[Federal Register Volume 65, Number 15 (Monday, January 24, 2000)]
[Notices]
[Pages 3682-3690]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-1553]


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ENVIRONMENTAL PROTECTION AGENCY

[PF-909; FRL-6399-6]


Notice of Filing Pesticide Petitions 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-909, must be 
received on or before February 23, 2000.

ADDRESSES:  Comments may be submitted by mail, electronically, or in

[[Page 3683]]

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-909 in the subject line on the first page of your 
response.

FOR FURTHER INFORMATION CONTACT:  The product manager listed in the 
table below:

----------------------------------------------------------------------------------------------------------------
                                      Office location/telephone
          Product Manager               number/e-mail address             Address           Petition  number(s)
----------------------------------------------------------------------------------------------------------------
Shaja R. Brothers..................  Rm. 284, CM 2, 703-308-      1921 Jefferson Davis    PP 9E6025
                                      3194, e-mail:                Hwy, Arlington, VA
                                      brothers.shaja<Register>epamail.epa.gov.
James A. Tompkins (PM 25)..........  Rm. 239, CM 2, 703-305-      Do.                     PP 5F4505; PP 6F4791
                                      5697, e-mail:
                                      tompkins.james<Register>epamail.epa.gov.
----------------------------------------------------------------------------------------------------------------


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-909. 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-909 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#8ae5fafaa7eee5e9e1effecaeffaeba4ede5fc"><span class="__cf_email__" data-cfemail="49263939642d262a222c3d092c3928672e263f">[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-909. 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

[[Page 3684]]

    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 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: January 7, 2000,
James Jones,
Director, Registration Division, Office of Pesticide Programs.

Summaries of Petitions

    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 petitioners and represent the views of 
the petitioners. EPA is publishing the petition summaries verbatim 
without editing them 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.

I. Acetochlor Registration Partnership

PP 5F4505 and 6F4791

    EPA has received pesticide petitions (PP 5F4505 and 6F4791) from 
Acetochlor Registration Partnership, c/o Zeneca Ag Products, 1800 
Concord Pike, Wilmington DE 19850 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 
acetochlor (2-chloro-2'-methyl-6'-ethyl-N-ethoxymethylacetanilide and 
it metabolites containing the ethyl methyl aniline (EMA) and the 
hydroxy methyl aniline (HEMA) moiety, to be expressed as acetochlor, 
EMA and HEMA and expressed as acetochlor equivalents in or on the raw 
agricultural commodity field, corn, forage at 3.0 part per million 
(ppm) (5F4505); corn, sweet, grain (K+CHWHR) at 0.05 ppm; corn, sweet, 
fodder at 1.0 ppm; and corn, sweet, forage at 1.4 ppm. (6F4791). PP 
5F4505 also proposes to divide 40 CFR 180.470 into two sections: (a) 
Specific tolerances (containing the tolerances for field corn and sweet 
corn) and (b) Indirect or inadvertent tolerances (containing the 
tolerances for the rotational crops sorghum, soybean, wheat, and 
nonanimal grass feeds). PP 6F4791 also proposes that tolerances be 
established for the indirect or inadvertent residues of acetochlor in 
or on the the raw agricultural commodities when present therein as a 
result of the application of acetochlor to growing crops and other 
nonfood crops as follows: nongrass animal feeds, forage at 0.6 ppm and 
nongrass animal feeds, hay at 1.0 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 
supports granting of the petition. Additional data may be needed before 
EPA rules on the petition.

A. Residue Chemistry

    1. Plant metabolism. The metabolism of acetochlor has been studied 
in corn and soybeans. The major metabolic pathways are: (i) Uptake of 
soil metabolites and subsequent metabolism, (ii) uptake of acetochlor 
followed by oxidative metabolism and conjugation, and (iii) uptake of 
acetochlor, conjugation with glutathione and subsequent catabolism. 
Acetochlor is completely metabolized in plants to produce a number of 
polar metabolites. EPA has determined that the residues of concern are 
those which contain the EMA and HEMA.
    2. Analytical method. An adequate enforcement method for residues 
of acetochlor in crops has been approved. Acetochlor and its 
metabolites are hydrolyzed to either EMA or to HEMA which are 
determined by GC-MSD and expressed as acetochlor.
    3. Magnitude of residues. Field residue trials in field corn with 
acetochlor were conducted in 32 plots in 8 states. The maximum combined 
residues (acetochlor and metabolites) were 2.52 ppm in corn forage, 
0.217 ppm in corn fodder and 0.04 ppm in corn grain.
    Fourteen field residue trials in sweet corn with acetochlor were 
conducted in 12 states. The maximum combined residues (acetochlor and 
metabolites) were 1.35 ppm in corn forage, 0.97 ppm in corn fodder and 
0.05 ppm in grain.
    Seventeen rotational crop residue trials were conducted in 17 
states representing the top corn, alfalfa and clover producing regions 
in the U.S. The maximum combined residue (acetochlor and metabolites) 
in alfalfa forage was 0.540 ppm and the maximum alfalfa hay residue was 
1.870 ppm. The maximum clover forage residue was 0.567 ppm, the maximum 
clover residue was 1.244 ppm.

B. Toxicological Profile

    1. Acute toxicity. Acute toxicology data place technical acetochlor 
in toxicity category III for eye irritation, toxicity category III for 
acute oral, acute dermal, and acute inhalation. Technical acetochlor is 
in category IV for primary skin irritation and it is a skin sensitizer.
    2. Genotoxicty. In mutagenicity testing, submitted by Monsanto, 
acetochlor was weakly positive in the Chinese hamster ovary/
hypoxanthine-guanine phosphoribosyltransferase (CHO/HGPRT) gene 
mutation assay with and without activation in the mouse lymphoma assay. 
Acetochlor was negative in a DNA damage repair assay in rat 
hepatocytes, a Salmonella assay, and two (2) in vivo chromosomal 
aberration studies.
    In mutagenicity tests conducted by ZENECA, acetochlor induced a 
reproducible, positive, mutagenic response in strain TA 1538 of 
Salmonella typhimurium with metabolic activation at 100 milligrams /
plate (mg/p) (however, this was less than the 2X background mutation, 
but was significant at p less than 0.05). Significant increases in 
number of revertant colonies were not induced in strains TA 1535, TA 
1537, TA98, and TA100. The effect in strain TA1538 although 
reproducible in the first study was not observed in a more extensive 
follow up study. Acetochlor was not

[[Page 3685]]

clastogenic in a mouse micronucleus test at doses tested (898 and 1,436 
milligrams/kilograms (mg/kg) in males; 1,075 and 1,719 mg/kg in 
females). Acetochlor was clastogenic in cultured human lymphocytes both 
in the presence and absence of S9 mix at 100 mg/milliliters (ml), and 
in the absence of S9 mix at 50 mg/ml. It has subsequently been shown 
that the chloroacetyl substituent on acetochlor is the clastogenic 
moeity, however two structurally related chemicals containing this 
moiety have been shown to be non-carcinogens as defined by the US NTP.
    Acetochlor induced a weak DNA repair (measured by UDS) in rat 
hepatocytes derived from animals exposed in vivo at 2,000 mg/kg. At 
this dose there is significant hepatotoxicity (depletion of 
glutathione, severe liver necrosis and substantial release of hepatic 
enzymes). Acetochlor was negative in the unscheduled DNA synthesis 
(UDS) assay at a maximum tolerated dose (MTD) of 1,000 mg/kg. In a 
structural chromosome aberration study, acetochlor at doses 1,000 and 
2,000 mg/kg resulted in reduced pregnancy incidence, decreased implants 
per pregnancy incidence, increased preimplantion loss, and decreased 
time implant per pregnancy at weeks 2, 3 and 4 of this study. Early and 
late intrauterine deaths were not affected in this study. The Agency 
concluded there was positive evidence of mutagenicity at the mid- and 
high-dose levels in this study. The Acetochlor Registration Partnership 
has submitted new data which show that there were no mutagenic effects 
in this study. Acetochlor was negative in a DNA damage (comet) assay 
conducted using nasal tissue derived from rats treated with a supra-MTD 
of 1,750 ppm of acetochlor in the diet for either 7 days or 18 weeks.
    3. Reproductive and developmental toxicity. In a developmental 
study submitted by Monsanto, with rats fed dosages of 0, 50, 200, and 
400 mg/kg/day, acetochlor did not induce developmental toxicity in rats 
up to 400 mg/kg/day, the highest dose tested (HDT). The maternal no 
observed adverse effect level (NOAEL) was 200 mg/kg/day based on 
matting and/or staining of the anogenital region, a decrease in mean 
maternal weight gain during the treatment period, and in adjusted mean 
weight gain on gestation day 20 at 400 mg/kg/day (HDT).
    In a developmental study submitted by ZENECA , with rats fed 
dosages of 0, 40, 150, and 600 mg/kg/day, the developmental NOAEL was 
150 mg/kg/day based on increased resorptions, post-implantation loss, 
and decrease in mean fetal weight at 600 mg/kg/day (HDT). The maternal 
toxicity NOAEL for this study was 150 mg/kg/day based on animals 
sacrificed moribund, clinical observations, and decreased body weight 
gain at 600 mg/kg/day (HDT).
    In a developmental study submitted by Monsanto, with rabbits fed 
dosages of 0, 15, 50, and 190 mg/kg/day, acetochlor did not induce 
developmental toxicity in rabbits up to 190 mg/kg/day (HDT). The 
maternal toxicity NOAEL was 50 mg/kg/day based on loss of body weight 
during dosing at 190 mg/kg/day (HDT).
    In a developmental study submitted by ZENECA, with rabbits fed 
dosages of 0, 30, 100, and 300 mg/kg/day, acetochlor did not induce 
either maternal or developmental toxicity up to 300 mg/kg/day (HDT).
    In a 2-generation reproduction study submitted by Monsanto, with 
rats fed dosages of 0, 30.4, 74.1, and 324.5 mg/kg/day (males) or 0, 
44.9, 130.1, and 441.5 mg/kg/day (females), the reproductive NOAEL was 
30.4 mg/kg/day for males and 44.9 mg/kg/day for females, based on 
decreased body weight gain of F2b pups at 74.1 mg/kg/day for males and 
130.1 mg/kg/day for females. A NOAEL for systemic effects was not 
established.
    In a 2-generation reproduction study submitted by ZENECA, with rats 
fed dosages of 0, 1.6, 21, and 160 mg/kg/day, the reproductive NOAEL 
was 21 mg/kg/day based on significant reductions in pup weight at 
lactational day 21 and total body weight gain during lactation at 160 
mg/kg/day (HDT). The parental NOAEL was 21 mg/kg/day based on 
reductions in body weight, accompanied by slight reductions in food 
consumption and significant increases in relative organ weights at 160 
mg/kg/day (HDT).
    Conclusion. Acetochlor is not considered to be a material that 
causes developmental or reproductive toxicity. The lowest NOAEL for 
fetotoxicity was 21 mg/kg/day in a 2-generation reproduction study and 
the lowest NOAEL for fetotoxicity in a developmental study was 150 mg/
kg/day.
    4. Subchronic toxicity. A 3-month feeding study submitted by 
Monsanto with rats fed dosages of 0, 40, 100, and 300 mg/kg/day 
resulted in a NOAEL of 40 mg/kg/day based on loss of body weight and 
decreased food consumption at 100 mg/kg/day.
    A 3-week dermal study submitted by Monsanto with rabbits fed 
dosages of 0, 100, 400, and 1,200 mg/kg/day resulted in a NOAEL for 
systemic effects of 400 mg/kg/day based on mortality and decreased body 
weight at 1,200 mg/kg/day, (HDT). The lowest effect level (LEL) for 
dermal irritation was 100 mg/kg lowest dose tested (LDT). A NOAEL for 
dermal irritation was not established.
    A 3-week dermal study submitted by ZENECA with rats fed dosages of 
0.1, 1.0, 10, or 100 mg/kg/day resulted in minimal to mild skin 
irritation after 21 days. Signs of systemic toxicity were not apparent 
at any level. Higher doses were not possible because of severe dermal 
toxicity at higher doses.
    5. Chronic toxicity. In a 1-year feeding study submitted by 
Monsanto, with dogs fed dosages of 0, 4, 12, and 40 mg/kg/day, the 
NOAEL was 12 mg/kg/day based on decreased body weight gains in males, 
decreased terminal body weight in females, testicular atrophy with 
accompanying decreases in absolute and relative testicular weight, 
increase in relative liver weights in male and females, and clinical 
chemistry changes at 40 mg/kg/day (HDT).
    In a 1-year feeding study submitted by ZENECA, with dogs fed 
dosages of 0, 2, 10, and 50 mg/kg/day, the NOAEL was 2 mg/kg/day based 
on increased salivation, ornithine carbamyl transferase, and 
triglyceride values accompanied by decreased blood glucose levels and 
liver glycogen levels at 10 mg/kg/day. Interstitial nephritis, tubular 
degeneration of the testes and hypospermia were reported.
    In a chronic feeding/carcinogenicity study submitted by Monsanto, 
in which rats were fed dose levels of 0, 22, 69, and 250 mg/kg/day, a 
NOAEL for chronic effects was not established.
    In a repeat chronic feeding/carcinogenicity study submitted by 
Monsanto, in which rats were fed dose levels of 0, 2, 10, and 50 mg/kg/
day, the NOAEL for chronic effects was 10 mg/kg/day.
    In a chronic feeding/carcinogenicity study submitted by ZENECA, in 
which rats were fed dose levels of 0, 0.8, 7.9, and 79.6 mg/kg/day, the 
NOAEL for chronic effects was 7.9 mg/kg/day.
    Conclusion. The lowest NOAEL for chronic effects in dogs was 2 mg/
kg/day and the lowest NOAEL for chronic effects in rats was 7.9 mg/kg/
day. EPA has established the Reference Dose (RfD) for acetochlor at 
0.02 mg/kg/day based on the 2.0 mg/kg/day NOAEL in the ZENECA dog study 
and the application of a 100-fold safety factor.
    In a chronic feeding/carcinogenicity study submitted by Monsanto 
with mice fed dosages of 0, 75, 225, and 750 mg/kg/day (high dose 
determined to be 973 mg/kg/day by the ARP) carcinogenic effects noted 
included increased incidence of liver carcinomas in high-

[[Page 3686]]

dose males, total lung tumors in females at all dose levels, carcinomas 
of lungs in females fed 75 and 750 (973) mg/kg/day, uterine histiocytic 
sarcomas in females at all dose levels, and total benign ovarian tumors 
in mid-dose females. Other dose-related changes included: (1) Increased 
mortality and decreased mean body weights in both high-dose males and 
females, (2) decreased red blood cell count, hematocrit, and hemoglobin 
in high-dose females at terminal sacrifice, (3) increased white blood 
count in high-dose males at terminal sacrifice, (4) increased platelet 
count in mid-and high-dose females at terminal sacrifice, (5) increased 
mean liver weight and liver-to-body-weight ratios at study termination 
in all dose groups of males and in high-dose females; increased 
absolute and relative kidney weights in all dose groups of males at 
termination; increased absolute and relative adrenal weights in all 
groups of males and in high-dose females at study termination; and (6) 
increased interstitial nephritis in high-dose males and females.
    In a chronic feeding/carcinogenicity study submitted by ZENECA with 
mice fed dosages 0, 1.1, 11, and 116 mg/kg/day in males and 0, 1.4, 13, 
and 135 mg/kg/day in females, carcinogenic effects noted included an 
increase in pulmonary adenoma in both male and females at the high 
dose. Pulmonary tumors were confirmed as adenomas or carcinomas of the 
lung parenchyma and were all of the alveolar type. The NOAEL for 
systemic toxicity in females was 13 mg/kg/day based on a significant 
increase in anterior polar vacuoles in the lens of the eye at 135 mg/
kg/day.
    In a chronic feeding/carcinogenicity study submitted by Monsanto, 
with rats fed dosages of 0, 22, 69, and 250 mg/kg/day (males) or 0, 30, 
93, and 343 mg/kg/day (females), carcinogenic effects noted at 250 
(highest dose determined to be 297 mg/kg/day) mg/kg/day in males and 
343 mg/kg/day in females included hepatocellular carcinoma in both 
sexes and thyroid follicular cell adenoma in males. Nasal papillary 
adenomas were noted in male rats at 69 mg/kg/day and above and in 
females at 93 mg/kg/day. A NOAEL for chronic effects was not 
established.
    In a repeat chronic feeding/carcinogenicity study submitted by 
Monsanto, in rats fed dosages of 0, 2, 10, and 50 mg/kg/day oncogenic 
effects noted at 50 mg/kg/day (HDT) included neoplastic nodules of the 
liver, follicular adenoma/cystadenoma of the thyroids and papillary 
edema of the mucosa of the nose/turbinates in high dose animals. The 
NOAEL for chronic effects was 10 mg/kg/day based on decreased body 
weights and body weight gain in both sexes, high cholesterol levels in 
males, increased absolute and relative kidney and liver weight in 
males, and increased testicular weights at 50 mg/kg/day (HDT).
    In a 2-year chronic feeding/carcinogenicity study submitted by 
ZENECA, with rats fed dosages of 0, 0.8, 7.9, and 79.6 mg/kg/day, 
carcinogenic effects noted at 79.6 mg/kg/day (HDT) included a 
significant increase in nasal epithelial adenomas and thyroid 
follicular cell adenomas in both sexes at 79.6 mg/kg/day. Also, at that 
dose nasal carcinoma was present in two males and one female rat at 
this dose. Rare tumors in the form of benign chondroma of the femur and 
basal cell tumor of the stomach were also observed at 79.6 mg/kg/day. 
The systemic NOEL was 7.9 mg/kg/day based on decreased body weight 
gain, decreased food efficiency, increased organ to body weight ratios, 
increased plasma GGT and cholesterol at 79.6 mg/kg/day (HDT).
    Conclusions. Three oncogenicity studies have been conducted with 
acetochlor in rats and two have been conducted in mice. In rats, 
increased incidences of tumors in nasal, thyroid and liver tissues were 
found only at dose levels equal to or exceeding the MTD. Liver tumors 
were found in only one rat study and at the highest dose tested (297mg/
kg/day), a dose which greatly exceeded the MTD. The nasal tumors, found 
only at and above the MTD, are the only biologically relevant and 
reproducible oncogenic effect in rats.
    In mice, increased incidences of tumors in liver, lung, and uterine 
tissues were observed. The liver tumors were observed only in one 
study, at the HDT (973mg/kg/day) a dose which greatly exceeded the MTD 
as evidenced by increased mortality of approximately 90%. The lung 
tumors and uterine histiocytic sarcomas were observed in all treated 
female groups in one study, but there was no dose-response relationship 
which makes the relationship to treatment and relevance equivocal. Lung 
tumors occurred only in high dose animals in the second mouse study and 
their incidence rate was within the historical control range for the 
laboratory. The rat and mouse liver tumors and the mouse lung and 
histiocytic sarcomas have been subjected to an independent pathology 
peer review.
    Overall, the only clear oncogenic responses in rats or mice are 
found only at high dose levels at or above the MTD. This suggests that 
such tumors are not produced by genotoxic mechanisms, but by other 
threshold-dependent mechanisms. The weight of the evidence of all the 
genotoxicity studies conducted with acetochlor also supports the 
conclusion that tumor formation is not driven by genotoxic mechanisms. 
An overview of the genotoxicity studies with acetochlor has been 
reported by Ashby, et al. in Human and Experimental Toxicology, 15, 
702, 1996 (EPA MRID NO. 44069503).
    Mechanistic studies with alachlor, a structural analog of 
acetochlor which produces the same nasal and thyroid tumors in the rat, 
provide additional evidence that rodent tumors incident to acetanilide 
dosing are produced by indirect threshold mechanisms that are unique to 
the rat and not relevant to humans under realistic exposure levels. The 
Acetochlor Registration Partnership (ARP) has conducted and submitted a 
number of studies on the mechanism of tumor formation with acetochlor. 
The ARP believes these studies establish the basis for the use of a 
Margin of Exposure (MOE) for the cancer risk assessment for acetochlor.
    6. Animal metabolism. The metabolism of acetochlor has been studied 
in goats, laying hens and rats. EPA has concluded that the nature of 
the residue in ruminants and poultry are adequately understood and the 
residue of concern is the same as that in corn.
    7. Metabolite toxicology. EPA has determined that the residues of 
concern are those which contain the EMA and HEMA.
    8. Endocrine disruption. Acetochlor is not a member of a class of 
chemicals associated with direct adverse effects on the endocrine 
system. The subchronic, chronic, developmental and reproductive studies 
with acetochlor satisfy the present data requirements, and they have 
measured many toxic endpoints which are sensitive to endocrine-
modulation activity. Acetochlor has not produced effects in these 
toxicity studies that can be related to direct interference with female 
or male endocrine systems.

C. Aggregate Exposure

    1. Dietary exposure. The nature of the residue in plants and 
animals is understood. Acetochlor metabolizes extensively to yield a 
number of polar metabolites. Tolerances have been established at 40 CFR 
180.470 for raw agricultural commodities of field corn and indirect or 
inadvertent residues in or on sorghum, soybean and wheat. The 
tolerances are combined acetochlor, and metabolites that contain the 
EMA and HEMA moieties expressed as acetochlor. No tolerances have been 
established for livestock commodities because there is

[[Page 3687]]

no reasonable expectation of finite residues based on the results of 
exaggerated rate feeding studies.
    i. Food --a. Acute. An acute dietary analysis was performed based 
on the EPA selected acute NOAEL of 150 mg/kg/day for developmental 
toxicity. The results of this analysis produced MOEs of greater than 
70,000 for all 23 subgroups of the U.S. population. The most highly 
exposed subgroup, non-nursing infants, has a MOE of 77,000. EPA 
generally considers MOEs of greater than 100 to provide adequate acute 
dietary safety. Therefore, this evaluation demonstrates that acetochlor 
does not represent an acute dietary concern.
    b. Chronic. The theoretical maximum residue contribution (TMRC) for 
the general U.S. population from all established uses combined with the 
proposed tolerance on corn forage is 1.11 x 10<SUP>-4</SUP> mg/kg/day. 
For non-nursing infants less than 1 year old, the most highly exposed 
subgroup, the TMRC is 3.24 x 10<SUP>-4</SUP> mg/kg/day. The TMRC is 
calculated assuming that all of the corn crop is treated with 
acetochlor, that all crop commodities bear tolerance-level residues, 
and that all rotation crops are grown in soil treated with acetochlor 
and thus all rotation crop commodities have tolerance level residues. A 
refined dietary exposure estimate, based on 30% of corn acres treated, 
actual maximum residues found in crop commodities, and reduction of 
residues in some processed commodities was calculated for the same 
population groups. The refined and more accurate exposure estimate, 
called the Anticipated Residue Contribution (ARC), is 1.0 x 
10<SUP>-5</SUP> for the U.S. general population and 2.7 x 
10<SUP>-5</SUP> for non-nursing infants. The TMRC represents only 0.55% 
of the RfD for the general population. The ARC represents only 0.05% of 
the RfD.
    ii. Drinking water. Acetochlor is not registered for direct 
application to bodies of water. Seasonal run-off from treated fields 
can be transported to surface water. Since March 1995, the ARP has been 
monitoring drinking water from 175 community water systems (CWSs) which 
take their water supplies from surface water sources. The 175 CWSs take 
water from watersheds of all sizes in major acetochlor use areas but 
primarily from small watersheds located in areas of high-intensity corn 
production. Water samples taken every 2 weeks from mid March through 
early September from each CWS are analyzed for acetochlor. The results 
to date show that acetochlor was non-detected in about 80% of all 
individual samples of drinking water, with peak concentrations 
occurring mainly in May and June, the peak use season for acetochlor. 
Only about 10% of the participating CWSs had time-weighted annualized 
mean concentrations (AMC) above 0.1 parts per billion (ppb). There were 
no CWSs that had AMCs exceeding 2 ppb, the annual AMC limit set for 
acetochlor in the EPA-ARP registration agreement.
    Although acetochlor is not expected to leach through most 
agricultural soils, there is a potential for limited ground water 
contamination in areas of highly permeable soils. To address this 
possibility, acetochlor products are labeled to prohibit use in fields 
where the depth to ground water is less than 30 feet and where the 
soils are ``sands'' with less than 3% organic matter; ``loamy sands'' 
with less than 2% organic matter; or ``sandy loams'' with less than 1% 
organic matter. However, shallow ground water contamination can also 
result from misuse, improper well construction and the movement of 
surface water into direct conduits to ground water. The ARP has been 
conducting a ground water monitoring (GWM) program consisting of 175 
wells immediately adjacent to acetochlor treated fields since 1995. The 
wells are located in a variety of soil types to cover the range from 
light permeable soils to heavy less vulnerable soils, reflecting the 
soils on which corn is grown in the seven major corn-producing states. 
The ARP GWM wells are agricultural monitoring wells and do not 
adequately represent the drinking water wells across the entire 
country. Therefore, sporadic detections at very low levels cannot be 
extrapolated to provide accurate estimates of acetochlor in drinking 
water derived from ground water. A series of eight Prospective Ground 
Water (PGW) studies are being conducted by the ARP to monitor the 
movement of acetochlor to ground water under intensively instrumented 
fields, across a range of soil textures. Two studies initiated during 
1995 are nearing completion and neither show any indication of 
acetochlor movement. Four studies commenced during 1996 and continue to 
show no acetochlor ground water contamination. Traces of acetochlor 
were detected at one of these sites at one sampling interval, soon 
after application. The residues were extremely low (0.06 ppb) and had 
dissipated by the next sampling interval.
    The conditions of the registration of acetochlor include 
cancellation triggers based on detection scenarios in the Surface Water 
Monitoring Program, the Ground Water Monitoring Program and the 
Prospective Ground Water Program that will preclude any significant, 
widespread contamination of drinking water.
    For the purpose of chronic risk assessment, a level of 0.1 ppb 
seems to represent a reasonable, upper-bound level for acetochlor in 
drinking water. Based on 0.1 ppb in the water and an assumed water 
consumption of 2 liters per day for an adult weighing 70 kg, the upper 
bound exposures would be 2.9 x 10<SUP>-6</SUP> mg/kg/day.
    For the purpose of assessing short term risk, a level of 2 ppb, the 
probable MCL, represents a reasonably conservative, upper bound level 
for acetochlor in drinking water. Based on 2 ppb in the water and an 
assumed water consumption of 2 liters per day for an adult weighing 70 
kg and 1 liter per day for a child weighing 10 kg, the short-term 
exposure for the adult would be 5.7 x 10<SUP>-5</SUP> mg/kg/day and for 
the child, 2.0 x 10<SUP>-4</SUP> mg/kg/day.
    2. Non-dietary exposure. Acetochlor is not registered for any use 
which would result in non-occupational, non-dietary exposure for the 
general population. Acetochlor is registered for use on corn, a 
commercial crop which is grown in fields remote from public-use areas. 
Acetochlor products are Restricted Use, for use only by Certified 
Applicators which means the general public cannot buy or use 
acetochlor.

D. Cumulative Effects

    Toxicological testing of the chloroacetamide herbicide family in 
animals with high doses has produced a number of observed effects. 
Certain effects in some tissues are observed in two, three, or four 
members of the family, but there is no single effect that represents 
conclusive evidence of a common mechanism of toxicity existing 
throughout the chloroacetamide family.
    EPA has not established procedures for determining when pesticides 
share a common toxic mechanism, or provided a definition of 
``concurrent exposure.'' At this time there is no established procedure 
for risk assessment of pesticides which may have a common mechanism by 
may differ in potency and exposure. Following an EPA proposal to the 
FIFRA Scientific Advisory Panel meeting on March 20, 1997 (Docket No. 
OPP-00466) that nasal tumors in alachlor, acetochlor, butachlor, and 
perhaps metolachlor may be formed by a common toxic mechanism, Monsanto 
Company has derived an equation to calculate a MOE for the combined, 
concurrent exposure to multiple chloroacetamide herbicides that may 
share a common mechanism for nasal tumors. The mechanism is thought to 
be metabolic production of

[[Page 3688]]

an electrophilic 3,5-dialkyl-benzoquinone-4-imine (DABQI) or similar 
compounds at sufficient levels to cause cytotoxicity, proliferation of 
nasal cells and neoplasms in nasal tissues. The equation, as presented 
in ``Summary Information and Assessment as Required for the 
Reregistration of Alachlor by the Food Quality Protection Act of 1996'' 
[MRID 44252200] is:
    MOE=1<divide>([ala]<divide>[ala]<INF>10</INF>) + 
([Chlor1]<divide>[Chlor1]) + ([Chlor2]<divide>[Chlor2]<INF>10</INF>) + 
([Chlor3]<divide>[Chlor3]<INF>10</INF>) + Etc
    In which, [ChlorX] represents the Aggregate Exposure to each 
individual chloroacetamide herbicide which shares the common mechanism 
with alachlor (ala), and [ChlorX]<INF>10</INF><ls-thn-eq> represents 
the toxicological dose of that same herbicide which produced a 
measurable (10%) increase in tumors in tested animals (i.e., the 
ED<INF>10</INF>). This equation gives the cumulative MOE relative to 
the ED<INF>10</INF> and is valid assuming approximately constant 
relative potencies among the chloroacetamides at exposures below the 
ED<INF>10</INF>. Since the ED<INF>10</INF> will almost always exceed 
the NOAEL, this MOE will be smaller than the NOAEL-based MOE.
    The ARP adopts this equation for the purpose of the cumulative risk 
assessment for chloroacetamides and to show that acetochlor uses meet 
the FQPA standard of reasonable certainty of no harm even if a common 
mechanism of toxicity is presumed to exist for several 
chloroacetamides.

E. Safety Determination

    1. U.S. population --i. U.S. general population -acetochlor alone. 
The upper bound Aggregate Exposure estimate for short-term exposures to 
acetochlor is 6.7 x 10<SUP>-5</SUP> mg/kg/day. The Toxicity Endpoint 
Reference Committee has established 150 mg/kg/day as the acute dietary 
endpoint for risk assessment. Comparing the aggregate exposure to this 
endpoint indicates that short-term exposures have a margin of safety of 
2,238,805.
    The Aggregate Exposure estimate for chronic exposures to acetochlor 
is 1.29 x 10<SUP>-5</SUP> mg/kg/day. This exposure utilizes only 0.065% 
of the RfD of 0.02 mg/kg/day. EPA generally has no concern about 
exposures below 100% of the RfD for the U.S population.
    For cancer risk assessment, the ARP proposes that acetochlor be 
assessed by the MOE method that has been approved for cancer risk 
assessment of alachlor, a close structural analog which produces the 
same nasal and thyroid tumors in the rat. The appropriate cancer 
reference endpoint for acetochlor is the lowest NOAEL for tumors which 
is 26 mg/kg/day, the NOAEL for nasal tumors in the rat. Comparison of 
the aggregate exposure estimate of 1.29 x 10<SUP>-5</SUP> mg/kg/day to 
the 26 mg/kg/day cancer endpoint gives a MOE (relative to this minimum 
NOAEL) of 2,015,504. The margins of safety for short-term exposure, 
chronic exposure and carcinogenicity are all adequate and support the 
conclusion that there is a reasonable certainty of no harm resulting 
from the established and proposed uses of acetochlor.
    ii. U.S. general population--acetamides common nasal mechanism. The 
Aggregate Exposure (chronic) estimate for acetochlor is given above as 
1.29 x 10<SUP>-5</SUP> mg/kg/day. Using Aggregate Exposure estimates 
and ED<INF>10</INF> derived by Monsanto for alachlor, butachlor and 
metolachlor, and this refined Aggregate Exposure estimate for 
acetochlor, the Common Mechanism MOE for all four pesticides was 
calculated.
    Because some of these active ingredients have more than one chronic 
rat study, MOE ED<INF>10</INF> was calculated using the lowest or worst 
case ED<INF>10</INF>'s. (The lowest ED<INF>10</INF>'s were 8.5 mg/kg/
day for alachlor, 40.7 mg/kg/day for acetochlor and 85.1 mg/kg/day for 
butachlor. For metolachlor there were insufficient data to estimate an 
ED<INF>10</INF> and a worst-case value of 150 mg/kg/day was used. The 
aggregate exposure estimates used for alachlor, butachlor, and 
metolachlor were 1.7 x 10<SUP>-5</SUP>, 5.2 x 10<SUP>-7</SUP>, and 2.1 
x 10<SUP>-4</SUP> mg/kg/day, respectively.) The Combined Mechanism MOE 
relative to the ED<INF>10</INF> was 268596. This MOE is sufficiently 
large to demonstrate that there is a reasonable certainty of no harm 
from cumulative exposure to these chloroacetamides even if they are 
considered to share a common toxic mechanism.
    2. Infants and children. In assessing the potential for additional 
sensitivity of infants and children to residues of acetochlor, EPA 
considers data from developmental studies in the rat and the 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 to female test 
animals. Reproduction studies provide information relating to effects 
from exposure to the pesticide on the reproductive capability of mating 
animals data on systemic toxicity and the survival, growth and 
development of the offspring.
    Based on the current toxicological data requirements, the 
acetochlor data base is complete and sufficient for assessing prenatal 
and postnatal effects on children. There are two developmental studies 
with acetochlor in both the rat and the rabbit and there are two 
reproduction studies in the rat. In the four developmental studies and 
two reproduction studies with acetochlor, the fetal NOAEL's were either 
equal to or higher than the maternal (systemic) NOAEL's, indicating 
that there is no increased sensitivity for offspring. The NOAEL of 2 
mg/kg/day in the dog study which was used to establish the RfD is lower 
than the lowest developmental NOAEL by a factor of 75, and lower than 
the lowest reproductive NOAEL by a factor of 10, suggesting that the 
RfD is appropriate for assessing aggregate risk to infants and 
children. The results of the acetochlor testing establishes that there 
is reasonable certainty of no harm to infants and children from the 
proposed uses of acetochlor.
    The upper bound Aggregate Exposure for infants or children is 2.27 
x 10<SUP>-4</SUP> mg/kg/day, representing the combination of dietary 
exposure for non-nursing infants less than 1 year old (the most highly 
exposed subgroup) with potential short-term exposure to drinking water 
containing 2.0 ppb acetochlor. This potential short-term exposure 
provides a margin of safety of 660,793 when compared to the 
toxicological reference point of 150 mg/kg/day for acute dietary 
exposures. Chronic exposure at this level would utilize only 1.1% of 
the RfD. EPA generally has no concern about chronic exposures that 
utilize less than 100% of the RfD. Cancer risk assessment for children 
is considered to be included in the adult assessment because of the 
long induction period for carcinogenic effects. The cumulative risk 
assessment for chloroacetamides is based on the proposed common 
mechanism for induction of nasal tumors, a process requiring a long 
dosing period. Therefore, the data presented support the conclusion 
that there is a reasonable certainty of no harm to infants or children 
will result from the established and proposed uses for acetochlor.

F. International Tolerances

    There are no Codex Alimentarius Commission (CODEX) Maximum Residue 
Levels established for residues of acetochlor on agricultural 
commodities.

II. Interregional Research Project Number 4

9E6025

    EPA has received a pesticide petition (9E6025) from the 
Interregional Project Number 4 (IR-4), New Jersey

[[Page 3689]]

Agricultural Experiment Station, Rutgers University, New Brunswick, New 
Jersey 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 pyridate, 0-(6-chloro-3-phenyl-4-pyridazinyl)-S-octyl 
carbonothioate and its metabolite 6-chloro-3-phenyl-pyridazine-4-ol 
(known as SAN 1367), and conjugates of SAN 1367 in or on the raw 
agricultural commodities peppermint tops and spearmint tops at 0.20 
parts per million (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 summary was prepared by Novartis Crop 
Protection, Inc., Greensboro, NC, 27419.

A. Residue Chemistry

    1. Plant metabolism. The metabolism of pyridate in plants is well 
understood based on studies with broccoli, corn, and peanut. Pyridate 
is rapidly broken down by hydrolysis to its major degraded, SAN 1367. 
The SAN 1367 metabolite is further conjugated to glucoside and 
degraded.
    2. Analytical method. The proposed analytical method is ``Method of 
Analysis of Determination of Residues of Pyridate and its Metabolites 
CL 9673 and Conjugated CL 9673 in Plant Materials.''

B. Toxicological Profile

    1. Acute toxicity. Results of a rat acute oral study showed a 
lethal dose (LD)<INF>50</INF> of 4,690 mg/body weight (bwt)/day (5,993 
mg/kg in males and 3,544 mg/kg in females).
    In a rat acute dermal study, the LD<INF>50</INF> was shown to be > 
2,000 mg/kg. A rat acute inhalation study yielded a LD<INF>50</INF> > 
4.37 mg/milliliter (ml).
    Results of a primary eye irritation study in the rabbit indicated 
that pyridate is a mild irritant.
    A primary dermal irritation study showed pyridate to be a moderate 
skin irritant, whereas, a dermal sensitization study indicated it is a 
sensitizer.
    2. Genotoxicity. Pyridate was tested in the Ames test, mouse 
micronucleus assay, chromosome aberration assay with Chinese hamster 
ovary cells (CHO), the REC assay, and rat hepatocyte unscheduled DNA 
synthesis assay. Results were negative for mutagenicity and chromosome 
aberrations.
    3. Reproductive and developmental toxicity. A developmental 
toxicity study in the rat dosed at 0, 55, 165, 400, or 495 mg/kg/day 
showed a maternal no observed adverse effect level (NOAEL) of 165 mg/
kg/day, and a developmental NOAEL > 495 mg/kg/day.
    A developmental toxicity study in the rabbit with doses of 0, 150, 
300, or 600 mg/kg/day showed a maternal NOAEL of 300 mg/kg/day and a 
developmental NOAEL > 600 mg/kg/day.
    Results of a multi-generational reproduction study with rats dosed 
at 0, 2.2, 10.8, or 67.5 mg/kg/day showed a NOAEL of 10.8 mg/kg/day for 
maternal and developmental toxicity.
    4. Subchronic toxicity. Results of a 21-day dermal study showed a 
NOAEL > 1,000 mg/kg. A 90-day feeding study in rats dosed at 0, 62.5, 
177, and 500 mg/kg/day showed a NOAEL of 62.5 mg/kg/day. No 
neuropathological effects were found.
    A 90-day feeding study in dogs with doses of 0, 20, 60, or 200 mg/
kg/day showed a NOAEL of 20 mg/kg/day. Slight degenerative myelopathy 
in the peripheral nerves was observed at the highest dose level, which 
is much higher than the NOAEL and the expected exposure from field use.
    5. Chronic toxicity. A 1-year feeding study in dogs was conducted 
with doses of 0, 5, 20 or 60 mg/kg/day for 34 weeks. After week 34, the 
doses were increased to 30, 100, or 150 mg/kg/day because no toxic 
effects were evident at the lower doses. The final results showed a 
systemic NOAEL of 20 mg/kg/day.
    A lifespan (121 week) chronic/carcinogenicity study in rats treated 
with analytical levels of 0, 2.2, 10.8, or 67.5 mg/kg/day (equivalent 
to 0, 48, 240, or 1,500 ppm) showed a systemic NOAEL of 10.8 mg/kg/day 
(240 ppm) based on body weight depression. No carcinogenic potential 
was observed.
    In an 18-month carcinogenicity study, mice were fed doses of 0, 
400, 800, 1,600 or 7,000 ppm of pyridate. In males, dose levels were 
approximately 0, 47.7; 97.1; 169.5, and 882.6 mg/kg bwt/day; in 
females, dose levels were approximately 0, 54.5, 114.6, 204.3, and 
1,044.6 mg/kg bwt/day with a NOAEL at 800 ppm (97.1 mg/kg in males and 
114.6 mg/kg in females). Results showed no evidence of carcinogenicity.
    Carcinogenicity. Existing data demonstrate that there is no 
evidence of carcinogenicity in rats at 1,500 ppm (67.5 mg/kg/day) or 
mice at 7,000 ppm (883 mg/kg bwt/day in males, and 1,044.6 mg/kg bwt/
day in females). These data have been obtained at dosing in excess of 
any dietary exposure.
    6. Animal metabolism. Pyridate has been tested in rats, dogs, 
cattle, goats, and hens. In every study, pyridate was hydrolyzed to SAN 
1367 and rapidly excreted, primarily through the urine as SAN 1367 or 
its glucoside or glucuronide conjugates. Pyridate and its metabolites 
are not persistent and do not accumulate in animal systems.

C. Aggregate Exposure

    1. Dietary exposure. Pyridate is registered for use in corn, 
peanut, and cabbage. The pending petition add the use in/on peppermint 
tops and spearmint tops. The potential dietary exposure of the 
population to residues of pyridate or its metabolites is calculated 
based on Theoretical Maximum Residue Contribution (TMRC) for all crops 
with pyridate use. The TMRC is a worst case estimate of dietary 
exposure since it assumes that 100% of all crops for which tolerances 
are established are treated with pyridate, and that pesticide residues 
are present at the tolerance levels. Novartis maintains that this 
method of calculation result in an overestimation of the exposure and 
is considered conservative. Dietary exposure is not expected in meat, 
milk, poultry, or eggs, based on cow and hen feeding studies, animal 
metabolism studies, and the fact the residue studies indicate that 
residues are not present in crops fed to animals above the limit of 
detection.
    i. Chronic effects. The chronic population adjusted dose (cPAD) has 
been established based on the chronic toxicity data base. The cPAD = 
0.11 mg/kg bwt/day based on the NOAEL of 10.8 from the lifespan rat 
carcinogenicity study due to body weight depression in males, and 
assuming a safety factor of 100.
    ii. Acute effects. Acute dietary analysis compared the daily 
dietary exposure to the lowest NOAEL for subchronic studies. EPA's 
current policy for Tier I analysis uses the conservation assumption 
that all residues are at a high end estimate or maximum, typically 
taken as the tolerance value. Acute dietary assessment for pyridate was 
generated by comparing the ratio of exposure and the NOAEL from the 90-
day feeding study in dogs of 20 mg/kg bwt/day to determine a margin of 
exposure (MOE). The exposure estimate includes all current and pending 
tolerances from Sandoz Agro, Inc. and IR-4. A MOE of 100 or more is 
considered acceptable. For all subgroups evaluated, the MOE is greater 
than 140,000.
    2. Drinking water. Drinking water is not expected to be a means of 
exposure to pyridate. Environmental studies indicate that pyridate 
binds to the soil and is rapidly hydrolyzed into its

[[Page 3690]]

metabolites. The metabolites are then photolyzed and further degraded 
and finally mineralized to CO<INF>2</INF>. Leaching studies and 
lysimeter studies indicate that under typical agricultural conditions, 
neither pyridate nor its metabolites were detected below 30 
centimeters. Ground water monitoring studies conducted in Europe have 
not confirmed any detection of pyridate or metabolites. Therefore, 
significant movement of pyridate is not likely and is not a 
considerable factor in assessing human health risk.
    3. Non-dietary exposure. There are no registered uses for pyridate 
on residential or recreational turf. Therefore, non-dietary exposure of 
pyridate is not likely and not a factor in assessing human health risk.

D. Cumulative Effects

    Pyridate belongs to the pyridazine group of herbicidal compounds 
and has a unique mode of action in plants. Sandoz does not have data to 
indicate a common mechanism of toxicity to other compounds in humans. 
Therefore cumulative effects from common mechanisms of action are 
unlikely.

E. Safety Determination

    1. U.S. population. The cPAD is calculated to be 0.11 mg/kg bwt/
day. The estimates of exposure are based on conservative assumptions 
that all crops with a tolerance for pyridate are treated and that all 
residues found are at the maximum or tolerance level. The dietary 
exposure to the U.S. population for the current uses plus the corn 
grain, peanut butter, and cabbage uses is estimated at most to be 6.0 x 
10<SUP>-5</SUP> mg/kg/bwt/day, which is 0.1% of the cPAD. Therefore, 
Novartis concludes that there is reasonable certainty of no harm from 
aggregate exposure of residues of pyridate or its metabolites including 
all dietary and other non-occupational exposures.
    2. Infants and children. Pyridate is not a reproductive or 
developmental toxicant. Therefore no specific effects on infants and 
children are expected. Based on the weight of evidence of the toxicity 
studies, an additional safety factor is not warranted.
    Using the same assumptions as above, the exposure to infants and 
children is presented as a percent of cPAD. The dietary exposure for 
the current uses plus the corn grain, peanut butter, and cabbage uses 
for non-nursing infants is estimated as 1.25 x 10<SUP>-4</SUP> mg/kg/
bwt/day, which is 0.1% of the cPAD. For children age 1-6, the estimated 
exposure is 1.43 x 10<SUP>-4</SUP> mg/kg/day, 0.1% of the cPAD. 
Therefore, Sandoz concludes that there is reasonable certainty of no 
harm from aggregate exposure of residues of pyridate or its metabolites 
including all dietary and other non-occupational exposures.

F. International Tolerances

    No international tolerances have been established for pyridate on 
peppermint tops and spearmint tops by CODEX Alimentarius Commission.
[FR Doc. 00-1553 Filed 1-21-00; 8:45 am]
BILLING CODE 6560-50-F


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