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pirimicarb (Pirimor) Pesticide Petition Filing 10/99



[Federal Register: October 15, 1999 (Volume 64, Number 199)]
[Notices]               
[Page 55914-55921]
>From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr15oc99-71]                         

-----------------------------------------------------------------------

ENVIRONMENTAL PROTECTION AGENCY

[PF-891; FRL-6099-6]

 
Notice of Filing Pesticide Petitions To Establish a Tolerance for 
Certain Pesticide Chemicals in or on Food

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice.

-----------------------------------------------------------------------

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-891, must be 
received on or before November 15, 1999.

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'' section. To 
ensure proper receipt by EPA, it is imperative that you identify docket 
control number PF-891 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)
----------------------------------------------------------------------------------------------------------------
Ann Sibold.........................  Rm. 212, CM #2, 703-305-     1921 Jefferson Davis    PP 6H5743
                                      6502, e-mail:                Hwy, Arlington, VA
                                      sibold.ann@epamail.epa.gov
                                      .
William Sproat.....................  Rm. 6044, CM #2, 703-308-    Do.                     PP 9F6043
                                      8587, e-mail:
                                      sproat.william@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            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 in the ``FOR FURTHER INFORMATION 
CONTACT'' section.

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-891. 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-891 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, 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, 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: ``opp-docket@epa.gov ,'' 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

[[Page 55915]]

and any form of encryption. Electronic submissions will be accepted in 
Wordperfect 5.1/6.1 or ASCII file format. All comments in electronic 
form must be identified by docket control number PF-891. 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 in the ``FOR FURTHER INFORMATION 
CONTACT'' section.

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 petition. Additional data 
may be needed before EPA rules on the petition.

List of Subjects

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

    Dated: October 7, 1999.

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 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.


2. ZENECA Ag Products

PP 9F6043

    EPA has received a pesticide petition [9F6043] from ZENECA Ag 
Products, 1800 Concord Pike, Wilmington, DE 19850 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 combined residues of pirimicarb 2-
(dimethylamino)-5,6-dimethyl-4-pyrimidinyl dimethylcarbamate (9Cl) and 
its two carbamate metabolites: desmethyl pirimicarb and 
desmethylformamido pirimicarb, expressed as desmethyl pirimicarb in or 
on the raw agricultural commodities (RAC): potatoes and pre-blossom 
apples at 0.01 ppm, head lettuce at 0.3 ppm, leaf lettuce at 2.0 ppm, 
and endive (curly and escarole) at 2.0 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. Studies of the nature of residues in three 
diverse crops, potatoes, apples, and lettuce, have demonstrated that 
pirimicarb undergoes very extensive metabolism, with the residues of 
concern in primary crops being both pirimicarb and its carbamate 
metabolites. Zeneca proposes that combined residues of pirimicarb, 2-
(dimethylamino)-5,6-dimethyl-4-pyrimidinyl dimethylcarbamate (9Cl), and 
its two carbamate metabolites (desmethyl pirimicarb and 
desmethylformamido pirimicarb) expressed as desmethyl pirimicarb are to 
be included in the tolerance.
    2. Analytical method. The analytical enforcement method uses Gas 
Chromatography (GC) equipped with a thermionic nitrogen specific 
detector. Crop samples are macerated with methanol and then filtered. 
After filtration, the methanol is evaporated and the samples 
resuspended and partitioned with hexane and hydrochloric acid. The 
samples are left overnight to allow conversion of the desmethylforamido 
pirimicarb metabolite to the desmethyl pirimicarb metabolite. The 
hexane layer is discarded and the acidic aqueous layer is further 
partitioned with ethyl acetate. Sodium hydroxide is added to the 
aqueous layer and pirimicarb and its carbamate metabolites are 
extracted with dichloromethane. This method has been validated by an 
independent laboratory, with a LOD of 0.01 ppm.
    3. Magnitude of residues. Residue trials were conducted on 
potatoes, pre-blossom apples, and lettuce in the major crop growing 
areas of the United States. Sixteen residue trials were done on 
potatoes at the maximum label rate. At time of harvest, there were no 
detectable residues of either pirimicarb or its carbamate metabolites 
at the LOD of 0.01 ppm. A processing study on potatoes at 5x the 
maximum label rate also demonstrated that there are no detectable 
residues of pirimicarb or its carbamate metabolites at the LOD of 0.01 
ppm on potatoes, potato peel, or any of the processed fractions (flakes 
and chips).
    Sixteen residue trials were conducted on apples at the pre-blossom 
stage, using one application at the maximum label rate. At time of 
harvest, there were

[[Page 55919]]

no detectable residues of pirimicarb or its carbamate metabolites at 
the LOD of 0.01 ppm. An apple processing study at 5x the maximum label 
rate also demonstrated that there were no detectable residues of 
pirimicarb or its carbamate metabolites at the LOD of 0.01 ppm on 
apples, or any of the processed fractions (pomace, juice).
    Six residue trials were completed on head lettuce at the maximum 
label rate. Mature lettuce leaves were analyzed for pirimicarb and its 
carbamate metabolites. Maximum residues of 0.24 ppm were detected for 
the combined residues of pirimicarb and its carbamate metabolites.
    Six residue trials were completed on leaf lettuce at the maximum 
label rate. Mature lettuce leaves were analyzed for pirimicarb and its 
carbamate metabolites. Maximum residues of 1.73 ppm were detected for 
the combined residues of pirimicarb and its carbamate metabolites. 
ZENECA requests that the Agency also use these leaf lettuce residue 
trials as surrogate data for the commodity endive (curly and escarole).

B. Toxicological Profile

    1. Acute toxicity. In common with other carbamate insecticides, 
pirimicarb induces toxic signs characteristic of cholinesterase 
inhibition. These effects are rapidly reversed on the cessation of 
treatment and recovery is usually full and complete.
    Formulated pirimicarb (PIRIMOR DF) is classed as Category II 
toxicity based on the highest hazard for either the technical or 
formulated product.

                       Pirimicarb Toxicity Summary
------------------------------------------------------------------------
          Toxicity test                 Results        Toxicity category
------------------------------------------------------------------------
Acute oral rat..................  LD<INF>50</INF> 152 mg/kg      II
                                   (m),142 mg/kg (f)
Acute dermal rat................  LD<INF>50</INF> >1,000 mg/kg   III
                                   (f)
Acute inhalation rat............  0.95 mg/L (m);      III
                                   0.86 mg/L (f)
Eye irritation rabbit...........  Non-irritant        IV
Skin irritation rabbit..........  Slight irritant     IV
Skin sensitization..............  Moderate            May cause allergic
                                                       reaction
------------------------------------------------------------------------


            Formulated Material (PIRIMOR DF) Toxicity Summary
------------------------------------------------------------------------
          Toxicity test                 Results        Toxicity category
------------------------------------------------------------------------
Acute oral rat..................  LD<INF>50</INF> 87 mg/kg       II
Acute dermal rat................  LD<INF>50</INF> > 2,000 mg/kg  III
Acute inhalation rat............  1.7 mg/L (f)        III
Eye irritation rabbit...........  Moderate irritant   II
Skin irritation rabbit..........  Slight irritant     IV
Skin sensitization..............  Not a sensitizer    - -
------------------------------------------------------------------------

    2. Genotoxicity. Pirimicarb has been evaluated for genotoxicity and 
mutagenicity. Pirimicarb does not induce gene mutation in either 
prokaryotic or non-mammalian eukaryotic cells.
    3. Reproductive and developmental toxicity. Pirimicarb was not 
teratogenic to rats when tested in a study using oral gavage dose 
levels of 0, 10, 25, and 75 mg/kg/day. Fetotoxicity in the presence of 
maternal toxicity was observed at 75 mg/kg/day, but there were no 
effects on mother or fetus at a dose level of 25 mg/kg/day. The overall 
NOAELs for fetotoxicity was therefore, 25 mg/kg/day in the rat.
    Pirimicarb was not teratogenic in the rabbit when tested in a study 
using oral gavage dose levels of 0, 2, 10, or 60 mg/kg/day. Maternal 
toxicity was observed at 60 mg/kg/day, but there were no effects on the 
fetus at any dose level. There was no evidence of fetotoxicity or 
teratogenicity in the rabbit at doses up to and including a maternally 
toxic dose of 60 mg/kg/day.
    Neither study showed effects on the fetus in the absence of effects 
on the mother, and thus there was no evidence of enhanced fetal 
susceptibility to pirimicarb.
    Pirimicarb showed no evidence of reproductive toxicity to rats in a 
2-generation reproductive toxicity study using dose levels of 0, 50, 
200, or 750 ppm. There were no effects on reproductive parameters at 
750 ppm (88 mg/kg/day), the highest dose tested (HDT).
    4. Subchronic toxicity--i. Ninety-day rat feeding. In an number of 
repeat dose studies, male and female rats were fed diets containing 0, 
175, 250, or 750 ppm of pirimicarb for a period of 56-90 days. There 
were no adverse clinical, hematological, or pathological effects. The 
only effect was a reduction in body weight gain, which was clearly 
evident at 750 ppm in 2 studies, and one study showed slight effects at 
250 ppm. The NOAEL for subchronic toxicity in the rat was concluded to 
be 175 ppm (17.5 mg/kg/day).
    a. Ninety-day dog feeding. Groups of four male and four female 
beagle dogs were dosed with pirimicarb by capsule at 0, 0.4 or 1.8 mg/
kg/day as an oral dose for a period of at least 90 days; a further 
group received pirimicarb at 4 mg/kg/day for 180 days. There were no 
adverse clinical or pathological effects, but the animals receiving 4 
mg/kg/day showed evidence of increased erythropoetic activity on the 
bone marrow. The NOAEL in this study was 1.8 mg/kg/day.
    b. Twenty-one-day dermal study. Pirimicarb was assessed for its 
sub-acute dermal toxicity. Groups of five male and five female rats 
were given 15, 6-hour dermal applications of 40, 200, or 1,000 mg/kg 
pirimicarb as a paste in deionized water over a period of 21 days. 
There was no signs of skin irritation and no indications of systemic 
toxicity. A small reduction in brain cholinesterase was found at 1,000 
mg/kg. The NOAEL was 200 mg/kg.
    5. Neurotoxicity-i. Acute neurotoxicity. In an acute neurotoxicity 
study, pirimicarb was administered as a single dose at levels of 0, 10, 
40, or 110 mg/kg body weight. The animals were observed up to 14 days. 
A neurotoxicity screening battery of tests including a functional 
observational battery and quantitative measurement of motor activity 
was evaluated 1-week prior to the study, and on days 1, 8, and 15. 
Administration of 110 mg/kg resulted in early mortalities and adverse 
clinical signs. Brain neurotoxic esterase activity was not affected by 
treatment. Changes at the 40 mg/kg dose were transient and not 
accompanied by biologically significant reductions in brain or 
erythrocyte cholinesterase activity. It is concluded that pirimicarb 
shows reversible clinical signs of neurotoxicity following 
administration of a single oral dose of 110 mg/kg. The NOAEL for 
clinical signs of transient acute neurotoxicity is 40 mg/kg/day. The 
NOAEL for this study is 10 mg/kg/day.
    ii. Subchronic neurotoxicity. A subchronic rat neurotoxicity study 
was performed. Pirimicarb was fed to rats at levels of 0, 75, 250, and 
1,000 ppm for 90 days. A neurotoxicity screening battery of tests, 
including functional observational battery and quantitative assessment 
of motor activity was evaluated in week -1, 5, 9, and 14. 
Histopathological assessment and neurotoxic esterase activity in the 
brain was performed after 90 days. Reduced growth and food consumption/
utilization were observed at 250 and

[[Page 55920]]

1,000 ppm. There were no treatment-related effects on the functional 
observational battery, motor activity, cholinesterase and neurotoxic 
esterase activities and neuropathology. The NOAEL for subchronic 
neurotoxicity was 1,000 ppm (approximately 81 mg/kg/day).
    6. Chronic toxicity. In two chronic dog studies, dogs were dosed at 
levels up to 25 mg/kg/day for either 1 or 2 years. Pirimicarb produced 
hemolytic anemia or related hematological changes in a very small 
proportion of dogs. This effect was shown to require prolonged 
administration of pirimicarb and was reversible on cessation of 
exposure to pirimicarb. It was not observed in toxicity studies in the 
rat and mouse. A clear NOAEL of 3.5 mg/kg/day was established based on 
hematological changes in all of the available studies.
    In a 2-year rat combined chronic toxicity and oncogenicity study, 
pirimicarb was fed for up to 2 years at 0, 75, 250, and 750 ppm. The 
maximum tolerated dose was 750 ppm, with no carcinogenic response over 
2 years. A NOAEL was established at 3.7 mg/kg/day.
    In an 80-week mouse carcinogenicity study, the mice were given 
pirimicarb at 0, 6.7, 26.6, and 93.5 mg/kg/day (0, 50 ppm, 200 ppm, and 
700 ppm). It was concluded that there was an increase of incidence of 
benign lung tumors in female at the top dose of 700 ppm, only. These 
tumors are benign and demonstrate a clear threshold for induction, 
leading to the conclusion that pirimicarb is not carcinogenic in the 
mouse. This conclusion is further supported by evidence that pirimicarb 
is non-genotoxic. A NOAEL of 26.6 mg/kg/day was established.
    7. Animal metabolism. Radiolabeled studies in the rat and dog have 
demonstrated that following oral administration, pirimicarb is well 
absorbed, extensively metabolized, and the metabolites are rapidly 
eliminated. Metabolism following a single oral dose is quantitatively 
similar in rats and dogs and there is no evidence of bioaccumulation.
    8. Metabolite toxicology. Pirimicarb and the carbamate metabolites 
are associated with acute effects in cholinesterase inhibition.
    9. Endocrine disruption. Pirimicarb shows no evidence of hormonal 
effects, therefore there is no evidence of endocrine disruption. There 
are no toxicity endpoints involving reproductive organs in either male 
or female animals in any of these studies.

C. Aggregate Exposure

    1. Dietary exposure. Pirimicarb is registered for non-food use on 
seed alfalfa. The current request is to register pirimicarb on endive 
(curly and escarole). An acute RfD of 0.1 mg/kg/day is proposed, based 
on clinical signs of systemic toxicity seen at 40 mg/kg/day in the rat 
acute neurotoxicity study and application of a standard 100-fold 
uncertainty factor to the NOAEL of 10 mg/kg. There is no indication of 
sensitivity to children and infants, and therefore, no requirement for 
additional FQPA safety factor. The chronic RfD is 0.035 mg/kg/day, 
based on hematological effects noted in the chronic dog studies at 4 
mg/kg/day and application of a standard 100-fold uncertainty factor to 
the NOAEL of 3.5 mg/kg/day.
    i. Food--a. Acute risk. An acute dietary (food) risk assessment 
(Dietary Exposure Evaluation Model, Novigen Sciences Inc., 1997; USDA 
Continuing Survey of Food Intake by Individuals (CSFII) 1994-96) was 
conducted using tolerance level residues for raw agricultural 
commodities (RACs) and average field residues with percent crop treated 
for blended commodities (apple juice and dried potatoes). Resulting 
exposure values and percent of the acute RfD utilized are shown below:

       Acute Dietary (Food only) exposure and risk for pirimicarb
------------------------------------------------------------------------
                                   Exposure @ 99.9th
       Population subgroup        Percentile (mg/kg/   Percent Acute RfD
                                         day)
------------------------------------------------------------------------
U.S. population (48 States).....  0.005044            5.04%
Non-nursing infants (<1 year)...  0.000252            0.25%
Children (1-6 years)............  0.003217            3.22%
Females (13-50).................  0.005924            5.92%
------------------------------------------------------------------------

    For pirimicarb, an acceptable acute dietary exposure (food plus 
water) of 100% or less of the acute RfD for all population subgroups is 
needed to protect the safety of all population subgroups. The estimated 
exposure for all population subgroups at the 99.9th percentile utilized 
less than 100% of the acute RfD, and does not exceed EPA's level of 
concern.
    b. Chronic risk. Chronic dietary risk assessments (Dietary Exposure 
Evaluation Model, Novigen Sciences Inc., 1997; USDA Continuing Survey 
of Food Intake by Individuals (CSFII) 1994-96) were conducted for 
pirimicarb using two approaches: (1) using tolerance level residues and 
assuming 100% crop treated, and (2) using anticipated residue 
concentration levels adjusted for percent crop treated and limit of 
detection residues. The Theoretical Maximum Residue Contribution (TMRC) 
and Anticipated Residue Contribution (ARC) from these two scenarios 
represents 0.3% and 0.1%, respectively, of the RfD for the U.S. 
population as a whole. The subgroup with the greatest chronic exposure 
is children ages one to six for which the TMRC and ARC estimates 
represented 0.4% and 0.1%, respectively of the RfD. The chronic dietary 
risks from these uses do not exceed EPA's level of concern.
    ii. Drinking water. Other potential sources of exposure of the 
general population are residues in drinking water. Laboratory data on 
pirimicarb indicate that its potential soil mobility ranges between low 
and very high, depending on a number of factors including pH. However 
field dissipation data on both the parent and its metabolites indicate 
that under agricultural conditions, degradation is so rapid (half-lives 
< 21 days) that significant leaching does not occur. In a 1995-96 field 
dissipation study conducted using <SUP>14</SUP>C labeled material, the 
half-life of pirimicarb was found to average 3.1 days, and no 
radioactive residue (pirimicarb and/or metabolites) of greater than 
0.01 ppm was found below 6 inches in depth. This study conducted in 
1995-96 confirms previous laboratory and field dissipation studies.
    Pirimicarb is rapidly dissipated under field conditions by both 
photolysis and microbial metabolism leading to significantly less 
persistence than demonstrated under conditions of laboratory soil 
degradation studies. This rapid dissipation under field conditions is 
independent of soil pH. Pirimicarb, therefore, does not leach and is 
unlikely to enter surface water under the conditions of the recommended 
label use patterns.
    Drinking water levels of comparison (DWLOC) were calculated for 
pirimicarb for adults and children for both acute and chronic 
exposures, in accordance with EPA's Standard Operating Procedure (SOP) 
for Drinking Water Exposure and Risk Assessments (November 20, 1997). 
Drinking water exposure from surface and ground water for pirimicarb 
was estimated using Tier II model EPA's pesticide root zone model 
(PRZM)/EXAMS and Tier I model SCI-GROW, respectively. The exposure 
estimates and DWLOCs are summarized below:

[[Page 55921]]



                 Drinking Water Levels of Comparison and Acute Exposure Estimates for Pirimicarb
----------------------------------------------------------------------------------------------------------------
         Population subgroup              SCI-GROW (ug/L)\1\      PRZM/EXAMS (ug/L)\2\      Acute DWLOC (ug/L)
----------------------------------------------------------------------------------------------------------------
Adult - U.S. population..............  0.25                     4.66                     3323
Children.............................  0.25                     4.66                     968
----------------------------------------------------------------------------------------------------------------
\1\ SCI-GROW estimate based on highest water estimate from all crop uses.
\2\ PRZM/EXAMS based on instantaneous concentration for total carbamate residues (parent + metabolites)


                Drinking Water Levels of Comparison and Chronic Exposure Estimates for Pirimicarb
----------------------------------------------------------------------------------------------------------------
         Population subgroup              SCI-GROW (ug/L)\1\      PRZM/EXAMS (ug/L)\2\     Chronic DWLOC (ug/L)
----------------------------------------------------------------------------------------------------------------
Adult - U.S. population..............  0.25                                        0.88                     1224
Children.............................  0.25                                        0.88                     350
----------------------------------------------------------------------------------------------------------------
\1\ SCI-GROW estimate based on highest water estimate from all crop uses.
\2\ PRZM/EXAMS based on annualized average value for total carbamate residues (parent + metabolites).

    Based on the estimated dietary and water exposures for pirimicarb, 
Zeneca has concluded that there is a reasonable certainty of no harm to 
infants, children and adults resulting from potential acute or chronic 
aggregate exposure to pirimicarb.
    2. Non-dietary exposure. Pirimicarb is not registered for either 
indoor or outdoor residential uses. There are no non-occupational 
exposures to pirimicarb. Non-food uses for alfalfa grown for seed and 
small seeded vegetable seeds are occupational exposures. These 
exposures are represented in inhalation, oral and dermal estimates 
contained in the acute toxicology summaries, as well as the dermal 
penetration studies.

D. Cumulative Effects

    Pirimicarb, as a carbamate insecticide, exerts its insecticidal 
effect through inhibition of acetyl-cholinesterase. At this time, 
methodologies and mechanistic data are not available to resolve this 
complex issue of cumulative effects concerning common mechanisms of 
toxicity. At this time, there are no available data to determine 
whether pirimicarb has a common mechanism of toxicity with other 
substances, or how to include this pesticide in a cumulative risk 
assessment.

E. Safety Determination

    1. U.S. population. Based on the available toxicity data, a chronic 
RfD is set for pirimicarb at 0.035 mg/kg/day. This RfD is based on 
chronic dog studies with a NOAEL of 3.5 mg/kg/day and an uncertainty 
factor of 100. The acute RfD is 0.01 mg/kg/day, based on clinical signs 
of toxicity at 40 mg/kg/day in the rat acute neurotoxicity study. No 
additional uncertainty factors are necessary.
    2. Infants and children. Developmental toxicity and reproductive 
toxicity studies have not shown fetal effects other than mild 
fetotoxicity in the rat (reduced fetus/litter weight and indications of 
delayed development) at doses which were also toxic to the mother. 
There was no evidence in these studies of any extra susceptibility of 
the fetus. Neither has there been any indication of any particular 
susceptibility of juvenile animals. Based on the data base, there is no 
reason to consider human infants and children to be inherently more at 
risk of toxicity from pirimicarb than adults.
    FFDCA section 408 provides that EPA may apply an additional safety 
factor for infants and children in the case of threshold effects to 
account for prenatal and postnatal toxicity and the completeness of the 
data base. Based on the current toxicological data requirements, the 
data base relative to prenatal and postnatal effects for children is 
complete. No additional FQPA safety factor is required for pirimicarb.

F. International Tolerances

    The CODEX maximum residue levels for pirimicarb and its carbamate 
metabolites (desmethyl and desmethyl formamido pirimicarb) are: 
potatoes 0.05 ppm, lettuce 1.0 ppm, and apples (pome fruit) 1.0 ppm.


[FR Doc. 99-26971 Filed 10-14-99; 8:45 am]
BILLING CODE 6560-50-F