[Federal Register Volume 62, Number 228 (Wednesday, November 26, 1997)]
[Notices]
[Pages 63170-63174]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-30812]


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ENVIRONMENTAL PROTECTION AGENCY

[PF-779; FRL-5755-6]


Notice of Filing of Pesticide Petition

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice.

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SUMMARY: This notice announces the initial filing of 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-779, must 
be received on or before December 26, 1997.
ADDRESSES: By mail submit written comments to: Public Information and 
Records Integrity Branch, Information Resources and Services Division 
(7502C), 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: <a href="/cdn-cgi/l/email-protection#0e617e7e23046a616d656b7a4e6b7e6f636f6762206b7e6f20696178">opp-
<span class="__cf_email__" data-cfemail="51353e323a3425113421303c30383d7f3421307f363e27">[email protected]</span></a>. 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.,

[[Page 63171]]

Monday through Friday, excluding legal holidays.

FOR FURTHER INFORMATION CONTACT: By mail: James Tompkins, Registration 
Division (7505C) Office of Pesticide Programs, Environmental Protection 
Agency, 401 M St., SW., Washington, DC 20460. Office location and 
telephone number: Rm. 265, CM #2, 1921 Jefferson Davis Highway, 
Arlington, VA 22202, (703) 305-7801; e-mail: 
<a href="/cdn-cgi/l/email-protection#1763787a677c7e7964397d767a7264577267767a767e7b3972677639707861"><span class="__cf_email__" data-cfemail="6a1e05071a0103041944000b070f192a0f1a0b070b0306440f1a0b440d051c">[email protected]</span></a>.
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-779] (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:
    <a href="/cdn-cgi/l/email-protection#80eff0f0ade4efe3ebe5f4c0e5f0e1ede1e9ecaee5f0e1aee7eff6"><span class="__cf_email__" data-cfemail="39564949145d565a525c4d795c495854585055175c4958175e564f">[email protected]</span></a>

    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 file format or ASCII 
file format. All comments and data in electronic form must be 
identified by the docket number [PF-779] and appropriate petition 
number. Electronic comments on 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.

 Rhone-Poulenc Ag Company

PP 3F4233

    EPA has received a pesticide petition (PP 3F4233) from Rhone-
Poulenc Ag Company, 2 Alexander Drive, Research Triangle Park, 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 part 180 to extend 
the current time-limited tolerances for bromoxynil and its metabolite 
DBHA (3,5-dibromo-4-hydroxybenzoic acid) resulting from the application 
of octanoic and heptanoic acid esters of bromoxynil to cotton in or on 
the raw agricultural commodities undelinted cottonseed at 7 parts per 
million (ppm), cotton gin byproducts at 50 ppm, and cotton hulls at 21 
ppm for a 1-year period and to increase the current acreage limitation 
from 3% to 10% of the U. S. cotton acreage (1,300,000 acres). 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. The nature of the bromoxynil residue in 
bromoxynil-tolerant cotton is considered to be adequately understood. 
The two major components of the terminal residue are parent bromoxynil 
and the metabolite 3,5-dibromo-4-hydroxybenzoic acid (DBHA).
    2. Analytical method. Adequate analytical methodologies for both 
parent bromoxynil and the DBHA are available for enforcement purposes. 
The method involves sample reflux in methanolic KOH, partitioning with 
ether/hexane and analysis by Gas Chromatography. Limits of quantitation 
allow monitoring of residues in cotton commodities at or above 
tolerance levels. Multiresidue testing with DBHA has been conducted and 
submitted to FDA.
    3. Magnitude of residues. Available magnitude of the residue data 
from a 60 day phi crop field residue study conducted at a maximum 
application rate of 4.5 lb active ingredient/acre indicate that the 
currently established time-limited tolerances for bromoxynil and DBHA 
will not be exceeded when Buctril 4EC herbicide is used according to 
approved label directions.

B. Toxicological Profile

    1. Acute toxicity. A complete battery of acute toxicity studies for 
bromoxynil (phenol) has been conducted. The acute oral toxicity study 
in rats resulted in a LD<INF>50</INF> of 81 milligrams/kilogram (mg/kg) 
(males) and a LD<INF>50</INF> of 93 mg/kg (females). The acute dermal 
toxicity study in rabbits resulted in a LD<INF>50</INF> of >2,000 mg/kg 
for both males and females. The acute inhalation study in rats resulted 
in a LC<INF>50</INF> of 0.269 milligram/liter (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.
    2. Genotoxicty. Mutagenicity studies conducted include 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 Salmonella typhimurium reverse mutation assay 
(negative with and without activation). Rhone-Poulenc considers 
bromoxynil (phenol) and DBHA to be non-mutagenic.
    3. Reproductive and developmental toxicity. 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 no-observed-effect 
level (NOEL) and lowest-observed-effect level

[[Page 63172]]

(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. 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 
maximum tolerance dose 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. 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 are 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. 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 consumption. 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. 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.
    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. 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.
    Based on the studies discussed above, it is concluded that 
bromoxynil is not teratogenic at doses that are not maternally toxic. 
In addition, bromoxynil is not considered a reproductive toxicant and 
shows no evidence of endocrine effects.
    4. Subchronic toxicity. In a 12-week range-finding study, 
bromoxynil (phenol) was administered in the diets of male and female 
CD-1 mice at dose levels of 0, 1.3, 3.9, 13, 39, 130, or 390 mg/kg/day. 
For male mice, the NOEL is 3.9 mg/kg/day and the LOEL is 13 mg/kg/day 
based on increased liver weights and hepatocellular hypertrophy. In 
female mice, the NOEL is 13 mg/kg/day and the LOEL is 39 mg/kg/day 
based on increased liver weights, hepatocellular hypertrophy, 
hepatocellular degeneration, and hepatocellular vacuolization. In a 13-
week subchronic feeding study, bromoxynil (phenol) was administered in 
the diet to male and female Sprague-Dawley rats at dose levels of 0, 
28, 58, or 168 mg/kg/day. For male rats, the NOEL is 28 mg/kg/day and 
the LOEL is 58 mg/kg/day based on decreased body weight gain, increased 
ALT and increased alkaline phosphatase. For female rats, no NOEL was 
determined in this study and the LOEL is 35 mg/kg/day based on 
decreased body weight gain. In a 13-week range-finding study, 
bromoxynil (phenol) was administered orally to male and female dogs at 
doses of 0, 1, 5, 8, 12, 16, 20, 30, 40, or 50 mg/kg/day. For males, no 
NOEL was determined and the LOEL is 1 mg/kg/day based on decreased body 
weight gain. For females, the NOEL is 1 mg/kg/day and the the LOEL is 5 
mg/kg/day based on decreased body weight gain, panting and liquid 
feces. In a 21 day subchronic dermal study, bromoxynil (phenol) was 
applied to skin of male and female New Zealand white rabbits at doses 
of 0, 30, 300, or 1,000 mg/kg/day for 6 hours/day, 5 days/week. 
Treatment produced no observable dermal or systemic toxicity, therefore 
the NOEL is 1,000 mg/kg/day.
    5. Chronic toxicity. A 1-year oral study was conducted 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, and increased liver 
weights. The chronic dog study was determined by Rhone-Poulenc to be 
the most appropriate study for setting the Reference Dose (RfD) of 
0.015 mg/kg/day (includes a hundredfold safety factor).
    A 2-year combined chronic toxicity/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.
    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. 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 100 ppm. Increased relative liver 
weights were also observed. In females,

[[Page 63173]]

increased absolute liver weights and relative liver and kidney weights 
were observed. The study was considered negative for carcinogenicity 
for females. 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 mice had statistically significant increased 
numbers of hepatocellular 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. It is concluded that 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. It is the opinion of Rhone-Poulenc that 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. For the purposes of this tolerance 
petition, risk assessments have been performed using a low dose linear 
extrapolation model (Q<INF>1</INF>* is 1.03  x  10<SUP>-1</SUP>).
    6. Animal metabolism. Results of a bromoxynil metabolism study with 
the rat (octanoate) demonstrated that 2 mg/kg of radiolabeled 
bromoxynil octanoate was rapidly absorbed, hydrolyzed to bromoxynil 
phenol, distributed, and excreted in rats following repeated oral 
administration. 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. Tissue distribution was similar for both 
sexes with the highest radioactivity recovered in the liver and kidney. 
Similar results were obtained in a separate rat metabolism study 
conducted with bromoxynil heptanoate.
    7. Metabolite toxicology. DBHA (3,5-dibromo-4-hydroxybenzoic acid) 
is a major plant metabolite of bromoxynil only in bromoxynil-resistant 
transgenic cotton. Acute oral toxicity testing with DBHA in rats 
resulted in an LD<INF>50</INF> of >2,000 mg/kg. Acute dermal toxicity 
testing with DBHA in rabbits resulted in an LD<INF>50</INF> of >2,000 
mg/kg. The primary dermal irritation study with DBHA in rabbits 
indicated DBHA to be a slight irritant, and DBHA was not a dermal 
sensitizer in Guinea pigs. Mutagenicity studies conducted with DBHA 
include a Salmonella typhimurium reverse mutation assay (negative with 
and without activation); micronucleus assay (negative); and 
TK<SUP>+/-</SUP> mouse lymphoma assay (negative with and without 
metabolic activation). In subchronic feeding studies in the rat, DBHA 
was administered by oral gavage to groups of Sprague-Dawley rats for 28 
days at dose levels of 25, 50, 100 and 250 mg/kg/day. No 
toxicologically meaningful changes were observed in any of the 
parameters measured in this study. The NOEL and LEL for this study were 
250 and >250 mg/kg/day, respectively.

C. Aggregate Exposure

    1. Dietary (food) exposure. For the purpose of estimating the 
potential human dietary exposure resulting from bromoxynil use on 
cotton under the existing tolerances, anticipated residues of 
bromoxynil and DBHA were used. Anticipated residue values of 1.44 ppm 
(cottonseed), 8.74 ppm (cotton gin trash), and 0.43 ppm (cottonseed 
meal) were derived by taking the mean residue values from available 
crop field trials conducted at the 4.5 lb/A broadcast rate and 
adjusting by a factor of 0.333 to extrapolate to the current 1.5 lb/A 
application rate. Adjusting these values for % dry matter and the 
proposed 10% of crop treated results in anticipated cotton feedstuff 
residue values of 0.14 ppm (cottonseed), 0.87 ppm (cotton gin trash), 
and 0.043 ppm (cottonseed meal). Based on the use of these exposure 
data and a unit risk (Q<INF>1</INF>* (mg/kg/day)<SUP>-1</SUP>, of 
bromoxynil of 1.03  x  10-<SUP>1</SUP>, the upper-bound human risk 
estimate for the general (U.S.) population represented by all sources 
of bromoxynil exposure, including use on up to 10% of the U.S. treated 
acreage is approximately 2  x  10<SUP>-6</SUP>.
    2. Drinking water. There is no Maximum Concentration Level or 
Health Advisory Level established for bromoxynil under the Safe 
Drinking Water Act. Based on field dissipation studies demonstrating a 
short half-life of bromoxynil in the environment (average half-life of 
3-7 days), bromoxynil residues will degrade in soil before residues can 
move downward into ground water. Therefore, no significant potential 
exists for bromoxynil residues to be present in drinking water from 
ground water. Likewise, contamination of drinking water supplies from 
bromoxynil movement through agricultural surface runoff is considered 
highly unlikely due to relatively low application rates and rapid 
degradation rates in soil. As demonstrated by available monitoring 
data, normal dilution and degradation processes will greatly reduce 
concentrations in surface water during movement from agricultural 
ditches near fields into streams of adequate size for use as drinking 
water. It is the conclusion of Rhone-Poulenc that the potential 
bromoxynil exposure derived from any use through drinking water is 
insignificant and does not significantly increase the aggregate risk 
assessment above that estimated to occur through food exposure alone.
    3. Non-dietary exposure. The potential for non-occupational 
exposure to bromxynil among the general public is insignificant. There 
are no residential lawn or garden uses for bromoxynil products where 
the general population might be exposed via inhalation or dermal 
routes. Turfgrass use is restricted to non-residential areas. Exposure 
to bromoxynil following application to non-residential turfgrass is not 
likely to be significant in either time or duration. This use will 
therefore not significantly add to the aggregate exposure.

D. Cumulative Effects

    There are no reliable data suggesting that any toxic effect that 
might be caused by bromoxynil would be cumulative with those of any 
other compound. Further, bromoxynil does not appear to produce a toxic 
metabolite that is produced by other substances. Therefore, 
consideration of potential cumulative effects is not appropriate at 
this time.

E. Safety Determination

    1. U.S. population. Using the present RfD for bromoxynil of 0.015 
mg/kg/day, it has been determined that aggregate chronic exposure to 
bromoxynil from all uses, including cotton, represents <1% of the RfD 
for all population sub-groups. A unit risk, Q<INF>1</INF>* (mg/kg/
day)<SUP>-1</SUP>, of bromoxynil of 1.03  x  10<SUP>-1</SUP> in human 
equivalents, has been calculated based on mouse liver tumors. It is the 
opinion of Rhone-Poulenc that the bromoxynil data are not suitable for 
quantitative risk assessment. A threshold safety factor approach is 
more appropriate and is

[[Page 63174]]

commonly used for single sex, single species carcinogens such as 
bromoxynil that are thought to work through secondary mechanisms. 
Nevertheless, the risk assessments filed with this petition have been 
performed using quantitative risk assessment methodology. Accordingly, 
the upper-bound risk estimate for the general U.S. population 
represented by all sources of bromoxynil exposure, including use of 
bromoxynil on up to 10% of the U.S. treated acreage is approximately 2 
x  10<SUP>-6</SUP>.
    2. Infants and children. To estimate acute dietary risk for 
systemic effects other than developmental from food sources, an MOE of 
270 was calculated using 1-day dietary exposure for infants (the most 
highly exposed population group) and a NOEL of 8 mg/kg/day derived from 
a 13-week oral toxicity study in dogs. It is concluded that reliable 
data support use of the standard hundredfold margin of exposure/safety 
factor in assessing the risk to children. The general U.S. population 
and all population sub-groups are estimated to be exposed at a level 
less than 1 percent of the bromoxynil RfD of 0.015 mg/kg/day. Both 
chronic and acute assessments show no appreciable threshold risks to 
children and the non-threshold cancer risk is no greater than 
negligible. Therefore, there is a reasonable certainty that no harm 
will result to infants and children from aggregate exposure to 
bromoxynil.
    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. It is therefore concluded that bromoxynil poses no 
additional risk for infants and children and no additional uncertainty 
factor is warranted.

F. International Tolerances

    There are no Codex tolerances established for bromoxynil residues, 
therefore international compatibility is not considered to be an issue 
at this time.
[FR Doc. 97-30812 Filed 11-25-97; 8:45 am]
BILLING CODE 6560-50-F


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