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Notice of Filing of Pesticide Petitions
Note: EPA no longer updates this information, but it may be useful as a reference or resource.
[Federal Register: November 26, 1997 (Volume 62, Number 228)]
[Notices]
[Page 63164-63168]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr26no97-96]
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ENVIRONMENTAL PROTECTION AGENCY
[PF-777; FRL-5754-4]
Notice of Filing of Pesticide Petitions
AGENCY: Environmental Protection Agency (EPA).
ACTION: Notice.
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SUMMARY: This notice announces the initial filing of pesticide
petitions proposing the establishment of regulations for residues of
certain pesticide chemicals in or on various food commodities.
DATES: Comments, identified by the docket control number PF-777, must
be received on or before December 26, 1997.
ADDRESSES: By mail submit written comments to: Public Information and
Records Integrity Branch (7502C), Information Resources and Services
Division, Office of Pesticides Programs, Environmental Protection
Agency, 401 M St., SW., Washington, DC 20460. In person bring comments
to: Rm. 1132, CM #2, 1921 Jefferson Davis Highway, Arlington, VA.
Comments and data may also be submitted electronically to: opp-
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
``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: By mail: Joanne Miller (PM 23),
Registration Division (7505C), Office of Pesticide Programs,
Environmental Protection Agency, 401 M St., S.W., Washington, DC 20460.
Office location, telephone number, and e-mail address: Rm. 237, CM #2,
1921 Jefferson Davis Highway, Arlington, VA 22202, (703 305-6224, e-
mail: miller.joanne@epamail.epa.gov.
SUPPLEMENTARY INFORMATION: EPA has received pesticide petitions as
follows proposing the establishment and/or amendment of regulations for
residues of certain pesticide chemicals in or on various food
commodities under section 408 of the Federal Food, Drug, and Comestic
Act (FFDCA), 21 U.S.C. 346a. EPA has determined that these petitions
contain data or information regarding the elements set forth in section
408(d)(2); however, EPA has not fully evaluated the sufficiency of the
submitted data at this time or whether the data supports granting of
the petition. Additional data may be needed before EPA rules on the
petition.
The official record for this notice of filing, as well as the
public version, has been established for this notice of filing under
docket control number [PF-777] (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 or ASCII file
format. All comments and data in electronic form must be identified by
the docket control number [PF-777] 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: November 4, 1997.
James Jones,
Acting Director, Registration Division, Office of Pesticide Programs.
Summaries of Petitions
Petitioner summaries of the pesticide petitions are printed below
as required by section 408(d)(3) of the FFDCA. The summaries of the
petitions were prepared by the petitioners and represent the views of
the petitioners. EPA is publishing the petition summaries verbatim
without editing them in any way. The petition summary announces the
availability of a description of the analytical methods available to
EPA for the detection and measurement of the pesticide chemical
residues or an explanation of why no such method is needed.
BASF Corporation
PP 6F4604, 4F3041 and FAP 4H5428
EPA has received pesticide petitions (PP 6F4604, 4F3041, and FAP
4H5428) from BASF Corporation, 26 Davis Drive, Research Triangle Park,
P.O. Box 13528, NC 27709, proposing pursuant to section 408 (d) of the
Federal Food, Drug and Cosmetic Act, 21 U.S.C. 346a(d), to amend 40 CFR
180.227 by
[[Page 63165]]
establishing and amending tolerances for residues of the herbicide
dicamba in or on the raw agricultural commodities soybeans, wheat,
barley, oats, corn, cotton, grasses and asparagus at the proposed
tolerances as described below. The proposed analytical methods involve
extraction, partition, clean-up and detection of residues by gas
chromatography/electron capture detector (gc/ecd). 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. Metabolism is adequately understood on the
basis of soybean, asparagus, cotton, sugarcane and published data on
grass. In the majority of registered crops, the major metabolite is the
3,6 dichloro-5-OH-o-anisic acid. Tolerances are expressed as the
dicamba parent plus the respective major metabolite.
2. Analytical method. BASF Corp. has provided suitable
independently validated analytical methods for detecting and measuring
levels of dicamba and its metabolites in or on food with a limit of
detection that allows monitoring of food with residues at or above the
levels described in these and the existing tolerances. Adequate methods
are available in PAM-II for enforcement purposes. The analytical method
involves extraction, partition, clean-up and detection of residues by
gas chromatography/electron capture detector (gc/ecd).
3. Magnitude of the residue--i. Plant. Residue trials have been
conducted with dicamba on the crops for expanded use requested in the
subject petitions. Multiple salts of dicamba were studied in side-by-
side testing to confirm that no effect on magnitude of the residues was
caused by the salt formulation type of the dicamba. The tolerances
listed below are based on the maximum expected residue from
geographically representative field trial data:
Proposed tolerances for combined residues of the herbicide dicamba
(3,6-dichloro-o-anisic acid) and its metabolite 3,6-dichloro-5-hydroxy-
o-anisic acid in or on the raw agricultural commodities as follows 40
CFR 180.227(a): Cottonseed 3.0 parts per million (ppm); Corn, forage
3.0 ppm; Corn, fodder 3.0 ppm; Crop Group 17, Grass forage, fodder and
hay Forage 125 ppm, Hay 200 ppm; Wheat, forage 80 ppm, Wheat, hay 20
ppm; 21 U.S.C. section 701 MRL Cottonseed meal 5.0 ppm; Wheat grain 2
ppm, Wheat straw 30 ppm; Barley grain 2 ppm; Barley straw 30 ppm.
Proposed tolerances for combined residues of the herbicide dicamba
(3,6-dichloro-o-anisic acid) and its metabolite 3,6-dichloro-2-
hydroxybenzoic acid in or on the raw agricultural commodities as
follows 40 CFR 180.227(b): Soybean grain 4 ppm, Soybean hulls 13 ppm;
Asparagus 3.5 ppm.
Only newly generated data, or data not implicated in the CRAVEN
Laboratories indictment are used to support the subject petitions.
Dicamba residues concentrate in the following commodities: soybean
hulls; sugarcane molasses; cottonseed meal.
ii. Animal. The amended uses proposed do not yield secondary
residues in meat and milk above the tolerances already published under
40 CFR 180.227. Data from metabolism and feeding studies in poultry
have established that the maximum expected dietary burden from crops
treated with dicamba will not result in quantifiable residues above the
limits of the analytical method.
B. Toxicological Profile
Data are provided that are representative of the mammalian toxicity
effects of dicamba and are part of the many studies conducted to
support the BASF Corp. assertion of safety of dicamba to humans.
1. Acute toxicity--i. Oral Rat LD50: 1,879 mg/kg (m);
1581 mg/kg (f).
ii. Acute Dermal Rat LD50: > 2,000 kg/kg (m/f).
iii. Acute Inhalation Rat LC50: > 9.6 mg/L (m/f).
iv. Primary Eye Irritation: Extremely irritating and corrosive to
the eye.
v. Primary Dermal Irritation Rabbits: Not a primary skin irritant.
vi. Dermal Sensitization Guinea Pigs: Moderate potential to cause
dermal sensitization.
vii. Acute Neurotoxicity: NOEL <300 mg/kg (lowest dose tested).
Neurobehavioral effects were observed at all dose levels but primarily
at the initial 1.5 hr post-dose testing only. No neurobehavioral
effects were noted by day 14 after treatment and no neuropathological
effects were found indicating there are no persistent effects on the
nervous system.
2. Genotoxicity. Ames: Negative; In vitro chromosome aberration in
Chinese Hamster Ovary: Negative; Sex-linked recessive lethal in
Drosophila: Negative; Chromosome aberrations in rat bone marrow:
Negative; Mitotic recombination: Negative; UDH (UDS with WI-38 human
lung fibroblasts: Negative; DNA damage as detected with repair
deficient prokaryote E. coli: Positive; DNA damage as determined with
repair deficient eukaryote S. typhimurium: Negative; UDS in human lung
lymphocytes with activation: Negative; Sister chromatid exchange in
human cultured lymphocytes: slight increase. Overall weight of the
evidence from all studies indicates that dicamba is not genotoxic.
3. Reproductive and developmental toxicity--i. Rodent developmental
toxicity rat. Oral doses of 0, 64, 160, or 400 mg/kg were administered
daily during gestation days 6 to 19. Maternal toxicity occurred at the
high dose as evidenced by mortality of four animals, clinical signs and
decreased weight gain. The numbers of implantations, resorptions, and
fetuses for test animals were similar to those numbers for control
animals. No fetal abnormalities were attributed to exposure to dicamba.
Therefore, technical dicamba was not found to be teratogenic. Maternal
toxicity was found only at the HDT with a NOEL of 160 mg/kg/day. The
developmental NOEL was the highest dose tested of 400 mg/kg/day.
ii. Rabbit developmental toxicity. Dicamba was administered orally
(undiluted) via capsule to groups of 20 artificially inseminated New
Zealand White rabbits at dose levels of 0, 30, 150, or, 300 mg/kg on
days 6-18 of presumed-gestation. Females were sacrificed on Day 29 of
presumed gestation. Maternal toxicity occurred at 150 and 300 mg/kg/day
as evidenced by clinical signs and either body weight loss or reduced
weight gain. Abortions occurred at 150 and 300 mg/kg/day. No
significant differences were obtained in litter averages for corpora
lutea, implants, litter sizes, resorption sites, percent male fetuses,
fetal body weight, percent resorbed conceptuses or number of does with
any resorptions. No gross external, soft tissue or skeletal alterations
in fetuses were considered to be related to treatment. Therefore,
dicamba was found to be not teratogenic. The maternal no-observed-
adverse-effect-level (NOAEL) for technical dicamba to pregnant rabbits
was 30 mg/kg/day. Levels of 150 and 300 mg/kg caused abortions, but
were at significant maternally toxic doses. The developmental NOAEL was
the highest dose tested, 300 mg/kg/day.
iii. Two-generation reproduction rat. Potential effects on growth
and reproductive performance were assessed over 2-generations of rats
maintained on diets containing Technical Dicamba at concentrations of 0
(control), 500, 1,500,
[[Page 63166]]
or 5,000 ppm. Parental toxicity occurred at 5,000 ppm in the form of
lower weight gain in females and increased liver weights of both sexes.
Exposure at 5,000 ppm was associated with a slower growth rate of F1
pups prior to weaning and resulted in lower initial body weights in
those selected as parental animals. The lower body weight was
associated with a decrease in both food consumption and water intake.
Sexual maturation was slightly delayed among males, but was likely
associated with the initial reduced growth rate. F2 pup weights were
reduced at 3,000 and 1,500 ppm. There were no treatment-related effects
on reproductive ability at any level. The NOEL and LOEL for systemic
toxicity were 1,500 (approx. 130 mg/kg/day) and 5,000 ppm,
respectively. The NOEL and LOEL for pup toxicity were 500 (approx. 45
mg/kg/day) and 1,500 ppm, respectively.
4. Subchronic toxicity--i. Twenty-one-day Dermal. Technical dicamba
was applied dermally to rabbits for 5 days a week for three weeks at
dosage levels of 0, 100, 500 and 2,500 mg/kg/day. There were no
systemic effects at any level of treatment. Skin irritation was evident
at all treatment levels, but consisted of only a slight erythema at 100
mg/kg/day. The systemic NOEL was the highest dose tested of 2,500 mg/
kg/day.
ii. Thirteen-week rodent feeding (rat). Rats were offered technical
dicamba at dietary concentrations of 0, 1,000, 5,000, or 10,000 ppm.
The mean body weight and food consumption values for the high dietary
level animals were decreased from the control values. No adverse
treatment-related findings were noted in either the blood parameters
investigated or necropsy evaluation. Microscopic examinations of the
liver revealed an absence or reduction of cytoplasmic vacuolation in
the hepatocytes of the high dietary level animals. The NOEL was 5,000
ppm (342 mg/kg/day males, 392 mg/kg/day females).
iii. Thirty-eight-week non-rodent (dog). In a dose-range finding
study for a subsequent chronic dog study, a small number of dogs were
treated via the feed with technical dicamba at dosage levels of 0,
1,000, 2,500 and 5,000 ppm for four to eight weeks. Decreased food
consumption occurred in all dose groups during the first week of
treatment, and persisted in some dogs at 2,500 and 5,000 ppm. Decreased
body weight gains or weight loss were noted in the treatment groups.
The NOEL from the one-year dog study discussed below is used to satisfy
the requirement for the subchronic dog NOEL.
iv. Sub-chronic neurotoxicity. Rats were fed technical dicamba for
13 weeks at dosage levels of 0, 3,000, 6,000 and 12,000 ppm. Body
weights were slightly reduced in high dose animals. Neurobehavioral
effects were noted at the high dose and consisted primarily of signs
associated with rigidity in response to handing. No histopathological
effects on the peripheral or central nervous system were noted. The
neurotoxicity NOEL was established at 6,000 ppm (401 mg/kg/day males,
and 472 mg/kg/day, females).
5. Chronic toxicity--i. Chronic toxicity-dog. Technical Dicamba
was offered orally at dietary concentrations of 0 (Control), 100, 500,
or 2,500 ppm to dogs for 1 year. Initially, a decrease in food
consumption was noted mainly among males at 500 and 2,500 ppm. This was
most notable in a single 2,500 ppm male resulting in almost no food
consumed for the 1st 3 weeks of feeding. Following administration of
the 2,500 ppm diet in a water slurry during weeks 4-6, this male was
placed back on feed and food consumption stabilized. There appears to
be a limit to the amount of material that can be added to the feed
before dogs will not consume the diet. The 2,500 ppm level was
considered close to the maximum that could be employed, as 1 dog failed
to consume the diet when offered in the usual form. Due mainly to the
aforementioned male, mean body weight of 2,500 ppm males did not
increase until week 5. The overall body weight gain for the 1 year
period was comparable for all groups. It was concluded that aside from
the lower food consumption, there were no effects due to treatment with
dicamba. The no-effect level for toxicity was the highest dose tested
of 2,500 ppm (approx. 59 mg/kg/day males, 57 mg/kg/day females).
ii. Chronic feeding/oncogenicity in rat. Groups of 60 rats/sex were
maintained on diets containing technical dicamba at concentrations of
either 0, 50, 250, or 2,500 ppm. An interim sacrifice of 10/sex/level
was conducted at 12 months. Initially scheduled as a 27 month (108
week) study, males were sacrificed at 115 weeks and females at 118
weeks due to high survival rates.
There were no effects due to treatment on any chronic toxicity
parameters investigated. In males, no statistically significant
differences in data for all tumors combined, all benign tumors
combined, and all malignant tumors combined were obtained. A slight
increase in malignant lymphoma was not statistically significant
(pairwise comparisons) and was not considered to be toxicologically
significant. A slight increase in thyroid parafollicular cell carcinoma
in the high treatment group was noted but was not statistically
significant in pairwise comparisons. In females, no statistically
significant differences were noted in comparisons with all tumors
combined, all benign tumors combined, and all malignant tumors combined
or in any individual tumor type.
In summary, no signs of toxicity related to administration of
dicamba were noted. Dicamba was not oncogenic. Based on the results of
the study, the no effect level was considered to be 2,500 ppm (107 mg/
kg/day males and 127 mg/kg/day females).
iii. Oncogenicity in mice. Groups of mice were fed diets containing
dicamba at concentrations of 0, 50, 150, 1,000, or 3,000 ppm. Males
were killed following 89 weeks of feeding and females were killed
following 104 weeks of feeding. Reduced body weight gain (not
statistically different) was noted among 3,000 ppm females. Increased
mortality noted among 3,000 ppm males was considered unlikely to be
related to treatment but could not be completely excluded. An increased
incidence in lymphoid tumors, showing a statistical significance at 150
and 1,000 ppm, occurred in females. However, the incidence at 3,000 ppm
did not statistically differ from control. Additionally, there was no
significant trend with dosage and the values for treated females were
within historical control data. The incidence of benign and malignant
tumors in all tissues were similar for treated and control animals. The
NOEL was determined to be 1,000 ppm (108 mg/kg/day in males and 121 mg/
kg/day in females). However, the RfD best committee chose to establish
the NOEL at 3,000 ppm and stated that no LOEL had been established.
6. Estrogenic or other endocrine effects. No specific tests have
been conducted to determine endocrine-disrupting effects. However,
extensive subchronic and chronic tests have been conducted in several
species, and results have demonstrated no effects on the endocrine system.
7. Animal metabolism. Dicamba has been tested in rats, dogs,
cattle, goats and hens. In all cases, dicamba is excreted very rapidly,
mainly as unchanged dicamba and to a lesser extent as 3,6-dichloro-2-
hydroxybenzoic acid with trace amounts of 3,6-dichloro-5-hydroxy-o-
anisic acid. The results of these studies demonstrate that dicamba is
not persistent and does not accumulate in animals.
8. Metabolite toxicity. Toxicity of the metabolites of dicamba to
humans is concurrently evaluated during toxicity testing because both
plant and animal
[[Page 63167]]
metabolites are formed during the course of toxicity tests. Both plant
and animal major metabolites are considered not of toxicological concern.
C. Aggregate Exposure
1. Dietary exposure. Exposure from the use of Dicamba in the
culture of wheat, barley, oats, millet, sorghum, corn, soybeans,
grasses, cotton, sugarcane and asparagus crops is discussed under the
below topics of food and drinking water.
2. Food. The subject petition amends these uses but does not add
new crops. The potential dietary exposure of the population to residues
of dicamba or its metabolites is calculated based on the Theoretical
Maximum Residue Contribution (TMRC) for all crops with dicamba use. The
TMRC is a worst case estimate of dietary exposure since it assumes that
100 percent of all crops for which tolerances are established are
treated with dicamba, and that pesticide residues are present at the
tolerance levels. The resulting dietary exposure estimate therefore
overestimates exposure and is considered conservative. The number is
then determined to be a percentage of the EPA decided Reference Dose
(RfD). Dietary exposure may occur from crop commodities and meat and
milk. Based on the EPA DRES model BASF Corp. has estimated that the
average US population dietary exposure to dicamba to be only 1.87%
percent of the RfD. This number is very low and considered very safe as
an active ingredient is allowed up to 100% before less conservative
risk assessment measures are initiated.
Acute dietary analysis compared the daily dietary exposure to the
lowest NOEL for acute and subchronic studies. EPA's current policy for
Tier I analysis uses the conservative assumption that all residues are
at a high end estimate or maximum, typically taken as the tolerance
value. Acute dietary assessment for dicamba is made by comparing the
ratio of exposure and the NOEL from acute neurotoxicity of 300 mg/kg/
day to achieve a Margin of Exposure (MOE). A MOE of 300 is required
because a NOEL was not reached in the acute neurotoxicity test. The
following MOE values are obtained for key population subgroups.
------------------------------------------------------------------------
Population Subgroup Margin of Exposure
------------------------------------------------------------------------
US Population 6000
Infants <1 year 3000
Children 1 to 6 3000
Females 13+ years 17000
Males 13+ years 10000
------------------------------------------------------------------------
3. Drinking water. Dicamba has been used commercially for in excess
of 30 years. From available public data, detections in ground water
from commercial uses have been very low and infrequent. The typical
level found in ground water is less than 5 ppb. This should be compared
to the current Health Advisory Level (HAL) of 200 ppb and the
anticipated HAL of 3,000 ppb under the newly revised RfD of 0.45 mg/kg/d.
These infrequent and low levels of detection in groundwater
demonstrate that significant movement of dicamba is not likely and is
not a considerable factor in assessing human health risk.
4. Non-dietary exposure. Non-dietary exposure would mainly occur
from the use of dicamba for broadleaf weed control on residential or
recreational turf. BASF is currently collecting data on the potential
exposure from non-dietary sources such as residential turf use.
However, no reliable information is currently available for risk
assessment at this time. This petition is only related to already
approved crop uses and therefore non-dietary route of exposure is not
considered to be a factor in assessing additional human risk.
D. Cumulative Effects
Dicamba belongs to the benzoic acid class of compounds. There are
no other compounds of this class in significant use and none in food
use. Therefore, cumulative effects from dietary or non-occupational
exposure from pesticides of similar chemistry are considered unlikely.
BASF Corp. does not have reliable data to indicate a common mechanism
of toxicity to other compounds. Therefore cumulative effects from
common mechanisms of action are also unlikely.
E. Safety Determination
The RfD for dicamba is 0.45 mg/kg/d. The RfD is a level at or below
which daily aggregate exposure over a lifetime will not cause
appreciable human health risk. The estimates of exposure are based on
conservative assumptions that all crops with a tolerance for dicamba
are treated and that all residues found are at the maximum or tolerance
level.
1. U.S. population. Using the conservative assumptions described
above, BASF Corp. has estimated that the US population dietary exposure
to dicamba is 1.87% percent of the RfD.
2. Infants and children. Dicamba was not teratogenic in either rats
or rabbits despite testing to maternally toxic doses. No developmental
toxicity was observed in rats and the only effect observed in rabbits
were abortions at clearly maternally toxic doses. Dicamba produced no
effects on reproduction in a 2-generation study in rats. The only
effect observed was a decrease in pup body weight at the high dose
which also produced parental toxicity, and at the mid-dose that was
relatively high (130 mg/kg/day). Based on the weight of evidence from
all reproductive and developmental studies, no selective toxic efects
on infants and children are expected, and no additional safety factor
is warranted.
Using the conservative assumptions described above, BASF Corp. has
estimated the dietary exposure to infants and children as percent of
the RfD. From the current and new proposed use of dicamba dietary
exposure for the most sensitive subgroups are 6.65% for non-nursing
infants (<1 yr old) and 4.6% for children 1 to 6 yrs old.
Aggregate exposure due to the combined residues in food, drinking
water and non-dietary exposure through direct contact with residues in
a residential setting (lawn) should be pursued through the use of a
reserve risk approach. The elements for consideration are therefore
estimated as follows:
Food: Total Population . . . . . .1.87%
Non-nursing Infants <6 yrs . . . 6.7%
Water/Lawn: Low human risk. . . . . .
expected to be inconsequential
BASF Corp. believes that the water and non-dietary exposure risk
for the most sensitive subgroup is inconsequential due to demonstrated
low findings in water relative to the HAL and low toxicity to humans
with respect to oral, dermal and inhalation exposure.
Aggregate exposure is therefore estimated to be less than 10% of
the RfD for the most sensitive population subgroup. Therefore, BASF
Corp. concludes that there is reasonable certainty that no harm will
result from aggregate exposure of residues of dicamba or its
metabolites including all dietary and other non-occupational exposures.
[[Page 63168]]
F. International Tolerances
No international tolerances have been established under CODEX.
Therefore there is no need to ensure consistency.
[FR Doc. 97-30813 Filed 11-25-97; 8:45 am]
BILLING CODE 6560-50-F