[Federal Register Volume 63, Number 6 (Friday, January 9, 1998)]
[Notices]
[Pages 1456-1464]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-557]


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ENVIRONMENTAL PROTECTION AGENCY

[PF-786; FRL-5762-6]


Notice of Filing of Pesticide Petitions

AGENCY: Environmental Protection Agency (EPA).


[[Page 1457]]


ACTION: Notice.

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SUMMARY: This notice announces the initial filing of pesticide 
petitions proposing the establishment of regulations for residues of 
certain pesticide chemicals in or on various food commodities.
DATES: Comments, identified by the docket control number PF-786, must 
be received on or before February 9, 1998.
ADDRESSES: By mail submit written comments to: Public Information and 
Records Integrity Branch (7502C), Information Resources and Services 
Division, 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: opp-
[email protected]. 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:

------------------------------------------------------------------------
                                   Office location/                     
        Product Manager            telephone number          Address    
------------------------------------------------------------------------
Joanne Miller (PM 23).........  Rm. 237, CM #2, 703-    1921 Jefferson  
                                 305-6224, e-mail:       Davis Hwy,     
                                 miller.joanne@epamail   Arlington, VA  
                                 .epa.gov.                              
Marion Johnson (PM 10)........  Rm. 217, CM #2, 703-    Do.             
                                 305-6788, e-mail:                      
                                 johnson.marion@epamai
l.epa.gov.                             
Cynthia Giles-Parker (PM 22)..  Rm. 229, CM #2, 703-    Do.             
                                 305-7740, e-mail:                      
                                 giles-
parker.cynthia@epamai
l.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-786] (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:
    [email protected]


    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 5.1/6.1 or ASCII file 
format. All comments and data in electronic form must be identified by 
the docket control number [PF-786] and appropriate petition number. 
Electronic comments on this 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: December 17, 1997.

James Jones,

Acting 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. BASF Corporation

PP 7F4881

    EPA has received a pesticide petition (PP 7F4881) from BASF 
Corporation, Agricultural Products, P.O. Box 13528, Research Triangle 
Park, NC 27709, 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 Pridaben, [2 tert-
butyl-5(4-tert-butylbenzylthio)-4- chloropyridazin-3(2H)-one] in or on 
the raw agricultural commodity. 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. BASF Corporation notes that metabolism in 
plants is understood.
    2. Analytical method. The proposed analytical method involves 
extraction, partition, clean-up and detection of residues by gc/ecd.
    3. Magnitude of residues. Eleven peach residue trials to determine 
residues in peaches and nectarines were conducted in eight states. 
Residues of pyridaben were measured by gc/ecd. The method of detection 
had a limit of detection of 0.05 parts per million (ppm). Residues 
ranged from <0.05 to 2.36.

[[Page 1458]]

    Eight plum residue trials to determine residues in plums and prunes 
were conducted in four states. Residues of pyridaben were measured by 
gc/ecd. The method of detection had a limit of detection of 0.05 ppm. 
Residues ranged from <0.05 to 0.683 ppm.
    No residues trials were conducted to determine residues in cherries 
and apricots. Only postharvest applications are requested. No residues 
will occur since pyridaben is not systemic and does not translocate. 
The limit of detection of 0.05 ppm is proposed as the tolerance.
    Fifteen grape residue trials were conducted in six states. Residues 
of pyridaben were measured by gc/ecd. The method of detection had a 
limit of detection of 0.05 ppm. Residues ranged from 0.168 to 1.38 ppm.
    Six pecan residue trials were conducted in four states to complete 
requirements for a group tolerance for nut crops. BASF Corporation was 
granted a tolerance of 0.05 ppm for use on almonds. Residues of 
pyridaben were measured by gc/ecd. The method of detection had a limit 
of detection of 0.05ppm. There were no residues above 0.05 ppm.

B. Toxicological Profile

    1. Acute toxicity--Acute toxicity testing. i. Acute Oral Toxicity 
(rat): LD50 = 1,100 mg/kg in males; 570 mg/kg in females. 
Tox Category: III.
    ii. Acute Oral Toxicity (mouse): LD50 = 424 mg/kg in 
males; 383 mg/kg in females. Tox Category: II.
    iii. Acute Dermal Toxicity (rat): LD50 = >2000 mg/kg in 
males and females. Tox Category: III.
    iv. Acute Inhalation Toxicity (rat): LC50 = 0.66 mg/l in 
males; 0.62 mg/l in females. Tox Category: III.
    v. Primary Eye Irritation (rabbit): Pyridaben is a slight ocular 
irritant. Tox Category: III.
    vi. Primary Dermal irritation (rabbit): Pyridaben is not a dermal 
irritant. Tox Category: IV.
    vii. Dermal Sensitization (guinea pig): Pyridaben is not a dermal 
sensitizer.
    viii. Acute Neurotoxicity (rat): Rats were dosed once with 0, 50, 
100 and 200 milligram/kilogram (mg/kg). The No Observed Effect Level 
(NOEL) for systemic toxicity was determined to be 50 mg/kg for both 
males and females. The Lowest Observed Effect Level (LOEL) for systemic 
effects was determined to be 100 mg/kg in both sexes based on decreased 
food consumption, decreased body weight gain and increased clinical 
signs. The LOEL for neurobehavioral effects was determined to be 200 
mg/kg in males and >200 mg/kg in females.
    2. Mutagenicity testing--Ames testing: Negative In vitro 
cytogenicity (Chinese hamster lung cells): Negative In vivo 
micronucleus assay (mouse): Negative DNA damage/repair (E. coli): 
Negative.
    3. Reproductive and developmental toxicity-- i. Developmental 
toxicity testing (rat). Sprague Dawley rats were dosed with 0, 2.5, 
5.7, 13 and 30 mg/kg/day pyridaben in the diet from days 6 through 15 
of gestation. The Maternal NOEL was determined to be 4.7 mg/kg/day and 
the maternal LOEL was determined to be 13 mg/kg/day based on decreased 
body weight gain, and decreased food consumption during the dosing 
period. The developmental NOEL was determined to be 13 mg/kg/day and 
the developmental LOEL was determined to be 30 mg/kg/day based on 
decreased fetal body weight and an increase in incomplete ossification 
in selected bones.
    ii. Developmental toxicity (rabbit). New Zealand white rabbits were 
dosed with 0, 1.5, 5, and 15 mg/kg/day pyridaben in the diet from days 
6 through 19 of gestation. The Maternal NOEL was determined to be 5 mg/
kg/day and the maternal LOEL was determined to be 15 mg/kg/day based on 
decreased body weight gain, and decreased food consumption during the 
dosing period. The developmental NOEL was determined to be >15 mg/kg/
day and the developmental LOEL was determined to be >15 mg/kg/day.
    iii. Developmental toxicity (rabbit). Himalayan rabbits were dosed, 
by dermal application, with 0, 70, 170 and 450 mg/kg/day pyridaben from 
days 6 through 19 of gestation. The Maternal systemic NOEL was 
determined to be 70 mg/kg/day and the maternal LOEL was determined to 
be 170 mg/kg/day based on decreased body weight gain, and decreased 
food consumption during the dosing period. The developmental NOEL was 
determined to be 170 mg/kg/day and the LOEL determined to be 450 mg/kg/
day based on decreased ossification of the skull.
    iv. Reproductive toxicity testing, multigeneration reproduction 
(rat). CD rats were dosed with 0, 10, 28 and 80 ppm pyridaben in the 
diet. The Parental/Systemic NOEL was determined to be 28 ppm in both 
sexes (equivalent to 2.20 mg/kg/day in males and 2.41 mg/kg/day in 
females). The Parental/Systemic LOEL was determined to be 80 ppm 
(equivalent to 6.31 mg/kg/day in males and 7.82 mg/kg/day in females) 
based on decreased body weight, decreased body weight gain and 
decreased food efficiency. The reproductive NOEL and LOEL were both 
determined to be >80 ppm in males and females.
    4. Subchronic toxicity-- i. A 21-day dermal (rat). Rats were 
repeatedly dosed with pyridaben at 0, 30. 100, 300 and 1,000 mg/kg/day 
for 21 days. The NOEL was determined to be 100 mg/kg/day and the LOEL 
300 mg/kg/day based on decreased body weight gain in females.
    ii. A 90-day rodent (rat). CD rats were dosed with pyridaben at 0, 
30, 65, 155 and 350 ppm in the diet for 13 weeks. The NOEL was 
determined to be 65 ppm (4.94 mg/kg/day) for males and 30 ppm (2.64 mg/
kg/day) in females. The LOEL for males was determined to be 155 ppm 
(11.55 mg/kg/day) based on reduced body weight gain, reduced food 
consumption, reduced food efficiency, and altered clinical pathology 
parameters. The LOEL for females was determined to be 65 ppm (5.53 mg/
kg/day) based on reduced body weight gain and reduced food efficiency.
    iii. A 90-day non-rodent (dog). Beagle dogs were dosed with 
pyridaben at 0, 0.5, 1,4, and 16 mg/kg/day in the diet for 13 weeks. 
The NOEL was determined to be 1 mg/kg/day and the LOEL determined to be 
4 mg/kg/day based on reduced body weight gain and an increase in 
clinical signs in both sexes.
    iv. A 90-day neurotoxicity (rat). Rats were dosed with pyridaben at 
0, 30, 100, and 350 ppm in the diet for 13 weeks. The systemic NOEL was 
determined to be 100 ppm (equivalent to 8.5 mg/kg/day in males and 9.3 
mg/kg/day in females). The systemic LOEL was determined to be 350 ppm 
(equivalent to 28.8 mg/kg/day in males and 31.1 mg/kg/day in females) 
based on decreased body weight gain, decreased food consumption and 
decreased food efficiency. No neuropathological effects were noted in 
the study.
    5. Chronic toxicity-- i. A 1-year non-rodent (dog). Two studies 
were run. In the first, beagle dogs were dosed with pyridaben at 0, 1, 
4, 16 and 32 mg/kg/day in the diet for 1-year. In the second, beagle 
dogs were dosed with pyridaben at 0 and 0.5 mg/kg/day in the diet for 
1-year. The NOEL was determined to be <0.5 ppm and LOEL determined to 
be 0.5 mg/kg/day based on increased clinical signs and decreased body 
weight gain in both sexes.
    ii. Combined rodent chronic toxicity/carcinogenicity (rat). Wistar 
rats were fed 0, 4, 10, 28 and 80 ppm pyridaben in the diet to assess 
carcinogenicity and 0, 4, 10, 28 and 120 ppm in the diet to assess 
chronic toxicity for 104 weeks. The NOEL was determined to be 28 ppm in 
both sexes (equivalent to 1.13 mg/kg/day in males and 1.46 mg/kg/day in 
females). The LOEL was determined

[[Page 1459]]

to be 120 ppm in both sexes (equivalent to 5.0 mg/kg/day in males and 
6.52 mg/kg/day in females) based on decreased body weight gain in both 
sexes and decreased ALT levels in males. Pyridaben was not carcinogenic 
under the conditions of the test.
    iii. Carcinogenicity in the rodent (mouse). CD-1 mice were fed 0, 
2.5, 8.0, 25 and 80 ppm pyridaben in the diet for 78 weeks. The NOEL 
was determined to be 25 ppm in both sexes (equivalent to 2.78 mg/kg/day 
in both sexes). The LOEL was determined to be 80 ppm in both sexes 
(equivalent to 8.88 mg/kg/day in males and 9.74 mg/kg/day in females) 
based on decreased body weight gain, decreased food efficiency and 
changes in organ weights and histopathology. Pyridaben was not 
carcinogenic under the conditions of the test.
    6. Animal metabolism. BASF Corporation notes that metabolism in 
animals is understood.
    7. Threshold effects. Based on the available chronic toxicity data, 
EPA has established the Reference Dose (RfD) for pyridaben at 0.005 mg/
kg/day. The RfD for pyridaben is based on a 1-year feeding study in 
dogs with a threshold Lowest-Observed Effect Level (LOEL) of 0.5 mg/kg/
day based on increased clinical signs and decreased body weight gain in 
both sexes and an uncertainty factor of 100.
    8. Non-threshold effects. Using its Guidelines for Carcinogenic 
Risk Assessment, EPA has classified pyridaben as Group ``E'' for 
carcinogenicity (no evidence of carcinogenicity) based on the results 
of carcinogenicity studies in two species. There was no evidence of 
carcinogenicity in an 18-month feeding study in mice and a 2-year 
feeding study in rats at the dosage levels tested. The doses tested 
were adequate for identifying a cancer risk. Thus, a cancer risk 
assessment is not necessary.

C. Aggregate Exposure

    1. Dietary exposure--i. Food. Since Pyridaben is regulated based 
upon non-carcinogenic chronic toxicity, BASF conducted a DRES analysis 
based on anticipated residue levels determined by the tolerance support 
branch of HED. The anticipated residue levels were derived from the 
average residue levels from field trials conducted at the maximum 
proposed use rate and minimum pre-harvest interval, and a correction 
factor of 2.3 to account for all organosoluble residues as determined 
by EPA HED. This analysis demonstrates that the exposure to non-nursing 
infants <1 year, the most sensitive sub-population is approximately 
128.6% of the RfD and to the general population exposure is 
approximately 18.6%. Assuming a conservative pyridaben market share of 
65% of all crop uses, then the most sensitive sub-population is 
approximately 83.8% of the RfD and to the general population exposure 
is approximately 12.1%.
    ii. Drinking water. Other potential sources of exposure of the 
general population to residues of pesticides are residues in drinking 
water and exposure from non-occupational sources. Based on the studies 
submitted to EPA for assessment of environmental risk, BASF does not 
anticipate exposure to residues of pyridaben in drinking water. There 
is no established Maximum Concentration Level for residues of pyridaben 
in drinking water under the Safe Drinking Water Act. BASF has not 
estimated non-occupational exposure for pyridaben since the current 
registration for pyridaben is limited to commercial greenhouse use for 
non-food ornamental plants and the only other use will be for 
commercial apple/pear and citrus production The potential for non-
occupational exposure to the general population is considered to be 
insignificant.

D. Cumulative Effects

    BASF also considered the potential for cumulative effects of 
pyridaben and other substances that have a common mechanism of 
toxicity. BASF has concluded that consideration of a common mechanism 
of toxicity is not appropriate at this time since there is no reliable 
information to indicate that toxic effects produced by pyridaben would 
be cumulative with those of any other chemical compounds.

E. Safety Determination

    1. U.S. population. Reference Dose (RfD), using the exposure 
assumptions described in section III, above, BASF concludes that 
aggregate exposure to pyridaben will utilize approximately 12.1% the 
RfD for the U.S. population. EPA generally has no concern for exposures 
below 100% of the RfD. Therefore, based on the completeness and 
reliability of the toxicity data and the conservative exposure 
assessment, BASF concludes that there is a reasonable certainty that no 
harm will result from aggregate exposure to residues of pyridaben, 
including all anticipated dietary exposure and all other non-
occupational exposures.
    2. Infants and children. Developmental toxicity (delayed 
ossification) was observed in developmental toxicity studies using rats 
and rabbits. The No-Observed Effect Level's (NOEL's) for developmental 
effects were established at 13 mg/kg/day in the rat study and 15 mg/kg/
day in the rabbit study. The developmental effect observed in these 
studies is believed to be a secondary effect resulting from maternal 
stress (decreased body weight gain and food consumption).
    In a 2-generation reproduction study in rats, pups from the high 
dose group, which were fed diets containing 80 ppm (equivalent to 6.31 
and 7.82 mg/kg/day in male and females, respectively) gained less 
weight beginning on lactation day 14. Parental systemic toxicity 
including decreased body weights, body weight gains and food efficiency 
in males, and slightly decreased body weights and body weight gains in 
females during lactation was also observed in the high dose group. The 
results of this study indicate that the loss in weight gain in pups 
from the high dose group was affected by nursing.
    No clear scientific consensus yet exists to define the most 
appropriate endpoints for assessing risk in children. However, in 
consideration of the data that show both developmental and reproductive 
toxicity were effects secondary to parental toxicity, BASF believes 
that the established Reference Dose (RfD) of 0.005 mg/kg/day is the 
most conservative approach for assessing risk in children. Using the 
exposure assumptions described in section 5, above, BASF has concluded 
that the percent of the RfD, when adjusted for a conservative market 
share of 65%, that will be utilized by aggregate exposure to residues 
of pyridaben from the proposed use in citrus, apples, pears, almonds, 
peaches, plums, and grapes is approximately 83.8% for non-nursing 
infants (< 1 year), the most sensitive sub-population. Based on the 
completeness and reliability of the toxicity data and the conservative 
exposure assessment, BASF concludes that there is a reasonable 
certainty that no harm will result to infants and children from 
aggregate exposure to the residues of pyridaben, including all 
anticipated dietary exposure and all other non-occupational exposures.

F. Other Considerations

    The qualitative nature of the residues in plants and animals is 
adequately understood. Residues of the parent molecule, pyridaben are 
the only residues of concern. Residues of pyridaben do not concentrate 
in the processed commodities apple and citrus juice. There is a 
practical analytical method for detecting and measuring levels of 
pyridaben in or on food with

[[Page 1460]]

a limit of detection that allows monitoring of food with residues at or 
above the levels set in these tolerances. Endocrine effects. No 
specific tests have been conducted with pyridaben to determine whether 
the chemical may have an effect in humans that is similar to an effect 
produced by a naturally occurring estrogen or other endocrine effects. 
However, there were no significant findings in other relevant toxicity 
studies, i.e., teratology and multi-generation reproductive studies, 
which would suggest that pyridaben produces endocrine related effects.

G. International Tolerances

    A maximum residue level has not been established for pyridaben by 
the Codex Alimentarius Commission.    (PM 10)

2. GMJA Specialties

PP 7G4891

    EPA has received a pesticide petition (PP 7G4891) from GMJA 
Specialties, 1001 13th Avenue East, Bradenton, FL 34208, 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 PT807-HCl in or on the raw agricultural commodity 
oranges at 0.01 ppm. The proposed analytical method is extracting 
PT807-HCl from whole oranges, juice, and dried pulp using organic 
solvents has been validated. Extracted PT807-HCl residues are analyzed 
using high performance liquid chromatography (HPLC) with a UV detector. 
The limit of quantitation (LOQ) of the method is 0.01 part per million 
(ppm). EPA has determined that the petition contains data or 
information regarding the elements set forth in section 408(d)(2) of 
the FFDCA; however, EPA has not fully evaluated the sufficiency of the 
submitted data at this time or whether the data supports granting of 
the petition. Additional data may be needed before EPA rules on the 
petition.

A. Residue Chemistry

    Plant metabolism. The metabolism of PT807-HCl in plants and animals 
is understood. In plants (oranges), unchanged parent is the only 
residue identified in fruit. Valencia orange trees were treated with 
14C PT807-HCl at a nominal rate of 1,000 ppm (approximately 
60x the maximum recommended application rate). Fruit from the previous 
season's crop present on the tree at the time of application was 
harvested 50 days after treatment (DAT) and mature fruit (not present 
on the tree at application) was harvested 370 DAT. Total radioactive 
residue (TRR) levels were 0.538 ppm in 50 DAT orange samples and were 
0.051 ppm in 370 DAT orange samples. Most of the radioactivity was 
present on the peel (88.63% TRR or 0.475 ppm in the 50 DAT fruit, and 
64.19% TRR or 0.033 ppm in the 370 DAT fruit). Unchanged parent PT807-
HCl was detected in 50 DAT mature fruit using organic solvents has been 
validated. Extracted PT807-HCl residues are analyzed using HPLC with a 
UV detector. The LOQ of the method is 0.01 ppm.

B. Toxicological Profile

    1. Acute toxicity. A battery of acute toxicity studies has been 
conducted and the results indicate that PT807-HCl exhibits low acute 
oral, dermal, and inhalation toxicity. PT807-HCl also has low potential 
as a skin or eye irritant and is not a skin sensitizer.
    2. Genotoxicity. The genotoxic potential of PT807-HCl has been 
assessed in an Ames Salmonella assay, a CHO HGPRT gene mutation assay, 
a mouse micronucleus assay, and an in vitro CHO assay for chromosomal 
aberrations. The in vitro chromosomal aberration assay was positive 
with and without metabolic activation; however, all of the remaining 
assays were negative, indicating very low genotoxic potential of PT807 
weakened by the negative finding in an in vivo study (mouse 
micronucleus) measuring a similar endpoint.
    3. Reproductive and developmental toxicity. A 2-generation 
reproductive toxicity study of PT807-HCl is ongoing.
    4. Analytical method. An analytical method capable of extracting 
PT807-HCl from whole oranges, juice, and dried pulp using organic 
solvents has been validated. Extracted PT807-HCl residues are analyzed 
using high performance liquid chromatography (HPLC) with a UV detector. 
The limit of quantitation (LOQ) of the method is 0.01 ppm.
    5. Magnitude of residues. Seventeen field trials were conducted 
using various varieties of oranges in California (4 trials), Florida 
(12 trials), and Texas (1 trial). Two of the trials (1 in California 
and 1 in Florida) were decline studies with sampling intervals of 0, 7, 
14, 30, and 60 days after application. For all other trials, oranges 
were harvested at the earliest possible time for normal commercial 
harvest after a single application with PT807-HCl at the maximum 
recommended application rate (6 g a.i./A). At some of the test sites 
(depending on the variety of oranges), the previous season's crops was 
present on the tree at application for these trials, oranges were 
collected 0 to 68 days after treatment (DAT). In all other trials, 
fruit were not present on the trees at applications and mature oranges 
were collected at normal harvest (197 to 359 DAT). Samples were 
analyzed for residues of PT807-HCl by HPLC with UV detection. Residues 
of PT807-HCl were nondetectable (<0.01 ppm) in all treated and control 
samples.
    A processing study was conducted using oranges treated at 5x the 
maximum application rate in California. The harvested oranges were from 
the previous season's crop and were on the tree at the time of 
application. Therefore the application represents the maximum possible 
residues. No detectable residues were measured in whole oranges, juice, 
or oil. Residues of PT807-HCl were detectable in dried pulp at 0.015 
and 0.017 ppm (average 0.016 ppm). Correcting the measured residues for 
the exaggerated application rate, no detectable residues are likely in 
any processed product of oranges.
    Residues of PT807-HCl were determined to be stable in whole orange 
fruit, oil, juice, and dried pulp stored frozen up to 113 days.
    6. Subchronic toxicity. Subchronic toxicity studies have been 
conducted with PT807-HCl in mice, rats, and dogs. In dietary studies in 
rats and dogs, the most notable findings include decreased food 
consumption and a consequent decrease in bodyweight gain.(resulting 
primarily from poor palatability of the test material). Dogs also 
showed a trend toward anemia, and males showed arrested or delayed 
sexual maturation at the high dose (equivalent to approximately 222 mg/
kg/day). Marked weight loss and decreased weight gain was observed at 
this dose and this dose level is considered to have exceeded a MTD. 
Rats dosed by gavage showed signs of neurotoxic effects (tremors, 
incoordination, changes in activity) at doses 3-- mg/kg/day. In mice 
treatment-related decreased food consumption and body weight gain were 
seen in males at 7,000 (HDT). No treatment-related toxicity was evident 
at dietary doses up to 3,500 ppm (479 and 635 mg/kg/day for males and 
females, respectively).
    7. Chronic toxicity. Chronic toxicity studies of PT807-HCl in rats 
and doges are currently ongoing.
    8. Animal metabolism. 14CPT807-HCl was extensively 
metabolized and readily eliminated in the urine and feces following 
oral administration to a lactating goat. The efficient elimination 
processes resulted in negligible to modest retention of radioactive 
residues in milk and tissues (<0.2 % of the administered dose). No 
residues of unchanged parent were identified in tissues or milk. The 
rapid elimination of the PT807-HCl and its metabolites

[[Page 1461]]

coupled with the highly exaggerated dose (approximately 3,600x the 
dietary burden) clearly indicates that no detectable residues of PT807-
HCl will accumulate in milk and tissues.
    9. Metabolite toxicology. The metabolism of PT807-HCl in oranges 
has been determined. The only significant metabolite is unchanged 
parent. No detectable residues of PT807-HCl are anticipated in oranges 
treated at the recommended application rate.

C. Aggregate Exposure

    1. Dietary exposure. There are no anticipated dietary exposures to 
PT807-HCl outside of those requested in this temporary tolerance 
petition. The chronic dietary exposure from the consumption of oranges 
and its processed products treated with PT807-HCl is very low. The 
exposure is only 5.0 % of the RfD (0.00063 mg/kg/day) for the most 
highly exposed sub-population, children 1 to 6 years old. The dietary 
exposure is only 1.7% of the RfD (0.00021 mg/kg/day) for the U.S. 
population.
    2. Food. The proposed temporary tolerance of 0.01 ppm was used for 
the residue level to calculate the dietary exposure from residues of 
PT807-HCl in or on oranges. Based on the processing study, there is no 
anticipated concentration of residues of PT807-HCl in processed 
products of oranges, therefore, the proposed temporary tolerance level 
for whole oranges was also used for the processed commodities. For the 
purpose of calculating a worst-case estimate, it was assumed that 100% 
of the oranges and their processed products were treated with PT807-
HCl.
    3. Drinking water. Based on the results of the GENEEC model, the 
56-day chronic EEC (calculated from the lowest Koc value 
measured for PT807-HCl) is 0.315 g/L. Using the standard 
drinking water consumption scenarios of 2 liters per day for a 70-kg 
adult and 1 liter per day for a 10 kg child, the calculated consumption 
of PT807-HCl in drinking is 0.009 g/kg/day for an adult and 
0.032 g/kg/day for a child. These consumption values 
correspond to 0.7% of the RfD for adults and 2.6% of the RfD for 
children. As discussed above, drinking water concentrations calculated 
by the GENEEC procedure represent very conservative screening level 
assessments of drinking water exposure. Finally, the above drinking 
water calculations use the water concentration calculated from the 
lowest Koc value measured for PT807-HCl. Three of four soils 
tested gave Koc values that are more than 10-fold higher, 
leading to correspondingly lower calculated water concentrations.
    4. Non-dietary exposure. There are currently no registered uses for 
PT807-HCl, and therefore, there is no anticipated non-occupational 
exposure to the chemical.

D. Cumulative Effects

    GMJA Specialities is not aware of any currently registered products 
that are structurally similar to PT-807-HCl or that would be likely to 
share a common mechanism of action. Therefore, no cumulative exposures 
are considered in the PT807-HCl dietary risk assessment.

E. Safety Determination

    1. U.S. population. The chronic dietary exposure from the 
consumption of oranges and its processed products treated with PT807-
HCl is very low. The exposure is only 5.0 % of the RfD (0.00063 mg/kg/
day) for the most highly exposed sub-population, children 1 to 6 years 
old. The dietary exposure is only 1.7% of the RfD (0.00021 mg/kg/day) 
for the U.S. population.
    2. Infants and children. The reference dose is conservatively 
calculated using a very high (10,000-fold ) safety factor for children. 
Based on currently available data, PT807-HCl does not present a unique 
hazard to infants or children and there is no evidence that children 
are likely to be more sensitive to the toxic effects of PT807-HCl. A 2-
generation reproductive toxicity study with PT807-HCl in rats is 
currently ongoing. PT807-HCl showed evidence of developmental effects 
in rats only at a severely maternally toxic dose level. No evidence of 
developmental toxicity was seen in rabbits.

F. International Tolerances

    There are no Codex Alimentarius Commission (Codex Maximum Residue 
Levels (MRLs) for PT807-HCl.    (PM 22)

3. Rohm & Haas Company

PP 3F4229

    EPA has received a pesticide petition (PP 3F4229) from Rohm & Haas 
Company, Philadelphia, PA, 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 oxyfluorfen in or 
on the raw agricultural commodities peanut meat, meal, vine, hay, crude 
oil, soap stock, and refined oil at 0.05 ppm and peanut hulls at 0.10 
ppm. The proposed analytical method involves extraction from the raw 
agricultural commodity with methanol or acetonitrite. Extracts are 
refluxed in presence of NaOH and Al to reduce and or hydrolyze residues 
to 4-(2-chloro-4-(trifluoromethyl)-phenoxy)-2-ethoxybenzenenamine. The 
derivatives are partitioned into hexane and heptafluorobutyryl 
derivatives prepared. Following Florisel cleanup, residues are 
determined by electron capture GLC. 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 and animal metabolism. The chemical identities of 
potential plant residues resulting from the use of oxyfluorfen have 
been elucidated. The principal residue in plants is parent oxyflurofen.
    The chemical identities of potential animal residues resulting from 
consumption of oxyfluorfen-treated crops have been elucidated. Parent 
oxyfluorfen is the principal residue in animal tissues. Oxyfluorfen 
residues do not transfer to milk (concentration <0.01 ppm at 10x dose). 
Residues also do not appreciably transfer to cow muscle, liver and 
kidney (highest level 0.011 ppm at 10x dose). Residues are present in 
cow fat at low levels (less than 0.01 at 1x dose). Residues in eggs and 
hen liver are 0.02 ppm or less on average at a 1x dose, and less than 
0.01 ppm in muscle at the 1x dose. Residues approach 0.2 ppm in hen fat 
at the 1x dose.
    2. Analytical method. There is a practical analytical method for 
detecting and measuring levels of oxyfluorfen in or on food with a 
limit of detection that allows monitoring of food with residues at or 
above the levels in these proposed tolerances. EPA has provided 
information on this method to FDA. The method is available to anyone 
who is interested in pesticide residue enforcement from: By mail, 
Calvin Furlow, Public Response and Program Resources Branch, Field 
Operations Division (7502C), Office of Pesticide Programs, 
Environmental Protection Agency, 401 M St., SW., Washington, DC 20460. 
Office location and telephone number: Crystal Mall #2, Rm. 1132, 1921 
Jefferson Davis Highway, Arlington, Virginia, 703-305-5805.
    3. Magnitude of the residues. Residue studies have been conducted 
in accordance with the geographic distribution mandated by the EPA for 
peanuts. Oxyfluorfen residues were not detectable in nutmeat [NDR 80 mg/kg/day (NOEL 20 
mg/kg/ day) in a rat 2-generation reproduction study.
    4. Subchronic and chronic toxicity. Adverse effects on the liver 
marked the LOEL in all three chronic toxicity studies with NOELs of 
2.5, 2.0, and 0.3 mg/kg/day seen in the dog, rat, and mouse studies 
respectively. A statistically significant positive dose-related trend 
for liver adenomas and carcinomas was observed in the chronic mouse 
study and oxyfluorfen is classified as a Group C chemical by EPA. A 
reference dose of 0.003 mg/kg/day and a Q1* of 0.128 (mg/kg/
day) -1 has been set by the Agency.
    5. Animal metabolism. Animal metabolism studies have been conducted 
on farm animals using laying hens and lactating goats and in a 
laboratory animal (rat). These studies were reviewed and accepted by 
the Agency. EPA has concluded that the metabolism of oxyfluorfen in 
animals is adequately understood.

C. Aggregate Exposure

    1. Food. To determine chronic (using the RfD) and cancer (using the 
Q1* approach) risks, refined dietary exposure estimates 
using percent of crop treated and anticipated residues were utilized 
for registered uses of oxyfluorfen with established tolerances on the 
following food and/or animal feed items: dates, figs, guava, loquats, 
olives, papaya, persimmon, pomegranate, plantains, kiwi, cocoa butter, 
coffee, artichokes, taro-roots and greens, garlic, shallots, 
cauliflower, bok-choy, and other Chinese variety cole crops, dry beans, 
crabapples, quince, blackberry, raspberry, Brazil nut, cashew, 
chestnuts, hazelnuts, hickory nuts, macadamias, pecans, horseradish, 
peppermint, spearmint, pistachio nuts, cotton, cherries, nectarines, 
plums, prunes, almonds, walnuts, bananas, broccoli, cabbage, apricots, 
nutmeat, milk, onions, soybeans, apples, pears, peaches, grapes, and 
corn. Actual residues are expected to be quite low because the majority 
of the use patterns direct sprays onto weeds or soil and away from the 
crop. There are long preharvest intervals for sprays which are directly 
applied to crops.
    Acute dietary exposure (food only) was calculated using the TMRC 
(worst case) assumptions.
    2. Drinking water. The Agency has reviewed environmental fate data 
which indicate that oxyfluorfen is persistent but nonmobile. There is 
no established Maximum Concentration Level (MCL) for residues of 
oxyfluorfen in drinking water. No health advisory levels for 
oxyfluorfen in drinking water have been established. As noted in 
``Pesticides in Groundwater Database'' EPA 734-12-92-001, September 
1992, 188 wells were monitored in Texas in 1987 and 1988. No detectable 
residues of oxyfluorfen were found in any of the samples.
    While EPA has not yet pinpointed the appropriate bounding figure 
for consumption of contaminated water, the ranges the Agency is 
continuing to examine are all below the level that would cause 
oxyfluorfen to exceed the RfD if the tolerance being considered in this 
document were granted. In addition, chronic exposure to oxyfluorfen 
residues resulting from potential water exposure would not increase the 
total cancer risk so that it exceeds the Agency's level of concern. The 
potential exposures associated with oxyfluorfen in water, even at the 
higher levels the Agency is considering as a conservative upper bound 
for RfD exposure considerations, would not prevent the Agency from 
determining that there is a reasonable certainty of no harm if the 
tolerance is granted.
    Despite the potential for acute exposure to oxyfluorfen in drinking 
water, it is not expected that the aggregate acute exposure will exceed 
the Agency's level of concern if the tolerance being considered in this 
document were granted. The potential acute term exposures associated 
with oxyfluorfen in water, even at the higher levels the Agency is 
considering as a conservative upper bound, would not prevent the Agency 
from determining that there is a reasonable certainty of no harm if the 
tolerance is granted.
    3. Non-dietary exposure. Oxyfluorfen is registered for outdoor 
residential use. Acceptable, reliable data are not currently available 
with which to assess acute risk. However, based on the available 
residential exposure data and the best professional judgment of 
scientists who have worked with the available occupational exposure 
data, 5% of the risk for outdoor residential uses is a reasonable, 
protective default assumption for this pesticide. Chronic exposure to 
oxyfluorfen residues resulting from potential outdoor residential 
exposure would not increase the total chronic or cancer risks so that 
they exceed the Agency's level of concern.
    Theoretically, it is also possible that a residential, or other 
non-dietary, exposure could be combined with the acute total dietary 
exposure from food and water. However, the Agency does not believe that 
aggregating multiple exposure to large amounts of pesticide residues in 
the residential environment via multiple products and routes for a one-
day exposure is a reasonably probable event. It is highly unlikely 
that, in one day, an individual would have multiple high-end exposures 
to the same pesticide by treating their lawn and garden, treating their 
house via crack and crevice application, swimming in a pool, and be 
maximally exposed in the food and water consumed.

D. Cumulative Effects

    EPA does not have, at this time, available data to determine 
whether oxyfluorfen has a common mechanism of toxicity with other 
substances or how to include this pesticide in a cumulative risk 
assessment. Unlike other pesticides for which EPA has followed a 
cumulative risk approach based on a common mechanism of toxicity, 
oxyfluorfen does not appear to produce a toxic metabolite produced by 
other substances. For the purposes of this tolerance action, therefore, 
EPA has not assumed that oxyfluorfen has a common mechanism of toxicity 
with other substances.

E. Endocrine Effects

    The toxicity studies required by EPA for the registration of 
pesticides measure numerous endpoints with sufficient sensitivity to 
detect potential endocrine-modulating activity. No effects have been 
identified in subchronic, chronic, reproductive, or developmental 
toxicity studies to indicate any endocrine-modulating activity by 
oxyfluorfen.

[[Page 1463]]

More importantly, the multi-generation reproduction study in rodents is 
a complex study design which measures a broad range of endpoints in the 
reproductive system and in developing offspring that are sensitive to 
alterations by chemical agents. Oxyfluorfen has been tested in two 
separate multi-generation studies and each time the results 
demonstrated that oxyfluorfen is not a reproductive toxin.

F. Safety Determination

    1. U.S. population-- i. Chronic RfD and cancer risk. Using the 
refined dietary exposure assumptions described above and taking into 
account the completeness and reliability of the toxicity data, it is 
concluded that aggregate dietary exposure (food only) to oxyfluorfen 
will utilize 0.04% of the RfD for the general United States population. 
EPA has no concern generally 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. Despite the potential for exposure to oxyfluorfen in 
drinking water and from the 5% default-level contribution from non-
dietary, nonoccupational exposure, it is not expected the aggregate 
exposure will exceed 100% of the RfD. As noted above, oxyfluorfen has 
been classified as a Group C chemical by the Agency based on liver 
adenomas and carcinomas in the 20-month mouse feeding study. The Agency 
recommends using the Q1* approach to assess cancer risk. A 
value of 0.067 (mg/kg/day)-1 is recommended.
    The refined dietary assumptions for existing oxyfluorfen tolerances 
plus those proposed for peanuts result in an Anticipated Residue 
Contribution (ARC) that is equivalent to a risk of 8.0 x 
10-8 (food only). Actual residues are expected to be quite 
low because the majority of the use patterns direct sprays onto weeds 
and away from the crop and there are long preharvest intervals for 
sprays which are directly applied to crops. Environmental fate data 
indicate that oxyfluorfen strongly adheres to soil, does not leach into 
groundwater and has not been detected in sampled groundwater. Based on 
this information, occurrence of oxyfluorfen in drinking water is 
unlikely. Outdoor residential uses of oxyfluorfen are limited and 
exposure is expected to be low. Oxyfluorfen is toxic to lawn grasses 
and certain ornamental plants, and use is generally limited to spot 
treatments for nonselective weed control. Chronic exposure to 
oxyfluorfen residues resulting from potential residential and/or water 
exposure would not increase the total cancer risk so that it exceeds 
the Agency's level of concern. There is a reasonable certainty that no 
harm will result from chronic aggregate exposure to oxyfluorfen 
residues.
    ii. Acute risk. The acute dietary exposure endpoint of concern for 
oxyfluorfen is fused sternebrae in developing pups which was observed 
in the rabbit developmental study. The population subgroup of concern 
is females 13+ years old (women of childbearing age). For this 
subgroup, the calculated MOE at the high end exposure is greater than 
5,000. The Agency considers dietary (food) MOEs of greater than 100 to 
be acceptable for oxyfluorfen. Acute dietary exposure (food only) was 
calculated using the TMRC (worst case) assumptions.
    In the absence of data for drinking water exposure, the ranges of 
exposure being considered by the Agency for consumption of contaminated 
water will be reserved for drinking water. The aggregate MOE level of 
concern for dietary plus the addition of upperbound estimates for 
drinking water is not likely to raise the MOE level of concern above 
150. Despite the potential for acute exposure to oxyfluorfen in 
drinking water, it is not expected that the aggregate exposure will 
exceed the Agency's level of concern if the tolerance being considered 
in this document were granted. It is therefore concluded that the 
potential acute exposure associated with oxyfluorfen in water, even at 
the higher levels the Agency is considering as a conservative upper 
bound, would not prevent the Agency from determining that there is a 
reasonable certainty of no harm if the tolerance is granted.
    2. Infants and Children. The toxicology database is complete for 
oxyfluorfen relative to prenatal and postnatal toxicity. In the 
developmental toxicity study in rabbits, at the maternally toxic dose 
of 30 mg/kg/day, there were developmental anomalies (fused sternebrae) 
in the fetuses which demonstrated that prenatal toxicity should be 
evaluated by an acute dietary risk estimate. The acute dietary MOE for 
pregnant women 13+ years old is greater than 5,000 based on a 
developmental NOEL of 10 mg/kg/day. This MOE is much higher than the 
minimal acceptable MOE (100 for dietary-food only) and suggests that 
prenatal developmental risks to infants and children from exposure to 
oxyfluorfen dietary residues is not a concern. Additionally, the rabbit 
developmental NOEL of 10 mg/kg/day is 33 times greater than the NOEL of 
0.3 mg/kg/day used to calculate the RfD. In the developmental toxicity 
study in rats, both the developmental and maternal NOEL and LOEL of 18 
and 183 mg/kg/day, respectively, occurred at the same dose levels and 
demonstrates that there is no special sensitivity in infants and 
children exposed to oxyfluorfen. Although the developmental findings in 
the rat were severe effects, the developmental NOEL of 18 mg/kg/day is 
greater than the rabbit developmental NOEL of 10 mg/kg/day used to 
calculate acute dietary MOEs. Therefore, the acute dietary risk 
estimates calculated from the rabbit developmental NOEL are lower than 
acute dietary MOEs which could be calculated for the more severe 
effects occurring in rats above the NOEL of 18 mg/kg/day. By basing the 
acute dietary MOEs on the NOEL in the most sensitive species (rabbit), 
pregnant women are protected against both types of prenatal toxicity 
effects as seen in the rat and rabbit developmental toxicity studies. 
Therefore, there are no significant prenatal toxicity concerns for 
infants and children due to the high MOE for pregnant women 13+ years 
old. In the 2-generation reproductive toxicity study in rats used to 
assess the postnatal toxicity potential of infants and children, the 
NOEL and LOEL of 20 mg/kg/day and 80 mg/kg/day, respectively, for 
developmental/reproductive and systemic toxicity demonstrated that 
there are no pup toxicity effects in the absence of parental toxicity 
(NOEL and LOEL are the same for pups and parental animals). Therefore, 
there are no special postnatal sensitivities in infants and children 
which can be attributed to the findings of the 2-generation 
reproductive toxicity study in rats. Additionally, the developmental/
reproductive NOEL of 20/mg/kg/day [which is the NOEL for decreased 
litter size at birth as well as decreased pup body weight] and the 
parental systemic NOEL of 20 mg/kg/day is 66 times greater than the 
NOEL of 0.3 mg/kg/day used to calculate the RfD.
    Based on the above, EPA concludes that reliable data support use of 
the standard hundredfold margin of exposure/uncertainty factor and that 
an additional margin/factor is not needed to protect the safety of 
infants and children.
    i. Chronic risk. Using the refined exposure assumptions described 
above and taking into account the completeness and reliability of the 
toxicity data, it is concluded that aggregate dietary exposure to 
oxyfluorfen will utilize 0.05% of the RfD for infants and 0.08% of the 
RfD for children. EPA generally has no concern for exposures below 100% 
of the RfD because the RfD represents the level at

[[Page 1464]]

or below which daily aggregate dietary exposure over a lifetime will 
not pose appreciable risks to human health. Despite the potential for 
exposure to oxyfluorfen in drinking water and from non-dietary, 
nonoccupational exposure, the chronic aggregate exposure is not 
expected to exceed 100% of the RfD. There is a reasonable certainty 
that no harm will result to infants and children from chronic aggregate 
exposure to oxyfluorfen residues.
    ii. Acute risk. As mentioned above, the acute dietary exposure 
endpoint of concern for oxyfluorfen is fused sternebrae in developing 
pups which was observed in the rabbit developmental study. The 
population subgroup of concern is females 13+ years old (women of 
childbearing age). For this subgroup, the calculated MOE at the high 
end exposure is greater than 5,000. The Agency considers dietary (food) 
MOEs of greater than 100 to be acceptable for oxyfluorfen. Acute 
dietary exposure (food only) was calculated using the TMRC (worst case) 
assumptions.
    In the absence of data for drinking water exposure, the ranges of 
exposure being considered by the Agency for consumption of contaminated 
water will be reserved for drinking water. Based on the ranges under 
consideration, the aggregate MOE level of concern for dietary plus the 
addition of drinking water is not likely to raise the MOE above the 
Agency's level of concern. The large MOE calculated for this use of 
oxyfluorfen provides assurance that there is a reasonable certainty of 
no harm for infants and children.

G. International Tolerances

    There are no Codex Alimentarius Commission (CODEX) maximum residue 
levels (MRL's) established for residue of oxyfluorfen in or on raw 
agricultural commodities.    (PM 23)
[FR Doc. 98-557 Filed 1-8-98; 8:45 am]
BILLING CODE 6560-50-F