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lactofen (Cobra) Pesticide Petition Filing 2/98

  

[Federal Register: February 25, 1998 (Volume 63, Number 37)]
[Notices]               
[Page 9532-9540]
>From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr25fe98-77]

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ENVIRONMENTAL PROTECTION AGENCY

[PF-789; FRL-5767-5]

 
Notice of Filing of Pesticide Petition

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice.

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SUMMARY: This notice announces the initial filing of a pesticide 
petition proposing the establishment of regulations for residues of a 
certain pesticide chemical in or on various food commodities.
DATES: Comments, identified by the docket control number PF-789, must 
be received on or before March 27, 1998.
ADDRESSES: By mail submit written comments to: Information and Records 
Integrity Branch, Public Information and Services Divison (7502C), 
Office of Pesticides Programs, Environmental Protection Agency, 401 M 
St., SW., Washington, DC 20460. In person bring comments to: Rm. 119, 
CM #2, 1921 Jefferson Davis Highway, Arlington, VA.
    Comments and data may also be submitted electronically to: opp-
docket @epamail.epa.gov. Follow the instructions under ``SUPPLEMENTARY 
INFORMATION.'' No confidential business information should be submitted 
through e-mail.
    Information submitted as a comment concerning this document may be 
claimed confidential by marking any part or all of that information as

[[Page 9533]]

``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. 119 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, Registration Support 
Branch, Registration Division (7505C), Office of Pesticide Programs, 
Environmental Protection Agency, 401 M St., SW., Washington, DC 20460. 
Office location, telephone number, and e-mail address: Rm. 237, Crystal 
Mall #2, 1921 Jefferson Davis Highway, Arlington, VA 22202, (703) 305-
6224; e-mail: miller.joanne@epamail.epa.gov.
SUPPLEMENTARY INFORMATION: EPA has received a pesticide petition as 
follows proposing the establishment and/or amendment of regulations for 
residues of certain pesticide chemical in or on various food 
commodities under section 408 of the Federal Food, Drug, and Comestic 
Act (FFDCA), 21 U.S.C. 346a. EPA has determined that this petition 
contains data or information regarding the elements set forth in 
section 408(d)(2); however, EPA has not fully evaluated the sufficiency 
of the submitted data at this time or whether the data supports 
granting of the petition. Additional data may be needed before EPA 
rules on the petition.
    The official record for this notice of filing, as well as the 
public version, has been established for this notice of filing under 
docket control number [PF-789] (including comments and data submitted 
electronically as described below). A public version of this record, 
including printed, paper versions of electronic comments, which does 
not include any information claimed as CBI, is available for inspection 
from 8:30 a.m. to 4 p.m., Monday through Friday, excluding legal 
holidays. The official record is located at the address in 
``ADDRESSES'' at the beginning of this document.
    Electronic comments can be sent directly to EPA at:
    opp-docket@epamail.epa.gov


    Electronic comments must be submitted as an ASCII file avoiding the 
use of special characters and any form of encryption. Comment and data 
will also be accepted on disks in Wordperfect 5.1/6.1 file format or 
ASCII file format. All comments and data in electronic form must be 
identified by the docket control number (PF-789) and appropriate 
petition number. Electronic comments on this notice may be filed online 
at many Federal Depository Libraries.

List of Subjects

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

    Dated: February 11, 1998

Peter Caulkins,

Acting Director, Registration Division, Office of Pesticide Programs.

Summary of Petition

    The petitioner summary of the pesticide petition is printed below 
as required by section 408(d)(3) of the FFDCA. The summary of the 
petition was prepared by the petitioner and represents the views of the 
petitioner. EPA is publishing the petition summary verbatim without 
editing it in any way. The petition summary announces the availability 
of a description of the analytical methods available to EPA for the 
detection and measurement of the pesticide chemical residues or an 
explanation of why no such method is needed.

 Valent U.S.A Corporation

PP 9F3798

    EPA has received a pesticide petition (PP 9F3798) from Valent U.S.A 
Corporation, 1333 North California Blvd., Suite 600, Walnut Creek, 
California 94596-8025 proposing pursuant to section 408(d) of the 
Federal Food, Drug and Cosmetic Act, 21 U.S.C. 346a(d), to amend 40 CFR 
part 180 by extending a time-limited tolerance for residues of 
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 parts per million (ppm). The tolerance would expire on December 
31, 1999. The time limitation on the tolerance would allow Valent to 
complete, and EPA to evaluate, additional prospective groundwater study 
data. EPA has determined that the petition contains data or information 
regarding the elements set forth in section 408(d)(2) of the FFDCA; 
however, EPA has not fully evaluated the sufficiency of the submitted 
data at this time or whether the data supports granting of the 
petition. Additional data may be needed before EPA rules on the 
petition.

A. Residue Chemistry

    1. Plant metabolism. Lactofen, formulated as COBRA<SUP></SUP> 
Herbicide, is used to control broadleaf weeds in soybeans by pre- and/
or post-emergent application and in cotton by post-directed 
application. Pre-harvest intervals are extended, 45 to 70 days. Plant 
metabolism protocols (cotton, peanut, soybean and tomato) have been 
designed to mimic the field applications with respect to application 
methods and timing. In the studies, plant material has been treated at 
rates exceeding normal field application to facilitate identification 
of metabolites. Postdirected application to cotton was simulated in the 
field using radiocarbon labeled lactofen and demonstrated that no 
radioactivity (> 0.001 ppm lactofen equivalent) was detected in the 
bolls.
    The lactofen molecule is rapidly degraded in the environment and in 
plants. Therefore, the consistent result of all detailed plant 
metabolism studies using radiolabeled lactofen has been:
    i. Low concentrations of radiocarbon are distributed throughout the 
plant,
    ii. Much of the radiocarbon is irreversibly bound and 
unextractible,
    iii. Very low concentrations of radiocarbon is found in the RAC 
(seeds), and
    iv. Very little of the terminal residue is identifiable as finite 
metabolites as a result of the extensive degradation and binding.
    To demonstrate plant metabolic pathways and to validate that the 
residue analytical methodology can extract, identify and quantitate 
lactofen and its metabolites as aged residues, plant samples from 
radiocarbon metabolism studies were analyzed soon after application, 
well before normal harvest. It is from these early samples that the 
definition of the regulated residue in RAC has been obtained. The 
residue of concern is defined by the Agency as parent and four 
degradates containing the intact diphenyl ether moiety. Parent lactofen 
(PPG-844) is degraded hydrolytically to corresponding carboxylic acid-
lactate ester (PPG-947), and further to the benzoic acid (PPG-847). In 
a separate pathway, the esters remain intact and the aromatic nitro 
group is reduced to the corresponding aniline (PPG-1576) and the 
aniline is formylated (PPG-2597). Further, there is good evidence that 
these lactofen metabolites are further degraded by cleavage of the

[[Page 9534]]

diphenyl ether. The sodium salt of the benzoic acid (PPG-847) is the 
commercial herbicide acifluorfen. All five of the compounds in the 
regulated residue as defined have never been found in a single RAC 
sample either from plant metabolism or from crop field studies. For 
example, at maximum treatment rates in crop field trials, only one 
soybean seed sample was found to have a residue of parent lactofen 
greater than the limit of detection, but less than the limit of 
quantitation and only a single cotton gin trash sample was found to 
contain a finite residue of lactofen. Even at exaggerated rates in 
metabolism or crop residue studies, residues are rarely above the limit 
of detection for any analyte. In fact, more than one analyte has never 
been found above the limit of detection in a single RAC sample from 
crop field trials.
    2. Analytical method. Adequate analytical methodology is available 
for detecting and measuring levels of lactofen and regulated 
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 method involves extraction with 
triethylamine/aqueous ethanol, partitioning, methylation of the 
carboxylic acids, column clean-up, and separation and quantitation by 
gas chromatography with electron capture detection. The method, RM-28D, 
has been validated by an independent laboratory on both cottonseed and 
peanuts and was found to be acceptable with comments for enforcement in 
cottonseed by the EPA Analytical Chemistry Laboratory. 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). There are existing tolerances 
for lactofen on soybeans, and snap beans. A time limited tolerance 
supported use on cotton, and a tolerance is pending for peanuts. 
Lactofen is a broad-spectrum broadleaf herbicide with the following use 
pattern on cotton:
    Post-emergence directed spray applications with a single 
application maximum of 0.2 lb. a.i./acre, a seasonal maximum total 
application of 0.4 lb. a.i./acre, and a PHI of 70 days.
    Because of relatively long pre-harvest interval, post-directed 
applications, and extensive degradation, finite lactofen residues have 
not been found in cottonseed or processed cottonseed commodities. 
Reports covering field residue trials from twenty-one sites in all 
cotton growing states, several at exaggerated rates, along with 
processing studies have failed to show detectable residues of lactofen 
or its regulated degradates in any sample. Consequently, a tolerance on 
cottonseed is proposed at 0.05 ppm, based on the sum of the 0.01 ppm 
limits of quantitation for lactofen and its four regulated metabolites 
containing the diphenyl ether linkage. Field residue data for cotton 
gin trash has recently been submitted. All other lactofen tolerances to 
date have been established similarly at 0.05 ppm.

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. This chemical therefore represents a minimal acute 
toxicity risk.
    2. Genotoxicty. Lactofen Technical has been tested and produced 
negative results in genotoxicity tests including unscheduled DNA 
synthesis in rat hepatocytes, DNA covalent binding in mouse liver, 
chromosomal aberration in CHO cells. Lactofen technical was also 
negative in an Ames assay. In repeat Ames assays, lactofen was shown to 
be positive without metabolic activation at 5,000 <greek-m>g/plate and 
above. Overall lactofen is not a genetic hazard.
    3. Reproductive and developmental toxicity. Reproduction and 
teratology studies indicate that adverse effects, including 
embryotoxicity, occur only at doses that are also maternally toxic. 
Since lactofen causes effects only at levels which also produce 
systemic toxicity the compound is not a reproductive hazard.
    4. Reproduction-- Rats. Groups of male and female rats were fed 0, 
50, 500 or 2,000 ppm of Lactofen Technical continuously in their diets 
for 2-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 No-Observed Effect-Level (NOEL) for 
both systemic and reproductive toxicity was 50 ppm (2.5 milligram/
kilogram/day (mg/kg/day).
    5. Developmental toxicity-- Rats. 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.
    6. Developmental toxicity-- Rabbits. 2 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 milligram/kilogram 
(mg/kg). The Agency concluded that the data were insufficient to 
establish a clear NOEL. 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.

C. Subchronic Toxicity

    1. Subchronic feeding-- Rat-- 4-week. Male and female rats were fed 
diets containing Lactofen Technical at concentrations of 0, 200, 1,000, 
5,000, and 10,000 ppm for four weeks. A slight increase in spleen 
weight was the basis for a Lowest-Observed Effect-Level (LOEL) of 200 
ppm (lowest dose tested). At doses of 1,000 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.
    2. Subchronic feeding-- Rat-- 3-month. Lactofen Technical was fed 
to male and female rats at dietary concentrations of 0. 40, 200, and 
1,000 ppm for 13-weeks. Histopathological changes in the liver and 
significant changes in clinical chemistry associated with the liver 
were observed in rats exposed to 1,000 ppm Lactofen Technical dosage. 
Decreased RBC, hemoglobin and hematocrit values were also observed at 
1,000 ppm. The NOEL in this study was 200 ppm.

[[Page 9535]]

    3. Subchronic feeding-- Dog-- 4-week. In a range finding study 
Lactofen Technical was fed in the diet of dogs at 0. 1,000, 3,000, and 
10,000 ppm for 4-weeks. Toxic effects noted in dogs fed 10,000 ppm 
included decreased rbc count and hemocrit, and increased BUN and SGPT. 
Food palatability problems led to greatly decreased feed consumption at 
higher dosages. The NOEL appeared to be 1,000 ppm.
    4. Subchronic feeding-- Mice-- 3-month. Groups of Male and female 
mice were fed diets containing Lactofen Technical at concentrations of 
0, 40, 200, 1,000, 5,000, and 10,000 for 13-weeks. At week 5, the 
dosage of the 40 ppm groups was increased to 2,000 ppm. Treatment 
related mortality occurred at dosages above 1,000 ppm. The LOEL 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. In general, effects were 
slight in the 200 ppm groups, and moderate to severe in the 1,000 ppm 
groups.
    5. Peroxisome proliferation-- Mice-- 7-weeks. Butler et al (1988) 
studied the effects of lactofen on peroxisome proliferation in mice 
exposed for 7-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 (7 mg/kg/
day), a dose which is not tumorigenic, would be considered a threshold 
dose in mice for peroxisome proliferation produced by lactofen. 
Peroxisome Proliferation -- Chimpanzees 14-weeks: 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.

D. Chronic Toxicity

    A complete chronic data base supported by appropriate subchronic 
studies for lactofen is available to the Agency. Lactofen Technical 
causes adverse health effects when administered to animals for extended 
periods of time. These 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 
1,000, a reference dose (RfD) of 0.002 mg/kg/day has been established 
for lactofen. An uncertainty factor of 1,000 was used since a clear 
NOEL was not established.
    1. Chronic/carcinogenicity feeding study-- Mouse-- 24-month. In a 
dietary 18-month oncogenicity study in mice at dosages 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.
    2. Chronic/carcinogenicity feeding study-- Rat-- 24-month. In a 2-
year chronic feeding/oncogenicity study of Lactofen Technical in rats 
at dosages of 0, 500, 1,000 and 2,000 ppm in the diet, an increase in 
liver neoplastic nodules and foci of cellular alteration was observed 
in both sexes at 2,000 ppm. The NOEL for systemic toxicity is 500 ppm 
based on kidney and liver pigmentation.
    3 Oral toxicity study-- Dog-- 12-month. In a 1-year study in dogs 
exposed to 40, 200, and 1,000 (wk.1-17) or 3,000 ppm (wk 18-52) 
Lactofen Technical in their diet, the NOEL was determined to be 200 ppm 
based on renal dysfunction and decreased RBC, hemoglobin hematocrit and 
cholesterol observed at 1,000/3,000 ppm.
    4. Carcinogenicity. The Toxicology Branch Peer Review Committee 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 the mouse oncogenicity study, a 
human upper-bound potency estimate (Q<INF>1</INF>*) was calculated as 
0.17 (mg/kg/day).
    The calculated human Q<INF>1</INF>* is based on the standard 
interspecies scaling factor of BW<SUP>0.67</SUP>. Recent EPA guidance 
indicates that BW<SUP>0.75</SUP> 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%.
    More importantly, evidence summarized above suggest that 
carcinogenic effects observed in rodent liver related to long term 
lactofen consumption are attributable 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. This change in the 
hazard assessment process for lactofen would have a profound effect on 
the exposure and risk assessments for this chemical.
    5. Animal metabolism. Single high, single low, and repeated low 
dose radiocarbon labeled lactofen metabolism studies have been 
performed in male and female rats. Radiocarbon is almost completely 
eliminated (>95%) in excreta within 3-days of oral dosing. Generally 
about 60% of orally administered radioactivity (<SUP>14</SUP>C-
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. Except for the formyl 
derivative (PPG-2597), a minor plant metabolite, there were no plant 
metabolites detected that were not also produced in mammals.
    Additional pharmacokinetic studies using both radiocarbon labeled 
and unlabeled lactofen were performed in rats, mice, rhesus monkeys, 
and chimpanzees. Little parent was seen in the plasma of any species 
tested. At steady state, the primary metabolite in the circulation of 
rodents was PPG-847. In the primates, PP-2053 was the primary 
circulating metabolite. Mice appeared to be least efficient in clearing 
PPG-844 and other lactofen metabolites from the circulation, while 
rats, and especially primates appeared to be more efficient.
    6. Metabolite toxicology. A major hydrolytic metabolite of lactofen 
is PPG-847, the benzoic acid. The sodium salt of this benzoic acid, 
sodium 5-[2-chloro-4-(trifluoromethyl)phenoxy]-2-nitrobenzoate, is the 
registered herbicide acifluorfen. This product has a complete data base 
supporting registration with a RfD of 0.013 mg/kg/day and a Cancer 
Potency Factor of 0.107 (mg/kg/day)<SUP>-1</SUP>. Exposure to 
acifluorfen from all sources must be evaluated to perform a cumulative 
risk analysis.
    7. Endocrine disruption. No special studies to investigate the 
potential for estrogenic or other endocrine effects of lactofen have 
been performed. However, as summarized above, a large and

[[Page 9536]]

detailed toxicology data base exists for the compound including studies 
acceptable to the Agency in all required categories. These studies 
include evaluations of reproduction and reproductive toxicity and 
detailed pathology and histology of endocrine organs following repeated 
or long term exposure. These studies are considered capable of 
revealing endocrine effects and no such effects were observed.

E. Aggregate Exposure

    1. Dietary exposure. A chronic dietary toxicity endpoint of 
concern, RfD, has been identified by the Agency 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 1,000. The RfD is 0.002 mg/kg/day for 
lactofen. An uncertainty factor of 1,000 was used since a clear NOEL 
was not established. The Toxicology Branch Peer Review Committee 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 the mouse oncogenicity study, a 
human upper-bound potency estimate (Q<INF>1</INF>*) was calculated as 
0.17 (mg/kg/day)<SUP>-1</SUP>. An acute or short term dietary endpoint 
of concern has not been established by the Agency. Valent has chosen to 
use the maternal NOEL for systemic toxicity of 4 mg/kg/day from the 
rabbit developmental toxicity study for acute and short term dietary 
risk analyses. Lactofen has no uses not associated with commercial 
agriculture. Therefore the only potential exposure possible to the U.S. 
Population is through the diet in food and drinking water. Risk 
analyses via other exposure routs, inhalation, dermal, are not 
necessary. Thus, only chronic and acute dietary exposure and risk 
analyses are necessary.
    2. Food. Lactofen is registered for use in the production of 
commercial agricultural crops including soybeans, cotton, snap beans, 
and conifer seedlings. Dietary exposures are expected to represent the 
major route of exposure to the public.
    3. Chronic. A chronic dietary assessment for lactofen has been 
conducted using Anticipated Residue Contributions (ARC) for existing 
and proposed uses of lactofen. This exposure/risk analysis has been 
submitted to the Agency along with a detailed description of the 
methodology and assumptions used. 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. The chronic exposure analysis 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 of future 
market penetration. 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 Dietary 
exposure was calculated for the U.S. population and 26 population 
subgroups. Chronic dietary exposure was less than 0.1% of the RfD for 
all subpopulations.
    4. Acute. A first tier acute exposure and risk analysis was 
performed for lactofen assuming tolerance level residues in soybeans, 
snapbeans, cotton, and peanuts (0.05 ppm) and 0.02 ppm in all meat and 
milk commodities. Using the acute dietary endpoint of 4.0 mg/kg/day, 
the NOEL from the rabbit developmental toxicity study, the calculated 
exposures and margins of exposure (MOE) for the higher exposed 
proportions of the subgroups are listed below. It should be noted that 
the population sizes are small at the lower probability exposures (e.g. 
99<SUP>th</SUP> and 99.9<SUP>th</SUP> percentiles) oftentimes leading 
to unrealistically high calculated exposures. In all cases, margins of 
exposure exceed 1,000.

                                             Calculated Acute Dietary Exposures to Lactofen Residues in Food                                            
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                       99<SUP>th Percentile                                  99.9<SUP>th Percentile               
                 Population Subgroup                 ---------------------------------------------------------------------------------------------------
                                                      Exposure (mg/kg bw/day)            MOE            Exposure (mg/kg bw/day)            MOE          
--------------------------------------------------------------------------------------------------------------------------------------------------------
U.S. Population.....................................                 0.001199                    3,337                 0.002211                    1,809
Females 13-50.......................................                 0.000464                    8,619                 0.000712                    5,616
Children 1-6........................................                 0.001911                    2,094                 0.002781                    1,438
Children 7-12.......................................                 0.001019                    3,927                 0.001472                    2,717
All Infants.........................................                 0.002887                    1,385                 0.003870                    1,034
Non-Nursing Infants(<1).............................                 0.002956                    1,353                 0.003901                    1,025
--------------------------------------------------------------------------------------------------------------------------------------------------------

    5. Drinking water. Drinking water represents a potential route of 
acute or chronic dietary exposure for lactofen and should be considered 
in an aggregate exposure assessment. Since lactofen is applied outdoors 
to growing agricultural crops, the potential exists for lactofen or its 
metabolites to leach into ground water or reach surface water that are 
used for drinking. There is no established Maximum Concentration Level 
for residues of lactofen in drinking water under the Safe Drinking 
Water Act.
    6. Ground water. Based on available lactofen studies used in EPA's 
assessment of environmental risk, EPA required a small scale 
prospective ground water 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). The final report demonstrated that lactofen 
degrades rapidly without downward movement in soil and did not 
contaminate even shallow ground water beneath light, sandy soils. There 
were no detections of lactofen (< 1 ppb) in lysimeter or monitoring 
well water samples. Lactofen degrades to acifluorfen, which was also 
monitored in 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. Acifluorfen 
was found to degrade

[[Page 9537]]

somewhat more slowly than lactofen, and it did not leach to ground 
water during the study. There were no detections of acifluorfen (> 1 
ppb) in lysimeter or monitoring well samples.
    Assuming that all ground water contains lactofen at one-half the 
limit of quantitation from this study, 0.005 ppm, is non-determinate, 
and overly conservative. SCI-GROW modeling, using the same 
environmental fate parameters utilized below gave a Ground Water 
Screening Concentration of 0.002 ppb.
    7. Surface water. Potential surface water concentrations for 
lactofen were estimated using GENEEC and the following conservative 
use, physical property, and environmental fate parameters: use rate, 
0.2 lb a.i./a; applications, 2 aerial broadcast; application interval, 
14 days; K<INF>OC</INF>, 6,600; water solubility 0.945 ppm; aerobic 
soil half-life, 2.2-days; hydrolysis (pH 7) half-life 11-days; and 
photolysis in water half-life, 2.75-days. The maximum concentration 
predicted in the hypothetical small stagnant farm pond water was 1.05 
ppb and 0.17 ppb for the 4 and 56 day average GEEC, respectively.
    Potential lactofen concentrations in actual drinking water would be 
much lower than one-half of the quantitation limit in the ground water 
study or the concentration modeled in ground water from the SCI-GROW 
Ground Water Screening Concentration or the concentration modeled by 
GENEEC in the hypothetical small stagnant farm pond. For this risk 
analyses, the finite concentrations modeled by GENEEC are selected. 
Based on this analyses, the lactofen exposure contribution from 
drinking water to realistic dietary risk analyses is negligible.

              Exposure to Lactofen from Drinking waterfor Adults and Children from GENEEC Modeling              
----------------------------------------------------------------------------------------------------------------
                                                                             Exposure (mg/kg bw/day)            
                                                               -------------------------------------------------
                           Exposure                              Adult (70 kg, 2 liter/   Child (10 kg, 1 liter/
                                                                          day)                     day)         
----------------------------------------------------------------------------------------------------------------
Acute (4-day average).........................................                 0.000030                 0.000105
Chronic (56-day average)......................................                0.0000049                 0.000017
----------------------------------------------------------------------------------------------------------------

    1. Summary-- Aggregate chronic dietary exposure. Aggregate chronic 
dietary exposure to lactofen is the sum of the contributions from food 
and water as shown in the table below. It can be seen that the total 
potential chronic exposure to lactofen to two representative population 
subgroups is dominated by the conservative estimation of residues in 
water, but even so, there is no cause for concern.

                  Aggregate Chronic Exposure to Lactofenfor Two Representative U.S. Populations                 
----------------------------------------------------------------------------------------------------------------
                                                                             Exposure (mg/kg bw/day)            
                                                               -------------------------------------------------
                        Exposure Medium                           U.S. Population (all      Non-Nursing Infant  
                                                                        seasons)            (less than 1 year)  
----------------------------------------------------------------------------------------------------------------
Food..........................................................                0.0000001                0.0000001
Drinking Water................................................                0.0000049                 0.000017
Sum of Chronic Exposures......................................                 0.000005                 0.000017
Occupancy of RfD(percent).....................................                     0.25                     0.85
----------------------------------------------------------------------------------------------------------------

    2. Summary-- Aggregate acute exposure. It is possible to sum 
calculated acute exposures from dietary sources as shown in the table 
below. However, summation is exceedingly conservative because the 
approach assumes that two low probability events occur simultaneously. 
For example, it is highly unlikely that an individual in a single day 
consumes the 99.9<SUP>th</SUP> percentile dietary exposure (one-in-a-
thousand), and also consumes all the daily drinking water from a pond 
surrounded by treated cotton fields. Even so, the acute exposures shown 
below that sum exposures from food and drinking water gives MOE values 
at or above 1,000. These calculated acute and short term exposures are 
very conservative, and are small enough to be of little significance.

Aggregate Acute Exposure to Lactofenfor Two Representative U.S. Populations(summation of low probability maximum
                                                     values)                                                    
----------------------------------------------------------------------------------------------------------------
                                                                             Exposure (mg/kg bw/day)            
                                                               -------------------------------------------------
                        Exposure Medium                           U.S. Population (all      Non-Nursing Infant  
                                                                        seasons)            (less than 1 year)  
----------------------------------------------------------------------------------------------------------------
Food..........................................................                 0.002211                 0.003901
Drinking Water................................................                 0.000030                 0.000105
Sum of Acute Exposures........................................                 0.002241                 0.004006
Margin of Exposure............................................                     1785                      999
----------------------------------------------------------------------------------------------------------------

    3. 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.

F. Cumulative Effects

    Section 408(b)(2)(D)(v) requires that the Agency must consider 
``available information'' concerning the cumulative effects of a 
particular pesticide's residues and ``other substances that have a 
common mechanism of toxicity.'' ``Available information'' in this 
context includes not only toxicity, chemistry, and exposure data, but 
also scientific policies and methodologies for understanding common 
mechanisms of toxicity and conducting cumulative risk

[[Page 9538]]

assessments. Valent will submit information for EPA to consider 
concerning potential cumulative effects of lactofen consistent with the 
schedule established by EPA at (62 FR 42020; August 4, 1997) (FRL 5734-
6) and other EPA publications pursuant to the Food Quality Protection 
Act.
    There are several other pesticide compounds which are structurally 
related to lactofen and may have similar effects on animals. 
Specifically, lactofen, acifluorfen, fomesafen, oxyfluorfen, and 
diclofop methyl are all diphenyl ethers and all have caused liver 
tumors in rodents. These chemicals are approved for food uses in the 
U.S. and could be considered in a cumulative exposure assessment. It is 
premature to simply add the risk from all these chemicals. Exposure 
considerations as well as toxicity endpoint, pharmacokinetic, and 
pharmacodynamic considerations may indicate that it is inappropriate to 
add the risks. Dietary exposures to these other diphenyl ethers are 
expected to represent the major route of exposure to the public.
    A major hydrolytic metabolite of lactofen representing perhaps 50% 
of the applied dose in animal and environmental fate studies, is PPG-
847, the benzoic acid. The sodium salt of this benzoic acid, sodium 5-
[2-chloro-4-(trifluoromethyl)phenoxy]-2-nitrobenzoate, is the 
registered herbicide acifluorfen. This product has a complete data base 
supporting registration with a RfD of 0.013 mg/kg/day and a Cancer 
Potency Factor of 0.107 (mg/kg/day)<SUP>-1</SUP>. Because lactofen and 
acifluorfen have a ``common metabolite'', exposure to both acifluorfen 
and lactofen from all sources must be evaluated to perform a cumulative 
risk analysis.
    It should be noted that acifluorfen, and the other related diphenyl 
ethers, would benefit from the use of the larger interspecies scaling 
factor as well as lactofen. Further, the rodent liver tumor effects of 
these other diphenyl ethers may 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.

G. Safety Determination

    The Food Quality Protection Act introduces a new standard of 
safety, a reasonable certainty of no harm. To make this determination 
exposure and consequent risk to both acifluorfen and lactofen from all 
sources must be evaluated.
    In evaluating chronic dietary exposures, the food and water 
consumed for a lifetime is assumed to contain a baseline amount of 
residues. Chronic risks are evaluated by comparing a conservatively 
calculated baseline exposure to the RfD. A long term exposure in mg/kg 
bw/day is compared to a NOEL from an appropriate long term animal 
exposure study adjusted by a safety factor. It is quite reasonable to 
suppose that daily baseline exposures to two or more compounds could 
occur simultaneously. That is, a consumer could have chronic dietary 
exposure to lactofen residues and acifluorfen residues at the same 
time, and because acifluorfen is a metabolite of lactofen, a cumulative 
risk analysis is appropriate. The situation is very different for acute 
dietary exposures. In an acute dietary risk analysis, exposures to 
residues are related to the probability of occurrence of a daily diet 
containing the residues. At its most simplified, the probability of 
consuming a diet simultaneously containing both lactofen and 
acifluorfen at the 99.9 th percentile diet is one in one-million. A 
simple, additive cumulative risk analysis cannot take the probability 
of simultaneous exposure into account and is not appropriate.
    1. U.S. population --i. Chronic-- Food. Using the dietary exposure 
assessment procedures described above (and performed by Valent) for 
lactofen, and a recent assessment for acifluorfen published in the 61 
FR 16740; (April 17, 1996) (FRL 5356-6) chronic dietary exposures 
resulting from existing and proposed uses of lactofen and acifluorfen 
were compared to their respective reference doses. 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:
    ii. Lactofen. Exposure 0.0000001 (mg/kg bw/day) less than 0.01% for 
all subpopulations.
    iii. Acifluorfen. Exposure 0.0000052 (mg/kg bw/day, 61 FR 16740) 
less than 0.04 % for all subpopulations.
    iv. Chronic-- Drinking water-- Lactofen. Using the conservative 
assumption that all drinking water contains lactofen at levels 
calculated by GENEEC for a small farm pond surrounded by lactofen 
treated fields, a very conservative estimate of risk can be made. Using 
standard assumptions about body weight and water consumption, the adult 
chronic exposure from this drinking water would be 4.9 x 
10<SUP>-6</SUP> mg/kg bw/day, 0.25% of the RfD.
    2. Acifluorfen. Acifluorfen that may be in drinking water can be 
derived directly from acifluorfen applied to crops, or may be 
acifluorfen derived from degradation of lactofen. The physical 
properties and soil stability of acifluorfen indicate that the compound 
may dissolve in surface water, or leach to groundwater that may be used 
for drinking water.
    The U.S. Geological Survey is engaged in a National Water Quality 
Assessment (NAWQA). This program samples both ground and surface water 
and analyzes the samples for 75 pesticides and metabolites including 
acifluorfen, but not lactofen. The data through August 1997 are 
available from USGS, on the internet at http://water.wr.usgs.govpnsp/
gwsw1.html. The NAWQA sampling program was designed to provide an 
overview of pesticide occurrence in water that could be used for 
drinking water. Specific types of agriculture or specific products, 
including acifluorfen, were not targeted. While the program is not 
exhaustive, it probably provides a reasonably unbiased estimate of the 
occurrence of agricultural chemical contaminants in potential drinking 
water. A table summarizing the data for acifluorfen is presented below.

                                         USGS NAWQA data on Acifluorfen                                         
----------------------------------------------------------------------------------------------------------------
                                                       Number of Samples                                        
              Water Type              --------------------------------------------------  Maximum Concentration 
                                                Total                  >0.05 ppb                  (ppb)         
----------------------------------------------------------------------------------------------------------------
Agricultural Streams.................                     1148                       10                      2.2
Urban Streams........................                      418                       ND                        -
Large Streams........................                      282                        6                     0.44
Total Surface Water..................                     1848                       16                         
Agricultural Shallow Ground Water....                     1069                       ND                       --
Urban Shallow Ground Water...........                      314                        1                    0.070
Major Ground Water Aquifer...........                      965                        1                    0.190

[[Page 9539]]

                                                                                                                
Total Groundwater....................                     2348                        2                         
----------------------------------------------------------------------------------------------------------------

    It is noteworthy that there were only 18 detections of acifluorfen 
in the nearly 4,200 samples analyzed for acifluorfen. More detections 
and highest concentrations were found in surface water than in 
groundwater. In light of all these monitoring data, it is unreasonable 
to choose the single highest concentration value from a small 
agricultural stream as representative of all drinking water. 
Accordingly, using the conservative assumption that all drinking water 
contains acifluorfen at 0.00044 ppm, the highest value in the USGS 
NAWQA data on acifluorfen from large streams, a very conservative 
estimate of risk can be made. Using standard assumptions about body 
weight and water consumption, the chronic exposure from this drinking 
water would be 1.26 x 10<SUP>-5</SUP> mg/kg bw/day for adults, 0.1% of 
the RfD of 0.013 mg/kg bw/day.
    Chronic exposure to drinking water:
    i. Lactofen. Less than 0.25% for the U.S. Population.
    ii. Acifluorfen. Less than 0.1% for the U.S. Population.
    1. Summary- cumulative aggregate chronic dietary risk-- i. U.S. 
population. The aggregate chronic dietary risks from both food and 
drinking water exposure expressed as a percentage of their respective 
RfD values is presented below for both lactofen and acifluorfen. It is 
noteworthy that the calculated exposures and consequent risks are very 
small, yet dominated by the very conservative estimates of residues in 
water.
    ii. Lactofen. Exposure 0.000005 (mg/kg bw/day) less than 0.25% for 
all subpopulations.
    iii. Acifluorfen. Exposure 0.0000178 (mg/kg bw/day) less than 0.14 
% for all subpopulations.
    EPA generally has no concern for exposures below 100% of the RfD 
because the RfD represents the level at or below which daily aggregate 
dietary exposure over a lifetime will not pose appreciable risks to 
human health. The current and proposed uses of these two chemicals, 
even when considered collectively, represent a minimal chronic 
toxicological risk to the general public and it can be concluded that 
there is reasonable certainty of no harm from chronic exposures..
    2. Acute. Assessment of aggregate acute exposure to food and 
drinking water residues of lactofen to the U.S. Population has 
demonstrated that exposures are small. MOE values using very 
conservative exposure assumptions and a conservative toxicity endpoint 
are all greater than 1,000 and it can be concluded that there is 
reasonable certainty of no harm to the U.S. Population from acute 
dietary exposures to lactofen residues.
    3. Carcinogenicity. Carcinogenic risks for both lactofen and 
acifluorfen can be calculated from the aggregate chronic dietary 
exposures presented above. Because both products are only used in 
agriculture, the exposure to the general population is exclusively 
dietary from potential residues in food and drinking water.
    4. Food. For lactofen, carcinogenic risks from exposure to residues 
in food were calculated by Valent using a potency factor 
(Q<INF>1</INF>*) of 0.17 (mg/kg/day) <SUP>-1</SUP>. The resulting 
carcinogenic risk from existing and proposed uses of lactofen was 
calculated at 1.54  x  10<SUP>-8</SUP> 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 from lactofen residues in food are 
conservative and are well within acceptable levels.
    For acifluorfen, carcinogenic risks from exposure to residues in 
food were published by EPA (61 FR 16740; April 17, 1996) (FRL-5356-6) 
using a Q<INF>1</INF>* value of 0.107 (mg/kg/day)<SUP>-1</SUP>. The 
resulting carcinogenic risk from existing and proposed uses of 
acifluorfen is calculated at 5.6  x  10<SUP>-7</SUP> or less. This is 
lower than the generally acceptable level of one-in-a-million 
additional lifetime cancers.
    5. Drinking water. In the discussions above, very conservative 
estimates of lactofen and acifluorfen residues in potential drinking 
water have been presented. The estimates are conservative in that 
common concentrations of the compounds in real drinking water are zero, 
or orders of magnitude below the estimates. Using the conservative 
exposure estimates and the corresponding cancer potency factors, the 
cancer risk from drinking water is 8.5  x  10<SUP>-7</SUP> and 6.7  x  
10<SUP>-6</SUP> or less for lactofen and acifluorfen, respectively.
    6. Summary- cumulative aggregate chronic cancer risk-- i. U.S. 
population. The aggregate chronic dietary risks of cancer from exposure 
to food and drinking water residues is presented below for both 
lactofen and acifluorfen.
    ii. Lactofen. Chronic Exposure less than 0.000005 mg/kg bw/day Q* 
0.17 (mg/kg bw/day)<SUP>-1</SUP> Cancer Risk: 8.5  x  10<SUP>-7</SUP>.
    iii. Acifluorfen chronic exposure. Less than 0.0000178 mg/kg bw/day 
Q* 0.107 (mg/kg bw/day)<SUP>-1</SUP> Cancer Risk 1.9  x  
10<SUP>-6</SUP>.
    It is noteworthy that the calculated exposures and consequent risks 
are dominated by the very conservative estimates of potential residues 
in water. The Agency has expressed concern about the potential for 
excess oncogenic risk of acifluorfen in drinking water. To evaluate 
drinking water exposures, groundwater monitoring studies have been 
required for both acifluorfen and lactofen. Additional time is required 
to allow registrants to complete the studies, to present real data in 
potential drinking water, and for EPA to evaluate the information and 
adequately address the drinking water exposure issue. The calculated 
cancer risks are for lifetime exposure to levels of all potential 
acifluorfen in drinking water little of which could possibly be 
attributable to lactofen use on cotton. There is a reasonable certainty 
of no harm during the time necessary to obtain and evaluate real 
exposure data.
    7. Non-dietary exposure. Lactofen and acifluorfen are currently 
approved only for the commercial production of agricultural crops. The 
potential for non-occupational exposure to the general public, other 
than through the diet or drinking water, is therefore insignificant.
    8. Infants and children -- Safety factor for infants and children. 
In assessing the potential for additional sensitivity of infants and 
children to residues of lactofen, FFDCA section 408 provides that EPA 
shall apply an additional margin of safety, up to 10-fold, for added 
protection for infants and children in the case of threshold

[[Page 9540]]

effects unless EPA determines that a different margin of safety will be 
safe for infants and children. The toxicological data base for 
evaluating pre- and post-natal toxicity for lactofen is complete with 
respect to current data requirements. There are no special pre- or 
post-natal toxicity concerns for infants and children, based on the 
results of the rat and rabbit developmental toxicity studies and the 
reproductive toxicity study in rats. Systemic toxicity effects, and not 
reproductive or developmental toxicity determined the no effect levels 
for these studies of 50, 4, and 2.5 mg/kg bw/day, respectively. Valent 
concludes that reliable data support use of the standard 100-fold 
uncertainty factor with respect to protection of infants and children, 
and that an additional uncertainty factor is not needed to be further 
protective.
    Furthermore, the chronic RfD for lactofen is based on the Lowest 
Effect Level (LEL) of 1.5 mg/kg/day in the 18-month mouse feeding study 
with an uncertainty factor of 1,000. An additional margin of safety, 
10-fold, was used since a clear NOEL was not established in the mouse 
study. Thus, although an extra safety factor is not needed to further 
protect infants and children, an extra 10-fold uncertainty factor has 
been included because of the lack of a clear NOEL in the mouse study.
    9. Chronic-- Food. Using the dietary exposure assessment procedures 
described above (and performed by Valent) for lactofen, and a recent 
assessment for acifluorfen published in the Federal Register (61 FR 
16740; April 17, 1996) total chronic dietary exposures resulting from 
existing and proposed uses of lactofen and acifluorfen were compared to 
their respective reference doses. The following contributions to the 
RfD were found for all of subpopulations including infants and children 
for which dietary consumption data are available:
    i. Lactofen. Exposure 0.0000001 (mg/kg bw/day) less than 0.01% of 
RfD.
    ii. Acifluorfen. Exposure 0.0000052 (mg/kg bw/day), (61 FR 16740; 
April 17, 1996) less than 0.04% of RfD.
    10. Chronic- drinking water- lactofen. Using the conservative 
assumption that all drinking water contains lactofen at levels 
calculated by GENEEC for a small farm pond surrounded by lactofen 
treated fields, a very conservative estimate of risk can be made. Using 
standard assumptions about body weight and water consumption, the child 
chronic exposure from this drinking water would be 1.7  x  
10<SUP>-5</SUP> mg/kg bw/day, 0.85 percent of the RfD.
    11. Acifluorfen. Using the very conservative assumption that all 
drinking water contains acifluorfen at 0.00044 ppm, from the USGS NAWQA 
data on acifluorfen, a very conservative estimate of risk can be made. 
Using standard assumptions about body weight and water consumption, the 
child chronic exposure from this drinking water would be 4.4  x  
10<SUP>-5</SUP> mg/kg bw/day, 0.34 percent of the RfD.
    Summary - Cumulative aggregate chronic dietary risk-- Infants and 
children. The aggregate chronic dietary risks from both food and 
drinking water exposure expressed as a percentage of their respective 
RfD values is presented below for children for both lactofen and 
acifluorfen. It is noteworthy that the calculated exposures and 
consequent risks are very small, yet dominated by the very conservative 
estimates of residues in water.
    (a) Lactofen. Less than 0.86 % for all infant and children 
subpopulations.
    (b) Acifluorfen. Less than 0.38 % for all infant and children 
subpopulations.
    EPA generally has no concern for exposures below 100% of the RfD 
because the RfD represents the level at or below which daily aggregate 
dietary exposure over a lifetime will not pose appreciable risks to 
human health. The current and proposed uses of these two chemicals, 
even when considered collectively, represent a minimal chronic 
toxicological risk to infants and children and it can be concluded that 
there is reasonable certainty of no harm from chronic exposures.
    1. Acute. Assessment of aggregate acute exposure to food and 
drinking water residues of lactofen to non-nursing infants has 
demonstrated that exposures are small. MOE values using very 
conservative exposure assumptions and a conservative toxicity endpoint 
approximate 1,000. It can be concluded that there is reasonable 
certainty of no harm to infants and children from acute dietary 
exposures to lactofen residues.

G. International Tolerances

    There are no Codex Maximum Residue Limits (MRL) established for 
lactofen on any commodity.
[FR Doc. 98-4811 Filed 2-24-98; 8:45 am]
BILLING CODE 6560-50-F