[Federal Register Volume 65, Number 11 (Tuesday, January 18, 2000)]
[Notices]
[Pages 2612-2617]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-1064]


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ENVIRONMENTAL PROTECTION AGENCY

[PF-913; FRL-6486-4]


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 initial filing of pesticide 
petitions proposing the establishment of regulations for residues of 
certain pesticide chemicals in or on various food commodities.

DATES:  Comments, identified by docket control number PF-913, must be 
received on or before February 17, 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-913 in the subject line on the first page of your 
response.

FOR FURTHER INFORMATION CONTACT:  By mail: Shaja R. Brothers, 
Registration Division (7505C), Office of Pesticide Programs, 
Environmental Protection Agency, 401 M St., SW., Washington, DC 20460; 
telephone number: (703) 308-3194; e-mail address: 
<a href="/cdn-cgi/l/email-protection#eb8999849f838e9998c598838a818aab8e9b8ac58c849d"><span class="__cf_email__" data-cfemail="4022322f34282532336e3328212a21002530216e272f36">[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-913. 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 (CM 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-913 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, 401 M St., SW., 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, CM 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#1e716e6e337a717d757b6a5e7b6e7f30797168"><span class="__cf_email__" data-cfemail="600f10104d040f030b0514200510014e070f16">[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-913. 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

[[Page 2613]]

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 pesticide petitions as follows proposing the 
establishment and/or amendment of regulations for residues of certain 
pesticide chemicals 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 these petitions contain 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 supports granting of the petitions. 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: January 6, 2000.
James Jones,
Director, Registration Division, Office of Pesticide Programs.

Summaries of Petitions

    The petitioner summaries of the pesticide petitions are printed 
below as required by section 408(d)(3) of the FFDCA. The summaries of 
the petitions were prepared by the petitioner and represents the view 
of the petitioners. EPA is publishing the petition summaries verbatim 
without editing them in any way. The petition summaries announce 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.

1. Interregional Project Number 4

 9E6012 and 9E6021

    EPA has received pesticide petitions (9E6012 and 9E6021) from the 
Interregional Project Number 4 (IR-4), New Jersey Agricultural 
Experiment Station, Rutgers University, New Brunswick, New Jersey 08903 
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 by 
establishing a tolerance for residues of sethoxydim in or on the raw 
agricultural commodities (RAC) pistachio and safflower at 0.2 and 15 
parts per million (ppm). EPA has determined that the petitions contain 
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 petitions. Additional data may be needed before 
EPA rules on the petitions. This notice includes a summary of petitions 
prepared by BASF Corporation Agricultural Products, P.O. Box 13528, 
Research Triangle Park, NC 27709.

A. Residue Chemistry

    1. Plant metabolism. The qualitative nature of the residues in 
plants is adequately understood for the purposes of registration.
    2. Analytical method. Analytical methods for detecting levels of 
sethoxydim and its metabolites in or on food with a limit of detection 
that allows monitoring of food with residues at or above the levels set 
in these tolerances were submitted to EPA. The proposed analytical 
method involves extraction, partition, and clean-up. Samples are then 
analyzed by gas chromatography with sulfur-specific flame photometric 
detection. The limit of quantitation is 0.05 ppm.

B. Toxicological Profile

    1. Acute toxicity. Based on the available acute toxicity data, 
sethoxydim does not pose any acute dietary risks. A summary of the 
acute toxicity studies are as follows:
    i. Acute oral toxicity-- Rat. Toxicity Category III; lethal dose 
(LD<SUP>50</SUP>) = 3,125 milligrams/kilograms (mg/kg) male, 2,676 mg/
kg female respectively.
    ii. Acute dermal toxicity-- Rat. Toxicity Category III; 
LD<SUP>50</SUP> > 5,000 mg/kg (male and female).
    iii. Acute inhalation toxicity-- Rat. Toxicity Category III; lethal 
concentration (LC<SUP>50</SUP>) (4-hour) = 6.03 milligram/liter (mg/L) 
(male), 6.28 mg/L (female) respectively.
    iv. Primary eye irritation-- Rabbit. Toxicity Category IV; no 
irritation.
    v. Primary dermal irritation-- Rabbit. Toxicity Category IV; no 
irritation.
    vi. Dermal sensitization-- Guinea pig. Waived because no 
sensitization was seen in guinea pigs dosed with the end-use product 
poast 18% active ingredient (a.i.).
    2. Genotoxicity. Ames assays were negative for gene mutation in 
Salmonella typhimurium strains TA98, TA100, TA1535, and TA 1537, with 
and without metabolic activity. A Chinese hamster bone marrow 
cytogenetic assay was negative for structural chromosomal aberrations 
at doses up to 5,000 mg/kg in Chinese hamster bone marrow cells in 
vivo. Recombinant assays and forward mutations tests in Bacillus 
subtilis, Escherichia coli, and S. typhimurium were all negative for 
genotoxic effects at concentrations of greater than or equal to 100%.
    3. Reproductive and developmental toxicity. A developmental 
toxicity study in rats fed dosages of 0, 50, 180, 650, or 1,000 mg/kg/
day with a maternal no observed adverse effect level (NOAEL) of 180 mg/
kg/day and a maternal lowest observed adverse effect level (LOAEL) of 
650 mg/kg/day (irregular gait, decreased activity, excessive 
salivation, and anogenital staining); and a developmental NOAEL of 180 
mg/kg/day, and a developmental LOAEL of 650 mg/kg/day (21 to 22% 
decrease in fetal weights, filamentous tail, and lack of tail due to 
the absence of sacral and/or caudal vertebrae, and delayed ossification 
in the hyoids, vertebral centrum and/or transverse processes, 
sternebrae and/or metatarsals, and pubes).

[[Page 2614]]

    A developmental toxicity study in rabbits fed doses of 0, 80, 160, 
320, or 400 mg/kg/day with a maternal NOAEL of 320 mg/kg/day and a 
maternal LOAEL of 400 mg/kg/day (37% reduction in body weight gain 
without significant differences in group mean body weights and 
decreased food consumption during dosing) and a developmental NOAEL 
greater than 400 mg/kg/day highest dose tested (HDT).
    A 2-generation reproduction study with rats fed diets containing 0, 
150, 600, or 3,000 ppm (approximately 0, 7.5, 30, and 150 mg/kg/day) 
with no reproductive effects observed under the conditions of the 
study.
    4. Subchronic toxicity. A 21-day dermal study in rabbits with a 
NOAEL of > 1,000 mg/kg/day limit dose. The only dose-related finding 
was slight epidermal hyperplasia at the dosing site in nearly all males 
and females dosed at 1,000 mg/kg/day. This was probably an adaptive 
response.
    5. Chronic toxicity. A summary of the chronic toxicity studies are 
as follows:
    i. A 1-year feeding study with dogs fed diets containing 0, 8.86/
9.41, 17.5/19.9, and 110/129 mg/kg/day (males/females) with a NOAEL of 
8.86/9.41 mg/kg/day (males/females) based on equivocal anemia in male 
dogs at the 17.5-mg/kg/day dose level.
    ii. A 2-year chronic feeding/carcinogenicity study with mice fed 
diets containing 0, 40, 120, 360, or 1,080 ppm (equivalent to 0, 6, 18, 
54, and 162 mg/kg/day) with a systemic NOAEL of 120 ppm (18 mg/kg/day) 
based on non-neoplastic liver lesions in male mice at the 360-ppm (54 
mg/kg/day) dose level. There were no carcinogenic effects observed 
under the conditions of the study. The maximum tolerated dose (MTD) was 
not achieved in female mice.
    iii. A 2-year chronic feeding/carcinogenic study with rats fed 
diets containing 0, 2, 6, or 18 mg/kg/day with a systemic NOAEL greater 
than or equal to 18 mg/kg/day HDT. There were no carcinogenic effects 
observed under the conditions of the study. This study was reviewed 
under current guidelines and was found to be unacceptable because the 
doses used were insufficient to induce a toxic response and an MTD was 
not achieved.
    A second chronic feeding/carcinogenic study with rats fed diets 
containing 0, 360, or 1,080 ppm (equivalent to 18.2/23.0, and 55.9/71.8 
mg/kg/day (males/females)). The dose levels were too low to elicit a 
toxic response in the test animals and failed to achieve an MTD or 
define a LOAEL. Slight decreases in body weights in rats at the 1,080-
ppm dose level, although not biologically significant, support a free-
standing NOAEL of 1,080 ppm (55.9/71.8 mg/kg/day (males/females)). 
There were no carcinogenic effects observed under the conditions of the 
study.
    6. Animal metabolism. In a rat metabolism study, excretion was 
extremely rapid and tissue accumulation was negligible.
    7. Metabolite toxicology. As a condition to registration, BASF had 
been asked to submit additional toxicology studies for the hydroxy-
metabolites of sethoxydim. EPA agreed with BASF's recommendation to use 
the most abundant metabolite, 5-OH-MSO2, as surrogate for all 
metabolites. Based on these data, it was concluded that the 
toxicological potency of the plant hydroxy-metabolites is likely to be 
equal or less than that of the parent compound. The tolerance 
expression for sethoxydim and its metabolites containing the 2-
cyclohexen-1-one moiety, measured as parent. Hence, the hyrdroxy-
metabolites are figured into all tolerance calculations.
    8. Endocrine disruption. No specific tests have been performed with 
sethoxydim to determine whether the chemical may have an effect in 
humans that is similar to an effect produced by naturally-occurring 
estrogen or other endocrine effects.

C. Aggregate Exposure

    1. Dietary exposure--i. Food. For purposes of assessing the 
potential dietary exposure, BASF has estimated aggregate exposure based 
on the theoretical maximum residue contribution (TMRC) from existing 
and pending tolerances for sethoxydim. (The TMRC is a ``worst case'' 
estimate of dietary exposure since it is assumed that 100% of all crops 
for which tolerances are established are treated and that pesticide 
residues are at the tolerance levels). The TMRC from existing 
tolerances for the overall U.S. population is estimated at 
approximately 44% of the chronic population adjusted dose (cPAD). BASF 
estimates indicate that dietary exposure will not exceed the cPAD for 
any population subgroup for which EPA has data. This exposure 
assessment relies on very conservative assumptions 100% of crops will 
contain sethoxydim residues and those residues would be at the level of 
the tolerance which results in an overestimate of human exposure.
    ii. Drinking water. Other potential sources of exposure of the 
general population to residues of pesticides are residues in drinking 
water and exposure from non-occupational sources. Based on the 
available studies submitted to EPA for assessment of environmental 
risk, BASF does not anticipate exposure to residues of sethoxydim in 
drinking water. There is no established maximum concentration level for 
residues of sethoxydim in drinking water under the Safe Drinking Water 
Act.
    2. Non-dietary exposure. BASF has not estimated non-occupational 
exposure for sethoxydim. Sethoxydim is labeled for use by homeowners on 
and around the following use sites: flowers, evergreens, shrubs, trees, 
fruits, vegetables, ornamental groundcovers, and bedding plants. Hence, 
the potential for non-occupational exposure to the general population 
exists. However, these use sites do not appreciably increase exposure. 
Protective clothing requirements, including the use of gloves, 
adequately protect homeowners when applying the product. The product 
may only be applied through hose-end sprayers or tank sprayers as a 
0.14% solution. Sethoxydim is not a volatile compound so inhalation 
exposure during and after application would be negligible. Dermal 
exposure would be minimal in light of the protective clothing and the 
low application rate. According to BASF, post-treatment (re-entry) 
exposure would be negligible for these use sites as contact with 
treated surfaces would be low. BASF concludes that the potential for 
non-occupational exposure to the general population is insignificant.

D. Cumulative Effects

    BASF also considered the potential for cumulative effects of 
sethoxydim and other substances that have a common mechanism of 
toxicity. BASF is aware of one other a.i. which is structurally 
similar, clethodim. However BASF believes that consideration of a 
common mechanism of toxicity is not appropriate at this time. BASF does 
not have any reliable information to indicate that toxic effects 
produced by sethoxydim would be cumulative with clethodim or any other 
chemical; thus, BASF is considering only the potential risks of 
sethoxydim in its exposure assessment.

E. Safety Determination

    1. U.S. population. Using the conservative exposure assumptions 
described above, BASF has estimated that aggregate exposure to 
sethoxydim will utilize 44% of the cPAD for the U.S. population. EPA 
generally has no concern for exposures below 100% of the cPAD. 
Therefore, based on the completeness and reliability of the toxicity 
data, and the conservative exposure assessment, BASF concludes that 
there is a reasonable certainty that

[[Page 2615]]

no harm will result from aggregate exposure to residues of sethoxydim, 
including all anticipated dietary exposure and all other non-
occupational exposures.
    2. Infants and children--i. Developmental toxicity. Developmental 
toxicity was observed in a developmental toxicity study using rats but 
was not seen in a developmental toxicity study using rabbits. In the 
developmental toxicity study in rats a maternal NOAEL of 180 mg/kg/day 
and a maternal LOAEL of 650 mg/kg/day (irregular gait, decreased 
activity, excessive salivation, and anogenital staining) was 
determined. A developmental NOAEL of 180 mg/kg/day and a developmental 
LOAEL of 650 mg/kg/day (21 to 22% decrease in fetal weights, 
filamentous tail and lack of tail due to the absence of sacral and/or 
caudal vertebrae, and delayed ossification in the hyoids, vertebral 
centrum and/or transverse processes, sternebrae and/or metatarsals, and 
pubes). Since developmental effects were observed only at doses where 
maternal toxicity was noted, the developmental effects observed are 
believed to be secondary effects resulting from maternal stress.
    ii. Reproductive toxicity. A 2-generation reproduction study with 
rats fed diets containing 0, 150, 600, or 3,000 ppm (approximately 0, 
7.5, 30, and 150 mg/kg/day) produced no reproductive effects during the 
course of the study. Although the dose levels were insufficient to 
elicit a toxic response, the registrant has considered this study 
usable for regulatory purposes and has established a free-standing 
NOAEL of 3,000 ppm (approximately 150 mg/kg/day).
    iii. Chronic population adjusted dose. Based on the demonstrated 
lack of significant developmental or reproductive toxicity, BASF 
believes that the cPAD used to assess safety to children should be the 
same as that for the general population, 0.09 mg/kg/day. Using the 
conservative exposure assumptions described above, BASF has concluded 
that the most sensitive child population is that of children ages 1 to 
6 years old. BASF calculates the exposure to this group to be 
approximately 95% of the cPAD for all uses (including those proposed in 
this document). Based on the completeness and reliability of the 
toxicity data and the conservative exposure assessment, BASF concludes 
that there is a reasonable certainty that no harm will result to 
infants and children from aggregate exposure to the residues of 
sethoxydim, including all anticipated dietary exposure and all other 
non-occupational exposures.

F. International Tolerances

    A maximum residue level has not been established for sethoxydim on 
pistachio and safflower by the Codex Alimentarius Commission.

2. Interregional Research Project Number 4

 9E6059

    EPA has received a pesticide petition (9E6059) from the 
Interregional Research Project Number 4 (IR-4), New Jersey Agricultural 
Experiment Station, P. O. Box 231 Rutgers University, New Brunswick, NJ 
08903 proposing, pursuant to section 408(d) of the FFDCA, 21 U.S.C. 
346a(d), to amend 40 CFR part 180 by establishing a tolerance for 
residues of prometryn in or on the raw agricultural commodity cilantro 
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. This notice includes a summary of the petition prepared by 
IR-4.

A. Residue Chemistry

    1. Plant metabolism. The metabolism of prometryn in plants is 
adequately understood for purposes of this tolerance.
    2. Analytical method. Method, gas chromatography is available in 
PAM Vol. II for plants to enforce the tolerance expression.
    3. Magnitude of residues. The nature of the residue in plants is 
adequately understood for the purposes of this tolerance. Secondary 
residues in animal commodities are not expected to exceed existing 
tolerances as result of this use.

B. Toxicological Profile

    1. Acute toxicity. A rat acute oral study with a LD<SUP>50</SUP> of 
1,802 mg/kg for males and a LD<SUP>50</SUP> of 2,076 mg/kg for females.
    2. Genotoxicity. An Ames salmonella test, prometryn was negative 
for gene mutation up to cytotoxic solubility limits (1,000-2,000 
<greek-m>g/plate). A chromosomal aberration in vivo Chinese hamster 
bone marrow test, prometryn was negative for nuclear anomalies 
(micronuclei) when animals were dosed orally up to 5,000 mg/kg. 
Prometryn was negative for bacterial DNA repair and gene mutation up to 
precipitating levels (1,000 <greek-m>g/plate). In an unscheduled DNA 
synthesis test, prometryn was negative (measured as UDS) in rat 
hepatocytes cultured in vitro up to cytotoxic levels (156.25 
<greek-m>g/mL).
    3. Reproductive and developmental toxicity. A developmental 
toxicity study in rats with a maternal and developmental NOAEL of 50 
mg/kg and a maternal LOAEL of 250 mg/kg based on salivation and 
decreases in body weight and food consumption. The developmental LOAEL 
is 250 mg/kg/day based on significantly decreased and incomplete 
ossification in the sternebrae and metacarpals. A developmental 
toxicity study in rabbits with a maternal and developmental NOAEL of 12 
mg/kg/day and a maternal LOAEL of 72 mg/kg based on decreased food 
consumption, and the developmental LOAEL of 72 mg/kg/day, based on 
increased fetal resorption.
    A 2-generation reproduction study in rats with a parental systemic 
NOAEL of 0.6 mg/kg/day in males and 0.7 mg/kg/day in females and a 
parental systemic LOAEL of 47.8 mg/kg/day in males and 53.6 mg/kg/day 
in females based on decreased food consumption, body weight and body 
weight gain. The reproductive systemic NOAEL is 0.65 mg/kg/day and the 
reproductive systemic LOAEL is approximately 50 mg/kg/day, based on 
decreased pup weight.
    4. Subchronic toxicity. A 28-day mice pilot feeding study with a 
NOAEL of 450 mg/kg/day and a LOAEL of 1,500 mg/kg/day based on 
decreased body weights.
    5. Chronic toxicity. A 102-week chronic feeding/carcinogenicity 
study in mice with a systemic NOAEL of 100 mg/kg/day for females and a 
systemic LOAEL of 300 mg/kg/day for females based on decreased body 
weight gain. No effects were observed in males.
     A 2-year rat chronic feeding/carcinogenicity study with a systemic 
NOAEL of 29.45 mg/kg/day for males and 37.25 mg/kg/day for females and 
a systemic LOAEL of 60.88 mg/kg/day for males and 80.62 mg/kg/day for 
females based on decreased body weight and body weight gain and an 
increase in the incidence of renal lesions (mineralized concretions) in 
males. Prometryn was not carcinogenic under the conditions of the 
study.
    6. Animal metabolism. The metabolism of prometryn in animals is 
adequately understood for purposes of this tolerance.
    7. Metabolite toxicology. Rat metabolism studies showed that radio 
labeled prometryn is distributed in blood greater than spleen greater 
than lungs (the three highest tissues measured). Distribution is not 
dosage-

[[Page 2616]]

dependant. It is extensively metabolized with less than 2% of recovered 
\14\C radioactivity representing the parent compound. Twenty-eight 
metabolites were identified in the urine, and 28 in the feces. Ten 
metabolites were identified in both urine and feces. Prometryn is 
excreted predominantly in the urine and feces, with slightly higher 
concentrations in the urine. The 7-day recovery of \14\C radioactivity 
averaged 95% for all dosing groups.

C. Aggregate Exposure

    1. Dietary exposure--Acute exposure and risk. Acute dietary risk 
assessments are performed for a pesticide if a toxicological study has 
indicated the possibility of an effect of concern occurring as a result 
of a 1-day or single exposure. The margin of exposure (MOE) value for 
females (13 years and older) was 1,200,000. This value is significantly 
higher than the Agency's level of concern.
    2. Chronic exposure and risk. Assuming 100% of the crop are treated 
and residues are at tolerance levels, the theoretical maximum residue 
contribution (TMRC) from the established and proposed tolerances is 
0.000056 mg/kg/day and utilizes less than 1% of the chronic population 
adjusted dose (cPAD) for the U.S. population. For exposure of the most 
highly exposed subgroup in the population, non-nursing infants, the 
TMRC is 0.0016 mg/kg/day which utilizes less than 1% of the cPAD.
    i. Food. Tolerances have been established 40 CFR 180.222(a) for the 
residues of prometryn, 2,4-bis(isopropylamino)-6-methylthio-s-triazine, 
in celery at 0.5 ppm; corn forage, fresh corn, and corn grain at 0.25 
ppm; cotton at 1 ppm; cottonseed at 0.25 ppm; and pigeon peas at 0.25 
ppm. Tolerances with regional registration have been established 40 CFR 
180.222(b) for the residues of prometryn in dill at 0.3 ppm and parsley 
at 0.1 ppm.
    ii. Drinking water. Despite the potential for exposure through 
drinking water, the percentage of the cPAD that will be utilized by 
dietary exposure (including drinking water exposure) to residues of 
prometryn does not exceed 100% for any of the population subgroups. 
Considering food only, the population subgroup with the largest 
percentage of the cPAD occupied is 0.0000056 mg/kg/day at  1% of the 
cPAD. Therefore taking into account the completeness and reliability of 
the toxicity data and the conservative exposure assessment, there is a 
reasonable certainty that no harm will result to infants and children 
from aggregate exposure to prometryn residues.
    2. Non-dietary exposure. Prometryn is currently not registered for 
residential use such as turf and ornamentals. Therefore, there is no 
expectation of non-occupational residential exposures.

D. Cumulative Effects

    Cumulative exposure to substances with a common mechanism of 
toxicity. Prometryn is a member of the triazine class of pesticides. 
Other members of this class include atrazine, simazine, cyanazine, 
prometon, propazine, metribuzin, hexazinone, ametryn, terbutryne, 
dipropetryn, and ethiozin.
    Section 408(b)(2)(D)(v) requires that, when considering whether to 
establish, modify, or revoke a tolerance, the Agency considers 
``available information'' concerning the cumulative effects of a 
particular pesticide's residues and ``other substances that have a 
common mechanism of toxicity.'' The Agency believes that ``available 
information'' in this context might include not only toxicity, 
chemistry, and exposure data, but also scientific policies and 
methodologies for understanding common mechanisms of toxicity and 
conducting cumulative risk assessments. IR-4 does not have, at this 
time, available data to determine whether prometryn has a common 
mechanism of toxicity with other substances or how to include this 
pesticide in a cumulative risk assessment. Since there are not 
metabolites of toxicological concern associated with prometryn, IR-4 
has not assumed that prometryn has a common mechanism of toxicity with 
other substances.

E. Safety Determination

    1. U.S. population-- Acute risk. The acute aggregate dietary MOE 
was estimated to be greater than 1,000,000 for females age 13 and older 
(accounts for both maternal and fetal exposure), the population 
subgroup of concern. The MOE calculations were based on the 
developmental NOAEL in rabbits of 12 mg/kg. This risk assessment 
assumed 100% of the crop was treated with tolerance level residues on 
all treated crops consumed, resulting in a significant over estimate of 
dietary exposure. The large acute dietary MOE calculated for females 
age 13 and older provides assurance that there is a reasonable 
certainty of no harm for infants and children to prometryn.
    2. Chronic risk. Using the conservative exposure assumptions 
described above, the aggregate exposure to prometryn from food will 
utilize less than 1% of the cPAD for infants and children. EPA 
generally has no concern for exposures below 100% of the cPAD because 
the cPAD represents the level at or below which daily aggregate dietary 
exposure over a lifetime will not pose appreciable risks to human 
health. There are no chronic exposure scenarios for non-dietary uses of 
prometryn which would contribute to the aggregate risk. Taking into 
account, the completeness and reliability of the toxicity data and the 
conservative exposure assessment, IR-4 concludes that there is a 
reasonable certainty that no harm will result from aggregate exposure 
to prometryn residue's.
    3. Infants and children-safety factor--i. In general. In assessing 
the potential for additional sensitivity of infants and children to 
residues of prometryn, data were considered from the developmental 
toxicity studies in the rat and rabbit and a 2-generation reproduction 
study in the rat. The developmental toxicity studies are designed to 
evaluate adverse effects on the developing organism resulting from 
pesticide exposure during prenatal development to one or both parents. 
Reproduction studies provide information relating to effects from 
exposure to the pesticide on the reproductive capability of mating 
animals and data on systemic toxicity.
    FFDCA section 408 provides that EPA shall apply an additional 
tenfold margin of safety for infants and children in the case of 
threshold effects to account for prenatal and postnatal toxicity and 
the completeness of the data base unless EPA determines that a 
different margin of safety will be safe for infants and children. 
Margins of safety are incorporated into EPA risk assessments either 
directly through use of a MOE analysis or through using uncertainty 
(safety) factors in calculating a dose level that poses no appreciable 
risk to humans. EPA believes that reliable data support using the 
standard MOE and uncertainty factor (usually 100 for interspecies and 
intraspecies variability) and not the additional tenfold MOE/
uncertainty factor when EPA has a complete data base under existing 
guidelines and when the severity of the effect in infants or children 
or the potency or unusual toxic properties of a compound do not raise 
concerns regarding the adequacy of the standard MOE/safety factor.
    ii. Developmental and reproductive toxicity studies. The prenatal 
and postnatal toxicology data base for prometryn is complete with 
respect to current toxicological data requirements. The results of 
these studies indicate that infants and children are not more sensitive 
to exposure, based on the

[[Page 2617]]

results of the oral rat and rabbit developmental toxicity studies and 
the 2-generation reproductive toxicity study in rats. The developmental 
studies in rats and rabbits demonstrate that no prenatal extra 
sensitivity is present. However, based on the developmental effects 
observed in rabbits, an acute dietary risk assessment was performed for 
women age 13 and older. The MOE was estimated greater than 1,000,000. 
Therefore, IR-4 concludes that reliable data support use of the 
standard 100-fold MOE/uncertainty factor and that an additional tenfold 
safety factor is not needed to protect infants and children.

F. International Tolerances

    There are no Codex or Mexican limits for prometryn on cilantro. 
This proposal will harmonize tolerances with 0.1 ppm Canadian maximum 
limit for residues in cilantro.
[FR Doc. 00-1064 Filed 1-14-00; 8:45 am]
BILLING CODE 6560-50-F


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