum sulfate woul d be expected to have minimal aquatic toxicity, based on the typical dilution to 10 ppm or less, which is eq uivalent to 10,000 ug/L.

Table 7. Aquatic Toxicity

Species Study Result (μg/L) Tox. Category

Invertebrates Daphnia magna (Water Flea) 24-hour LC 50 7,000 - 16,000 Moderately Toxic

Daphnia magna (Water Flea) 48-hour LC 50 3,200 - 8,000 Moderately Toxic

Ceriodaph niadubia (Water Flea) 48-hour LC 50 23,630 – 35,970 Slightly Toxic

Fish Oncorhynchus mykiss (Rainbow Trout) 144-hour (6 day) LC 50 88 – 1,050 Very Highly Toxic

Pimephales promelas (Fathead Minnow) 96-hour (4 day) LC 50 4,400 – 36,100 Moderately Toxic

Pimephales promelas (Fathead Minnow) 192-hour (8 day) LC 50 19,300 – 25,500 Slightly Toxic21 Algae Aphanizomenon flos-aqua e (Blue-Green Algae) 1.5-hour EC 50 >25,000 Practi cally Non-toxic

Acute and Chronic Toxicity to Invertebrates

A 336-Hour (14 day) Daphnia similis study (Sotero-Santos, et al., 2005) showed no acute toxicity after 48 hours and a mortalit y rate equivalent to the control after 14 days in untreated sludge from two water treatment plants locate d in neighboring cities in Brazil.

US EPA Ver. 3.16, 03-08-d DEEM-FCID Chronic analysis for ALSULFATE NHANES 2003-2008 2-day

Residue file name: J:\AlSulfate\I NERTS_57ACTIVE_100PPBH2OREV1PCT.R08 Adjustment factor #2 used. Analysis Date 04-14-2015/11:26:38 Residue file dated: 04-14-2015/11:25:29 Reference dose (RfD, Chronic) = .41 mg/kg bw/day COMMENT 1: Inert 57 active ingredients + drinking water (100ppb) @ 1% Formulation

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

============ Total exposure by population subgroup

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

Total Exposure

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

------------------ ------------------ -- ------------- ---------------- Total US Population 0.003787 0.9% Hispanic 0.004135 1.0% Non-Hisp-White 0.003716 0.9% Non-Hisp-Black 0.003519 0.9% Non-Hisp-Other 0.004467 1.1% Nursing Infants 0.004964 1.2% Non-Nursing Infants 0.009195 2.2%

Female 13+ PREG 0.003305 0.8%

Children 1-6 0.010933 2.7%

Children 7-12 0.004548 1.1%

Male 13-19 0.002675 0.7%

Female 13-19/NP 0.002719 0.7%

Male 20+ 0.002820 0.7%

Female 20+/NP 0.003063 0.7%

Seniors 55+ 0.003054 0.7%

All Infants 0.007889 1.9%

Female 13-50 0.002928 0.7%22 Children 1-2 0.014125 3.4%

Children 3-5 0.009713 2.4%

Children 6-12 0.005011 1.2%

Youth 13-19 0.002696 0.7%

Adults 20-49 0.002895 0.7%

Adults 50-99 0.003036 0.7%

Female 13-49 0.002927 0.7%

------------------ ------------------ --------------- --------------- ------------- APPENDIX B

Summary of Parameters used for Diet ary Exposure Estimation for Food Contact Surface Sanitizing Uses for Aluminum Sulfate

Parameter Definition Value/Units

AR Application rate 50 ppm RS Residual solution 1 mg/cm 2
(worse case assumption)

SA Treated surface area

that comes into contact

with food Assumed to be 2000 cm 2
for counter tops and cutting boards;

assumed to be 4000 cm 2

for food utensils

F % fraction of the inert (migration factor) No units; assume 100%, F=1

CF1 Conversion Factor mg/day 10 -6 (1/1,000,000) EDI Estimated Daily Intake DDD Daily Dietary Dose BW Body Weight (adult): 70 kg; (child): 15 kg Child = 3-1 yr. toddler DDD (adult) Daily Dietary Dose for adult EDI/BW (adult) DDD (child) Daily Dietary Dose for child EDI/BW (child) cPAD Chronic Dietary end poin t 1 mg/kg/day

% cPAD Ratio of DDD and cPAD E xposure expessed as % of chronic population adjusted dose



### Food Contact Surface Sanitizer Exposure:

Formulas:

EDI=AR*RS*SA*F*CF1

DDD (adult)=EDI/BW (adult)

DDD (child)=EDI/BW (child)

Parameter Result Formula23 

### EDI 0.2 mg per day =50 mg*1 mg/cm 2 *4000 cm 2 *

%* 10 -6 

### DDD(adult) 0.00286 mg/kg/day =0.2 mg/70 kg


### DDD(child) 0.0133 mg/kg/ day =0.2 mg/15 kg24