[Federal Register Volume 62, Number 185 (Wednesday, September 24, 1997)]
[Notices]
[Pages 49979-49983]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-25234]
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ENVIRONMENTAL PROTECTION AGENCY
[PF-764; FRL-5745-8]
E.I. DuPont de Nemours and Co., Inc.; Pesticide Tolerance
Petition Filing
AGENCY: Environmental Protection Agency (EPA).
ACTION: Notice.
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SUMMARY: This notice announces the initial filing of a pesticide
petition proposing the establishment of regulations for residues of a
certain pesticide chemical in or on various food commodities.
DATES: Comments, identified by the docket control number PF-764, must
be received on or before October 24, 1997.
ADDRESSES: By mail submit written comments to: Information and Records
Integrity Branch, Public Information and Services Division (7506C),
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 by following
the instructions under ``SUPPLEMENTARY INFORMATION.'' No confidential
business information should be submitted through e-mail.
Information submitted as a comment concerning this document may be
claimed confidential by marking any part or all of that information as
``Confidential Business Information'' (CBI). CBI should not be
submitted through e-mail. Information marked as CBI will not be
disclosed except in accordance with procedures set forth in 40 CFR part
2. A copy of the comment that does not contain CBI must be submitted
for inclusion in the public record. Information not marked confidential
may be disclosed publicly by EPA without prior notice. All written
comments will be available for public inspection in Rm. 1132 at the
address given above, from 8:30 a.m. to 4 p.m., Monday through Friday,
excluding legal holidays.
FOR FURTHER INFORMATION CONTACT: James Stone, PM-25 Team, Registration
Division (7505C), Office of Pesticide Programs, Environmental
Protection Agency, 401 M St., SW., Washington, DC 20460. Office
location, telephone number, and e-mail address: Rm. 257, Crystal Mall
#2 1921 Jefferson Davis Highway, Arlington, VA 22202, (703) 305-7391;
e-mail: stone.james@epamail.epa.gov.
SUPPLEMENTARY INFORMATION: EPA has received a pesticide petition as
follows proposing the establishment and/or amendment of regulations for
residues of certain pesticide chemical in or on various food
commodities under section 408 of the Federal Food, Drug, and Comestic
Act (FFDCA), 21 U.S.C. 346a. EPA has determined that this petition
contains data or information regarding the elements set forth in
section 408(d)(2); however, EPA has not fully evaluated the sufficiency
of the submitted data at this time or whether the data supports
granting of the petition. Additional data may be needed before EPA
rules on the petition.
The official record for this notice of filing, as well as the
public version, has been established for this notice of filing under
docket control number [PF-764] (including comments and data submitted
electronically as described below). A public version of this record,
including printed, paper versions of electronic comments, which does
not include any information claimed as CBI, is available for inspection
from 8:30 a.m. to 4 p.m., Monday through Friday, excluding legal
holidays. The official record is located at the address in
``ADDRESSES'' at the beginning of this document.
Electronic comments can be sent directly to EPA at:
opp-docket@epamail.epa.gov
Electronic comments must be submitted as an ASCII file avoiding the
use of special characters and any form of encryption. Comment and data
will also be accepted on disks in Wordperfect 5.1 file format or ASCII
file format. All comments and data in electronic form must be
identified by the docket control number (PF-764) and appropriate
petition number. Electronic comments on this notice may be filed online
at many Federal Depository Libraries.
List of Subjects
Environmental protection, Agricultural commodities, Food additives,
Feed additives, Pesticides and pests, Reporting and recordkeeping
requirements.
Dated: September 11, 1997.
Peter Caulkins,
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.
E.I. DuPont de Nemours and Co., Inc
PP 4F4391
EPA has received a pesticide petition (PP 4F4391) from E.I. DuPont
de Nemours and Co., Inc (DuPont), Barley Mill Plaza, P.O. Box 80083,
Wilmington, DE 19880-0038 proposing pursuant to section 408(d) of the
Federal Food, Drug and Cosmetic Act, 21 U.S.C. 346a(d), to amend 40 CFR
part 180 by establishing a tolerance for residues of pyrithiobac sodium
salt (sodium 2-chloro-6-[(4,6-dimethoxypyrimidin-2-yl)thio]benzoate) in
or on the raw agricultural commodities cottonseed at 0.02 part per
million (ppm) and cotton gin byproducts at 0.10 (ppm). The proposed
analytical method involves homogenization, filtration, partition and
cleanup with analysis by using ultraviolet detection. 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.
[[Page 49980]]
A. Residue Chemistry
1. Plant metabolism. The qualitative nature of the residues of
pyrithiobac sodium in cotton is adequately understood. Metabolism
studies with pyrithiobac sodium indicate the major metabolic pathway
being o-dealkylation of the parent compound resulting in o-desmethyl
pyrithiobac sodium (O-DPS). O-DPS, both free and conjugated, was the
major metabolite identified in cotton foliage. The results of a
confined crop rotation study with pyrithiobac sodium revealed the
presence of a metabolite 2-chloro-6-sulfobenzoic acid (CSBA) not seen
in the cotton metabolism study. This metabolite appeared to originate
from soil metabolism of pyrithiobac sodium. Since preemergence
applications of pyrithiobac sodium are allowed, crop residues of CSBA
were considered a possibility. In consideration of PP 4F4391 CBTS, in
consultation with the HED Metabolism Committee has previously concluded
that for the proposed use on cotton, none of the pyrithiobac sodium
metabolites including O-DPS and CSBA warrant inclusion in the tolerance
regulation, and that the only residue of concern is the parent,
pyrithiobac sodium.
2. Analytical method. There are independently validated practical
analytical methods available using liquid chromatography (HPLC) with
column switching and ultraviolet (UV) detection, to measure levels of
pyrithiobac sodium in or on cottonseed and cotton gin byproducts, with
limits of quantitation that will allow for monitoring of crop residues
at or above tolerance levels. EPA has previously provided information
on the method for cottonseed to FDA for future publication in PAM II.
3. Magnitude of residues. Crop field trial residue data from 60 day
PHI studies show that the proposed pyrithiobac sodium tolerances on
these raw agricultural commodities will not be exceeded when
pyrithiobac sodium is used as directed. An adequate cottonseed
processing study shows that pyrithiobac sodium does not concentrate in
cottonseed processed commodities. No tolerances on processed
commodities are required.
B. Toxicological Profile
1. Acute toxicity. Pyrithiobac sodium technical has been placed in
EPA Toxicity Category II for acute eye irritation based on the test
article inducing irritation in the form of corneal opacity, iritis and
conjunctival redness, and discharge in the eyes of rabbits after
receiving ocular doses of 36 mg (0.1 ml). Signs of irritation were
clear within 14 days of treatment. Pyrithiobac sodium has been placed
in Toxicity Category III for acute dermal toxicity based on the test
article being nonlethal and nonirritating at the limit dose of 2,000
mg/kg, the highest dose tested (HDT). Pyrithiobac sodium has been
placed in Toxicity Category III for acute oral toxicity based on acute
oral LD50s of 3,200 mg/kg for both male and female rats.
Pyrithiobac sodium has been placed in Category IV for the remaining
acute toxicity tests based on the following: a rat acute inhalation
study with an LC50 of > 6.9 mg/l; and a primary dermal
irritation test that did not induce a dermal irritation response. A
dermal sensitization test with pyrithiobac sodium technical in guinea
pigs demonstrated no significant effects. Based on these results,
pyrithiobac sodium does not pose an acute dietary or exposure risk.
2. Genotoxicty. Pyrithiobac sodium technical was negative (non-
mutagenic and non-genotoxic) in the following tests: Ames microbial
mutation assay; the hypoxanthine-guanine phosphoribosyl transferase
gene mutation assay using Chinese hamster ovary cells; and induction of
unscheduled DNA synthesis (UDS) in primary rat hepatocytes. Pyrithiobac
sodium was positive in an in vitro assay for chromosome aberrations in
human lymphocytes. It was negative for the induction of micronuclei in
the bone marrow cells of male and female CD-1 mice administered the
test article by oral gavage at 500, 1,000 or 2,000 mg/kg. Based on the
weight of these data, pyrithiobac sodium is neither genotoxic nor
mutagenic.
3. Reproductive and developmental toxicity. A two generation, 4
litter reproduction study with CD rats treated at dietary levels of 0,
25, 1,500, 7,500 or 20,000 ppm of pyrithiobac sodium demonstrated a
maternal NOEL of 1,500 ppm (103 mg/kg/day) and a maternal LOEL of 7,500
ppm (508 mg/kg/day), based on decreased body weight gain and food
efficacy. An offspring NOEL of 7,500 ppm (508 mg/kg/day) and LOEL of
20,000 ppm (1,551 mg/kg/day) were also demonstrated based on decreased
offspring body weight. Pyrithiobac sodium was not teratogenic when
administered to rats or rabbits.
A developmental toxicity study with pyrithiobac sodium in rats
demonstrated a maternal NOEL of 200 mg/kg and LOEL of 600 mg/kg due to
increased incidence of salivation. A developmental NOEL of 600 mg/kg
and LOEL of 1,800 mg/kg were demonstrated based on an increased
incidence of skeletal variations.
A developmental toxicity study with pyrithiobac sodium in rabbits
demonstrated maternal and developmental NOELs of 300 mg/kg and a
maternal LOEL of 1,000 mg/kg based on mortality, decreased body weight
gain and feed consumption, increased incidence of clinical signs, and
an increase in early resorptions. A developmental LOEL of 1,000 mg/kg
was based on decreased fetal body weight gain. Based on the weight of
these data, pyrithiobac sodium is not considered a reproductive or
developmental hazard.
4. Subchronic toxicity. In a 90-day feeding study in rats conducted
with pyrithiobac sodium at dietary levels of 0, 10, 50, 500, 7,000 and
20,000 ppm, the NOEL was 500 ppm (31.8 and 40.5 mg/kg/day, m/f and the
LOEL was 7,000 ppm (466 and 588 mg/kg/day, m/f) based on decreased body
weight gains and increased rate of hepatic B-oxidation in males.
In a 90-day feeding study in mice conducted with pyrithiobac sodium
at dietary levels of 0, 10, 50, 500, 1,500 and 7,000 ppm, the NOEL was
500 ppm (83.1 and 112 mg/kg/day, m/f) and the L0EL was 1,500 ppm (263
and 384 mg/kg/day, m/f) based on increased liver weight and increased
incidence of hepatocellular hypertrophy in males and decreased
neutrophil count in females.
In a 90-day feeding study in dogs conducted with pyrithiobac sodium
at dietary levels of 0, 50, 5,000, or 20,000 ppm, the NOEL was 5,000
ppm (165 mg/kg/day) and the LOEL was 20,000 ppm (626 mg/kg/day) based
on decreased red blood cell count, hemoglobin, and hematocrit in
females and increased liver weight in both sexes.
In a 21-day dermal study with rats conducted with pyrithiobac
sodium at exposure levels of 0, 50, 500, or 1,200 mg/kg/day, the dermal
irritation NOEL was 500 mg/kg/day and the dermal irritation LOEL was
1,200 mg/kg/day. There were no systemic effects observed at this high
dose; therefore, the systemic NOEL is considered to be 1,200 mg/kg/day.
5. Chronic toxicity. A 1-year feeding study in dogs conducted with
pyrithiobac sodium at dietary levels of 0, 100, 5,000, and 20,000 ppm
resulted in a NOEL of 5,000 ppm (143 and 166 mg/kg/day, m/f) and a LOEL
of 20,000 ppm (580 and 647 mg/kg/day, m/f) based on decreases in body
weight gain and increased liver weight.
A 78-week oncogenicity study in mice was conducted with pyrithiobac
sodium at dietary levels of 0, 10, 150, 1,500 and 5,000 ppm. The
systemic
[[Page 49981]]
NOEL is 1,500 ppm (217 and 319 mg/kg/day, m/f) and the LEL is 5,000 ppm
(745 and 1,101 mg/kg/day, m/f), based on decreased body weight gain and
liver lesions. Kidney effects were also observed at 5,000 ppm; however,
these were present at low incidence and were of minimal severity and
were considered to be of only minimal biological significance.
Increased incidence of foci/focus of hepatocellular alteration was
observed in males fed 5,000 ppm diets. Increased incidences of
hepatocellular neoplasms (adenomas or adenomas plus carcinomas) were
observed only in 150 and 1,500 ppm males. The incidence of these liver
tumors was not significantly increased in the 5,000 ppm males or in
females at any dose level; the 5,000 ppm male tumor incidence was
within the historical control range.
A 2-year study in rats was conducted at dietary pyrithiobac sodium
levels of 0, 5, 25, 1,500 or 5,000 ppm for males and 0, 5, 25, 5,000 or
15,000 ppm for females. The NOEL for systemic effects was 1,500 ppm
(58.7 mg/kg/day) for males and 5,000 ppm (278 mg/kg/day) for females.
The LEL was 5,000 ppm (200 mg/kg/day for males)/15,000 ppm (918 mg/kg/
day) for females. The LEL was based on the following: decreased body
weight, body weight gain and food efficiency (for females); mild
changes in hematology and urinalysis, clinical signs indicative of
urinary tract dysfunction (both sexes); increased incidence of focal
cystic degereration in the liver and increased rate of hepatic
peroxisome beta-oxidation (males); and an increased incidence of
inflammatory and degenerative microscopic lesions in the kidney
(females). There was evidence of oncogenicity based on an increased
trend for kidney tubular combined adenoma/carcinoma in male rats and an
increased trend for kidney tubular adenomas in female rats. Although
the incidences were low, they were statistically significant. The
highest dose level tested in male rats (5,000 ppm) was considered
adequate for assessment of oncogenic potential, that in female rats
(15,000 ppm) exceeded the Maximum Tolerated Dose (MTD).
Carcinogenicity. In consideration of PP 4F4391 the HED
Carcinogenicity Peer Review Committee has previously concluded that the
available data provide limited evidence of the carcinogenicity of
pyrithiobac sodium in mice and rats and has classified pyrithiobac
sodium as a Group C (possible human carcinogen with limited evidence of
carcinogenicity in animals) in accordance with Agency guidelines
published in the Federal Register in 1986 (51 FR 33992, Sept. 24, 1986)
and recommend that for the purpose of risk characterization a low-dose
extrapolation model should be applied to the experimental animal tumor
data for quantification for human risk (Q1*). This decision
was based on liver adenomas, carcinomas and combined adenoma/carcinomas
in the male mouse and kidney tubular adenomas, carcinomas and combined
adenoma/carcinomas in the male rat. The unit risk, Q1* (mg/
kg/day)-1, of pyrithiobac sodium is 1.05 x 10-3
(mg/kg/day)-1 in human equivalents based on male kidney tumors.
6. Animal metabolism. Disposition and metabolism of pyrithiobac
sodium were tested in male and female rats using two radiolabeled forms
of pyrithiobac sodium. Either phenyl-labeled or pryimidine-labeled
compounds were administered orally at 5 or 250 mg/kg. In addition, i.v.
administration was evaluated at 5 mg/kg. Essentially all of the dose
was excreted in the urine and feces, with greater than 90% being
excreted within 48 hours. No label was detected in the expired air.
Only minute quantities of radioactivity (at or near the limit of
detection) were detected in the major organs of metabolism and
excretion. This study indicates that pyrithiobac sodium has low
toxicity and does not accumulate within the body. The major compound
eliminated in urine and feces was O-DPS (desmethyl metabolite), formed
by demethylation of the pyrimidine ring. There was evidence that
conjugation with glucuronic acid and 5-hydroxylation of the pyrimidine
ring of pyrithiobac sodium were additional minor routes of metabolism
in the rat. The ruminant metabolism of pyrithiobac sodium was studied
in lactating goats fed at a level of 15 mg/kg for 5 consecutive days,
equaling a dose greater than 1000 times the anticipated residues of
pyrithiobac sodium and its metabolites in cottonseed, and greater than
100 times the anticipated residues in cotton gin byproducts. Of the
total administered dose 76-80% was recovered in the excreta plus
cagewashes. Concentrations of radioactivity in milk, muscle, fat,
whole-blood, and plasma were negligible. Biotransformation of the
parent compound was not substantial with 90% of urine radioactivity and
40% of fecal extract corresponding to parent test substance. The major
biotransformation pathway was O-demethylation. The results of this
study indicate low potential for transfer of residues of pyrithiobac
sodium and/or its metabolites into edible tissues or milk of ruminants,
even at highly exaggerated feeding levels.
7. Metabolite toxicology. There is no evidence that the metabolites
of pyrithiobac sodium as identified in either the plant metabolism,
confined crop rotation, or animal metabolism studies are of any
toxicological significance.
i. Neurotoxicity. A 90-day rat neurotoxicity screen battery
conducted with pyrithiobac sodium resulted in a systemic no observed-
effect level (NOEL) of 7,000 ppm (466 and 588 mg/kg/day, m/f) and a
systemic lowest-observed-effect level (LOEL) of 20,000 ppm (1,376 and
1,609 mg/kg/day, m/f) based on reduced body weight gain and food
efficiency and increased liver weight. Slight reductions in hind-leg
grip strength and slightly increased foot splay in males were observed
in 20,000 ppm males. However, because these were of small magnitude,
lacked statistical significance and corresponding histopathology,
pyrithiobac sodium was not considered a neurotoxin. The NOEL for
neurotoxicity was 20,000 ppm (HDT).
ii. Endocrine effects. No special studies investigating potential
estrogenic or other endocrine effects of pyrithiobac sodium have been
conducted. However, the standard battery of required toxicology studies
has been completed and found acceptable. These include an evaluation of
the potential effects on reproduction and development, and an
evaluation of the pathology of the endocrine organs following repeated
or long-term exposure to doses that far exceed likely human exposures.
Based on these studies there is no evidence to suggest that pyrithiobac
sodium has an adverse effect on the endocrine system.
C. Aggregate Exposure
1. Dietary exposure. It is proposed that pyrithiobac sodium be
defined as the residue for enforcement purposes. Monitoring for
pyrithiobac sodium residues in field samples will provide an adequate
estimate of this compound in edible portions of treated crops.
2. Food--i. acute dietary exposure. A Tier I acute dietary exposure
analysis was conducted using the Dietary Exposure Evaluation Model
(DEEM ver. 5.10) and assuming tolerance level residues for cottonseed
oil, cottonseed meal, and a very conservative residue value of 6 parts
per billion (ppb) for all sources of dietary water. Using the acute
endpoint of 200 mg/kg from a developmental toxicity study in rats, the
margins of exposure were greater than 100,000 for all 22 population
subgroups at the 95th percentile exposure.
[[Page 49982]]
ii. Chronic dietary exposure. For purposes of assessing the
potential chronic dietary exposure under this tolerance, an estimate of
aggregate exposure is made using the proposed tolerance on cottonseed
at 0.02 ppm, cotton gin byproducts at 0.10 ppm, and a very conservative
contribution from drinking water based on GENEEC modeling. The
potential exposure is obtained by multiplying the tolerance level
residues by the consumption data which estimates the amount of
cottonseed products translated as cottonseed meal and cottonseed oil
eaten by various population subgroups. Cottonseed and cotton gin
byproducts are fed to animals, thus exposure of humans to residues of
pyrithiobac sodium might result if such residues are transferred to
meat, milk, poultry, or eggs. However, in previous consideration of PP
4F4391 CBTS has concluded that secondary residues in meat, milk,
poultry and eggs are not expected from the use of cottonseed as an
animal feed. A ruminant (goat) metabolism study further demonstrates
that residues of pyrithiobac sodium in cotton gin byproducts will not
result in secondary meat or milk residues when this commodity is fed to
livestock. There are no other established tolerances or registered uses
for pyrithiobac sodium in the United States. Based on a NOEL of 58.7
mg/kg/day, from the chronic rat toxicity study and a 100-fold safety
factor, the reference dose (RfD) is 0.58 mg/kg/day. Assuming residues
at tolerance levels and that 100% of the crop is being treated, a
theoretical maximum residue contribution (TMRC) of < 0.1="" mg/kg/day="" is="" calculated="" using="" the="" deem="" computer="" software="" (version="" 5.1,="" novigen="" sciences,="" inc.,="" 1997).="" with="" the="" above="" assumptions="" which="" clearly="" overestimate="" potential="" human="" exposure="" and="" are="" a="" most="" conservative="" assessment="" of="" risk,="" dietary="" (food)="" exposure="" to="" pyrithiobac="" sodium="" will="" utilize="" significantly="" less="" than="" 1%="" of="" the="" rfd="" for="" the="" overall="" u.s.="" population.="" for="" the="" most="" highly="" exposed="" subgroup,="" non-nursing="" infants="" less="" than="" 1="" year="" old,="" the="" tmrc="" is="" also="">< 0.1="" mg/kg/day,="" which="" is="" still="" less="" than="" 1%="" of="" the="" rfd.="" the="" unit="" risk,="">1* (mg/kg/
day)-1, of pyrithiobac sodium is 1.05 x 10-3
(mg/kg/day)-1 in human equivalents based on male kidney
tumors. Based on this upper bound potency factor (Q*), a 70-
year lifespan, and the assumption that 100% of the crop is treated with
pyrithiobac sodium, the upper-bound limit of a dietary carcinogenic
risk is calculated in the range of 1 incidence in a billion (1.0 x
10-9).
3. Drinking water . Other potential dietary sources of exposure of
the general population to pesticides are residues in drinking water.
There is no Maximum Contaminant Level established for residues of
pyrithiobac sodium. The petitioner has reported to the Environmental
Fate and Groundwater Branch of EPA (EFGWB) the results of a prospective
groundwater monitoring study conducted at a highly vulnerable site.
This study confirms the previous interim conclusions of EFGWB that
pyrithiobac sodium may not be stable enough to leach to groundwater at
most use sites, even in sandy soils. The potential for pyrithiobac
sodium to enter surface water is also very low. This is supported by
modeling done using GENEEC which under worst case conditions (100% of
area treated, long half-life, etc.) predicted peak surface water
concentrations of only 6 ppb. All environmental fate data requirements
for pyrithiobac sodium have now been satisfied and based on these
studies, the conditions of use, and worst-case modeling, the potential
for finding pyrithiobac sodium residues in drinking water is minimal.
4. Non-dietary exposure. Pyrithiobac sodium is not registered for
any use which could result in non-occupational, non-dietary exposure to
the general population.
D. Cumulative Effects
Pyrithiobac sodium is based on a new chemical class; there are no
known registered herbicides with similar structure. Therefore, EPA
should consider only the potential risks of pyrithiobac sodium in its
exposure assessment. The herbicidal activity of pyrithiobac sodium is
due to the inhibition of acetolactate synthase (ALS), an enzyme only
found in plants. ALS is part of the biosynthetic pathway leading to the
formation of branched chain amino acids. Animals lack ALS and this
biosynthetic pathway. This lack of ALS contributes to the low toxicity
of pyrithiobac sodium in animals. There is no evidence to indicate or
suggest that pyrithiobac sodium has any toxic effects on mammals that
would be cumulative with those of any other chemical.
E. Safety Determination
1. U.S. population. Based on a complete and reliable toxicity
database, the EPA has adopted an RfD value of 0.58 mg/kg/day using the
NOEL of 58.7 mg/kg/day, from the 2-year chronic toxicity study in rats
and a 100-fold safety factor. Using crop tolerance levels and assuming
100% of the crop treated, a Theoretical Maximum Residue Contribution
(TMRC) was calculated for the overall U.S. population and 22 population
subgroups. This analysis concluded that aggregate exposure to
pyrithiobac sodium will utilize significantly less than 1% of the RfD
for either the entire U.S. population or any subgroup population. The
TMRC for the most highly exposed subgroup identified as non-nursing
infants less than 1 year old was also < 0.1="" mg/kg/day.="" epa="" generally="" has="" no="" concern="" for="" exposure="" below="" 100%="" of="" the="" rfd="" because="" the="" rfd="" represents="" the="" level="" at="" or="" below="" which="" daily="" aggregate="" dietary="" exposure="" over="" a="" lifetime="" will="" not="" pose="" appreciable="" risk="" to="" human="" health.="" thus,="" there="" is="" a="" reasonable="" certainty="" that="" no="" harm="" will="" result="" from="" aggregate="" exposure="" to="" pyrithiobac="" sodium="" residues.="" the="" unit="" risk,="">1*
(mg/kg/day)-1, of pyrithiobac sodium is 1.05 x
10-3 (mg/kg/day)-1 in human equivalents based on
male kidney tumors. Based on this upper bound potency factor
(Q1*) and assuming a 70 year lifetime exposure an upper-
bound limit of a dietary carcinogenic risk is calculated in the range
of 1 incidence in a billion (1.0 x 10-9). This
indicates a negligible cancer risk.
2. Infants and children. In assessing the potential for additional
sensitivity of infants and children to residues of pyrithiobac sodium,
data from the previously discussed developmental and reproduction
toxicity studies were considered. Developmental studies are designed to
evaluate adverse effects on the developing organism resulting from
pesticide exposure during pre-natal development. Reproduction studies
provide information relating to reproductive and other effects on
adults and offspring from pre-natal and post-natal exposure to the
pesticide. Based on the weight of these data, pyrithiobac sodium was
not a reproductive toxicant. Maternal and developmental effects
(NOEL's, LOEL's) were comparable indicating no increase in
susceptibility of developing organisms. No evidence of endocrine
effects were noted in any study. FFDCA section 408 provides that EPA
may apply an additional safety factor for infants and children in the
case of threshold effects to account for pre and post-natal toxicity
and the completeness of the database. Based on current toxicological
data requirements, the database for pyrithiobac sodium relative to pre-
and post-natal effects for children is complete. The NOEL of 58.7 mg/
kg/day from the 2-year rat study with pyrithiobac sodium, which was
used to calculate the RfD, is lower than any of the NOEL's defined in
the developmental and reproductive toxicity studies with pyrithiobac
[[Page 49983]]
sodium. When the weight of these facts is considered an additional
safety factor is not warranted for developmental effects. As stated
above, aggregate exposure assessments utilized significantly less than
1% of the RfD for either the entire U.S. population or any of 22
population subgroups including infants and children. Therefore, it may
be concluded that there is reasonable certainty that no harm will
result to infants and children from aggregate exposure to pyrithiobac
sodium residues.
F. International Tolerances
There are no established Codex MRLs for pyrithiobac sodium on
cottonseed. An established Mexican tolerance for pyrithiobac sodium on
cottonseed is identical to the U.S. tolerance. Compatibility is not a
problem at this time.
[FR Doc. 97-25234 Filed 9-23-97; 8:45 am]
BILLING CODE 6560-50-F
