            EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR
             PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER
                                       
          EPA Registration Division contact: PV Shah, (703) 308-1846

Ecolab Inc.
IN-11113

EPA has received a pesticide petition (IN-11113) from Ecolab Inc., 655 Lone Oak Drive, Eagan, MN 55121 proposing, 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

      lactic acid (CAS Reg. No. 50-21-5) when used as an acidifier under 40 CFR 180.940(a) in pesticide formulations applied to food-contact surfaces in public eating places, dairy processing equipment, food-processing equipment and utensils at 10,000 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 NA-Remove

      1. Plant metabolism.
      2. Analytical method. [NA-Remove]
      3. Magnitude of residues. [NA-Remove]

B. Toxicological Profile
Lactic acid is practically non-toxic to mammals, apart from irritation stemming from its
low pH. It is an endogenous compound produced in the mammalian system. L-lactic acid (lactate) is a product of fermentation in the muscles produced from pyruvate via lactate
dehydrogenase. Lactate is also generated from glucose under aerobic conditions in some tissues and cell types. L-Lactic acid is normally found in the blood and interstitial fluid of humans. In addition, lactic acid occurs naturally in several foods, primarily found in fermented milk products such as sour milk, cheese, buttermilk and yogurt. It also occurs naturally in meats,  fruits, tomato juice, beer, wine, molasses, blood and muscles of animals, and in the soil.

      1. Acute toxicity. The acute oral LD50 for -lactic acid was 3543  -  4936 mg/kg-bw for male and female Charles River rats, which places it in Acute Toxicity Category III for this endpoint. Clinical signs included lethargy, ataxia, prostration, irregular breathing, piloerection, squinting, lacrimation, salivation, crusty eyes and muzzle, loose stools, damp or yellow/brown stained fur and moribund. US EPA considered lactic acid Acute Toxicity Category III for dermal toxicity. The acute dermal LD50 of lactic acid in male and female New Zealand white rabbits was >2000 mg/kg bw following a 2-hour exposure to L(+)-lactic acid. No mortality or clinical signs of toxicity were seen. US EPA considered lactic acid Acute Toxicity Category IV for inhalation toxicity. The acute (4-hour) inhalation LC50 of lactic acid in male and female Fischer rats was >7.9 mg/L. Rats exposed via nose only demonstrated lethargy, rapid breathing, lacrimation, hunched posture, ruffled fur and unkempt appeared with soiled fur. By 24 hours, most animals appeared to have recovered from lethargy and unkempt fur although females (4/5) had ruffled and ungroomed fur until post-treatment day 4. One exposed female died on the 8[th] day post-treatment. No gross lesions were observed at necropsy.

      2. Genotoxicity. There is no evidence that lactic acid is genotoxic. The Cosmetic Ingredient Review (CIR) Expert Panel reviewed 15 mutagenicity and clastogenicity studies on lactic acid and ammonium, calcium, and sodium lactate. Results in all of these were negative. For example, in an Ames test in S. typhimurium strains TA92, TA1535, TA100, TA98, TA1537, and TA94, at a concentration of <10 mg/plate, 90.5% pure lactic acid did not induce reverse mutations with and without metabolic activation. In an in vitro chromosomal aberration study, Chinese hamster ovary K1 cells were exposed to 8-35 mM lactic acid in the presence or absence of metabolic activation. Lactic acid was not clastogenic with or without metabolic activation when the medium was neutralized to physiological pH 6.4 or when medium contained 30 mM HEPES as buffer. When the pH was not neutralized pseudo-positive reactions were observed. Cytotoxicity was noted at 14-35 mM, when pH was <5.8.

      3. Reproductive and developmental toxicity. Lactic acid was neither toxic to dams nor offspring when administered to pregnant Swiss mice via gavage at doses of 0 or 570 mg/kg bw/day during days 6-15 of gestation. Live fetuses were sexed, weighed and examined for morphological defects. The NOAEL for maternal and developmental toxicity was >570 mg/kg bw.

      4. Subchronic toxicity. The first in a series of three toxicity studies of lactic acid was a drinking water study in which F344 rats (5/sex/dose) received doses of 0.3%-5%, equivalent to approximately 0, 30, 60, 125, 250 or 500 mg/kg-bw/day, for 13 weeks. Effects reported were a slightly decreased body weight gain (<10%) at all doses compared to control group. Some changes in hematological and biochemical parameters were observed but no severe toxicological findings were reported in the histological examination in any dose group. The NOAEL was >500 mg/kg bw/day.

In the second study, F344 rats (5/sex/dose) received a synthetic diet containing 0, 5, 10, 20, or 30% calcium lactate. Body weight gain was decreased at the highest dose compared to control rats. The histological exam showed calcium salt deposition in the kidneys (nephrocalcinosis) in all groups including the controls; the degree of calcification was dose dependent, and was attributed to the low calcium/phosphorus ratio of the synthetic diet.

In the third study, rats were given either the basic or synthetic diet for 8 weeks. Calcium deposits in kidneys were observed only in the group given the synthetic diet and it was concluded that this effect was due to low Ca/P ratio (less than 1) of that diet.

A 14-week study was carried out in 8 male and 7 female Syrian hamsters per group. Group 1, the control group, received Diet 1: 20% sucrose plus pure water to drink. Group 2 received Diet 1 with 0.057 mL of 80%-pure lactic acid per 100 g of feed and pure water to drink. Group 3 received Diet 1, and drinking water containing 0.05% v/v 80%-pure lactic acid. Animals of groups 2 & 3 ingested the same amount lactic acid. After exposure, animals were sacrificed and autopsied. There were no differences in appearance or growth rate between the groups, and no gross changes were observed at necropsy.

No overt toxic effects were observed in pigs given approximately 3600 -18,000 mg/kg lactic acid in feed or water for up to 5 months. No further information was available on this study.

A group of white rats was fed 4 mL of 10% lactic acid mixed with 20 g of feed each day for 90 days. This dose was approximately 2042 mg/kg/day. A concurrent control received no lactic acid. No differences in appearance, gross observations at necropsy, or organ weights were observed between the test and control animals. Changes in blood carbon dioxide were slight.

F344 rats (50/sex/dose) received calcium lactate in the drinking water at levels of 0, 2.5 or 5% for 2 years. According to the Joint FAO/WHO Expert Committee on Food Additives, this provided doses of 0, 2500, and 5000 mg/kg bw per day, respectively, of calcium lactate. Rats were then given distilled water for a recovery period of 9 weeks. At week 113, all surviving animals were killed and autopsied. Gross and microscopic examinations were carried out for presence of non-neoplastic and neoplastic lesions. High-dose male and female rats showed a significant reduction (13%) in mean body weight gain. A significant dose-dependent increase was observed in the relative brain weights of both male and female rats without accompanying histological change. Study authors concluded this effect was a result of the decrease in body weight gain. There was no further evidence of organ-specific toxicity and there was no evidence of carcinogenicity. Based on body weight gain reduction, the NOAEL of this study is 2500 mg/kg bw/day calcium lactate, which is equivalent to 1032 mg/kg bw/day lactic acid.

      5. Chronic toxicity. The authors of the 90-day study described in the previous paragraph found no evidence of carcinogenicity in F355 rats in the 2-year drinking water study at doses up to 5000 mg/kg/day. Furthermore, lactic acid is an endogenous compound produced in the mammalian system and lactate is a product of anaerobic and aerobic respiration. It is not likely to be carcinogenic.

      6. Animal metabolism. Animals readily absorb both isomers of lactic acid or lactate from the gastrointestinal tract and have the capacity to completely metabolize both. In rats intubated with DL- sodium lactate containing radiolabeled C in the carboxyl position, an average of 20% of the administered radioactivity was expired as CO2 during the 2.5 hours following administration. Lactic acid/lactate is a product of fermentation in the muscles produced from pyruvate via lactate dehydrogenase. Lactic acid produced during anaerobic metabolism enters the lactic acid (Cori) cycle, diffusing into blood and then to the liver where it is converted back into pyruvate by lactic acid dehydrogenase. Lactate is also generated from glucose under aerobic conditions in some tissues and cell types.

      7. Metabolite toxicology. NA Remove

      8. Endocrine disruption. Toxicity related to endocrine disruption was not observed in the lactic acid database. As the scientific knowledge develops, screening of additional compounds may be added to the Endocrine Disruptor Screening Program (EDSP). When additional screening and/or testing is conducted lactic acid may be the focus of screening and/or testing to better characterize effects related to endocrine disruption.

C. Aggregate Exposure

      1. Dietary exposure. The estimated dietary exposure to lactic acid was determined using the FDA method in Sanitizing Solutions: Chemistry Guidelines for Food Additive Petitions, which is recommended for estimating dietary exposure to components of food contact sanitizing solution formulations intended for uses described under section 180.940a. Assumptions made in this model are:
:: 1 mg/cm² of product residue is present on the surface
:: The surface work area is 2000 cm2
:: 100% of residues transfer from the surface into food consumed by each individual daily
:: 100% of food contacts treated surfaces
:: Body weight default is 70 kg (adult) and 12.6 kg (1-2 yr old child)

The Estimated Daily Intake (EDI; mg/kg bw/day) was calculated to be 0.286 mg/kg bw/day for an adult and 1.59 mg/kg bw/day for a 1-2 year old child. This is 0.29% of the chronic population adjusted dose (cPAD) for an adult and 1.6% for a 1-2 year old child.

      i. Food. The approximate concentration of lactic acid in the American diet is 20.8 mg/kg/day.

      ii. Drinking water. Lactic acid is not expected to be present in drinking water.

      2. Non-dietary exposure. Lactic acid is a component of cosmetics.

D. Cumulative Effects Section 408(b)(2)(D) (9v) of the FFDCA requires that, when considering whether to establish, modify, or revoke a tolerance, the Agency consider "available information" concerning the cumulative effects of a particular pesticide's residues and "other substances that have a common mechanism of toxicity." EPA has not made a common mechanism of toxicity finding as to lactic acid and other compounds. Lactic acid does not produce toxic metabolites in common with other substances.

E. Safety Determination

      1. U.S. population. There is a reasonable certainty that no harm to humans will result from the use of lactic acid as an inert ingredient in antimicrobial pesticide products. The limit dose NOAEL of 1000 mg/kg/day was used to represent a substance that is essentially nontoxic because lactic acid is endogenous and has been consumed by people for centuries as part of the diet. This value was used to derive the chronic population adjusted dose (cPAD) along with a safety factor of 10 to account for sensitivity in the population. The resulting cPAD is 100 mg/kg/day. The estimated dietary exposure from food to lactic acid, assuming 100% of residues transfer from the surface into food and 100% of food contacts treated surfaces, is 0.29% of the cPAD for a 70-lb adult, well below any level of potential concern.

      2. Infants and children. There is a reasonable certainty that no harm to infants and children will result from the use of lactic acid as an inert ingredient in antimicrobial pesticide products. Lactic acid was not toxic to the development of mice when gestating mothers received 570 mg/kg bw/day lactic acid during gestation days 6-15. Thus at this time there is no concern for potential sensitivity to infants and children, and therefore the default 10X FQPA safety factor may be reduced to 1X.

F. International Tolerances

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