**BIOPESTICIDE S**  **REGISTRATION ACTION DOCUMENT**

**Salicylic Acid** PC Code: 076602

**U.S. Environmental Protection Agency Office of Pesticide Programs**  **Biopesticides and Pollution Prevention Division**

**January 10, 2012**Salicylic Acid Page 2

Biopestici des Registration Action Document **TABLE OF CONTENTS I.**  **EXECUTIVE SUMMARY ................................**  **................................ ................................**  **.... 4**  **II. ACTIVE INGREDIENT OVERVIEW**  **................................ ................................**  **................. 5**  **III .**  **REGULATORY BACKGROUND ................................**  **................................ ........................**  **5 A.**  **C lassification**  ................................ ................................ ................................ ................................ ................ 5 **B. Food Clearances/Tolerances**  ................................ ................................ ................................ ....................... 6 **IV. RISK**  **ASSESSMENT ................................**  **................................ ................................**  **............. 6**  **A. P**  **roduct Analysis Assessment** ................................ ................................ ................................ ..................... 7 **B. H**  **um an Health Assessment**  ................................ ................................ ................................ ......................... 8 **C. E**  **nvironmental Assessment** ................................ ................................ ................................ ....................... 15 **V. ENVIRONMENTAL JUSTICE ................................**  **................................ ............................**  **18 VI. RISK MANAGEMENT AND REGISTRATION DECISIONS**  **................................ .......**  **18 A.**  **Determ ination of Eligibility**  ................................ ................................ ................................ ...................... 19 **B. Regulatory**  **Decision** ................................ ................................ ................................ ................................ ... 19 **C. Labeling**  ................................ ................................ ................................ ................................ ...................... 19 **VII. ACTIONS REQUIRED OF**  **THE REGISTRANT ................................**  **........................... 19**  **A .**  **R eporting of Adverse Effects and Hypersensitivity Incidents**  ................................ ............................... 20 **VIII. GLOSSARY OF ACRONYMS AND ABBREVIATIONS ................................**  **............... 20**  **IX. BIBLIO**  **GRAPHY STUDIES SUBMITTED IN SUPPORT OF TH ESE**  **REGISTRATION S**  **................................ ................................**  **................................ ...............**  **21 A.**  **Studies Submitted in Support of Salicylic Acid** . ................................ ................................ ..................... 21 **B. EPA Risk Assessment Memoranda**  ................................ ................................ ................................ .......... 28 **C. References**  ................................ ................................ ................................ ................................ .................. 28Salicylic Acid Page 3

Biopestici des Registration Action Document

**BIOPESTICIDES REGISTRATION ACTION DOCUMENT TEAM**

**Office of Pesticide Programs Biopesticides and Pollution Prevention Division**  **Biochemical Pesticides Branch (BPB)** Chris Pfeifer Regulatory Action Leader Linda Hollis Branch Chief Angela Gonzales Lead Science Reviewer Russel l Jones, Ph.D . Senior BiologistSalicylic Acid Page 4

Biopestici des Registration Action Document **I. EXECUTIVE SUMMARY** Salicylic Acid is a naturally occurring plant regulator present in most plants. Data indicate that it triggers immune respon ses in plants and act s as a mild antibiotic. Humans consume Salicylic Acid regularl y as it is naturall y present in most fruits and vegetables. In its concentrated state, it is a white cry stalline powder with a sweetish acrid taste. It is known for its many useful es ter derivatives and can be found in a range of commercial products such as antiseptics, preservatives , and medicines. Salicylic Acid is perhaps best known as the principal metabolite and component of aspirin. Humans have a long history of natural exposure to Salicylic Acid without incident. As an active ingredient , it is intended for use as a treatment for seeds that are not meant for human or animal consumption . Its mode of action is as a Sy stemic Acquired Resistance (SAR) inducer for seedlings

– i.e. a trigger for invoking a seedling ’s natural defenses against pathogens , allowing for greater plant vigor and survivability . Because there are no residues taken up sy stemicall y, and treated seeds are not allowed for food or feed uses, this seed treatment is not considered to be a food use. Negligible dietary exposure s to the pesticidal active ingredient notwithstanding, there are few apparent risks related to regular exposure to this natural acid . D ata from a Dutch Food Consumption Survey show the av erage daily intake (ADI) for this chemical has been estimated to be 0 - 5 milligrams per day from the consumption of fruits and vegetables . Also, consumption of S alicylic Acid in aspirin exposes a person to greater doses than would an y p otential residues as sociated with seed treatment . (HSDB, 2008 ) Furthermore, Salicylic A cid is approved for use b y the U.S. Food and Drug Administration (FDA) as an indirect food additive under 21 CFR 175.105; and the U.S. Environmental Protection Agency ( EPA or Agency) has a

pprov ed the use of the chemical as an ‘other ingredient ’ in pesticide products. Insum , no hazards have been identified yet with regard to an y of these regular exposures . Moreover, data demonstrate that Salicylic Acid po se s minimal hazards for humans and the environment. Acute human health toxicity data indicate negligible human toxicity for all routes of exposure. Acute nontarget organism toxicology data indicate marginal toxicity for aquatic organisms , birds , mammals, insect s and plants . Subchronic and chronic toxicity data suggest no hazard relative to longer term exposure s, although no long - term exposures to Salicylic Acid formulated as a pesticidal active ingredient are anticipated given that Salicylic Acid biodegrades rapidly . No human health or enviro nmental risks are anticipated for Salicylic Acid due to its low toxicity and minimal opportunity for significant exposure. O n October 1, 2009, the EPA announced a new policy to provide a more meaningful opportunity for the public to participate in major registration decisions before they occur. According to this policy , EPA intends to provide a public comment period prior to making a registration decision for, at minimum, the following t ypes of applications: new active ingredients; first food uses; first outdoor uses; first residential uses; or any other registration actions for which EPA believes there may be significant public interest.Salicylic Acid Page 5

Biopestici des Registration Action Document Consistent with the policy of making registration actions more transparent, the proposed pesticide products c ontaining Salicylic Acid , a new active ingredient, are subject to a 30 - day comment period. In addition to containing a new active ingredient, the registration of these products would result in the first outdoor use for Salicylic Acid . The docket identification number associated with these registration actions, EPA - HQ - OPP - 2011 - 000 9 , can be accessed through http://www.regulations.gov/ . The following documents are available for comment in the docket: (1) Salicylic Acid Biopesticides Registration Action Document; (2) a draft label for the M anufacturing - use Product, EPA File Sy mbol 34704 - RNL T ; and (3) draft label s for the End - use P roduct s , EPA File Sy

mbol s 34704 - RNLL and 34704 - RNLA . While a final decision on registration is contingent upon review and consideration of public comments, EPA presently believes that, based upon the risk assessment and information submitted in support of Salicylic Acid , it is in the best interest of the public and the environment to issue these registrations. The basis for this preliminary decision can be found in the risk assessment for Salicylic Acid , which is presented in this document. **II. ACTIVE INGREDIENT OVERVIEW**  **Common Name:** Salicylic Acid **Chemical Names :**  2 - Hy drox ybenzoic aci d , Carbox yl ic Acid **Trade & Other Names :**  Salicylic Acid , SA **CAS Registry Number:** 69 - 72 - 7 **OPP Chemical Code:** 076602 **Type of Pesticide:** Plant Regulator **III. REGULATORY BACKGROUND** On February

2, 2011 , EPA published in the Federal Register ( 76 FR 5805 ) a notice announcing that Lo veland Products, Inc. , c/o Py xis Consulting, Inc., 4110 136th St., NW., Gig Harbor, WA 98332 , submitted an application to register a Manufacturing - use P r oduct (MP), EPA File Sy mbol 34704 - RNL T, and two End - use Products (EPs) , EPA File Sy mbols 34704 - RNLL and 34704 - RNLA, containing a new active ingredient ( Salicylic Acid) not included in any currently registered products . No comments were received fol lowing publication of the notice. **A. CLASSIFICATION**  Salicylic Acid was classi fied as a Biochemical Pesticide by the Classification Committee on November 20, 1997. The Classification C ommittee confirmed its nontoxic m ode of action , itsSalicylic Acid Page 6

Biopestici des Registration Action Document natural occurrence in the environment, and its history of exposure to humans and the environment w ithout known toxicity . S alicylic Acid is a naturally occurring plant hormone present in all terrestrial plants. Historically , it has been commerciall y distilled from willow bark, where it is found in high concentration. With regard to its active properti es, Salicylic Acid is a plant regulator that has mediating roles on plant growth, photosy

nthesis, transpiration , and ion uptake. When applied to seeds as an active ingredient, Salicylic Acid acts as a SAR inducer

– i.e. it triggers a plants immuno - defense sy stem to defend against pathogens, allowing for gre ater survivability of seedlings . **B. FOOD CLEARANCES/TOLERANCES**  Salicylic Acid is intended for use as a seed treatment for nonfood and non feed uses (i.e. treated seeds are not for animal or human consump tion) . Because no residues are sy stemicall y expressed through the planted seed to the fruit and vegetables, the use of Salicylic Acid is not considered to be a food use. **IV . RISK**  **ASSESSMENT** On October 26, 2007, the Agenc y issued a Final Rule in the Federal Register on the data requirements to support registration of biochemical and microbial pesticides, and updated the definitions for biochemical and microbial pesticides ( 72 FR 61002 ). The rule became effective on December 26, 2007. The data and information evaluated for this Biopesticides Registration Action Document (BRAD) were considered in light of these requirements. The classificatio ns that are found for each data submission are assigned b y EPA science reviewers and are an indication of the usefulness of the information contained in the documents for risk assessment. A rating of “ACCEPTABLE” indicates the study is scientifically

sound and is useful for risk assessment. A “SUPPL EMENTAL” rating indicates the data provide some information that can be useful for risk assessment. The studies may have certain aspects determined not to be scientifically

acceptable (“SUPPL EMENTAL: UPGRADABLE”) . If a study is rated as “SUPPL EMENTAL: UPGRADABLE,” EPA alway s provides an indication of what is lacking or what can be provided to change the rating to “ACCEPTABLE.” If there is simply a “SUPPL EMENTAL” rating, the reviewer will often state that the study is not required b y the current 40 CFR Part 158. Both “ACCEPTABLE” and “SUPPL EMENTAL” studies may be used in the risk assessment process as appropriate. An “UNACCEPTABLE” rating indicates that new data need to be submitted. For the acute toxicity

dat a requirements, Toxicity C ategories are assigned for providing the appropriate precautionary labeling statement s and are based on the hazard(s) identified from studies and/or other information submitted to EPA in support of a pesticide registration. The active ingredient or a particular product is classified into Toxicity Category I , II, III, or IV, where Toxicity Category Iindicates the highest toxicity and Toxicity

Category I V indicates the lowest toxicity .Salicylic Acid Page 7

Biopestici des Registration Action Document **A. PRODUCT ANALYSIS ASESSMENT 1.**  **Product Chemistry and Composition** Salicylic A cid (2 - hy droxy benzoic acid) is an aromatic carbox yl ic acid that is commercially derived from the bark of the willow tree . It is a naturall y occurring plant r egulator with various roles regulating photos ynthesis and transpiration and mediating plant defenses against pathogens ( U.S. EPA. 2011b. ) . Inpurest form, it is a white cry stalline powder with a sweetish acrid flavor . It is used in a variet y of topical cos metics and pharmaceutical products as a mild antibiotic (HDSB, 2011) . Salicylic Acid is naturally found in significant concentrations in a wide variet y of foods such as apples, plums, grapes, oranges, tomatoes, cinnamon, oregano, thy me, beer, honey

and rai sins (HDSB, 2011) . All product chemistry

data requirements for Salicylic Acid have been satisfied. As a manufactured active ingredient, Salicylic Acid extract is indistinguishable from the plant hormone that is produced naturall y in p l ants (MRID 47206713 ) . The extract has a high degree of purity and contains no impurities of toxicological significance (MRID 47206713, 47760931 and 47206714) . All data requirements for phy sical and chemical characteristics have been adequatel y addressed (U.S. EPA. 2011b.) . **2. Analysis and Certification of Limits**  The submitted data satisfied the requirement s for Analy sis and Certification of L imits. Five - batch anal ys es and the anal yt ical method used to determine the purity of Salicylic Acid were examined and determine d to be acceptable by the Agency . The information submitted on the anal ys es and certified limits are summarized in Table 1.

**TABLE 1. Product Chemistry Data Requirements for Salicylic Acid**  **Technical (40 CFR § 158.2030)**  **OSCPP Guideline No. Study**  **Results MRID**  **No.** 8 80.110 0 880.1200 880.140 0 Product identity;

Manufacturing process; Discussion of formation of im purities Submitted data satisfy the requirements for product identity, manufacturing process, and discussion of formation of im purities. 47206713 4 7760931 830.1700 Analysis of samples Submitted data satisfy the requirements for analysis of samples. 47206714 830.1750 Certification of limits Limits listed in the confidential statement of formula are acceptable 47206714 830.1800 Analytical method A cceptable. 47206714 **3. Physical and Chemical Characteristics**  The Agency

has determined that the submitted data adequately describe the phy sical and chemical characteristics of Salicylic Acid . See Table 2 below for details.Salicylic Acid Page 8

Biopestici des Registration Action Document

**TABLE 2. Physical and Chem**  **ical Properties of Salicylic Acid**  **Technical (40 CFR § 158.2030)**  **OCSPP Guideline No.**  **Property Description of Result**  **MRID No.**  830.6302 Color White 48225202 830.6303 Phy sical State Solid crystalline powder 48225202 830.6304 Odor Odorless 48225202

830.6313 Stability to Normal and

Elevated Temperatures, Metals and Metal Ions Stable for 14 days at room temperature, degrades slightly (below

certified limits) after 4 days at 54oC. Data on metals were not submitted; SA is not stored in or expected to c ome into contact with metal or metal ions during storage or use. 48225201 48225202 830.6315 Flammability Flash point: 315oF (157o C) HSDB , 200 8 830.6317 Storage Stability **In progress** 48225202 830.6319 Miscibility N/A: not an emulsifiable liquid that will be diluted with petroleum solvents. 48225202 830.6320 Corrosion Characteristics **In progress** 48225202 830.7000 pH 2.56 48225201 48225202 830.7050 UV/Visible Light

A bsorption Neutral: 231 nm (ε 1 = 6794), 296 nm (ε = 3567) Basic: 219.5 nm (ε = 7046), 296.5 nm (ε = 3535) Acidic: 236.5 nm (ε = 8538), 302 nm (ε = 3632) 48225201 48225202 830.7100 Viscosity N/A: product is a solid 48225202 830.7200 Melting Point/Ra nge 159.3 - 161.5 o C 48225202 830.7220 Boiling Point/ Range N/A: SA is a solid 48225202 830.7300 Density 1.429 g/mL 48225202 830.7520 Particle Size, Fiber Length

and Diameter Distribution N/A: SA is not water insoluble nor is it a fibrous substance with a diameter ≥ 0.1μm . 48225202 830.7550 830.7560 830.7570 Partition Coefficient (n Octanol/Water) Log P ow = 2.1 48225201 48225202 830.7840 Water Solubility 1.71 mg/mL in water 0.05 g/100 mL in hexane 32.12 g/100 mL in methanol 16.02 g/100 mL in n - octanol 48225201 48225202 830.7950 Vapor Pressure 114 Pa at 130oC 8.2X10 - 5 mm Hg at 25 o C 48225202 **B. HUMAN HEALTH ASSESSMENT**  **1. Toxicological Hazard Assessment**  Adequate mammalian toxicology studies were provided in support of the registration of Salicylic Acid for ea ch data requirement . Acute toxicology data indicates that the act ive ingredient is virtually nontoxic to mammals, and that there are no toxicological endpoints relative to its use as a SAR - inducer in plants . Accordingl y, the data submitted demonstrate that the proposed uses of Salicylic Acid pose no significant risks to human health and support a finding of reasonable certaint y that no harm to the general U.S. population, including infants and children, will result from exposure to this active ingredient ( U .S. EPA. 2011b; MRI Ds 48225203 - 48225208 ) .Salicylic Acid Page 9

Biopestici des Registration Action Document

**Table 3 . Mam**  **malian Toxicology Data for Salicylic Acid**  **Technical (40 CFR § 158.2050)**  **Study/OCSPP Guideline No. Results**  **Toxicity Description**  **MRID No.**  Acute oral toxicity (rat) (870.1100) LD 50 = 890 mg/kg III 472 06707 Acute dermal toxicity (rabbit ) (870.1200) LD 50 > 5 , 05 0 mg/kg IV 47206711 Acute inhalation toxicity (rat) (870.1300) LC 50 > 2.21 mg/ L IV 47206710 Primary eye irritation (rabbit) (870.2400) Moderately irritating III 47206706 Primary dermal irr i tation (rabbit) (870.2500) Non - irritating IV 47206709 Dermal sensitization (guinea pig) (870.2600) Not a sensitizer N/A 47206708 Hy persensitivity incidents (None ) Must be reported N/A 90 - Day oral toxicity (870.3100) Proposed products are nonfood use. Subchronic and chronic oral toxicity studies were submitted for methyl salicylate and acetylsalicylic acid , which are rapidly converted to SA and/or an SA ester in the body. Data indicate negligible toxicity. R isk to humans is not anticipated based on the lack of repeat oral exposure to SA due to the use pattern. 48225204 48225206

90 - Day dermal toxicity (870.3250) Purposeful application and prolonged exposure to the human skin is not anticipated based on the use pattern (seed treatment). Significant dermal exposure to handlers/applicators is unlikely as E nd - use P roduct (EP) labels require appropriate personal protective equipment (PPE) to mitigate dermal exposure. Risk is expected to be negligible based on the lack of anticipated exposure and dermal toxi cology data. 48225204 48225206

90 - Day inhalation toxicity (870.3465) S ignifi cant repeat inhalation exposure to SA as a gas, vapor or aerosol is unlikely based on use pattern as a seed treatment and physical properties of the active ingredient in that i t degrades rapidly in the environment. 48225204 48225206 Mutagenicity - bacterial reverse mutation test (modified Ames) (870.5100) Significant human exposure is unlikely based on use pattern as a seed treatment and rapid biodegradation in the environment . The risk of mutagenicity is expected to be negligible based on th e lack of anticipated exposure and mutagenicity data . HSDB, 2011 Mutagenicity - in vitro mammalian cell assay (870.5300 and 870.5375) Significant human exposure is unlikely based on use p attern as a seed treatment and rapid biodegradation in the environment. The risk of mutagenicity is expected to be negligible based on the lack of anticipated exposure and mutagenicity data. 48225207 Developmental toxicity (870.3700) Significant expos ure to female humans is unlikely based on use pattern as a seed treatment. S ignificant exposure to handlers/applicators is unlikely as EP labels require appropriate PPE to mitigate exposure. R isk is expected to be negligible based on th e lack of anticipate d exposure and the available developmental toxicology data . 48225205

**a. Acute Toxicity**  **– Tier I (40 CFR**  **§ 158.2050)**  Acute Oral Toxicit

y – Rat ( O CSPP Guideline 870.1100; MRID No . 4720670 7 ) : An acute oral toxicity study shows that the active ingr edient , Salicylic Acid , has an acute oral median lethal dose ( LD 50 ) of greater than 890 milligrams per kilogram ( mg/k g ) in rats. The study was foundSalicylic Acid Page 10

Biopestici des Registration Action Document “ACCEPTABLE , ” and Salicylic Acid was cla ssified as TOXI CI TY CATEGORY III for this route of exposure when us ed as a seed treatment . Acute Dermal Toxicity

– Rabbit (O CSPP Guideline 870.1200; MRID No . 4 7206711 ) : An acute dermal toxicity

study shows that the active ingredient , Salicylic Acid , has an LD 5 0 of greater than 5 , 05 0 mg/k g in rabbits , which is consider ed to be virtually nontoxic . Data substantiate the active i ngredient’s relative dermal nontoxicity to both occupational users and the general public. The study was found “ACCEPTABLE , ” and Salicylic Acid was classified as TOXI CI TY CATEGORY IV for this route of exposure when used as a seed treatment . Acute Inhalation Toxicity

– Rat (O CSPP Guideline 870.1300; MRID No. 47206710 ) : An acute oral inhalation study

shows that the active ingredient , Salicylic Acid , has a median lethal concentration ( LC 5 0 ) of greate r than 2.21 milligrams per liter ( mg/L ) in rats, which shows no significant inhalation toxicity . This was the maximum dose rate, and no toxicological effects were observed on the test subjects. The stud y was found “ACCEPTABLE , ” and Salicylic Acid was cla ss ified as TOXICITY CATEGORY IV for this route of exposure when used as a seed treatment . Primary Eye Irritation

– Rabbit (O CSPP Guideline 870.2400; MRID No. 47206706 ) : A primary ey e irritation study

on rabbits demonstrated Salicylic Acid to be moderatel y irritating to the ey e ; h owever, all i ritis and conjunctivitis cleared after 24 hours. The study was found “ACCEPTABLE , ” and Salicylic Acid was cl assified as TOXI CI TY CATEGORY III for this route of exposure when used as a seed treatment . Primary Dermal Irritation

– Rabbit (O CSPP Guideline 870.2500; MRID No. 4720670 9 ) : A skin irritation study

on rabbits demonstrated that Salicylic Acid was not irritating to the skin. The findings are consistent with the other dermal studies and confirm that Salicylic Ac id is not toxic through this route of exposure. The stud y was found “ACCEPTABLE , ” and Salicylic Acid was c lassified as TOXICITY CATEGORY IV for this route of exposure when used as a seed treatment . Skin Sensitization

– Guinea Pig (O CSPP Guideline 870.2600 ; MRID No . 4720670 8 ) : Data indicate Salicylic Acid is not a dermal sensitizer. Any reported incidents , however, may cause this position to be reconsidered. Subchronic Testing (O CSPP Guidelines 870.3100, 870.3250, and 870.3465; MRID Nos. 4 8225204 and 48 225206

) : In accordance with footnote s six, seven and eight in the Biochemical Pesticides Human Health Assessment Data Requirements table in 40 CFR § 158.2050, subchronic oral, subchronic dermal and subchronic inhalation testing were not required in this c ase because of a lack of exposure. Nonetheless, two subchronic oral tests , two subchronic dermal tests and one subchronic inhalation study were submitted. These studies are considered “SUPPL EMENTAL.” One subchronic oral test used methyl salicylate as its t est substance; and the other study used acet yl salicylic acid as its test substance. Both test substances readily metabolize into Salicylic Acid and are considered applicable to this risk assessment. The subchronic oral toxicity studies confirm that Salicyl ic Acid is not subchronicall y toxic through the oral route of exposure. With regard toSalicylic Acid Page 11

Biopestici des Registration Action Document subchronic dermal tests on Salicylic Acid , two studies on a Salicylic Acid test substance showed no sy stemic toxicity

and indicate d no subchronic toxicity through a derm al route of exposure. With regard to subchronic inhalation toxicity , a subchronic inhalation test on methyl salicylate was submitted in lieu of a study on Salicylic Acid. The supplemental information suggests that there is no subchronic toxicity

for Salicylic Acid through an inhalation route of exposure. A ll this supplemental information is secondary to the determination that there is virtually no exposure to this active ingredient when it is used as a seed treatment. Developmental Toxicity (O CSPP Guidelin e 870.3700; MRID No . 48225205 ) : Developmental toxicity data are conditionally

required if significant exposure to female humans is expected from the proposed product’s use under widespread and commonly recognized practice. Significant exposure to females is unlikely : Salicylic Acid is to be applied i n a closed sy stem that precludes significant exposure . E xposure to handlers/applicators is negligible as applications are seasonal , and EP labels require appropriate PPE . Additionally , e xposure during planting is unlikely because planting is done mechanically , users are required to wear PPE and Salicylic Acid biodegrades rapidly in the environment, further mitigating exposure (HSDB, 2011). Although risk to humans is anticipated to be negligible because significant human exposure is not anticipated, “SUPPL EMENTAL” developmental toxicity studies were submitted from the open scientific lit erature with MRID No. 48225205 . Each stud y s uggested that the risk for developmental toxicity was negligible . T he maternal no obs erved effect level (NOEL ) in the study was 75 mg/kg Salicylic Acid , and the lowest observed effect level ( LOEL ) was 150 mg/kg . These finding s suggest negligible developmental toxicity relative to an y potential exposures to Salicylic A cid when used as a see d treatment Mutagenicity Testing (O CSPP Guidelines 870.5100, 870.5300, and 870.5375; MRID No. 48225207) : Mutagenicity data are conditionally

required to support nonfood uses if the use is likely to result in significant human exposure or if the active in gredient or its metabolites are structurally

related to a known mutagen or belong to any chemical class of compounds containing a known mutagen. Significant exposure t o humans is unlikely based on Salicylic Acid ’s use pattern as a seed treatment. Significant exposure to handlers/applicators is unlikely as EP label s require PPE to further mitigate exposure. Finally , S alicylic Acid biodegr ades rapidly in the environment, further mitigating exposure (HSDB, 2008 ). Although risk to humans has been determined to be negligible because significant human exposure is not anticipated, “SUPP LE MENTAL” mutagen i city data were submitted . Results were negative in a modified Ames mutagenicity assay with and without metabolic activation at 1, 10, and 100 μ g SA/plate using Salm onella typhimurium strains TA1535, TA1537, TA1538, and TA1536 (HSDB, 2011). Furthermore, a stud y from the open scientific lit erature was provided in which Salicylic Acid and other S alicylic A cid derivatives were tested for their capacity to induce sister c hromatid exchange (SCE) and chromosomal aberrations (CA) in the bone marrow of Swiss albino male mice. There was no increased incidence of SCE in the assay , indicating that Salicylic A cid is not anticipated to be mutagenic. The information submitted was de termined to be adequate to support this seed treatment use .

**b. Acute Toxicity**  **– Tier II and Tier III (40 CFR**  **§ 158.2050)**  No Tier II and Tier III studies were required , based on a lack of acute toxicity in the Tier I studiesSalicylic Acid Page 12

Biopestici des Registration Action Document and a lack of exposure relative to Salicylic Acid’s pre - planting use pattern as a seed treatment .

**c. Effects on the Endocrine System** As required under Federal Food, Drug, and Cosmetic Act ( FFDCA ) section 408(p), EPA has developed the Endocrine Disruptor Screening Progr am (EDSP) to determine whether certain substances (including pesticide active and other ingredients) may have an effect in humans or wildlife similar to an effect produced b y a “naturally occurring estrogen, or other such endocrine effects as the Administr ator may designate.” The EDSP employ s a two - tiered approach to making the statutorily

required determinations. Tier 1 consists of a battery of 11 screening assay s to identify the potential of a chemical substance to interact with the estrogen, androgen, or thy roid (E, A, or T) hormonal s ys tems. Chemicals that go through Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal s ys tems will proceed to the next stage of the EDSP where EPA will determine which, if an y, of the Ti er 2 tests are necessary based on the available data. Tier 2 testing is designed to identify an y adverse endocrine - related effects caused by the substance, and establish a quantitative relationship between the dose and the E, A, or T effect. Between Octo ber 2009 and February 2010, EPA issued test orders/data call - ins for the first group of 67 chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. This list of chemicals was selected based on the potential for human exposure thro ugh pathway s such as food and water, residential activity , and certain post - application agricultural scenarios. This list should not be construed as a list of known or likel y endocrine disruptors. Salicylic Acid is not among the group of 58 pesticide act ive ingredients on the initial list to be screened under the EDSP. Under FFDCA section 408(p), EPA must screen all pesticide chemicals. Accordingl y, EPA anticipates issuing future EDSP orders/data call - ins for all pesticide active ingredients. For further information on the status of the EDSP, the policies and procedures, the list of 67 chemicals, the test guidelines and the Tier 1 screening battery , please visit our website: http://www.epa.gov/endo/ . **2. Dose R esponse Assessment**  No toxicological endpoints were identified; therefore, a dose response assessment was not required. **3. Dietary Exposure and Risk Characterization** Salicylic Acid is intended for use as a pre - planting seed treatment, and is consi dered to be a nonfood use. Exposure to residues of Salicylic Acid is not expected. Data indicate that Salicylic Acid is not taken up into the plant sy stemically , and that endogenous application s biodegrade rapidly , long before a plant might fruit. Even in the incidental event of exp osure to residues , no dietary risks are anticipated. Acute, subchronic, and teratogenicit y studies support Salic yl ic Acid’s nontoxic profile. It is already present in the human diet

– in all fruits and vegetables

– without any kn own detrimental effect. Furthermore, there is no information in the public literature suggesting any health issues to either animals or plants relative to this compound. In sum, no dietary exposureSalicylic Acid Page 13

Biopestici des Registration Action Document is expected; and an y potential dietary exposures would not be expected to pose an y quantifiable risk, due to Salicylic Acid’s nontoxic profile. **4. Drinking Water Exposure Risk Characterization** No residues are expected in drinking water as a result of the use of Salicylic Acid as a seed treatment. Applicati ons of Salicylic Acid are to be made directl y to seeds in a closed s ys tem . Seeds are then planted directl y i nto the soil. B ecause the se seeds are contained in the soil , run - off due to watering seems unlikely . Even in the incidental event of exp osure to res idues, no dietary risks are anticipated. Acute, subchronic, and teratogenicit y studies support Salicylic Acid’s nontoxic profile. It is alread y present in the human diet

– in all fruits and vegetables

– without any known detrimental effect. Furthermore, there is no information in the public literature suggesting any health issues to either animals or plants relative to this compound. Negligible residues might migrate through the soil after a rain event or watering but would not be expected to reach surface water or percolate through the soil to ground water given the rapid biodegradation of Salicylic Acid and the rapid metabolization of Salicylic Acid by s oil microbes . Therefore, the Agency concludes that the use of Salicylic Acid as a pre - planting seed tre atment is not expected to result in any significant drinking water exposure. Altogether, drinking water exposure is not expected to pose an y quantifiable risk, due to both a lack of residues and the nontoxicity of Salicylic Acid . **5. Acute and Chronic Di etary Exposure and Risks for Sensitive Subpopulations,**  **Particularly Infants and Children** Dietary exposure to humans, including infants and children, is not anticipated with regard to the pesticidal use of Salicylic Acid as a seed treatment. The applicati on is considere d a non food use because the residue is not expressed sy stemically into the plant; and the active ingredient is expected to biodegrade soon after planting. In the event that there are an y residues, a cute toxicity studies indicate that Salicyl ic Acid has negligible toxicity . It is ubiquitous in nature and present in all edible plants, and there is no history of toxicological incident involving its consumption. While no dietary

exposures are expected, the Agency has determined there is a reasona ble certainty

of no harm to the general U . S . population, including infants and children, from exposure to this active ingredient. **6. Occupational, Residential, School and Day Care Exposure and Risk Characterization**  O ccupational exposure to Salicylic Aci d is anticipated to be minimal when Salicylic Acid is used as a seed treatment . It is expected to be de minimis for residential, school, or day care areas . In the event of incidental exposure, health risks to humans, including infants and children, are con sidered negligible, given Salicylic Acid ’s nontoxic profile.

**a. Occupational Exposure and Risk Characterization**  An occupational exposure assessment was not conducted for Salicylic A cid. Based on the proposed use pattern and toxicity data available to the Agency , there are no exposure scenariosSalicylic Acid Page 14

Biopestici des Registration Action Document likely to result in unreasonable risk to humans. With regard to risks to incidental exposure, n o relevant toxicologic al endpoints were identified . The rationale follows: Seeds are treated in a closed sy stem; and then seeds are incorporated directly into the soil. Pre - planting s eed treatments are infrequent and seasonal. Workers treating seeds and workers planting treated seed will have PPE . Finally , given the rapid rate of biodegradation, incidental exposures related to reentry into a newly

planted area are anticipated to be negligible (U.S. EPA. 2011b.) . But even in the event of occupational exposure, an y health risks associated with regular expos ure seem unlikely . People regularl y consume Salicylic Acid in their fruits and vegetables , and apply it topicall y in many over - the - counter antiseptics, antibiotics and cleaners. With regard to these regular exposures, there is no history of detrimental effects. Moreover , all acute, subchronic, and developmental toxici ty data submitted to support th e registration application s for Salicylic Acid confirm its lack of toxicity through all routes of exposure. **b. Residential, School, and Day**  **C are Exposure and Risk Characterization**  A residential, school and day care ex posure assessment was not conducted for S alicylic A cid. Products containing S alicylic A cid will be used in an agricultural setting. Based on the use pattern, residential, school and day care exposures are unlikely . In the remote event of incidental exposur e to residue s , the active ingredient has a nontoxic profile for all routes of exposure and a long history of consumption without incident. Due to limited exposure scenarios and negligible toxicity hazards, no risks are expected relative to these exposure s cenarios. **7. Aggregate Exposure from Multiple Routes Including Dermal, Oral, and**  **Inhalation** The potential for aggregate exposure is expected to be insignificant. No exposures are anticipated in non - occupational environments . Seeds treated with Sali cylic Acid are incorporated into the soil directly . It has been established that Salicylic Acid biodegrades rapidly in soil; and the residues are not taken up into the plant sy stemicall y (HDSB, 2008). (Indeed, no residues are expected to be present in the seedlings.) Given a lack of an y significant non - occupational exposure, a lack of concern regarding its naturally occurring background levels, and a lack of any acute toxicological endpoints for Salicylic Acid , the aggregate exposure scenario presents no si gnificant concerns for risk. **8. Cumulative Effects** Pursuant to FFDCA section 408(b)(2)(D)(v), EPA has considered available information concerning the cumulative effects of Salicylic Acid residues and other substances that have a common mechanism of toxicity . These considerations include the potential for cumulative effects on infants and children of Salicylic Acid residues and other substances with a common mechanism of toxicity . Because Salicylic Acid has a long history of dietary

consumption without incident, and because no toxicological endpoints have been established, the Agency concludes that SalicylicSalicylic Acid Page 15

Biopestici des Registration Action Document Acid does not share a common mechanism of toxicity , and that there are no potential cumulative effects arising from incidental exposures to Salicy lic Acid residues in or on food commodities . **9. Risk Characterization**  The Agency

considered human exposure to Salicylic Acid in light of the standard for registration in the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and the relevant safet y factors in F FDCA. A determination has been made that no unreasonable adverse effects to the U.S. population in general, and to infants and children in particular, will result from the use of Salicylic Acid when label instructions are followed. **C . ENVIRONMENTAL ASSESSMENT**  **1. Ecological Hazards**  **(Relative to the Biochemical Pesticides Nontarget Organisms and Environmental Fate Data Requirements**  **- 40 CFR**  **§ 158.2060)**  Adequate nontarget toxicology data/information are available to support registration of Salicylic Acid . All nontarget toxicology data requirements for Salicylic Acid have been satisfied. Th ere are no concerns for an y nontarget organisms when Salicylic Acid is applied as a seed treatment . No toxic endpoints have been identified for nontarget mammals, nontarget bird s, nontarget aquatic organisms and nontarget insects .Salicylic Acid Page 16

Biopestici des Registration Action Document

Avian Testing (O C

SPP Guidel ines 850.2100 and 850.2200 ; MRID No s . 47 206704 and 47206702

) : No avian toxicity

is expected with regard to the pesticidal use of Salicylic Acid . Two acute oral toxi city studies were found “ACCEPTABLE.” The studies established the following thres holds: LD 50 = 494 mg/kg, an LC 50 > 5,000 ppm , and an NOAEL = 2,500 ppm . Each threshold is far in excess of an y anticipated exposure; and no toxicological endpoints were established . The data indicate that Sa licylic Acid is practicall y nontoxic to birds. A quatic Organism Testing (O CSPP Guidelines 850.1010 and 850.1075 ; MRID Nos. 47206703 and 4720670 5 ) : No risks are expected with regard to the exposure of aquatic organisms to Salicylic Acid . Aquatic exposure is unlikely because seed treatments are conducted in closed sy stems, treated seeds are incorporated directly into soil, and Salicylic Acid is known to rapidly biodegrade in soil. In the event of any aquatic exposures, the data indicate that Sa licylic Acid is practicall y nontoxic to aquatic organisms. A n ontarget aquatic invertebrate study and a freshwater fish study were found “ACCEPTABLE.” The studies established the following thresholds: L C 50 = 134.8 mg/L and an E C 50 > 184.88 mg/L . Each threshold is far in excess of an y anticipated exposure; and no toxi cological endpoints were established. The data indicate that Sa licylic Acid is practically nontoxic to aquatic nontarget organisms .

**TABLE 4. Nontarget Organism Toxicity Requirements for Salicylic A**  **cid Technical**  **(40 CFR § 158.2060) Study/OCSPP Guideline No.**  **Results Toxicity**  **Category/ Description**  **MRID No.**  Avian acute oral toxicity Colinus virginianus (850.2100) LD 50 = 494 mg/kg (95% confidence interval = 396 - 614 mg/kg) Moderately toxic 47206704 Avian dietary toxicity Colinus virginianus and Anas platyrhynchos (850.2200) LC 50 > 5,000 ppm NOAEL = 2 ,500 ppm (for both species) Practically nontoxic 47206702 47229501 Aquatic invert ebrate acute toxicity ( Daphnia magna ) (850.1010) 48 - hour EC 50 = 184.88 mg/L (95% confidence interval = 182.1 - 187.7 mg/L) Practically nontoxic 47206703 Freshwater fish LC 50 ( Oncorhynchus mykiss ) (850.1075) 96 - hour L C 50 = 134.8 mg/L (95% confidence interval = 125 - 145 mg/L) Practically nontoxic 47206705 Non target plant studies - seedling em ergence (850.4100) Based on the proposed use pattern (SA is directly applied to target se eds only prior to planting) and that SA biodegrades rapidly in the environment, seedling emergence in nontarget plants is not anticipated to be adversely im pacted . 48225210 Nontarget plant studies - vegetative vigor (850.4150) T he proposed use of SA a s eed treatment is not expected to result in adverse effects to vegetative vigor, as the active ingredient will not be used on seedlings or mature plants. SA is directly applied to target seeds only prior to planting . Additionally, the active ingredient biod egrades quickly in the environment , which further precludes exposure to nontarget plants. 48225211

Non target insect testing ( Apis mellifera ) (880.4350) 96 - hour acute contact LD 50 > 100 μg/bee Practically nontoxic 48225212Salicylic Acid Page 17

Biopestici des Registration Action Document Non target Plant Testing (O CSPP Guidelines 850.4100 and 850.4150 ; MRID No s . 4 825210 and 482521 1 ) : Two nontarget plant stud ies were conducted. In one stud y, a solution containing 0.039% Salicylic Acid (the maximum dose for the proposed EP) was tested for effects on seedling emergence in ten species of plants for 21 day s , during which time seedling emergence and plant height we re observed. Based on the findings , there were no attributable effects to seedling emergence on no ntarget plants . Inthe second study , a solution contain ing 0.039% Salicylic Acid (the maximum dose for the proposed EP) was tested for effects on vegetative v igor in ten species of plants for 21 day s, during which time plant survival, growth and condition were observed. There were no reported adverse effects (25% or greater) in nine of the ten species tested when compared to controls. A statistically significant (

p <0.05) reduction of 25% was reported for the mean dry weight of ry egrass. Phy

totoxic effects such as chlorosis, insect damage, leaf curl, necrosis and wilt were noted on some plants but were infrequent, generall y not severe and present in both treatment and control groups. A lthough some phy totoxic effects were noted in this study , the proposed use of Salicylic A cid as a seed treatment is not expected to result in adverse effects to vegetative vigor, as the active ingredient will not be used on seedlings or mature plants. Moreover, the active ingredient biodegrades quickly in the environment , which further precludes exposure to nontarget plants. No toxic effects are anticipated to nontarget plants when Salicylic Acid is applied as a seed treatment. Non target Insect Testing (O CSPP Guidelines 880.4350; M RID No . 48225212): An acute contact toxicity test was conducted to evaluate the toxicity to the honey

bee from exposure to Saly cylic Acid . Groups of young adult honey bees ( Apis mellifera ) were d osed topically with the active ingredient at 100, 50, 25, 12.5 and 6.25 μg/bee. Bees were observed for mortality and other toxic effects twice within the four hours post - treatment and at 24, 48, 72 and 96 hours. Based on the observed effects, the NOEC was determined to be 25 μg/bee and the 96 - hour acute contact LD 50 > 100 μg/bee. No such exposures are anticipated for nontarget insects. Nevertheless, the findings indicate that Sa licylic Acid is practicall y nontoxic to nontarget insects. **2. Environmental F**  **ate and Ground Water Data** Environmental fate and groundwater data are not required at this time because the results of the nontarget organism toxicity assessment (Tier I data requirements) did not trigger these Tier II data requirements. **3. Ecologica**  **l Exposure and Risk Characterization** No significant exposure to nontarget organisms is anticipated when Salicylic Acid is applied as a seed treatment. Treatment occurs in a closed environment; and treated seeds are incorporated directly into the soil. Add itionally , the active ingredient biodegrades rapidly in the environment , further precluding exposure. Regardless, the risk to nontargets is minimal. Salicylic A cid is practicall y nontoxic to fish, birds, mammals, aquatic invertebrates and insects. W hile s o me phy totoxicity was observed in one species of plant (of the ten tested), the effects were minimal and not attributable to Salicylic Acid.Salicylic Acid Page 18

Biopestici des Registration Action Document The Agency

was able to quantify

the risk to terrestrial nontarget organisms through modeling. Using the Agency ’s Terrestrial Residue Exposure model (T - REX) version 1.4.1, risk quotients (RQs) were calculated to assess potential risk to birds. The risk quotients that were conservativel y calculated using the hazard data and estimated dietary exposure (calculated using T - REX) were determined to be significantly less than the Agency ’s level of concern (LOC) of 0.1 for threatened and endangered avian species. This information is summarized in Table 5 below. Anticipated exposures are unlikel y to result in unreasonable risk to avian species when Salicylic A cid is used as a seed treatment . **TABLE 5. Determination of Avian Risk Quotients (RQs) for Salicylic Acid Technical**  **Species LD**  **50 /NOEL**  **Acute RQ ([mg/kg bw**  **- day]/LD**  **50 )**  **Crops** Colinus virginian LD 50 = 494 mg/kg

(95% confidence interval = 396 - 614 mg/kg) 0.03 (for all crops) Barley , beans, dried beans, lima beans, snap beans, canola, corn, cotton, oats, onion, blackey ed peas, pea, lupine, grain lupine, field peas, peanuts, rice, ry e, safflower, sorghum, so ybeans, so yb eans (edible), sugar beets, triticale, wheat . **4. Threatened and Endangered Species Assessment**  The Agency

has not conducted a risk assessment that supports a complete endangered species determination. The ecological risk assessment planned during regi stration review will allow the Agency to determine whether Salicylic A cid’s use has “no effect” or “may effect” federally listed threatened or endangered species (listed species) or their designated critical habitats. When an assessment concludes that a pe sticide’s use “may affect” a listed species or its designated critical habitat, the Agency

will consult with the U.S. Fish and Wildlife Service and/or National Marine Fisheries Services (the Services) as appropriate. **V. ENVIRONMENTAL JUSTICE** EPA seek s to achieve environmental justice, the fair treatment and meaningful involvement of all people, regardless of race, color, national origin, or income, in the development, implementation, and enforcement of environmental laws, regulations, and policies. To help address potential environmental justice issues, the Agency seeks information on any groups or segments of the population who, as a result of their location, cultural practices, or other factors, may have aty pical, unusually high exposure to Salicylic Acid , compared to the general population. Please comment if yo u are aware of an y sub - populations that may have at ypical, unusuall y high exposure compared to the general population. **VI. RISK MANAGEMENT AND REGISTRATION DECISIONS**Salicylic Acid Page 19

Biopestici des Registration Action Document **A. Determination of Eligibility** Section 3(c)(5) of FIFRA provides for the registration of new active ingredients if it is determined that (A) its composition is such as to warrant the proposed claims for it; (B) its labeling and other materials required to be submitted comply with the requirements of FIFRA; (C) it will perform its intended function without unreasonable adverse effects on the environment; and (D) when used in acco rdance with widespread and commonly recognized practice , it will not generall y cause unreasonable adverse effects on the environment. The four criteria of the Eligibility Determination for Pesticidal Active Ingredients are satisfied b y the science assess ments supporting products containing Salicylic Acid . Such products are not expected to cau se unreasonable adverse effects and are likel y to provide protection as claimed when used according to label instructions. Therefore, EPA concludes that Salicylic Aci d is eligible for registration for the labeled uses. **B. Regulatory**  **Decision** O n October 1, 2009, the EPA announced a new policy to provide a more meaningful opportunity for the public to participate in major registration decisions before they occur. Acc ording to this policy , EPA intends to provide a public comment period prior to making a registration decision for, at minimum, the following t ypes of applications: new active ingredients; first food uses; first outdoor uses; first residential uses; or any other registration actions for which EPA believes there may be significant public interest. A ccordingl y, this pesticide i s subject to a 30 - day comment period as a new active ingredient with outdoor uses. At this time, EPA believes, the data submitted fu lfill the requirements of registration for products containing Salicylic Acid for use as a seed treatment and SAR inducer . Acute toxicity data for Salicylic Acid demonstrate that it is toxicity category I II and IV for all routes of exposure. (No toxicologi cal endpoints were established.) Data confirm that Salicylic Acid does not demonstrate subchronic or developmental toxicity , and it is not mutagenic or genotoxic. EPA has no concerns for an y nontarget organisms exposed to Salicylic Acid in accordance with its approved uses. EPA has not identif

ied an y toxic endpoints for nontarget mammals, birds, plants, aquatic, or soil organisms. Nor are there any anticipated concerns for any threatened and endangered species. Given the nontoxic character of Salicylic Aci d and because all applicable data requirements have been fulfilled , EPA supports its registration under FIFRA section 3(c)(5) . **C. Labeling** Before releasing pesticide products containing Salicylic Acid for shipment, the applicant is required to provid e appropriate labels. **VII. ACTIONS REQUIRED OF**  **THE REGISTRANT**Salicylic Acid Page 20

Biopestici des Registration Action Document The Agency

evaluated the data submitted in connection with the initial registration of Salicylic Acid and determined that these data fulfill current registration guideline requirements. No a dditional data are required to be submitted to the Agency at this time. Additional data may be required for new uses and/or changes to existing uses. Notwithstanding the information stated in the previous paragraph, it should be clearly understood that certa in, specific data are required to be reported to the Agency as a requirement for maintaining the Federal registration for a pesticide product. A brief summary of these t ypes of data are listed below. **A. R eporting of Adverse Effects and Hypersens**  **itivity Incidents** Reports of all incidents of adverse effects to the environment must be submitted to the Agency under the provisions stated in FIFRA s ection 6(a)(2). Additionally , all incidents of hy persensitivity

(including both suspected and confirmed incidents) must be reported to the Agency under the provisions of 40 CFR § 158.2050(e) . **VIII. GLOSSARY OF ACRONYMS AND ABBREVIATIONS**  ADI average dail y intake BPB Biochemical Pesticides Branch BRAD Biopesticide s Registration Action Document CA chromoso mal aberrations CAS Chemical Abstracts Service CFR Code of Federal Regulations EDSP Endocrine Disruptor Screening Program EP End - use Product EPA United States Environmental Protection Agency (Agency) FDA United States Food and Drug Administration FFDCA Fe deral Food, Drug, and Cosmetic Act FIFRA Federal Insecticide, Fungicide, and Rodenticide Act FR Federal Register g gram g/m L gram per milliliter Hg mercury HSDB Hazardous Substances Data Bank LC 50 median lethal concentration. A statistically derived con centration of a substance that can be expected to cause death in 50% of test animals. It is usually expressed as the weight of substance per weight or volume of water, air, or feed (e.g., mg/L, mg/kg, or ppm). LD 50 median lethal dose. A statistica lly derived single dose that can be expected to cause death in 50% of the test animals when administered by the route indicated (oral, dermal, or inhalation). It is expressed as a weight ofSalicylic Acid Page 21

Biopestici des Registration Action Document

substance per unit weight of animal (e.g., mg/kg). LOC level of concern LOEL lowest observed effect level μg microgram μm micrometer MRI D No. Master Record Identification Number mg/kg milligram per kilogram mg/L milligram per liter mg/ml milligram per milliliter ml milliliter mm millimeter MP M anufacturing - use P roduct nm nanometer NOAEL no observed adverse eff ect level NOEC no observed effect concentration NOEL no observed effect level OCSPP Office of Chemical Safety and Pollution Prevention OPP Office of Pesticide Programs Pa pascal PC Code Pesticide Chemical Code ppb parts per billion PPE personal protectiv e equipment ppm parts per million RQ risk quotient SA Salicylic Acid SAR Sy stemic Acquired Resistance SCE sister chromatid exchange **IX. BIBLIOGRAPHY STUDIES SUBMITTED IN SUPPORT OF TH**  **ESE REGISTRATION**  **S A.**  **Studies Submitted in Support of Salicylic A**  **cid MRID**  **No. Citation**  **Receipt Date**  47206700 NCA Biotech, Inc. (2007) Submission of Product Chemistry and Toxicity Data in Support of the

Application for Registration of Technical Salicylic Acid. Transmittal of 14 Studies. 14 - Aug 2007 47206701 Kaminsky, M . (2007) Salicylic Acid Technical: Product Chemistry: Final Report. Project Number:

10913/07. Unpublished study prepared by Stillmeadow, Inc. 14 p. 14 - Aug 2007 47206702 Gallagher, S.; Martin, K.; Beavers, J. (2006) Salicylic Acid Technical: A Dietary LC50 Study with the

Mallard. Project Number: 627/102. Unpublished study prepared by Wildlife International, Ltd. 56 p. 14 - Aug 2007 47206703 Rodrigue, N. (2006) Salicylic Acid Technical: Daphnia magna 48 - Hour Acute Toxicity Test: Final

Report. Project Number: 9599/05. Unpublished study prepared by Stillmeadow, Inc. 12 p. 14 - Aug 2007Salicylic Acid Page 22

Biopestici des Registration Action Document **MRID No.**  **Citation Receipt**  **Date** 47206704 Gallagher, S.; Beavers, J. (2006) Salicylic Acid Technical: An Acute Oral Toxicity Study with the

Northern Bobw

hite. Project Number: 627/103. Unpublished study prepared by Wildlife International, Ltd. 50 p. 14 - Aug 2007 47206705 Rodrigue, N. (2006) Salicylic Acid Technical: Rainbow Trout 96 - Hour Acute Toxicity Test: Final Report. Project Number: 9600/05. Unpublished study prepared by Stillmeadow, Inc. 14 p. 14 - Aug 2007 47 206706 Jia, S. (2006) Salicylic Acid Technical: Acute Eye Irritation Study in Rabbits: Amended Final Report.

Project Number: 9583/05. Unpublished study prepared by Stillmeadow, Inc. 23 p. 14 - Aug 2007 47206707 Jia, S. (2006) Salicylic Acid Technical: Acute Oral Toxicity Study (UDP) in Rats: Amended Final

Report. Project Number: 9580/05. Unpublished study prepared by Stillmeadow, Inc. 19 p. 14 - Aug 2007 47206708 Jia, S. (2006) Salicylic Acid Technical: Skin Sensitization Study in Guinea Pigs: Amended Final

R eport. Project Number: 9585/05. Unpublished study prepared by Stillmeadow, Inc. 24 p. 14 - Aug 2007 47206709 Jia, S. (2006) Salicylic Acid Technical: Acute Dermal Irritation Study in Rabbits: Amended Final

Report. Project Number: 9584/05. Unpublished study prepared by Stillmeadow, Inc. 18 p. 14 - Aug 2007 47206710 Jia, S. (2006) Salicylic Acid Technical: Acute Inhalation Toxicity Study in Rats: Amended Final

Report. Project Number: 9582/05. Unpublished study prepared by Stillmeadow, Inc. 24 p. 14 - Aug 2007 47 206711 Jia, S. (2006) Salicylic Acid Technical: Acute Dermal Toxicity Study in Rabbits: Amended Final

Report. Project Number: 9581/05. Unpublished study prepared by Stillmeadow, Inc. 18 p. 14 - Aug 2007 47206712 Kaminsky, M. (2006) Salicylic Acid Technical: Accelerated Storage Stability: Final Report. Project

Number: 9578/05. Unpublished study prepared by Stillmeadow , Inc. 12 p. 14 - Aug 2007 47206713 Aiguo, Z.; Wang, D. (2005) Product Identity and Composition, Description of the Materials Used,

Description o f the Production Process and Discussion of the Formation of Impurities for Salicylic Acid (SA) Technical. Project Number: LTB/02018. Unpublished study prepared by LT Biosyn, Inc. 20 p. 14 - Aug 2007 47206714 Shi, X.; Xu, F. (2005) Preliminary Analysis, Cert ified Limits and Enforcement Analytica l Method for

Salicylic Acid Technical. Project Number: NCA/0 2018. Unpublished study by LT Biosyn, Inc. 34 p. 14 - Aug 2007 47229500 NCA Biotech, Inc. (2007) Submission of Toxicity Data in Support of the Application for Registration

of Technical Salicylic Acid. Transmittal of 1 Study. 13 - Sep 2007 47229501 Gallagher, S.; Martin, K.; Beavers, J. (2006) Salicylic Acid Technical: A Dietary LC50 Study with the

Northern Bobw

hite. Project Number: 627/101. Unpublished study prep ared by Wildlife International, Ltd. 56 p. 13 - Sep 2007 47464500 U.S. Environmental Protection Agency (2008) Submission of Risk, Exposure, Toxicity and Safety

Data. Transmittal of 50 Studies. 02 - Jul 2008 47464504 Ridout, G.; Guy, R. (1988) Structure - Penetration Relationships in Percutaneous Absorption. Pesticide

Form ulations: Innovations and Developments: 112 - 123. 02 - Jul 2008 47760900 NCA Biotech, Inc. (2009) Submission of Fate, Toxicity and Product Chemistry Data in Support of the

Application for Registr ation of Technical Salicylic Acid. Transmittal of 46 Studies. 22 - May 2009 47760901 Millar, R.; Kay, J. (2009) Background Information of Salicylic Acid. Project Number: NCA/200901.

Unpublished study prepared by NCA Biotech, Inc. 7 p. 22 - May 2009Salicylic Acid Page 23

Biopestici des Registration Action Document **MRID No.**  **Citation Receipt**  **Date** 47760902 Raskin, I. (1992) Salicylic, A New Plant Hormone. Plant Physiology 99: 799 - 803. 22 - May 2009 47760903 Metraux, J. (2002) Recent Breakthroughs in the Study of Salicylic Acid Biosynthesis. Trends in Plant

Science 7(8): 332 - 334. 22 - May 2009 47760904 Silverma n, P; Seskar, M.; Kanter, D.; et al. (1995) Salicylic Acid in Rice. Plant Physiology 108: 633 -

639. 22 - May 2009 47760905 Coquoz, J.; Buchala, A.; Metraux, J. (1998) The Biosynthesis of Salicylic Acid in Potato Plants. Plant

Phy siology 117: 1095 - 1101. 22 - Ma y 2009 47760906 Chen, Z.; Klessig, D. (1991) Identification of a Soluble Salicylic Acid - Binding Protein that may

Function in Signal Transduction in the Plant Disease - Resistance Response . National Academy of Science, USA 88: 8179 - 8183. 22 - May 2009 477609 07 Delaney, T.; Friedrich, L.; Ryals, J. (1995) Arabidopsis Signal Transduction Mutant Defective in

Chemically and Biologically Induced Disease Resistance. Proceedings, National Academy of Science USA 92(JUL): 6602 - 6606. 22 - May 2009 47760909 Gaffney, T.; Friedrich, L.; Vernooij, B.; et al. (1993) Requirement of Salicylic Acid for the Induction

of Systemic Acquired Resistance. Science 261: 754 - 755. 22 - May 2009 47760910 Hunt, M.; Neuenschwander, R.; Delaney, T.; et al. (1996) Recent Advances in Systemic Acquired

Resistance Research - A Review . Gene 179: 89 - 95. 22 - May 2009 47760911 Jirage, D.; Tootle, T.; Reuber, T.; et al. (1999) Arabidopsis Thaliana PAD4 Encodes a Lipase - Like

Gene that is Important for Salicylic Acid Signaling. National Academy of Sciences 96(23): 13583 - 13588. 22 - May 2009 47760912 Kumar, D.; Klessig, D. (2003) High - Affinity Salicylic Acid - Binding Protein 2 is Required for Plant

Innate Immunity and Has Salicylic Acid - Stimulated Lipase Activity. National Academy of Science 100(26): 16101 - 161 06. 22 - May 2009 47760913 Metraux, J.; Signer, H.; Ryals, J.; et al. (1990) Increase in Salicylic Acid at the Onset of Systemic

Aq uired Resistance in Cucumber. Science 250: 1004 - 1006. 22 - May 2009 47760914 Naw

rath, C.; Metraux, J. (1999) Salicylic Acid Induction - Deficient Mutants of Arabidopsis Express PR - 2 am d PR - 5 and Accumulate High Levels of Camalexin after Pathogen Inoculation. The Plant Cell 11: 1393 - 1404. 22 - May 2009 47760915 Rairdan, G.; Delaney, T. (2002) Role of Salicylic Acid and N1M1/NPR1 in Ra ce - Specific Resistance

in Arabidopsis. Genetics 161: 803 - 811. 22 - May 2009 47760916 Rasmussen, J.; Hammerschmidt, R.; Zook, M. (1991) Systemic Induction of Salicylic Acid

Accumulation in Cucumber after Inoculation with Pesudomonas Syringae PV Syringae. Plant Phy siology 97: 1342 - 1347. 22 - May 2009 47760917 Ry als, J.; Neuenschwander, U.; Willits, M.; et al. (1996) Systemic Acquired Resistance. The Plant Cell

8: 1809 - 1819. 22 - May 2009 47760918 Shah, J. (2003) The Salicylic Acid Loop in Plant Defense. Current Opinion in Plant Biology 6: 365 -

371. 22 - May 2009Salicylic Acid Page 24

Biopestici des Registration Action Document **MRID No.**  **Citation Receipt**  **Date** 47760919 Shulaev, V.; Leon, J.; Raskin, I. (1995) Is Salicylic Acid a Translocated Signal of Systemic Acquired

Resistance in Tobacco? The Plant Cell 7: 1691 - 1701. 22 - May 2009 47760920 Yalpani, N.; Silverma n, P.; Wilson, T.; et al. (1991) Salicylic Acid is a Systemic Signal and an Inducer

of Pathogenesis - Related Proteins in Virus - Infected Tobacco. The Plant Cell 3: 809 - 818. 22 - May 2009 47760921 Zhang, Y.; Tessaro, M.; Lassner, M.; et al. (2003) Knockout Ana lysis of Arabidopsis Transcription

Factors TGA2, TGA5 and TGA6 Reveals Their Redundant and Essential Roles in Systemic Acquired Resistance. The Plant Cell 15: 2647 - 2653. 22 - May 2009 47760922 Zhang, Y.; Fan, W.; Kinkema, M.; et al. (1999) Interaction of NP R1 with Basic Leucine Zipper Protein

Transcription Factors that Bind Sequences Required for Salicylic Acid Induction of PR - 1 Gene. Proceedings of the National Academy od Sciences 96: 6523 - 6528. 22 - May 2009 47760923 Wildermuth, M.; Dewdnwy, J.; Wu, G.; et al. (2001) Isochorismate Synthase is Required to Synthesize

Salicylic Acid for Plant Defense. Nature 414: 562 - 571. 22 - May 2009 47760924 Gutierrez - Coronado, M.; Trejo - Lopez, C.; Larque - Saavedra, A. (1998) Effects of Salicylic Acid on the

Grow th of Roots an d Shoots in Soybean. Plant Physiology and Biochemistry 36(8): 563 - 565. 22 - May 2009 47760925 Abreu, M.; Munne - Bosch, S. (2008) Salicylic acid may be Involved in the Regulation of Drought Induced Leaf Senescence in Perennials: A Case Study in Field Grown Sa lvia Oficinalis L. Plants. Environmental and experimental Botany 64: 105 - 112. 22 - May 2009 47760926 Srivastava, M.; Dwivedi, U. (1999) Delayed Ripening of Banana Fruit by Salicylic Acid. Plant Science

158: 87 - 96. 22 - May 2009 47760927 Babalar, M.; Asghari, M.; Talaei, A.; et al. (2006) Effect of Pre - and Postharvest Salicylic Acid

Treatment on Ethylene Production, Fungal Decay and Overall Quality of Selva Straw berry Fruit. Food Chemistry 105: 449 - 453. 22 - May 2009 47760928 Zhang, Y.; Chen, K.; Zhang, S.; et al. (2002) The Role of Salicylica Acid in Postharvest Ripening of

Kiwifruit. Postharvest Biology and Technology 28: 67 - 74. 22 - May 2009 47760929 Rajjou, L.; Belghazi, M.; Huguet, R.; et al. (2006) Proteomic Investigation of the Effect of Salicylic

Acid on Arabidopsis Seed Germination and Establishment of Early Defense Mechanisms. Plant Phy siology 141: 910 - 923. 22 - May 2009 47760930 Janssen, K.; Hollman, P.; Venema, D.; et al. (1996) Salicylates in Foods. Nutrition Reviews 54: 357 -

359. 22 - May 2009 47760931 Kay , J. (2009) Supplement to 47206713; Additional Manufacturing Process Information (Salicylic

Acid). Project Number: NCA/200902. Unpublished study prepared by NCA Biotech, Inc. 33 p. 22 - May 2009 47760932 Kay , J. (2009) Summary of Salicylic Acid Toxicity Data. Project Number: NCA/200903. Unpublished

study prepared by NCA Biotech, Inc. 8 p. 22 - May 2009 47760933 Fiume, M. (2003) Safety Assessment of Salicylic Acid, Butyloctyl Salicylate, Calcium Salicylate,

C12 - 15 Alkyl Salicylate, Capryloyl Salicylic Acid , Hexyldodecyl Salicylate, Isocetyl Salicylate, Isodecyl Salicylate, Magnesium Salicylate, MEA - Salicylate, Ethylhexyl Salicylate, Potassium Salicylate, Methyl Salicylate, Myristyl Salicylate, Sodium Salicylate, TEA - Salicylate, and Tridecyl Salicylate. Inte rnational Journal of Toxicology 22: 1 - 108. 22 - May 2009Salicylic Acid Page 25

Biopestici des Registration Action Document **MRID No.**  **Citation Receipt**  **Date** 47760934 Scientific Committee on Cosmetic Products and Non - Food Products (2002) Opinion of the Scientific

Committee on Cosmetic Products and Non - Food Products Intended for Consumers Concerning Salicyl ic Acid. 36p. 22 - May 2009 47760935 Rocher, F.; Chollet, J.; Jousse, C.; et al. (2006) Salicylic Acid, an Ambimobile Molecule Exhibiting a

High Ability to Accumulate in the Phloem. Plant Physiology 141: 1684 - 1693. 22 - May 2009 47760936 Metw ally , A.; Finkem eier, I.; Georgi, M.; et al. (2003) Salicylic Acid Alleviates the Cadmium Toxicity

in Barley Seedlings. Plant Physiology 132: 272 - 281. 22 - May 2009 47760937 Scotter, M.; Roberts, D.; Wilson, L.; et al. (2006) Free Salicylic Acid and Acetyl Salicylic Acid

C ontent of Foods Using Gas Chromatography - Mass Spectrometry. Food Chemistry 105: 273 - 279. 22 - May 2009 47760938 Amann, R.; Peskar, B. (2002) Anti - Inflammatory Effects of Aspirin and Sodium Salicylate. European

Journal of Pharmacology 447: 1 - 9. 22 - May 2009 47760939 Shakirova, F. (2007) Role of Hormonal System in the Manifestation of Growth Promoting and

Antistress Action of Salicylic Acid. Biochemistry. The Netherlands: Springer. 22 - May 2009 47760941 Foltinova, P.; Grones, J. (1996) Euglena gracilis as an E ukaryotic Test Organism for Detecting

Mutagens and Antimutagens (Salicylic Acid). Mutation Research 393: 1 - 6. 22 - May 2009 47760942 San, R.; Chan, R. (1986) Inhibitory Effect of Phenolic Compounds on Aflatoxin B1 Metabolism and

Induced Mutagenesis (Salicyl ic Acid). Mutation Research 177: 229 - 239. 22 - May 2009 47760943 Sheu, C.; Salomon, D.; Simmons, J.; et al. (1974) Inhibitory Effects of Lipophilic Acids and Related

Com pounds on Bacteria and Mammalian Cells. Antimicrobial Agents and Chemotherapy 7: 349 - 363 . 22 - May 2009 47760944 Kleinerman, E.; Louie, J.; Wahl, L.; et al. (1980) Pharmacology of Human Spontaneous Monocyte Mediated Cytotoxicity. Arthritis and Rheumatism 24: 774 - 780. 22 - May 2009 47760946 Waltman, R.; Tricomi, V.; Shabanah, E.; et al. (1973) T he Effect of Anti - Inflammatory Drugs on

Parturition Parameters in the Rat. Prostaglandins 4: 93 - 106. 22 - May 2009 47760947 Tanaka, S.; Kaw ashim a, K.; Nakaura, S.; et al. (1973) Studies on Teratogenic Effects of Salicylic Acid

and Aspirin in Rats as Related to Fetal Distribution. Cong. Anom. 13: 73 - 84. 22 - May 2009 47760948 Jones, A. (1994) Surprising Signals in Plant Cells. Science 263(Jan 14): 183 - 184. 22 - May 2009 47760949 Morris, K.; Mackerness, S.; Page, T.; et al. (2000) Salicylic Acid Has a Role in R egulating Gene

Expression During Leaf Senescence. The Plant Journal 23: 677 - 685. 22 - May 2009 47775300 NCA Biotech, Inc. (2009) Submission of Toxicity Data in Support of the Registration of Technical

Salicylic Acid. Transmittal of 3 Studies. 11 - Jun 2009 4 7775301 Delaney, T.; Uknes, S.; Vernooij, B.; et al. (1994) A Central Role of Salicylic Acid in Plant Disease

Resistants. Science 266: 1247 - 1249. 11 - Jun 2009 47775302 McCann, J.; Choi, E.; Yamasaki, E.; et al. (1995) Detection of Carcinogens as Mutagens i n the

Salmonella/ Microsome Test: Assay of 300 Chemicals. Proceedings of National Academy of Science 72(12): 5135 - 5139. 11 - Jun 2009Salicylic Acid Page 26

Biopestici des Registration Action Document **MRID No.**  **Citation Receipt**  **Date** 47775303 Commoner, B. (1976) Reliability of Bacterial Mutagenesis Techniques to Distinguish Carcinogenic

and Noncarcinogeni c Chemicals. Project Number: EPA/600/1/76/022, 68/01/2471. Unpublished study prepared by Washington University. 113 p. 11 - Jun 2009 48224600 Loveland Products, Inc. (2010) Submission of Product Chemistry, Toxicity and Fate Data in Support

of the Applicatio n for Registration of LPI 6194 Concentrate. Transmittal of 5 Studies. 14 - Sep 2010 48224601 Wo, C. (2010) LPI 6194 Concentrate: Physical and Chemical Characteristics: Color, Physical State,

Odor, Flammability, pH, Viscosity, and Density/Relative Density. P roject Number: 29844, P801. Unpublished study prepared by Eurofins/Product Safety Laboratories. 16 p. 14 - Sep 2010 48224602 Knox III, D. (2010) LPI 6194 Concentrate: Enforcement Analytical Method for the Determination of

Salicylic Acid by High Pressure Liquid Chromatography. Project Number: 29843. Unpublished study prepared by Eurofins/Product Safety Laboratories. 10 p. 14 - Sep 2010 48224603 Tillman, A. (2010) LPI 6194 Concentrate: Waiver Requests for Certain Phys - Chem Property Data.

Project Number: LPI/201 0017. Unpublished study prepared by Loveland Products, Inc. 6 p. 14 - Sep 2010 48224604 Tillman, A. (2010) LPI 6194 Concentrate and LPI 6194 RTU: Waiver Request for Tier I Mammalian

Toxicity Data. Project Number: LPI/201021. Unpublished study by Loveland Pr oducts, Inc. 10 p. 14 - Sep 2010 48224605 Tillman, A. (2010) LPI 6194 Concentrate and LPI 6194 RTU: Summary of Tier I Nontarget Organism

Data Requirements . Project Number: LPI/20 1020. Unpublished study by Loveland Products, Inc. 27 p. 14 - Sep 2010 48224700 Loveland Products, Inc. (2010) Submission of Product Chemistry and Toxicity Data in Support of the

Application for Registration of LPI 6194 RTU. Transmittal of 3 Studies. 14 - Sep 2010 48224701 Tillman, A. (2010) Product Identity and Composition, Descriptio n of the Materials Used, Description

of the Formulation Process, Discussion of the Formation of Impurities, Certified Limits, and Enforcement Analytical Method for LPI 6194 RTU. Project Number: LPI/201022. Unpublished study prepared by Loveland Products, I nc. 84 p. 14 - Sep 2010 48224702 Tillman, A. (2010) LPI 6194 RTU: Phys - Chem Characteristics Data and Waiver Requests for Certain

Data. Project Number: LPI/2010015. Unpublished study by Loveland Products, Inc. 12 p. 14 - Sep 2010 48224703 Tillman, A. (2010) L PI 6194 RTU: Request to Bridge Acute Toxicity Data. Project Number:

LPI/201016. Unpublished study prepared by Loveland Products, Inc. 21 p. 14 - Sep 2010 48225200 Loveland Products, Inc. (2010) Submission of Product Chemistry, Toxicity and Fate Data in Supp ort

of the Application for Registration of Salicylic Acid Technical. Transmittal of 13 Studies. 14 - Sep 2010 48225201 Sinning, D. (2010) Physical and Chemical Characteristics of 98.7% Salicylic Acid Technical: Stability,

Oxidation/Reduction, pH, UV/Vis, Partition Coefficient (n - Octanol/Water) and Water Solubility: Final Report. Project Number: 4670/01. Unpublished study by Case Consulting Laboratories, Inc. 29 p. 14 - Sep 2010 48225202 Tillman, A. (2010) Summary of and Waiver Request for Physical and Chemica l Properties of Salicylic

Acid Technical. Project Number: LPI/201018. Unpublished study by Loveland Products, Inc. 11 p. 14 - Sep 2010 48225203 Hauswirth, J. (2010) Summary of the Acute Toxicity of Salicylic Acid. Project Number: LPI/201008.

Unpublished stu dy

prepared by Loveland Products, Inc. 13 p. 14 - Sep 2010 48225204 Hauswirth, J. (2010) Subchronic Toxicity of Salicylic Acid. Project Number: LPI/201009.

Unpublished study prepared by Loveland Products, Inc. 99 p. 14 - Sep 2010Salicylic Acid Page 27

Biopestici des Registration Action Document **MRID No.**  **Citation Receipt**  **Date** 48225205 Hauswirth, J. (2010 ) Developmental and Reproduction Toxicity of Salicylic Acid. Project Number:

LPI/201012. Unpublished study prepared by Loveland Products, Inc. 175 p. 14 - Sep 2010 48225206 Hauswirth, J. (2010) Metabolism of Salicylic Acid. Project Number: LPI/201011. Unpub lished study

prepared by Loveland Products, Inc. 50 p. 14 - Sep 2010 48225207 Hauswirth, J. (2010) Mutagenicity and Genotoxicity for Salicylic Acid. Project Number: LPI/201010.

Unpublished study prepared by Loveland Products, Inc. 137 p. 14 - Sep 2010 482252 08 Hauswirth, J. (2010) Dermal Penetration of Salicylic Acid. Project Number: LPI/201013. Unpublished

study prepared by Loveland Products, Inc. 45 p. 14 - Sep 2010 48225209 Tillman, A. (2010) Summary of Tier 1 Nontarget Organism Data Requirements for Salicy lic Acid

Technical. Project Number: LPI/201019. Unpublished study by Loveland Products, Inc. 24 p. 14 - Sep 2010 48225210 Porch, J.; Krueger, H. (2010) LPI 6194 Concentrate: A Toxicity Test to Determine the Effects of the

Test Substance on Seedling Emergenc e of Ten Species of Plants: Final Report. Project Number: 224/102. Unpublished study prepared by Wildlife International, Ltd. 68 p. 14 - Sep 2010 48225211 Porch, J.; Krueger, H. (2010) LPI 6194: A Toxicity Test to Determine the Effects of the Test

Substance on Vegetative Vigor of Ten Species of Plants: Final Report. Project Number: 224/103. Unpublished study prepared by Wildlife International, Ltd. 87 p. 14 - Sep 2010 48225212 Porch, J.; Krueger, H. (2010) Salicylic Acid Technical: An Acute Contact Toxicity S tudy with the

Honey Bee: Final Report. Project Number: 224/101. Unpublished study prepared by Wildlife International, Ltd. 21 p. 14 - Sep 2010 48225213 Tillman, A. (2010) Salicylic Acid Mode of Action. Project Number: LPI/201014. Unpublished study

prepared by Loveland Products, Inc. 153 p. 14 - Sep 2010 48562300 Loveland Products, Inc. (2011) Submission of Product Chemistry Data in Support of the Application

for Registration of LPI 6194 RTU. Transmittal of 2 Studies. 48562301 Tillman, A. (2011) Product Ide ntity and Composition, Description of Starting Materials, Production

and Formulation Process for LPI 6194 RTU: Supplemental Report to MRID 48224701. Project Number: LPI/201108. Unpublished study prepared by Loveland Products, Inc. 26p. 48562302 Wo, C. ( 2011) LPI 6307: Physical and Chemical Characteristics: pH. Project Number: 32722 P8001.

Unpublished study prepared by Eurofins/Product Safety Laboratories. 11p. 48562400 Loveland Products, Inc. (2011) Submission of Product Chemistry and Toxicity Data in Support of the

Application for Registration of LPI 6134 Concentrate. Transmittal of 7 Studies. 48562401 Tillman, A. (2011) Product Identity and Composition, Description of Starting Materials, Production

and Formulation Process for LPI 6194 Concentrate: Supplemental Report to MRID 46964301. Project Number: LPI/201107. Unpublished study prepared by Loveland Products, Inc. 76p. 48562402 Durando, J. (2010) LPI 6194 Concentrate: Acute Oral Toxicity Up and Down Procedure in Rats.

Project Number: 39845 P320 /UDP. Unpublished study by Eurofins/Product Safety Laboratories. 16p. 48562403 Durando, J. (2010) LPI 6194 Concentrate: Acute Dermal Toxicity Study in Rats - Limit Test. Project

Number: 29846 P322/RAT. Unpublished study prepared by Eurofins/Product Safe ty Laboratories. 15p.Salicylic Acid Page 28

Biopestici des Registration Action Document **MRID No.**  **Citation Receipt**  **Date** 48562404 Durando, J. (2010) LPI 6194 Concentrate: Acute Inhalation Toxicity Study in Rats. Project Number:

29847 P330. Unpublished study prepared by Eurofins/Product Safety Laboratories. 23p. 48562405 Durando, J. (2010) LPI 6194 Concentrate: Primary Eye Irritation Study in Rabbits. Project Number:

29848 P324. Unpublished study prepared by Eurofins/Product Safety Laboratories. 16p. 48562406 Durando, J. (2010) LPI 6194 Concentrate: Primary Skin Irritation Study in Rabbits. Proje ct Number:

28949 P326. Unpublished study prepared by Eurofins/Product Safety Laboratories. 16p. 48562407 Durando, J. (2010) LPI 6194 Concentrate: Dermal Sensitization Study - Guinea Pigs (Buehler Method).

Project Number: 29850 P328. Unpublished study by Eurofins/Product Safety Laboratories. 25p. **B. EPA Risk Assessment Memoranda**  U.S. EPA. 2011a. Gonzales, Angela L . Science Review in Support of Salicylic Acid Technical, Containing 98.7% Salicylic Acid as Its Active In gredient. Memorandum dated 1 2/8/2011 . U.S. EPA. 2011b. Gonzales, Angela L. Science Review in Support of Salicy lic Acid Technical, Containing 98.7% Salicylic Acid as Its Active In gredient. Memorandum dated 06/16/2011 . **C. References** Hazardous Substances Data B ank (HSDB). 2008. “S alicylic Acid”. U.S. Department of Health and Human Services, National L ibrary of Medicine. March 31, 2011. < http://www.toxnet.nlm.nih.gov/cgi - bin/sis/search/f?./temp/~TE3afi:1 > U.S. EPA 2008. Terrestrial Residue Exposure Model (T - REX) Version 1.4.1. EFED/OPP/USEPA.