[Federal Register Volume 62, Number 195 (Wednesday, October 8, 1997)]
[Notices]
[Pages 52552-52558]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-26535]


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

ENVIRONMENTAL PROTECTION AGENCY

[PF-765; FRL-5745-9]


Notice of Filing of Pesticide Petitions

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 the docket control number PF-765, must 
be received on or before November 7, 1997.
ADDRESSES: By mail submit written comments to: Public Information and 
Records Integrity Branch, Information Resources and Services Division 
(7506C), Office of Pesticides Programs, Environmental Protection 
Agency, 401 M St., SW., Washington, DC 20460. In person bring comments 
to: Rm. 1132, CM #2, 1921 Jefferson Davis Highway, Arlington, VA.
    Comments and data may also be submitted electronically to: <a href="/cdn-cgi/l/email-protection#c7a8b7b7eacda3a8a4aca2b387a2b7a6aaa6aeabe9a2b7a6e9a0a8b1">opp-
<span class="__cf_email__" data-cfemail="3b5f5458505e4f7b5e4b5a565a5257155e4b5a155c544d">[email protected]</span></a>. Follow the instructions under ``SUPPLEMENTARY 
INFORMATION.'' No confidential business information should be submitted 
through e-mail.
    Information submitted as a comment concerning this document may be 
claimed confidential by marking any part or all of that information as 
Confidential Business Information (CBI). CBI should not be submitted 
through e-mail. Information marked as CBI will not be disclosed except 
in accordance with procedures set forth in 40 CFR part 2. A copy of the 
comment that does not contain CBI must be submitted for inclusion in 
the public record. Information not marked confidential may be disclosed 
publicly by EPA without prior notice. All written comments will be 
available for public inspection in Rm. 1132 at the address given above, 
from 8:30 a.m. to 4 p.m., Monday through Friday, excluding legal 
holidays.

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

[[Page 52553]]



------------------------------------------------------------------------
                                   Office location/                     
        Product Manager            telephone number          Address    
------------------------------------------------------------------------
Joe Tavano....................  Rm. 214, CM #2, 703-    1921 Jefferson  
                                 305-6411, e-mail:       Davis Hwy,     
                                 <a href="/cdn-cgi/l/email-protection" class="__cf_email__" data-cfemail="e3978295828d8ccd898c86a38693828e828a8fcd8693">[email protected]</a>   Arlington, VA  
                                 a.gov.                                 
Bipin Gandhi,.................  Rm. 4W53, CS #1, 703-   2800 Crystal    
                                 308-8380, e-mail:       Drive,         
                                 <a href="/cdn-cgi/l/email-protection" class="__cf_email__" data-cfemail="2146404f4549480f434851484f614451404c40484d0f">[email protected]</a>   Arlington, VA  
                                 epa.gov.                               
Eugene Wilson.................  Rm. 245, CM #2, 703-    1921 Jefferson  
                                 305-6103, e-mail:       Davis Hwy,     
                                 <a href="/cdn-cgi/l/email-protection" class="__cf_email__" data-cfemail="8ef9e7e2fde1e0a0ebfbe9ebe0ebceebfeefe3efe7e2">[email protected]</a>   Arlington, VA  
                                 .epa.gov.                              
------------------------------------------------------------------------

SUPPLEMENTARY INFORMATION: 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.
    The official record for this notice of filing, as well as the 
public version, has been established for this notice of filing under 
docket control number [PF-765] (including comments and data submitted 
electronically as described below). A public version of this record, 
including printed, paper versions of electronic comments, which does 
not include any information claimed as CBI, is available for inspection 
from 8:30 a.m. to 4 p.m., Monday through Friday, excluding legal 
holidays. The official record is located at the address in 
``ADDRESSES'' at the beginning of this document.
    Electronic comments can be sent directly to EPA at:
    <a href="/cdn-cgi/l/email-protection#0d627d7d2069626e6668794d687d6c606c646123687d6c236a627b"><span class="__cf_email__" data-cfemail="442b343469202b272f21300421342529252d286a2134256a232b32">[email protected]</span></a>


    Electronic comments must be submitted as an ASCII file avoiding the 
use of special characters and any form of encryption. Comment and data 
will also be accepted on disks in Wordperfect 5.1 file format or ASCII 
file format. All comments and data in electronic form must be 
identified by the docket number PF-765 and appropriate petition number. 
Electronic comments on notice may be filed online at many Federal 
Depository Libraries.

List of Subjects

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

    Dated: September 25, 1997.

James Jones,

Actinig 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.

1. B2E Corporation

PP 7E4907

    EPA has received a pesticide petition (PP 7E4907) from B2E 
Corporation, 16 School Street, Rye, NY 10580 proposing pursuant to 
section 408(d) of the Federal Food, Drug and Cosmetic Act,(FFDCA) 21 
U.S.C. 346a(d), to amend 40 CFR part 180 to establish an exemption from 
the requirement of a tolerance for 2-Hydroxyacetophenone (2-HAP) in or 
on the raw agricultural commodity. The proposed analytical method 
involves homogenization, filtration, partition and cleanup with 
analysis by high performance liquid chromatography using UV detection. 
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. Toxicological Profile

    1. Acute toxicity. A rat acute oral study with an LD<INF>50</INF> > 
500 milligrams/kilogram (mg)/(kg), a rabbit acute dermal toxicity study 
with an LD<INF>50</INF> > 2,000 mg/kg, a primary eye irritation study 
in the rabbit showing no irritation, a rabbit primary dermal irritation 
study showing 2-HAP is not an irritant, a skin sensitization study in 
guinea pigs showing 2-HAP is a slight skin sensitizer, and a 28 day rat 
inhalation study with a no observed-effect-level (NOEL) of 160 
milligrams/cubic meter (mg)/(m<SUP>3</SUP>).
    2. Genotoxicty. 2-HAP was tested in the Ames Salmonella/microsome 
plate incorporation assay both in the presence and the absence of a 
metabolic activation system. Under the conditions of the assay, 2-HAP 
did not exhibit genetic activity according to the assay criteria. It 
can therefore be considered non-mutagenic.
    3.  Ecotoxicity. A study of acute toxicity to Bluegill Sunfish was 
conducted at five nominal concentrations, selected on the basis of 
preliminary toxicity screening, as well as a control and the solvent 
(acetone). The fish (10 in each replicate) were observed at 24, 48, 72 
and 96 hour intervals for signs of toxic effects and mortality. 2-HAP 
was determined to have an LC<INF>50</INF> (96 hours) of 115 milligrams/
liter (mg)/(L) and a no observed effect-concentration (NOEC) of 31.3 
mg/L.
    A study of acute toxicity to Daphnids was conducted at five nominal 
concentrations as well as a control and solvent (acetone) over 48 hours 
(hrs). They were observed at 24 and 48 hours for signs of toxic effects 
and mortality. 2-HAP was calculated to have an EC<INF>50</INF> (48 hr) 
of 57 mg/L under these conditions. The NOEC was found to be 25 mg/L.

B. Environmental Fate

    Aerobic soil metabolism was evaluated by a Ready Biodegradation by 
CO<INF>2</INF> Production study. The test liquid was added to test 
medium at 10 and 20 mg/L. Unacclimated diluted inoculum (20 ml, 1.3 
million CFU. ml) was added to 2 liters of diluted test material, 
positive control material (glucose at 20 milligrams/milliter (mg)/(ml) 
or control medium. Carbon dioxide free air was bubbled through the 
stirred 22.6-23.2  deg. C. incubation mixtures and carbon dioxide 
collected for 28 days. Carbon dioxide was measured by titration of 
barium hydroxide traps at regular intervals of the study. Percent 
biodegradation was estimated by percent of theoretical carbon dioxide

[[Page 52554]]

(TCO<INF>2</INF>) production achieved based on the empirical formula, 
assuming that all organic carbon in the test material is converted to 
carbon dioxide, and by measurement of total organic carbon (TOC) 
remaining after the 28 day incubation.
    After a lag of about 1 day, test material carbon dioxide production 
achieved 93.2% (at 10 mg/L) and 86.7% (at 20 mg/l) TCO<INF>2</INF> 28 
days after study start. The soluble organic carbon content at study 
termination was < 0.5 mg/L and 0.7 mg/l initial concentrations of test 
material respectively. This corresponds to 100% (at 10 mg/L) and 98.6% 
(at 20 mg/L) removal of test material also indication effective 
mineralization.
    The 2-HAP produced greater than 60% of the TCO<INF>2</INF> within 
28 days of incubation and can be considered readily biodegradable.
    Anaerobic degradation is not expected to be a factor given the 
application of the product.

C. Aggregate Exposure

    1. Dietary exposure. Dietary exposure for 2-HAP is expected to be 
negligible for the application of 2-HAP in non-food use pesticides. If 
2-HAP were to be incorporated in pesticides used for food crops, the 
level of 2-HAP would be at most, a small fraction of the acceptable 
tolerances of the pesticides. The use level within the pesticide is 
only a maximum of 0.1% by weight. The rapid biodegradability make 
significant uptake into plant tissue unlikely. Human exposure may be 
expected to be within acceptable (note: FDA classifies this as a GRAS 
material for use in meat products, poultry, condiments, soups and 
seasonings) limits.
    2. Drinking water. Although 2-HAP is not considered to be 
hydrolyzable, it is readily biodegradable. Use levels at a maximum of 
0.1% within pesticides also make it unlikely that there will be a 
presence in groundwater. Based on this data, exposure to residues in 
drinking water in not anticipated. The EPA has not established a 
Maximum Concentration Level for residues of 2-HAP in drinking water.
    3. Non-dietary exposure. Evaluations by B2E Corporation of the 
estimated non-occupational exposure to 2-HAP have concluded that the 
potential exposure for the general population may be from residues in 
food crops discussed above. Another possible exposure is from the use 
on turf of pesticides containing 2-HAP as an inert. The route of 
exposure would be dermal (assuming that people would be walking 
barefoot on treated areas) and the material has been shown to have a 
low order of acute dermal toxicity (rabbit - LD<INF>50</INF> 10,300 mg/
kg).

D. Cumulative Effects

    B2E Corporation considered the potential for cumulative effects of 
2-HAP and similar substances that may have a common mechanism of 
toxicity. there is no information to indicate that toxic effects that 
might be found at high levels of exposure to 2-HAP would be cumulative 
with other chemical compounds. The potential risks of 2-HAP are judged 
solely in its aggregate exposure.

E. Safety Determination

    1. U.S. population. Based on the exposure assumptions and the 
toxicity data described above, there is no appreciable risk to human 
health. It can be concluded that there is a reasonable certainty that 
no harm will result from aggregate exposure to 2-HAP residues.
    2. Infants and children. Based on the use patterns of the material 
and the levels of exposure, there is a reasonable certainty that no 
harm will result to infants and children from aggregate exposure to 2-
HAP residue.

F. International Tolerances

    No international tolerances have been established.

2. Novartis Crop Protection, Inc.

PP 6F4616, 6F4617, 6F4618, & 6F4633

    EPA has received a pesticide petition (PP 6F4616, 6F4617, 6F4618, & 
6F4633) from Novartis Crop Protection, Inc., P.O. Box 18300, 
Greensboro, NC 27419-8300 proposing pursuant to section 408(d) of the 
Federal Food, Drug and Cosmetic Act, 21 U.S.C. 346a(d), to amend 40 CFR 
part 180 by establishing a tolerance for residues of Fenoxycarb, 
ethyl[2-(4-phenoxyphenoxy)ethyl]carbamate in or on the raw agricultural 
commodities: pome fruit at 0.02 parts per million (ppm); nutmeat at 
0.05 ppm; almond hulls at 4.0 ppm; citrus fruit at 0.05 ppm; grass 
Forage (except Bluegrass) at 0.6 ppm; grass hay (except Bluegrass) at 
0.5 ppm; milk, meat and meat byproducts of cattle, goats, hogs, horses 
and sheep at 0.01 ppm; and fat of cattle, goats, hogs, horses and sheep 
at 0.05 ppm. The proposed analytical method involves Column switching 
high performance liquid chromatography and UV detection. EPA has 
determined that the petitions contain data or information regarding the 
elements set forth in section 408(d)(2) of the FFDCA; however, EPA has 
not fully evaluated the sufficiency of the submitted data at this time 
or whether the data 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 fenoxycarb in plants 
(apples, citrus and grass) is well understood. Identified metabolic 
pathways are similar in plants and animals. It has been determined that 
fenoxycarb, per se, is the residue of concern for tolerance setting 
purposes.The metabolism of fenoxycarb in plants (apples, citrus and 
grass) is well understood. Identified metabolic pathways are similar in 
plants and animals. It has been determined that fenoxycarb, per se, is 
the residue of concern for tolerance setting purposes.
    2. Analytical method. Novartis Crop Protection Inc. has submitted 
practical analytical methodology for detecting and measuring levels of 
fenoxycarb in or on food. The limits of detection (2.5 ng) and 
quantitation (0.01 ppm) allow monitoring of food with residues at or 
above the levels in the proposed tolerances. All methods are based on 
crop specific cleanup procedures and determination nce liquid 
chromatography with column-switching and UV detection.
    3. Magnitude of residues. Residue trials: 15 residue trials in 8 
states on apples and pears; 16 field trials in 13 states on grasses; 13 
residue trials in 4 states on citrus; 8 residue trials in 6 states on 
tree nuts. No residues of fenoxycarb (0.01 ppm) were found in apples or 
pears treated at the maximum labeled rate. The maximum residues found 
in grasses were 0.056 ppm in forage and 0.041 in hay. Only one 
detectable residue at 0.02 ppm was found on citrus. This grapefruit 
sample was aerially treated with the maximum labeled rate. The maximum 
residue found in nutmeats treated at the maximum labeled rate was 0.02 
ppm.

B. Toxicological Profile

    1. Acute toxicity. The following acute toxicity studies have been 
conducted to support the proposed tolerance for fenoxycarb. The studies 
indicate that fenoxycarb has a low order of acute toxicity with effects 
in catgegory III and IV.
    \  Rat acute oral study with an LD<INF>50</INF> >10,000 mg/kg.
    \  Rabbit acute dermal study with an LD<INF>50</INF> > 2,000 mg/kg.
    \  Rat inhalation study with an LC<INF>50</INF> > 4.4 mg/L.
    \  Primary eye irritation study in the rabbit showing slight eye 
irritation.
    \  Primary dermal irritation study in the rabbit showing fenoxycarb 
is not a skin irritant.

[[Page 52555]]

    \  Skin sensitization study showing fenoxycarb is not a skin 
sensitizer in the Guinea pig.
    \  Dermal absorption study showing a maximum of 30.2% of fenoxycarb 
is absorbed by the rat following a 24 hour dermal exposure.
    2. Genotoxicty. Results from the following assays indicate that 
fenoxycarb is not genotoxic: Ames Assay - Negative; Mouse Micronucleus 
Test - Negative; Saccharomyces cerevisiae D7 test - Negative.
    3. Reproductive and developmental toxicity. Novartis conducted a 
teratogenicity study in the rat at doses of 0, 50, 150, or 500 mg/kg/
day by gavage with maternal and developmental NOELs of <gr-thn-eq> 500 
mg/kg/day.
    Novartis also conducted a teratogenicity study in the rabbit at 
doses of 0, 30, 100, 200 or 300 mg/kg/day. The maternal NOEL based on 
reduced body weight gains was 100 mg/kg/day. The developmental NOEL was 
<gr-thn-eq> 300 mg/kg/day.
    In a 2-generation reproduction study, rats were dosed of 0, 200, 
600 or 1,800 ppm. The systemic NOEL was 200 ppm based on decreased body 
weight gains and food consumption, increased gonad weights (without 
effects on reproductive performance or a morphological correlate), 
liver hypertrophy and focal necrosis and increased liver weights. There 
were no effects on fertility or reproductive performance. Based on 
decreased pup weights and slight delays in pinna unfolding and eye 
opening, there was no clear developmental NOEL. A derived NOEL (DNOEL), 
determined using analysis of variance and regression, was 40 ppm.
    4. Subchronic toxicity. Novartis conducted a 21-day dermal study in 
which fenoxycarb was applied to the shaved skin of 5 male and 5 female 
New Zealand White rabbits at dose levels of 0, 20, 200, or 2,000 mg/kg 
for 21 consecutive days. The only effect observed was a slight increase 
in liver weights at the high dose. However, there was no 
histopathological correlate to this finding and the change was 
interpreted as representing an adaptive response. The NOEL was 200 mg/
kg.
    In a 6-month oral (capsule) study of dogs dosed at 0, 50, 150 or 
500 mg/kg/day, the NOEL was 150 mg/kg/day based on reduced weight gain 
in females.
    In a 90-day feeding study, Sprague Dawley rats were fed fenoxycarb 
at dietary concentrations to result in doses of 0, 80, 250 or 800 mg/
kg/day. Based on slight liver weight increases at 80 mg/kg/day, the 
NOEL was < 80 mg/kg/day.
    Novartis conducted a 90-day feeding study in mice in which mice 
were fed dietary concentrations of fenoxycarb to result in doses of 0, 
100, 300 or 900 mg/kg/day. Based on increased liver weight accompanied 
by fatty changes, glycogen depletion and increased multinucleated 
hepatocytes, the NOEL was 100 mg/kg/day.
    Rats in a 21-day inhalation study were exposed to 0, 0.01, 0.10 or 
1.13 mg/L for 6 hrs/day/5 days/week. Based on decreased body weight 
gain in males and increased liver weight in females the NOEL was 0.10 
mg/L.
    5. Chronic toxicity. In a 52 week oral (capsule) study, dogs were 
dosed at levels of 0, 25, 80 or 260 mg/kg/day. Based on decreased body 
weight gain and food consumption and decreases in adrenal weights and 
inorganic phosphorous the NOEL was 25 mg/kg/day.
    In a 24-month chronic feeding and oncogenicity study, rats were 
dosed at levels of 0, 200, 600 or 1,800 ppm. Based on liver toxicity 
(non-neoplastic histopathology and increased liver enzymes) the NOEL 
was 200 ppm. There was no evidence of carcinogenic potential.
    In an 80-week chronic feeding and oncogenicity study, mice were 
dosed at 0, 30, 110 or 420 ppm for males and 0, 20, 80 or 320 ppm for 
females. Systemic toxicity was not observed at any level. The NOEL for 
chronic toxicity was <gr-thn-eq> 420 ppm and 320 ppm for males and 
females, respectively. There was evidence of carcinogenic potential. 
Lung adenomas and combined adenoma/carcinoma in addition to Harderian 
gland tumor incidences were increased in males at 420 ppm.
    In an 18-month oncogenicity study, mice were dosed at 0, 10, 50, 
500 or 2,000 ppm with a NOEL of 50 ppm (5 - 6 mg/kg/day). A 
carcinogenic response was noted in the lung in males and females at 500 
and 2,000 ppm and in the liver of male mice at 500 and 2,000 ppm.
    In a study investigating biochemical parameters in livers, mice 
were treated at doses of 0, 50, 500 or 2,000 ppm showing that 
fenoxycarb is a strong inducer of hepatic xenobiotic metabolizing 
enzymes in the mouse and can be classified as a peroxisome 
proliferator..
    6. Animal metabolism. The metabolism of fenoxycarb in animals (goat 
and rat) is well understood. It has been determined that fenoxycarb, 
per se, is the residue of concern in animal commodities for tolerance 
setting purposes.

C. Aggregate Exposure

    1. Food. For purposes of assessing the potential dietary exposure 
under the proposed tolerances, Novartis has estimated aggregate 
exposure based on exposure from anticipated residues on pome fruit, 
tree nuts, citrus, cattle meat and milk. Since there were no detections 
of fenoxycarb in pome fruit, tree nuts or citrus treated according to 
label directions, the anticipated residue of 0.005 ppm, one-half the 
limit of quantitation, was used. Exposure via meat and milk comes from 
the possible consumption by cattle of almond hulls, grass, citrus pulp 
and apple pomace. Theoretical residues in milk make up greater than 50% 
of the possible exposure to fenoxycarb. Almost all of the theoretical 
residue in milk comes from almond hulls in the theoretical diet for 
cattle. The anticipated residue in milk is greatly exaggerated since 
almond hulls, in general, are not a significant portion of cattle diet. 
Percent crop treated figures for food crops and cattle feed were also 
used in the analysis.
    2. Drinking water. The product chemistry data for fenoxycarb 
indicate that movement of fenoxycarb into drinking water would be 
unlikely and that fenoxycarb would be expected to have a strong 
affinity for binding to the soil. Soil metabolism data further 
demonstrate that fenoxycarb and its residues have an affinity for 
binding to soil, and thus a low propensity to move from the soil 
surface. Field studies in Washington, Georgia and in California showed 
that fenoxycarb did not move below the top 6 inches of the soil. Based 
on the available data, Novartis does not anticipate exposure to 
residues of fenoxycarb in drinking water. There is no established 
Maximum Contaminant Level for residues of fenoxycarb in drinking water 
The product chemistry data for fenoxycarb indicate that movement of 
fenoxycarb into drinking water would be unlikely and that fenoxycarb 
would be expected to have a strong affinity for binding to the soil. 
Soil metabolism data further demonstrate that fenoxycarb and its 
residues have an affinity for binding to soil, and thus a low 
propensity to move from the soil surface. Field studies in Washington, 
Georgia and in California showed that fenoxycarb did not move below the 
top 6 inches of the soil. Based on the available data, Novartis does 
not anticipate exposure to residues of fenoxycarb in drinking water. 
There is no established Maximum Contaminant Level for residues of 
fenoxycarb in drinking water.

[[Page 52556]]

    3. Non-dietary exposure. Other potential sources of exposure of the 
general population to residues of pesticides are exposure from non-
occupational sources. Novartis has estimated non-occupational exposure 
to fenoxycarb and concludes that the potential for exposure is 
insignificant. The potential for non-occupational exposure to 
fenoxycarb resulting from use of pet sprays or carpet sprays containing 
fenoxycarb is not included in safety determinations for the U.S. 
population and infants (shown below) since the registrations for these 
uses have been canceled. Exposure through turf uses of fenoxycarb as a 
fire ant bait is also considered not significant. Used as a fire ant 
bait, fenoxycarb is only applied to turf with active fire ant 
infestations and has no efficacy as a preventive treatment. Turf 
infested with fire ants is not commonly used for recreational 
activities because of the danger presented by fire ants. In addition, 
studies demonstrate that > 95% of the bait applied to fire ant 
infestations is removed by the ants within 24 hours. Therefore 
opportunity for exposure to fenoxycarb as a fire ant bait through 
treated turf is extremely small.

D. Cumulative Effects

    Novartis also considered the potential for cumulative effects of 
fenoxycarb and other substances that have a common mechanism of 
toxicity. Novartis concluded that consideration of a common mechanism 
of toxicity is not appropriate at this time. Novartis does not have 
reliable information to indicate that toxic effects produced by 
fenoxycarb would be cumulative with those of any other chemical 
compounds; thus Novartis is considering only the potential risks from 
dietary exposure of fenoxycarb in its aggregate exposure assessment.

E. Safety Determination

    1. U.S. population. Using the exposure assumptions described above 
and based on the completeness and reliability of the toxicity data base 
for fenoxycarb, Novartis has calculated that aggregate exposure to 
fenoxycarb will utilize 0.016% of the Reference Dose (RfD) for the U.S. 
population - 48 states - all seasons, based on chronic toxicity 
endpoints. Lifetime carcinogenic risk for dietary exposure based on 
quantitative risk assessment and a Q<INF>1</INF>* of 5.6  x  
10<SUP>-2</SUP> (mg/kg/day)<SUP>-1</SUP>, is 7.31  x  10<SUP>-7</SUP>. 
EPA generally has no concern for exposures below 100% of the RfD or 
lifetime carcinogenic risks less than 1  x  10<SUP>-6</SUP>. Since 
anticipated residues of fenoxycarb in food are extremely low and all 
short term NOELs are at least an order of magnitude higher than the 
chronic NOEL, no acute risk from exposure to residues of fenoxycarb is 
anticipated. Therefore, Novartis concludes that there is a reasonable 
certainty that no harm will result from aggregate exposure to 
fenoxycarb residues.
    2. Infants and children. In assessing the potential for additional 
sensitivity of infants and children to residues of fenoxycarb, Novartis 
considered data from developmental toxicity studies in the rat and 
rabbit and a 2-generation reproduction study in the rat. No evidence of 
developmental toxicity was observed in rats or rabbits. Fenoxycarb did 
not impair any reproductive or postnatal development parameters and was 
neither embryotoxic nor teratogenic. The NOELs for maternal and 
developmental toxicity in the rat were determined to be <gr-thn-eq> 500 
mg/kg/day. The NOEL for maternal toxicity in the rabbit, based on 
reduced body weight gains, was 100 mg/kg/day and the NOEL for 
developmental toxicity was <gr-thn-eq> 300 mg/kg/day. In a 2-generation 
reproduction study in rats, the systemic NOEL for parental animals was 
200 ppm based on decreased body weight gains and food consumption, 
increased gonad weights (without effects on reproductive performance or 
a morphological correlate), liver hypertrophy and focal necrosis and 
increased liver weights. There were no effects on fertility or 
reproductive performance. Based on decreased pup weights and slight 
delays in pinna unfolding and eye opening, there was no clear 
developmental NOEL. A NOEL of 40 ppm was derived using analysis of 
variance and regression. The mild nature of the effects of fenoxycarb 
on rat pups and the lack of effects in the developmental toxicity 
studies suggest that there is no particular sensitivity to fenoxycarb 
for infants and children.
    Using the same exposure assumptions used for the determination in 
the general population, Novartis has concluded that the percent of the 
RfD that will be utilized by aggregate exposure to residues of 
fenoxycarb is 0.038% for nursing infants less than 1 year old, 0.098% 
for non-nursing infants, 0.048% for children 1-6 years old and 0.028% 
for children 7-12 years old. Therefore, based on the completeness and 
reliability of the toxicity data base, Novartis concludes that there is 
a reasonable certainty that no harm will result to infants and children 
from aggregate exposure to fenoxycarb residues.

F. International Tolerances

     No Codex MRLs have been established for residues of fenoxycarb.

3. Novartis Crop Protection, Inc.

PP 7F4897

    EPA has received a pesticide petition (PP 7F4897) from Novartis 
Crop Protection, Inc., Greensboro, NC 27419, proposing pursuant to 
section 408(d) of the Federal Food, Drug and Cosmetic Act, 21 U.S.C. 
346a(d), to amend 40 CFR 180.368 by establishing a tolerance for 
residues of metolachlor in or on the raw agricultural commodities 
sunflower seed at 0.3 ppm and sunflower meal at 0.6 ppm. The proposed 
analytical method involves extraction by acid reflux, filtration, 
partition and cleanup with analysis by gas chromatography using 
Nitrogen/Phosphorous (N/P) detection. 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 qualitative nature of the metabolism of 
metolachlor in plants is well understood. Metabolism in plants involves 
conjugation of the chloroacetyl side chain with glutathione, with 
subsequent conversion to the cysteine and thiolactic acid conjugates. 
Oxidation to the corresponding sulfoxide derivatives occurs and 
cleavage of the side chain ether group, followed by conjugation with 
glucose.
    2. Analytical method. Novartis Crop Protection has submitted a 
practical analytical method involving extraction by acid reflux, 
filtration, partition and cleanup with analysis by gas chromatography 
using Nitrogen/Phosphorous (N/P) detection. The methodology converts 
residues of metolachlor into a mixture of CGA-37913 and CGA-49751. The 
limit of quantitation (LOQ) for the method is 0.03 ppm for CGA-37913 
and 0.05 ppm for CGA-49751.
    3. Magnitude of residues. Eight residue trials were conducted in 
major sunflower growing areas of the United States [CA, KS, TX (2), 
MN(2), ND, IL). Five tests were conducted with metolachlor alone and 
three were conducted as a tank mix of metolachlor and another product. 
Metolachlor residues were analyzed for in all trials. Applications were 
made at the

[[Page 52557]]

maximum labeled rate of 3.0 lbs. active ingredient/Acre (ai/A) and at 2 
times the maximum labeled rate (6.0 lbs. ai/A). A processing study was 
also conducted with seeds processed into meal, hulls, crude oil, 
refined oil and soapstock. According to the Revised Table II of 
Subdivision O, only meal and refined oil are now required. Based on 
these studies and an earlier EPA review of these data, tolerances are 
proposed in sunflower seeds at 0.3 ppm and in sunflower meal at 0.6 
ppm.

B. Toxicological Profile

    1. Acute toxicity. Metolachlor has a low order of acute toxicity. 
The combined rat oral LD<INF>50</INF> is 2,877 mg/kg. The acute rabbit 
dermal LD<INF>50</INF> is > 2,000 mg/kg and the rat inhalation 
LC<INF>50</INF> is > 4.33 mg/L. Metolachlor is not irritating to the 
skin and eye. It has been shown to be positive in guinea pigs for skin 
sensitization. End use formulations of metolachlor also have a low 
order of acute toxicity and cause slight skin and eye irritation.
    2. Genotoxicty. Assays for genotoxicity were comprised of tests 
evaluating metolachlor's potential to induce point mutations 
(Salmonella assay and an L5178/TK+/- mouse lymphoma assay), chromosome 
aberrations (mouse micronucleus and a dominant lethal assay) and the 
ability to induce either unscheduled or scheduled DNA synthesis in rat 
hepatocytes or DNA damage or repair in human fibroblasts. The results 
indicate that metolachlor is not mutagenic or clastogenic and does not 
provoke unscheduled DNA synthesis.
    3. Reproductive and developmental toxicity. The developmental and 
teratogenic potential of metolachlor was investigated in rats and 
rabbits. The results indicate that metolachlor is not embyrotoxic or 
teratogenic in either species at maternally toxic doses. The NOEL for 
developmental toxicity for metolachlor was 360 mg/kg/day for both the 
rat and rabbit while the NOEL for maternal toxicity was established at 
120 mg/kg/day in the rabbit and 360 mg/kg/day in the rat. A 2-
generation reproduction study was conducted with metolachlor in rats at 
feeding levels of 0, 30, 300 and 1,000 ppm. The reproductive NOEL of 
300 ppm (equivalent to 23.5 to 26 mg/kg/day) was based upon reduced pup 
weights in the F1a and F2a litters at the 1,000 ppm dose level 
(equivalent to 75.8 to 85.7 mg/kg/day). The NOEL for parental toxicity 
was equal to or greater than the 1,000 ppm dose level.
    4. Subchronic toxicity. Metolachlor was evaluated in a 21-day 
dermal toxicity study in the rabbit and a 6-month dietary study in 
dogs; NOELs of 100 mg/kg/day and 7.5 mg/kg/day were established in the 
rabbit and dog, respectively. The liver was identified as the main 
target organ.
    5. Chronic toxicity. A 1-year dog study was conducted at dose 
levels of 0, 3.3, 9.7, or 32.7 mg/kg/day. The Agency-determined RfD for 
metolachlor is based on the 1-year dog study with a NOEL of 9.7 mg/kg/
day. The RfD for metolachlor is established at 0.1 mg/kg/day using a 
100-fold uncertainty factor. A combined chronic toxicity/oncogenicity 
study was also conducted in rats at dose levels of 0. 1.5, 15 or 150 
mg/kg/day. The NOEL for systemic toxicity was 15 mg/kg/day. An 
evaluation of the carcinogenic potential of metolachlor was made from 
two sets of oncogenicity studies conducted with metolachlor in rats and 
mice. Using the Guidelines for Carcinogenic Risk Assessment published 
September 24, 1986 (51 FR 33992) and the results of the November, 1994 
Carcinogenic Peer Review, EPA has classified metolachlor as a Group C 
carcinogen and recommended using a Margin of Exposure (MOE) approach to 
quantify risk. This classification is based upon the marginal tumor 
response observed in livers of female rats treated with a high 
(cytotoxic) dose of metolachlor (3,000 ppm). The two studies conducted 
in mice were negative for oncogenicity.
    6. Animal metabolism. The qualitative nature of the metabolism of 
metolachlor in animals is well understood. Metolachlor is rapidly 
metabolized and almost totally eliminated in the excreta of rats, 
goats, and poultry. Metabolism in plants and animals proceeds through 
common Phase 1 intermediates and glutathione conjugation.
    7. Metabolite toxicology. The metabolism of metolachlor has been 
well characterized in standard FIFRA rat metabolism studies. The 
metabolites found are considered to be toxicologically similar to 
parent. Metolachlor does not readily undergo dealkylation to form an 
aniline or quinone amine as has been reported for other members of the 
chloroacetanilide class of chemicals. Therefore, it is not appropriate 
to include metolachlor with the group of chloroacetanilides that 
readily undergo dealkylation, producing a common toxic metabolite 
(quinone imine).

C. Aggregate Exposure

    1. Dietary exposure. Dietary exposure consists of exposures from 
food and drinking water.
    2. Food. For purposes of assessing the potential dietary exposure 
to metolachlor, aggregate exposure has been estimated based on the TMRC 
from the use of metolachlor in or on raw agricultural commodities for 
which tolerances have been previously established (40 CFR 180.368). The 
incremental effect on dietary risk resulting from the addition of 
sunflowers to the label was assessed by conservatively assuming that 
exposure would occur at the proposed tolerance level of 0.3 ppm with 
100% of the crop treated.
    The TMRC is obtained by multiplying the tolerance level residue for 
all these raw agricultural commodities by the consumption data which 
estimates the amount of these products consumed by various population 
subgroups. Some of these raw agricultural commodities (e.g. corn forage 
and fodder, peanut hay, sunflower meal) are fed to animals; thus 
exposure of humans to residues in these fed commodities might result if 
such residues are transferred to meat, milk, poultry, or eggs. 
Therefore, tolerances of 0.02 ppm for milk, meat and eggs and 0.2 ppm 
for kidney and 0.05 ppm for liver have been established for 
metolachlor. In an EPA review of sunflower residue data previously 
submitted by Novartis, the EPA has indicated that any secondary 
residues in meat, milk, poultry and eggs will be covered by existing 
metolachlor tolerances.
    In conducting this exposure assessment, it has been conservatively 
assumed that 100% of all raw agricultural commodities for which 
tolerances have been established for metolachlor will contain 
metolachlor residues and those residues would be at the level of the 
tolerance--which results in an overestimation of human exposure.
    3. Drinking water. Another potential source of exposure of the 
general population to residues of pesticides are residues in drinking 
water. Based on the available studies used by EPA to assess 
environmental exposure, it is not anticipated that exposure to residues 
of metolachlor in drinking water will exceed 20% of the RfD (0.02 mg/
kg/day), a value upon which the Health Advisory Level of 70 ppb for 
metolachlor is based. In fact, based on experience with metolachlor, it 
is believed that metolachlor will be infrequently found in groundwater 
(less than 5% of the samples analyzed), and when found, it will be in 
the low ppb range.
    4. Non-dietary exposure. Although metolachlor may be used on turf 
and ornamentals in a residential setting, that use represents less than 
0.1% of the total herbicide market for residential turf and landscape 
uses. Currently, there

[[Page 52558]]

are no acceptable, reliable exposure data available to assess any 
potential risks. However, given the small amount of material that is 
used, it is concluded that the potential for non-occupational exposure 
to the general population is unlikely.

D. Cumulative Effects

     The potential for cumulative effects of metolachlor and other 
substances that have a common mechanism of toxicity has also been 
considered. It is concluded that consideration of a common mechanism of 
toxicity with other registered pesticides in this chemical class 
(chloroacetamides) is not appropriate. Since EPA has concluded that the 
carcinogenic potential of metolachlor is not the same as other 
registered chloroacetamide herbicides, based on differences in rodent 
metabolism (EPA Peer Review of metolachlor, 1994), it is believed that 
only metolachlor should be considered in an aggregate exposure 
assessment.

E. Safety Determination

    1. U.S. population. Using the conservative exposure assumptions 
described above, based on the completeness and reliability of the 
toxicity data, it is concluded that aggregate exposure to metolachlor 
will utilize 1.3% of the RfD for the U.S. population. EPA generally has 
no concern for exposures below 100% of the RfD because the RfD 
represents the level at or below which daily aggregate dietary exposure 
over a lifetime will not pose appreciable risks to human health. 
Therefore, it is concluded that there is a reasonable certainty that no 
harm will result from aggregate exposure to metolachlor or metolachlor 
residues.
    2. Infants and children. In assessing the potential for additional 
sensitivity of infants and children to residues of metolachlor, data 
from developmental toxicity studies in the rat and rabbit and a 2-
generation reproduction study in the rat have been considered. The 
developmental toxicity studies are designed to evaluate adverse effects 
on the developing organism resulting from chemical exposure during 
prenatal development to one or both parents. Reproduction studies 
provide information relating to effects from exposure to a chemical on 
the reproductive capability of mating animals and data on systemic 
toxicity.
    Developmental toxicity (reduced mean fetal body weight, reduced 
number of implantations/dam with resulting decreased litter size, and a 
slight increase in resorptions/dam with a resulting increase in post-
implantation loss) was observed in studies conducted with metolachlor 
in rats and rabbits. The NOEL's for developmental effects in both rats 
and rabbits were established at 360 mg/kg/day. The developmental effect 
observed in the metolachlor rat study is believed to be a secondary 
effect resulting from maternal stress (lacrimation, salivation, 
decreased body weight gain and food consumption and death) observed at 
the limit dose of 1,000 mg/kg/day.
    A 2-generation reproduction study was conducted with metolachlor at 
feeding levels of 0, 30, 300 and 1,000 ppm. The reproductive NOEL of 
300 ppm (equivalent to 23.5 to 26 mg/kg/day) was based upon reduced pup 
weights in the F1a and F2a litters at the 1,000 ppm dose level 
(equivalent to 75.8 to 85.7 mg/kg/day). The NOEL for parental toxicity 
was equal to or greater than the 1,000 ppm dose level.
    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 pre- and post-natal toxicity and the completeness of the 
database. Based on the current toxicological data requirements, the 
database relative to pre- and post-natal effects for children is 
complete. Further, for the chemical metolachlor, the NOEL of 9.7 mg/kg/
day from the metolachlor chronic dog study, which was used to calculate 
the RfD (discussed above), is already lower than the developmental 
NOEL's of 360 mg/kg/day from the metolachlor teratogenicity studies in 
rats and rabbits. In the metolachlor reproduction study, the lack of 
severity of the pup effects observed (decreased body weight) at the 
systemic lowest observed-effect-level (equivalent to 75.8 to 85.7 mg/
kg/day) and the fact that the effects were observed at a dose that is 
nearly 10 times greater than the NOEL in the chronic dog study (9.7 mg/
kg/day) suggest there is no additional sensitivity for infants and 
children. Therefore, it is concluded that an additional uncertainty 
factor is not warranted to protect the health of infants and children 
and that the RfD at 0.1 mg/kg/day based on the chronic dog study is 
appropriate for assessing aggregate risk to infants and children from 
use of metolachlor.
    Using the conservative exposure assumptions described above, the 
percent of the RfD that will be utilized by aggregate exposure to 
residues of metolachlor including the proposed use on sunflowers is 
1.1% for nursing infants less than 1 year old, 3.3% for non-nursing 
infants, 2.7% for children 1 to 6 years old and 2.0% for children 7 to 
12 years old. Therefore, based on the completeness and reliability of 
the toxicity data and the conservative exposure assessment, it is 
concluded that there is a reasonable certainty that no harm will result 
to infants and children from aggregate exposure to metolachlor 
residues.

F. International Tolerances

     There are no Codex Alimentarius Commission (CODEX) maximum residue 
levels (MRL's) established for residues of metolachlor in or on raw 
agricultural commodities.

[FR Doc. 97-26535 Filed 10-7-97; 8:45 am]
BILLING CODE 6560-50-F


</pre><script data-cfasync="false" src="/cdn-cgi/scripts/5c5dd728/cloudflare-static/email-decode.min.js"></script></body>
</html>