[Federal Register Volume 66, Number 74 (Tuesday, April 17, 2001)]
[Notices]
[Pages 19773-19779]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 01-9489]


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ENVIRONMENTAL PROTECTION AGENCY

[PF-1015; FRL-6773-3]


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

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice.

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

DATES: Comments, identified by docket control number PF-1015, must be 
received on or before May 17, 2001.

ADDRESSES: Comments may be submitted by mail, electronically, or in 
person. Please follow the detailed instructions for each method as 
provided in Unit I.C. of the SUPPLEMENTARY INFORMATION. To ensure 
proper receipt by EPA, it is imperative that you identify docket 
control number PF-1015 in the subject line on the first page of your 
response.

FOR FURTHER INFORMATION CONTACT: By mail: Dennis McNeilly, Insecticide/
Rodenticide Branch, Registration Division (7505C), Office of Pesticide 
Programs, Environmental Protection Agency, 1200 Pennsylvania Ave., NW., 
Washington, DC 20460; telephone number: (703) 308-6742; e-mail address: 
[email protected].

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this Action Apply to Me?

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

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

[[Page 19774]]

 
                                  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'' ``Regulation and Proposed Rules,'' and then look up the 
entry for this document under the ``Federal Register--Environmental 
Documents.'' You can also go directly to the Federal Register listings 
at http://www.epa.gov/fedrgstr/.
    2. In person. The Agency has established an official record for 
this action under docket control number PF-1015. 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-1015 in the subject line on the 
first page of your response.
    1. By mail. Submit your comments to: Public Information and Records 
Integrity Branch (PIRIB), Information Resources and Services Division 
(7502C), Office of Pesticide Programs (OPP), Environmental Protection 
Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460.
    2. In person or by courier. Deliver your comments to: Public 
Information and Records Integrity Branch (PIRIB), Information Resources 
and Services Division (7502C), Office of Pesticide Programs (OPP), 
Environmental Protection Agency, Rm. 119, Crystal Mall #2, 1921 
Jefferson Davis Highway, Arlington, VA. The PIRIB is open from 8:30 
a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The 
PIRIB telephone number is (703) 305-5805.
    3. Electronically. You may submit your comments electronically by 
e-mail to: [email protected], or you can submit a computer disk as 
described above. Do not submit any information electronically that you 
consider to be CBI. Avoid the use of special characters and any form of 
encryption. Electronic submissions will be accepted in Wordperfect 6.1/
8.0 or ASCII file format. All comments in electronic form must be 
identified by docket control number PF-1015. Electronic comments may 
also be filed online at many Federal Depository Libraries.

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

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

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

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

II. What Action is the Agency Taking?

    EPA has received 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 Cosmetic Act (FFDCA), 21 U.S.C. 346a. 
EPA has determined that the 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 support granting of the petitions. Additional data 
may be needed before EPA rules on the petitions.

List of Subjects

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

    Dated: March 27, 2001.
James Jones,
Director, Registration Division, Office of Pesticide Programs.

Summary of Petitions

PP 6F4677 and 9E6013

    The petitioner summary of the pesticide petitions is printed below 
as

[[Page 19775]]

required by section 408(d)(3) of the FFDCA. The summary of the 
petitions was prepared by the petitioner and represents the view of the 
petitioner. EPA is publishing the petition summary verbatim without 
editing it in any way. The petition summary announces the availability 
of a description of the analytical methods available to EPA for the 
detection and measurement of the pesticide chemical residues or an 
explanation of why no such method is needed.
    EPA has received a pesticide petition (6F4677) from Aventis 
CropScience, P.O Box 12014, 2 T.W., Alexander Drive, Research Triangle 
Park, NC 27709 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 aldicarb and 
its metabolites aldicarb sulfoxide and aldicarb sulfone for the crop 
group #10 ``citrus fruits'' at 0.3 parts per million (ppm). This crop 
group includes: calamondin, citrus citron, citrus hybrids (includes 
chironja, tangelo, tangor), grapefruit, kumquat, lemon, lime, mandarin 
(tangerine), orange (sour), orange (sweet), pummelo, and Satsuma 
mandarin. There are currently aldicarb tolerances (40 CFR 180.269) for 
orange, lemon, lime, and grapefruit at 0.3 ppm.
    EPA has also received a pesticide petition (9E6013) from Aventis 
CropScience, proposing, pursuant to section 408(d) of FFDCA, 21 U.S.C. 
346a(d), to amend 40 CFR part 180 by establishing an import tolerance 
for residues of aldicarb and its metabolites aldicarb sulfoxide and 
aldicarb sulfone in banana, pulp at 0.008 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 petitions prepared by the petitioner, Aventis, CropScience.

A. Residue Chemistry

    1. Plant metabolism. The metabolism of aldicarb in plants is 
adequately understood. Adequate data on the nature of the residues in 
plants, including identification of major metabolites and degradates of 
aldicarb in citrus and other crops are available.
    2.  Analytical method. There is an adequate method available for 
enforcement purposes to detect and measure levels of aldicarb, aldicarb 
sulfoxide and aldicarb sulfone in bananas with a limit of quantitation 
(LOQ) of 0.008 ppm. The high performance liquid chromotography (HPLC) 
method can detect residues at levels of detection (LOD) of 0.003 and 
0.005 ppm for aldicarb and its primary metabolites, respectively. 
Residue studies to support tolerances of aldicarb and its primary 
degradates on oranges, lemons, lime and grapefruit were conducted 
between 1977 and 1993. Samples from earlier studies were analyzed via a 
gas chromotography (GC) method which converted aldicarb and aldicarb 
sulfoxide to aldicarb sulfone and reported total toxic residue. Later 
an HPLC method was developed which was capable of quantifying each of 
the three toxic residues. The LOQ for both methods was 0.02 ppm.
    3. Magnitude of residues. No new citrus residue data are being 
filed with this petition. Aventis believes that adequate residue data 
have been provided to the EPA to support the proposed crop group 
tolerance for citrus at the current tolerance level of 0.3 ppm already 
established for oranges, lemons, limes and grapefruit. The EPA crop 
grouping #10 citrus requires that data be filed for representative 
commodities to include sweet orange, lemon and grapefruit. Aventis has 
submitted extensive data for these representative crops that serves as 
a strong basis for the proposed crop group tolerance.
    Banana crop residue trials were conducted using a new application 
methodology that will be used to treat bananas. A total of 15 field 
sites in 7 Latin American countries were treated with 1 application at 
0.8 grams of aldicarb per banana plant mat in a GLP RAC study. In 
addition, a GLP study to determine the magnitude of residues for 
processed banana fractions was conducted in Costa Rica at a 5X rate of 
4.0 grams of aldicarb per plant mat. The application for each study was 
made using a new patented application method developed by Aventis, the 
aldicarb Banana In-Plant System. The System utilizes a unique 
package or ``sachet'' to deliver an exact dose of granules containing 
15% aldicarb into the already harvested ``mother'' banana plant. Within 
a short time after the fruit is harvested, the mother plant is cut into 
a stump, leaving a single selected sucker or offshoot plant (the 
``daughter plant'') to produce the next crop. A ``plug'' is first 
removed from the stump with a special tool. The sachet is then placed 
into the hole and the plug is replaced. The fluids from the mother 
plant are slowly transferred to the daughter plant, taking with them 
the aldicarb from the granules in the sachet to provide nematode 
protection for the daughter plant's roots. Only one application is made 
per crop, compared to two applications that are required with typical 
soil applied nematicides. When TEMIK brand 15G aldicarb was 
previously used in this region as a soil treatment, two applications of 
2 grams active ingredient per mat were applied. Due to the necessity to 
apply the Banana In-Plant System sachet soon after harvest of 
the previous crop, the minimum preharvest interval to obtain mature 
green fruit is approximately 190 days. No residues were detected in 
either composite or individual pulp or peel samples from the 15 RAC 
study sites. Likewise, no residues were detected in samples of 
processed fractions from the processing study.

B. Toxicological Profile

    1. Acute toxicity. Aldicarb is highly acutely toxic. Signs of 
toxicity are those commonly associated with acetylcholinesterase 
inhibition (ChEI) caused by a carbamate pesticide; that is, cholinergic 
signs and symptoms. These symptoms are dose-dependent, and are rapidly 
reversible. Aldicarb is in acute toxicity category I by the oral, 
dermal and inhalation routes of exposure, is in toxicity category III 
for eye irritation and IV for dermal irritation. Aldicarb is not a 
sensitizer. Aldicarb has two metabolites of toxicological significance, 
aldicarb sulfoxide and aldicarb sulfone. The sulfoxide has comparable 
toxicity to parent aldicarb while the sulfone is approximately 20-fold 
less toxic.
    There is a complete neurotoxicity data base consisting of acute, 
subchronic, and developmental neurotoxicity studies. In addition, there 
is a time to peak behavioral effects study of a single oral 
administration of aldicarb technical. Finally, there are acute 
neurotoxicity studies on both aldicarb sulfoxide and aldicarb sulfone. 
Effects on ChEI were always the most sensitive indicators of both 
exposure and toxicity in these studies. The aldicarb dose-effect 
relationship for ChEI was quite consistent across studies. A dose of 
0.05 mg/kg gives the first indications of plasma and erythrocyte 
inhibition with no concomitant brain inhibition nor behavioral changes. 
At 0.2 mg/kg, marked plasma and erythrocyte ChEI is observed 
accompanied by measurable inhibition in the brain and moderate clinical 
signs. Higher dose levels result in nearly complete plasma ChEI, marked 
erythrocyte and brain ChEI and clinical signs, the magnitude of which 
increases with dose.
    2. Genotoxicity. In a September 15, 1998 Hazard Identification 
Assessment Review Committee (HIARC) report, EPA reported that studies 
covering gene

[[Page 19776]]

mutations, chromosomal aberrations, unscheduled DNA synthesis, and 
dominant lethal effects were all negative. The Agency stated that there 
was no concern for mutagenicity for aldicarb. A limited battery of 
studies on the primary aldicarb metabolites, aldicarb sulfoxide and 
sulfone, were also negative.
    3. Reproductive and developmental toxicity. There is a complete 
developmental and reproductive toxicity data base on aldicarb including 
a developmental neurotoxicity study; aldicarb did not cause 
developmental or reproductive effects in studies in the absence of 
maternal (or parental) toxicity.
    i.  Rat. In a developmental study, rats were given doses of 0, 
0.125, 0.25 or 0.5 mg/kg/day. Maternal toxicity was indicated by 
maternal death and other effects (NOAEL of 0.125 mg/kg/day). 
Gestational parameters were not affected. No increased incidence of 
malformation was observed in the absence of clear maternal toxicity. 
The NOAEL for fetal toxicity was 0.25 mg/kg/day; fetal effects at the 
highest dose included dilated ventricles. In a 2-generation 
reproductive toxicity study, rats were fed a diet with 0, 2, 5, 10, or 
20 ppm aldicarb (0, 0.1, 0.25, 5, or 10 mg/kg/day). Parental toxicity 
was indicated by ChEI and body weight changes (NOAEL 0.25 mg/kg/day). 
The reproductive NOAEL was 0.5 mg/kg/day based on decreased pup weight 
and reduced viability. There were no reproductive effects in the 
absence of parental toxicity. In a developmental neurotoxicity study in 
rats, the dose levels were 0, 0.05, 0.1, or 0.3 mg/kg/day. This study 
provides strong evidence that aldicarb does not cause permanent effects 
on the nervous system, and that the young are not more sensitive to the 
effects of aldicarb than mature animals. The maternal NOAEL was 0.05 
mg/kg/day based on miosis at 0.1 mg/kg/day. The developmental NOAEL was 
0.05 mg/kg/day based on post-weaning body weight decrement, reduced 
hindlimb grip strength, and foot splay in F1 females on 
post-partum day 35. The dose of 0.05 mg/kg/day was a clear 
developmental NOAEL in the developmental neurotoxicity study. These 
results demonstrate the lack of increased sensitivity to developing 
animals relative to adults because there were no developmental effects 
even in the presence of maternal ChEI.
    ii.  Rabbit. In a rabbit developmental study with doses of 0, 0.1, 
0.25 or 0.5 mg/kg/day, there were no fetal effects. Maternal toxicity 
was clearly established. The maternal NOAEL was 0.1 mg/kg/day based on 
body weight changes at 0.25 mg/kg/day.
    4. Subchronic toxicity. In an oral study, rats were fed aldicarb in 
their diet for 93 days at dose levels of 0, 0.02, 0.1, or 0.5 mg/kg/
day. The no observed adverse effect level (NOAEL) was 0.1 mg/kg/day, 
and the lowest observed adverse effect level (LOAEL) was 0.5 mg/kg/day. 
There were no consistent dose-related effects on ChEI except for plasma 
ChEI in both sexes after 30 days at the highest dose tested. In 
addition, mortality was increased and food consumption and body weight 
were decreased at the highest dose level. There were no compound-
related effects noted in organs examined. There was no indication in 
the study as to how soon after feeding the ChE determinations were 
performed, which could account for sporadic ChEI results in the study.
    In an oral study in dogs, animals were fed aldicarb in the diet at 
dose levels of 0, 0.2, 0.3, or 0.7 mg/kg/day for 100 days. There was no 
mortality in the study, and growth was comparable within all dose 
groups. A slight decrease in testes weight and a slight increase in 
adrenal weight were noted in males in the highest dose tested. 
Microscopic analyses did not reveal any abnormalities in these tissues. 
ChE values were unaffected by the presence of aldicarb in the diet. 
However, the animals were removed from aldicarb exposure for 24 to 48 
hours prior to ChE analysis. Since ChEI caused by aldicarb is rapidly 
reversible, this procedure could well have influenced study results. 
The NOAEL was 0.3 mg/kg/day.
    Another oral dog study was conducted to further investigate the 
ChEI dose-response curve of aldicarb. During the 5-week study, the dogs 
were fed diets mixed with aldicarb technical at levels of 0.35, 0.7, 
and 2 ppm (0.013, 0.023, and 0.069 kg/kg/day in males, and 0.012, 
0.025, and 0.067 in females). There was also a control group. There was 
no mortality or any changes in body weight, food consumption or 
clinical observation data indicative of a compound effect. Plasma ChEI 
by more than 20% occurred in high dose males and females.
     In a 21-day dermal toxicity study in rats, the effect of 
TEMIK 15G (an aldicarb 15% granular product) on plasma, 
erythrocyte, and brain ChEI was evaluated. The dose levels were 0, 100, 
250, and 500 mg/kg/day. Blood samples were taken 1 hour post-dosing on 
the first and fifth day of each week of the study. For both males and 
females, there were no effects on daily body weights, absolute and 
relative brain weights, and food consumption. There were no dose-
related clinical signs of toxicity. The NOAEL for plasma ChEI was 100 
mg/kg/day, for erythrocyte ChEI was 250 mg/kg/day, and for brain ChEI 
was at least 500 mg/kg/day.
    5. Chronic toxicity. Aldicarb has been shown to have no oncogenic 
potential when administered to rats and mice in lifetime experiments. 
ChEI is the most sensitive indicator of exposure in chronic studies in 
rats and dogs. No other clear indicators of toxicity have been 
demonstrated. A chronic NOAEL of 0.05 mg/kg/day and 0.59 mg/kg/day 
based on plasma and erythrocyte ChEI has been determined for aldicarb 
in male and female rats, respectively. A chronic NOAEL of 0.027 mg/kg/
day based on plasma ChEI and 0.054 mg/kg/day based on erythrocyte ChEI 
has been determined for aldicarb in dogs. In addition, there is a 
chronic NOAEL of 0.54 mg/kg/day for aldicarb sulfone based on plasma 
and erythrocyte ChEI in dogs.
    i. Rat. In a 2-year study, rats were fed aldicarb at levels of 0, 
1, 10, or 30 ppm in the diet. There were no compound-related effects on 
survival. The principal treatment-related clinical effect was limited 
use of the tail in high dose males and females. Body weights and body 
weight gains were reduced in high dose males and females. Atrophy of 
the iris also occurred in this dose group. There was no evidence of 
direct organ toxicity, and no evidence of oncogenic effects. The NOAEL 
was 0.05 mg/kg/day in males and 0.59 mg/kg/day in females based on 
plasma and erythrocyte ChEI.
    In a National Cancer Institute (NCI) study, rats were fed aldicarb 
in the diet at concentrations of 0, 2 or 6 ppm. There was no mortality 
attributed to aldicarb and no effect on body weight was noted. It was 
concluded that aldicarb was not oncogenic.
    In a third rat study, groups of rats were fed aldicarb at dose 
levels of 0 or 0.3 mg/kg/day. In addition, other groups were fed 
aldicarb sulfoxide at dose levels of 0, 0.3, or 0.6 mg/kg/day, aldicarb 
sulfone at dose levels of 0, 0.6, or 0.24 mg/kg/day, or a mixture of 
aldicarb sulfoxide and aldicarb sulfone at doses of 0, 0.5 or 1.2 mg/
kg/day. Neither aldicarb nor its major metabolites was found to be 
oncogenic. There were slight increases in mortality and slight 
depressions in growth at certain stages for some of the test materials. 
ChE activity was measured at 6, 12 and 24 months during the study. 
Plasma, erythrocyte, and brain ChE activity were examined only at a 
time 24 hours after animals were removed from test diets; this may have 
influenced results. No ChEI was noted other than a slight inhibition 
with respect to plasma ChE.

[[Page 19777]]

    ii. Mouse. There are three mouse oncogenicity studies. The first is 
an NCI study in which mice were fed 0, 2 or 6 ppm of aldicarb in the 
diet. It was concluded that aldicarb was not oncogenic. No effects on 
mortality or body weights were noted.
    In a second study, mice were fed aldicarb at doses of 0, 0.1, 0.2, 
0.4, or 0.7 mg/kg/day. Mortality was evident in males at the two 
highest dose levels, and in females at the three highest dose levels 
during the first few months of the study. Following this period, 
aldicarb was mixed in the diet in a different manner that appeared to 
eliminate the acutely toxic effects. Based on the mortality observed in 
this study, these data are not appropriate for the evaluation of an 
oncogenic response.
    In a third study, conducted in an effort to verify the results of 
the previous mouse study, mice were fed aldicarb at dose levels of 0, 
0.1, 0.3, or 0.7 mg/kg/day. There was no effect on mortality or growth. 
Inclusion of aldicarb in the diet did not result in an increased 
incidence of oncogenic response.
    iii.  Dog. In a 1 year study in dogs, groups of beagles were fed 
dietary concentrations of 0, 1, 2, 5, or 10 ppm daily for 52 weeks. The 
study was designed to produce maximum ChEI by limiting feeding time to 
2 hours per day to mimic a bolus administration of aldicarb. Plasma and 
erythrocyte ChE activity was measured from blood samples approximately 
2 hours after the feeding period. There were no observable effects 
other than ChEI. The NOAEL for plasma ChEI was 1 ppm or 0.027 mg/kg/
day.
    In another 1 year feeding study, aldicarb sulfone was administered 
at dietary concentrations of 0, 5, 25 or 100 ppm. ChE determinations 
were taken approximately 2 hours after feeding to measure maximum ChEI. 
No mortality or treatment-related clinical signs were seen. Some slight 
changes in spleen and thyroid/parathyroid weights were noted. Slight 
effects in the mandibular lymph nodes and adrenal cortex were observed. 
The NOAEL based on plasma and erythrocyte ChEI was 25 ppm, equal to 
0.54 mg/kg/day.
    6. Animal metabolism. The mode of biochemical conversion of 
aldicarb to a variety of metabolites has been evaluated in rats, dogs, 
dairy cows, goats and hens. The metabolic pathway for aldicarb appears 
to be the same in all animals studied. In animals, aldicarb is 
metabolized predominantly via biochemical oxidation, hydrolysis and 
elimination reactions. Aldicarb is oxidized to aldicarb sulfoxide; then 
a small portion of aldicarb sulfoxide is oxidized to aldicarb sulfone. 
Both products further undergo detoxification either through hydrolysis 
or elimination process to the corresponding oximes and nitriles, 
respectively. The oximes and nitriles, in turn, slowly degrade into the 
corresponding aldehydes, acids, and alcohols, none of which are 
toxicologically relevant.
    The presence of aldicarb metabolites in tissues, urine and feces 
has been examined in several mammalian species following administration 
of radiolabelled aldicarb under a variety of treatment regimes. Similar 
results have been found in all species tested, regardless of sex, and 
under all treatment regimes. When aldicarb is given orally to mammals, 
it is absorbed readily and excreted rapidly.
     When rats were administered single oral doses of radiolabelled 
aldicarb, most of the aldicarb metabolites were excreted within 24 
hours; after 4 days, more than 95% of the administered dose had been 
excreted and no residues were detected in body tissues by the fifth 
day. Within the first 24 hours of the study, 80% of the administered 
dose of aldicarb was eliminated in the urine and 5% in the feces. 
Aldicarb given orally to rats as a single acute dose was excreted 
primarily as aldicarb sulfoxide (40%) and the sulfoxide oxime (30%); 
only trace amounts of aldicarb were found in the urine.
    The principal metabolites found in milk following acute 
administration of aldicarb to cows were aldicarb sulfoxide oxime and 
nitrile. When dairy cows were given aldicarb for 14 days, however, the 
major metabolite in the milk was aldicarb sulfone and its nitrile 
derivative, with little aldicarb sulfoxide present. This suggests that 
more complete metabolism occurs with continuous dietary exposure to 
aldicarb. The major urinary metabolites in dogs and in dairy cows were 
the same as in rats.
    In summary, aldicarb ingested by animals is rapidly absorbed and 
metabolized and is not stored in body tissues. Its metabolites are 
mostly excreted in the urine within 24 hours, and elimination is 
complete in about 5 days.
    7. Metabolite toxicology. There have been a number of acute, 
subacute, and subchronic studies using aldicarb sulfoxide and aldicarb 
sulfone, which are the major metabolites of aldicarb, as, discussed in 
the metabolism section. The sulfoxide metabolite is of similar or 
lesser toxicity in comparison to aldicarb and the sulfone metabolite is 
much less toxic than aldicarb. In each case, ChEI is the indicator of 
exposure.
    8. Endocrine disruption. The existing aldicarb toxicity data base, 
including reproduction and developmental toxicity studies, a dominant 
lethal study, chronic toxicity and oncogenicity studies, and a 
developmental neurotoxicity study all provide no indication that 
aldicarb is a potential endocrine disruptor.

C. Aggregate Exposure

    1. Dietary exposure--i. Chronic risk. The toxic effects of aldicarb 
are limited to rapidly reversible cholinesterase inhibition. EPA 
determined the chronic RfD is the same as the acute RfD based upon 
acute exposure symptoms from a study conducted with human volunteers 
with a NOAEL of 0.01 mg/kg body weight/day. Only acute risk is 
considered for dietary exposure. This NOAEL was established primarily 
on the basis of plasma cholinesterase inhibition. Although EPA also 
cites sweaty palms and red blood cells (RBC) inhibition at this dose, 
Aventis does not believe that these effects were statistically 
significant at this dose. Since review of this human study, EPA has 
revised their policy on endpoint selection for cholinesterase 
inhibition. According to current policy, inhibition of RBC 
cholinesterase is the appropriate toxicological endpoint. The European 
Union currently regulates aldicarb on the basis of RBC cholinesterase 
inhibition in this human study. Based on RBC cholinesterase inhibition, 
they have concluded that 0.025 mg/kg/day is the appropriate regulatory 
endpoint for the aldicarb human study. For purposes of this petition, 
the acute dietary risk assessment has been based on a RfD of 0.001 mg/
kg/day as recommended by EPA in a 1998 and 1999 HIARC report.
    The remainder of this notice will reference this EPA established 
RfD. However, as current EPA policy states, the correct RfD for 
aldicarb should be 0.0025 mg/kg/day based on RBC cholinesterase 
inhibition in the human study.
    ii. Acute risk. Based upon all available data, EPA has established 
a reference dose (RfD) of 0.001 mg/kg/day using a 10 fold safety factor 
to account for intraspecies differences and a NOAEL of 0.01 mg/kg body 
weight/day based upon a human subject study. In September 1998, the EPA 
FQPA Safety Factor Committee recommended an additional 3X margin of 
safety be applied for all populations containing infants and children 
based solely upon an unpublished study. Aventis CropScience and 
independent reviewers have determined that the conduct of the study and 
related studies were seriously flawed; therefore, Aventis contends that

[[Page 19778]]

the additional 3X is inappropriate. An acute dietary risk assessment 
was prepared. The assessment included residue trial and monitoring data 
from treated fields, including individual commodity item residue data, 
from established and proposed uses of aldicarb, including bananas and 
citrus. USDA's 1989-91 Continuing Survey of Food Intake by Individuals 
(CSFII) consumption data, actual and anticipated market share, 
processing factors, and the 8-hour cholinesterase reversibility 
approach. The assessment assumes that the duration of exposure is 8 
hours. However, data from the aldicarb human study confirm that at 
doses comparable to expected exposure levels, cholinesterase inhibition 
is reversed much faster thus shortening the actual exposure period. 
Thus 8 hours is a conservative assumption for the analysis. In previous 
assessments, children 1 to 6 years of age had the highest theoretical 
exposure; therefore, the analyses were conducted for children 1-6 
years. The estimate of the 99.9th percentile of the per-
capita 8-hour exposure distribution to aldicarb in food from all 
current and proposed uses for children 1-6 years old, is 0.000191 mg/kg 
body weight or 19.1% of the RfD.
    iii. Food. The conservatively estimated exposure to aldicarb from 
use on bananas for children 1-6 years old is 0.000016 mg/kg body weight 
or 1.6% of the RfD. Including the entire citrus crop group in the risk 
assessment increased exposure estimates by less than 0.5%. While this 
analysis confirms the acceptability of the establishment of the 
proposed tolerances for the citrus crop group and bananas, Aventis is 
currently developing further state-of-the-art refinements to the acute 
dietary risk assessment.
    iv. Drinking water. There currently are no known drinking water 
wells with aldicarb residues above guideline outside of Long Island, NY 
(NY guideline of 7 ppb); wells with residues above guideline on Long 
Island are fitted with maintained filters that mitigate exposure. The 
absence of contamination to drinking water in current use areas is 
attributable to label use restrictions that regulate use of the product 
based upon vulnerable soils and mandated minimum setbacks from drinking 
water wells. The potential for aldicarb to contaminate surface water is 
low since the product is soil incorporated. The proposed citrus hybrid 
and banana import tolerance uses are not expected to increase dietary 
risk from drinking water. For purposes of determining aggregate 
exposure from drinking water, a conservative assessment for all current 
and proposed uses was conducted. The assessment utilized data from 
sampled wells and conservatively assumed that those wells represent all 
private rural wells in regions where aldicarb is used, when in fact the 
monitoring program only obtained samples from susceptible areas. In 
addition, the assessment assumed that all private wells in states where 
aldicarb could be used are expected to contain aldicarb residues, and 
used a national estimate of the proportion of the population drinking 
from private wells, rather than state-specific proportions. This 
approach potentially overestimates the proportion of private wells that 
could contain aldicarb and conservatively omits consideration of the 
label use restrictions. Water consumption data for children 1 to 6 
years old from USDA's 1989-91 CSFII were used in the assessment. The 
data refer to 24-hour intervals and represent all tap water and non-
food based water consumption. This approach results in a conservative 
estimate of the potential exposure to aldicarb in water since 
cholinesterase inhibition from aldicarb exposure is rapidly reversible 
(8 hours or less). In previous assessments, children 1 to 6 years of 
age had the highest theoretical exposure, therefore the analyses were 
conducted for children 1-6 years. The estimate of the 99.9th 
percentile of the per capita 24-hour exposure distribution to aldicarb 
in water for that subpopulation is 0.000120 mg/kg body weight or 12.0% 
of the RfD. (It should be noted that the calculated exposures for food 
and drinking water cannot be added since the calculations for food are 
based upon 8-hour consumption data and the water calculations are based 
upon consumption data for a 24-hour period.) For obvious reasons, an 
import tolerance for the use of aldicarb on bananas will not contribute 
to increased exposure in drinking water in the U.S. Since the planned 
banana use is not soil applied, minimal risk to ground water exists in 
banana growing areas as well.
    2. Non-dietary exposure. There are no residential, non-dietary uses 
for aldicarb.

D. Cumulative Effects

    An aggregate assessment based upon common mechanisms of toxicity 
has not been conducted for aldicarb since EPA policies and consensus 
scientific methodology have not been established to conduct a 
cumulative assessment. Aldicarb, a carbamate, is a rapidly reversible 
cholinesterase inhibitor and therefore generally shares a common 
mechanism of toxicity with other carbamates; however, for aldicarb's 
food crop uses, the application of aldicarb generally precludes the use 
of other carbamates and therefore minimizes the potential for multiple 
carbamate residues to include aldicarb. At planting, and uses of 
aldicarb also replace the use of organophosphates at planting reduce 
the number of foliar applications of those products and as well as 
other carbamates. Since no residues result from the application of 
aldicarb to bananas with the Banana In-Plant System, 
cumulative exposure with products sharing a common mechanism of 
toxicity is not a concern for that use.

E. Safety Determination

    1. U.S. population. Aggregate acute dietary exposure assessments 
previously demonstrated that there is a reasonable certainty that no 
harm will occur to the U.S. population from aggregate exposure (food 
and drinking water) to aldicarb from current and pending uses.
    2. Infants and children. Based upon all available data, EPA has 
established a reference dose (RfD) of 0.001 mg/kg/day using a 10 fold 
safety factor to account for intraspecies differences and a NOAEL of 
0.01 mg/kg body weight/day based upon a study conducted with human 
volunteers. In September 1998, the EPA FQPA Safety Factor Committee 
recommended an additional 3X margin of safety be applied for all 
populations containing infants and children based solely upon an 
unpublished study. Aventis CropScience and independent reviewers have 
determined that the conduct of the study and related studies were 
seriously flawed; therefore Aventis contends that the additional 3X is 
inappropriate. In previous assessments, children 1 to 6 years of age 
had the highest theoretical exposure, therefore the analyses were 
conducted for children 1-6 years. The estimate of the 99.9th 
percentile of the per-capita 8-hour exposure distribution to aldicarb 
in food from all current and proposed uses, including citrus and 
banana, for children 1-6 years old, is 0.000191 mg/kg body weight or 
19.1% of the RfD. The conservatively estimated exposure to aldicarb 
from use on bananas for children 1-6 years old is 0.000016 mg/kg body 
weight or 1.6% of the RfD. Including the entire citrus crop group in 
the risk assessment increased exposure estimates by less than 0.5%. The 
estimate of the 99.9th percentile of the per-capita 24-hour 
exposure distribution to aldicarb in water for children 1 to 6 years of 
age is 0.000120 mg/kg body weight or 12.0% of the RfD. Considering that 
the proposed import tolerance for the use of aldicarb on bananas is for 
use outside the U.S. and that the unique

[[Page 19779]]

application method for the use does not expose the product to the soil 
in the locations of use, the proposed use on bananas will not 
contribute to exposure in drinking water. There are no residential, 
non-dietary uses for aldicarb. Based on the above conservative 
estimates, Aventis CropScience does not expect the aggregate exposure 
to aldicarb for children ages 1 to 6 (the population subgroup with the 
highest theoretical exposure) to exceed one third of the RfD. 
Therefore, Aventis CropScience concludes that no harm will result to 
infants and children from aggregate exposure to aldicarb residues.

F. International Tolerances

    Codex maximum residue levels are established for residues of 
aldicarb on barley, barley straw and fodder (dry), beans, Brussels 
sprouts, citrus fruits, coffee bean, cotton seed, cotton seed oil 
(edible), grape, maize, maize fodder, maize forage, meat, milk, onion 
(bulb), peanut, peanut oil (edible), pecan, potato, sorghum, sorghum 
straw and fodder (dry), soya bean (dry), sugar beet, sugar beet leaves 
or tops, sugarcane, sunflower seed, sweet potato, wheat, wheat straw 
and fodder (dry).

[FR Doc. 01-9489 Filed 4-16-01 8:45 am]
BILLING CODE 6560-50-S