[Federal Register Volume 61, Number 248 (Tuesday, December 24, 1996)]
[Notices]
[Pages 67807-67811]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 96-32530]
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ENVIRONMENTAL PROTECTION AGENCY
[PF-681; FRL-5576-8]
Rhone-Poulenc Ag Company; Pesticide Tolerance Petition Filing
AGENCY: Environmental Protection Agency (EPA).
ACTION: Notice of filing.
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SUMMARY: This notice announces the filing of a pesticide petition
proposing the establishment of a regulation for residues of the
herbicide bromoxynil (3,5-dibromo-4 hydroxybenzonitrile), resulting
from the application of its octanoic and heptanoic acid esters. The
proposal would extend the time-limited tolerance in or on the raw
agricultural commodity (RAC) cottonseed (transgenic BXN varieties only)
at 0.04 part per million. This notice includes a summary of the
petition that was prepared by the petitioner, Rhone-Poulenc Ag Company.
DATES: Comments, identified by the docket number [PF-681], must be
received on or before, January 23, 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.,
Washington, DC 20460. In person, bring comments to Rm. 1132, CM#2, 1921
Jefferson Davis Highway, Arlington, VA 22202.
Comments and data may also be submitted electronically by sending
electronic mail (e-mail) to: 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. Comments and data will also be
accepted on disks in WordPerfect in 5.1 file format or ASCII file
format. All comments and data in electronic form must be identified by
the docket number [PF-681]. Electronic comments on this proposed rule
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 of 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
[[Page 67808]]
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: Robert Taylor Product Manager (PM 25)
Rm., 241, CM #2, 1921 Jefferson Davis Highway, Arlington, VA 703-305-
6224, e-mail: Taylor.Robert@epamail.epa.gov.
SUPPLEMENTARY INFORMATION: EPA has received a pesticide petition (PP)
3F4233 from Rhone-Poulenc Ag Company, PO Box 12014 T.W. Alexander
Drive, Research Triangle Park, North Carolina 27709 porposing pursuant
to section 408(d) of the Federal Food, Drug and Cosmetic Act (FFDCA),
21 U.S.C. section 346a(d), to amend CFR part 180 by establishing a
tolerance for residues of the herbicide bromoxynil (3,5-dibrom-4-
hydroxybenxonitrile), resulting from the application of its octanoic
and heptanoic acid esters in or on the raw agricultural commodity
cottonseed at 0.04 ppm. The proposed analytical method is a revised
version of Method 1 in the Pesticide Analytical Manual (PAM), Vol II.
As required by section 408(d) of the FFDCA, as recently amended by
the Food Quality Protection Act, Rhone-Poulenc included in the petition
a summary of the petition and authorization for the summary to be
published in the Federal Register in a notice of receipt of the
petition. The summary represents the views of Rhone-Poulenc; EPA is in
the process of evaluating the petition. As required by section
408(d)(3) EPA is including the summary as a part of this notice of
filing. EPA has made minor edits to the summary for the purpose of
clarity.
EPA invites interested persons to submit comments on this notice of
filing. Comments must bear a notification indicating the document
control number [PF-681]. All written comments filed in response to this
petition will be availble, in the Public Response and Program Resources
Branch, at the address given above from 8:30 a.m. to 4 p.m., Monday
through Fridy, except legal holidays.
A record has been established for this notice under docket numbers
[PF-681] (including com ents 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-docket@epamail.epa.gov
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.
I. Petition Summary
There is an extensive data base supporting the registration of
Bromoxynil and its esters. This data base is current as the majority of
the studies have been submitted and accepted under the reregistration
process mandated by FIFRA 88. The Reregistration Eligibility Document
(RED) for Bromoxynil has been scheduled by the Agency for early in
fiscal year 1997. Included in this data submitted were studies which
showed the nature and magnitude of Bromoxynil residue in ruminants and
poultry. Based on these studies the Agency has determined that the
nature of the residue in ruminants and poultry are understood and that
any secondary residues from this tolerance occurring in the fat, meat,
and meat byproducts of cattle, goats, horses, poultry, and sheep will
be covered by existing tolerances.
The nature of the residue in Transgenic Cotton is considered to be
adequately understood. The primary Bromoxynil metabolite is 3,5-dibrom-
4-hydroxybenzoic acid (DBHA). DBHA is only a major metabolite in/on
transgenic cotton treated with Bromoxynil. For the purposes of
extending the time-limited tolerance, only the parent compound should
be regulated as in 40 CFR 180.324. This interim decision is based on
several factors. There will be very minimal risk from total residues of
the parent compound and the DBHA metabolite in cotton seed contributing
only about 1/1000th of the total dietary exposure from all registered
uses of Bromoxynil. The registration of Bromoxynil on Transgenic Cotton
in 1997 will be limited to 400,000 acres. This represents less than 3%
of the total cotton acres anticipated to be planted in 1997. The only
other potential source of dietary exposure from this use would be from
cattle fed cotton gin trash. Any potental dietary risk from this source
would be even less than the risk from cottonseed. This is based on
again less than 3% of the cotton acres being treated with Bromoxynil.
It is also based on the fact that the majority of the cotton gin trash
is disked back into the fields and not fed to cattle. Even when the
cotton gin trash is fed to cattle it represents only a maximum of 30%
of the diet.
Adequate methodology is available for enforcement purposes, based
upon methods for the parent compound. The method involves sample reflux
in methanolic KOH, partitioning with ether/hexane and analysis by GC.
The limit of detection (LOD) for this method is 0.02 ppm. The method is
a modified version of Method I in the Pesticide Analytical Manual
(PAM), Vol. II.
A. Toxicological Profile
The following mammalian toxicity studies have been conducted to
support the tolerance of bromoxynil:
1. Acute Toxicity--Bromoxynil Phenol Technical. A complete battery
of acute toxicity studies for Bromoxynil Phenol were completed. The
acute oral toxicity study resulted in a LD50 of 81 mg/kg (males)
and a LD50 of 93 mg/kg (females). The acute dermal toxicity study
in rabbits resulted in a LD50 of >2000 mg/kg for both males and
females. The acute inhalation study in rats resulted in a LC50 of
0.269 mg/L for males and 0.150 for females. The primary eye irritation
study showed corneal opacity resolved within 3 days, iritis resolved
within 4 days and conjuctival irritation which persisted for 10 days.
There was no irritation in the Primary dermal irritation study and the
dermal sensitization study in guinea pigs was negative. Based on the
results of these studies Bromoxynil Phenol is placed in toxicity
Category II.
2. Acute Toxicity--Bromoxynil Octanoate Technical. A complete
battery of acute toxicity studies for Bromoxynil Octanoate technical
were completed. The acute oral toxicity study resulted in a LD50
of 400 mg/kg (males) and a LD 50 of 238 mg/kg (females). The acute
dermal toxicity study in rabbits resulted in a LD50 of 2000 mg/kg
for males with abraded skin, 1310 mg/kg for females with intact skin
and 1660 mg/kg for females with abraded skin. The
[[Page 67809]]
acute inhalation study in rats resulted in a LC50 of 0.81 mg/L for
males and 0.72 mg/L for females. The primary eye irritation study
showed corneal opacity and irritation lasting for 24-72 hours. It had
cleared by 96 hours. The primary dermal irritation study showed
erythema for 72 hours and no edema. The dermal sensitization study in
guinea pigs showed compound to be a positive contact sensitizer in
modified Draize test. Based on the results of these studies Bromoxynil
Octanoate is placed in toxicity category II.
3. Acute Toxicity--Bromoxynil Heptanoate Technical. A complete
battery of acute toxicity studies for Bromoxynil Heptanoate were
completed. The acute toxicity study resulted in a LD50 of 362 mg/
kg (males) and a LD50 of 292 mg/kg (females). The acute dermal
toxicity study in rabbits resulted in a LD50 of >2020 mg/kg. The
acute inhalation study in rats resulted in a LC50 of 1.975 mg/L
for males and 1.479 mg/L for females. Based on the results of these
studies Bromoxynil Heptanoate is placed in toxicity Category II.
Conclusion: Based on the acute toxicity data cited above and a
margin of safety between the most conservative acute oral toxicity
value and the oral RfD of 0.015 mg/kg/day of >9000, Rhone-Poulenc it is
concludeds that neither Bromoxynil nor its octanoic or heptanoic acide
esters pose any acute dietary risks.
B. Mutagenicity
1. Mutagenicity--Bromoxynil Phenol Technical. Mutagenicity studies
completed included an unscheduled DNA synthesis study-rat primary
hepatocytes (negative); in vitro transformation assay--mouse cells
(negative); sister chromosomal exchange study--CHO cells (negative);
forward mutation study--mouse lymphoma cells (negative without
activation and positive with activation); DNA repair test--E. Coli
(positive); in vitro chromosomal aberration (negative without
activation and positive with activation); two separate micronucleus
assays (both negative); forward mutation-- CHO cells (negative); and an
Ames Study--Salmonella typhimurium (negative with and without
activation).
2. Mutagenicity--Bromoxynil Octanoate Technical. Mutagenicity
studies completed included an Ames Study--Salmonella typhimurin
(negative with and without activation); micronucleus assay (negative);
and an unscheduled DNA synthesis--rat primary hepatocytes (negative).
Conclusion. Based on the data cited above Rhone-Poulenc concludes
neither Bromoxynil nor its octanoic or heptanoic acid esters are
considered to be mutagenic.
C. Rat Metabolism
1. Rat Metabolism--Bromoxynil Heptanoate Technical. Similar results
were obtained when a single low dose (2 mg/kg), a single high dose (20
mg/kg) and a low dose (2 mg/kg) administered for 14 consecutive days
were fed to rats. Bromoxynil Heptanoate is rapidly absorbed and widely
distributed in most tissues. The highest concentrations were found in
the blood, plasma, liver, kidney and thyroid. Higher tissue
concentrations were found in females than in males while excretion was
more rapid in males. Most of the radioactivity was excreted in the
urine. Most of this was in the form of Bromoxynil Phenol. Both
Bromoxynil Phenol and Bromoxynil Heptanoate were present in the feces.
There was no significant retention in tissues after 7 days. Bromoxynil
Heptanoate was essentially metabolized to Bromoxynil Phenol via ester
hydrolysis.
2. Rat Metabolism--Bromoxynil Octanoate Technical. The study
demonstrated that 2 mg/kg of radiolabeled Bromoxynil Octanoate was
rapidly absorbed, distributed, and excreted in rats following repeated
oral administration. A sex-related difference was seen in the excretion
of Bromoxynil Octanoate. The urine was the major route of excretion,
representing 80.24% of the administered dose in males and 67.91% in
females at 7 days post-dosing. The urinary excretion rate was also
higher in males than in females. The feces accounted for 7 - 10% of the
administered dose at 7 days post-dosing. A sex-related difference was
also noted in tissue bioaccumulation of Bromoxynil Octanoate with
1.482% of the dose in males and 8.036% in females. Tissue distribution
was similar for both sexes with the highest radioactivity recovered in
the liver and kidney. Bromoxynil Octanoate was essentially metabolized
to Bromoxynil Phenol via ester hydrolysis.
D. Chronic Effect:
A 1 year oral dog study was run with dogs administered Bromoxynil
Phenol at dose levels of 0, 0.1, 0.3, 1.5, and 7.5 mg/kg/day in
capsules. The NOEL/LEL is 1.5 mg/kg/day for both females and males
based on decreased body weight gain, decreased RBC count, decreased
hemoglobin, decreased PCV, increased liver weights.
Conclusion: The chronic dog study was determined by the EPA to be
the most appropriate study for setting the RfD of 0.015 mg/kg/day
(includes a 100 fold safety factor). Based on the chronic toxicity data
cited above Rhone-Poulenc concludes that neither Bromoxynil nor its
octanoic or heptanoic acid esters pose any chronic dietary risks.
E. Carcinogenicity
Several feeding/carcinogenicity studies were conducted with
Bromoxynil Phenol. These studies are summarized below.
1. A 2 year combined feeding/carcinogenicity study was conducted
with rats administered (oral) dosages of 0, 60, 190, or 600 ppm (0,
2.6, 8.2, or 28 mg/kg/day in males; 0, 3.3, 11.0, or 41 mg/kg/day in
females) Bromoxynil Phenol in the diet. In males the no-observed-
effect-level (NOEL) for systemic toxicity is 2.6 mg/kg/day, and the
Lowest-effect-level (LEL) is 8.2 mg/kg/day. In females, the NOEL is 3.3
mg/kg/day, and the LEL is 11.0 mg/kg/day. This study did not
demonstrate any increase in tumor incidences in either male or female
rats.
2. A 2 year combined feeding/carcinogenicity study was conducted
with rats administered Bromoxynil Phenol in the diet at dose levels of
0, 10, 30, or 100 ppm (0, 0.5, 1.5, or 5 mg/kg/day). In both males and
females, the NOEL and LOEL for systemic toxicity was 5 mg/kg/day and >5
mg/kg/day, respectively. At the highest dose tested, increased liver
weights were observed at 12 months, but not at 24 months. This study
was considered negative for carcinogenicity.
3. An 18 month carcinogenicity study was conducted with mice
administered Bromoxynil Phenol at dose levels of 0, 10, 30, or 100 ppm
(0, 1.3, 3.9, or 13 mg/kg/day) in the diet. For males, dose related
increases in hyperplastic nodules and liver adenomas/carcinomas were
observed which were statistically significant at the 13 mg/kg/day
level. Increased relative liver weights were also observed. In females,
increased absolute liver weights and relative liver and kidney weights
were observed. The study was considered negative for carcinogenicity
for females.
4. An 18 month carcinogenicity study was conducted with mice
administered Bromoxynil Phenol at dose levels of 0, 20, 75, or 300 ppm
(0, 3.1, 12 or 46 mg/kg/day in males and 0, 3.7, 14, or 53 mg/kg/day in
females). Mice given 300 ppm had significantly increased absolute and
relative liver weights. Histopathology of the liver revealed increased
hepatocellular hypertrophy, hepatocellular degeneration, necrosis of
individual hepatocytes, and pigment accumulation in hepatocytes and
Kupffer cells. Male
[[Page 67810]]
mice had statistically significant increased numbers of hepatocellur
adenomas and carcinomas at 20 ppm, but not 75 ppm. In contrast, no
significant increase in tumor incidence was observed for female mice by
pair-wise analysis. The trend test was significant for adenomas or
carcinomas in females, only at p<0.05, not=""><0.01 as="" would="" be="" appropriate="" for="" this="" type="" of="" tumor.="" the="" trend="" is="" due="" entirely="" to="" the="" high="" dose="" group="" and="" therefore="" is="" of="" questionable="" validity.="" conclusion.="" bromoxynil="" is="" a="" weak,="" single="" sex,="" single="" species,="" non-="" metastic,="" single="" target="" organ="" carcinogen,="" inducing="" hepatocellular="" tumors="" in="" male="" mice="" exposed="" to="" 300="" ppm="" for="" 18="" months.="" these="" tumors="" and="" associated="" histopathological="" findings="" are="" consistent="" with="" secondary="" mechanisms="" such="" as="" peroxisome="" proliferation,="" a="" mechanism="" known="" to="" have="" marked="" species="" differences="" and="" questionable="" relevance="" for="" humans.="" the="" data="" are="" not="" suitable="" for="" quantitative="" risk="" assessment.="" a="" threshold="" safety="" factor="" approach="" is="" more="" appropriate="" and="" is="" commonly="" used="" for="" single="" sex,="" single="" species="" carcinogens="" such="" as="" bromoxynil="" that="" are="" thought="" to="" work="" through="" secondary="" mechanisms.="" based="" on="" these="" data,="" rhone-poulenc="" concludes="" bromoxynil="" is="" not="" expected="" to="" pose="" any="" increased="" dietary="" risks.="" f.="" teratology="" 1.="" bromoxynil="" phenol="" technical.="" several="" teratology="" studies="" were="" conducted="" with="" bromoxynil="" phenol="" technical.="" these="" are="" summarized="" below:="" a.="" a="" teratology="" study="" was="" conducted="" with="" rats="" administered="" (orally)="" bromoxynil="" phenol="" at="" dose="" levels="" of="" 0,="" 4,="" 12.5,="" or="" 40="" mg/kg/="" day.="" the="" maternal="" noel="" and="" lel="" are="" 12.5="" and="" 40="" mg/kg/day="" respectively.="" the="" developmental="" noel="" and="" lel="" are="" 4.0="" and="" 12.5="" mg/kg/day,="" respectively.="" maternal="" body="" weights="" and="" food="" consumption="" were="" reduced="" in="" the="" high="" dose="" group.="" fetal="" effects="" observed="" were="" reduced="" body="" weight,="" with="" associtaed="" decreases="" in="" ossification.="" an="" increase="" in="" 14th="" ribs,="" was="" observed="" in="" the="" mid="" and="" high="" dose="" levels.="" b.="" a="" teratology="" study="" was="" conducted="" with="" rats="" administered="" (orally)="" bromoxynil="" phenol="" at="" dose="" levels="" of="" 0,="" 5,="" 15,="" or="" 35="" mg/kg/day.="" the="" maternal="" noel="" and="" lel="" are="" 5.0="" and="" 15="" mg/kg/day,="" respectively.="" the="" fetotoxicity="" and="" developmental="" noel="" and="" lel="" are="" less="" than="" 5="" and="" 5="" mg/="" kg/day,="" respectively.="" significant="" maternal="" mortality="" and="" decreased="" body="" weight="" gain="" were="" associated="" with="" the="" high="" dose,="" indicating="" that="" the="" mtd="" was="" exceeded.="" decreases="" in="" maternal="" body="" weight="" gain="" were="" also="" observed="" in="" the="" mid="" and="" low="" dose="" levels.="" at="" the="" mid-dose="" level="" a="" statistically="" significant="" increase="" in="" the="" number="" of="" fetuses="" with="" supernumerary="" ribs,="" a="" common="" fetal="" variant="" was="" observed.="" c.="" a="" teratology="" study="" was="" conducted="" with="" rats="" administered="" (orally)="" bromoxynil="" phenol="" at="" dose="" levels="" of="" 0,="" 1.7,="" 5,="" or="" 15="" mg/kg/="" day.="" the="" maternal="" noel="" and="" lel="" sre="" 5="" and="" 15="" mg/kg/day,="" respectively.="" the="" developmental="" noel="" and="" lel="" are="" 5="" and="" 15="" mg/kg/day,="" respectively.="" this="" study="" was="" classified="" as="" unacceptable,="" primarily="" due="" to="" reporting="" deficiendies.="" d.="" a="" teratology="" study="" was="" conducted="" with="" rabbits="" administered="" (orally)="" bromoxynil="" phenol="" at="" dose="" levels="" of="" 0,="" 15,="" 30,="" or="" 60="" mg/kg/="" day.="" the="" maternal="" noel="" and="" lel="" are="" 15="" and="" 30="" mg/kg/day,="" respectively.="" the="" developmental="" noel="" and="" lel="" are="" less="" than="" 15="" and="" 15="" mg/kg/day,="" respectively.="" significant="" body="" weight="" gain="" decrements="" were="" reported="" at="" the="" two="" highest="" dose="" levels="" along="" with="" observed="" decreases="" in="" food="" sonsumption.="" the="" severe="" maternal="" toxicity="" among="" high="" dose="" dams="" was="" associated="" with="" fetoxicity="" and="" teratogenicity.="" a="" slight,="" nonsignificant="" increase="" in="" supernumerary="" ribs="" was="" reported="" at="" the="" mid="" and="" low="" dose="" levels.="" e.="" a="" teratology="" study="" was="" conducted="" with="" mice="" administered="" (orally)="" bromoxynil="" phenol="" at="" dose="" levels="" of="" 0,="" 11,="" 32,="" or="" 96="" mg/kg/="" day.="" maternal="" mortality="" was="" observed="" at="" 32="" and="" 96="" mg/kg/day.="" fetal="" body="" weight="" was="" decreased="" at="" the="" top="" dose="" level,="" associated="" with="" a="" decrease="" in="" caudal="" vertebral="" ossification="" and="" an="" increase="" in="" supernumerary="" ribs.="" the="" maternal="" noel="" and="" lel="" are="" 11="" and="" 32="" mg/kg/day="" respectivel.="" the="" developmental="" noel="" and="" lel="" are="" 32="" and="" 96="" mg/kg/day,="" respectively.="" 2.="" bromoxynil="" octanoate="" technical.="" a="" teratology="" study="" was="" conducted="" with="" bromoxynil="" octanaote="" administered="" (orally)="" to="" rats="" at="" dose="" levels="" of="" 0,="" 2.4,="" 7.3="" or="" 21.8="" mg/kg/day.="" this="" is="" equivalent="" to="" 0,="" 1.7,="" 5,="" or="" 15="" mg/kg/day="" bromoxynil="" phenol.="" transient="" decreases="" in="" maternal="" body="" weight="" were="" observed="" at="" the="" highest="" dose="" level.="" fetal="" body="" weight="" was="" also="" decreased="" and="" the="" incidence="" of="" supernumerary="" ribs="" was="" increased="" at="" this="" dose="" level.="" the="" maternal="" noel="" and="" lel="" are="" 5="" and="" 15="" mg/kg/day,="" respectively.="" the="" developmental="" noel="" and="" lel="" are="" also="" 5="" and="" 15="" mg/kg/day,="" respectively.="" conclusion.="" based="" on="" all="" the="" studies="" cited="" above="" rhone-poulenc="" concludes="" that="" neither="" bromoxynil="" nor="" bromoxynil="" octanoate="" are="" teratogens="" at="" doses="" that="" are="" not="" maternally="" toxic.="" g.="" reproductive="" effects="" 1.="" two="" reproduction="" studies="" were="" conducted="" with="" bromoxynil="" phenol.="" these="" are="" summarized="" below:="" a.="" a="" reproduction="" study="" was="" conducted="" with="" rats="" administered="" (orally)="" bromoxynil="" phenol="" at="" dose="" levels="" of="" 0.="" 0.8,="" 4,="" or="" 21="" mg/kg/day="" in="" the="" diet.="" the="" systemic="" adult="" rat="" noel="" is="" 4="" mg/kg/day="" and="" the="" lel="" is="" 21="" mg/kg/day.="" the="" reproductive="" noel="" is="" 21="" mg/kg/day,="" and="" the="" lel="" is="" greater="" than="" 21="" mg/kg/day.="" the="" postnatal="" developmental="" noel="" is="" 4="" mg/kg/="" day,="" and="" the="" lel="" is="" 21="" mg/kg/day.="" body="" weight="" gain="" decrements="" were="" reported.="" however,="" no="" adverse="" effects="" on="" fertility,="" fecundity,="" reproductive="" performance="" or="" pre="" and="" postnatal="" development="" were="" observed.="" b.="" a="" reproduction="" study="" was="" conducted="" with="" rats="" administered="" (orally)="" bromoxynil="" phenol="" at="" dose="" levels="" of="" 0,="" 1.5,="" 5,="" or="" 15="" mg/kg/day="" in="" the="" diet.="" the="" systemic="" rat="" noel="" is="" 1.5="" mg/kg/day,="" and="" the="" lel="" is="" is="" 5="" mg/kg/day.="" the="" reproductive="" noel="" is="" 15="" mg/kg/day,="" and="" the="" lel="" is="" greater="" than="" 15="" mg/kg/day.="" the="" offspring="" developmental="" noel="" is="" 5="" mg/kg/="" day="" and="" the="" lel="" is="" 15="" mg/kg/day.="" body="" weight="" gain="" decrements="" were="" reported.="" however,="" no="" adverse="" effects="" on="" fertility,="" fecundity,="" reproductive="" performance="" or="" pre="" and="" postnatal="" development="" were="" observed.="" conclusion.="" based="" on="" the="" studies="" cited="" above="" rhone-poulenc="" concludes="" bromoxynil="" is="" not="" considered="" a="" reproductive="" toxicant="" and="" shows="" no="" evidence="" of="" endocrine="" effects.="" 2.="" aggregate="" exposure.="" the="" food="" quality="" protection="" act="" of="" 1996="" list="" three="" other="" potential="" sources="" of="" exposure="" to="" the="" general="" population="" that="" must="" be="" addressed.="" these="" are="" pesticides="" in="" drinking="" water,="" exposure="" from="" non-occupational="" sources,="" and="" the="" potential="" cumulative="" effect="" of="" pesticides="" with="" similar="" toxicological="" modes="" of="" action.="" based="" on="" available="" studies="" which="" show="" a="" short="" half-life="" of="" bromoxynil="" in="" the="" environment="" (average="" half-life="" of="" 3-7="" days="" under="" actual="" field="" conditions),="" rhone-poulenc="" does="" not="" anticipate="" residues="" of="" bromoxynil="" in="" drinking="" water.="" there="" is="" no="" established="" maximum="" concentration="" level="" or="" health="" advisory="" level="" for="" bromoxynil="" under="" the="" safe="" drinking="" water="" act.="" the="" potential="" for="" non-occupational="" exposure="" to="" the="" general="" public="" is="" also="" insignificant.="" there="" are="" no="" residential="" lawn="" or="" garden="" uses="" for="" bromoxynil="" products="" where="" the="" general="" population="" may="" be="" exposed="" via="" inhalation="" or="" dermal="" routes.="" bromoxynil="" is="" registered="" for="" use="" on="" grass="" grown="" for="" seed="" or="" sod="" [[page="" 67811]]="" production="" and="" for="" non-residential="" turfgrass.="" these="" uses="" are="" very="" minor="" and="" applied="" at="" only="" 0.5="" lbs="" per="" acre.="" these="" uses="" will="" therefore="" not="" significantly="" add="" to="" the="" aggregate="" exposure.="" rhone-poulenc="" concludes="" that="" consideration="" of="" a="" common="" mechanism="" of="" toxicity="" is="" not="" appropriate="" at="" this="" time="" since="" there="" is="" no="" reliable="" data="" to="" indicate="" that="" the="" toxic="" effects="" caused="" by="" bromoxynil="" would="" be="" cumulative="" with="" those="" of="" any="" other="" compound.="" based="" on="" this="" point,="" rhone-poulenc="" has="" considered="" only="" the="" potential="" risks="" of="" bromoxynil="" in="" its="" exposure="" assessment.="" c.="" safety="" determination="" 1.="" dres-u.s.="" population,="" infants,="" children="" (1-6="" years="" old)="" a.="" general="" u.s.="" population.="" using="" the="" stated="" epa="" rfd="" for="" bromoxynil="" of="" 0.015="" mg/kg/day="" and="" the="" conservative="" assumptions="" stated="" above,="" and="" based="" on="" the="" completeness="" of="" the="" toxicology="" database,="" it="" has="" been="" determined="" that="" aggregate="" exposure="" to="" bromoxynil="" will="" use="" 2.4%="" of="" the="" rfd="" for="" the="" us="" population.="" this="" is="" assuming="" that="" 100%="" of="" the="" acres="" for="" each="" crop="" for="" which="" a="" tolerance="" has="" been="" established="" (including="" transgenic="" cotton)="" was="" treated="" and="" the="" residue="" found="" was="" at="" the="" tolerance="" level.="" if="" one="" assumes="" market="" share="" values="" this="" number="" is="" decreased="" to="" 1.4%.="" b.="" infants="" and="" children="" (1-6="" years="" old).="" the="" food="" quality="" protection="" act="" of="" 1996="" provides="" that="" an="" additional="" safety="" factor="" for="" infants="" and="" children="" may="" be="" applied="" in="" the="" case="" of="" threshold="" effects.="" the="" noel/lel="" of="" 1.5="" mg/kg/day="" in="" the="" chronic="" dog="" study,="" on="" which="" the="" rfd="" is="" based,="" is="" already="" lower="" than="" the="" noels="" from="" the="" developmental="" and="" reproductive="" toxicity="" studies.="" rhone-poulenc="" concludes="" that="" an="" adequate="" margin="" of="" safety="" is="" therefore="" provided="" by="" the="" currents="" rfd.="" using="" the="" stated="" epa="" rfd="" for="" bromoxynil="" of="" 0.015="" mg/kg/day="" and="" the="" conservative="" assumptions="" stated="" above,="" it="" has="" been="" determined="" that="" aggregate="" exposure="" to="" bromoxynil="" will="" use="" 2.3%="" for="" infants="" and="" 4.9%="" for="" children="" under="" 6="" years="" old.="" this="" is="" assuming="" that="" 100%="" of="" the="" acres="" for="" each="" crop="" for="" which="" a="" tolerance="" has="" been="" established="" (including="" transgenic="" cotton)="" was="" treated="" and="" the="" residue="" found="" was="" at="" the="" tolerance="" level.="" if="" one="" assumes="" market="" share="" values="" these="" values="" are="" decreased="" to="" 1.8%="" for="" infants="" and="" 2.8%="" for="" children="" under="" 6="" years="" old.="" c.="" additional="" comments="" on="" safety="" to="" infants="" and="" children.="" in="" assessing="" the="" potential="" for="" additional="" sensitivity="" of="" infants="" and="" children="" to="" residues="" of="" bromoxynil,="" the="" available="" teratology="" and="" reproductive="" toxicity="" studies="" and="" the="" potential="" for="" endocrine="" modulation="" by="" bromoxynil="" were="" considered.="" developmental="" toxicity="" studies="" in="" three="" species="" indicates="" that="" bromoxynil="" is="" not="" a="" teratogen="" at="" doses="" that="" are="" not="" maternally="" toxic.="" two="" multi-generation="" rodent="" reproduction="" studies="" demonstrated="" that="" there="" were="" no="" adverse="" effects="" on="" reproductive="" performance,="" fertility,="" fecundity,="" pup="" survival,="" or="" pup="" development.="" maternal="" and="" developmental="" noels="" and="" loels="" were="" comparable="" indicating="" no="" increase="" susceptibility="" of="" developing="" organisms.="" no="" evidence="" of="" endocrine="" effects="" were="" noted="" in="" any="" study.="" rhone-poulence="" concludesit="" is="" therefore="" concluded="" that="" bromoxynil="" poses="" no="" additional="" risk="" for="" infants="" and="" children="" and="" no="" additional="" uncertainty="" factor="" is="" warrented.="" d.="" environmental="" fate.="" extensive="" laboratory="" and="" field="" studies="" indicate="" that="" bromoxynil="" has="" little="" tendency="" to="" move="" within="" or="" persist="" in="" soil="" or="" water="" under="" field="" conditions.="" once="" in="" contact="" with="" soil,="" bromoxynil="" rapidly="" degrades.="" an="" average="" half-life="" of="" 3-7="" days="" for="" bromoxynil="" has="" been="" demonstrated="" under="" field="" conditions.="" the="" soil="" breakdown="" process="" begins="" almost="" immediately="" and="" involves="" hydrolysis,="" dehalogenation,="" as="" well="" as="" other="" complex="" metabolic="" pathways="" carried="" out="" by="" soil="" bacteria="" and="" other="" microorganisms.="" 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-681].="" all="" written="" comments="" filed="" in="" response="" to="" this="" petition="" will="" be="" available="" in="" the="" public="" response="" and="" program="" resources="" branch,="" at="" the="" address="" given="" above="" from="" 8:30="" a.m.="" to="" 4="" p.m.,="" monday="" through="" friday,="" except="" legal="" holidays.="" a="" record="" has="" been="" established="" for="" this="" notice="" of="" filing="" under="" docket="" number="" [pf-681]="" 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,="" except="" 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-docket@epamail.epa.gov
Electronic comments must be submitted as an ASCII file avoiding the
use of special characters and any form of encryption.
The official record for this notice of filing, 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 they are received and will place the paper
copies in the official 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, Pesticide and pest, Reporting and
recordkeeping requirements.
Dated: December 13, 1996.
Peter Caulkins,
Acting Director, Registration Division, Office of Pesticide Programs.
[FR Doc. 96-32530 Filed 12-23-96; 8:45 am]
BILLING CODE 6560-50-F
