[Federal Register Volume 62, Number 53 (Wednesday, March 19, 1997)]
[Notices]
[Pages 13000-13005]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-6909]



[[Page 13000]]

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ENVIRONMENTAL PROTECTION AGENCY
[PF-720; FRL-5592-6]


BASF Corporation; 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 regulations establishing tolerances for residues of 
vinclozolin [3-(3,5-di-chlorophenyl)-5-methyl-5-vinyl-1,3-oxazolidine-
2,4-dione)] and metabolites containing the 3.5-dichloroanaline moiety 
at 5.0 ppm to control Botrytis gray mold and Scelertinia white mold on 
succulent beans. In conjunction with this petition, BASF is requesting 
that the tolerances for prunes, plums, tomatoes grapes (excluding 
grapes grown for wine production) and raisins be withdrawn by the 
Agency. This notice includes a summary of the petition that was 
prepared by the petitioner, BASF Corporation.

DATES: Comments, identified by the docket number [PF-720], must be 
received on or before April 18, 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 be 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 5.1 file format or in ASCII file format. All 
comments and data in electronic form must be identified by docket 
control number [PF-720]. Electronic comments on this notice may be 
filed online at many Federal Depository Libraries. Additional 
information on electronic submissions can be found below this document.
    Information submitted as a comments 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: Connie Welch, Product Manager (PM) 21, 
Registration Division, (7505C), Office of Pesticide Programs, 
Environmental Protection Agency, 401 M. St., SW., Washington, DC. 
Office location, telephone number and e-mail address: Rm. 227, CM#2, 
1921 Jefferson Davis Highway, Arlington, VA 703-305-6226. e-mail: 
welch.connie @epamail.epa.gov.

SUPPLEMENTARY INFORMATION: EPA has received pesticide petition (PP) 
9F3762 from BASF Corporation, Agricultural Products, PO Box 13528, 
Research Triangle Park, NC 27709, proposing pursuant to section 408(d) 
of the Federal Food, Drug and Cosmetic Act (FFDCA), 21 U.S.C section 
346a (d), to amend 40 CFR part 180 by establishing tolerances for 
residues of vinclozolin [3-(3,5-dichlorophenyl)-5-methyl-5-vinyl-1,3-
oxazolidine-2,4-dione) and metabolites containing the 3,5-
dichloroanaline moiety when used as a fungicide in or on raw 
agricultural commodity succulent beans at 5.0 ppm. EPA has determined 
that the petition contains data or information 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 these data 
support granting of the petition. Additional data may be needed before 
EPA rules on the petition. The proposed analytical method is gas 
chromatography using Electron Capture detection.
    As required by section 408(d) of the FFDCA, as recently amended by 
the Food Quality Protection Act, BASF Corporation 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 BASF; EPA, as mentioned 
above, 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 may have made minor edits to the summary for the purpose 
of clarity.

I. Petition Summary

A. Plant Metabolism

    BASF Corporation notes that metabolism in plants is understood, the 
residues of concern are vinclozolin [3-(3,5-dichlorophenyl)-5-methyl-5-
vinyl-1,3-oxazolidine-2,4-dione) and metabolites containing the 3,5-
dichloroanaline moiety.

B. Analytical Method

    The proposed analytical method involves extraction, hydrolysis, 
distillation, partition, and deriviatization followed by detection of 
residues by gc/ecd. An enforcement method has been published in FDA's 
Pesticide Analytical Methods, Volume II pg. 876-887.

C. Magnitude of the Residues

    Sixteen residue trials were carried out in 7 succulent bean 
producing states; CA, FL, MI, NY, NC, OR, and WI. Residue in the 
succulent beans ranged from 0.38 to 2.40 ppm and averaged 0.83 ppm.

D. Toxicological Profile

    1. Acute Toxicity. The acute toxicity studies place technical 
vinclozolin in acute toxicity category IV for acute oral (LD50 of 
>15,000 mg/kg), and inhalation (LD50 of 29.1 mg/l) and acute 
toxicity category III for acute dermal (LD50 of >5,000 mg/kg) , eye 
(minimal) and dermal (minimal) irritation and the technical material is 
a positive skin sensitizer.
    2. Chronic Toxicity Testing.
    a. Chronic feeding Nonrodent. A 1-year feeding study in dogs fed 
dosages of 0, 1.1 , 2.4, 4.9, and 48.7 mg/kg/day with a No-Observed 
Adverse-Effect Level (NOAEL) of 2.4 mg/kg/day based on the following 
effects: (1) slight decrease in hematological and increase clinical 
chemistry values in the 48.7 mg/kg/day dose group (highest dose tested 
- (HDT)); (2) increased absolute and/or relative weights for the testes 
(male only), adrenals, liver, spleen, and thyroids in the either the 
4.9 or 48.7 mg/kg/day dose groups; and (3) a dose- related atrophy of 
the prostate in the 4.9 or 48.7 mg/kg/day dose groups; and (4) 
microscopic findings in the adrenal and testes (males) in the 48.7 mg/
kg/day dose group and liver findings for both male and female dogs in 
the 48.7 mg/kg/day dose groups and in the females in the 4.9 mg/kg/day 
dose group, only.
    b. Chronic feeding/Oncogenicity - Rats. A combination of 2 chronic 
feeding and one carcinogenicity studies that were performed separately, 
resulted in rats being fed combined dosages of 0, 1.2, 2.4, 7.0, 23, 
71, 143, and 221 mg/kg/day (males) and 0, 1.6, 3.1, 7.0, 23, 71, 180, 
and 221 mg/kg/day (females) with a NOAEL of 1.2 mg/kg/day (males) and 
1.6 mg/kg/day (females) based on the following effects: (1) decreased 
body weights in both males and female rat at

[[Page 13001]]

dose levels 23 mg/kg/day dose groups with a progression of 
severity to the upper levels; (2) decreased food consumption in both 
males and female rats at dose levels 71 mg/kg/day dose 
groups with a progression of severity to the upper dose levels; (3) 
cataracts with associative histopathology at dose levels 23 
mg/kg/day and lenticular changes at dose levels 7.0 mg/kg/
day for male and female rats; (4) hematological and clinical chemistry 
value changes at dose levels 71 mg/kg/day dose groups with 
increase of severity at the higher doses tested; (5) increased absolute 
and/or relative weights for adrenals at dose levels 143 mg/
kg/day, for the liver at dose levels 71 mg/kg/day, for the 
testes at dose levels 23 mg/kg/day, and for the ovaries at 
dose levels 143 mg/kg/day; (6) microscopic findings were 
observed in the liver, adrenal, pancreas, testes (males), ovaries and 
uterus (females) were seen in dose levels of 7.0 mg/kg/day 
with a progression of severity of histological effects in the upper 
dose levels; and (7) an increased incidence of neoplasms occurred at 
dose levels greater than the maximum tolerated dose (MTD) of 23 mg/kg/
day in the liver, adrenals, pituitary, prostate (males), uterus 
(females), and ovaries (females) at dose levels 143 mg/kg/
day. In the testes (males), neoplasms were seen slightly below the MTD 
at dose levels 7.0 mg/kg/day due the antiandrogenic nature 
of vinclozolin.
    3. Oncogenicity - Mice. An oncogenicity study in mice fed dosages 
of 0, 2.1, 20.6, 432, and 1,225 (HDT) mg/kg/day (males) and 0, 2.8, 
28.5, 557, and 1,411 (HDT) mg/kg/day (females) with a NOAEL of 20.6 mg/
kg/day (males) and 28.5 mg/kg/day (females) based on the following 
effects: (1) increased mortality in the highest dose tested (HTD) as 
compared to controls; (2) decreased body weights and significant signs 
of clinical toxicity were observed in both males and female mice at the 
upper two dose levels with a progression of severity; (3) hematological 
and clinical chemistry value changes were observed at the highest dose 
tested; (4) increased absolute and/or relative weights for adrenals and 
liver were observed at the upper two dose levels, atrophic seminal 
vesicles and coagulation glands with reduction of the prostate (males) 
and atrophic uteri were observed at the upper two dose levels; (5) 
microscopic findings were observed in the liver, adrenal, testes 
(males), ovaries and uterus (females), and related sexual organs were 
seen in the upper two dose levels; (6) an increased incidence of 
neoplasms occurred at dose levels greater than the maximum tolerated 
dose (>28.5 mg/kg/day) in the liver of female mice.
    4. Developmental Toxicity Testing
    a. Teratology - Rat. A combination of four developmental studies in 
rats via oral gavage resulted in dosages of 0, 15, 50, 100, 150, 200, 
400, 600, and 1000 (HDT) mg/kg/day with a development toxicity NOAEL of 
15 mg/kg/day and a maternal toxicity NOAEL equal to or greater than 400 
mg/kg/day based on the following: (1) no obvious signs of maternal 
toxicity were observed at dose levels less than or equal to 400 mg/kg/
day; (2) an increased number of fetus with retarded ossification of 
thoracic vertebral bodies at dose levels greater than or equal to 200 
mg/kg/day and increased number of fetus with soft tissue variations at 
dose levels greater than or equal to 400 mg/kg/day, both findings are 
regarded as unspecific embryo-/fetotoxic effects indicating transient 
delays in development but not indicative of a teratogenic effect; and 
(3) a statistical significant decrease or reduction of the anogenital 
index (AGI) in male was observed at levels greater than or equal to 50 
mg/kg/day.
    In a developmental study in rats via dermal exposure for six hours/
day on intact skin with dosages of 0, 60, 180, and 360 mg/kg/day (HDT) 
with a development toxicity NOAEL of 60 mg/kg/day and a maternal 
toxicity NOAEL of 60 mg/kg/day based on the following: (1) increased 
absolute liver weights at dose levels >180 mg/kg/day; and (2) decreased 
anogenital distance and index at dose levels >180 mg/kg/day.
    b. Teratology - Rabbits. A developmental study in rabbits via oral 
gavage resulted in dosages of 0, 20, 80, and 300 mg/kg/day (HDT) with a 
development toxicity NOAEL of 300 mg/kg/day and a maternal toxicity 
NOAEL of 300 mg/kg/day based on no signs of maternal or meaningful 
fetal toxicity were observed at any of the dose levels mentioned.
    A second developmental study in rabbits via oral gavage resulted in 
dosages of 0, 50, 200, and 800 mg/kg/day (HDT) with a development 
toxicity NOAEL of 200 mg/kg/day and a maternal toxicity NOAEL of 50 mg/
kg/day based on the following: (1) severe maternal toxicity with 
simultaneous change in hematological values changes and high number of 
abortions at the HDT; and (2) increased absolute and/or relative 
weights for adrenals in the mid and high dose groups.
    5. Reproductive Toxicity Testing
    a. Two-Generation Reproduction - Rat. A two-generation reproduction 
study (consisting of two studies: study A - dose levels of 0, 2.0 and 
4.1 mg/kg/day; study B - dose levels of 0, 4.9, 29 100, and 307 mg/kg/
day) with rats fed dosages of 0, 2.0, 4.1, 4.9, 29, 100, and 307 mg/kg/
day with a reproductive NOAEL of 4.9 mg/kg/day based on feminization of 
male and the ability not to mate at dose levels >100 mg/kg/day and pup 
effects at 29 mg/kg/day; and with a parental NOAEL of 4.9 mg/kg/day 
based on general toxicity consistent with previous rat studies at 
levels >29 mg/kg/day. Study A was performed to clarify an equivocal 
finding of decreased absolute and relative weight of the epididymides 
without any morphological correlation in the male FY and FZ generations 
in Study B. However, EPA stated ``the effects at the 4.9 mg/kg/day dose 
level was minimal and considered sufficiently close to a NOAEL. The 
study is acceptable and 4.9 mg/kg/day dose level was considered to be 
the No Observed-Effect Level (NOEL).''
    6. Mutagenicity
    A Modified Ames Test (3 studies; point mutation): Negative; Host-
Mediated Assay (point mutation): Negative; Mouse Lymphoma Test (point 
mutation): Negative; In Vitro CHO Cells (point mutation): Negative; In 
Vitro Cytogentics - CHO Cells (Chromosome Aberrations): Negative; In 
Vivo Dominant Lethal Test - Male NMRI Mouse (Chromosome 
Aberrations):Negative; Rec Assay (2 test; DNA damage and repair): 
Negative; In Vitro UDS Test Using Hepatocyte ( DNA damage and repair): 
Negative; In Vivo SCE Using Chinese Hamster ( DNA damage and repair): 
Negative
    Based on the data present and weight of evidence, BASF concludes 
that vinclozolin does not pose a mutagenic hazard to humans.
    7. Other Relevant Testing
    a. Mechanistic Studies/Mode of Action - Anti-androgenicity Activity
    A series of mechanistic studies were performed to elucidate and 
define the anti-androgenic properties of vinclozolin. The following 
conclusions can be drawn from the in vivo data:
    The anti-androgenic effects observed are not related to an 
inhibition of androgen-steroid hormone synthesis.
    The anti-androgenic effects are not related to an inhibition of 5 
alpha-reductase activity.
    The anti-androgenic effects are a result of a competitive binding 
to the androgen receptor resulting in an inactivation of this receptor.
    The anti-androgenic effects are mediated by the hydrolysis 
metabolite M1 and probably not by vinclozolin or the main metabolite, 
R8.
    The anti-androgenic effects are related to a second hydrolysis 
metabolite M2 which is a slightly more potent anti-

[[Page 13002]]

androgen than M1. However M2 concentrations are very low and the 
compound may not contribute much to the in vivo effects.
    b. Metabolism - Rat
    i. Oral studies. BASF has submitted results from a number of 
metabolism studies using wistar rats. The results of these studies can 
be summarized as follows: vinclozolin is well absorbed (@85 percent) 
and intensively metabolized, the liver playing an important role (@65 
percent of the radioactivity administered was found in the bile and no 
unchanged active ingredient was excreted in the urine). The 
determination of radioactivity in the plasma over a period of seven 
days showed that slight accumulation took place.
    ii. Dermal study. In an in vivo dermal absorption study, male 
Wistar rats were dosed with, 14C vinclozolin. Dose levels of 
0.002, 0.02, 0.2, and 2.0 mg/cm2 were administered to 24 rats per 
dose level, applied to a shaved area of approx. 13 cm2 on the back 
of the rat. Groups of 4 rats were sacrificed at 0.5, 1, 2, 4, 10, or 72 
hours following application of the dose. Urine and feces were collected 
during this period. At the end of the exposure period (10 hours in the 
case of the 72 hour treatment group), the skin site was washed with 
cotton swabs moistened with water. A blood sample was taken prior to 
sacrifice. The treated skin along with the GI tract, liver, kidneys, 
adrenals, testes, eyes, brain and carcass were subjected to radioactive 
mass balance analysis. Urine from the bladder was added to the voided 
samples. Results of this analysis showed recoveries of between 81.6-104 
percent. The lowest dose of 0.002 mg/cm2 from the 10-hour exposure 
period is considered to be the most appropriate dose for use in the 
occupational risk assessment, as this dose most closely approximates 
the dermal deposition results obtained in the worker exposure studies. 
After the 10-hour exposure the total percent absorbed at this dose 
level was 29.l percent.
    Percutaneous absorption of [14C]-vinclozolin was also assessed 
in vitro using rat and human epidermis in flow-through diffusion cells. 
The test substance was applied at two dose levels, 200 ug/cm2 
(high) and 2 ug/cm2 (low), and assessed over 24 hours. A total of 
32 samples (16 rat and 16 human) were used at the high dose level, and 
34 (17 rat and 17 human) at the low dose level. Samples of human skin 
were obtained at postmortem. Human epidermis was prepared from full 
thickness skin by immersion in water at 60 degrees Celsius for one 
minute. Rat epidermis was prepared by soaking the skin in 2M sodium 
bromide for approximately 24 hours. With respect to the worker exposure 
relevant time of eight hours, penetration through human skin was 16.7 
times less at the high dose tested and 4.2 times less at the low dose 
tested than through rat skin.

E. Threshold Effects

    The established Reference Dose (RfD) for vinclozolin is based on a 
2-year feeding study in rats with a threshold NOAEL of 1.2 mg/kg/day. 
Using an uncertainty factor of 100, the RfD is calculated to be 0.012 
mg/kg/day.

F. Non-Threshold Effects

    Vinclozolin is known to be an anti-androgenic agent, thus the 
consequence of hormonal imbalance are two-fold; the primary anti-
androgenic effect is a suppression in androgen target organs such as 
epidymides, prostate or seminal vesicle, whereas stimulation is seen in 
organs involved in steroid hormone synthesis (testes, adrenals, 
ovaries). Target organs for hormones must be able to respond to changes 
in physiological levels of hormones, which can fluctuate significantly 
as evidenced by the hormone changes during the female estrus cycle. It 
was indeed demonstrated that changes induced in these organs were be 
reversible when hormone levels return to normal concentrations. It is 
only when hormone imbalance continues over a long time that 
irreversible changes occur.
    In the case of suppression the affected organ is forced into a 
hypofunctional state. Progressively, the organ becomes hypotrophic and 
hypoplastic. With stimulation on the other hand the initial changes can 
be described as hyperfunction, hypertrophy and hyperplasia. As 
mentioned before, it is only when the hormonal imbalance continues over 
a long time that the ultimate reversible adaptation of the affected 
organ (hypoplasia or hyperplasia) is still not sufficient to handle the 
situation and only then an irreversible transition takes place. In the 
case of hormonal suppression atrophy is the ultimate consequence, in 
the case of stimulation, the ultimate consequence are tumors in the 
affected organs.
    It is thus plausible that at dose levels which do not result in 
hypertrophy/hyperplasia or hypotrophy/hypoplasia the ultimate 
consequence of these adaptive changes, i.e. tumors or-atrophy, 
respectively, cannot occur. For risk assessment purposes this mode of 
action offers the possibility to determine a threshold for both tumor 
formation and atrophy by histopathological examination of the hyper- or 
hypo-functional organ. Thus, at dose levels which do not affect these 
organs, a mechanistic NOAEL can be defined and risk assessment can be 
carried out using assessment or safety factors.
    The increase in neoplasia observed in the adrenals, ovaries and 
uterus were only seen in female rats at the high dose levels which was 
143 mg/kg/day of the chronic toxicity study and/or 
carcinogenicity study. As determined by BASF and EPA, the 71 mg/kg/day 
dose level of the rat chronic/oncogenicity toxicity study exceeded the 
criteria for a MTD. Therefore, based the physiological status of the 
animals may be deteriorated in such a way that low dose extrapolation 
of results obtained at this dose level is not possible. Similarly, the 
liver tumors arising in the mouse oncogenicity at the 1,411 mg/kg/day 
dose level in which severe body weight losses and significant mortality 
were observed, clearly exceeding the MTD (as determined by BASF and EPA 
- Cancer Peer Review Document, September, 1996) and is not relevant for 
risk assessment purposes.
    Additionally, vinclozolin is not a genotoxic agent and mechanistic 
studies have shown the increased incidence of liver tumors in male rat 
and female mice is a result of liver tumor promoting properties of the 
test substance. Vinclozolin is not an initiator of the carcinogenic 
event. Based on the available data, the mechanism of promotion is the 
induction of liver cell proliferation of the test substance. The data 
available also indicate that dose levels which do not induce liver 
toxicity also do not induce cell proliferation nor enhance the 
carcinogenic process. Therefore, BASF concludes that a threshold for 
liver carcinogenicity can be defined to be at least 143 mg/kg/day in 
the rat and at least 557 mg/kg/day in the mouse.
    Concerning the testicular tumors (Leydig cell tumors), results of 
the long-term studies with vinclozolin demonstrate that hormone-related 
carcinogenesis was only observed in rats, and with the exception of 
Leydig cell tumors only at dose levels which exceeded the MTD criteria. 
The relevance of Leydig cell tumors to men should be seen in the light 
that this is a very rare human tumor and that the precursor change 
(i.e. Leydig cell hyperplasia) has not been observed in patients 
treated with flutamide. In addition, the toxicology of cimitidine, a 
H2-receptor antagonist with anti-androgenic properties resulting in a 
size reduction and atrophy of the prostate and seminal vesicles in 
chronic rat studies. Moreover, an increase in benign Leydig cell 
tumors, and a decrease in

[[Page 13003]]

pituitary and mammary tumor incidence were noted; hence a toxicity 
potential not unlike that of vinclozolin is evident. Despite the fact 
that over 30 million patients have been treated with cimitidine, this 
therapeutic agent has been demonstrated to be extremely safe, clearly 
indicating that the rat Leydig cell tumors have very little relevance 
for humans. A similar conclusion is drawn by other investigators 
``Leydig cell tumors of the rat have limited significance because of 
the fundamental differences in testicular control mechanisms.'' It is 
therefore concluded that the observed neoplastic changes do not pose a 
relevant hazard to humans. EPA in the September, 1996, Cancer Peer 
Review Document, came to the same basic conclusion that the Leydig cell 
tumors are a very uncommon tumor type in humans which implies the 
threshold dose for humans would be greater than for rats. EPA based 
this conclusion on the work performed by Dr. C. Capen (Professor 
Charles C. Capen, Leydig Cell Tumors: Pathology, Physiology, and 
Mechanistic Considerations in Rats, The Toxicology Forum, 1994 Annual 
Summer Meeting, p. 110).
    In the EPA Carcinogenicity Peer Review Document of September 1996, 
the Agency stated ``[T]his classification of Group B2 was based on 
statistically significant increases in multiple tumor types in male 
Wistar rats and ovarian tumors in female Wistar rats at a dose which 
was excessive. The MOE approach was chosen because the tumors were 
benign at dose levels which were considered to be excessive, and there 
was little concern for mutagencity of vinclozolin. Mechanistic data for 
the Leydig cell tumors also provided further support for the use of the 
MOE approach.'' It is BASF's understanding that EPA has performed 
another Cancer Peer Review in January, 1997. This rereview is based the 
pathology peer review performed by Dr. Charles Capen (Professor of 
Pathology at The Ohio State University) concerning the criteria used in 
diagnosing the ovarian and prostate tumors seem in the chronic/
oncogenicity rat study for vinclozolin and the report of the FIFRA 
Scientific Advisory Panel (SAP) concerning vinclozolin. The data 
generated by Dr. Capen were also presented to the SAP by BASF and are a 
bases for the conclusions drawn by the Panel. BASF is awaiting the 
result of this second Cancer Peer Review.
    To further support the conclusion stated above, the most recent 
meeting of the FIFRA SAP concluded the following: (Proceeding of the 
October, 1996, meeting were issued in December, 1996)
    ``[B]ased on these data (as presented by BASF Corporation and 
EPA), it is far from established that vinclozolin is carcinogenic to 
the rat. It is not ruled out, however. In addition, there is little 
concern for mutagenicity as expressed by the Agency reviews...


    ``[B]ased on (1), we would consider the possibility that 
vinclozolin is a carcinogen in rats or mice, but the evidence for 
this is not compelling. The Panel believes that the classification 
of vinclozolin using the new guidelines would be ``not likely to be 
a carcinogenic hazard to humans...''


    ``[T]he most appropriate method of risk quantification is on a 
non-linear model, MOE approach based on a NOEL for non-neoplastic 
effects...''


    Therefore both the Agency and the SAP have agreed that vinclozolin 
should be regulated as a threshold chemical using the standard margin 
of exposure approach, BASF concurs with those opinions.

G. Aggregate Exposure

    1. Dietary exposure. For the purpose of assessing the potential 
chronic dietary exposure, BASF has estimated aggregate exposure based 
on Theoretical Maximum Residue Contribution (TMRC) for all exisiting 
tolerances and registered uses of vinclozolin including the proposed 
tolerance of vinclozolin on succulent beans at 5.0 ppm. In this 
analysis tolerance levels were used for all crops except stonefruit 
were used. In the case of stonefruit, anticipated residues based on the 
available residue data. Where reliable data were available and 
acceptable to the Agency percent crop treated was also used. This 
analysis revealed that for the general U.S. population and children - 
ages 1-6 (the most sensitive sub-population), vinclozolin treated crops 
utilized 25 percent and 45 percent, respectively, of the RfD (0.012 /
kg/day). BASF estimates that withdrawal of the tolerances in prunes, 
plums, tomatoes, grapes (except those grown for wine production) and 
raisins will reduce the percent RfD consumed by at least one-third; 
reducing the percent RfD consumed in children - ages 1-6 from 45 
percent to 30 percent and for the general population from 25 percent to 
16 percent. BASF is currently analyzing the available monitoring data 
for vinclozolin residues to determine the actual exposure to 
vinclozolin residues. Preliminary analysis indicates that no sub-
population in the United States is exposed to over 1 percent of the 
RfD.
    EPA has expressed concern for acute dietary risk in the draft RED 
for the subgroup population -women of childbearing age (13 years and 
older) due to the hormonal effects of vinclozolin.
    In response to this concern, BASF requested that Technical 
Assessment Systems, Inc. (TAS), conduct an acute dietary analysis for 
vinclozolin that used the current consumption data and exposure models 
capable of calculating a real world estimates of potential exposure to 
residues in food.
    The acute exposure analysis, utilized the principles of Tier 1 and 
Tier 3 analyzes presented to the FIFRA Science Advisory Panel in 
September, 1995, and subsequently implemented by OPP/EPA. Using 
appropriate methodology, available residue distribution data, and 
percent crop treated information it was determined the margin of 
exposure to the most sensitive sub-population exceeded 100 (the value 
generally accepted by the Agency as sufficient) at the very 
conservative 99.9th percentile of the population; when all crops having 
tolerances; plus succulent beans and cranberries were included in the 
analysis. When prunes, plums tomatoes, grapes (excluding those grown 
for wine production) and raisins were removed from the analysis, the 
margin of exposure at the 99.9th percentile was determined to be 425 
for women of childbearing age.
    2. ``Other'' Exposure. Other potential sources of potential 
exposure to vinclozolin for the general population to residues of 
vinclozolin are residues in drinking water and exposure from non-
occupational sources. For drinking water, based on the available 
environmental fate data, BASF does not anticipate routine exposure to 
residues of vinclozolin in drinking water. There is no established 
Maximum Concentration Level (MCL) or Health Advisory Level (HAL) for 
vinclozolin under the Safe Drinking Water Act (SDWA).
    For non-occupational exposure, vinclozolin is included in a number 
of formulations used for professional treatment of golf-courses and 
turf. Posting and notification procedures ensure that there is no 
exposure to the general public either during or following treatment.
    BASF has a flowable formulation containing vinclozolin which is 
available to the homeowner for use on residential lawns. Treatment 
rates (1.0 oz a.i./1,000 sq. ft.) and the number of treatments allowed 
per year are low. BASF believes that this minor use will not impact 
significantly on the aggregate exposure to vinclozolin since this use 
represents less than 0.5 percent of total vinclozolin use.

[[Page 13004]]

    Additionally, for the homeowner handler and homeowner 
postapplication, EPA has estimated these non-occupational exposure for 
vinclozolin in the draft Registration Eligibility Document issued to 
BASF on February 2, 1996. EPA stated the following:
    a. ``The MOE's for homeowners handlers were greater than 100 for 
both the low-pressure hand-held sprayer and backpack sprayer assuming 
long-sleeve shirt, long pants, shoes, and socks are worn. All homeowner 
handlers were assumed not be exposed seven days or more in a 90-day 
period and, the short-term endpoint is used in determining the MOE's. 
The Application rate for homeowners was assumed to be five gallons of 
dilute spray per day.''
    b. In a simmilar analysis for postapplication exposure for 
homeowners a margin of exposure greater than 100 was calculated based 
on a worst case analysis using strawberry data as a surrogate.
    Therefore, based on the completeness and reliability of the 
toxicity data, and the assessment discussed above, BASF concludes that 
there is a reasonable certainty that no harm will result from aggregate 
exposure to residues of vinclozolin, including all anticipated dietary 
exposure.

H. Cumulative Exposure

     BASF has considered the potential for cumulative effects of 
vinclozolin and other substances that have a common mechanism of 
toxicity. BASF is aware of two other substance active ingredients which 
are structurally similar, iprodione and procymidone. However, BASF 
believes that consideration of a common mechanism of toxicity is not 
appropriate at this time. This conclusion was similarly drawn by Rhone-
Poulenc the manufacturer of iprodione in a recent Notice of Filing for 
that compound.
    The Agency has previously noted both structural and toxicological 
similarities between iprodione, procymidone, and vinclozolin. BASF 
believes that there are clear differences in both the type and 
magnitude of effects observed after exposure to vinclozolin when 
contrasted with iprodione. BASF believes that there is no reliable data 
to indicate cumulative effects should be considered in reference to 
iprodione. As to procymidone, BASF is unaware of any conclusive data 
that would indicate a common mode of action with procymidone. It should 
also be noted that procymidone's tolerances are limited to grapes grown 
for wine production outside the United States.

I. Determination of Safety for U.S. Population

    Reference Dose (RfD): Using the exposure assumptions described 
above and the completeness and the reliability of the toxicity data, 
BASF has estimated that aggregate exposure to vinclozolin will utilize 
less than 16 percent of the RfD for the US population. EPA generally 
has no concern for exposure below 100 percent of the RfD. Therefore, 
based on the completeness and reliability of the toxicity data, and the 
exposure assessment discussed above, BASF concludes that there is a 
reasonable certainty that no harm will result from aggregate exposure 
to residues of vinclozolin, including all anticipated dietary exposure 
and all other non-occupational exposures.

J. Determination of Safety for Infants and Children

    Reference Dose: Based on the completeness of vinclozolin's 
toxicological database and the risk assessment information cited above 
BASF believes the RfD used to assess safety to children should be the 
same as that for the general population, 0.012 mg/kg/day. BASF 
concluded that the most sensitive child population group is that of 
children ages 1 to 6. BASF has calculated that the exposure to this 
group to be <30 percent of the RfD for all uses including that proposed 
in this document. Therefore, based on the completeness and reliability 
of the toxicity data, and the exposure assessment discussed above, BASF 
concludes that there is a reasonable certainty that no harm will result 
to infants and children from aggregate exposure to residues of 
vinclozolin, including all anticipated dietary exposure and all other 
non-occupational exposures.

K. Other Considerations

    The qualitative nature of the residues in plants is adequately 
understood. Residues of the parent molecule, and metabolites containing 
the 3,5-dichloroaniline moiety are the only residues of concern. There 
is a practical analytical method for detecting and measuring levels of 
vinclozolin in or on food with a limit of detection that allows 
monitoring of food with residues at or above the levels set in these 
tolerances. There has been no need to establish meat, milk, poultry or 
egg tolerances as the crops including succulent beans on which 
vinclozolin is used do not represent animal feed items.

L. International Tolerances

    A maximum residue level for succulent beans has not been 
established for vinclozolin by the Codex Alimentarius Commission.

M. Conclusions

    BASF Corporation believes that the proposed use of vinclozolin on 
snap beans would not pose a significant risk to human health, including 
that of infants and children, and is in compliance with the 
requirements of the Food Quality Protection Act of 1996. Moreover, BASF 
believes that the proposed tolerance for vinclozolin on snap beans 
should be established.

II. Public Record

    Interested persons are invited to submit comments on this notice of 
filing. Comments must bear a notation indicating the docket control 
number, [PF-720]. 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 under docket control 
number [PF-720] 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 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 notice, 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 
record which will also include all comments submitted directly in 
writing. The official record is the paper record maintained at the 
address in ``ADDRESSES'' at the beginning of this document.

    Authority: 21 U.S.C. 346a.


[[Page 13005]]



List of Subjects

    Environmental protection, Administrative practice and procedure, 
Agricultural commodities, Pesticides and pests, Reporting and 
recordkeeping.

    Dated: March 10, 1997.

Stephen L. Johnson,
Director, Registration Division, Office of Pesticide Programs.

[FR Doc. 97-6909 Filed 3-18-97; 8:45 am]
BILLING CODE 6560-50-F