[Federal Register Volume 66, Number 221 (Thursday, November 15, 2001)]
[Notices]
[Pages 57446-57450]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 01-28637]


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ENVIRONMENTAL PROTECTION AGENCY

[PF-1054; FRL-6809-6]


Notice of Filing a Pesticide Petition to Establish a Tolerance 
for a Certain Pesticide Chemical in or on Food

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice.

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SUMMARY:  This notice announces the initial filing of a pesticide 
petition proposing the establishment of regulations for residues of a 
certain pesticide chemical in or on various food commodities.

DATES: Comments, identified by docket control number PF-1054, must be 
received on or before December 17, 2001.

ADDRESSES: Comments may be submitted by mail, electronically, or in 
person. Please follow the detailed instructions for each method as 
provided in Unit I.C. of the SUPPLEMENTARY INFORMATION. To ensure 
proper receipt by EPA, it is imperative that you identify docket 
control number PF-1054, in the subject line on the first page of your 
response.

FOR FURTHER INFORMATION CONTACT:  By mail: Cynthia Giles-Parker, 
Fungicide Branch, Registration Division (7505C), Office of Pesticide 
Programs, Environmental Protection Agency, 1200

[[Page 57447]]

Pennsylvania Ave., NW., Washington, DC 20460; telephone number: (703) 
305-7740; e-mail address: [email protected].

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this Action Apply to Me?

    You may be affected by this action if you are an agricultural 
producer, food manufacturer or pesticide manufacturer. Potentially 
affected categories and entities may include, but are not limited to:

------------------------------------------------------------------------
                                                          Examples of
           Categories                 NAICS codes         potentially
                                                       affected entities
------------------------------------------------------------------------
Industry                          111                 Crop production
                                  112                 Animal production
                                  311                 Food manufacturing
                                  32532               Pesticide
                                                       manufacturing
------------------------------------------------------------------------

     This listing is not intended to be exhaustive, but rather provides 
a guide for readers regarding entities likely to be affected by this 
action. Other types of entities not listed in the table could also be 
affected. The North American Industrial Classification System (NAICS) 
codes have been provided to assist you and others in determining 
whether or not this action might apply to certain entities. If you have 
questions regarding the applicability of this action to a particular 
entity, consult the person listed under FOR FURTHER INFORMATION 
CONTACT.

B. How Can I Get Additional Information, Including Copies of this 
Document and Other Related Documents?

    1. Electronically. You may obtain electronic copies of this 
document, and certain other related documents that might be available 
electronically, from the EPA Internet Home Page at http://www.epa.gov/. 
To access this document, on the Home Page select ``Laws and 
Regulations,'' ``Regulations and Proposed Rules,'' and then look up the 
entry for this document under the ``Federal Register--Environmental 
Documents.'' You can also go directly to the Federal Register listings 
at http://www.epa.gov/fedrgstr/.
    2. In person. The Agency has established an official record for 
this action under docket control number PF-1054. The official record 
consists of the documents specifically referenced in this action, any 
public comments received during an applicable comment period, and other 
information related to this action, including any information claimed 
as confidential business information (CBI). This official record 
includes the documents that are physically located in the docket, as 
well as the documents that are referenced in those documents. The 
public version of the official record does not include any information 
claimed as CBI. The public version of the official record, which 
includes printed, paper versions of any electronic comments submitted 
during an applicable comment period, is available for inspection in the 
Public Information and Records Integrity Branch (PIRIB), Rm. 119, 
Crystal Mall #2, 1921 Jefferson Davis Highway, Arlington, VA, from 8:30 
a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The 
PIRIB telephone number is (703) 305-5805.

C. How and to Whom Do I Submit Comments?

     You may submit comments through the mail, in person, or 
electronically. To ensure proper receipt by EPA, it is imperative that 
you identify docket control number PF-1054, in the subject line on the 
first page of your response.
    1. By mail. Submit your comments to: Public Information and Records 
Integrity Branch (PIRIB), Information Resources and Services Division 
(7502C), Office of Pesticide Programs (OPP), Environmental Protection 
Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460.
    2. In person or by courier. Deliver your comments to: Public 
Information and Records Integrity Branch (PIRIB), Information Resources 
and Services Division (7502C), Office of Pesticide Programs (OPP), 
Environmental Protection Agency, Rm. 119, Crystal Mall #2, 1921 
Jefferson Davis Highway, Arlington, VA. The PIRIB is open from 8:30 
a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The 
PIRIB telephone number is (703) 305-5805.
    3. Electronically. You may submit your comments electronically by 
e-mail to: [email protected], or you can submit a computer disk as 
described above. Do not submit any information electronically that you 
consider to be CBI. Avoid the use of special characters and any form of 
encryption. Electronic submissions will be accepted in Wordperfect 6.1/
8.0 or ASCII file format. All comments in electronic form must be 
identified by docket control number PF-1054. Electronic comments may 
also be filed online at many Federal Depository Libraries.

D. How Should I Handle CBI That I Want to Submit to the Agency?

     Do not submit any information electronically that you consider to 
be CBI. You may claim information that you submit to EPA in response to 
this document as CBI by marking any part or all of that information as 
CBI. Information so marked will not be disclosed except in accordance 
with procedures set forth in 40 CFR part 2. In addition to one complete 
version of the comment that includes any information claimed as CBI, a 
copy of the comment that does not contain the information claimed as 
CBI must be submitted for inclusion in the public version of the 
official record. Information not marked confidential will be included 
in the public version of the official record without prior notice. If 
you have any questions about CBI or the procedures for claiming CBI, 
please consult the person identified under FOR FURTHER INFORMATION 
CONTACT.

E. What Should I Consider as I Prepare My Comments for EPA?

     You may find the following suggestions helpful for preparing your 
comments:
    1. Explain your views as clearly as possible.
    2. Describe any assumptions that you used.
    3. Provide copies of any technical information and/or data you used 
that support your views.
    4. If you estimate potential burden or costs, explain how you 
arrived at the estimate that you provide.
    5. Provide specific examples to illustrate your concerns.
    6. Make sure to submit your comments by the deadline in this 
notice.
    7. To ensure proper receipt by EPA, be sure to identify the docket 
control number assigned to this action in the subject line on the first 
page of your response. You may also provide the name, date, and Federal 
Register citation.

II. What Action is the Agency Taking?

     EPA has received a pesticide petition as follows proposing the 
establishment and/or amendment of regulations for residues of a certain 
pesticide chemical in or on various food commodities under section 408 
of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a. 
EPA has determined that this petition contains data or information 
regarding the elements set forth in section 408(d)(2); however, EPA has 
not fully evaluated the sufficiency

[[Page 57448]]

of the submitted data at this time or whether the data support granting 
of the petition. Additional data may be needed before EPA rules on the 
petition.

List of Subjects

     Environmental protection, Agricultural commodities, Feed 
additives, Food additives, Pesticides and pests, Reporting and 
recordkeeping requirements.


    Dated: October 30, 2001.

 Peter Caulkins,
Acting Director, Registration Division, Office of Pesticide Programs.

Summary of Petition

     The petitioner summary of the pesticide petition is printed below 
as required by section 408(d)(3) of the FFDCA. The summary of the 
petition was prepared by the petitioner and represents the view of the 
petitioners. EPA is publishing the petition summary verbatim without 
editing it in any way. The petition summary announces the availability 
of a description of the analytical methods available to EPA for the 
detection and measurement of the pesticide chemical residues or an 
explanation of why no such method is needed.

 PP 1F6250

    EPA has received a pesticide petition (PP 1F6250) from BASF 
Corporation, P. O. Box 13528, Research Triangle Park, NC 27709-3528 
proposing, pursuant to section 408(d) of the FFDCA, 21 U.S.C. 346a(d), 
to amend 40 CFR part 180 by establishing tolerances for residues of the 
plant growth regulator mepiquat resulting from the use of mepiquat 
chloride (N,N-dimethylpiperdinium chloride) or mepiquat pentaborate 
(N,N-dimethylpiperidinium pentaborate hemi-hydrate) in or on the 
following raw agricultural and processed commodities: Cottonseed at 2.0 
parts per million (ppm); cotton, gin by-products at 6.0 ppm, and meat 
byproducts of cattle, goat, hog, horse, and sheep at 0.1 ppm. EPA has 
determined that the petition contains data or information regarding the 
elements set forth in section 408(d)(2) of the FFDCA; however, EPA has 
not fully evaluated the sufficiency of the submitted data at this time 
or whether the data support granting of the petition. Additional data 
may be needed before EPA rules on the petition.

A. Residue Chemistry

    1. Plant metabolism. The metabolism of mepiquat chloride in plants 
and animals is well understood. Based on the identical dissociation 
behavior of mepiquat pentaborate and mepiquat chloride, the nature of 
the residue for mepiquat pentaborate would be the same as that for 
mepiquat chloride (based on analysis of the mepiquat cation). Thus, the 
nature of residue for mepiquat pentaborate in cotton is supported by 
the mepiquat chloride studies available in cotton. The residue of 
concern from mepiquat pentaborate use in cotton consists only of the 
parent compound.
    2. Analytical method. An adequate analytical method for enforcement 
of the tolerances exists. The analytical method used for quantitative 
determinations was designed to measure mepiquat chloride or mepiquat 
pentaborate residues present as mepiquat cation. The metabolism of 
mepiquat chloride in plants and animals is well understood. Based on 
the identical dissociation behavior of mepiquat pentaborate and 
mepiquat chloride, the nature of the residue for mepiquat pentaborate 
would be the same as that for mepiquat chloride (based on analysis of 
the mepiquat cation). Thus, the nature of residue for mepiquat 
pentaborate in cotton is supported by the mepiquat chloride studies 
available in cotton. The residue of concern from mepiquat pentaborate 
use in cotton consists only of the parent compound.
    3. Magnitude of residues. Adequate field trial data are available 
to support the established tolerance of 2 ppm mepiquat for cottonseed. 
The field trials supporting mepiquat chloride will adequately support 
the establishment of the tolerance for mepiquat pentaborate (as 
mepiquat).

B. Toxicological Profile

     Since the tolerance for mepiquat pentaborate is based on an 
expression as mepiquat, BASF is relying on the data for mepiquat 
chloride to support the requirement for all toxicological studies 
except for the acute studies. Acute toxicology studies were conducted 
with mepiquat pentaborate technical in support of the end use product. 
The mepiquat chloride data base is also used in support of the risk 
assessments presented in this document.
    1. Acute toxicity. Based on the acute toxicity data, mepiquat 
pentaborate does not pose any acute toxicity risks. The acute 
toxicology studies place mepiquat pentaborate in toxicity category III 
for acute oral toxicity, acute dermal, acute inhalation toxicity, and 
primary eye irritation. The primary dermal irritation for mepiquat 
pentaborate is in toxicity category IV and mepiquat pentaborate is not 
a skin sensitizer.
    2. Genotoxicty. An Ames assay using mepiquat chloride was negative 
for genotoxicity. A chromosome aberration assay in Chinese Hamster 
Ovary cells was performed up to the limit dose of 5.0 milligrams/
milliliter (mg/mL) without seeing evidence of genotoxicity. An 
Unscheduled DNA Synthesis assay was performed using primary rat 
hepatocyte cultures up to a limit dose of 5.0 mg/ml without seeing 
evidence of genotoxicity.
    3. Reproductive and developmental toxicity. In a 2-generation 
reproductive toxicity study, Wistar rats were fed mepiquat chloride in 
their diets at concentrations of 0, 500, 1,500, or 5,000 parts per 
million (ppm) for 10 weeks (F0) or 14 weeks (F1) before mating, and 
during mating, gestation, and lactation. The F0 parents were mated a 
second time 2 weeks after weaning the first litter. The doses 
corresponding to the dietary concentrations are 51.2 and 48.6, 153.1 
and 146.6, and 499.3 and 574.5 milligrams/kilograms/day (mg/kg/day), 
respectively for F0 and F1 males and 54.0 and 53.3, 163.6 and 162.0, 
and 530.0 and 626.5 mg/kg/day, respectively for F0 and F1 females. The 
lowest observed adverse effect level (LOAEL) for systemic toxicity is 
5,000 ppm (499 mg/kg/day) for male and female rats based on 
neurological impairment, decreased body weight and body weight gain in 
the adults, and retarded growth of F0 and F1 pups. The corresponding no 
observed adverse effect level (NOAEL) is 1,500 ppm (147 mg/kg/day). The 
OPP's Reference Dose (RfD)/Peer Review Committee concluded on May 2, 
1996, that, because of the retarded growth of the pups in the 5,000 ppm 
(499 mg/kg/day) group, the systemic NOAEL of 1,500 ppm (147 mg/kg/day) 
would also be regarded as the reproductive NOAEL.
    4. Subchronic toxicity. Two 90-day feeding studies in the rat and a 
90-day feeding study in the dog are available. The first rat study saw 
no compound-related adverse effects at the high dose tested (HDT) of 
4,632 ppm (330 mg/kg/day). Thus, a second study was performed with only 
a control and 12,000 ppm (889 mg/kg/day) dose group. Adverse effects 
were seen in this study and so the rodent subchronic LOAEL/NOAEL is 
12,000/4,632 ppm (889/330 mg/kg/day). A subchronic dog study found a 
LOAEL/NOAEL of 3,000/1,000 ppm (95.3/32.4 mg/kg/day).
    5. Chronic toxicity. On May 2, 1996, the OPP's RfD/Peer Review 
Committee recommended that the RfD for mepiquat chloride be established 
at 0.6 mg/kg/day. This value was based on the systemic NOAEL of 1,800 
ppm (58.4 mg/kg/day) from the 1-year dog feeding

[[Page 57449]]

study and the uncertainty factor (UF) of 100.
    i. Chronic feeding--nonrodent. In a chronic toxicity study, 
mepiquat chloride (99.5%) was administered to beagle dogs in the diet 
at dose levels of 0, 200, 600 or 1,800 ppm (0, 6.3, 19.9 or 58.4 mg/kg/
day, respectively) for 12 months. There were no significant treatment-
related effects. In order to establish a LOAEL, a second chronic 
toxicity study was conducted at dose levels of 0 or 6,000 ppm (170 mg/
kg/day) for 12 months. Based on the results of the two chronic dog 
studies, the NOAEL is 1,800 ppm (58.4 mg/kg/day) and the LOAEL is 6,000 
ppm (170 mg/kg/day). This endpoint is used for the acute dietary and 
chronic RfD.
    ii. Chronic feeding--rats. In a chronic feeding study, mepiquat 
chloride (58%) was administered for 24 months in the diet to Wistar 
rats at concentrations of 0, 290, 2,316, or 5,790 ppm (active 
ingredient), equivalent to doses of 0, 13, 106, 268 mg/kg/day for males 
and 0, 18, 146, or 371 mg/kg/day for females, respectively. The NOAEL 
is 2,316 ppm (105 mg/kg/day). The LOAEL is 5,790 ppm (268 mg/kg/day).
    iii. Carcinogenic effects. The carcinogenic potential of mepiquat 
chloride was evaluated by the OPP's RfD/Peer Review Committee on May 2, 
1996. The Committee classified mepiquat chloride into Group E (evidence 
of noncarcinogenicity for humans), based on a lack of carcinogenicity 
in acceptable studies with two animal species, rat and mouse.
    6. Animal metabolism. In a metabolism study, mepiquat chloride, 
labeled with C14 (radiochemical purity: 98%), was 
administered to young adult Sprague-Dawley rats either intravenously or 
orally. Mepiquat chloride was absorbed rapidly from the stomach, 
distributed evenly in the intra-and extracellular compartments of the 
blood, demonstrated high bioavailability via the oral route, was 
excreted mostly in urine, and did not accumulate in tissues. Urine, 
feces and bile samples from various treatments were used for studies of 
the metabolic fate of mepiquat chloride. In all cases, only the 
unchanged compound could be detected. Therefore, there was no 
biotransformation of mepiquat chloride in vivo. The potential 
metabolites, such as 1-methylpiperidine or piperidine, were not 
detected.
    7. Metabolite toxicology. No additional studies were required for 
metabolite toxicology.
    8. Endocrine disruption. No specific tests have been conducted with 
mepiquat to determine whether the chemical may have an endocrine like 
effect in humans. However, there were no significant findings in other 
relevant tests (developmental and reproductive toxicity tests) which 
would suggest that mepiquat produces endocrine like effects.

C. Aggregate Exposure

    1. Dietary exposure. The mepiquat chloride RED indicates that EPA 
has found no dietary risks of concern for mepiquat chloride for the 
general U.S. population nor any subgroup. Pursuant to the requirements 
under the Food Quality Protection Act (FQPA) of 1996, the Agency has 
determined that the use of mepiquat will not pose dietary risks to 
infants and children due primarily to the chemical's low toxicity and 
its low usage rate.
    i. Food--a. Chronic dietary exposure. A Dietary Risk Evaluation 
System (DRES) chronic exposure analysis was conducted by EPA for the 
RED. The analysis was performed using tolerance level residues and the 
three expired grape and raisin temporary tolerances previously 
established for an Experimental Use Permit and an assumption of 100% 
crop treated to estimate the Theoretical Maximum Residue Contribution 
(TMRC) for the general population and 22 subgroups. No Anticipated 
Residue (AR) information was used in this analysis. Existing tolerances 
result in a Theoretical Maximum Residue Contribution (TMRC) which 
represents less than 1% of the RfD for the U.S. general population and 
each of the 22 subgroups, including non-nursing infants (< 1-year old). 
The TMRC calculation results in a significant overestimate of human 
dietary exposure.
     Another dietary assessment was performed, by the Agency, for 
mepiquat chloride assuming tolerance levels residues and 100% crop 
treared on cotton, grape, meat, fat, and meat by-products (D260557, 
November 1, 1999, W. Cutchin). Risk estimates for exposure to mepiquat 
chloride were below HED's level of concern.
     These chronic analyses for mepiquat are worst case estimates of 
dietary exposure with all residues at tolerance level and 100% of the 
commodities assumed to be treated with mepiquat. Based on the risk 
estimates calculated in these analyses, it has been concluded that 
dietary exposure to mepiquat does not pose any risk concerns.
    b. Acute dietary exposure. The margin of exposure (MOE) is a ratio 
of the NOAEL to the exposure. Generally, the Agency concludes that 
there is no dietary concern when the acute dietary margins of exposure 
are greater than 100. The results of the acute analysis conducted for 
the RED indicate that mepiquat in the diet represents no serious risk 
concern for acute exposure. All MOEs were well above the Agency's level 
of concern for acute dietary risk (ranging from a low of 3,893 for 
infants to a high of 29,200 for females 13+ years old).
    ii. Drinking water. Neither a Maximum Contaminant Level (MCL) nor a 
Hazard Advisory (HA) has been established for mepiquat. According to 
the EPA's Pesticides in Ground Water Database, there have been no 
mepiquatchloride detections reported in monitoring wells. Based on its 
low application rate, relatively rapid degradation rate, and soil 
binding ability, the Agency does not expect mepiquat to contaminate 
ground water or surface water. Consequently neither a chronic or acute 
drinking water assessment was performed.
    2. Non-dietary exposure. Mepiquat has no residential or other non-
occupational uses that might result in exposures to humans.

D. Cumulative Effects

    EPA has addressed the issue of the potential risk from the 
cumulative effects of mepiquat chloride and other pesticides with a 
common mechanism of toxicity in the RED document. In assessing the 
potential risks, the Agency first considered structural similarities 
and common effects that exist between mepiquat chloride and other 
related compounds such as paraquat, diquat and difenzoquat. The Agency 
then considered other compounds which could potentially result in 
neurotoxic effects similar to mepiquat chloride.
     With one substance, difenzoquat, there appears to be similar 
neurotoxic effects. The Agency has concluded that the cumulative 
effects from the combined dietary exposure to mepiquat and difenzoquat 
would be virtually nil because the chronic dietary exposure for all 
population subgroups is less than 1% of the RfD for both difenzoquat 
and mepiquat chloride. The acute dietary MOE range for difenzoquat is 
16,000 to 50,000 while the acute dietary MOE range for mepiquat 
chloride is 3,900 to 29,000.
     In evaluating other chemicals with neurotoxic effects similar to 
mepiquat chloride, the Agency determined that it is unlikely that these 
other chemicals share a common mode/mechanism of toxicity with mepiquat 
chloride, or that cumulative risk assessment would be required. 
Although the mode/mechanism of toxicity of mepiquat chloride has not 
been well defined, the effects noted on the nervous system

[[Page 57450]]

appear to be secondary to general systemic toxicity that occurs at high 
dose levels. Based on available data and structure-activity 
relationship analyses, mepiquat chloride would be considered to have 
minimal neurotoxic activity.

E. Safety Determination

    1. U.S. population. In the mepiquat chloride RED, EPA has 
determined that the established tolerances for mepiquat chloride meet 
the safety standards under the FQPA amendments to section 408(b)(2)(D) 
for the general population. In reaching this determination, EPA has 
considered the available information on the aggregate exposures (both 
acute and chronic) from the feed use on cotton, as well as the 
possibility of cumulative effects from mepiquat chloride and other 
chemicals with a similar mode/mechanism of toxicity. BASF does not 
believe that the use of mepiquat pentaborate on cotton alters these 
conclusions.
     Since there are no residential or lawn uses of mepiquat, no dermal 
or inhalation exposure is expected in and around the home. No acute 
toxicity endpoints of concern have been identified for mepiquat.
    In assessing chronic dietary risk, EPA estimates that mepiquat 
residues in food account for <1% of the RfD and residues in drinking 
water are not expected. Thus, the aggregate exposures from all sources 
of mepiquat (in this case, only dietary is relevant) account for <1% of 
the RfD for the general population. Therefore, the Agency concludes 
that aggregate risks for the general population resulting from mepiquat 
uses are not of concern.
    In evaluating the potential for cumulative effects, EPA compared 
structural similarities and toxic effects seen in mepiquat chloride 
studies with other related compounds. With one substance, difenzoquat, 
there appears to be similar neurotoxic effects. However, the Agency has 
concluded that the cumulative effects from the combined dietary 
exposure to mepiquat chloride and difenzoquat would be virtually nil 
because the chronic dietary exposure for all population subgroups is 
less than 1% of the RfD for both difenzoquat and mepiquat chloride.
    2. Infants and children. In the RED, EPA has determined that the 
established tolerances for mepiquat chloride (including the previously 
established temporary tolerances for grapes) meet the safety standard 
under the FQPA amendment to section 408(b)(2)(C) for infants and 
children. The safety determination for infants and children considers 
the factors noted above for the general population, but also, takes 
into account the possibility of increased dietary exposure due to the 
specific consumption patterns of infants and children, as well as the 
possibility of increased susceptibility to the toxic effects of 
mepiquat chloride residues in this population subgroup.
    In the developmental studies, effects were seen in the fetuses only 
at the same or higher dose levels than effects on the mothers. In the 
reproduction study, no effects on reproductive performance were seen. 
Also, because the NOAELs from the developmental and reproduction 
studies were equal to or greater than the NOAEL used for establishing 
the RfD, EPA concludes that it is unlikely that there is additional 
risk concern for immature or developing organisms. Finally, the Agency 
has no epidemiological information suggesting special sensitivity of 
infants and children to mepiquat chloride. Therefore, EPA finds that 
the uncertainty factor (100X) routinely used in RfD calculations is 
adequately protective of infants and children, and an additional 
uncertainty factor is not warranted for mepiquat.
    EPA estimates that mepiquat residues in the diet of infants and 
children account for less than 1% of the RfD and residues in drinking 
water are not expected. Thus, the chronic aggregate exposure from all 
sources of mepiquat account for less than 1% for infants and children. 
The acute dietary MOE for infants and children exposed to mepiquat is 
3,893. Therefore, the Agency concludes that aggregate risks for infants 
and children resulting from mepiquat uses are not of concern.

F. International Tolerances

    There are no Codex, Canadian, or Mexican tolerances established for 
mepiquat on cotton. Thus, international harmonization is not an issue 
for these tolerances.
[FR Doc. 01-28637 Filed 11-14-01; 8:45 am]
BILLING CODE 6560-50-S