[Federal Register Volume 62, Number 127 (Wednesday, July 2, 1997)]
[Notices]
[Pages 35804-35812]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-17176]


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ENVIRONMENTAL PROTECTION AGENCY

[PF-740; FRL-5722-9]


Notice of Filing and Withdrawal of Pesticide Petitions

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice.

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SUMMARY: This notice announces the initial filing of pesticide 
petitions proposing the establishment of regulations for residues of 
certain pesticide chemicals in or on various food commodities, as well 
as the withdrawal of a pesticide petition.

DATES: Comments, identified by the docket control number PF-740, must 
be received on or before August 1, 1997.

ADDRESSES: By mail submit written comments to: Public Response and 
Program Resources Branch, Field Operations Divison (7505C), Office of 
Pesticides Programs, Environmental

[[Page 35805]]

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 by following 
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    
------------------------------------------------------------------------
James Tompkins, (PM 25).......  Rm. 237, CM #2, 703-    1921 Jefferson  
                                 305-7740; e-mail:       Davis Hwy,     
                                 Tompkins.James@epamai   Arlington, VA  
                                 l.epa.gov.                             
Mary L. Waller, (PM 21).......  Rm. 265, 703 308-9354;  Do.             
                                 e-mail:                                
                                 [email protected]
pa.gov.                                
George LaRocca (PM 13)........  Rm. 204, 703-305-5540,  Do.             
                                 e-mail:                                
                                 LaRocca.george@epamai
l.epa.gov.                             
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SUPPLEMENTARY INFORMATION: EPA has received pesticide petitions as 
follows proposing the establishment, amendment and/or withdrawal of 
regulations for residues of certain pesticide chemicals in or on 
various raw 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 grantinig of the petition. Additional data may be needed 
before EPA rules on the petition.
    The official record for this notice, as well as the public version, 
has been established for this notice of filing under document control 
number PF-740 (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''.
    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 file format or ASCII 
file format. All comments and data in electronic form must be 
identified by the document control number (insert docket number) and 
appropriate petition number. Electronic comments on this notice may be 
filed online at many Federal Depository Libraries.
    Authority: 21 U.S.C. 346a.

List of Subjects

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

    Dated: June 23, 1997.

James Jones,
Acting Director, Registration Division, Office of Pesticide Programs.

Summaries of Petitions

    Below summaries of the pesticide petitions are printed. The 
summaries of the petitions were prepared by the petitioners. 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. Bayer Corporation Withdrawal Of Pesticide Petition

PP 6E3182

    On November 8, 1984 Bayer Corporation, P.O. Box 4913, Kansas City, 
MO 64120, filed an import petition on behalf of the Ministry of 
Agriculture, Fisheries and Forestry in Japan, requesting establishment 
of a permanent tolerance (0.1 ppm) for the insecticide prothiophos 
(Tokuthion) in/on Japanese sand pears being imported from Japan. On 
March 27, 1997 Bayer notified EPA that it requests that the petition be 
withdrawn without prejudice to future filing. The Agency has withdrawn 
the subject petition.   (PM 13).

2. Merck Research Laboratories, Inc.

PP 6F4628

    EPA has received pesticide petition 6F4628 from Merck Research 
Laboratories, Inc, P.O. Box 450, Hillsborough Road, Three Bridges, NJ 
08887-0450, proposing pursuant to section 408 of the Federal Food, Drug 
and Cosmetic Act (FFDCA), 21 U.S.C section 346a (d), to amend 40 CFR 
part 180 by establishing tolerances for residues of the insecticide 
Emamectin Benzoate, 4'-epi-methylamino-4'-deoxyavermectin B1 benzoate 
[a mixture of a minimum of 90% 4'-epi-methylamino-4'-deoxyavermectin 
B1a and a maximum of 10% 4'-epi-methylamino-4'-deoxyavermectin B1b 
benzoate] and it degradates (with Merck research numbers in 
parentheses) 8,9- isomer of the B1a and of the B1b component of the 
parent insecticide (C-695,638); 4'-deoxy-4'-epi-amino- avermectin B1 
(L-653,64); 4'-deoxy-4'-epi-(N-formyl-N-methyl)amino-avermectin B1 (L-
660,599); and 4'-deoxy-4'-epi(N-formyl)amino-avermectin B1 (L-657,831) 
in or on the raw agricultural commodities cole crops vegetables 
(cabbage, broccoli, cauliflower and brussels sprouts) at 0.025 parts 
per million (ppm) and leafy vegetables (celery and head lettuce) at 
0.025 ppm. The proposed analytical method is high performance liquid 
chromatography (HPLC).

A. Residue Chemistry

    1. Plant metabolism. The metabolism of emamectin benzoate in plants 
has been studied in lettuce, cabbage, and sweet corn. The major portion 
of the residue is parent compound and its delta 8,9-photoisomer. 
Studies of the metabolism of emamectin in animals are not required 
because the commodities

[[Page 35806]]

that are the subject of the petition are not significant animal feed 
items.
    2. Analytical method. Adequate analytical method (HPLC-fluorescence 
methods) are available for enforcement purposes.
    3. Magnitude of residues. Eighteen field trials have been 
conducted: 10 on cabbage, 4 on broccoli, and 4 on cauliflower. These 
trials were conducted in the major U.S. growing areas for these crops. 
In samples taken after passage of the proposed interval between last 
treatment and harvest, the highest combined residue of emamectin 
benzoate and the degradates, which occurred in one cabbage sample, was 
0.020 ppm (actually quantified) of the main component, an 
unquantifiable amount that could be almost as high as the 0.005 limit 
of quantification or as low as the 0.001 ppm limit of detection, and 
undetectable amounts of the other two components, for a total somewhere 
between 0.021 part per million (ppm) and 0.027 ppm (total of actually 
quantified residues plus maximum possible levels of detectable but 
nonquantifiable residues between 0.001 and 0.005 ppm). In all other 
samples taken the combined measurable and nonquantifiable residues were 
well below the 0.025 ppm level.

B. Toxicological Profile

    The primary toxic effect seen in animal studies of emamectin 
benzoate is neurotoxicity. No-observed-effect-levels (NOELs) for this 
effect have been well-characterized in multiple studies. Emamectin 
benzoate has not been shown to be oncogenic or teratogenic in animal 
studies, it lacks mutagenic activity, and it is not selectively 
developmentally toxic. The petition refers to toxicity data that 
establish the following information about the toxicity of emamectin 
benzoate:
    1. Acute toxicity. Acute oral LD50: rat, 76-89 mg/kg; 
CD-1 mouse 107-120 mg/kg; CF-1 mouse, 22-31 mg/kg. Acute oral 
neurotoxicity: rat, No observed effect level (NOEL) = 5 mg/kg, Lowest 
observed effect level (LOEL) = 10 mg/kg. Acute dermal LD50: 
rat and rabbit, >2,000 mg/kg. Dermal irritation: rabbit, not irritating 
to skin. Eye irritation: rabbit, severe eye irritant. Acute inhalation 
4-hour LC50: rat, 2.12-4.44 mg/l.
    2. Reproductive/developmental toxicity. Developmental toxicity: 
rat, maternal NOEL = 2 mg/kg/day, developmental NOEL = 4 mg/kg/day, 
developmental LOEL = maternally toxic 8 mg/kg/day (HDT) for 
developmental delay; rabbit, maternal NOEL = 3 mg/kg/day, developmental 
NOEL = 6 mg/kg/day (maternally toxic HDT). Developmental neurotoxicity: 
rat, maternal NOEL = 3.6/2.5 mg/kg/day (HDT), developmental NOEL = 0.6 
mg/kg/day, developmental LOEL = 3.6/2.5 mg/kg/day for signs of 
neurotoxicity in pups. Two-generation reproductive toxicity: rat, 
parental and reproductive NOEL = 0.6 mg/kg/day, parental LOEL = 3.6/1.8 
mg/kg/day (for decreased weight gain and neuronal lesions); 
reproductive toxicity LOEL = 3.6/1.8 mg/kg/day (for decreased fecundity 
and signs of neurotoxicity in pups).
    3. Subchronic And chronic toxicity and oncogenicity. With the 
single exception of the chronic rat study, LOELS for the following 
studies are based on clinical signs and/or histopathological evidence 
of neurotoxicity (described further below). Subchronic (90-day) 
toxicity: rat, NOEL = 0.5 mg/kg/day, LOEL = 2.5 mg/kg/day; CD-1 mouse, 
NOEL = 5.4 mg/kg/day (TWA), LOEL = 0.5 mg/kg/day; dog, NOEL = 0.25 mg/
kg/day, LOEL = 0.5 mg/kg/day Subchronic (90-day) neurotoxicity; rat, 
NOEL = 1 mg/kg/day, LOEL = 5 mg/kg/day. Chronic (105-week) toxicity/
oncogenicity, rat: NOEL = 0.25 mg/kg/day, LOEL = 1 mg/kg/day (based on 
decreased body weight and clinical chemistry changes), neurotoxicity 
NOEL = 1 mg/kg/day, not oncogenic. Chronic (79-week) toxicity/
oncogenicity, CD-1 mouse: NOEL = 2.5 mg/kg/day, LOEL = 5 mg/kg (males), 
7.5 mg/kg/day (females), not oncogenic. Chronic (53-week) toxicity, 
dog: NOEL = 0.25 mg/kg/day, LOEL= 0.5 mg/kg./day.
    Exposure to sufficiently high doses of emamectin benzoate may be 
associated with clinical signs of central nervous system (CNS) toxicity 
and microscopic evidence of CNS/peripheral nervous system (PNS) damage. 
Neurotoxicity has generally been the most sensitive endpoint for 
toxicity in oral animal studies with emamectin benzoate. Clinical signs 
of CNS toxicity resulting from emamectin benzoate exposure include 
tremors, mydriasis, and changes in motor activity (e.g., lethargy, 
hyperactivity, and/or ataxia). Nervous system lesions (generally focal 
and of a low degree of severity) have been observed microscopically in 
white and gray matter in the brain stem, spinal cord, and peripheral 
nerves. Sporadic lesions of the optic nerve and/or retina have also 
been seen at higher dose levels. NOELs have been determined in all 
studies. The lowest toxic dose level of emamectin benzoate for CNS/PNS 
lesions (0.5 mg/kg/day) was identified in a 1-year study in dogs (NOEL 
of 0.25 mg/kg/day).
    The CF-l mouse is uniquely sensitive to emamectin benzoate-induced 
neurotoxicity. Studies have shown that a significant fraction of the 
members of this strain inherit an inability to produce a P-glycoprotein 
one that most strains and species do produce that functions to resist 
the entrance of avermectin-type compounds into the central nervous 
system. P-glycoprotein is also present in the gut of most species and 
limits absorption of avermectin-type compounds following oral exposure. 
In a 16-day feeding study in the CF-1 mouse, tremors were seen at 0.3 
mg/kg/day of emamectin benzoate with a NOEL of 0.1 mg/kg/day. No 
histopathologic evidence of neurotoxicity was seen in this study up to 
the highest dose tested (0.9 mg/kg/day).
    Emamectin benzoate photodegrades on plants and in soil. The major 
photodegradates that are not animal metabolites were tested in a 15-day 
neurotoxicity study in CF-1 mice. Only one photodegradate showed 
neurotoxicity (Merck research number L-660,599, the N-formyl-N-methyl 
degradate). Its NOEL was found to be 0.075 mg/kg/day, slightly lower 
than the value for the parent compound in the same kind of study, and 
both clinical signs and peripheral nerve lesions were observed at 
levels of 0.1 mg/kg/day and higher.
    4. Mutagenicity. Emamectin benzoate was tested in a battery of in 
vitro and in vivo mutagenicity assays and showed no evidence of 
mutagenic potential.. The photodegradates have also been tested in the 
Ames bacterial mutagenicity assay and show no mutagenic potential in 
this test system.
    5. Endpoint selection. Merck is proposing that the 0.075 mg/kg/day 
NOEL from the CF-1 mouse 15-day neurotoxicity study with the L-660,599 
photodegradate be used as the basis for acute dietary risk assessment. 
For evaluation of chronic dietary risks, Merck is proposing that the 
one-year dog chronic study NOEL of 0.25 mg/kg/day be used. The dog 
appears to be the most sensitive species to long-term exposure to 
emamectin benzoate. Accordingly, chronic exposure is compared against a 
RfD of 0.0025 mg/kg/day, based on the dog study results and an 
uncertainty factor of 100.

C. Aggregate Exposure

    1. Dietary exposure. Except for a temporary tolerance associated 
with an experimental use permit, no tolerances for residues of 
emamectin benzoate have been established. Merck projects that by the 
year 2001, emamectin benzoate will be used on approximately 17% of the 
acreage for the six crops covered by this petition. Chronic dietary 
exposure analyses were conducted for the overall

[[Page 35807]]

U.S. population and 26 population subgroups. Assuming 100% of the crop 
treated, chronic exposure for the overall U.S. population was estimated 
to be 0.000003 mg/kg BW/day, and for the most highly exposed subgroup, 
nursing females 13 years and older, 0.000004 mg/kg BW/day.
    2. Nondietary exposure. No products containing emamectin benzoate 
have yet been registered under the Federal Insecticide, Fungicide, and 
Rodenticide Act (FIFRA) for any food or nonfood use. The environmental 
fate of emamectin has been evaluated, and the compound is not expected 
to contaminate groundwater or surface water to any measurable extent. 
No significant nondietary, nonoccupational exposure is anticipated.

D. Cumulative Effects

    Emamectin is a member of the avermectin family of natural and 
synthetic compounds that includes the Merck products abamectin (a 
naturally occurring compound that is the active ingredient of several 
insecticides registered under FIFRA) and ivermectin (a human and animal 
drug made from abamectin). Emamectin is made from abamectin but is less 
similar to abamectin than is ivermectin. Other companies produce 
certain other drugs that are members of the avermectin family. Some of 
the effects seen in toxicity studies of abamectin and ivermectin are 
similar to some of the effects seen in toxicity studies of emamectin. 
See the discussion of abamectin and ivermectin in 61 FR 65043 (Dec. 10, 
1996). Merck is not aware of any information indicating what, if any, 
cumulative effect would result from exposure to two or more of these 
compounds.

E. Safety Determination

    1. U.S. population chronic risk. Chronic exposures were analyzed 
with reference to the chronic effects referenced dose (RfD) NOEL of 
0.0025 mg/kg/day. Assuming 100% of the crop treated, the chronic 
exposure estimate was 0.1% of the RfD for the overall U.S. population, 
and 0.2% of the RfD for the most highly exposed subgroup, nursing 
females 13 years and older. If 25% crop treatrment is assumed, exposure 
estimates were less than 0.1% of the RfD for all population groups.
    2. U.S. population acute risk. Acute dietary exposures were 
analyses for the overall U.S. population, and the population subgroups 
(1) women 13 years and older, (2) infants, and (3) children. In 
addition, Tier 2 and Tier 3 acute analyses were conducted assessing 
acute exposures against the 0.075 mg/kg/day NOEL. These analyses showed 
that the margins of exposure (MOEs) calculated from the proposed uses 
of emamectin benzoate are acceptable whether using a highly 
conservative approach (Tier 2) or a more realistic (Tier 3) 
methodology. In the Tier 2 analysis, MOEs were well over 1,000 up to 
the 95th percentile of exposure for all population groups. In the Tier 
3 analysis and assuming 100% of the crop treated, MOEs up to the 99th 
percentile of exposure were greater than 1,000. Assuming 25% of the 
crop treated, MOEs were greater than 1,000 up to the 99.9th percentile 
of exposure. Results of both the chronic and acute dietary exposure 
analyses clearly demonstrate a reasonable certainty that no harm will 
result from the use of emamectin benzoate.
    3. Infants and children. It is Merck's position that the 
administration of emamectin benzoate has not been shown to cause 
developmental or reproductive effects at dose levels below those that 
are maternally toxic. Even if it were decided to use the 0.6 mg/kg NOEL 
from the rat developmental neurotoxicity study as an endpoint from 
which to calculate an RfD, the resulting RfD would not yield a 
different regulatory outcome unless a very high additional uncertainty 
factor were also employed. Use of such an extra uncertainty factor is 
not justified for several reasons. Emamectin benzoate is not a 
teratogen. In developmental toxicity testing, the compound caused no 
developmental effects in rabbits; in rats, it caused no malformations, 
and caused skeletal effects typical of developmental delay only at 
severely maternally toxic doses. Likewise, no reproductive toxicity or 
toxicity to pups was seen in the two-generation reproductive toxicity 
study except at parentally toxic doses. In the developmental 
neurotoxicity study, tremors, hind-leg splay, and behavioral effects 
were seen in pups at a dose level (3.6/2.5 mg/kg/day) at which no 
maternal clinical signs were noted. However, the dams in the study were 
discarded after the lactation period without gross necropsy or 
microscopic examination. In studies in which rats dosed at similar 
levels were examined microscopically, effects (central and peripheral 
neural lesions) were seen.
    The clinical signs of avermectin-family neurotoxicity seen in 
neonatal rats are unlikely to be useful predictors of human risk. Young 
rats are considerably more sensitive to avermectin-type compounds than 
either adult rats or humans and other primates. (In neonatal rats, 
unlike humans, the P-glycoprotein levels are only a small fraction of 
the levels seen in adult rats.) Moreover, data from clinical experience 
with ivermectin, a related human drug, and studies on ivermectin and 
abamectin, a related pesticide, demonstrate that both the neonatal rat 
and the CF-1 mouse overpredict the toxicity of the avermectin-type 
compounds to humans and to non-human primates.

F. International Tolerances

    No Codex maximum residue levels (MRLs) have been established for 
residues of emamectin benzoate.   (PM 13)


3. Novartis Crop Protection Inc.

PP 0E3875

    EPA has received a pesticide petition (0E3875) from Novartis Crop 
Protection Inc., PO Box 18300, Greensboro, NC 27419. The petition 
proposes, to amend 40 CFR part 180, by establishing a permanent import 
tolerance for the residues of the fungicide cyproconazole, (2RS,3RS)-2-
(4-chlorophenyl)-3-cyclopropyl-1-1(1H-1,2,4-triazole-1-yl)butan-2-ol, 
(CAS #94361-06-5; PC Code 128993) in or on the raw agricultural 
commodity coffee beans at 0.1 part per million (ppm). The time-limited 
tolerance of 0.1 ppm in or on coffee beans established in the Federal 
Register of September 27, 1995 (60 FR 49795) will expire July 1, 1997.

A. Chemical Uses

    Cyproconazole, (2RS,3RS)-2-(4-chlorophenyl)-3-cyclopropyl-1-(1H-1, 
2, 4-triazole-1-yl)butan-2-ol, is a broad spectrum fungicide that has 
been classified as an ergosterol-biosynthesis inhibitor. It is used to 
control a variety of fungi, including coffee rust, in several coffee 
producing countries. Rates range from a preventative treatment of 20 g 
ai/ha to a maximum curative treatment of 50 g ai/ha with a 30 day pre-
harvest interval (PHI) and annual maximum of 100 g ai/ha.
    1. Cyproconazole safety. A battery of acute toxicity studies was 
conducted placing technical cyproconazole in Toxicity Category III and 
IV.
    i. 90-day rat study. A NOEL for this study was not attained, but 
the NOEL is estimated to be less than 1.0 mg/kg.
    ii. 13-week feeding study in dogs. NOEL of 20 ppm (0.8 mg/kg/day) 
and an LEL of 100 ppm (4 mg/kg/day) based on included slack muscle 
tone, depressed body weight gain, and decreases in bilirubin, total 
cholesterol, HDL-cholesterol, triglycerides, total protein, and 
albumin. There were increases in platelet counts, alkaline phosphatase, 
gamma glutamyl transferase, absolute

[[Page 35808]]

and relative liver weights, relative kidney weights, and relative brain 
weights. Liver toxicity was indicated by hepatomegaly.
    iii. 21-day dermal study. NOEL was 250 mg/kg and the LEL was 1,250 
mg/kg. Effects included depressed body weight gain and food consumption 
and increased levels of AST, creatinine, and cholesterol.
    iv. 1-year dog study. NOEL of 30 ppm (1.0 mg/kg/day) and an LEL of 
100 ppm (3.2 mg/kg/day) based on laminal eosinophilic intrahepatocytic 
bodies observed in all males and two females at the high dose, and in 
one male at the mid-level dose.
    v. A mouse carcinogenicity study. NOEL for systemic toxicity of 15 
ppm (1.8 mg/kg for males and 2.6 mg/kg for females). The LEL was 100 
ppm (13.2 mg/kg for males and 17.7 mg/kg for females) based on a 
significantly increased incidence of hepatic single cell necrosis and 
diffuse hepatocytic hypertrophy at the two highest levels.
    vi. A rat chronic/carcinogenicity study. The NOEL for systemic 
toxicity was 50 ppm. The LEL was 350 ppm based on slightly decreased 
body weights in the high-dose females and increased incidence of fatty 
infiltration of the liver in the high-dose males.
    vii. A rat developmental toxicity study. NOEL for maternal toxicity 
was 6 mg/kg, and the LEL was 12 mg/kg based on decreased body weight 
gain during dosing. The NOEL for developmental toxicity was 6 mg/kg. 
The LEL was 12 mg/kg based on the increased incidence of supernumerary 
ribs.
    viii. A chinchilla rabbit developmental toxicity study. NOEL for 
maternal toxicity was 10 mg/kg (equivocal). The LEL was 50 mg/kg based 
on decreased body weight gain during dosing. Developmental effects were 
also evaluated. Hydrocephalus internus was observed in 1 fetus at each 
treatment level. Therefore, the NOEL for developmental toxicity was set 
at less than 2 mg/kg, and the LEL was 2 mg/kg.
    ix. A New Zealand white rabbit developmental toxicity study. NOEL 
for maternal toxicity was 10 mg/kg, and the LEL was 50 mg/kg based on 
decreased body weight gain. There was also evidence of developmental 
toxicity. The NOEL for developmental toxicity was 2 mg/kg, and the LEL 
was 10 mg/kg based on the increased incidence of malformed fetuses and 
litters with malformed fetuses.
    x. A rat two-generation reproduction study. systemic NOEL for 
parental toxicity was set at 20 ppm (1.7 mg/kg) based on liver effects 
at 10.6 mg/kg/day. For reproductive toxicity, the NOEL was set at 4 ppm 
(0.4 mg/kg) and the LEL at 20 ppm (1.7 mg/kg) based on increased 
gestation length in the F0 dams and decreased F1 litter sizes.
    xi. Several mutagenicity studies. Mutagenicity potential of 
cyproconazole was tested in several studies considered acceptable by 
the Agency. Since the results of two chromosomal aberration assays 
indicated the cyproconazole is clastogenic, additional mutagenicity 
data were requested to address an identified heritable risk concern. 
For the potential to induce chromosome aberrations in CHO cells, 
cyproconazole was positive under non-activated and activated 
conditions, thus supporting the evidence that cyproconazole is 
clastogenic in this test system. However, cyproconazole was negative in 
Salmonella, mouse micronucleus, and SHE/cell transformation assays. A 
dominant-lethal assay in rats was submitted and was negative. Based on 
this evidence, the concern for a possible heritable effect was not 
pursued.
    xii. Metabolism/pharmacokinetics studies. Cyproconazole was shown 
to be extensively metabolized in the rat. Unchanged cyproconazole and 
13 metabolites were isolated and identified, and 35 metabolites were 
detected in the excreta. Excretion was relatively rapid with the 
majority of the radioactivity appearing in the feces as a result of 
biliary elimination. Residues were found in renal fat, adrenals, kidney 
and liver, although no significant tissue radioactivity was observed at 
168 hours post-dose.
    2. Threshold effects.--i. Chronic effects. Based on available 
chronic toxicity data, EPA has set the reference dose (RfD) used in the 
dietary exposure analysis at 0.01 mg/kg bwt/day. This RfD is based on a 
NOEL of 30.0 ppm (1.00 mg/kg bwt/day) from a 1-year dog feeding study 
and an uncertainty factor of 100 to account for interspecies 
extrapolation and intraspecies variability.
    ii. Acute effects. The risk from acute dietary exposure to 
cyproconazole is considered by Novartis to be very low. The lowest NOEL 
in a short term exposure scenario, identified as 2 mg/kg in the rabbit 
teratology study, is 2-fold higher than the chronic NOEL (see above). 
Since chronic exposure assessment (see below), based on some worst-case 
assumptions, resulted in margins of exposure in the thousands for even 
the most impacted population subgroup, Novartis believes that the 
margin of exposure for acute exposure would be much higher than one 
hundred for any population groups; margins of exposure of 100 or more 
are considered satisfactory by the Agency.
    3. Non-threshold effects. The HED Carcinogenicity Peer Review 
Committee has classified cyproconazole as a Group ``B2'' carcinogen 
(probable human carcinogen) based on findings of liver tumors in both 
sexes of mice administered adequate doses of cyproconazole, its 
possible clastogenic activity, tumors in rats and mice administered 
structurally related analogues and the lack of an adequate rat 
carcinogenicity study. The committee assigned cyproconazole a risk 
characterization value, Q1*, of 3.0  x  10-1 (mg/kg/day)-1 derived from 
liver tumor data obtained in male mice.

B. Aggregate Exposure

    The anticipated residue contributions (ARC) as percentages of the 
RfD are <0.1% for the general population and all sub-populations and 
geographic regions. The chronic dietary exposure analysis for 
cyproconazole is calculated using anticipated residues for coffee and 
100% treatment of all crops. This estimate is not a worst-case estimate 
of dietary exposure but still exaggerates exposure. Based on this 
calculation, Novartis believes the chronic dietary risk from the 
recommended use is far below the level which would trigger a concern.
    Other potential sources for exposure are drinking water and non-
occupational exposure. No cyproconazole-based products are labeled for 
residential use. Non-occupational exposure for cyproconazole has not 
been estimated since the current registrations for cyproconazole-based 
products are limited to commercial and agricultural turf treatment. 
Field studies have demonstrated that cyproconazole does not leach to 
groundwater or accumulate in the soil. The average half life of 
cyproconazole in field dissipation studies was <50 days. The field 
characteristics of cyproconazole, combined with its use pattern, make 
surface water contamination unlikely. Thus, Novartis believes the 
potential for non-occupational and drinking water exposure to the 
general population is insignificant.

C. Safety Determination

    1. U.S. population. All non-occupational exposure of cyproconazole 
in the U.S. is due to its use in the production of imported coffee 
beans. The anticipated residue contribution (ARC) is 0.000001 mg/kg/day 
for the general population and, 0.000002 mg/kg/day for females, 20 
years old and older. Novartis has calculated that the ARC will consume 
0.01% and 0.02% of the RfD for the general population and

[[Page 35809]]

females 20 years old or older, respectively. Lifetime carcinogenic risk 
for dietary exposure based on quantitative risk assessment and a 
Q1* of 3.0  x  10-1 (mg/kg/day)-1, is 3.15  x  
10-7. EPA generally has no concern for exposures below 100 
percent of the RfD or lifetime carcinogenic risks less than 1  x  
10-6. Therefore, Novartis concludes that there is a 
reasonable certainty that no harm will result from aggregate exposure 
to cyproconazole residues via the use on coffee beans.
    The consideration of a common mechanism of toxicity is not 
appropriate at this time because Novartis and EPA do not have 
information to indicate that toxic effects produced by cyproconazole 
would be cumulative with those of any other chemical compounds.
    2. Infants and children. For dietary risk assessments, no exposure 
is apportioned to infants and children because they do not normally 
consume coffee. There is also no non-occupational exposure to infants 
and children. Based on the completeness and reliability of the toxicity 
data and the practical non-exposure to cyproconazole, Novartis 
concludes that there is a reasonable certainty that no harm will result 
to infants and children from the aggregate exposure of residues of 
cyproconazole including all anticipated dietary exposure and all other 
non-occupational exposures.

D. Estrogenic Effects

    Cyproconazole does not belong to a class of chemicals known for 
having adverse effects on the endocrine system. No estrogenic effects 
have been observed in the various short and long term studies conducted 
with various mammalian species.

E. Chemical Residue

    The nature of the residue in coffee is fully understood. A 
metabolism study in coffee, using triazole-labeled cyproconazole, was 
submitted and was acceptable. Cyproconazole per se was the primary 
component of the residue. A metabolism study in wheat was conducted to 
determine the fate of the phenyl portion of cyproconazole in plants. 
Results of the study have been submitted and the Agency found that 
residues from the wheat metabolism study were not significantly 
different from the coffee metabolism study.
    Adequate enforcement methodology has been submitted to the EPA and 
has passed a method validation trial by EPA's analytical laboratories. 
Additional data has been submitted to demonstrate that residues of 
several other pesticides registered for use on coffee do not interfere 
with the method. Prior to publication in the Pesticide Analytical 
Manual, Vol. II, the enforcement methodology is being made available in 
the interim to anyone who is interested in pesticide enforcement when 
requested from: Calvin Furlow, Public Response and Program Resource 
Branch, Field Operations Division (7506C), Office of Pesticide 
Programs, Environmental Protection Agency, 401 M St., SW., Washington, 
DC 20460. Office location and telephone number: Rm. 1130A, CM#2, 1921 
Jefferson Davis Hwy., Arlington, VA (703) 305-5937.

F. Environmental Fate

    No domestic use of cyproconazole is associated with the established 
tolerance in coffee.

G. International Tolerances

    No international tolerances have been established under CODEX for 
cyproconazole.   (PM 21)

4. ZENECA Ag Products

PP 6F4790

    EPA has received a pesticide petition (PP 6F4790) from ZENECA Ag 
Products, 1800 Concord Pike, P.O. Box 15458, Wilmington, DE 19850-5458, 
proposing to amend 40 CFR part 180 by establishing a tolerance for 
residues of tralkoxydim, 2-cyclohexen-1-one, 2[1-(ethoxyimino) propyl]-
3-hydroxy-5-(2,4,6-trimethylphenyl)-(9CI) in or on the food commodities 
barley grain, barley straw, barley hay, wheat grain, wheat forage, 
wheat straw, and wheat hay at 0.1 parts per million (ppm). The proposed 
analytical method is High Pressure Liquid Chromatography with ultra-
violet detection (HPLC-UV).

A. Residue Chemistry

    1. Plant metabolism. Wheat Plant metabolism was evaluated in wheat. 
14C-Tralkoxydim, labeled in the equivalent C4/C6 positions of the 
cyclohexenone ring, was applied as a foliar spray to field-grown spring 
wheat. A single application was made at a rate of 0.31 lb ai/acre at 
Zadok's growth stage 31. A representative forage sample was harvested 
22 days post-application. The remainder of the crop was harvested at 
maturity, 96 days post-application, then separated into straw and grain 
prior to analysis.
    The total radioactive residues (TRR) in forage, straw and grain 
were 0.71, 1.29 and 0.013 mg/kg tralkoxydim equivalents, respectively. 
No residues of parent were detected and at least ten individual 
components were initially observed, demonstrating extensive metabolism 
of tralkoxydim. Characterization of the total radioactive residue in 
grain by extraction indicates that no single component exceeds 0.01 mg/
kg. Also, in both forage and straw, the same complex metabolic profile 
was evident. Characterization showed that none of the metabolites 
exceeded 3.6% TRR (0.05 mg/kg) in any of the fractions examined.
    2. Analytical method. The method of analysis uses High Pressure 
Liquid Chromatography. It is method PRAM 99A and it has been validated 
using independent laboratory confirmatory trials as described in US EPA 
PR Notice 88-5. The method is for extraction and quantification of 
tralkoxydim residues in wheat and barley crops. Grain, straw, or forage 
is extracted into acetonitrile, filtered, and re-extracted into 
dichloromethane. The organic layer is used for analysis. The limit of 
detection of the analytical method is 0.02 ppm, while the limit of 
quantification is 0.1 ppm.
    3. Magnitude of residues. ZENECA requests registration of 2 
concentrations of tralkoxydim, 80% and 40% for ACHIEVE 80DG and ACHIEVE 
40DG, respectively. These products use the same rate of application and 
demonstrate that there are no detectable residues on wheat and barley 
crops when either product is used according to the label directions.
    Wheat: ACHIEVE 80DG containing 80% tralkoxydim. Residue data are 
available for tralkoxydim applied postemergence on wheat at the maximum 
label rate of 0.25 lb ai/A. Application was made from full tillering to 
first detectable node growth stage. In 1995, a total of 20 magnitude of 
the residue trials were conducted on spring wheat. There were no 
detectable residues (<0.02 ppm LOD) on wheat grain or straw in any of 
the trials at the pre-harvest interval of 60 days. There were no 
detectable residues on hay at the pre-harvest interval of 45 days. 
There were no detectable residues on immature forage at the pre-harvest 
interval of 30 days.
    Two (2) winter wheat trials were conducted in 1995 to determine 
forage residues of tralkoxydim in winter wheat, using ACHIEVE DG, 80% 
concentration (ACHIEVE 80DG). The product was applied at the maximum 
label rate at growth stages from advanced tillering to full tillering. 
The winter wheat forage data showed no detectable residues at either 16 
or 18 days after treatment. These results fall well within the proposed 
forage pre-harvest interval of 30 days.
    ACHIEVE 40DG containing 40% tralkoxydim. There were 3 magnitude of 
the residue trials conducted on spring wheat in 1994 and one trial was

[[Page 35810]]

conducted in 1993. In addition, 6 trials were conducted in Canada 
during 1986 and 1987. (Note: The Canadian trials were conducted using a 
50% concentration of tralkoxydim at a higher use rate of 0.3 - 0.6 lb 
ai/A). There were no detectable residues (<0.02 ppm LOD) on wheat grain 
or straw in any of the trials at the pre-harvest interval of 60 days. 
There were no detectable residues on hay at the pre-harvest interval of 
45 days. There were no detectable residues on immature forage at the 
pre-harvest interval of 30 days. Despite having no detectable residues 
of tralkoxydim at 0.02 ppm, it is proposed that the tolerance level be 
based on the limit of quantification (LOQ) of the tolerance enforcement 
method, which has been validated to 0.1 ppm for tralkoxydim. The 
proposed tolerance of 0.1 ppm for wheat grain, forage, straw and hay is 
five (5) times greater than any residue that would result from the 
application of ACHIEVE DG arising from the proposed use pattern.
    Wheat Products (processing). The wheat processing study 
demonstrated that there are no detectable residues (<0.02 ppm) in the 
bran, flour, middlings, shorts, and germ. Therefore, no food or feed 
additive tolerances are required for processed wheat commodities.
    Barley:  ACHIEVE 80DG containing 80% tralkoxydim. A total of 12 
magnitude of the residue trials were conducted in 1995 on barley crops 
for tralkoxydim applied postemergence at the maximum label rate of 0.25 
lb ai/A. The product was applied at full tillering to first detectable 
node growth stage. There were no detectable residues (<0.02 ppm) on 
barley grain or straw at the pre-harvest interval of 60 days. There 
were no detectable residues in hay at the pre-harvest interval of 45 
days.
    ACHIEVE 40DG containing 40% tralkoxydim. In 1994, 3 magnitude of 
the residue trials were conducted on barley using ACHIEVE DG, 40% 
concentration (ACHIEVE 40DG). In addition, 6 magnitude of the residue 
trails that were conducted in Canada during 1986 and 1987. (Note: The 
Canadian trials were conducted using a 50% concentration of tralkoxydim 
at a higher use rate of 0.3 - 0.6 lb ai/A). There were no detectable 
residues (<0.02 ppm) on barley grain or straw at the pre-harvest 
interval of 60 days. There were no detectable residues in hay at the 
pre-harvest interval of 45 days.
    Despite having no detectable residues of tralkoxydim at 0.02 ppm, 
it is proposed that the tolerance level be based on the limit of 
quantification (LOQ) of the tolerance enforcement method, which has 
been validated to 0.1 ppm for tralkoxydim. The proposed tolerance of 
0.1 ppm for barley grain, hay and straw is five (5) times greater than 
any residue that would result from the application of ACHIEVE DG 
arising from the proposed use pattern.
    Barley Products (processing). The barley processing study 
demonstrated that there are no detectable residues (<0.02 ppm) in the 
pearled barley, flour and bran. Therefore, no food or feed additive 
tolerances are required.
    Animal Products. Based on the results of the poultry and ruminant 
metabolism studies, the extensive metabolism and rapid excretion of 
either tralkoxydim or any of its metabolites, and the poultry and 
ruminant consumption of commodities used in animal feed, there are no 
expected residues of tralkoxydim in meat, milk, or eggs.

B. Toxicological Profile

    1. Acute toxicity. Tralkoxydim technical results of the acute 
toxicity testing: acute oral in the rat LD50 > 934 mg/kg, acute dermal 
in the rat LD50 > 2,000 mg/kg, acute inhalation in the rat LD50 > 3.5 
mg/L, eye irritation in the rabbit showed mild irritancy, skin 
irritation in the rabbit showed a slight irritancy. Tralkoxydim is not 
a skin sensitizer.
    2. Genotoxicity.

------------------------------------------------------------------------
             Assay                       Type                Result     
------------------------------------------------------------------------
In vitro                        Ames                    negative        
                                Mouse lymphoma          negative        
                                Human lymphocyte        negative        
                                 cytogenetics                           
In vivo                         Mouse micronucleus      negative        
                                UDS                     negative        
------------------------------------------------------------------------


    3. Reproductive and developmental toxicity. (Reproductive toxicity) 
Tralkoxydim showed no evidence of reproductive toxicity to rats. 
Tralkoxydim was dosed to rats at levels of 2.5 mg/kg/day (50 ppm), 10 
mg/kg/day (200 ppm) and 50 mg/kg/day (1,000 ppm) in a 3 generation 
reproductive toxicity study.

----------------------------------------------------------------------------------------------------------------
     Study Type Reproductive Toxicity                  NOEL                        Effect Description           
----------------------------------------------------------------------------------------------------------------
Rat (diet) 3 generation..................  NOEL = 10 mg/kg/day (200     LEL is 1,000 ppm based on reduced litter
                                            ppm).                        weights and weight gain in pups and    
                                                                         bodyweight gain effects, food          
                                                                         consumption and reduced liver weights  
                                                                         in adults                              
----------------------------------------------------------------------------------------------------------------


    (Developmental toxicity) Tralkoxydim caused no clear dose related 
developmental effects in the rabbit. At a dose of 30 mg/kg/day, 
tralkoxydim caused some developmental effects in the rat manifested by 
skeletal defects including single misshapen centra. The NOEL for 
developmental toxicity was established at 3 mg/kg/day.

----------------------------------------------------------------------------------------------------------------
   Study Type Developmental Toxicity                 NOEL/LEL                       Effect Description          
----------------------------------------------------------------------------------------------------------------
Rabbit (by gavage).....................  NOEL = 2.5 mg/kg/day             No clear dose-related developmental   
                                          fetotoxicity LEL = 20 mg/kg/     effects. LEL effect, increased       
                                          day NOEL = 20 mg/kg/day          partially ossified 2nd lumbar        
                                          maternal.                        transverse process.                  
Rat (by gavage)........................  NOEL = 3 mg/kg/day fetotoxicity  LEL for maternal toxicity is 300 mg/kg/
                                          and developmental LEL = 30 mg/   day maternal death and overt         
                                          kg/day NOEL = 30 mg/kg/day       toxicity. Developmental LEL is 30 mg/
                                          maternal.                        kg/day, skeletal defects includes    
                                                                           single misshapen centra.             

[[Page 35811]]

                                                                                                                
Rat (by gavage)........................  NOEL = 3 mg/kg/day LEL = 200 mg/ LEL for fetotoxicity effect, increased
                                          kg/day maternal, fetotoxicity    post-implantation loss. Developmental
                                          and developmental.               effect fused or misshapen centra.    
                                                                           Maternal LEL is based on moralities &
                                                                           overt signs of toxicity.             
----------------------------------------------------------------------------------------------------------------


    4. Subchronic toxicity. Tralkoxydim is of low subchronic toxicity 
in 21-day dermal testing.
    5. Chronic toxicity. Tralkoxydim is not a carcinogen in the rat. 
The dose levels used in the 2 year combined chronic/oncogenicity study 
on rats were as follows.

------------------------------------------------------------------------
                                   Male rat (mg/kg/   Female rat (mg/kg/
    Tralkoxydim in Diet (ppm)            day)                day)       
------------------------------------------------------------------------
50                                2.3                 3.0               
500                               23.1                30.1              
2,500                             117.9               162.8             
------------------------------------------------------------------------

    Tralkoxydim administration was associated with an increase in the 
incidence of benign Leydig cell tumors in the male rat at the top-dose 
of 2,500 ppm, only. This increase represented an exacerbation of a 
naturally occurring tumor type in the male rat and was considered to be 
the result of a physiological response to tralkoxydim administration. 
There was no evidence of a treatment-related effect or incidence of any 
other tumor type (malignant or benign) in male or female rats at any 
dose.
    Oncogenicity - Hamster. Tralkoxydim is not an oncogen in the 
hamster. The dose levels used in the combined chronic toxicity/
oncogenicity study on hamsters were as shown in the table below.

----------------------------------------------------------------------------------------------------------------
       Tralkoxydim in Diet (ppm)             Male hamster (mg/kg/day)           Female hamster (mg/kg/day)      
----------------------------------------------------------------------------------------------------------------
250                                      14.9                             14.8                                  
2,500                                    153.0                            148.3                                 
7,500                                    438.6                            427.9                                 
----------------------------------------------------------------------------------------------------------------


    There was no increased tumor incidence or early onset of tumors in 
hamsters receiving up to 7,500 ppm tralkoxydim in the diet. The NOEL 
was established at 250 ppm, equivalent to 15 mg/kg bodyweight/day.

----------------------------------------------------------------------------------------------------------------
        Study Type Oncogenicity                      NOEL/LEL                       Effect Description          
----------------------------------------------------------------------------------------------------------------
Hamster (diet)                           NOEL = 250 ppm (15 mg/kg/day)    LEL effect: decreased lymphocyte      
                                          LEL = 2,500 ppm                  numbers (in males only) and increased
                                                                           liver lipofuscin pigment at 2,500 and
                                                                           7,500 ppm.                           
----------------------------------------------------------------------------------------------------------------


    The hamster instead of the mouse was selected as the second test 
species for oncogenicity testing because laboratory mice developed 
hepatic porphyria at low doses of tralkoxydim. Extensive mechanism data 
in support of the mouse specific porphyria has been provided. The 
results of these studies led ZENECA to the conclusion that the mouse 
was not an appropriate second test species for chronic toxicity/
oncogenicity testing of tralkoxydim since the level of sensitivity in 
the mouse precluded the administration of a dose sufficient to 
determine chronic/oncogenicity effects in a lifetime feeding study.
    One-Year Feeding Study - Dog. Tralkoxydim was administered to 
groups of 4 beagle dogs at dose levels of 0, 0.5, 5.0, and 50 mg/kg/
day, as a daily oral dose in the food. At 50 mg/kg/day there was 
hepatotoxicity (marked increase in liver weight) and an effect on the 
adrenal gland (increase in weight and cortical vacuolation). At a dose 
of 5 mg/kg/day, the following changes were not considered 
toxicologically significant: a slight increase in adrenal weight 
relative to body weight in males, and a slight adaptive effect in the 
liver of one male dog considered to be abnormally susceptible. These 
changes are of no toxicological significance.
    The resulting NOEL from this study is 0.5 mg/kg/day. Based on the 
EPA review of tralkoxydim toxicity data, the NOEL from this study was 
recommended for use in establishing a provisional RfD.
    The resulting RfD, with an uncertainty factor of 100 is 0.005 mg/
kg/day.
    6. Animal metabolism. Tralkoxydim is well absorbed and completely 
metabolized in the rat. Excretion is rapid and there is no accumulation 
of tralkoxydim or metabolites. There are no significant plant 
metabolites that are not animal metabolites.
    7. Metabolite toxicology. Toxicity testing results for the 
tralkoxydim parent compound is indicative of any metabolites, either in 
the plant or animal.

C. Aggregate Exposure

    1. Dietary exposure (Food). Tralkoxydim is to be used on wheat and 
barley crops, only. For the purposes of assessing the potential dietary 
exposure, ZENECA estimated aggregate exposure based on the Theoretical 
Maximum Residue Contribution (TMRC) from the tolerances of tralkoxydim 
on wheat at 0.1 ppm and barley at 0.1 ppm. This is a worst case 
estimate of aggregate exposure and assumes 100% of the wheat and barley 
crops in the United States will have residues of tralkoxydim at the 0.1 
ppm. Dietary exposure to residues of tralkoxydim in or on food

[[Page 35812]]

will be limited to residues on wheat and barley, and food derived from 
wheat and barley. Based on animal metabolism data and because there are 
no residues on the crops at time of harvest or at grazing intervals, we 
have concluded that there is reasonable expectation that no measurable 
residues of tralkoxydim will occur in meat, milk, poultry, or eggs from 
this use. Since tralkoxydim is a new herbicide, there are no other 
established U.S. tolerances for tralkoxydim.
    Due to no detectable residues in grain at harvest, even after 
processing, the dietary risk assessment has been conducted on the basis 
of the limit of quantification of 0.1 mg/kg. This is significantly 
above (5 x  ) the limit of detection of tralkoxydim residues of 0.02 
mg/kg determined by ZENECA's analytical methods used in the magnitude 
of residue studies. However, even using a tolerance level of 0.1 mg/kg 
(limit of quantification) the chronic assessment for tralkoxydim 
indicates less than 10% of the RfD is consumed, for any given 
subpopulation, even assuming 100% market share. Based on a review of 
available toxicity data for tralkoxydim, there are no toxicological 
endpoints of concern for acute dietary risk.
    Agricultural use of tralkoxydim on wheat and barley, therefore, 
does not represent an acute or chronic risk to the U.S. population, 
infants, children, or any other of the 23 subpopulations evaluated in 
this assessment.
    2. Drinking water. Based on the available studies, exposures are 
not anticipated to residues of tralkoxydim in drinking water. 
Tralkoxydim does not leach. It is unlikely that tralkoxydim would be in 
drinking water. Tralkoxydim is unlikely to enter surface water bodies 
to any significant degree except by direct accidental over-spray. 
Should this arise, tralkoxydim will be readily degraded by one or more 
of a number of contributory processes; studies have shown that 
degradation in flooded anaerobic soil occurs with a half-life of 
approximately 25 days, aqueous hydrolysis (pH 5) with a half-life of 
less than 7 days and aqueous photolysis also with a half-life of less 
than 7 days. All these processes will ensure that any tralkoxydim 
entering surface water bodies will be short-lived and tralkoxydim will 
not result in any significant contamination of potential drinking water 
sources. Therefore, it is not appropriate to assess aggregate exposure 
from drinking water.
    3. Non-dietary exposure. Since tralkoxydim is not registered for 
residential or turf uses, and does not represent a groundwater 
contamination concern, exposures from other than dietary or 
occupational sources are extremely unlikely.

D. Cumulative Effects

    Tralkoxydim is a new class of chemistry for herbicides used on 
wheat and barley. Although tralkoxydim is in the chemical class of 
compounds called cyclohexanediones, it is the only herbicide in this 
class to be used on wheat and barley crops. No evidence or information 
exists to suggest that the toxic effects produced by tralkoxydim would 
be cumulative with those of any other chemical compound.

E. Safety Determination

    1. U.S. population. Using the conservative assumptions described 
above, based on the completeness and reliability of the toxicity data, 
the aggregate exposure to tralkoxydim will utilize less than 4% of the 
RfD for the U.S. Population. EPA generally has no concern for exposures 
below 100 percent of the RfD. There is reasonable certainty that no 
harm will result from aggregate exposure to residues of tralkoxydim, 
including all anticipated dietary exposure.
    2. Infants and children. In assessing the potential for additional 
sensitivity for infants and children to residues of tralkoxydim, the 
three-generation reproductive study in rats and the developmental 
toxicity studies in the rat and rabbit were considered. Tralkoxydim 
showed no evidence of reproductive toxicity. Tralkoxydim caused no 
developmental toxicity in the rabbit. At a dose of 30 mg/kg/day, 
tralkoxydim caused some developmental effects in the rat manifested by 
skeletal defects including single fused or misshapen centra. The NOEL 
for developmental toxicity was established at 3 mg/kg/day.
    Based on the current toxicological data requirements, the database 
relative to pre- and post-natal effects for children is complete. 
Further, for the chemical tralkoxydim, the NOEL at 0.5 mg/kg/day from 
the dog feeding study which was used to calculate the RfD, is already 
lower than the NOEL from the developmental study in rats by a factor of 
approximately 10-fold. In addition, residue field trials have shown 
that there are no detectable residues of tralkoxydim on wheat and 
barley, indicating negligible exposure potential. Therefore, an 
additional uncertainty factor is not warranted and the RfD at 0.005 mg/
kg/day is appropriate for assessing aggregate risk to infants and 
children.
    The percentage of the RfD that will be utilized by aggregate 
exposure to tolerance level residues of tralkoxydim are: 2% for nursing 
infants, 6% for children 1-6 years, and 5% for children 7-12 years. 
Therefore, there is reasonable certainty that there will be no harm to 
these sensitive subgroups of the U.S. population. The agricultural use 
of tralkoxydim on wheat and barley does not represent an acute or 
chronic risk to the U.S. population, infants, children or any of the 23 
subgroups that were evaluated.

F. International Tolerances

    There are no Codex Maximum Residue Levels established for 
tralkoxydim.  (PM 25)

[FR Doc. 97-17176 Filed 7-1-97; 8:45 am]
BILLING CODE 6560-50-F