cryolite (Kryocide) Pesticide Tolerance and Feed Additive Regulation 6/96
ENVIRONMENTAL PROTECTION AGENCY
40 CFR Parts 180 and 186
[PP 9F3739 FAP 1H5604/P654; FRL-5362-6]
Fluorine Compounds; Pesticide Tolerance and Feed Additive Regulation
AGENCY: Environmental Protection Agency (EPA).
ACTION: Proposed rule.
SUMMARY: EPA proposes to establish a pesticide tolerance for residues
of the insecticidal fluorine compounds cryolite and/or synthetic
cryolite (sodium aluminum fluoride) in or on the raw agricultural commodity
potatoes at 2.0 parts per million (ppm) and a feed additive regulation for the
animal feed commodity, potato waste resulting from the processing of treated
potatoes at 22.0 ppm. The proposed tolerance and regulation to establish
maximum permissible levels for residues of the pesticide in or on the
commodities were requested in petitions submitted by Attochem North America,
DATES: Comments, identified by the docket control number [PP 9F3739 and
FAP 1H5604/P654], must be received on or before June 7, 1996.
ADDRESSES: Submit written comments by mail to: Public Response and
Program Resources Branch, Field Operations Division (7506C), Office of
Pesticide Programs, Environmental Protection Agency, 401 M St., SW.,
Washington, DC 20460. In person, bring comments to: Public Docket, Rm.
1132, Crystal Mall #2, 1921 Jefferson Davis Highway, Arlington, VA.
Comments and data may also be submitted electronically by sending
electronic mail (e-mail) to: firstname.lastname@example.org. Electronic
comments must be submitted as an ASCII file avoiding the use of special
characters and any form of encryption. Comments and data will also be
accepted on disks in WordPerfect in 5.1 file format or ASCII file
format. All comments and data in electronic form must be identified by
the docket number (PP 9F3739 and FAP 1H5604/P654). No Confidential
Business Information (CBI) should be submitted through e-mail.
Electronic comments on this proposed rule may be filed online at many
Federal Depository Libraries. Additional information on electronic
submissions can be found below in this document.
Information submitted as a comment concerning this document may be
claimed confidential by marking any part or all of that information as
CBI. Information so marked will not be disclosed except in accordance
with procedures as set forth in 40 CFR part 2. A copy of the comment
that does not contain CBI must be submitted for inclusion in the public
record. Information not marked confidential will be included in the
public docket by EPA without prior notice. The public docket is
available for public inspection in Rm. 1132 at the above address, from
8 a.m. to 4:30 p.m., Monday through Friday, excluding legal holidays.
FOR FURTHER INFORMATION CONTACT: By mail: Robert A. Forrest, Product
Manager (PM) 14, Registration Division (7505C), Office of Pesticide
Programs, Environmental Protection Agency, 401 M St., SW., Washington,
DC 20460. Office location, telephone number, and e-mail address: Rm.
219, CM #2, 1921 Jefferson Davis Highway, Arlington, VA, (703) 305-6600,
SUPPLEMENTARY INFORMATION: EPA issued a notice, published in the
Federal Register of May 5, 1993 (58 FR 26687), which announced the
establishment of a 3-year time-limited tolerance for residues of the
insecticidal fluorine compounds cryolite and synthetic cryolite (sodium
aluminum fluoride) on potatoes and the establishment of a 3-year time-
limited feed additive regulation for residues of these compounds in
processed potato waste (wet or dry).
These regulations were established for a period extending to May 6,
1996, to cover residues existing from the conditional registration of
the insecticidal compounds on potatoes extending to September 30, 1995.
The Agency limited the period of time the conditional registration and
the regulations were to be in effect because of the lack of a chronic
dog feeding study and a two-generation rat reproduction study. These
two studies have been received and have been found to be acceptable.
Pesticide petition 9F3739 requests that the Administrator, pursuant
to section 408(d) of the Federal Food, Drug, and Cosmetic Act (FFDCA),
21 U.S.C. 346a(d), amend 40 CFR 180 by establishing a tolerance for
residues of the insecticidal fluorine compounds in or on the raw
agricultural commodity potatoes at 2.0 ppm with no time limitations.
Food additive petition 1H5604 requests that the Administrator, pursuant
to section 409(b) of the FFDCA (21 U.S.C. 348), amend 40 CFR part 186
by establishing a feed additive regulation for residues of the
insecticidal compounds in or on the processed animal feed commodity
processed potato waste (wet or dry) at 22.0 ppm with no time
To meet the current definition, the commodity, "processed potato
waste (wet or dry)" is corrected to read as follows: potatoes, waste
I. Background Information
Fluoride has been identified as the residue of toxicological
concern in cryolite and synthetic cryolite and the available data show
that these compounds which are approximately 52.8% fluoride, act as
free fluoride. Fluoride is ubiquitous and may be present at low levels
in air, soils and in foodstuffs that have not been treated with
cryolite and/or synthetic cryolite as well as in drinking water. The
atmospheric levels of fluoride and incidental dietary exposures to
fluoride as a toothpaste additive or as a dental treatment contribute
relatively little to the average level of dietary fluoride exposure and
are not further considered in the exposure estimate.
Data submitted in support of the subject petition show background
levels of fluoride in untreated potatoes ranged from 0.14 ppm to 0.31
ppm and are consistent with the ranges reported in the open literature.
Levels of fluoride found in the treated potatoes ranged from 0.18 ppm
to 0.94 ppm. The residue analytical method used for enforcing the
subject tolerance and regulation cannot distinguish between the
naturally occurring fluoride and the fluoride resulting from use of
cryolite and/or synthetic cryolite.
Fluoride levels in public drinking water are regulated under the
Safe Drinking Water Act. EPA has established a Maximum Concentration
Limit (MCL) at 4.0 mg/L [0.114 mg/kg/day] to protect against crippling
skeletal fluorosis (51 FR 11396, April 2, 1986). The MCL established on
April 2, 1986, finalizes interim regulations set in November 14, 1985
(50 FR 47142), and proposed in the Federal Register of May 14, 1985 (50
FR 20164). In addition, these FR notices established a Secondary
Maximum Contaminant Level (SMCL) at 2.0 mg/L [0.057 mg/kg/day] for
cosmetic effects (objectionable dental fluorosis) which are not
considered to be adverse health effects by the Surgeon General.
The EPA Office of Drinking Water issued a Drinking Water Criteria
Document on Fluoride (October 21, 1985) which presents summaries of
experimental and clinical data on the health effects of fluoride in
animals and humans. In general, the health effects of fluoride include
dental fluorosis and skeletal fluorosis.
At the request of the EPA, the U.S. Surgeon General examined the
nondental health aspects associated with fluoride in drinking water.
The Surgeon General concluded that he did not consider changes in
bone density to be an adverse health effect and that adverse effects
(arthralgias) are not likely to occur at human dose levels below 20
mg F/day (10 mg F/L for an adult consuming 2 L water/day [0.29 mg/
kg/day]). The ad hoc committee concluded that four times the optimal
fluoride concentration (approximately 4 mg F/L [0.114 mg/kg/day]) in
drinking water should provide an adequate margin of safety for
preventing adverse health effects which were not documented to occur
in the U.S. population below 8 mg F/L [0.23 mg/kg/day]. (Water
Criteria Document p. IX-21).
II. Toxicological Data
The scientific data submitted in the petitions and other relevant
material have been evaluated. The toxicological data considered in
support of the proposed tolerance and regulation include:
1. A 2-year rat bioassay conducted by the National Toxicology
Program (NTP) using sodium fluoride as the test material at dose levels
of 0, 25, 100, and 175 ppm, in water, representing 0, 1.3, 5.2 and 8.6
mg/kg/day in males and 0, 1.3, 5.5 and 9.5 mg/kg/day in females.
Osteosarcoma of the bone was only observed in one male in the 100
ppm group and in three males in the 175 ppm group. NTP considers this
to be equivocal evidence of carcinogenicity in male F344/N rats. The
NOEL is less than 25 ppm (1.3 mg/kg/day). The LOEL is 25 ppm (1.3 mg/
kg/day) based on mottling of teeth, dentine incisor dysplasia,
increased serum, urine and bone fluoride levels in males and females
and incisor odontoblast and incisor ameloblast degeneration in males.
There was "equivocal evidence" of carcinogenic activity in male rats
and "no evidence" of carcinogenic activity in female rats.
The NTP study utilizing sodium fluoride as the test material in
lieu of cryolite or synthetic cryolite satisfies the guideline study
requirement for both the rodent chronic feeding study and the rat
carcinogenicity study. Fluoride has been identified as the residue of
toxicological concern in cryolite and synthetic cryolite and the
available data show that these compounds act as free fluoride.
2. A 2-year mouse bioassay conducted by the NTP utilizing sodium
fluoride as the test material at dose levels of 0, 25, 100, and 175
ppm, in water, representing 0, 2.4, 9.6 and 16.7 mg/kg/day in males and
0, 2.8, 11.3 and 18.8 mg/kg/day in females.
The NOEL is less than 25 ppm (2.4 mg/kg/day). The LOEL is 25 ppm
(2.4 mg/kg/day) based on attrition of the teeth in males, discoloration
and mottling of the teeth in males and females and increased bone
fluoride in both sexes. There was "no evidence" of carcinogenic
activity in male and female mice.
This study utilizing sodium fluoride in lieu of cryolite or
synthetic cryolite as the test material satisfies the guideline study
requirement for a mouse carcinogenicity study for the reason described
above under item one.
3. A 1-year chronic dog feeding study conducted with cryolite at
dose levels of 0, 3,000, 10,000 and 30,000 ppm, representing 0, 95, 366
and 1,137 mg/kg/day in males and 0, 105, 387 and 1139 mg/kg/day in
females (in terms of fluoride the doses are 0, 51, 198, and 614 mg F/
kg/day for males and 0, 57, 209 and 615 mg F/kg/day for females).
The NOEL (in terms of cryolite) is less than 3,000 ppm (95 mg/kg/
day in males and 105 mg/kg/day in females). The LOEL is 3,000 ppm (95
mg/kg/day) based on increases in emesis, nucleated cells in males,
renal lesions and a decrease in urine specific gravity in females.
4. A two-generation reproduction study conducted with cryolite in
the diet of rats at dose levels of 0, 200, 600, and 1,800 ppm
(representing 0, 14, 42, and 128 mg/kg/day for males and 0, 16, 49, and
149 mg/kg/day for females, respectively, during premating).
The systemic toxicity NOEL was not determined. The LOEL for
systemic toxicity was 200 ppm (15 mg/kg/day) based on dental fluorosis.
The NOEL and LOEL for reproductive toxicity were 600 and 1,800 ppm,
respectively (46 and 138 mg/kg/day) based on decreased pup body
5. A developmental toxicity study conducted with cryolite in rats
at dose levels of 0, 750, 1,500, and 3,000 mg/kg/day (gavage). The NOEL
for both developmental and maternal toxicity is 3,000 mg/kg/day. At
this dose level, the only observation was whitening of the teeth of
6. A developmental toxicity study conducted in female mice with
cryolite at dose levels of 0, 30, 100 and 300 mg/kg/day (gavage).
The NOEL for maternal toxicity is 30 mg/kg/day and the LOEL is 100
mg/kg/day based on the occurrence of dark red contents of the stomach.
Fetuses at 300 mg/kg/day exhibited bent ribs and bent limb bones.
The NOEL for developmental toxicity is 100 mg/kg/day. The LOEL is 300
mg/kg/day based on an increase in bent ribs and bent limbs.
7. A range-finding developmental toxicity study conducted in female
rabbits with cryolite at dose levels of 0, 10, 30, 100, 300 and 1,000
The NOEL for maternal toxicity is 10 mg/kg/day and the LOEL is 30
mg/kg/day based on an increased incidence of soft stool and dark
colored feces and decreased defecation and urination. The NOEL for
developmental toxicity is 30 mg/kg/day. The LOEL could not be assessed
due to excessive toxicity at dose levels of <gr-thn-eq>30 mg/kg/day.
This study suggested that severe maternal toxicity occurred at
lower doses than external developmental toxicity. However, following an
extensive literature evaluation, the National Research Council
(National Academy of Sciences Subcommittee of Health Effects of
Ingested Fluoride) (NAS) determined that,
There have been reports of adverse effects on reproductive
outcomes associated with high levels of fluoride intake in many
animal species. In most of the studies, however, the fluoride
concentrations associated with adverse effects were far higher than
those encountered in drinking water. . . .
Based on these findings, the subcommittee concludes that the
fluoride concentrations associated with adverse reproductive effects
in animals are far higher than those to which human populations are
exposed. Consequently, ingestion of fluoride at current
concentrations should have no adverse effects on human reproduction.
Therefore, an additional developmental study in rabbits is not
8. A 28-day range-finding feeding study conducted with cryolite in rats at
dose levels of 0, 250, 500, 1,000, 2,000, 4,000, 10,000, 25,000 and 50,000 ppm
in the diet (representing approximately 0, 25, 50, 100, 200, 400, 1,000, 2,500
and 5,000 mg/kg/day) with the only compound related effect being a change in
coloration and physical property of the teeth.
The NOEL was not determined. The LOEL is 250 ppm (25 mg/kg/day)
based on dental fluorosis.
9. A 90-day rat feeding study conducted with cryolite at dose
levels of 0, 50, 5,000, and 50,000 ppm (corresponding to 0, 3.8, 399.2
and 4,172.3 mg/kg/day in males and 0, 4.5, 455.9 and 4,758.1 mg/kg/day
The NOEL is 50 ppm (3.8 mg/kg/day) for effects other than fluoride
accumulation. The LOEL is 5,000 ppm (399.2 mg/kg/day) based on lesions
observed in the stomach. Fluoride accumulated at all dose levels.
10. A 90-day dog feeding study conducted with cryolite at dose
levels of 0, 500, 10,000, and 50,000 ppm (corresponding to 0, 17, 368
and 1,692 mg/kg/day).
The NOEL is 10,000 ppm (368 mg/kg/day). The LOEL is 50,000 ppm
(1,692 mg/kg/day) for effects other than fluoride accumulation.
Fluoride accumulation occurred at all dose levels.
11. Genotoxicity studies including an Ames test (negative) at dose
levels of 167, 500, 1,670, 5,000, 7,500 and 10,000 ug/plate; an in
vitro assay in human lymphocytes (negative) at 100, 500, and 1,000 ug/
ml; and an unscheduled DNA synthesis study in rat hepatocytes
(negative) at dose levels up to and including 50 ug/ml.
12. Open literature studies showing that human and animal
metabolism of cryolite and/or synthetic cryolite manifests itself as normal
free fluoride metabolism. That is, dissociation occurs, producing free
fluoride ions which are assimilated into bone.
The available toxicity data are considered adequate to support the
proposed regulations to establish maximum permissible levels for
residues of the insecticidal fluorine compounds in or on potatoes and
in processed potato waste.
The available information does not support the regulation of the
cryolite insecticides as carcinogens.
Fluoride has been the subject of a comprehensive review by the
National Research Council (National Academy of Sciences Subcommittee of
Health Effects of Ingested Fluoride) who concluded that ". . . the
available laboratory data are insufficient to demonstrate a
carcinogenic effect of fluoride in animals." and that ". . . the
weight of evidence from more than 50 epidemiological studies does not
support the hypothesis of an association between fluoride exposure and
increased cancer risk in humans." EPA is in agreement with the
conclusions reached by the National Academy of Science (NAS).
Rather than the establishment of the traditional Reference Dose
(RfD), a weight-of-the-evidence risk assessment was determined by the
Agency to be a more appropriate approach for the assessment of the
dietary exposure to fluoride residues as a result of agricultural uses
of cryolite for the following reasons:
-- National and international regulatory organizations (U.S.
EPA Office of Water, U.S. DHHS, the Canadian Government, and the World
Health Organization) have assessed potential health risks from exposure
to fluoride. The endpoints and estimated effect levels documented by
these organizations are similar.
-- The U.S. Surgeon General (Koop, 1984 and Elders, 1994)
has recommended a guideline level of exposure that should provide an
adequate "margin of safety" based on a large amount of human data,
including epidemiology studies.
-- Animal data considered in evaluating the proposed
regulations are consistent with human data with respect to dose-related
The weight-of-the-evidence dietary risk assessment was conducted
utilizing the following factors. All calculations are based on 2 L/day
water consumption and 70 kg adult.
-- There exists no directly applicable scientific
documentation of adverse medical effects at levels of fluoride below 8
mg/L [0.23 mg/kg/day]. (U.S. EPA. 1985. National Primary Drinking Water
Regulations; Fluoride. Proposed Rulemaking. (50 FR 20166, May 14,
-- Less than 0.4% of the U.S. population (on public water
supplies) is exposed to greater than 2 mg/L fluoride [0.057 mg/kg/day]
in the public water supply. (U.S. EPA. 1985. Drinking Water Criteria
Document on Fluoride. U.S. EPA Office of Drinking Water, Washington,
D.C. TR-832-5. pg. IV-3, Table IV-1.)
-- Dietary exposure estimates using reassessed tolerances
including the subject proposed tolerance and regulation for potatoes
and percent of crops treated are approximately 0.029 mg/kg/day for the
U.S. population and 0.038 mg/kg/day for the highest exposed subgroup
(females 20 years old and over).
Therefore, it can be concluded that levels of fluoride in/on food
from the agricultural use of cryolite plus fluoride levels in U.S.
drinking water supplies results in a daily dietary intake of fluoride
of approximately 0.095 mg/kg/day. This is less than the Maximum
Concentration Limit (MCL) of 4.0 mg/L [0.114 mg/kg/day], a level which
provides no known or anticipated adverse health effect as determined by
the Surgeon General.
The estimated dietary exposure resulting from the subject proposed
tolerance on potatoes is approximately 0.00016 mg/kg/day.
The metabolism of the subject insecticides in plants and animals is
adequately understood. Plant residues are inorganic surface residues of
cryolite which are measured as total fluoride. Cryolite metabolism in
animals manifests itself as free fluorine metabolism and the residue of
concern in animals is total fluoride.
An adequate analytical method (fluoride specific electrode) is
available for enforcement purposes for the RAC potatoes and the animal
feed, potato waste. Because the subject compounds are inorganic
compounds, the requirement for data using the multiresidue protocols in
PAM Vol. I is not applicable.
Because of the long lead time from establishing this tolerance and
regulation to publication of the enforcement methodology in the
Pesticide Analytical Manual, Vol. II, the analytical methodology is
being made available in the interim to anyone interested in pesticide
enforcement when requested from: Calvin Furlow, Public Information
Branch, Field Operations Division (H7506C), Office of Pesticide
Programs, Environmental Protection Agency, 401 M St., SW., Washington,
DC 20460. Office location and telephone number; Rm. 1128, CM #2, 1921
Jefferson Davis Hwy., VA 22202, (703)-305-5232.
There is no reasonable expectation of finite residues of cryolite
or synthetic cryolite occurring in the meat, milk, poultry, and eggs of
animals fed potato waste resulting from the processing of treated
potatoes and 40 CFR 180.6(a)(3) applies. Thus, secondary tolerances are
not necessary at this time in meat, milk, poultry, and eggs.
There are presently no actions pending against the continued
registration of these insecticidal compounds.
The pesticide is considered useful for the purpose for which the
tolerance is sought and capable of achieving its physical or technical
Based on the information and data considered, the Agency has
determined that the tolerance established by amending 40 CFR part 180
would protect the public health, and the establishment of a feed
additive regulation by amending 40 CFR part 186 would be safe.
Therefore, it is proposed that they be established as set forth below.
Any person who has registered or submitted an application for
registration of a pesticide, under the Federal Insecticide, Fungicide,
and Rodenticide Act (FIFRA) as amended, which contains any of the
ingredients listed herein, may request within 30 days after publication
of this notice in the Federal Register that this rulemaking proposal as
it relates to the section 408 tolerance be referred to an Advisory
Committee in accordance with section 408(e) of the FFDCA.
Interested persons are invited to submit written comments on the
proposed regulation. Comments must bear a notation indicating the
document control number, PP 9F3739 and FAP 1H5604/P. All written
comments filed in response to this petition will be available in the
Public Response and Program Resources Branch at the above address from
8 a.m. to 4:30 p.m., Monday through Friday, except legal holidays.
A record has been established for this proposal under docket number
(PP 9F3739 and FAP 1H5604/P654) (including comments and data submitted
electronically as described below). A public version of this record,
including printed, paper versions of electronic comments, which does
not include any information claimed as CBI, is available for inspection
from 8 a.m. to 4:30 p.m., Monday through Friday, excluding legal
The public record is located in Room 1132 of the Public Response
and Program Resources Branch, Field Operations Division (7506C), Office
of Pesticide Programs, Environmental Protection Agency, Crystal Mall
#2, 1921 Jefferson Davis Highway, Arlington, VA.
Electronic comments can be sent directly to EPA at:
Electronic comments must be submitted as an ASCII file avoiding the
use of special characters and any form of encryption.
The official record for this proposal, as well as the public
version, as described above will be kept in paper form. Accordingly,
EPA will transfer all comments received electronically into printed,
paper form as they are received and will place the paper copies in the
official rulemaking record which will also include all comments
submitted directly in writing. The official rulemaking record is the
paper record maintained at the address in ADDRESSES at the beginning of
Under Executive Order 12866 (58 FR 51735, October 4, 1993), the
Agency must determine whether the regulatory action is "significant"
and therefore subject to all the requirements of the Executive Order
(i.e., Regulatory Impact Analysis, review by the Office of Management
and Budget (OMB)). Under section 3(f), the order defines
"significant" as those actions likely to lead to a rule (1) having an
annual effect on the economy of $100 million or more, or adversely and
materially affecting a sector of the economy, productivity,
competition, jobs, the environment, public health or safety, or State,
local or tribal governments or communities (also known as
"economically significant"); (2) creating serious inconsistency or
otherwise interfering with an action taken or planned by another
agency; (3) materially altering the budgetary impacts of entitlement,
grants, user fees, or loan programs; or (4) raising novel legal or
policy issues arising out of legal mandates, the President's
priorities, or the principles set forth in this Executive Order.
Pursuant to the terms of this Executive Order, EPA has determined
that this rule is not "significant" and is therefore not subject to
In addition, this action does not impose any enforceable duty, or
contain any "unfunded mandates" as described in Title II of the
Unfunded Mandates Reform Act of 1995 (Pub. L. 104-4), or require prior
consultation as specified by Executive Order 12875 (58 FR 58093,
October 28, 1993), entitled Enhancing the Intergovernmental
Partnership, or special consideration as required by Executive Order
12898 (59 FR 7629, February 16, 1994).
Pursuant to the requirements of the Regulatory Flexibility Act
(Pub. L. 96-354, 94 Stat. 1164, 5 U.S.C. 601-612), the Administrator
has determined that regulations establishing new tolerances or raising
tolerance levels or establishing exemptions from tolerance
requirements, or establishing or raising food additive regulations do
not have a significant economic impact on a substantial number of small
entities. A certification statement to this effect was published in the
Federal Register of May 4, 1981 (46 FR 24950).
List of Subjects in 40 CFR Parts 180 and 186
Environmental protection, Administrative practice and procedure,
Agricultural commodities, Animal feed, Food additive, Pesticides and
pests, Reporting and recordkeeping requirements.
Dated: April 30, 1996.
Stephen L. Johnson,
Director, Registration Division, Office of Pesticide Programs.
Therefore, it is proposed that chapter I of title 40 be amended as
1. In part 180:
a. The authority citation for part 180 continues to read as
Authority: 21 U.S.C. 346a and 371.
b. In Sec. 180.145, by adding a commodity to paragraph (a) in the
table therein and deleting paragraph (c) to read as follows:
Sec. 180.145 Fluoride compounds; tolerances for residues.
(a) * * *
Commodity Parts per million
* * * * *
* * * * *
* * * * *
2. In part 186:
a. The authority citation for part 186 continues to read as
Authority: 21 U.S.C. 348.
b. Section 186.3375 is revised to read as follows:
Sec. 186.3375 Fluorine compounds.
A tolerance is established for residues of the insecticidal
fluorine compounds cryolite and synthetic cryolite (sodium aluminum
fluoride) in the following ready-to-eat animal feed resulting from
application of the compounds to growing crops:
Commodity Parts per million
Potatoes, waste from processing 22.0