[Federal Register Volume 61, Number 240 (Thursday, December 12, 1996)]
[Notices]
[Pages 65395-65400]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 96-31556]


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ENVIRONMENTAL PROTECTION AGENCY
[PF-677; FRL-5576-1]


Valent U.S.A. Corporation; Pesticide Tolerance Petition Filing

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice of filing.

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SUMMARY: This notice is a summary of a pesticide petition proposing to 
renew a time-limited tolerance for residues of the herbicide lactofen, 
1-(carboethoxy)ethyl 5-[2-chloro-4- (trifluoromethyl)phenoxy]-2-
nitrobenzoate, and its associated metabolites containing the diphenyl 
ether linkage on the raw agricultural commodity (RAC) cottonseed at 
0.05 part per million (ppm). This summary was prepared by the 
petitioner, Valent U.S.A. Corporation (Valent).

DATES: Comments, identified by the docket number [PF-677], must be 
received on or before, January 13, 1997.

ADDRESSES: By mail, submit written comments to Public Response and 
Program Resources Branch, Field Operations Division (7506C), Office of 
Pesticide Programs, Environmental Protection Agency, 401 M St., SW.,

[[Page 65396]]

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 sending electronic mail (e-mail) to: 
[email protected]. Electronic comments must be submitted as an 
ASCII file avoiding the use of special characters and any form of 
encryption. Comments 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 docket number [PF-677]. 
Electronic comments on this notice may be filed online at many Federal 
Depository Libraries. Additional information on electronic submissions 
can be found below in this document.
    Information submitted as comments 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: Joanne I. Miller, Product Manager (PM 
23), Rm. 237, CM#2, 1921 Jefferson Davis Highway, Arlington, VA 22202; 
(703) 305-6224. e-mail: [email protected].

SUPPLEMENTARY INFORMATION: In the Federal Register of June 14, 1990, 
(55 FR 24084), EPA established a time-limited tolerance under section 
408 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 346a) for 
residues of the herbicide lactofen, 1-(carboethoxy)ethyl 5-[2-chloro-4- 
(trifluoromethyl)phenoxy]-2-nitrobenzoate, and its associated 
metabolites containing the diphenyl ether linkage in or on the raw 
agricultural commodity cottonseed at 0.05 ppm. The time-limited 
tolerance expires on December 31, 1996. This tolerance was requested in 
pesticide petition (PP) 9F3798 by Valent U.S.A. Corporation, 1333 N. 
California Blvd., Walnut Creek, CA 94596, and establishes the maximum 
permissible level for residues of the herbicide in or on this RAC. The 
tolerance was issued as a time-limited tolerance because EPA required 
additional residue chemistry data. The petitioner proposes to renew the 
time-limited tolerance for a one-year period. Valent requested this 
tolerance extension pursuant to the Federal Food, Drug, and Cosmetic 
Act (FFDCA) as amended by the Food Quality Protection Act of 1996 (Pub. 
L. 104-170). The request addresses the requirements of the new FFDCA 
Section 408(d)(2). The time-limited tolerance would expire on December 
31, 1997. The proposed analytical method is RM-28D, a gas 
chromatography method.
    Pursuant to the Section 408(d)(2)(A)(i) of the FFDCA, as amended, 
Valent has submitted the following summary of information, data and 
arguments in support of their pesticide petition. This summary was 
prepared by Valent and EPA has not fully evaluated the merits of the 
petition. EPA edited the summary to clarify that the conclusions and 
arguments were the petitioner's and not necessarily EPA's and to remove 
certain extraneous material.

I. Valent Petition Summary

A.   Residue Chemistry

    1.   Plant metabolism. Lactofen is used to control broad leaved 
weeds in crops by preemergent (soybean, peanut), or early postemergent 
(soybean, cotton, peanut) applications with extended pre-harvest 
intervals (45 to 70 days). Plant metabolism protocols (soybean, peanut, 
and tomato) have been designed to mimic the field applications with 
respect to timing, but have been applied at rates exceeding normal 
application to facilitate identification of metabolites.
    The lactofen molecule is rapidly degraded in the environment and in 
plants. Therefore, the consistent result of all plant metabolism 
studies using lactofen has been: radiocarbon is distributed throughout 
the plant; much of the radiocarbon is irreversibly bound; little 
radiocarbon is found in the RAC (seeds, fruit); and very little 
terminal residue is identified as finite metabolites due to extensive 
degradation.
    To demonstrate plant metabolic pathways and to prove the analytical 
methods can isolate, recover, and identify lactofen and its 
metabolites, plant samples were analyzed soon after application and 
well before normal harvest. It is from these early samples that the 
definition of the residue has been obtained. The regulated residue is 
defined as parent and four metabolites containing the diphenyl ether 
moiety. Parent lactofen is identified as PPG-844 and the metabolites 
are identified as PPG-847, PPG-947, PPG-1576, and PPG-2597. The 
regulated residue as defined has never been found in a RAC sample 
either from plant metabolism or from crop field studies. At maximum 
treatment rates in crop field trials, only one soybean seed sample was 
found to have residues of lactofen greater than the limit of detection, 
but less than the limit of quantitation. Even at exaggerated rates in 
metabolism or crop residue studies, residues are rarely above the limit 
of detection for any analyte. In addition, more than analyte has never 
been found above the limit of detection in a single RAC sample from 
crop field trials. See further discussion in the Magnitude of Residue 
section.
    2.   Analytical method. Adequate analytical methodology (gas 
chromatography) is available for detecting and measuring levels of 
lactofen and its metabolites in or on food with a limit of detection 
that allows monitoring of food with residues at or above the level set 
in the time-limited tolerance on cotton. The current method, RM-28D, 
has been validated by an independent laboratory on both cottonseed and 
peanuts and is still undergoing PMV trials at the EPA. In general, the 
analytical method has a limit of detection of 0.005 ppm and limit of 
quantitation of 0.01 ppm in crops.
    3.   Magnitude of residues. Lactofen is the active ingredient in 
COBRA Herbicide (EPA Reg. No. 59639-34) and STELLAR Herbicide (EPA Reg. 
No. 59639-92). Tolerances have been established for lactofen on cotton, 
soybeans, and snap beans. A tolerance is also pending for peanuts. 
Lactofen is a broad-spectrum broadleaf herbicide with the following use 
patterns:
    Soybeans:   pre-emergence and/or post-emergence, broadcast 
application with a PHI of 45 days.
    Cotton:   post-emergence, directed spray application with a PHI 
of 70 days.
    Snap Beans:   pre-emergence, soil application with a PHI of 55 
days.
    Peanuts:   (pending) pre-emergence and/or post-emergence, 
broadcast application with a PHI of 70 days.

    Due to relatively long pre-harvest intervals and extensive 
metabolism by plants, lactofen residues are rarely found in treated raw 
agricultural or processed commodities. Consequently, tolerances have 
been established based on the limit of quantitation for lactofen and 
its metabolites containing the diphenyl ether linkage. To date, 
tolerances have been established at 0.05 ppm based on a limit of 
quantitation of 0.01 ppm for lactofen and four plant metabolites.

[[Page 65397]]

B. Toxicological Profile

    1.   Acute toxicity. Lactofen (PPG-844) Technical has been placed 
in EPA Toxicity Category III for dermal toxicity and Category IV for 
the other four acute toxicity tests. It has also been found to be a 
weak skin sensitizer. Teratology and reproduction studies indicate that 
adverse effects, including embryotoxicity, occur only at doses that are 
also maternally toxic. This chemical therefore represents a minimal 
acute toxicity risk.
    2.   Genotoxicity. Lactofen Technical has been tested and produced 
negative results in a number of genotoxicity tests including 
unscheduled DNA synthesis in rat hepatocytes, DNA covalent binding in 
mouse liver, chromosomal aberration in CHO cells, and an Ames assay. In 
a second Ames assay lactofen was positive without metabolic activation 
at 5000 ug/plate and above. Overall lactofen is not considered a 
genetic hazard.
    3.   Reproductive and developmental toxicity. Pregnant rats were 
administered oral doses of 0, 15, 50 and 150 mg/kg/day Lactofen 
Technical on days 6-19 of gestation. Maternal toxicity (death, abortion 
and reduced body weight gain) was observed at 150 mg/kg/day. 
Developmental toxicity (reduced fetal weight, slightly reduced 
ossification, bent ribs and bent limb bones) was also observed at 150 
mg/kg/day. The NOEL for this study was 50 mg/kg/day.
    Two developmental toxicity studies were conducted in rabbits with 
Lactofen Technical. In the first study, pregnant rabbits were 
administered oral doses of 0, 5, 15 or 50 mg/kg/day Lactofen Technical 
on days 6-18 of gestation. Maternal toxicity (clinical signs and 
reduced weight gain) and developmental effects (increased embryonic 
death, decreased litter size and increased post-implantation loss) were 
reported at 15 and 50 mg/kg, however EPA concluded that the data were 
insufficient to establish a clear NOEL. The study was classified as 
core-supplementary. In the second rabbit developmental toxicity study, 
pregnant rabbits were exposed to 0, 1, 4 or 20 mg/kg/day oral doses on 
days 6-18 of gestation. Maternal toxicity (reduced food consumption) 
was observed at 20 mg/kg/day, while no developmental effects were 
observed at any dose. Therefore, the maternal NOEL was 4 mg/kg/day and 
the developmental NOEL was greater than 20 mg/kg/day.
    Groups of male and female rats were administered 0, 50, 500 or 2000 
ppm of Lactofen Technical for two generations. Adult systemic toxicity 
(mortality, reduced body weight, increased liver and spleen weight, 
decreased kidney weight and histological changes in the liver and 
testes) was observed at levels of 500 ppm and greater. Reproductive 
toxicity (lower pup survival rates, reduced pup weight and pup organ 
weight effects) was also observed at levels of 500 ppm and greater. The 
NOEL for both systemic and reproductive toxicity was 50 ppm (2.5 mg/
kg).
    Since lactofen causes teratogenic and reproductive effects only at 
levels which also produce systemic toxicity it is not considered a 
reproductive hazard.
    4.   Subchronic toxicity. In a 4-week oral toxicity study of 
Lactofen Technical in rats, a slight increase in spleen weight was the 
basis for a LOEL of 200 ppm (lowest dose tested). At doses of 1000 ppm 
or higher the following findings were reported: clinical signs of 
toxicity; decreased RBC, hemoglobin, hematocrit, and increased WBC; 
increased relative liver and spleen weights; and necrosis and 
pigmentation of hepatocytes. At 10,000 ppm severe toxic signs were 
observed by day 7 and all animals were dead or killed in extremis by 
day 11. Hypocellularity of the spleen, thymus and bone marrow was also 
observed in animals exposed to 10,000 ppm.
    Histopathological changes in the liver and significant changes in 
clinical chemistry associated with the liver were observed in rats 
exposed to 1000 ppm Lactofen Technical in the diet for 90 days. 
Decreased RBC, hemoglobin and hematocrit values were also observed at 
1000 ppm. The NOEL in this study was 200 ppm.
    In a 90-day study in mice, the LOEL for Lactofen Technical was 200 
ppm based on: increased WBC; decreased hematocrit, hemoglobin and RBC; 
increased alkaline phosphatase, SGOT, SGPT, cholesterol and total serum 
protein levels; increased weights or enlargement of the spleen, liver, 
adrenals, heart and kidney; histopathological changes of the liver, 
kidney, thymus, spleen, ovaries and testes observed at 1000 ppm.
    Butler et al (1988) studied the effects of lactofen on peroxisome 
proliferation in mice exposed for seven weeks to dietary concentrations 
of 2, 10, 50 and 250 ppm. Liver-weight to body-weight ratio, liver 
catalase, liver acyl-CoA oxidase, liver cell cytoplasmic eosinophilia, 
nuclear and cellular size, and peroxisomal staining were increased by 
the tumorigenic dose of lactofen, i.e. 250 ppm. Lower doses of lactofen 
had little to no effect on these parameters. Thus, this study indicates 
that lactofen induces peroxisome proliferation and further, that 50 
ppm, a dose which is not tumorigenic, would be considered a threshold 
dose for peroxisome proliferation produced by lactofen.
    As noted in the study by Butler et al (1989), the NOEL for 
peroxisome proliferation in mice following a seven week exposure period 
is 50 ppm (7 mg/kg/day) and the LOEL is 250 ppm (36 mg/kg/day). A 
subchronic study conducted in chimpanzees (Couch and Erickson, 1986), 
indicated no effect on clinical chemistry or histological endpoints 
that would suggest liver toxicity or peroxisome proliferation at doses 
up to 75 mg/kg/day administered for 93 days. Therefore, Valent believes 
that 75 mg/kg/day is a clear NOEL for peroxisome proliferation observed 
in a species closely related to man.
    5.   Chronic toxicity. In an 18-month oncogenicity study in mice at 
doses of 10, 50 and 250 ppm Lactofen Technical, an increase in liver 
adenomas and carcinomas, cataracts and liver pigmentation was observed 
at 250 ppm. The lowest dose, 10 ppm, was the LOEL based on increased 
liver weight and hepatocytomegaly.
    In a 2-year chronic feeding/oncogenicity study of Lactofen 
Technical in rats at doses of 500, 1000 or 2000 ppm in the diet, an 
increase in liver neoplastic nodules and foci of cellular alteration 
was observed in both sexes at 2000 ppm. The NOEL for systemic toxicity 
is 500 ppm based on kidney and liver pigmentation.
    In a 1-year study in dogs exposed to 40, 200, or 1000(wk1-17)/3000 
ppm(wk 18-52) ppm of Lactofen Technical, the NOEL was determined to be 
200 ppm based on renal dysfunction and decreased RBC, hemoglobin 
hematocrit and cholesterol observed at 1000/3000 ppm.
    Lactofen (PPG-844) Technical causes adverse health effects when 
administered to animals for extended periods of time. The effects 
include proliferative changes in the liver, spleen, and kidney; 
hematological changes; and blood biochemistry changes. Based on the 
Lowest Effect Level (LEL) of 1.5 mg/kg/day in the 18-month mouse 
feeding study and an uncertainty factor of 1000, a reference dose (RfD) 
of 0.002 mg/kg/day has been established for lactofen. An uncertainty 
factor of 1000 was used since a NOEL was not be established.
    The Toxicology Branch Peer Review Committee in EPA's Office of 
Pesticide Programs has determined that lactofen meets the criterion for 
a B2 (possible human) carcinogen since it caused an increase in liver 
tumors (adenomas and/or carcinomas) in two species. Based on

[[Page 65398]]

the mouse oncogenicity study, a human upper-bound potency estimate 
(Q1*) was calculated as 0.17 (mg/kg/day)-1.
    The calculated human Q1* was based on the standard interspecies 
scaling factor of BW0.67 and recent EPA guidance indicates that BW0.75 
is a more appropriate factor for general use. This change alone would 
result in a reduction of the calculated human potency factor and a 
reduction in the calculated carcinogenic risk by about 20%. In 
addition, evidence suggests that carcinogenic effects caused by 
lactofen in rodent livers may be due to peroxisomal proliferation as 
opposed to a direct genotoxic effect. This mechanism of action would 
more appropriately be regulated as a threshold effect (similar to RfD 
comparisons) as opposed to a non-threshold effect with a quantitative 
potency factor derived from low dose extrapolations. These changes in 
the hazard assessment process for lactofen would have a profound effect 
on the exposure and risk assessments for this chemical.
    6.   Animal metabolism. Rat metabolism studies have been conducted 
for lactofen and demonstrate that lactofen is almost completely 
eliminated (>95%) in excreta within three days of oral dosing. 
Generally about 60% of orally administered radioactivity (14C-lactofen) 
is found in the feces with lactofen itself being the major component. 
About 40% of radioactivity is recovered in urine and PPG-847 
(hydrolyzed side chain) is the major metabolite. Other metabolites 
include PPG-947, PPG-1576, and PPG-2053.

C.   Aggregate Exposure

    Complete information to perform an aggregate exposure assessment 
may be available to the Agency, but is not available to Valent, and an 
extension of the lactofen cotton tolerance has been requested by Valent 
in order to allow EPA time to perform a complete aggregate exposure 
assessment. As discussed below, lactofen contributes insignificant 
chronic toxicity and carcinogenic risks as compared to the other 
diphenyl ethers.
    1.   Dietary exposure. (a)   Food.   Lactofen is approved for use 
in the production of commercial agricultural crops including soybeans, 
cotton, snap beans, and pine seedlings. Dietary exposures are expected 
to represent the major route of exposure to the public.
    A chronic dietary assessment for lactofen has been conducted by the 
registrant using Anticipated Residue Contributions (ARC) for existing 
and proposed uses of lactofen. Since crop field trial data indicate 
that quantifiable residues of lactofen are rarely found in raw 
agricultural and processed commodities , ARCs were estimated based on 
the analytical method limit of detection (LOD) for each commodity. When 
available, analytical results for control samples were used to 
determine the method LOD for lactofen and its related metabolites. When 
all control samples contained no detectable residues, the limit of 
detection was determined to be 0.005 ppm. Mean anticipated residues 
were determined based on the sum of residues found above the LOD, or 
when no detectable residues were present for lactofen or any 
metabolite, one-half the greatest LOD for any analyte was used as the 
anticipated residue level. Anticipated residue levels also considered 
the percent of crop treated with lactofen as follows: 5% of soybeans, 
2.5% of cotton, 4.5% of snap beans, and 5% of peanuts. The soybean and 
cotton values are based on 1995 marketing research data (Maritz) and 
the snap bean and peanut values are estimates for the future from the 
registrant. Note that a lactofen peanut tolerance is still pending at 
the Agency and no lactofen is used on this crop even though peanuts are 
included in the dietary exposure assessment. The assessment results are 
summarized below in the Safety Determination section.
    EPA has performed chronic dietary exposure assessments for the 
related diphenyl ethers mentioned above in conjunction with tolerance 
approvals. For acifluorfen and fomesafen, recent assessments were 
performed with anticipated residues, but did not consider percent of 
crop treated. For oxyfluorfen, anticipated residues were considered for 
only some crops and the same is true for percent of crop treated. And 
for diclofop, neither anticipated residues nor percent of crop treated 
were considered. Therefore, the current dietary assessments performed 
by EPA are highly conservative, but not worst case. Additional time is 
necessary for the Agency to perform a consistent and integrated dietary 
exposure assessment for these related chemicals. The assessment results 
are summarized below in the Safety Determination section.
    (b)   Drinking water.   Since lactofen is applied outdoors to 
growing agricultural crops, the potential exists for lactofen or its 
metabolites to leach into groundwater. Drinking water, therefore 
represents a potential route of exposure for lactofen and should be 
considered in an aggregate exposure assessment.
    Based on available lactofen studies used in EPA's assessment of 
environmental risk, EPA required a prospective groundwater study for 
lactofen. Valent conducted a study using the maximum application rate 
applied to a site which was extremely vulnerable to leaching to a 
shallow aquifer. The water table was at a depth of 6 to 9 feet, the top 
two feet of soil were classified as loamy sand (78 - 82% sand), and the 
deeper soil was classified as sand (88 - 94% sand).
    A final report was submitted in 1994 which indicates that lactofen 
degrades rapidly without downward movement in soil and will not 
contaminate even shallow groundwater beneath light, sandy soils. There 
were no reported or possible detections of lactofen (< 1 ppb) in 
lysimeter or monitoring well water samples with the exception of 
apparent detections (1.4 - 1.6 ppb) in two well water samples which 
were determined to be due to matrix interferences. Reanalysis to 
resolve the interference problem indicated that lactofen was not 
present at the 1 ppb level. Lactofen degrades to acifluorfen, which was 
also monitored in the study. Although acifluorfen was found to degrade 
somewhat more slowly than lactofen, it did not leach to groundwater 
during the study. Since acifluorfen results from lactofen degradation, 
but is not the only degradation product, concentrations are expected to 
be lower for acifluorfen than for lactofen. In fact, there were no 
reported or possible detections of acifluorfen (< 1 ppb) in lysimeter 
or monitoring well samples. This report has been placed in review at 
EPA, but a review has not been completed.
    There is no established Maximum Concentration Level for residues of 
lactofen in drinking water under the Safe Drinking Water Act.
    Based on this information, lactofen appears to represent an 
insignificant risk for exposure through drinking water.
    2.   Non-dietary exposure. Lactofen is currently approved only for 
the commercial production of agricultural crops including cotton, 
soybeans, snap beans, and pine seedlings. The potential for non-
occupational exposure to the general public, other than through the 
diet or drinking water, is therefore insignificant.

D.   Cumulative Effects.

    There are several other pesticide compounds which are structurally 
related and may have similar effects on animals. Specifically, 
lactofen, acifluorfen, fomesafen, oxyfluorfen, and diclofop methyl are 
all diphenyl ethers which have caused liver tumors in

[[Page 65399]]

rodents. These chemicals are approved for food uses in the U.S. and 
could be considered in an aggregate exposure assessment. Dietary 
exposures to these other diphenyl ethers are expected to represent the 
major route of exposure to the public. It is premature to add the risk 
from these chemicals since exposure considerations as well as endpoint, 
pharmacokinetic, and pharmacodynamic considerations may indicate that 
it is inappropriate to add the risks. However, to meet the requirements 
of the FQPA of 1996, it is prudent to consider if it is likely that 
these chemicals violate the provisions of the new law. The information 
presented below indicates that while more study is necessary, it is 
unlikely that these materials violate the provisions of the act.
    Summaries of the established reference doses, quantitative cancer 
potency factors, and cancer sites in animals for these structurally 
related chemicals are presented below.


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                                        Reference Dose (mg/kg/   Cancer Potency Factor                          
               Chemical                          day)                (mg/kg/day)-1             Cancer Site      
----------------------------------------------------------------------------------------------------------------
Lactofen                               0.002                    0.17                     Liver                  
Acifluorfen                            0.013                    0.107                    Liver, Stomach         
 Fomesafen                             0.0025                   0.19                     Liver                  
Oxyfluorfen                            0.003                    0.13                     Liver                  
Diclofop Methyl                        0.002                    0.231                    Liver                  
----------------------------------------------------------------------------------------------------------------


    This comparison indicates that reference doses determined from 
chronic toxicity studies and cancer potency factors for these related 
chemicals are on the same order of magnitude as for lactofen.
    It should be noted that these related chemicals would benefit from 
the use of the EPA's new interspecies scaling factor as well as 
lactofen, and that the rodent liver tumor effects may also be due to 
peroxisome proliferation which would more appropriately be regulated as 
a threshold effect. The carcinogenic risk assessments performed to date 
are, therefore, highly conservative.

E.   Safety Determination

    1.   U.S. population. Using the dietary exposure assessment 
procedures described above (and performed by Valent) for lactofen, and 
recent EPA assessments for related chemicals, chronic dietary exposures 
resulting from existing and proposed uses of lactofen and related 
chemicals were compared to the reference dose (RfD) for each chemical. 
The following contributions to the RfD were found for the U.S. 
Population and all of the subpopulations for which dietary consumption 
data are available:
    Lactofen:  less than 0.1% for all subpopulations.
    Acifluorfen:  less than 1% for all subpopulations.
    Fomesafen:  less than 1% for all subpopulations.
    Oxyfluorfen:  less than 1% for all subpopulations.
    Diclofop:  not available to Valent.


    EPA generally has no concern for exposures below 100 percent 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. The current and proposed uses of these 
chemicals, even when considered collectively, represent a minimal 
chronic toxicological risk to the general public.
    Carcinogenic risks were calculated by Valent using a potency factor 
(Q1*) for lactofen of 0.17 (mg/kg/day)-1. The dietary carcinogenic 
risk resulting from existing and proposed uses of lactofen is 
calculated at 1.54 X 10-8 or less for several lifetime population 
groups. This is approximately 65 times lower than the acceptable level 
of one-in-a-million additional lifetime cancers. It should be noted 
that the proposed use on peanuts, which is not being considered in the 
current action, accounts for more than a third of the exposure 
contributing to the calculated carcinogenic risk. Therefore, these 
estimates of carcinogenic risk are conservative and are well within 
acceptable levels.
    EPA has performed dietary carcinogenic risk assessments for the 
related diphenyl ethers mentioned above in conjunction with tolerance 
approvals. The following table summarizes the dietary risk assessment 
made by Valent for lactofen and the most recent dietary risk 
assessments performed by EPA for related chemicals.


----------------------------------------------------------------------------------------------------------------
               Chemical                      Data Source                  Date              Carcinogenic Risk   
----------------------------------------------------------------------------------------------------------------
Lactofen                               Valent Report            8/20/96                  1.54 X 10-8            
Acifluorfen                            61 FR 16740              4/17/96                  5.8 X 10-7             
Fomesafen                              61 FR 31057              6/19/96                  1.56 X 10-6            
Oxyfluorfen                            60 FR 49816              9/27/95                  1.8 X 10-6             
Diclofop methyl                        51 FR 19176              5/28/86                  1 X 10-5               
----------------------------------------------------------------------------------------------------------------


    Regarding drinking water exposures, groundwater monitoring studies 
have been required for acifluorfen, fomesafen, and diclofop methyl as 
well as for lactofen. Detections in groundwater have been reported for 
acifluorfen and fomesafen. Complete information may be available to the 
Agency, but is not to available to Valent, and additional time is 
requested to allow time for EPA to adequately address the drinking 
water exposure issue. However, based on the lactofen groundwater study, 
lactofen exposures to the public through drinking water are expected to 
be insignificant compared to these other chemicals.
    Regarding non-dietary exposures, the other diphenyl ethers are also 
used primarily for commercial agricultural production. However, some of 
these chemicals may involve some uses around the home which could lead 
to non-occupational exposure. Information about this small potential 
exposure is not available to Valent, but if a significant potential 
exists for non-occupational exposure, is should be considered in an 
aggregate risk assessment by EPA. Some exposures to residential 
pesticides are being evaluated by an industry task force, the Outdoor 
Residential Exposure Task Force (ORETF), of which Valent is a member.
    In summary, this comparison shows that lactofen's contribution to 
aggregate cancer risk is insignificant compared to the other diphenyl 
ethers, based on

[[Page 65400]]

current registrant and EPA assessments. In addition, the conservative 
risks calculated by EPA for fomesafen and oxyfluorfen are slightly 
above the new standard set by FQPA and for diclofop methyl is 
significantly above the new standard. Valent believes that when these 
other diphenyl ethers are evaluated using anticipated residues, percent 
of crop treated, revised cancer potency factors, and up-to-date 
exposure methodology the projected risks will be much lower than 1 X 
10-6 for all of these chemicals. Industry and EPA are also 
developing methodology for determining whether or not multiple 
exposures will occur and with what frequency for these and other 
chemicals. If multiple exposures do not occur, or occur with a low 
frequency, it is not appropriate to add risks. For these reasons, 
additional time will be necessary for the Agency to address the 
aggregate risk to the U.S. population for this group of related 
chemicals.
    2.   Infants and children. As stated above, dietary exposure 
assessments utilize less than 1% of the RfD for all subpopulations 
including infants and children. Reproduction and developmental effects 
have been found in toxicology studies for lactofen, however, the 
adverse effects were seen at levels that were also maternally toxic. 
This indicates that developing animals are not more sensitive than 
adults. FQPA requires an additional safety factor of up to 10 for 
chemicals which present special risks to infants or children. Lactofen 
does not meet the criterion for application of an additional safety 
factor for infants and children.
    Information on the reproduction and developmental effects caused by 
the other diphenyl ethers is not available to Valent. Additional time 
is necessary for the Agency to evaluate the need for an additional 
safety factor related to these other chemicals. However, even if an 
additional safety factor were deemed necessary, the dietary exposures 
are still expected to be well below the established reference doses.

F.   International Tolerances

    There are no Codex Maximum Residue Limits (MRL) established for 
lactofen on cotton commodities, so there is not conflict between this 
proposed action and international residue limits.

II.   Administrative Matters

    Interested persons are invited to submit comments on this notice of 
filing. Comments must bear a notation indicating the document control 
number, [PF-677]. All written comments filed in response to this 
petition will be available in the Public Response and Program Resources 
Branch, at the address give above from 8:30 a.m. to 4 p.m., Monday 
through Friday, except legal holidays.
    A record has been established for this notice under docket number 
[PF-677] 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 public 
record is located in Rm. 1132 of the Public Response and Program 
Resources Branch, Field Operations Division (7506C), Office of 
Pesticide Programs, Environmental Protection Agency, Crystal Mall #2, 
1921 Jefferson Davis Highway, Arlington, VA.
    Electronic comments can be sent directly to EPA at:
    opp-D[email protected]


    Electronic comments must be submitted as ASCII file avoiding the 
use of special characters and any form of encryption.
    The official record for this rulemaking, as well as the public 
version, as described above will be kept in paper form. Accordingly, 
EPA will transfer all comments received electronically into printed, 
paper form as they are received and will place the paper copies in the 
official rulemaking record which will also include all comments 
submitted directly in writing. The official rulemaking record is the 
paper record maintained at the address in ``ADDRESSES'' at the 
beginning of this document.

List of Subjects

    Environmental protection, Administrative practice and procedure, 
Agricultural commodities, Pesticides and pests, Reporting and 
recordkeeping requirements.

    Dated: December 4, 1996.

Stephen L. Johnson,
Director, Registration Division, Office of Pesticide Programs.

[FR Doc. 96-31556 Filed 12-11-96; 8:45 am]
BILLING CODE 6560-50-F