Document ID: EPA-HQ-OPP-2012-0207-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2012-09-19T04:00Z

EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER  

EPA Registration Division contact: [Janet Whitehurst 703 305-6129]

[Ecolab, Inc.]

[1E7933]

	EPA has received a pesticide petition ([1E7933]) from [Ecolab, Inc. (Ecolab, EPA Company Number 1677)], [370 N. Wabasha Street, St. Paul, Minnesota, 55102] requesting, pursuant to section 408(d) of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to amend 40 CFR part 180 to establish an exemption from the requirement of a tolerance for [Aluminum Sulfate (CAS # 10043-01-3) under 40 CFR 180.940(a) for use as an inert ingredient as a defoamer in antimicrobial pesticide formulations applied to food-contact surfaces in public eating places, dairy-processing equipment, and food-processing equipment and utensils] at [50] parts per million (ppm).  EPA has determined that the petition contains data or information regarding the elements set forth in section 408 (d)(2) of  FDDCA; however, EPA has not fully evaluated the sufficiency of the submitted data at this time or whether the data supports granting of the petition. Additional data may be needed before EPA rules on the petition.

A. Residue Chemistry

	1. Plant metabolism. [Not applicable/Not required for the establishment of a tolerance exemption for inert ingredients.]

	2. Analytical method. [Not applicable/Not required for the establishment of a tolerance exemption for inert ingredients.]

	3. Magnitude of residues. [Not applicable/Not required for the establishment of a tolerance exemption for inert ingredients.]

B. Toxicological Profile

   1. Acute toxicity.  [The acute toxicity data indicate that aluminum sulfate has a low hazard potential. The International Uniform Chemical Information Database (IUCLID) references a GLP study conducted according to OECD 401 guidelines in 1990 that concluded that the oral LD50 for aluminum sulfate is >5000 mg/kg. No studies have been found to address dermal or inhalation toxicity. Aluminum sulfate is completely soluble in water therefore dermal toxicity should be of negligible concern.  Since the product will be used in closed loop cleaning systems and not sprayed or misted inhalation toxicity is of negligible concern. IUCLID references two GLP dermal irritation studies conducted in rabbits according to OECD 404 guidelines that concluded aluminum sulfate is not a dermal irritant at up to a 27% solution (IUCLID 2000).  EPA's TSCATS V2.01 concludes that ocular irritation is of medium concern.]
      
	2. Genotoxicty. [Aluminum sulfate has been assessed for mutagenic/genotoxic potential in a variety of in vitro assays, specifically: IUCLID 2000 references two in vitro studies (Bacillus subtilis recombination assay and SOS Chromotest) conducted for genotoxicity that were negative. The Rec-assay with B. subtilis H17 rec+ and M45 rec- stains showed no mutagenic activity for aluminum sulfate and showed no sign of morphological transformations of Syrian hamster embryo cells (Nishioka, 1975; Lippman, 1992). ]

	3. Reproductive and developmental toxicity. [An OECD 416 guideline two-generation reproductive toxicity study (Hirata-Koizumi M, et al. 2011) was conducted using concentrations of 0, 120, 600, and 3000 ppm aluminum sulfate (98.5% purity) in drinking water.  The NOAEL was found to be 600 ppm for parental systemic toxicity and reproductive/ development toxicity.  No developmental effects or maternal toxicity were observed.  Aluminum sulfate is not considered to be a developmental toxicant. ]

	4. Subchronic toxicity. [A 21-day oral toxicity study was performed in two month old male albino rats (Rattus norvegicus) (Roy, et al., 1991). Doses were selected based on an unreferenced LD50 of 10,600 mg/kg body weight.  A NOAEL was not established, as dose dependent effects were observed in the liver at the lowest dose tested, 212 mg/kg body weight/day. ]

	5. Chronic toxicity. [A 10-month repeat dose oral study (Stacchiotti, A., et al., 2008) was conducted on male adult C57BL/6 mice. Eight adult male mice of an unspecified age were treated with 2.5% aluminum sulfate dissolved in tap water administered orally. No adverse effects were reported. ]

	6. Animal metabolism. [There are no adsorption, distribution or metabolism and elimination studies for aluminum sulfate.  However, based on available physicochemical properties and available toxicological information no metabolites of toxicological concern are expected.]

	7. Metabolite toxicology. [No metabolites of toxicological concern are expected.]

	8. Endocrine disruption. [Aluminum sulfate does not belong to a class of chemicals known or suspected of having adverse effects on the estrogen receptor or endocrine system.]

C. Aggregate Exposure

	1. Dietary exposure. [Based on the literature search conducted for aluminum sulfate, there is no study available that provides relevant acute effects for the determination of an acute reference dose.  Additionally, the dietary intake assessment does not differentiate between acute and chronic exposures.  Therefore, no separate acute reference dose has been determined.   Based on the results of the developmental toxicity study in rats, there was no increased sensitivity to infants and children from aluminum sulfate in the absence of parental toxicity and therefore no need for an additional 10X FQPA safety factor when determining the chronic reference dose.  The chronic reference dose (cRfD) and the chronic population adjusted dose (cPAD) were calculated using the NOAEL of 8.06 mg Al/kg bw/day and the standard 10X uncertainty factors for each of intra- and inter- species variability.  Based on this information, the chronic reference dose (cRfD) and chronic population adjusted dose (cPAD) are equal and are calculated to be 0.0806 mg/kg/day.

	i. Food. [Low residues, based on an evaluation of potential residues of aluminum sulfate from the dairy and beverage production scenarios show that exposures are well below 100% of the cPAD, and are therefore below EPA's established level of concern for all U.S. subpopulations.]

	ii. Drinking water. [Aluminum sulfate is readily biodegradable according to OECD criteria; exposures to residues above toxicity levels of concern are not anticipated.]

	2. Non-dietary exposure. [In aggregating exposure, FFDCA section 408 directs EPA to consider available reliable information concerning exposures from pesticide residues in food and all other non-occupational exposures, including drinking water from groundwater or surface water and exposures through pesticide use in gardens, lawns, or buildings (residential and other indoor uses).

Given the low estimate of dietary exposure, there is ample room in the overall aggregate MOE to conservatively account for non-dietary uses of aluminum sulfate.]

D. Cumulative Effects

	[Based on information provided in the ATSDR Aluminum review, "No specific molecular mechanisms have been elucidated for human toxicity to aluminum."  Furthermore, there is no information in the public literature to suggest that aluminum sulfate would have a common mechanism of toxicity with other substances.  For the purpose of the tolerance exemption action cited herein, Ecolab has assumed that aluminum sulfate will not have a common mechanism of toxicity with other substances.]

E. Safety Determination

	1. U.S. population. [Based on the conservative exposure estimates, there is a reasonable certainty that no harm will result to the U.S. population from the aggregate exposure to aluminum sulfate.]

	2. Infants and children. [The FFDCA Section 408 requires an additional tenfold margin of safety for the protection of infants and children in case of threshold effects to account for prenatal and postnatal toxicity, and an inadequate toxicity database.  Where an adequate and reliable database is available and there is a lack of evidence for increased susceptibility, the FQPA safety factor may be reduced or removed.  

Based on available information for aluminum sulfate, Ecolab supports reducing the FQPA safety factor to 1X.  An OECD guideline two-generation reproduction study in rats indicated that there was no evidence of developmental or reproductive toxicity nor was there evidence of increased susceptibility of developing offspring in the absence of parental toxicity.  Ecolab requests that the additional tenfold safety factor for the protection of infants and children be removed for the purposes of this tolerance exemption.  For the reasons described above, the default 10X FQPA safety factor may be reduced to 1X, and the cRfD is therefore equivalent to the chronic population adjusted dose (cPAD) for aluminum sulfate. ]

F. International Tolerances

	[There are no known international tolerances for aluminum sulfate specified in this petition.]