[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: [email protected]. Electronic 
comments must be submitted as an ASCII file avoiding the use of special 
characters and any form of encryption. Comments and data will also be 
accepted on disks in WordPerfect 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.R[email protected].

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:
    [email protected]


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

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 p<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:
    [email protected]


    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