Docket Number EPA-HQ-OPP-2011-0173 

www.regulations.gov 

Cryolite Final Work Plan 

Registration Review 

September 2011 
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Introduction:

This is the Environmental Protection Agency’s (EPA or the Agency) Final Work Plan (FWP) for 

the registration review of cryolite. The FWP includes 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 additional risk analyses and data or information 

the Agency believes are needed to make a registration review decision. 

The Agency’s implementation of the registration review program requires review of each 

registered pesticide every 15 years to determine whether it continues to meet the Federal 

Insecticide, Fungicide, and Rodenticide Act (FIFRA) standard for registration. Changes in 

science, public policy, and pesticide use practices occur over time. The registration review 

program is intended to make sure that, as the ability to assess risk evolves and as policies and 

practices change, all registered pesticides continue to meet that statutory standard. The public 

phase of registration review begins when the initial docket is opened for each case. Information 

on this program is provided at http://www.epa.gov/oppsrrd1/registration_review/. 

Cryolite is a naturally-occurring mineral of sodium 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 treated food. As a result, there are tolerances 

(maximum allowable residue limits) for fluoride on the food commodities approved for treatment 

with cryolite. Cryolite was subject to a Reregistration Eligibility Decision (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 comment a Proposed Order on sulfuryl fluoride, 

another pesticide that leaves residues 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 meet 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 reviewing those comments. 

While EPA works toward a final decision on the sulfuryl fluoride and fluoride tolerances, the 

Agency plans to continue with the current registration review timeline for cryolite. This 

document makes final the work plan for the registration review process. However, the Agency 

may adjust the cryolite registration review timeline and work plan in the future as necessary 

based on the timing and outcome of the sulfuryl fluoride and fluoride tolerances final decision. 

Updates Since the Summary Document:

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

Network North America filed a lawsuit in the United States District Court for the Northern 

District of California, against the EPA for allegedly failing to undergo consultation with the 
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United States Fish and Wildlife Service and the National Marine Fisheries Service (the Services) 

regarding the effects of over 350 pesticides, including cryolite, on over 200 endangered and 

threatened species throughout the United States (Center for Biological Diversity, 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 reflected in this FWP. 

Comments Received on the Preliminary Work Plan:

The cryolite docket was open for a 60-day comment 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 extension to the comment period to afford time for 

further public discussion. This request was granted by the Agency and the closing date was 

extended to July 5, 2011. 

 

A total of 31 public sets of comments were received in the cryolite docket during the comment 

period. The Fluoride Action Network (FAN) submitted extensive comments on the fluoride 

aggregate risk assessment to the cryolite docket. FAN also separately submitted comments on 

the fluoride aggregate risk assessment 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 fluoride aggregate risk assessment. The cryolite 

technical registrant, Gowan Company, 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 Proposed Order to withdraw tolerances – both those 

received in the cryolite docket and those received in the sulfuryl fluoride docket. These 

comments will be addressed in a separate document. 

The comments specific to cryolite registration review 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 additional data requirement (Guideline 850.2300, Avian 

Reproduction) not identified in the cryolite PWP or Problem Formulation, has been added. The 

comments did not result in a change to the work plan or timeline described in the Summary 

Document. 

EPA also solicited comments, through the PWP, on three specific topics: environmental 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 detailed description of the comments received and the Agency’s 

response to these comments please refer to the following two documents: Cryolite. Response to 
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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 for cryolite, but not a 

member of the FESTF (or a company having met its data compensation obligations), to provide a 

formal offer-to-pay to FESTF in conjunction with 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 testing for adverse effects include 

cryolite and all of its degradation 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 concentrations 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. Aluminofluoride complexes are formed spontaneously in 

water containing fluoride and trace amounts of aluminum. These complexes have been found to 

stimulate various G proteins, and thus may “mimic or potentiate the action of numerous 

extracellular signals and significantly affect many cellular responses.” EPA should require that 

human health toxicity testing be extended to include all of its degradation products, including the 

various aluminofluoride complexes formed 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 commonly 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 antacids 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 people is so ubiquitous, the small amount of 

aluminum in dietary residues from cryolite is not expected to have an adverse health effect. 

FAN was specifically concerned that aluminofluoride complexes would affect G proteins and 

cellular signaling pathways. However, cryolite has already been evaluated in a number of 

toxicity studies, including a battery of acute toxicity studies in different species, subchronic oral 

toxicity studies in rats and dogs, chronic toxicity in rats and dogs, 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 toxicity 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 for terrestrial and aquatic species, and additional chronic toxicity 

data for aquatic species, stating that cryolite may have a greater potential adverse effect on 

developing embryos and fetuses than adults. EPA assumed that because cryolite is “practically 
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nontoxic to avian species on an acute 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 and fetus are more vulnerable to toxins than the 

adult form. Furthermore, for all but mammalian species, acute exposure of the female at the time 

of ovulation and fertilization potentially establishes a situation 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 environments would buffer concentrations of cryolite 

residues. Therefore the Agency will not be requesting additional toxicity data on aquatic 

animals. However, the Agency agrees that risk to birds and mammals from chronic exposure via 

the ingestion of contaminated vegetative dietary items should be assessed. Currently there are 

acceptable reproductive toxicity data available for mammals, but chronic data are not available 

for avian species. EPA added an avian reproduction study (850.2300) to the list of data 

requirements to address this data gap. The additional data requirement is reflected in this FWP. 

Comment 4: FAN commented that while OPP uses a surrogate 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 toxicity to fish is similar to aquatic-phase amphibian), these toxicity 

assumptions “ignore that amphibians have been shown to be extremely sensitive to toxins, and 

are considered ‘valuable indicators of environmental stress.” FAN requests that OPP require 

cryolite toxicity data on amphibians and conduct a risk assessment for amphibians in the cryolite 

risk assessment conducted for 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 Al3+ and F-

. As a result, exposure to amphibians to aluminum, 

fluorine or sodium from cryolite use, 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 cryolite risk conclusions. Therefore, the 

Agency is not requiring toxicity data on amphibians for the cryolite 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 potentially eliminating tolerances for cryolite due to its importance to 

growers. Usage information was provided indicating 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 this information during 

registration review. 
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Comment 6: The technical registrant, Gowan Company, stated that because of cryolite’s low 

toxicity to bees, residual profile, and the absence of known resistance by pest populations, 

cryolite is an essential component of integrated pest management (IPM) and resistance 

management programs in a number of high-value specialty crops, particularly grapes, peppers 

and citrus. 

EPA Response 6: The Agency thanks Gowan Company for its comments and will consider this 

information during registration review.

Risk Assessment and Data Needs:

The Agency will conduct a comprehensive ecological risk assessment, including an endangered 

species assessment, and intends to update the existing human health toxicity data base and risk 

assessments for all uses of cryolite. The Agency will require data in order to conduct the 

planned ecological and human health 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 for 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 Agency to determine whether cryolite’s use has 

“no effect” or “may affect” federally listed threatened or endangered species (listed 

species) or their designated critical habitats. 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 Wildlife Service (FWS) and/or National Marine 

Fisheries Service (NMFS) (the Services), as appropriate. 

 The Agency is requiring the following environmental 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 Toxicity 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 Phytotoxicity: Tier II, Seedling Emergence 

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

o GLN No. 850.4400 – Non-target Area Phytotoxicity: Tier II, Aquatic Plant 

Growth (Aquatic Vascular Plants) 

o GLN No. 850.5400 – Non-target Area Phytotoxicity: Tier II, Aquatic Plant 

Growth (Algal Plants) 
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 Please refer to Registration Review – Preliminary Problem Formulation for the 

Ecological Risk and Drinking Water Exposure Assessments for Cryolite, March 8, 2011, 

and the Response to Comments on the Preliminary Problem Formulation for the 

Ecological Risk and Drinking Water Exposure Assessments for Cryolite, dated August 1, 

2011, located in the docket, for a detailed discussion of these risk assessment and data 

needs. 

Human Health Risk: 

 A comprehensive human health risk assessment 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 cryolite’s toxicity is 

attributed to its dissociation into fluoride ions. 

 On January 7, 2011, the Office of Pesticide Programs and the Office of Water completed 

an aggregate risk assessment for all dietary exposure sources of fluoride in food and 

drinking water, including the pesticide cryolite and sulfuryl fluoride. 

 Based on an endpoint of severe dental fluorosis, exposures for some sub-populations 

exceeded the Agency’s level of concern particularly for children living in areas with high 

levels of naturally-occurring fluoride in their 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 risk assessment for cryolite is needed; and 3) 

determine whether cryolite meets the FFDCA safety 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 inhalation exposures resulting from off-site 

transport (e.g., spray drift) may occur as a result 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 Inhalation Toxicity study, 

the Agency will conduct a quantitative risk assessment for occupational exposure. The 

Agency is currently evaluating the March 2, 2010 Scientific Advisory Panel (SAP) final 

report on issues related to volatilization of pesticides and may, as appropriate, develop 

policies and procedures to identify whether to incorporate post-application inhalation 

exposure into the Agency’s risk assessments, and methods to assess post-application 

inhalation exposure. If new policies or procedures are implemented, the Agency would 

anticipate revisiting the need for a quantitative occupational post-application inhalation 

exposure assessment for cryolite. 
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 Since the residue of concern for cryolite applications is fluoride, tolerance levels and 

residue definition may need to be modified or revoked in the future based on a 

determination of fluoride aggregate risks and 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 complete 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 Document in Support of Registration 

Review, March 16, 2011, located in the docket, for a detailed discussion of the risk 

assessment and data needs for human health. 

Endocrine Disruptor Screening Program:

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse 

outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and 

chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, 

reproductive, and general or systemic toxicity. These studies include endpoints which may be 

susceptible to endocrine influence, including effects on endocrine target organ histopathology, 

organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, 

and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and 

chronic studies that assess growth, developmental and reproductive 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 section 408(p), cryolite is subject to the endocrine 

screening part of the Endocrine Disruptor Screening Program (EDSP). 

EPA has developed the 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 by a “naturally occurring estrogen, or other such endocrine effects as the Administrator 

may designate.” The EDSP employs a two-tiered approach to making the statutorily required 

determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a 

chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal 

systems. Chemicals that go through Tier 1 screening and are found to have the potential to 

interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA 

will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 

testing is designed to identify any adverse endocrine-related effects 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. Between 
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October 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. 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 issue future EDSP orders/data callins, requiring the submission of EDSP screening assays for cryolite. For further information on 

the status of the EDSP, the policies and procedures, the list 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 the cryolite registration 

review. 

Registration Review for Cryolite – Projected Registration Review Timeline*

Activities Estimated Date 

Opening the Docket 

Open Docket and Public Comment 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 timeline and work plan may be adjusted in the future as necessary 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 the planned ecological and human 

health risk assessments for the cryolite registration review. 
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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) TGAI1 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 Emergence2 TGAI 12

850.4150 Non-target Area Phytotoxicity: 

Tier II, Vegetative Vigor2 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

 

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 Technical Grade Active Ingredient (TGAI) 

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 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.