Document ID: EPA-HQ-OPP-2012-0251-0003
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2014-02-26T05:00Z

BIOPESTICIDES REGISTRATION ACTION DOCUMENT
                                       
                                       
                                       
                                       
                                       
                                       
                                       
                                    Humates
(Humic acid; Humic acids, potassium Salts; Humic acids, sodium salts; and Humates derived from Leonardite)
                     PC Codes: 700132, 800286, and 021818
               
                                       
                                       
                                       
                                       
                                       
                                       
                                       
                                       
                                       

   
	U.S. Environmental Protection Agency
	Office of Pesticide Programs
                Biopesticides and Pollution Prevention Division
                                       
                                       
                       (Last updated February 25, 2014)
	Table of Contents	
I.	EXECUTIVE SUMMARY	1
II.	ACTIVE INGREDIENT OVERVIEW	2
III.	REGULATORY BACKGROUND	2
A.	Application for Pesticide Registration	2
B.	Food Clearances/Tolerances	3
IV.	RISK ASSESSMENT	3
A.	Product Analysis Assessment (40 CFR § 158.2030)	3
B.	Human Health Assessment	3
1.	Tier I Toxicology	3
2.	Tier II and Tier III Toxicity Studies	4
3.	Endocrine Disruptors	4
4.	Dose-Response Assessment	5
6.	Occupational Exposure and Risk Characterization	7
7.	Human Health Risk Characterization	7
C.	Environmental Assessment	8
1.	Ecological Hazards	8
2.	Environmental Fate and Ground Water Data	8
3.	Ecological Exposure and Risk Characterization	8
4.	Endangered Species Assessment	9
D.	Product Performance Data	9
V.	RISK MANAGEMENT DECISION	9
A.	Determination of Eligibility for Registration	9
B.	Regulatory Decision	10
C.	Environmental Justice	10
VI.	ACTIONS REQUIRED BY REGISTRANTS	10
A.	Reporting of Adverse Effects	11
B.	Reporting of Hypersensitivity Incidents	11
VII.	Appendix A.  Data Requirements (40 CFR Part 158, Subpart U)	12
VIII.	Appendix B. References	16
IX.	GLOSSARY OF ACRONYMS AND ABBREVIATIONS	17

BIOPESTICIDES REGISTRATION ACTION DOCUMENT (BRAD) TEAM

Branch Chief
Linda A. Hollis, M.S.

Product Chemistry/Human Health Effects/Nontarget Organisms
Russell Jones, PhD, Senior Scientist
Sadaf Shaukat, Biologist

Regulatory Action Leader
Menyon Adams, Biologist

EXECUTIVE SUMMARY

Humates derived from Leonardite are collectively a new biochemical active ingredient (hereafter referred to as humates) intended for use as a plant growth regulator (PGR) to control the vegetative growth and maturation of agricultural and greenhouse crops. Treatment of plants with humates enhances root growth, improves the uptake of nitrogen, potassium and phosphate, increases the treated plants' ability to resist plant disease, and reduces the need to add soil nutrients and fertilizers during the growing season. 

Humates are naturally occurring substances formed by the biodegradation of dead organic matter, and are often associated with deposits of coal, lignite and mudstone. They are ubiquitous in the environment in soil and water, including agricultural areas where crops are grown for human and animal consumption. Commonly used to condition soil, humates are widely regarded as being beneficial to plants. From a structural perspective, humates include a complex mixture of compounds, including humic acids and their potassium and sodium salts, fulvic acids, and humins, with humic acids being the major extractable component.

In terms of their safety to humans, including infants and children, humates have been previously evaluated and well-characterized by the U.S. Environmental Protection Agency (EPA or Agency). They are also listed among those substances that are exempt from the requirement of a tolerance under section 408 of the Federal Food, Drug, and Cosmetic Act (FFDCA) as either inert or active ingredients in a pesticide formulation when used  in accordance with good agricultural and/or manufacturing practices (40 CFR Part180.950 (e)).

BPPD has reviewed all of the data and other information submitted in support of the registration of humates as a PGR under Section 3(c)(5) of the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA), and has determined that the current data requirements (40 CFR part 158.2010 through 158.2070) for registration of a biochemical pesticide have been satisfied. Given that humates are of very low toxicity and present little, if any, risks to humans and the environment, EPA has concluded that it is in the best interest of the public to issue registrations for the manufacturing-use product (MP), PM-4300 Organic Acids (EPA File Symbol No. 82940-G) and the end-use product (EP), Phocon (EPA File Symbol No. 82940-E), which contain humates as the active ingredient. The basis for this decision is described in more detail in section IV of this draft Biopesticide Registration Action Document (BRAD).  

On October 1, 2009, EPA announced a policy to provide a more meaningful opportunity for the public to participate in major registration decisions before they occur. According to this policy, EPA provides a public comment period prior to making a registration decision for the following types 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. 

Consistent with the policy of making registration decisions more transparent, humates are subject to a 15 day comment period as a "new active ingredient." The notice for this comment period includes the draft BRAD and draft labels for two products (PM-4300 Organic Acids (EPA File Symbol 82940-G) and Phocon (EPA File Symbol 82940-E)) that contain this new active ingredient. The docket identification (ID) number is EPA-HQ-OPP-2012-0251.  
For definitions of scientific terms, please refer to http://www.epa.gov/pesticides/glossary/.

ACTIVE INGREDIENT OVERVIEW

      Common Name: 			N/A

      Chemical Names:			Humates
      					Humic Acids, Potassium Salts
      					Humic Acids, Sodium Salts
      					Humates derived form Leonardite

      Trade & Other Names: 		N/A

      CAS Registry Number: 		N/A

      OPP Pesticide Chemical Code: 	700132
      					800286
      					021818

      Type of Pesticide:            		Biochemical Pesticide  -  Plant Growth Regulator

Biochemical Classification

On February 12, 2009, the Biochemical Classification Committee classified humates as a biochemical active ingredient, based upon the nontoxic mode of action as a PGR, natural occurrence in the environment, and history of human and animal exposure to humates with no toxic or other adverse effects.

For more information regarding product chemistry data requirements, please refer to Tables 1, 2, and 3 in Appendix A of this document.

REGULATORY BACKGROUND

Application for Pesticide Registration

On December 16, 2011, Ann Tillman of Pyxis regulatory Consulting, Inc., on behalf of Actagro LLC., 4110 136[th] St. NW, Gig Harbor, WA 98332, submitted applications to register an MP, "PM-4300 Organic Acids" (EPA File Symbol No. 82940-G), and an EP, "Phocon" (EPA File Symbol No. 82940-E), containing the new biochemical active ingredient, humates, at 18.5% and 12.0%, respectively. A notice of receipt (NOR) of the applications was published in the Federal Register on June 27, 2012, (77 FR 38285). No comments were received during the 30-day comment period following publication of the NOR.

Food Clearances/Tolerances 

Residues resulting from the use of humates (humic acid; humic acids, potassium salts; humic acids, sodium salts) as either an inert or an active ingredient in a pesticide chemical formulation, including antimicrobial pesticide chemicals, are exempt from the requirement of a tolerance under FFDCA section 408, if such use is in accordance with good agricultural or manufacturing practices (40 CFR part 180.950 (e)). (Ref.1)

RISK ASSESSMENT
 
A. Product Analysis Assessment (40 CFR § 158.2030)

Biochemical pesticide product analysis data requirements include product chemistry and composition, analysis and certified limits, and physical and chemical characteristics. Product chemistry and composition data include information about the identity of the active ingredient, the manufacturing process, and discussion of the potential for formation of unintentional ingredients. Analysis and certified limits data include information on analysis of samples and certification of the upper and lower limits for the ingredients in a formulated product. Physical and chemical characteristics data describe basic characteristics of the registered pesticide products, including color, physical state, odor, stability, miscibility, pH, corrosion characteristics, viscosity and density.

EPA's Office of Pesticide Programs (OPP) has assigned unique pesticide chemical (PC) codes to humic acid, humic acids, potassium salts, and humic acids, sodium salts (700132, 800286 and 021818, respectively), and all of the product analysis data required for an unconditional registration have been fulfilled. (See Tables 1 and 2 in Appendix A of this document for a summary of product chemistry and composition, analysis and certified limits, physical and chemical characteristics data.)

Human Health Assessment 

Tier I Toxicology 

All of the toxicology data requirements have been satisfied and support the proposed registration of humates as a biochemical PGR. The data and other information submitted are summarized below (see also Tables 3 and 4 in Appendix A of this document).

         a.       Acute Toxicity (OCSPP Guideline Nos. 870.1100, 870.1200, 870.1300, 870.2400, 870.2500, and 870.2600; Master Record Identification (MRID) Nos. 48711105, 48711106,48711107, 48711108, 48711109, 48711110, 49080301,  48711115 ): 

Acute toxicity testing of a pesticide active ingredient and/or product is required to: 1) determine systemic toxicity from acute exposure via the dermal, inhalation and oral routes; 2) determine irritant effects from exposure to the eyes and skin; and 3) determine the potential for skin sensitization (allergic contact dermatitis). Acute Toxicity Categories I, II, III, or IV (Toxicity Category I indicates the highest toxicity, and Toxicity Category IV is the lowest) are assigned to an active ingredient and EPs containing that active ingredient, and are based on the hazard(s) identified from studies and/or other information submitted to support an application to register a pesticide in the U.S.  

In an acute oral toxicity test in rats, the LD50 for a single dose of humic acids was >11,500 mg/kg (EAEMP, 1999). Further, the results from the Tier I acute testing on the MP classify humates in Toxicity Category IV for the dermal, oral, and inhalation routes of exposure, based on the doses tested in laboratory rats. In addition, minimal eye irritation cleared in less than 24 hours and slight dermal irritation resolved within 72 hours in rats, and humates were not dermal sensitizers in guinea pigs. (For the results of these studies (i.e., LD50, LC50), refer to Table 3 in Appendix A of this document.)

         b.       Subchronic Toxicity, Developmental Toxicity, and Mutagenicity (OCSPP Guideline Nos. 870.3100, 870.3250, 870.3465; 870.3700, 870.5100, 870.5300, 870.5375; MRID Nos. 48975101, 48975102): 

The data submitted to fulfill the requirement for a Bacterial Reverse Mutation Test (OCSPP 870.5100) demonstrated that humates did not cause base pair changes or frame shift mutations, and there was no evidence of cytotoxicity at highest dose tested. 

In lieu of conducting guideline studies, rationales were submitted to address the following:  90-Day Oral (OCSPP 870.3100), 90-Day Dermal (OCSPP 870.3250), 90-Day Inhalation (OCSPP 870-3465) and Prenatal Development (OCSPP 870.3700) toxicity studies, and the in vitro Mammalian Cell Assay (OCSPP 870.5300/5375). BPPD determined that the rationales are acceptable, based on the results of the studies conducted with humates as the test substance and its presence as a natural component of soil and water with no known adverse effects to humans and the environment.

Tier II and Tier III Toxicity Studies

Tier II and Tier III toxicity testing was not required due to humates' low toxicity and the low levels of human exposure expected from its intended use as a PGR.

Endocrine Disruptors	

As required by the Administrator under the Federal Food, Drug, and Cosmetic Act (FFDCA) section 408(p), the EPA has developed the Endocrine Disruptor Screening Program (EDSP) and has begun to implement the screening program that is to be used to test all pesticides in order to determine whether certain substances (including pesticide active and other ingredients) may have an effect in humans or wildlife similar to an effect produced by a "naturally occurring estrogen, or other such endocrine effects as the Administrator may designate." FFDCA section 408(p)(4) authorizes the Administrator, by order, to exempt from the requirements of the Estrogenic Substances Screening Program a biologic substance or other substance if a determination is made that the substance is not anticipated to produce any effect in humans similar to an effect produced by a naturally occurring estrogenic substance. Between October 2009 and February 2010, the EPA issued test orders/data call-ins for the first group of 67 chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. A second list of chemicals identified for screening under the EDSP was published on June 14, 2013, and includes some pesticides scheduled for registration review and chemicals found in water. Humates are not among the group of pesticide active ingredients on the lists to be screened under the EDSP.
The Agency believes that humates would not likely produce any effect in humans similar to an effect produced by a naturally occurring estrogenic substance.  As such, and pursuant to Section 408(p)(4), EPA will determine in the future whether it can exempt humates from the requirements of the Section 408(p) EDSP.  In the event the EPA does determine to exempt this substance from the EDSP, an order will be issued.  
For further information on the status of the EDSP, the policies and procedures, the lists of chemicals, future lists, the test guidelines, and the Tier 1 screening battery, please visit our website at http://www.epa.gov/endo/.

Dose-Response Assessment

No toxicological endpoints were identified for humates; therefore, a dose-response assessment was not required.  

	5.  Federal Food, Drug, and Cosmetic Act (FFDCA) Considerations 

Section 408(c)(2)(A)(i) of FFDCA allows EPA to establish an exemption from the requirement for a tolerance (the legal limit for a pesticide chemical residue in or on a food) only if EPA determines that the exemption is "safe." Section 408(c)(2)(A)(ii) of FFDCA defines "safe" to mean that "there is a reasonable certainty that no harm will result from aggregate exposure to the pesticide chemical residue, including all anticipated dietary exposures and all other exposures for which there is reliable information." This includes exposure through drinking water and in residential settings but does not include occupational exposure. Pursuant to section 408(c)(2)(B) of FFDCA, in establishing or maintaining in effect an exemption from the requirement of a tolerance, EPA must take into account the factors set forth in section 408(b)(2)(C) of FFDCA, which require EPA to give special consideration to exposure of infants and children to the pesticide chemical residue in establishing a tolerance exemption and to "ensure that there is a reasonable certainty that no harm will result to infants and children from aggregate exposure to the pesticide chemical residue...." Additionally, section 408(b)(2)(D) of FFDCA requires that EPA consider "available information concerning the cumulative effects of [a particular pesticide's] . . . residues and other substances that have a common mechanism of toxicity." 

EPA performs a number of analyses to determine the risks from aggregate exposure to pesticide residues. First, EPA determines the toxicity of pesticides. Second, EPA examines exposure to the pesticide through food, drinking water, and other routes as a result of pesticide use in residential settings. 

Consistent with section 408(b)(2)(D) of FFDCA, EPA reviewed the available scientific data and other relevant information, and considered its validity, completeness, and reliability, and the relationship of this information to human risk. EPA also considered available information concerning the variability of the sensitivities of major identifiable subgroups of consumers, including infants and children. Based on the acute toxicity data and information discussed previously and presented in Table 3 in Appendix A of this document, the data requirements for a human health dietary risk assessment for humates have been fulfilled.

      a.    Aggregate Exposure

In examining aggregate exposure, section 408 of FFDCA directs EPA to consider available information concerning exposures from the pesticide residue in food and all other non-occupational exposures, including drinking water from ground or surface water, pesticide use in gardens, residential and other lawns and landscapes, and buildings (residential and other indoor uses). EPA expects the aggregate exposure to residues of humates from the PGR use to be negligible when compared to the ordinary, everyday levels to which individuals are already exposed in the natural environment, since humates are commonly found in soil and water. The aggregate exposure potential for humates is discussed below.

Food Exposure and Risk Characterization: Since humates are common components of agricultural soil, EPA expects that human dietary exposure to residues of humates resulting from its pesticidal uses would be negligible in comparison to naturally occurring humates. Further, residues of humates from use as a PGR would be very low, since they are not absorbed by plants, and rainfall and irrigation would reduce the amount of applied product during the growing season. In the unlikely event that any residues of the pesticide remain in or on consumed food, no adverse effects would be expected, based on the lack of toxicity demonstrated in the submitted studies and other information described previously and presented in Table 3 in Appendix A of this document. 

Drinking Water Exposure and Risk Characterization: According to the directions for use on the EP label, humates are not to be applied directly to bodies of water. It is possible, however, that some residues may reach bodies of water via runoff or spray drift.  Since humates are common components of water, EPA expects that human exposure to residues of humates in drinking water resulting from its use as a PGR would be negligible in comparison to naturally occurring humates.  In the unlikely event that any residues of the pesticide remain in drinking water, no adverse effects would be expected, based on the lack of toxicity demonstrated in the submitted studies and other information described previously and presented in Table 3 in Appendix A of this document. 

Non-occupational, Residential Exposure and Risk Characterization: The PGR use of this active ingredient is intended only for agricultural environments, so non-occupational and residential exposures are expected to be minimal to non-existent. Should exposure occur, the risks to humans is expected to below level of concern, based upon the low toxicity of humates demonstrated in the data and other information submitted and evaluated by the EPA. (Ref. 1; see also Section IV.B.1.a  of this BRAD).

	b. Cumulative Effects from Substances with a Common Mechanism of Toxicity.

Section 408(b)(2)(D)(v) of FFDCA requires that, when considering whether to establish, modify, or revoke a tolerance exemption, EPA consider "available information concerning the cumulative effects of [a particular pesticide's] . . . residues and other substances that have a common mechanism of toxicity."

Humates are not known to have a common mechanism of toxicity with other substances; therefore, cumulative effects with other substances are not anticipated. For information regarding EPA's efforts to identify chemicals that may have a common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see EPA's website at http://www.epa.gov/pesticides/cumulative.

	c.   Determination of Safety for the U.S. Population, Infants and Children
 
Based on its analyses of the submitted toxicity data (refer to Section IV.B.1. a and Table 3 in Appendix A), EPA concludes that there are no threshold effects of concern to infants, children, or adults when PGR products containing humates as an active ingredient are used as labeled in accordance with good agricultural practices. No toxicological effects or endpoints were identified in mammalian studies.  The Agency does not expect that infants and children will have special sensitivity to residues of humates.  As a result, no additional margin of exposure (safety) is necessary to protect infants and children and that not adding an additional margin of exposure (safety) will be safe for infants and children.

The Agency also concludes that there is a reasonable certainty that no harm will result to the U.S. population, including infants and children, from aggregate exposure to the residues of humates when used as labeled and in accordance with good agricultural practices as a PGR. Such exposure includes all anticipated dietary exposures and all other exposures for which there is reliable information. EPA arrived at this conclusion because, considered collectively, the data available on humates do not demonstrate toxic potential to humans, including infants and children.

   1. Occupational Exposure and Risk Characterization

An occupational exposure assessment was not conducted and is not required for biochemical pesticides (40 CFR part 158.2010). Appropriate personal protective equipment (PPE) requirements on the label will mitigate any unintentional exposures to applicators and/or handlers.  

 Human Health Risk Characterization

EPA considered human exposure to humates in light of the standard for registration in FIFRA and the relevant safety factors in FFDCA. Since there were no toxicological effects or endpoints identified in mammalian studies, 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 when humate products are used in accordance with EPA-approved labeling.

Environmental Assessment

   2. Ecological Hazards

Adequate nontarget toxicology data/information submitted and reviewed by the Agency satisfies the non-target toxicology data requirements for humates. 

Avian Oral Acute Toxicity, Avian Dietary Toxicity, Fish Acute Toxicity, Freshwater and Marine, and Aquatic Invertebrate Acute Toxicity (OCSPP Guideline Nos. 850.2100, 850.2200,850.1075, and 850.1010)  (see also Tables 5 and 6 in Appendix A of this document).

Humates have historically been applied to soil with no reports of adverse effects to humans, other mammals, or the environment. Since humates are ubiquitous in soil and water, birds, fish, and other living organisms are already naturally exposed. The data and other information submitted to support the registration of humates as a PGR demonstrate that humates are practically nontoxic to birds on a dietary basis (LC50 > 5620 ppm), practically nontoxic to fish (LC50 > 100mg/L), and practically nontoxic to aquatic invertebrates (EC50 > 100mg/L). 

Seedling Emergence and Vegetative Vigor (OCSPP Guidelines Nos. 850.4100 and 850.4150)

Humates are intended to be applied to growing crops, and are not absorbed by plants when applied to crops or to soil near growing crops. The major component, humic acids, enriches the soil and stimulates root growth and uptake of nutrients by the treated plants. They have historically been applied to crops with no reports of adverse effects to the environment. Humates provide benefits to soils and plants, and are considered to have a nontoxic mode of action. 

Non-target Insect Testing (OCSPP Guideline 880.4350)

Humates are intended to be formulated into EP's and intended for application to growing crops. There have been no reports in the public literature of deleterious effects to honey bees from exposures to humic acid or other humic substances. 

Environmental Fate 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.  

Ecological Exposure and Risk Characterization

Humates are naturally occurring and ubiquitous in both soil and aquatic environments. The proposed EP label rates would result in little net increase in the background amount of humates already present in the environment. Based on the review of this body of information in conjunction with the proposed labeling, the Agency believes that when used in accordance with the label directions, the use of humates should not result in adverse effects to birds, fish, aquatic invertebrates, and plant or nontarget insects. (Ref. 1)

Endangered Species Assessment

EPA has determined that no adverse effects are anticipated for nontarget species exposed to humates when used as a PGR; therefore, effects to federally-listed threatened and endangered species and their designated critical habitats are also not expected. Therefore, a "No Effect" determination is made for direct and indirect effects to federally-listed endangered and threatened species and their designated critical habitats for the proposed uses of humates as a PGR in agricultural settings. 

Product Performance Data 

Product performance (efficacy) data must be developed for all pesticides to ensure that the products will perform as intended and that unnecessary pesticide exposure to the environment will not occur as a result of the use of ineffective products. The Agency reserves the right to require, on a case-by- case basis, the submission of efficacy data for any pesticide product registered or proposed for registration, but applications to register pesticide products intended to control a pest of significant public health importance, as defined in FIFRA section 28(d) and section 2(nn), must include such data. For further guidance on the product performance data requirement, refer to Pesticide Registration (PR) Notices 96-7, 2002-1 and Explanation of Statutory Framework for Risk-Benefit Balancing for Public Health Pesticides (http://www.epa.gov/PR _Notices/pr1996-7.pdf, http://www.ea.gov/PR_Notices/pr2002-1.pdf, and http://www.epa.gov/pesticides/health/risk-benefit.htm).

Humates are not intended to be formulated into products to control public health pests, and product performance was not evaluated by the Agency.  
 
RISK MANAGEMENT DECISION

A. Determination of Eligibility for Registration 

Section 3(c)(5) of FIFRA provides for the registration of a pesticide provided that all the following determinations are made: (1) its composition is such as to warrant the claims for it; (2) its labeling and other materials required to be submitted comply with the requirements of FIFRA; (3) it will perform its intended function without unreasonable adverse effects on the environment; and (4) when used in accordance with widespread and commonly recognized practice, it will not generally cause unreasonable adverse effects on the environment. 

To satisfy criterion (1), EPA believes the composition the proposed MP and EP warrants the claims made on the labels. Criterion (2) is satisfied, since the proposed product labels, as well as the data and information presented in this document, are in compliance with the requirements of FIFRA. Criterion (3) is satisfied in that humates are expected to function as PGRs without causing unreasonable adverse effects on the environment. Criterion (4) is satisfied in that no unreasonable adverse effects are expected when products containing humates are used in accordance with label directions and commonly recognized agricultural practices. Therefore, PM-4300 Organic Acids (EPA File Symbol No. 82940-G), and Phocon (EPA File Symbol No. 82940-E) meet the requirements for registration under FIFRA section 3(c)(5) for use in agricultural settings.

Regulatory Decision

The data submitted fulfill the requirements for the unconditional registration of humates for use as a plant growth regulator. For product-specific information, please refer to http://www.epa.gov/pesticides/pestlabels.

Environmental Justice

For additional information regarding environmental justice issues, please visit EPA's website at http://www.epa.gov/compliance/environmentaljustice/index.html.

EPA seeks to achieve environmental justice -- the fair treatment and meaningful involvement of all people regardless of race, color, national origin, or income -- with respect to the development, implementation, and enforcement of environmental laws, regulations, and policies. Fair treatment means that no group of people, including racial, ethnic, or socioeconomic groups, should bear a disproportionate share of the negative environmental consequences resulting from industrial, municipal, and commercial operations or the execution of federal, state, local, and tribal environmental programs and policies. Meaningful involvement means that (1) potentially affected community residents have an appropriate opportunity to participate in decisions about an activity that will affect their environment and/or health; (2) the public's contribution can influence the regulatory agency's decision; (3) the concerns of all participants involved will be considered in the decision-making process; and (4) the decision-makers seek out and facilitate the involvement of those potentially affected. EPA has this goal for all communities and persons across the U.S. 

At this time, EPA does not believe that use of humates pesticide products will cause harm or a disproportionate impact on at-risk communities; however, please comment if you are aware of any groups or segments of the population who, as a result their location, cultural practices, or other factors, may have atypical, unusually high exposure to humates compared to the general population. 

For additional information regarding environmental justice issues, please visit EPA's web site at http://www.epa.gov/compliance/environmentaljustice/index.html.

ACTIONS REQUIRED BY REGISTRANTS

EPA evaluated all data submitted in connection with the registration of the new active ingredient, humates, and determined that these data are sufficient to satisfy current registration data requirements. At this time, no additional data must be submitted to EPA for these particular products. For new uses and/or changes to existing uses, EPA may require additional data.  

Notwithstanding the information stated in the previous paragraph, it should be clearly understood that before releasing the registered products for shipment, the registrant will be required to provide appropriate final printed labeling to EPA. Further, certain specific data, briefly described below, are required to be reported to EPA, as a requirement for maintaining the federal registration for all pesticide products.

B. Reporting of Adverse Effects

Pursuant to FIFRA section 6(a)(2), reports of all incidents of adverse effects to the environment must be submitted to EPA.

REPORTING OF HYPERSENSITIVITY INCIDENTS

Under the provisions of 40 CFR part 158.2050(d), all incidents of hypersensitivity (including both suspected and confirmed incidents) must be reported to the Agency. 
APPENDIX A.  Data Requirements (40 CFR Part 158, Subpart U)

Master Record Identification (MRID) numbers listed in the following tables are representative of supporting data/information for the original registration of the product containing this active ingredient. Subsequent to this registration, there may be additional MRIDs that support registration of other products containing this active ingredient.   

TABLE 1. Product Identify, Composition, Analysis and Certified Limits for  PM-4300 Organic Acids (40 CFR 158.2030) 
                        OPPTS Guideline Reference No. 
                                     Study
                                   Results 
                                   830.1550
                                      to
                                   830.1670
                               Product identity;
                            Manufacturing process;
             Discussion of formation of unintentional ingredients
              Acceptable; Confidential Business Information (CBI)
                                   830.1700
                              Analysis of samples
                                Acceptable; CBI
                                   830.1750
                            Certification of limits
                                Acceptable; CBI
                                   830.1800
                               Analytical method
                                Acceptable; CBI

TABLE 2.  Physical and Chemical Properties for PM-4300 Organic Acids (40 CFR 158.2030)
                                                    MRID Nos. 48711101- 48711104 and 49080300

                           Property/OCSPP Guideline 

                             Description of Result

                                    Methods

Color/ 830.6302
                                     Black
                                Munsell N1 1/N
                         Visual inspection at 21.4°C

Physical State/ 830.6303
                                    Liquid
                         Visual inspection at 21.5°C

Odor/830.6304
                                Mild, alcoholic
                        Olfactory inspection at 21.5°C

Stability/830.6313
Stable for 14 days at ambient and elevated (54 +- 2°C) temperature in HDPE containers. Stability to metals and metal ions is not applicable, since the product will not be stored or packaged in metal containers.
                                OCSPP 830.1637

Oxidation/Reduction: Chemical Incompatibility/830.6314
Not applicable, the product does not contain oxidizing ingredients.
                                      N/A

Flammability/830.6315
Not applicable, the product is 70% water and contains no flammable ingredients. >100°C[b]
                                      N/A

Explodability/830.6316
Not applicable, the product is 70% water and contains no explosive ingredients.
                                      N/A

Storage Stability/830.6317
Study is ongoing. Results will be submitted upon completion.
                                      N/A

Miscibility/830.6319
Not applicable, the product is not an emulsifiable liquid to be diluted with petroleum solvents.
                                      N/A

Corrosion Characteristics/830.6320
Study is ongoing. Results will be submitted upon completion.
                                      N/A

Dielectric Breakdown Voltage/830.6321
Not applicable, the product is not for use around electrical equipment.
                                      N/A

pH/830.7000
10.67 +- 0.005(1% solution  in CO2-free water at 21.1°C)
                                   pH meter
                              Maxxam SOP 91-M-014
Viscosity/830.7100
                     3.01 +- 0.00 mm[2]/s (cSt) at 19.8°C
                     2.53 +- 0.00 mm[2]/s (cSt) at 39.9°C
                             Ubbelohde viscometer
Melting Range/830.7200
                   Not applicable; the product is a liquid.
                                      N/A

Boiling Range/830.7220
                                102.6 +- 0.1°C
                             Ebulliometric method

Density/Relative Density/Bulk Density/830.7300
                               1.14 +- 0.00 g/mL
                                   OECD 109

Dissociation Constant in Water/830.7370
                   Not applicable, the product is 70% water.
                                      N/A

Partition Coefficient/830.7550
Not applicable, the product is 70% water and the components are not expected to partition into octanol.
                                      N/A

Water Solubility/830.7840
                   Not applicable, the product is 70% water.
                                      N/A

Vapor Pressure/830.7950
 Not applicable, the product is 70% water and contains non-volatile solutes. 
                                      N/A

   TABLE 3.  Acute Toxicity Data for PM-4300 Organic Acids (40 CFR 158.2050)

                          Study Type/OCSPP Guideline
                                       
                               LD50/LC50/Results
                                       
                               Toxicity Category
                                     MRID

Acute Oral Toxicity/870.1100
                                >5,000 mg/kg
                                       
                                      IV
                                   48711105

Acute Dermal Toxicity/870.1200
                               > 5,000 mg/kg
                                       
                                      IV
                                   48711106

Acute Inhalation Toxicity870.1300
                                 >2.05 mg/L
                                      IV
                                   48711107

Acute Eye Irritation/870.2400

Minimal effects clearing in less than 24 hours
                                      IV
                                   48711108

Acute Dermal Irritation/870.2500
Slight irritation resolved within 72 hours
                                       
                                      IV
                                   48711109

Skin Sensitization/870.2600
                               Not a sensitizer
                                      N/A
                                   48711110

Bacterial Reverse Mutation Testing/870.5100
PM-4300 did not cause gene mutations by base pair changes or frame shifts; no evidence of cytotoxicity at highest does tested; non-mutagenic/Acceptable
                                      N/A
                                   49080301

In vitro Mammalian Cell Assay/870.5300/5375
                             Rationale/Acceptable
                                      N/A
                                   48711115

90-Day Oral Toxicity/870.3100
                             Rationale/Acceptable
                                      N/A
                                   48711115

90-Day Dermal Toxicity/870.3250
                             Rationale/Acceptable
                                      N/A
                                   48711115

90-Day Inhalation Toxicity/870.3465
                             Rationale/Acceptable
                                      N/A
                                   48711115

Prenatal Development/870.3700
                             Rationale/Acceptable
                                      N/A
                                   49080301

The request to bridge acute toxicity data produced for PM-4300 (TGAI/MP) to Phocon was acceptable. 

          TABLE 4.  Acute Toxicity Data for Phocon (40 CFR 158.2050)
                              Acute Oral Toxicity
                             Rationale-acceptable
                             Acute Dermal Toxicity
                             Rationale-acceptable
                            Primary Eye Irritation
                            Minimal irritation: IV
                           Primary Dermal Irritation
                             Rationale-acceptable
                             Dermal Sensitization
                             Rationale-acceptable
                           Acute Inhalation Toxicity
                             Rationale-acceptable

TABLE 5. Ecological Toxicity Data Requirements for PM-4300 Organic Acids (40 CFR 158.2060)
                          Study Type/OCSPP Guideline
                                    Results
                                     MRID

Avian Acute Oral/850.2100
                             Rationale/Acceptable
                                   49080302

Avian Dietary/850.2200
                                       
               96 hour LC50 > 5620ppm;  Practically Nontoxic
                                   48711112

Freshwater Fish LC50/850.1075
                                       
                         96 hour LC50 > 100 mg/L; 
                             Practically Nontoxic
                                   48711113

Freshwater Invertebrate/850.1010
                                       
                48 hour EC50 > 100 mg/L Practically Nontoxic
                                   48711114

Non-target Plants/850.4100/4150
                             Rationale/Acceptable
                                   48711116

Non-target Insects/850.3020
                                       
                             Rationale/Acceptable
                                   48711116

  TABLE 6. Ecological Toxicity Data Requirements for Phocon (40 CFR 158.2060)
                          Study Type/OCSPP Guideline
                           Results/Toxicity Category
                                     MRID
                               Study Conclusion

Avian Acute Oral/850.2100
                  Information submitted to justify rationale
                                       
                                  Acceptable
                                   49080203

Avian Dietary/850.2200
                  Information submitted to justify rationale
                                       
                                  Acceptable
                                       
                                   48711116

Freshwater Fish LC50/ 850.1075
                  Information submitted to justify rationale
                                       
                                  Acceptable
                                       
                                   48711116

Freshwater Invertebrate/ 850.1010
                  Information submitted to justify rationale
                                       
                                  Acceptable
                                       
                                   48711116

Non-target Plants/850.4100
Pre-emergence application at 24 qt/A did not reduce by 25% or greater any of the 21-day growth endpoints for species tested
                                  Acceptable
                                       
                                   48710906

Non-target Plants/850.4150
Foliar application at 24 qt/A did not reduce by 25% or greater any of the growth endpoints for species tested at 21 days post application
                                  Acceptable
                                       
                                   48710907

Non-target Insects/850.3020

48-hr contact LD50 >100ug/bee; relatively nontoxic to honey bee
                                       
                                  Acceptable
                            48710908  and 49080203

APPENDIX B. References

1. U.S. EPA, 2012. Memorandum from Sadaf Shaukat to Menyon Adams. Science Review in support of the Registration of PM-4300 Organic Acids Containing 18.5% Organic Acids derived from Leonardite as its Active Ingredient. U.S. Environmental Protection Agency, Office of Pesticide Programs. December 18, 2012. 

2. U.S. EPA, 2013. Memorandum from Sadaf Shaukat to Menyon Adams. Science Review in support of the Registration of PM-4300 Organic Acids Containing 18.5% Organic Acids derived from Leonardite as its Active Ingredient. U.S. Environmental Protection Agency, Office of Pesticide Programs. September 6, 2013. 
   
3. U.S. EPA, 2012. Memorandum from Sadaf Shaukat to Menyon Adams. Science Review in support of the Registration of Phocon Containing 12.0% Organic Acids derived from Leonardite as its Active Ingredient. U.S. Environmental Protection Agency, Office of Pesticide Programs. December 22, 2012. 

4. U.S. EPA, 2013. Memorandum from Sadaf Shaukat to Menyon Adams. Science Review in support of the Registration of Phocon Containing 12.0% Organic Acids derived from Leonardite as its Active Ingredient. U.S. Environmental Protection Agency, Office of Pesticide Programs. January 23, 2013. 

5. U.S. EPA, 2013. Memorandum from Sadaf Shaukat to Menyon Adams. Science Review in support of the Registration of Phocon Containing 12.0% Organic Acids derived from Leonardite as its Active Ingredient. U.S. Environmental Protection Agency, Office of Pesticide Programs. September 6, 2013.  

6. OECD. 2004. SIDS Initial Assessment Report. Gluconic Acid and its Derivatives. Paris, France.

7. Pena-Mendez, E. M., Havel, J., Patocka, J. 2005. J. Applied Biomedicine. 3: 13-24.

8. Thurman EM. 1985. Organic Geochemistry of Natural Waters. Kluwer, Boston, MA, USA.

9. (40 CFR §180.950 (e)).

10. ASA Analytics. 2010. Natural organic matter (NOM) in water. 
   http://www.anaanalytics.com/natural-organic-matter.php 

GLOSSARY OF ACRONYMS AND ABBREVIATIONS
      
   a.i.	active ingredient
   BPPD	Biopesticides and Pollution Prevention Division
   BRAD	Biopesticide Registration Action Document
   bw	body weight
   CBI	Confidential Business Information
   CFR	Code of Federal Regulations
   cm[3] 	cubic centimeter
   CSF	Confidential Statement of Formula
   °C 	degrees Celsius
   EC50	median effective concentration. A statistically derived single concentration in environmental medium that can be expected to cause an effect in 50% of the test animals when administrated by the route indicated (inhalation). It is expressed as a concentration in air or water (e.g. mg/L).
   EDSP	Endocrine Disruptor Screening Program
   EDSTAC	Endocrine Disruptor Screening and Testing Advisory Committee
   EP	end-use product
   EPA	Environmental Protection Agency (the "Agency")
   FDA	Food and Drug Administration
   FFDCA	Federal Food, Drug, and Cosmetic Act
   FIFRA	Federal Insecticide, Fungicide, and Rodenticide Act
   FQPA 	Food Quality Protection Act
   FR	Federal Register
   g 	gram
   ha	hectare
   kg	kilogram
   Kow	octanol-water partition coefficient
   L                   liter
   LC50	median lethal concentration. A statistically derived single concentration in air or water that can be expected to cause death in 50% of the test animals when administrated by the route indicated (inhalation and environment). It is expressed as a concentration in air or water (e.g. mg/L).
   LD50	median lethal dose. A statistically derived single dose that can be expected 
   	to cause death in 50% of the test animals when administered by the route 
   	indicated (oral and dermal). It is expressed as a weight of 
   	substance per unit weight of animal (e.g., mg/kg).
   MRID No.	Master Record Identification Number
   mg	milligram
   mPa	millipascal
   mL	milliliter
   MP	manufacturing-use product
   N/A	not applicable
   NE	"No Effect"
   NIOSH 	National Institute for Occupational Safety and Health
   nm	nanometer
   NOEL	no-observed-effect-level
   NOF	notice of filing
   NOR	notice of receipt
   OPP	Office of Pesticide Programs
   OCSPP 	Office of Chemical Safety and Pollution Prevention
   pa	pascal
   PPE 	personal protective equipment
   PR Notice	Pesticide Registration Notice
       TGAI 	   technical grade of the active ingredient
       ug 		   microgram
       USDA 	   United States Department of Agriculture
       UV 	   ultra-violet