[Federal Register Volume 65, Number 76 (Wednesday, April 19, 2000)]
[Notices]
[Pages 20972-20976]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-9796]



[[Page 20972]]

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ENVIRONMENTAL PROTECTION AGENCY

[PF-936; FRL-6554-3]


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

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice.

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SUMMARY: This notice announces the amendment of a pesticide petition 
(PP7E4920), 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-936, must be 
received on or before May 19, 2000.

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-936 in the subject line on the first page of your 
response.

FOR FURTHER INFORMATION CONTACT:  By mail: Treva C. Alston, 
Registration Support Branch, Registration Division (7505C), Office of 
Pesticide Programs, Environmental Protection Agency, Ariel Rios Bldg., 
1200 Pennsylvania Ave., NW., Washington, DC 20460; telephone number: 
(703) 308-8373; e-mail address: <a href="/cdn-cgi/l/email-protection#1a7b76696e7574346e687f6c7b5a7f6a7b347d756c"><span class="__cf_email__" data-cfemail="2948455a5d4647075d5b4c5f48694c5948074e465f">[email protected]</span></a>.

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'' 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-936. 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-936 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, Ariel Rios Bldg., 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: ``<a href="/cdn-cgi/l/email-protection#5d322d2d7039323e3638291d382d3c733a322b"><span class="__cf_email__" data-cfemail="bad5caca97ded5d9d1dfcefadfcadb94ddd5cc">[email protected]</span></a>,'' 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-936. 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.

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    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 Comestic 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 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: April 10, 2000.
James Jones,
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 
petitioner. 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.

Novartis Crop Protection, Inc.

7E4920

Amended Pesticide Petition

    On April 15, 1998, EPA published a notice that it had received a 
pesticide petition (7E4920) from Novartis Crop Protection, Inc., P.O. 
Box 18300, Greensboro, NC 27419, proposing tolerances for the herbicide 
safener cloquintocet-mexyl acetic acid, (5-chloro-8-quinolinyl)oxy-,1-
methylhexylester; CGA-185072) in or on raw agricultural commodities 
(RACs) of wheat. EPA has received an amendment to PP 7E4920 from 
Novartis Crop Protection, Inc., proposing, pursuant to section 408(d) 
of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), 
to amend 40 CFR part 180 to increase, as requested by EPA, the original 
proposed tolerances; thereby establishing tolerances for the combined 
residues of cloquintocet-mexyl and its acid metabolite, CGA-153433 (5-
chloro-8-quinolinyl)oxy-acetic acid), in or on the RACs wheat, grain at 
0.1 part per million (ppm); wheat, forage at 0.1 ppm; wheat, hay at 0.1 
ppm; and wheat, straw 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 cloquintocet-mexyl in wheat 
has been investigated. Total residues in all crop samples are low. 
Metabolism involves primarily rapid hydrolysis of the parent to the 
resulting acid followed by conjugation.
    2. Analytical method. Novartis has submitted practical analytical 
methods for the determination of cloquintocet-mexyl and its major plant 
metabolite CGA-153433 in wheat RACs. Cloquintocet-mexyl is extracted 
from crops with acetonitrile, cleaned up by solvent partition and solid 
phase extraction and determined by column switching high performance 
liquid chromotography (HPLC) with ultra violet (UV) detection. CGA-
153433 is extracted from crops with an acetone-buffer (pH=3) solution, 
cleaned up by solvent partition and solid phase extraction, and 
determined by HPLC with UV detection. The limits of quantification 
(LOQ) for the methods are 0.02 ppm for cloquintocet-mexyl in forage and 
grain, 0.05 ppm for cloquintocet-mexyl in straw, and 0.05 ppm for CGA-
153433 in forage, straw and grain.
    3. Magnitude of residues. Both Canadian and United States spring 
wheat residue trials were conducted. Twelve residue trials were 
conducted from 1989-1992 in the major spring wheat growing areas of 
Manitoba, Alberta, and Saskatchewan, which share compatible crop zones 
with the major spring wheat growing areas of the United States (MT, ND, 
SD, MN). Nine trials were conducted in 1989-91 with a tank mix of 
clodinafop-propargyl active ingredient (a.i.) and the cloquintocet-
mexyl safener as separate EC formulations and three trials in 1992 were 
conducted with clodinafop-propargyl and the cloquintocet-mexyl safener 
as a pre-pack EC formulation. All trials had a single post-emergence 
application of CGA-185072 at a rate of 20 gram active ingredient/
hectacre (g a.i./ha). In 1998, an additional six spring wheat trials 
were conducted in the major growing areas of the United States. In 
these trials, cloquintocet-mexyl was applied as a safener in 
conjunction with clodinafop-propargyl as a 240EC formulation. The rate 
of cloquintocet-mexyl applied was 17 g a.i./ha as a single application. 
Samples of 30-day forage and hay, and mature straw and grain treated 60 
days prior to harvest were taken for analysis. Grain treated at an 
exaggerated rate in one trial was processed under simulated commercial 
processing conditions. At pre-harvest intervals (PHIs) of 55-97 days, 
no detectable residues of cloquintocet-mexyl or its metabolite CGA-
153433 were found in mature grain or straw from these trials. Separate 
decline studies three on green forage showed no detectable residues of 
cloquintocet-mexyl or CGA-153433 at 3 days after application. Freezer 
storage stability studies indicated reasonable stability of both 
analytes for a period of 1 year, with cloquintocet-mexyl declining to 
83% in grain and 67% in straw after 2 years, while CGA-153433 was 
stable for at least 2 years.

B. Toxicological Profile

    1. Acute toxicity. The acute oral and dermal LD<INF>50</INF> values 
for cloquintocet-mexyl are greater than 2,000 milligrams/kilograms (mg/
kg) for rats of both sexes, respectively. Its acute inhalation 
LC<INF>50</INF> in the rat is greater than 0.935 milligram/liter (mg/
L), the highest attainable concentration. Cloquintocet-mexyl is 
slightly irritating to the eyes, minimally irritating to the skin of 
rabbits, but was found to be sensitizing to the skin of the guinea pig. 
This technical will carry the EPA signal word ``Caution.''

[[Page 20974]]

    2. Genotoxicity. The mutagenic potential of cloquintocet-mexyl was 
investigated in six independent studies covering different end points 
in eukaryotes and prokaryotes in vivo and in vitro. These tests 
included: Ames reverse mutation with Salmonella typhimurium and Chinese 
hamster V79 cells in vitro; chromosomal aberrations using human 
lymphocytes in vitro and the mouse micronucleus test in vivo; and DNA 
repair using rat hepatocytes and human fibroblasts in vitro. 
Cloquintocet-mexyl was found to be negative in all these tests and, 
therefore, is considered devoid of any genotoxic potential at the 
levels of specific genes, chromosomes or DNA primary structure.
    3. Reproductive and developmental toxicity. Dietary administration 
of cloquintocet-mexyl over 2 generations at levels as high as 10,000 
part per million (ppm) did not affect mating performance, fertility, or 
litter sizes, but a slightly reduced body weight development of adults 
and pups was noted at this level. The target organ was the kidney in 
adults and pups. The treatment had no effect on reproductive organs. 
The no observed adverse effect level (NOAEL) for toxicity to the 
offspring and parental toxicity was 5,000 ppm, corresponding to a mean 
daily intake of 370 to 422 mg/kg/day of cloquintocet-mexyl. The 
reproductive NOAEL was > 10,000 ppm (722 mg/kg/day).
    In a developmental toxicity study in rats, the highest dose level 
of 400 mg/kg bwt day resulted in reduced body weight gain of the dams 
and signs of retarded fetal development. No teratogenic activity of the 
test article was detected. The NOAEL for dams and fetuses was 100 mg/kg 
bwt day.
    In a developmental toxicity study in rabbits, mortality was 
observed in dams at dose levels of 300 mg/kg. No teratogenic effects 
were noted. Fetuses showed signs of slightly retarded development. The 
NOAEL for both dams and fetuses was 60 mg/kg bwt day. EPA's Hazard 
Identification Assessment Review Committee (HIARC) suggested the 
maternal NOAEL was 60 mg/kg, but the developmental toxicity NOAEL is > 
300 mg/kg/day.
    4. Subchronic toxicity. In a 90-day study, rats fed 6,000 ppm 
exhibited reduced body weight gain and one male died with acute 
nephritis and inflamed urinary bladder. Reduced liver and kidney 
weights were observed in males fed 1,000 and 6,000 and in females fed 
6,000 ppm. Target organs were identified to be kidney and urinary 
bladder. The NOAEL was 150 ppm (9.66 mg/kg in males and 10.2 mg/kg in 
females). EPA's HIARC concluded that the NOAEL in females was 6,000 ppm 
(407 mg/kg/day).
    In a 90-day study in beagle dogs, a level of 40,000 ppm resulted in 
deterioration of general condition so that the feeding level was 
reduced in a stepwise fashion to 15,000 ppm. Anemia was noted at 15,000 
and 1,000 ppm. The NOAEL of 100 ppm was equivalent to a mean daily 
intake of 2.9 mg/kg in males and females.
    5. Chronic toxicity. In a 12-month feeding study in dogs, 15,000 
ppm resulted in inappetence and body weight loss. As a result, this 
feeding level was adjusted to 10,000 ppm after 2 weeks. Animals fed 
this level exhibited anemia and an elevation in blood urea levels. The 
kidney was considered the target organ. The NOAEL of 1,500 ppm was 
equivalent to a mean daily intake of 43.2 mg/kg in males and 44.8 mg/kg 
in females.
    Lifetime dietary administration of cloquintocet-mexyl to mice 
resulted in reduced body weights in both sexes at 5,000 ppm. Overall 
body weight gain was reduced by 17% to 22% in males and females, 
respectively, indicating the MTD was achieved or exceeded. 
Histopathological examination revealed chronic inflammation of the 
urinary bladder. There was no indication of any tumorigenic response 
due to treatment. The NOAEL of 1,000 ppm was equivalent to a mean daily 
dose of 111 mg/kg in males and 102 mg/kg in females.
    Rats were fed a top feeding level of 2,000 ppm, based on the 90-day 
subchonic study, for a lifetime. This feeding level was well-tolerated, 
but produced hyperplasia of the thymus in males at the top dose and 
hyperplasia of the thyroid in females at 1,000 and 2,000 ppm. There was 
no increase in tumors of any type and the total number of tumor-bearing 
animals showed no dose-related trends. The NOAEL of 100 ppm was 
equivalent to a mean daily dose of 4.33 mg/kg in females. EPA's HIARC 
suggested that the NOAEL in male rats was 1,000 ppm (36.4 mg/kg/day).
    6. Carcinogenicity. There is no evidence supporting any oncogenic 
potential associated with cloquincet-mexyl. EPA's HIARC classified 
cloquintocet-mexyl as a ``not likely'' human carcinogen according to 
the proposed guidelines for carcinogen risk assessment.
    7. Animal metabolism. In rats, approximately 50% of an oral dose of 
cloquintocet-mexyl was rapidly absorbed through the gastrointestinal 
tract and excreted via urine and bile. The administered dose was 
excreted independent of sex and was essentially complete within 48 
hours. Ninety-five percent of the excreted dose was associated with one 
metabolite, an acid residue of cloquintocet-mexyl, CGA-153433. 
Simultaneous administration of the cloquintocet-mexyl and clodinafop-
propargyl did not alter the rate of excretion of cloquintocet-mexyl or 
its metabolite pattern.
    8. Metabolite toxicology. At the present time there is no evidence 
which affords an association of the toxicity noted with the highest 
feeding levels of cloquintocet-mexyl with its primary metabolite, CGA-
153433.
    9. Endocrine disruption. A special study was conducted to 
investigate a histological finding of hyperplasia of thyroid gland 
epithelium noted in the female rat in the standard lifetime combined 
chronic toxicity and carcinogenicity study. This study was a 28-day 
oral gavage study with a 28-day recovery period at dose levels as high 
as 400 mg/kg/day or approximately 4,000 ppm. No effect was noted on the 
level of thyroid hormones at any of the treatment levels. Although a 
slight stimulation of the thyroid and an accompanying increase in 
pituitary basophilic cells were noted at the end of 28-days, these 
effects were reversible in the recovery period.

C. Aggregate Exposure

    1. Dietary exposure. Cloquintocet-mexyl is intended as a safener 
for the postemergence herbicide, clodinafop-propargyl, used on wheat. 
The use rate for cloquintocet-mexyl is very low (formulated at a 1:4 
ratio of safener to active ingredient and results from plant metabolism 
and residue studies show that residues are below the detection limit in 
wheat grain and other wheat fractions. The tolerance expression will 
include parent cloquintocet-methyl and the corresponding hydrolysis 
product, CGA-153433, and tolerances are being proposed at 0.1 ppm in 
wheat grain, forage, hay, and straw. No tolerances are proposed for 
secondary residues in animal commodities since residues would be far 
below the LOQ of existing analytical methodology.
    i. Food. Chronic and acute dietary exposure analyses were conducted 
using the dietary exposure evaluation model (DEEM) from Novigen 
Sciences and the 1994-96 Continuing Survey of Food Intake by 
Individuals (CSFII). Chronic and acute tier one dietary assessments 
were made assuming tolerance-level residues and treatment of 100% of 
all planted wheat.
    a. Chronic. Chronic exposure was compared to a reference dose (RfD) 
of 0.04 mg/kg/day which was derived from

[[Page 20975]]

a NOAEL of 4.3 mg/kg/day in a chronic toxicity/carcinogenicity study in 
female rats and a 100x uncertainty factor (UF). Exposure was calculated 
assuming that 100% of crop was treated and residues were at the 
proposed tolerance levels of 0.1 ppm for wheat grain and associated 
fractions. Exposure for the U.S. population was minimal with 0.4% of 
the RfD utilized and this result was the same for the U.S. population 
through all seasons and all ethnic groups. The most sensitive 
subpopulation was children (1-6 years old) with an exposure of 0.9% of 
the chronic RfD. These results are extremely conservative since 
tolerance values were used and are reflective of the maximum 
application rate and minimum PHI. In addition, it was assumed that all 
planted acres are treated. Therefore, there is more than a reasonable 
certainty of no harm resulting from exposure to residues of 
cloquintocet-mexyl.
    b. Acute. Acute exposure was assessed for the female population 
(13+ years) only and was compared to an acute RfD of 1.0 mg/kg/day 
based on a NOAEL of 100 mg/kg/day from a developmental toxicity study 
in rats and a 100x UF. The resulting assessment revealed that exposures 
to all female subpopulations reported in the DEEM were between 0.03%-
0.04% of the RfD at the 95<SUP>th</SUP> percentile of exposure. The 
95<SUP>th</SUP> percentile is the appropriate percentile to consider 
since this assessment is based on tolerance-level residues and 100% of 
crop treated was assumed. Even at the 99.9<SUP>th</SUP> percentile of 
exposure, the results show that females (13-50 years old) utilize only 
0.07% of the acute RfD. EPA's HIARC concluded that no acute dietary 
assessment was necessary for the general population because a suitable 
toxicological endpoint (resulting from a single dose exposure) was not 
identified in either the rat or rabbit developmental studies.
    ii. Drinking water. Another potential route of exposure to residues 
of pesticides includes drinking water. Field and laboratory study 
results have demonstrated that cloquintocet-mexyl and its degradation 
products have minimal potential to reach surface or ground water. Thus, 
drinking water exposure to cloquintocet-mexyl and its degradation 
products was not included in the aggregate risk assessment. Also, since 
cloquintocet-mexyl is not intended for uses other than the agricultural 
use on wheat, there is no potential for non-occupational exposure.
    The estimated exposures of cloquintocet-mexyl and its main 
environmental degradate were combined and the hazards for both 
compounds were based on the RfD values determined for cloquintocet-
mexyl alone. The estimated water concentrations for cloquintocet-mexyl 
and the degradate were estimated, weighted and combined based on 
applications rates adjusted for the maximum concentration of the 
degradate present in the aerobic soil metabolism studies.
    The GENEEC and SCI-GROW models respectively provided the estimated 
surface water and ground water concentrations. The estimated acute 
exposures from drinking surface and ground water were 0.04964 part per 
billion (ppb) and 0.006166 ppb, respectively. The females 13+ years 
sub-population was the only subgroup which was required for the acute 
exposure assessment. The acute exposures for females 13+ years were 
based on 1.0 mg/kg/day. Based on the 95<SUP>th</SUP> percentile acute 
dietary assessment, the females (13+/nursing) was the most exposed 
female sub-population at 3.71E-6 mg/kg/day. This resulted in an acute 
DWLOC of 30,000 ppb. Therefore, the estimated acute surface and ground 
water exposures for cloquintocet-mexyl and its degradate did not exceed 
the exposure allowed by the risk cup. The chronic dietary exposures for 
all sub-populations provided DWLOC values of 224 to 1,396 ppb. The 
estimated chronic exposures from drinking surface and ground water were 
0.00316 ppb and 0.006166 ppb, respectively. Therefore, the estimated 
acute and chronic drinking water exposures of cloquintocet-mexyl and 
its degradate did not exceed the exposures allowed by the risk cup.
    2. Non-dietary exposure. Exposure to cloquintocet-mexyl for the 
mixer/loader/ground-boom/aerial applicator and flagger was calculated 
using the pesticide handlers exposure data base. It was assumed that 
the product would be applied 6 days per year by ground-boom application 
to a maximum of 80 acres per day by the grower, 15 days per year by 
ground-boom application to a maximum of 80 acres per day by the 
commercial ground-boom applicator, and 15 days per year to a maximum of 
350 acres per day by the aerial applicator, at a maximum use rate of 
7.1 grams cloquintocet-mexyl per acre. For purposes of this assessment, 
it was assumed that an applicator would be wearing a long-sleeved shirt 
and long pants and the mixer/loader would, in addition, wear gloves. 
Daily doses were calculated for a 70 kg person assuming 100% dermal 
penetration. Short-term and intermediate-term dermal and inhalation 
risk assessments were performed. Doses and endpoints used for risk 
assessments were based on Agency determined toxicological endpoints 
recommended by the HIARC. The NOAEL of 200 mg/kg/day from the 28-day 
rat dermal toxicity study was used for short-term and intermediate-term 
dermal risk assessments. The NOAEL of 100 mg/kg/day from the 
developmental toxicity study in rats was used for short-term inhalation 
risk assessments. The NOAEL of 4.3 mg/kg/day from the 2-year chronic 
toxicity study in rats was used for intermediate-term risk assessments. 
Based on the use pattern, no long-term dermal or inhalation exposure is 
expected to occur and long-term risk assessments are not required.
    Large margins of exposure (MOE) exist for all occupational exposure 
scenarios. Short-term dermal exposure MOEs ranged from 6.4E+04 for the 
commercial open mixer-loader to 2.8E+06 for the commercial or grower 
groundboom enclosed-cab applicator. Intermediate-term dermal exposure 
MOEs ranged from 1.6E+06 for the commercial open mixer-loader to 
1.7E+08 for the grower ground-boom enclosed-cab applicator. Short-term 
inhalation exposure MOEs ranged from 2.8E+06 for the commercial open 
mixer-loader to 1.3E+08 for the commercial or grower ground-boom 
enclosed-cab applicator. Intermediate-term inhalation exposure MOEs 
ranged from 3.0E+06 for the commercial open mixer-loader to 3.4E+08 for 
the grower ground-boom enclosed-cab applicator.
    Although there are no residential uses of cloquintocet-mexyl, there 
is potential for residential exposure to spray drift resulting from 
aerial application. No standard operating procedure exists for 
performing this risk assessment; however, a very conservative risk 
assessment was performed assuming dermal exposure equal to total 
deposition to outside clothing for a flagger as well as inhalation 
exposure equivalent to a pesticide flagger, as reflected in PHED. A 
dermal absorption factor of 100% and offsite drift of 15% were assumed. 
The area assumed to be adjacent to the sensitive area was one acre. 
Large MOEs exist for this potential exposure scenario. Dermal exposure 
MOEs were 2.4E+07 for a 15 kg child and 1.1E+08 for a 70 kg adult. 
Inhalation MOEs were 1.8E+09 for a 15 kg child and 8.6E+09 for a 70 kg 
adult.

D. Cumulative Effects

    Novartis has considered the potential for a cumulative exposure 
assessment for effects of cloquintocet-mexyl and other substances with 
the same mechanism of toxicity. It is concluded that such a 
determination would be

[[Page 20976]]

inappropriate at this time because of the unique role of cloquintocet-
mexyl as a product-specific safener.

E. Safety Determination

    1. U.S. population. Acute and chronic dietary exposure is minimal 
for cloquintocet-mexyl and corresponding hydrolysis product, CGA-
153433. Both chronic and acute exposure estimates at the 95th 
percentile showed that less than 1.0% of the reference dose is utilized 
in all populations. These exposure estimates are extremely conservative 
and are based on tolerance-level residues and assume all planted acres 
are treated.
    Exposure through the consumption of drinking water is minimal from 
both surface water and ground water model estimates and in all cases 
less than 1% of the risk cup is utilized. The estimated water 
concentrations are very conservative since conservative model 
parameters were assumed.
    There are no residential uses of cloquintocet-mexyl that would 
result in non-dietary exposure. However, there is a remote possibility 
that spray drift resulting from aerial application could lead to 
residential exposure. Since exposure from spray drift would be an 
unlikely event, it is not appropriate to include non-dietary exposure 
into the aggregate assessment. Therefore, it is concluded that there is 
a more than a reasonable certainty that no harm will result from 
aggregate exposure to residues of cloquintocet-mexyl.
    2. Infants and children. In assessing the potential for additional 
sensitivity of infants and children to residues of cloquintocet-mexyl, 
data from developmental toxicity studies in the rat and rabbit and a 2-
generation reproduction study in the rat have been considered. The 
developmental toxicity studies are designed to evaluate adverse effects 
on the developing organism resulting from chemical exposure during 
prenatal development to one or both parents. Reproduction studies 
provide information relating to effects from exposure to a chemical on 
the reproductive capability of mating animals and data on systemic 
toxicity.
    The highest dose level of 400 mg/kg/day in a developmental toxicity 
study in rats resulted in reduced body weight gain of the dams and 
signs of retarded fetal development. No teratogenic activity due to the 
test article was detected. The NOAEL for dams and fetuses was 100 mg/
kg/day. Although mortality was observed in rabbit dams at the dose 
level of 300 mg/kg/day, no teratogenic effects were noted. The maternal 
NOAEL was 60 mg/kg/day, but the developmental NOAEL was > 300 mg/kg/
day.
    Dietary administration of cloquintocet-mexyl over 2-generations at 
levels as high as 10,000 ppm did not affect mating performance, 
fertility, or litter sizes in rats, but a slightly reduced body weight 
development of adults and pups was noted at this level. The target 
organ was kidney in adults and pups. The treatment had no effect on 
reproductive organs. The parental and developmental NOAEL was 5,000 
ppm, corresponding to a mean daily intake of 370 to 422 mg/kg/day of 
cloquintocet-mexyl. The reproductive NOAEL was > 10,000 ppm (722 mg/kg/
day). FFDCA section 408 provides that EPA may apply an additional 
safety factor for infants and children in the case of threshold effects 
to account for prenatal and postnatal toxicity and the completeness of 
the data base. Based on the current toxicological data requirements, 
the data base relative to prenatal and postnatal effects for children 
is complete. EPA's HIARC concluded that there was no concern for an 
increased susceptibility for cloquintocet-mexyl based on the 
reproduction study in rats and the developmental studies in rat and 
rabbit. Further, for cloquintocet-mexyl, the NOAEL of 4.3 mg/kg/day 
from the combined chronic/oncogenicity study in rats, which was used to 
calculate the RfD, is already lower than the developmental NOAEL of 100 
mg/kg/day for the rat developmental toxicity study. Further, the 
developmental and parental NOAEL of 370 mg/kg/day from the 
cloquintocet-mexyl reproduction study is nearly 100 times greater than 
the NOAEL for the combined chronic/oncogenicity rat study. These data 
would indicate that there is no additional sensitivity of infants and 
children to cloquintocet-mexyl. Therefore, it is concluded that an 
additional UF is not warranted to protect the health of infants and 
children from the use of cloquintocet-mexyl.
    Using conservative exposure assumptions, dietary exposure to the 
most sensitive subpopulation, children (1-6 years old), is 0.9% of the 
chronic reference dose (RfD). Chronic dietary exposure to infants (non-
nursing, 1-6 years old) is 0.2% of the chronic RfD. EPA's HIARC 
concluded that no acute dietary assessment was necessary for the 
general population (infants and children) because a suitable 
toxicological endpoint (resulting from a single dose exposure) was not 
identified in either the rat or rabbit developmental studies.
    Although not required, acute dietary exposure to infants and 
children was assessed. Acute exposures for all infants and children at 
the 95<SUP>th</SUP> percentile are less than 1.0% of the acute RfD 
(0.08% of the RfD for the most sensitive subpopulation, children 1-6 
years). Exposures to drinking water for children (1-6 years old) and 
infants utilize less than 1% of the chronic and acute RfD values 
(worst-case surface water estimates). These results show that aggregate 
exposure to residues of cloquintocet-mexyl in the diet and drinking 
water is negligible. Based on the completeness and reliability of the 
toxicity data and the conservative nature of the exposure assumptions, 
it is concluded that there is a more than reasonable certainty that no 
harm will result to infants and children from exposure to residues of 
cloquintocet-mexyl.

F. International Tolerances

    Cloquintocet-mexyl is used as a safener for the herbicide, 
clodinafop-propargyl. There are no Codex Alimentarius Commission 
(CODEX) maximum residue levels (MRLs) established for residues of 
cloquintocet-mexyl in or on RACs.

[FR Doc. 00-9796 Filed 4-18-00; 8:45 am]
BILLING CODE 6560-50-F


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