Docket Number EPA-HQ-OPP-2011-0173 www.regulations.gov



## Cryolite Final Work Plan Registration Review

September 201123 Introduction:

This is the Environmental Protection Agency’s (EPA or the Agency) Final Work Plan (FWP) for the registration review of cryolite. The FWP incl udes the expected registration review timeline. The FWP also addresses any public comments received on the Preliminary Work Plan (PWP) in

the Summary Document, which was posted in the cryolite registration review docket (EPA-HQOPP-2011-0173). The Summary Document, dated March 25, 2011, provided information on what EPA knows about the pesticide and what add itional risk analyses and data or information the Agency believes are needed to ma ke a registration review decision.

The Agency’s implementation of the registrati on review program requi res review of each registered pesticide every 15 years to determin e whether it continues to meet the Federal Insecticide, Fungicide, and Rode nticide Act (FIFRA) standard for registration. Changes in science, public policy, and pestic ide use practices occur over time. The registration review program is intended to make sure that, as the ab ility to assess risk evolves and as policies and practices change, all registered pesticides contin ue to meet that statutory standard. The public phase of registration review begins when the ini tial docket is opened for e ach case. Information on this program is provided at http://www.epa.gov/oppsrrd1/registration_review/

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Cryolite is a naturally-occurring mineral of sodi um aluminum fluoride, and is part of the inorganic fluorine chemical family. Cryolite is registered for use in agricultural settings on various fruits and vegetables, as well as for some uses on ornamental plants. There are no residential or public recreational uses of cryolite. Cryolite breaks down to form fluoride when it is applied and can leave fluoride residues on tr eated food. As a result , there are tolerances (maximum allowable residue limits) for fluorid e on the food commodities approved for treatment with cryolite. Cryolite was subject to a Rere gistration Eligibility D ecision (RED), which was completed in June 1996. The 1996 RED evaluated data on both cryolite and fluoride. Cryolite tolerances were reassessed in 1997 in conjunction with a registration action.

On January 19, 2011, EPA published for public comme nt a Proposed Order on sulfuryl fluoride, another pesticide that leaves residue s of fluoride on treated food (see docket EPA-HQ-OPP2005-0174 ). In that Proposed Order, EPA proposed to withdraw all fluoride tolerances because aggregate exposure to fluoride appears to not m eet the safety standard under the Federal Food, Drug, and Cosmetic Act (FFDCA). The comment period for the proposed order closed on July 5, 2011, and EPA is currently re viewing those comments.

While EPA works toward a final decision on the su lfuryl fluoride and fl uoride tolerances, the Agency plans to continue with the current re gistration review timeline for cryolite. This document makes final the work plan for the regist ration review process. However, the Agency may adjust the cryolite registration review timelin e and work plan in the future as necessary based on the timing and outcome of the sulfuryl fluoride and fluoride tole rances final decision.

Updates Since the Summary Document:

Litigation - On January 19, 2011, the Center for Biologi cal Diversity and the Pesticide Action

Network North America filed a lawsuit in the Un ited States District Court for the Northern District of California, agains t the EPA for allegedly failing to undergo consultation with the4 United States Fish and Wildlife Service and the Na tional Marine Fisheries Service (the Services) regarding the effects of over 350 pesticides, including cryolit e, on over 200 endangered and threatened species throughout the United States (C enter for Biological Divers ity, et al. v. EPA, et al., No. C 11-00293 (N.D.Cal.).

Additional Data Requirements:

In response to a public comment, the Agency has determined that Guideline 850.2300, Avian Reproduction, is needed to assess chronic exposure to birds. This requirement was not identified in the PWP or in the Problem Formulation; however, it is refl ected in this FWP.

Comments Received on the Preliminary Work Plan:

The cryolite docket was open for a 60-day co mment period, beginning March 30, 2011. The comment period was originally scheduled to expire May 31, 2011. During this 60-day period, four comments were received requesting an exte nsion to the comment period to afford time for further public discussion. This request was gr anted by the Agency and the closing date was extended to July 5, 2011.

A total of 31 public sets of comments were re ceived in the cryolite docket during the comment period. The Fluoride Action Network (FAN) s ubmitted extensive comments on the fluoride aggregate risk assessment to the cryolite docket. FAN also separately submitted comments on the fluoride aggregate risk assessmen t to the sulfuryl fluoride docket ( EPA-HQ-OPP-2005-

0174 ). Twenty-one individuals submitted comments to the cryolite docket indicating that they

concurred with FAN’s submission on the fluorid e aggregate risk assessment. The cryolite technical registrant, Gowan Co mpany, also submitted comments on the fluoride aggregate risk assessment to the cryolite docket. EPA is currently reviewing all comments relating to the fluoride aggregate risk assessment and the Propose d Order to withdraw to lerances – both those received in the cryolite docket and those rece ived in the sulfuryl fluoride docket. These comments will be addressed in a separate document.

The comments specific to cryolite registration re view and data requirements, as well as the Agency’s responses, are summarized in this FWP. As a result of a comment received on the ecological data requirements, one additiona l data requirement (Guideline 850.2300, Avian Reproduction) not identified in the cryolite PWP or Problem Form ulation, has been added. The

comments did not result in a ch ange to the work plan or tim eline described in the Summary

Document.

EPA also solicited comments, through the PWP, on th ree specific topics: e nvironmental justice, water body impairment, and trade irritants. No comments or information were received during the comment period concerning these issues.

Summary of Comments & Agency Responses:

A general summary of the comments specific to cryolite and the Agency’s response to comments are provided below. For a de tailed description of the commen ts received and the Agency’s response to these comments please refer to the following two documents: Cryolite. Response to5 comments by the Fluoride Action Network (FAN ) on the Registration Review for Cryolite , dated September 6, 2011, and Response to Comments on the Preliminary Problem Formulation for the Ecological Risk and Drinking Water Exposure Assessments for Cryolite , dated August 1, 2011.

These documents are available in the cryolite docket (EPA-HQ-OPP-2011-0173).

Comment 1: The FIFRA Endangered Species Task Force (FESTF) submitted a comment that the Agency should inform any company who is a technical registrant fo r cryolite, but not a member of the FESTF (or a company having met its data compensation oblig ations), to provide a formal offer-to-pay to FESTF in conjunction wi th their support of the active ingredient.

EPA Response 1: The Agency thanks FESTF for its comment and will take this under

consideration.

Comment 2: FAN commented that OPP should require that testi ng for adverse effects include cryolite and all of its degradat ion products and complexes. Cryolite degrades to fluoride, aluminum, and sodium in the environment. EPA considers the only degradation product of

concern to be fluoride. EPA is requiring that free ion concentr ations of aluminum ion (Al3+), fluoride anion (F-), and sodium ion (Na+) be used to estimate toxicity, and not the effects of complexes formed from these ions. Aluminofl uoride complexes are formed spontaneously in water containing fluoride and trace amounts of alum inum. These complexes have been found to stimulate various G proteins, and thus may “m imic or potentiate th e action of numerous extracellular signals and signifi cantly affect many cellu lar responses.” EPA should require that human health toxicity testing be extended to in clude all of its degrada tion products, including the various aluminofluoride complexes form ed under different aquatic conditions.

EPA Response 2: Aluminum is the third most abundant element in the earth's crust and is a component in food ingredients, food containers , drinking water, and utensils used in food preparation. As a consequence, aluminum is co mmonly found in foods. Most foods that have been tested were found to contain 0.1 – 10 ppm aluminum. A much larger source of oral exposure to aluminum is reportedly from ant acids and buffered analgesics. A 2001 review article reported that "(n)o reports of dietary aluminum toxicity to healthy individuals exist in the literature." Because aluminum exposure to peop le is so ubiquitous, the small amount of aluminum in dietary residues from cryolite is not expected to have an ad verse health effect.

FAN was specifically concerned that aluminoflu oride complexes would affect G proteins and cellular signaling pathways. Ho wever, cryolite has already b een evaluated in a number of toxicity studies, including a batt ery of acute toxicity studies in different sp ecies, subchronic oral toxicity studies in rats and dogs, chronic toxicity in rats and d ogs, carcinogenicity in rats and mice, developmental toxicity in rats, rabbits , and mice, reproductive toxicity in rats, and in vitro mutagenicity studies. The oral exposure to cryolite in the many toxicity studies with different animal species has allowed evaluation of the toxi city potential for cryolite and its aluminum and fluoride degradation products and complexes. Therefore, no additional testing is required.

Comment 3: FAN commented that EPA should require reproductive/developmental toxicity/teratogenicity testing fo r terrestrial and aquatic species, and additional chronic toxicity data for aquatic species, stati ng that cryolite may have a grea ter potential adverse effect on developing embryos and fetuses than adults. EPA assumed that because cryolite is “practically6 nontoxic to avian species on an acu te oral and sub-acute dietary basis” and is “no more than slightly toxic to small mammals on an acute oral basis,” chronic risk to birds and small mammals is not expected. However, developing embryo an d fetus are more vulnerabl e to toxins than the adult form. Furthermore, for all but mammalian sp ecies, acute exposure of the female at the time of ovulation and fertilization pot entially establishes a situati on of chronic exposure for the duration of embryological development.

EPA Response 3: The incremental addition of cryolite is not expected to cause elemental exceedances of natural background concentrations , especially residue in soil and water. Chemical equilibrium in soil and aquatic enviro nments would buffer concentrations of cryolite residues. Therefore the Agency will not be requesting additi onal toxicity data on aquatic animals. However, the Agency agrees that risk to birds and mammals from chronic exposure via the ingestion of contaminated ve getative dietary items should be assessed. Currently there are acceptable reproductive toxicity da ta available for mammals, but ch ronic data are not available for avian species. EPA added an avian repr oduction study (850.2300) to the list of data requirements to address this data gap. The additi onal data requirement is reflected in this FWP.

Comment 4: FAN commented that while OPP uses a su rrogate approach in its ecological risk assessments ( i.e ., OPP assumes that toxicity to birds is similar to terrestrial-phase amphibians and reptiles and that cryolite toxici ty to fish is similar to aquatic-phase amphibian), these toxicity assumptions “ignore that amphibians have been s hown to be extremely sensitive to toxins, and

are considered ‘valuable indicators of envir onmental stress.” FAN requests that OPP require cryolite toxicity data on amphibi ans and conduct a risk assessment for amphibians in the cryolite

risk assessment conducted fo r registration review.

EPA Response 4: The incremental addition of cryolite is not expected to cause elemental exceedances of natural background concentrations, especially for aluminum and sodium, in soil or water. More importantly, chemical equilibrium in soil and aquatic environments is expected

to buffer concentrations of Al 3+ and F - . As a result, exposure to amphibians to aluminum, fluorine or sodium from cryolite us e, either via contact with soil or in the aquatic environment, is not expected to exceed normal background levels for these elements. Therefore, additional toxicity data using amphibians would not likely alter cr yolite risk conclusions. Therefore, the Agency is not requiring toxic ity data on amphibians for the cr yolite ecological risk assessment.

Comment 5: The California Citrus Quality Council, California Grape & Tree Fruit League, and the Raisin Bargaining Association (RBA) all submitted comments to the Agency expressing support of the registration of cryolite products. The groups described the benefits of cryolite, which included its use in an Integrated Pest Management (IPM) program because of its capacity to control target pests (katydids and Lepidoptera) without affecting beneficial species. They also expressed concern for EPA potentiall y eliminating tolerances for cryolite due to its importance to growers. Usage information was provided indica ting it is widely used in California.

EPA Response 5: The Agency thanks the California Citrus Quality Council, California Grape & Tree Fruit League, and RBA for their comments and will consider th is information during registration review.7 Comment 6: The technical registrant, Gowan Compa ny, stated that because of cryolite’s low toxicity to bees, residual pr ofile, and the absen ce of known resistance by pest populations, cryolite is an essential com ponent of integrated pest management (IPM) and resistance management programs in a number of high-value sp ecialty crops, particularly grapes, peppers

and citrus.

EPA Response 6: The Agency thanks Gowan Company fo r its comments and will consider this information during registration review.

Risk Assessment and Data Needs:

The Agency will conduct a comprehensive ecologi cal risk assessment, including an endangered species assessment, and intends to update the exis ting human health toxicity data base and risk assessments for all uses of cryolite. The Ag ency will require data in order to conduct the planned ecological and human hea lth risk assessments. Below is a summary of the ecological

and human health issues relevant to the registration review of cryolite.

Ecological Risk:

 The most recent ecological risk assessment fo r cryolite was completed in 1996 in support

of the RED.

 The Agency has not conducted an ecological risk assessment that supports a complete endangered species determination for cryolite. The ecological risk assessment planned during registration review will allow the Agen cy to determine whether cryolite’s use has “no effect” or “may affect” federally liste d threatened or endangered species (listed species) or their designated critical habita ts. When an assessment concludes that a pesticide’s use “may affect” a listed species or its designated critical habitat, the Agency

will consult with the U.S. Fish and Wildli fe Service (FWS) and/or National Marine Fisheries Service (NMFS) (the Services), as appropriate.

 The Agency is requiring the following envir onmental effects data for use in conducting a complete ecological risk assessment, including an endangered species assessment, for all

uses:

o Guideline (GLN) No. 850.1025 – Acute Toxi city Estuarine/Marine Organisms (Oyster)

o GLN No. 850.1075 – Freshwater Fish Toxicity (Estuarine/Marine)

o GLN No. 850.2100 – Avian Oral Toxicity (passerine species)

o GLN No. 850.2300 – Avian Reproduction

o GLN No. 850.4100 – Non-target Area Phytot oxicity: Tier II, Seedling Emergence

o GLN No. 850.4150 – Non-target Area Phytot oxicity: Tier II, Vegetative Vigor

o GLN No. 850.4400 – Non-target Area Phyt otoxicity: Tier II, Aquatic Plant Growth (Aquatic Vascular Plants)

o GLN No. 850.5400 – Non-target Area Phyt otoxicity: Tier II, Aquatic Plant Growth (Algal Plants)8  Please refer to Registration Review – Preliminar y Problem Formulation for the Ecological Risk and Drinking Water Ex posure Assessments for Cryolite, March 8, 2011,

and the Response to Comments on the Prelimi nary Problem Formulation for the Ecological Risk and Drinking Water Exposure Assessments for Cryolite , dated August 1, 2011, located in the docket, for a detailed disc ussion of these risk assessment and data

needs.

Human Health Risk:

 A comprehensive human health risk asse ssment was completed in 1996 in support of reregistration, which assessed dietary (food and water) and occupational exposures. The 1996 RED evaluated data on both cryolite and fluoride because cryol ite’s toxicity is

attributed to its dissociation into fluoride ions.

 On January 7, 2011, the Office of Pesticide Pr ograms and the Office of Water completed an aggregate risk assessment for all dietar y exposure sources of fluoride in food and drinking water, including the pestic ide cryolite and su lfuryl fluoride.

 Based on an endpoint of severe dental fluorosis, exposures for some sub-populations exceeded the Agency’s level of concern particul arly for children living in areas with high levels of naturally-occurring fluoride in th eir drinking water. The Agency published the aggregate risk assessment (EPA-HQ-OPP-2005-0174) for public comment, and the comment period closed on July 5, 2011.

 Since fluoride is the only residue of concern from cryolite applications, the Agency will: 1) review all the comments received on the January 2011 fluoride aggregate risk assessment; 2) determine if a new aggregate ri sk assessment for cryolite is needed; and 3) determine whether cryolite meets the FFDCA sa fety standard. The cryolite registration review timeline, described on page 10 of this document, may be adjusted in the future as necessary based on the timing and outcome of the sulfuryl fluoride final decision.

 Currently, there are no registered uses for cryolite that would result in residential exposure. However, residential bystander i nhalation exposures resulting from off-site transport (e.g., spray drift) may occur as a resu lt of applications of cryolite. The Agency is in the process of examining its policies and refining the methods used to complete residential exposure assessments. Therefore, the potential need for a bystander inhalation risk assessment for cryolite will be examined during registration review.

 If an applicable endpoint is identified in the required 90-Day Inha lation Toxicity study, the Agency will conduct a quantitative risk a ssessment for occupational exposure. The Agency is currently evaluating the March 2, 2010 Scientific Advisory Panel (SAP) final report on issues related to volatilization of pe sticides and may, as appropriate, develop policies and procedures to identify whethe r to incorporate post-application inhalation exposure into the Agency’s risk assessmen ts, and methods to assess post-application inhalation exposure. If new policies or pr ocedures are implemented, the Agency would anticipate revisiting the need for a quantitative occupational post-application inhalation exposure assessment for cryolite.9  Since the residue of concern fo r cryolite applications is fl uoride, tolerance levels and residue definition may need to be modified or revoked in the future based on a determination of fluoride aggregate risks a nd whether cryolite meets the FFDCA safety

standard.

 For a discussion of tolerances, see Cryolite: Registration Review Scoping Document for Human Health Assessments, dated March 16, 2011.

 The toxicity database is complete except for the following studies, which the Agency is requiring in order to conduct a co mplete human health assessment:

o GLN No. 870.3465 – 90-Day Inhalation Toxicity

o GLN No. 870.7800 – Immunotoxicity

 Please refer to the Cryolite. Human Health Scoping Do cument in Support of Registration
Review, March 16, 2011

, located in the docket, for a de tailed discussion of the risk

assessment and data needs for human health.

Endocrine Disruptor Screening Program:

As required by FIFRA and FFDCA, EPA reviews num erous studies to asse ss potential adverse outcomes from exposure to chemicals. Collectiv ely, these studies includ e acute, subchronic and chronic toxicity, including asse ssments of carcinogenicity, ne urotoxicity, developmental, reproductive, and general or systemic toxicity. These studies include endpoints which may be susceptible to endocrine influe nce, including effects on endocri ne target organ histopathology, organ weights, estrus cyclicity, sexual maturatio n, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and chronic studies that assess gr owth, developmental and reprod uctive effects in different taxonomic groups. As part of its reregistration decision

, EPA reviewed these data and selected the most sensitive endpoints for relevant risk assessment scenarios from the existing hazard database. However, as required by FFDCA secti on 408(p), cryolite is subj ect to the endocrine screening part of the Endocrine Di sruptor Screening Program (EDSP).

EPA has developed the EDSP to determine whet her certain substances (including pesticide active and other ingredients) may have an effect in humans or wildlife similar to an effect produced by a “naturally occurring estrogen, or ot her such endocrine effect s as the Administrator may designate.” The EDSP employs a two-tiered approach to making th e statutorily required

determinations. Tier 1 consists of a battery of 11 scr eening assays to identify the potential of a chemical substance to interact with the estrog en, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go th rough Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stag e of the EDSP where EPA will determine which, if any, of th e Tier 2 tests are necessary base d on the available data. Tier 2 testing is designed to identify a ny adverse endocrine-related eff ects caused by the substance, and establish a dose-response relationship between the dose and the E, A, or T effect.

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between10 October 2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 chemicals, which contains 58 pest icide active ingredients and 9 inert ingredients. Cryolite is not among the group of 58 pesticide active ingredients on the initial list to be screened under the EDSP. Accordingly, as part of registration review, EPA will issu e future EDSP orders/data callins, requiring the submission of EDSP screening assays for cryolite. For further information on the status of the EDSP, the policie s and procedures, the lis t of 67 chemicals, future lists, the test guidelines and the Tier 1 screening battery, please visit our website: http://www.epa.gov/endo/

.

Timeline:

EPA has created the following estimated timeline for the completion of th e cryolite registration

review.

Registration Review for Cryolite – Proj ected Registration Review Timeline*

Activities Estimated Date Opening the Docket Open Docket and Public Co mment Period 2011 – March Close Public Comment 2011 – July Case Development Final Work Plan 2011 – Sept. Issue DCI 2012 – April – June Data Submission 2014 – April – June Open Public Comment Period for Draft Risk Assessments 2015 – Oct. – Dec.

Close Public Comment Period 2016 – Jan. – March Registration Review Decision Open Public Comment Period for Proposed Registration Review

Decision 2016 – April – June

Close Public Comment Period 2016 – July – Sept. Registration Review Decision and Begin Post-Decision Follow-up 2017 Total (years) 6
* The cryolite registration review timelin e and work plan may be adjusted in the future as neces sary based on the timing and outcome of the sulfuryl fluoride and fluoride tolerance final decision.

Next Steps:

The Agency plans to develop a Data Call-In (DCI) Notice for this pesticide and plans to issue it in spring 2012. This new information will be used to conduct complete risk assessments for all registered uses of cryolite.

Summary of Data Gaps – Cryolite:

The EPA is requiring the following studies in order to conduct th e planned ecological and human

health risk assessments for the cryolite registration review.11 Table 1. Summary of Cryolite Data Gaps

Guideline

Number Data Requirement Test

Material Estimated

Timeframe

Environmental Fate and Effects

850.1075 Freshwater Fish Toxicity (Estuarine/Marine) TGAI 1 12

850.2100 Avian Acute Oral Toxicity (Passerine Species) TGAI 12

850.2300 Avian Reproduction TGAI 24
Toxicity to Sediment Dwelling Organisms

850.1025 Acute Toxicity Estuarine/Marine Organisms (Oyster) TGAI 12
Toxicity to Non-target Plants

850.4100 Non-target Area Phytotoxicity: Tier II, Seedling Emergence 2 TGAI 12

850.4150 Non-target Area Phytotoxicity: Tier II, Vegetative Vigor 2 TGAI 12

850.4400 Non-target Area Phytotoxicity: Tier II, Aquatic Plant Growth (Aquatic Vascular Plants) 2 TGAI 12

850.5400 Non-target Area Phytotoxicity: Tier II, Aquatic Plant Growth (Algal Plants) 2 TGAI 12

Human Health Effects

870.3465 90-Day Inhalation Toxicity TGAI 24

870.7800 Immunotoxicity Study TGAI 12

1 Technical Grade Active Ingredient (TGAI)

2 A Tier II study is required. The DCI being issued will provide that a Tier I plant study may be conducted in lieu of a Tier II study with the understanding that any adverse effects observed by the Tier I study would necessitate

conduct and submission of a Tier II study as well.