[Federal Register Volume 63, Number 150 (Wednesday, August 5, 1998)]
[Notices]
[Pages 41828-41835]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-20768]


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ENVIRONMENTAL PROTECTION AGENCY

[PF-817; FRL-5799-6]


Notice of Filing of Pesticide Petitions

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-817, must 
be received on or before September 4, 1998.
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. 119, 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. 119 at the 
address given above, from 8:30 a.m. to 4 p.m., Monday through Friday, 
excluding legal holidays.

FOR FURTHER INFORMATION CONTACT: The product manager listed in the 
table below:

------------------------------------------------------------------------
                                   Office location/                     
        Product Manager            telephone number          Address    
------------------------------------------------------------------------
Hoyt Jamerson.................  Rm. 268, CM #2, 703-    1921 Jefferson  
                                 308-9368, e-            Davis Hwy,     
                                 mail:<a href="/cdn-cgi/l/email-protection" class="__cf_email__" data-cfemail="ed878c80889f9e8283c385829499ad889d">[email protected]</a>   Arlington, VA  
                                 amail.epa.gov.                         
Cynthia Giles-Parker..........  Rm. 247, CM #2, 703-                    
                                 305-7740, e-                           
                                 mail:<a href="/cdn-cgi/l/email-protection#63040a0f06104e691302110806114d001a0d170b0a02230613020e020a690f4d0613024d040c15">giles-
<span class="__cf_email__" data-cfemail="4939283b222c3b672a30273d212028092c3928242820">[email protected]</span>
l.epa.gov</a>.                             
Jim Tomopkins.................  Rm. 239, CM #2, 703-    Do.             
                                 305-5697,e-                            
                                 mail:<a href="/cdn-cgi/l/email-protection#b3c7dcdec3d8daddc09dd9dadef3d6c3d2b9ded2dadf9dd6c3d29dd4dcc5"><span class="__cf_email__" data-cfemail="3642595b465d5f5845185c5f5b76534657">[email protected]</span>
mail.epa.gov</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 support 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-817] (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#224d52520f464d41494756624752434f434b4e0c4752430c454d54"><span class="__cf_email__" data-cfemail="ed829d9dc089828e868899ad889d8c808c8481c3889d8cc38a829b">[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 (insert docket number) 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: July 15, 1998.

James Jones,

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

[[Page 41829]]

measurement of the pesticide chemical residues or an explanation of why 
no such method is needed.

1. BASF Corporation

PP 6F4695

     EPA has received a pesticide petition (PP 6F4695) 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, 21 U.S.C. 346a(d), to amend 40 CFR part 
180 by establishing tolerances for residues of sethoxydim (2-[1-
ethoxyimino]butyl)-5-[2-(ethylthio)propyl]-3-hydroxy-2-cyclohexen-1-
one) and its metabolites containing the 2-cyclohexen-1-one moiety 
(calculated as the herbicide) in or on the raw agricultural commodities 
(RACs) grapes at 1.0 part per million (ppm), succulent beans at 15.0 
ppm, bean forage at 15.0 ppm, soybeans at 16.0 ppm, and raisins at 2.0 
ppm. BASF Corporation also requested that the established tolerances 
for raisin waste at 1.0 ppm and grape pomace (dry and wet) at 6.0 ppm 
be revoked, since they are considered insignificant animal feed 
commodities and are no longer of regulatory concern.

PP 4F4075

     EPA has received a pesticide petition (PP 4F4075) from BASF 
Corporation, 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 tolerances for residues of sethoxydim (2-[1-
ethoxyimino]butyl)-5-[2-(ethylthio)propyl]-3-hydroxy-2-cyclohexen-1-
one) and its metabolites containing the 2-cyclohexen-1-one moiety 
(calculated as the herbicide) in or on the raw agricultural commodities 
(RACs) rice grain at 0.1 ppm, rice straw at 0.5 ppm, rice hulls at 0.2 
ppm, and rice bran at 0.2 ppm.

2. Interregional Research Project Number 4 (IR-4)

PP 6E4753, 6E4725, 6E4698, 6E4697

    EPA has received pesticide petitions (PP 6E4753, 6E4725, 6E4698, 
and 6E4697) from IR-4, New Jersey Agricultural Experiment Station, 
Rutgers University, New Brunswick, New Jersey 08903 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 tolerances for 
residues of the herbicide sethoxydim (2-[1-(ethoxyimino)butyl]-5-[2-
(ethylthio)propyl]-3-hydoxy-2-cyclohexen-1-one) and its metabolites 
containing the 2-cyclohexen-1-one moiety (calculated as the herbicide)) 
in or on the raw agricultural commodities as follows:

PP 6E4753

    Petition submitted on behalf of Agricultural Experiment Stations of 
Oregon and Washington proposing tolerances for the leafy vegetable 
(except Brassica) crop group at 4.0 ppm and cilantro at 4.0 ppm. The 
petitioner also requested that established tolerances for combined 
residues of sethoxydim and its metabolites on celery at 1.0 ppm, head 
lettuce at 1.0 ppm, leaf lettuce at 2.0 ppm, spinach at 4.0 ppm, and 
endive (escarole) at 2.0 ppm be removed, since these commodities are 
members of the leafy vegetable (except Brassica) crop group.

PP 6E4725

    Petition submitted on behalf of the Agricultural Experiment 
Stations of California, Florida, Georgia, Illinois, Michigan, New York, 
Oklahoma, Oregon, South Carolina, Virginia, Washington, and Wisconsin 
proposing tolerances for the tuberous and corm vegetable subgroup at 
4.0 ppm and garden beet at 1.0 ppm. The petitioner also requested that 
established tolerances for combined residues of sethoxydim and its 
metabolites in or on potato and sweet potato at 4.0 ppm be removed, 
since these commodities are members to the tuberous and corm vegetable 
subgroup.

PP 6E4698

    Petition submitted on behalf of the Agricultural Experiment Station 
of California proposing that the existing tolerance for combined 
residues of sethoxydim and its metabolites in or on artichoke be 
increased from 3.0 ppm to 5.0 ppm

PP 6E4697

    Petition submitted on behalf of the Agricultural Experiment Station 
of Oregon proposing a tolerance for the caneberry crop subgoup at 5.0 
ppm. The petitioner also requested that the established tolerance for 
combined residues of sethoxydim and its metabolites in or on raspberry 
at 5.0 ppm be removed, since the caneberry subgroup includes raspberry.
    EPA has determined that the petitions contain 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 support granting of the 
petitions. Additional data may be needed before EPA rules on the 
petitions. This notice includes a summary of the petitions prepared by 
BASF Corporation, Agricultural Products, P.O. Box 13528, Research 
Triangle Park, NC 27709.

A. Residue Chemistry

    1. Plant metabolism. The qualitative nature of the residues in 
plants and animals is adequately understood for the purposes of 
registration. Analytical method for detecting levels of sethoxydim and 
its metabolites 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 were submitted to EPA.
    2. Analytical method. The proposed analytical method involves 
extraction, partition, and clean-up. Samples are then analyzed by gas 
chromatography with sulfur-specific flame photometric detection. The 
limit of quantitation is 0.05 ppm.

B. Toxicological Profile

    1. Acute toxicity. Based on the available acute toxicity data, BASF 
concludes that sethoxydim does not pose any acute dietary risks. A 
summary of the acute toxicity studies follows.
    i. Acute oral toxicity--Rat. Toxicity Category III; lethal dose 
(LD)<INF>50</INF>=3125 milligram/kilogram (mg/kg) (male), 2676 mg/kg 
(female)
    ii. Acute dermal toxicity-Rat. Toxicity Category III; 
LD<INF>50</INF><ls-thn-eq>5,000 mg/kg (male and female)
    iii. Acute inhalation toxicity--Rat. Toxicity Category III; lethal 
concentration (LC)<INF>50</INF> (4-hour)=6.03 mg/liter (L) (male), 6.28 
mg/L (female)
    iv. Primary eye irritation-rabbit. Toxicity Category IV; no 
irritation
    v. Primary dermal irritation-rabbit. Toxicity Category IV; no 
irritation
    vi.  Dermal sensitization- guinea pig. Waived because no 
sensitization was seen in guinea pigs dosed with the end-use product 
Poast (18% active ingedient).
    2. Genotoxicity. Ames assays were negative for gene mutation in 
Salmonella typhimurium strains TA98, TA100, TA1535, and TA 1537, with 
and without metabolic activity.
    A Chinese hamster bone marrow cytogenetic assay was negative for 
structural chromosomal aberrations at doses up to 5,000 mg/kg in 
Chinese hamster bone marrow cells in vivo.
    Recombinant assays and forward mutations tests in Bacillus 
subtilis, Escherichia coli, and S typhimurium were all negative for 
genotoxic effects at concentrations of greater than or equal to 100%.
    3. Reproductive and developmental toxicity. A developmental 
toxicity study

[[Page 41830]]

in rats fed dosages of 0, 50, 180, 650, and 1,000 mg/kg/day with a 
maternal no-observed adverse effect level (NOAEL) of 180 mg/kg/day and 
a maternal lowest effect level (LEL) of 650 mg/kg/day (irregular gait, 
decreased activity, excessive salivation, and anogenital staining); and 
a developmental NOAEL of 180 mg/kg/day, and a developmental LEL of 650 
milligram/killograms/day (mg/kg/day) (21 to 22 percent decrease in 
fetal weights, filamentous tail, and lack of tail due to the absence of 
sacral and/or caudal vertebrae, and delayed ossification in the hyoids, 
vertebral centrum and/or transverse processes, sternebrae and/or 
metatarsals, and pubes).
    A developmental toxicity study in rabbits fed doses of 0, 80, 160, 
320, and 400 mg/kg/day with a maternal no-observed effect level (NOEL) 
of 320 mg/kg/day and a maternal LOEL of 400 mg/kg/day (37% reduction in 
body weight gain without significant differences in group mean body 
weights and decreased food consumption during dosing); and a 
developmental NOEL greater than 400 mg/kg/day (highest dose tested).
    A 2-generation reproduction study with rats fed diets containing 0, 
150, 600, and 3,000 ppm (approximately 0, 7.5, 30, and 150 mg/kg/day) 
with no reproductive effects observed under the conditions of the 
study.
    4. Subchronic toxicity. A 21-day dermal study in rabbits with a 
NOAEL of <ls-thn-eq>1,000 mg/kg/day limit dose (LD). The only dose-
related finding was slight epidermal hyperplasia at the dosing site in 
nearly all males and females dosed at 1,000 mg/kg/day. This was 
probably an adaptive response.
    5. Chronic toxicity. A summary of the chronic toxicity studies 
follows.
    A 1-year feeding study with dogs fed diets containing 0, 8.86/9.41, 
17.5/19.9, and 110/129 mg/kg/day (males/females) with a NOEL of 8.86/
9.41 mg/kg/day (males/females) based on equivocal anemia in male dogs 
at the 17.5-mg/kg/day dose level.
    A 2-year chronic feeding/carcinogenicity study with mice fed diets 
containing 0, 40, 120, 360, and 1,080 ppm (equivalent to 0, 6, 18, 54, 
and 162 mg/kg/day) with a systemic NOEL of 120 ppm (18 mg/kg/day) based 
on non-neoplastic liver lesions in male mice at the 360-ppm (54 mg/kg/
day) dose level. There were no carcinogenic effects observed under the 
conditions of the study. The maximum tolerated dose (MTD) was not 
achieved in female mice.
    A 2-year chronic feeding/carcinogenic study with rats fed diets 
containing 0, 2, 6, and 18 mg/kg/day with a systemic NOEL greater than 
or equal to 18 mg/kg/day HDT. There were no carcinogenic effects 
observed under the conditions of the study. This study was reviewed 
under current guidelines and was found to be unacceptable because the 
doses used were insufficient to induce a toxic response and a MTD was 
not achieved.
    A second chronic feeding/carcinogenic study with rats fed diets 
containing 0, 360, and 1,080 ppm (equivalent to 18.2/23.0, and 55.9/
71.8 mg/kg/day (males/females). The dose levels were too low to elicit 
a toxic response in the test animals and failed to achieve a MTD or 
define a LEL. Slight decreases in body weight in rats at the 1,080-ppm 
dose level, although not biologically significant, support a free-
standing NOAEL of 1,080 ppm (55.9/71.8 mg/kg/day (males/females)). 
There were no carcinogenic effects observed under the conditions of the 
study.
    In a rat metabolism study, excretion was extremely rapid and tissue 
accumulation was negligible.
    6. Metabolite toxicology. As a condition to registration, BASF had 
been asked to submit additional toxicology studies for the 
hydroxymetabolites of sethoxydim. BASF's recommendation is to use the 
most abundant metabolite, 5-OH-MSO2, as surrogate for all metabolites. 
Based on these data, it was concluded that the toxicological potency of 
the plant hydroxymetabolites is likely to be equal to or less than that 
of the parent compound. The tolerance expression for sethoxydim 
measures sethoxydim and its metabolites containing the 2-cyclohexen-1-
one moiety, measured as parent. Hence, the hydroxymetabolites are 
figured into all tolerance calculations.
    7. Endocrine disruption. No specific tests have been performed with 
sethoxydim to determine whether the chemical may have an effect in 
humans that is similar to an effect produced by naturally-occurring 
estrogen or other endocrine effects.

C. Aggregate Exposure

    1. Dietary exposure. For purposes of assessing the potential 
dietary exposure, BASF has estimated aggregate exposure based on the 
Theoretical Maximum Residue Contribution (TMRC) from existing and 
pending tolerances for sethoxydim. (The TMRC is a ``worst case'' 
estimate of dietary exposure since it is assumed that 100% of all crops 
for which tolerances are established are treated and that pesticide 
residues are at the tolerance levels.) The TMRC from existing 
tolerances for the overall US population is estimated at approximately 
35% of the RfD. Dietary exposure to residues of sethoxydim in or on 
food from these proposed tolerances increases the TMRC by approximately 
8% of the RfD for the overall US population. BASF estimates indicate 
that dietary exposure will not exceed the RfD for any population 
subgroup for which EPA has data. This exposure assessment relies on 
very conservative assumptions that 100% of crops will contain 
sethoxydim residues and those residues would be at the level of the 
tolerance which results in an overestimate of human exposure.
    2. Food-other- exposure. Other potential sources of exposure of the 
general population to residues of pesticides are residues in drinking 
water and exposure from non-occupational sources. Based on the 
available studies submitted to EPA for assessment of environmental 
risk, BASF does not anticipate exposure to residues of sethoxydim in 
drinking water. There is no established Maximum Concentration Level 
(MCL) for residues of sethoxydim in drinking water under the Safe 
Drinking Water Act (SDWA).
    BASF has not estimated non-occupational exposure for sethoxydim. 
Sethoxydim is labeled for use by homeowners on and around the following 
use sites: flowers, evergreens, shrubs, trees, fruits, vegetables, 
ornamental groundcovers, and bedding plants. Hence, the potential for 
non-occupational exposure to the general population exists. However, 
these use sites do not appreciably increase exposure. Protective 
clothing requirements, including the use of gloves, adequately protect 
homeowners when applying the product. The product may only be applied 
through hose-end sprayers or tank sprayers as a 0.14% solution. 
Sethoxydim is not a volatile compound so inhalation exposure during and 
after application would be negligible. Dermal exposure would be minimal 
in light of the protective clothing and the low application rate. Post-
treatment (re-entry) exposure would be negligible for these use sites 
as contact with treated surfaces would be low. Dietary risks from 
treated food crops are already adequately regulated by the established 
tolerances. BASF concludes that the potential for non-occupational 
exposure to the general population is insignificant.

D. Cumulative Effects

    BASF also considered the potential for cumulative effects of 
sethoxydim and other substances that have a common mechanism of 
toxicity. BASF is aware of one other active ingredient which is 
structurally similar, clethodim. However, BASF believes that

[[Page 41831]]

consideration of a common mechanism of toxicity is not appropriate at 
this time. BASF does not have any reliable information to indicate that 
toxic effects produced by sethoxydim would be cumulative with clethodim 
or any other chemical; thus BASF is considering only the potential 
risks of sethoxydim in its exposure assessment.

E. Safety Determination

    1. U.S. population. Reference Dose (RfD) using the conservative 
exposure assumptions described above, BASF has estimated that aggregate 
exposure to sethoxydim will utilize 43% of the RfD for the U.S. 
population. EPA generally has no concern for exposures below 100% of 
the RfD. Therefore, based on the completeness and reliability of the 
toxicity data, and the conservative exposure assessment, BASF concludes 
that there is a reasonable certainty that no harm will result from 
aggregate exposure to residues of sethoxydim, including all anticipated 
dietary exposure and all other non-occupational exposures.
    2. Infants and children--i. developmental toxicity. Developmental 
toxicity was observed in a developmental toxicity study using rats but 
was not seen in a developmental toxicity study using rabbits. In the 
developmental toxicity study in rats a maternal NOAEL of 180 mg/kg/day 
and a maternal LEL of 650 mg/kg/day (irregular gait, decreased 
activity, excessive salivation, and anogenital staining) was 
determined. A developmental NOAEL of 180 mg/kg/day and a developmental 
LEL of 650 mg/kg/day (21 to 22% decrease in fetal weights, filamentous 
tail and lack of tail due to the absence of sacral and/or caudal 
vertebrae, and delayed ossification in the hyoids, vertebral centrum 
and/or transverse processes, sternebrae and/or metatarsals, and pubes). 
Since developmental effects were observed only at doses where maternal 
toxicity was noted, BASF concludes that the developmental effects 
observed are believed to be secondary effects resulting from maternal 
stress.
    ii. Reproductive toxicity. A 2-generation reproduction study with 
rats fed diets containing 0, 150, 600, and 3,000 ppm (approximately 0, 
7.5, 30, and 150 mg/kg/day) produced no reproductive effects during the 
course of the study. Although the dose levels were insufficient to 
elicit a toxic response, the Agency has considered this study usable 
for regulatory purposes and has established a free-standing NOEL of 
3,000 ppm (approximately 150 mg/kg/day) (ref. Proposed Rule 60 FR 
13941).
    iii. Reference dose. Based on the demonstrated lack of significant 
developmental or reproductive toxicity BASF believes that the RfD used 
to assess safety to children should be the same as that for the general 
population, 0.09 mg/kg/day. Using the conservative exposure assumptions 
described above, BASF has concluded that the most sensitive child 
population is that of children ages 1 to 6. BASF calculates the 
exposure to this group to be approximately 85% of the RfD for all uses 
(including those proposed in this document). Based on the completeness 
and reliability of the toxicity data and the conservative exposure 
assessment, BASF concludes that there is a reasonable certainty that no 
harm will result to infants and children from aggregate exposure to the 
residues of sethoxydim, including all anticipated dietary exposure and 
all other non-occupational exposures.

F. International Tolerances

    A maximum residue level has not been established for sethoxydim on 
artichoke, caneberry, leafy vegetables (except Brassica), root and 
tuber vegetables, cilantro, grapes, succulent beans, bean forage, 
soybeans or raisins by the Codex Alimentarius Commission. Individual 
countries have established tolerances on beans ranging from 0.1 to 5.0 
ppm and soybeans ranging from 0.05 ppm to 5.0 ppm. No tolerances have 
been established for grapes in other countries. The proposed tolerances 
for leafy vegetables (except Brassica), cilantro, and root and tuber 
vegetables at 4.0 ppm are consistent with the international tolerances 
as they fall within the range of established tolerances and reflect the 
differences in application parameters and conditions (e.g., application 
rate, pre-harvest intervals, and environmental conditions). (Hoyt 
Jamerson).

3. K-I Chemical U.S.A., Inc.

PP 8F4941

    EPA has received a pesticide petition (PP8F4941) from K-I Chemical 
U.S.A., Inc., Westchester Financial Center, 11 Martine Avenue, 9th 
Floor, White Plains, NY 10606 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 
cyclohexanecarboxylic acid, 3, 5-dioxo-4-(1-oxopropyl)-, ion(1-), 
calcium, calcium salt in or on the raw agricultural commodity peanut 
nutmeat and hay at 0.8 and 0.4 ppm respectively. 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 metabolism in plants (peanuts) is 
adequately understood.
    2. Analytical method. The proposed analytical method involves 
homogenization, extraction, filtration, partition and cleanup, 
methylation and analysis by a gas chromatography system with a mass 
selective detector. The limit of quantitation is 0.05 ppm.
    3. Magnitude of residues. Peanut trials were conducted with 
prohexadione calcium in the principle peanut growing regions of the 
country (NC, SC, GA, AL, FL, OK, TX). Prohexadione calcium was applied 
to peanuts 3- times at the rate of 0.125 lbs ai/A. Peanut hay and 
nutmeat were analyzed for residues of prohexadione (free acid). 
Prohexadione residues in the nutmeat ranged from <0.05 to 0.30 ppm. 
Residues in hay ranged from <0.05 to 0.26 ppm. A study was conducted to 
determine the level of prohexadione calcium derived resides in or on 
processed commodites.
    The proposed tolerance for prohexadione calcium in/on peanut 
nutmeat is 0.8 ppm and it is calculated by converting the highest 
peanut nutmeat RAC ppm for prohexadione (0.3 ppm) to prohexadione 
calcium equivalents (0.36 ppm), correcting for 50% storage stability 
loss (0.72), and rounding up to 0.8 ppm. The proposed tolerance for 
prohexadione calcium in/on peanut hay is 0.4 ppm and it is calculated 
by converting the highest peanut hay RAC ppm for prohexadione (0.26 
ppm) to prohexadione calcium equivalents (0.31 ppm) and rounding up to 
0.4 ppm.
    Peanut samples treated at an exaggerated rate were processed into 
peanut meal and refined oil. Peanut nutmeat and processed commodities 
were analyzed for prohexadione. Residues in the meal were less than in 
the nuts, and no residues were detected in the refined oil. Therefore, 
there was no concentration of prohexadione residues in processed 
commodities.

B. Toxicological Profile

    1. Acute toxicity. Based on available acute toxicity data 
prohexadione calcium does not pose any acute toxicity risks. The acute 
toxicity studies place technical prohexadione calcium in

[[Page 41832]]

acute toxicity category III for acute dermal; and in acute toxicity 
category IV for acute oral, acute inhalation, eye irritation, and skin 
irritation and the technical material is not a skin sensitizer.
    2. Genotoxicty. Ames Test (1 Study; point mutation): Negative; In 
Vitro V79 Cells CH/HGPRT Locus Mammalian Cell Mutation Assay (1 Study; 
point mutation): Negative; In Vitro CHO Cytogenetic Assay (1 Study; 
Chromosome Damage): Negative; In Vivo Mouse Micronucleus (1 Study; 
Chromosome Damage): Negative; In vivo Rat Bone Marrow Cytogenetic Assay 
(1 Study; Chromosomal Damage): Negative; Rec Assay (1 Study; DNA damage 
and repair): Negative; In Vitro Rat Hepatocyte (1 Study; DNA damage and 
repair): Negative.
    Prohexadione calcium has been tested in a total of 7 genetic 
toxicology assays consisting of in vitro and in vivo studies. Based on 
the results described above, it can be stated in summary that 
prohexadione calcium did not show any mutagenic activity when tested 
under the conditions of the studies mentioned above. Therefore, 
prohexadione calcium does not pose a mutagenic hazard to humans.
    3. Reproductive and developmental toxicity-developmental toxicity-- 
i. Rat. A developmental study was conducted via oral gavage in rats 
with dosages of 0, 100, 300, and 1,000 higest dose tested (HDT) mg/kg/
day with a No-Adverse-Effect Level (NOAEL) of 1,000 mg/kg/day the HDT 
for developmental and maternal toxicity based on the fact that no 
effects were observed for any test parameter measured in this study. 
Therefore, these NOAEL values are significantly higher than the NOAEL 
from the 1-year feeding study in dogs used to establish the RfD.
    ii. Rabbit. A developmental study was conducted via oral gavage in 
rabbits with dosages of 0, 40, 200, and 750 (HDT) mg/kg/day with a 
development toxicity NOAEL of 40 mg/kg/day and a maternal toxicity 
NOAEL of 40 mg/kg/day based on the following: (a) Excessive maternal 
mortality of 4/20 and 16/20 was observed in the 200 and 750 mg/kg/day 
dose levels tested, respectively; (b) significant weight loss was 
similarly observed in the 200 and 750 mg/kg/day dose group with 
accompanying clinical signs; (c) microscopic findings in the 750 mg/kg/
day dose group revealed stomach erosion and lung congestion in many of 
the animals that died; (d) in the 40 mg/kg/day dose group a single 
rabbit lost its righting reflex and showed splayed limbs on day 25 due 
to a back injury it sustained; and (e) no teratogenic effects, as well 
as incidence of malformations and developmental effects were observed 
at any dose level tested (DLT), however due to the mortality seen in 
the 200 and 750 mg/kg/day dose groups and limited number of fetuses 
produced at these dose levels, an additional study was performed. (It 
should be noted that a oral gavage range-finding study of six rabbits 
per dose level was performed at dose levels of 0, 100, 250, 500, and 
1,000 mg/kg/day, in which similar excessive mortality was observed in 
the 500 and 1,000 mg/kg/day dose groups test as shown above. 
Additionally, body weight was affected for all dose groups tested and 
the clinical signs and macroscopic findings observed in the study 
discussed above were also noted in the range-finding study. However, 
body weight gain (BWG) was not affected in the lowest dose group 
tested.)
    The doses selected for the additional teratology study in the same 
strain of rabbits were 0, 30,75, and 150 mg/kg/day with a development 
toxicity NOAEL of 150 mg/kg/day and a maternal toxicity NOAEL that 
could not be determined in this study based on the following: (a) one 
low-, two mid-, and three high-dose animals died prior to cesarean 
section on day 29, however, at the high dose group one cause of death 
was determined to be due to gavage error during test substance 
administration, another dam in this dose level died as a result of 
pneumonia, and all other deaths could not be determined; (b) at 
cesarean section one to three animals/test group were found to be not 
pregnant, but this was not considered to be dose related; (c) as a 
result of the unusual sex ratio in the control group, a statistically 
significant change in sex distribution was found at the low dose group 
level, however, these finding in b and c were not dose dependent and 
were considered to be within the range of historical control data of 
this laboratory, they were not regarded as treatment related; and (d) 
no teratogenic effects, as well as incidence of malformations and 
developmental effects were observed at any dose level tested, however 
due to the inconsistent mortality (0 (control)-1-2-1) seen at all 
treated dose levels, an additional study with a range-finder was 
performed at a different independent laboratory.
    An oral range-finding gavage teratology study in the same strain of 
rabbits (5 animals/dose level) was examined in another independent 
laboratory. The dose levels selected were 0, 20,100, 250, 500, and 1000 
mg/kg/day. The finding in this study consist of the following: (a) one 
animal died in the 500 and 1,000 mg/kg/day dose groups, however, the 
animal which died in the 500 mg/kg/day dose group was due to 
administration error detected after necropsy; (b) no clinical signs 
were noted and body weights was unaffected throughout gestation, 
however, bwg and food consumption was effected temporarily from 250 mg/
kg/day onwards during the early stages of test substance administration 
(day 6 to 9 of gestation); (c) the number of viable fetuses and fetal 
weights were unaffected; and (d) no teratogenic effects, as well as 
incidence of malformations and developmental effects were observed at 
any dose level tested.
    Based on these results the dose levels selected for the main study 
at this independent laboratory were 0, 30, 100, and 350 mg/kg/day with 
a development toxicity NOAEL of 350 mg/kg/day and a maternal toxicity 
NOAEL of 100 mg/kg/day based on the following: (a) clinical signs were 
restricted to premature delivery in 2 dams at the 350 mg/kg/day dose 
level; (b) average body weights and food intake was not affected at any 
dose levels tested, however, body weight gain was temporarily affected 
at the beginning of test substance administration period at the high 
dose group level; and (c) no teratogenic effects, as well as incidence 
of malformations and developmental effects were observed at any dose 
level tested.
    4. Conclusions from the teratology studies. Conflicting results 
have been reported from one laboratory (initial laboratory) at 
comparable dose levels using the same study protocol with respect to 
maternal toxicity in New Zealand White rabbits. The conclusion from the 
second study that maternal toxicity is obvious by effects on body 
weight during test substance administration and the death of one out of 
20 does at the low dose level (30 mg/kg/day) does not appear to be 
plausible because:
    i. Mortalities in this study showed no dose depended trend (O 
(control)-l-2-1). The cause of death of the other four animals 
including the one of the 30 mg/kg body weight group remained 
undetermined even after necropsy. Typical treatment related signs 
(gastric lesions) as described at high doses in range-finding or main 
studies were not reported. Furthermore no mortality was observed up to 
350 mg/kg/day (approximately 12-fold the NOAEL of 30 mg/kg in question) 
in a collective of 54 dams (three test groups) of the same strain of 
rabbits under comparable experimental conditions in the independent 
different laboratory.

[[Page 41833]]

    ii. The effect on body weight gain showed no statistical 
significance at 30 mg/kg body weight and the standard deviation was 
high. In addition, at the dose of 40 mg/kg/day there was no effect in 
the same strain of rabbits examined by the same laboratory in a 
previous study and no effect on body weight, body weight gain or food 
consumption were noted at doses of 30 or 100 mg/kg/day in a study 
performed in the same animal strain by the independent laboratory.
    Thus the following overall NOAELs can be derived for the teratology 
studies:
    a. NOAEL maternal toxicity. 100 mg/kg body weight (rabbit) and 
1,000 mg/kg body weight (rat).
    b.  NOAEL prenatal toxicity. 100 mg/kg body weight (rabbit) and 
1000 mg/kg body weight (rat).
    The overall NOAEL on maternal toxicity in rabbits is based on the 
independent laboratory rabbit study due to reduction of bwg and food 
intake at dose levels of 250 mg/kg body weight onwards.
    The NOAEL (100 mg/kg body weight) for prenatal toxicity in rabbits 
is based on abortions observed at doses equal or above 200 mg/kg body 
weight. The NOAEL for malformations and other developmental effects is 
even higher (350 mg/kg body weight). Due to excessive lethality of dams 
at doses above this value, no evaluation of fetuses was possible. No 
teratogenic effects have been observed up to the HDT of 350 mg/kg BW 
which could be evaluated for developmental effects.
    The teratogenicity study in rabbits resulted in a developmental 
toxicity NOAEL of 100 mg/kg and a maternal toxicity NOAEL of 100 mg/kg. 
These NOAEL values are higher than the NOAEL from the 1-year feeding 
study in dogs used to establish the RfD.

B. Reproductive Toxicity

    A 2-generation reproduction study with rats fed dosages of 0, 500, 
5,000, and 50,000 ppm with a reproductive/developmental NOAEL of 50,000 
ppm and a maternal/parental/offspring toxicity NOAEL of 500 ppm based 
on the following: (1) mortalities were noted for two mid-dose males 
(week 7 or 11), two males and one female of the high-dose (week 1), and 
one female died on gestation day 13 without visible abnormalities prior 
to death; (2) in the high-dose parental F0 and F1 statistically 
significant decreased body weights and increased water consumption was 
observed; (3) in the mid-dose level similar reduced body weights were 
observed in the F1 offspring and F1 parents and with increased water 
consumption being seen in the F0 and F1 animals; (4) for both high-dose 
generations, offspring growth was slightly reduced; (5) microscopic 
lesions in the glandular and non-glandular stomach consisting of 
papillary ancadthosis, diffuse ancanthosis, and hyperkeratosis were 
observed in male and female rats of the mid-dose and high-dose levels 
tested with slight progression of severity from the mid- to upper dose 
level; and (6) no effects on reproductive or fertility parameter was 
observed for any dose group tested.
    Therefore, these NOAEL values are similar for maternal toxicity and 
significantly higher for reproductive effects (above the limit dose of 
1,000 mg/kg/day) than the NOAEL from the 1-year feeding study in dogs 
used to establish the RfD.
    1. Subchronic toxicity-- teratology-- Rat. A developmental study 
was conducted via oral gavage in rats with dosages of 0, 100, 300, and 
1,000 HDT mg/kg/day with a NOAEL of 1,000 mg/kg/day the HDT for 
developmental and maternal toxicity based on the fact that no effects 
were observed for any test parameter measured in this study.
    2. Teratology-- Rabbits. A developmental study was conducted via 
oral gavage in rabbits with dosages of 0, 40, 200, and 750 (HDT) mg/kg/
day with a development toxicity NOAEL of 40 mg/kg/day and a maternal 
toxicity NOAEL of 40 mg/kg/day based on the following: (a) excessive 
maternal mortality of 4/20 and 16/20 was observed in the 200 and 750 
mg/kg/day dose levels tested, respectively; (b) significant weight loss 
was similarly observed in the 200 and 750 mg/kg/day dose group with 
accompanying clinical signs; (c) microscopic findings in the 750 mg/kg/
day dose group revealed stomach erosion and lung congestion in many of 
that animals that died; (d) in the 40 mg/kg/day dose group a single 
rabbit lost its righting reflex and showed splayed limbs on day 25 due 
to a back injury it sustained; and (e) no teratogenic effects, as well 
as incidence of malformations and developmental effects were observed 
at any dose level tested, however due to the mortality seen in the 200 
and 750 mg/kg/day day dose groups and limited number of fetuses 
produced at these dose levels, an additional study was performed. (It 
should be noted that an oral gavage range-finding study of six rabbits 
per dose level was performed at dose levels of 0, 100, 250, 500, and 
1,000 mg/kg/day, in which similar excessive mortality was observed in 
the 500 and 1,000 mg/kg/day dose groups test as shown above. 
Additionally, body weight was affected for all dose groups tested and 
the clinical signs and macroscopic findings observed in the study 
discussed above were also noted in the range-finding study. However, 
body weight gain was not affected in the lowest dose group tested.)
    The doses selected for the additional teratology study in the same 
strain of rabbits were 0, 30, 75, and 150 mg/kg/day with a development 
toxicity NOAEL of 150 mg/kg/day and a maternal toxicity NOAEL that 
could not be determined in this study based on the following: (a) one 
low-, two mid-, and three high-dose animals died prior to cesarean 
section on day 29, however, at the high dose group one cause of death 
was determined to be due to gavage error during test substance 
administration, another dam in this dose level died as a result of 
pneumonia, and all other deaths could not be determined; (b) at 
cesarean section one to three animals/test group were found to be not 
pregnant, but this was not considered to be dose related; (c) as a 
result of the unusual sex ratio in the control group, a statistically 
significant change in sex distribution was found at the low dose group 
level, however, these finding in (b) and (c) were not dose dependent 
and were considered to be within the range of historical control data 
of this laboratory, they were not regarded as treatment related; and 
(d) no teratogenic effects, as well as incidence of malformations and 
developmental effects were observed at any dose level tested, however 
due to the inconsistent mortality (0 (control)-1-2-1) seen at all 
treated dose levels, an additional study with a range-finder was 
performed at a different independent laboratory.
    An oral range-finding gavage teratology study in the same strain of 
rabbits (5 animals/dose level) was examined in another independent 
laboratory. The dose levels selected were 0, 20, 100, 250, 500, and 
1000 mg/kg/day. The finding in this study consist of the following: (a) 
one animal died in the 500 and 1,000 mg/kg/day dose groups, however, 
the animal which died in the 500 mg/kg/day dose group was due to 
administration error detected after necropsy; (b) no clinical signs 
were noted and body weights was unaffected throughout gestation, 
however, body weight gain and food consumption was effected temporarily 
from 250 mg/kg/day onwards during the early stages of test substance 
administration (day 6 to 9 of gestation); (c) the number of viable 
fetuses and fetal weights were unaffected; and (d) no teratogenic 
effects, as well as incidence of malformations and developmental

[[Page 41834]]

effects were observed at any dose level tested.
    Based on these results the dose levels selected for the main study 
at this independent laboratory were 0, 30, 100, and 350 mg/kg/day with 
a development toxicity NOAEL of 350 mg/kg/day and a maternal toxicity 
NOAEL of 100 mg/kg/day based on the following: (1) clinical signs were 
restricted to premature delivery in 2 dams at the 350 mg/kg/day dose 
level; (2) average body weights and food intake was not affected at any 
dose levels tested, however, body weight gain was temporarily affected 
at the beginning of test substance administration period at the high 
dose group level; and (3) no teratogenic effects, as well as incidence 
of malformations and developmental effects were observed at any dose 
level tested.
    3. Conclusions from the teratology studies. i. Conflicting results 
have been reported from one laboratory (initial laboratory) at 
comparable dose levels using the same study protocol with respect to 
maternal toxicity in New Zealand White rabbits. The conclusion from the 
second study that maternal toxicity is obvious by effects on body 
weight during test substance administration and the death of one out of 
20 does at the low dose level (30 mg/kg/day) does not appear to be 
plausible because: i. Mortalities in this study showed no dose depended 
trend (O (control)-l-2-1). The cause of death of the other four animals 
including the one of the 30 mg/kg body weight group remained 
undetermined even after necropsy. Typical treatment related signs 
(gastric lesions) as described at high doses in range-finding or main 
studies were not reported. Furthermore no mortality was observed up to 
350 mg/kg/day (approximately 12-fold the NOAEL of 30 mg/kg in question) 
in a collective of 54 dams (three test groups) of the same strain of 
rabbits under comparable experimental conditions in the independent 
different laboratory.
    ii. The effect on BWG showed no statistical significance at 30 mg/
kg body weight and the standard deviation was high. In addition, at the 
dose of 40 mg/kg/day there was no effect in the same strain of rabbits 
examined by the same laboratory in a previous study and no effect on 
body weight, BWG or food consumption were noted at doses of 30 or 100 
mg/kg/day in a study performed in the same animal strain by the 
independent laboratory.
    iii. Thus the following overall NOAELs can be derived for the 
teratology studies:
    iv. NOAEL maternal toxicity. 100 mg/kg body weight (rabbit) and 
1,000 mg/kg body weight (rat).
    v. NOAEL prenatal toxicity. 100 mg/kg body weight (rabbit) and 
1,000 mg/kg body weight (rat).
    The overall NOAEL on maternal toxicity in rabbits is based on the 
independent laboratory rabbit study due to reduction of BWG and food 
intake at dose levels of 250 mg/kg body weight onwards.
    The NOAEL (100 mg/kg body weight) for prenatal toxicity in rabbits 
is based on abortions observed at doses equal or above 200 mg/kg body 
weight. The NOAEL for malformations and other developmental effects is 
even higher (350 mg/kg body weight). Due to excessive lethality of dams 
at doses above this value, no evaluation of fetuses was possible. No 
teratogenic effects have been observed up to the highest dose level of 
350 mg/kg body weight which could be evaluated for developmental 
effects.
    4. Chronic toxicity. Based on review of the available data, the 
Reference Dose (RfD) for prohexadione calcium will be based on a 1-year 
feeding study in dogs with a threshold NOAEL of 20 mg/kg/day. Using an 
uncertainty factor of 100, the RfD is calculated to be 0.2 mg/kg/day. 
The following are summaries of studies submitted to EPA.
    i. Chronic feeding - Nonrodent. A 1-year feeding study in dogs fed 
dosages of 0, 20, 200, or 1,000 mg/kg/day (HTD) with a NOAEL of 20 mg/
kg/day for female and male dogs based on the following effects: (a) 
clinical signs consisting of pale colored feces were observed with the 
highest incidence being recorded at HDLT; (b) slightly reduced clinical 
chemical values were observed in high dose male and female dogs for 
serum albumin and potassium and increased phosphorus levels for both 
male and female dogs of the HDT; (c) red blood cell parameters (packed 
cell volume, hemoglobin, and red blood cell count) were slightly lower 
at the HDT for males and females dogs, only red blood cell counts were 
reduced in the male and female dogs at the 200 mg/kg/day dose level in 
week 52; and (d) histopathological examination revealed dilated/
basophilic renal cortical tubules with and without fibrosis in both 
male and female dogs at the 200 and 1,000 mg/kg/day dose levels.
    ii. Chronic feeding/oncogenicity -- Rats. A combined chronic/
oncogenicity in rats (Fischer 344) fed dosages of 0, 18, 94, 469, and 
968 mg/kg/day for male rats and 0, 22, 114, 572, and 1,180 mg/kg/day 
for female rats with a NOAEL of 94 mg/kg/day for male rats and 114 mg/
kg/day for female rats based on the following effects: (a) decreased in 
body weights were observed in both male and female rat at the 968 and 
1,180 mg/kg/day DLT; (b) clinical chemical effects (i.e., lower 
potassium, bilirubin, and glucose levels) were observed in male and 
female rats at the 968 and 1,180 mg/kg/day DLT, in the 469 mg/kg/day 
dose level, reduced glucose levels were only seen in the males, and 
increased albumin/globulin ratios, sodium, chloride and calcium levels 
were observed only in the 1,180 mg/kg/day dose level in females; (c) 
increased urine volumes and lower specific gravity were observed in the 
mid-high and high-dose groups for both male and female rats; (d) minor 
changes in organ weights were noted for animals of the high dose group 
only, which consisted of increased relative liver, adrenal and kidney 
weights, the latter also absolute in females only, at week 26; at the 
end of the study decreased liver weights and increased relative brain 
and testis weights were noted and these changes were considered to be 
associated with the decreased body weights; (e) macroscopic finding 
revealed an increase of pituitary nodules in the high dose group tested 
for male and female rats which was not confirmed histopathologically 
and submucosal ectopic tissue in the glandular stomach was found in 
both male and female rats in the highest dose levels that was confirmed 
by histopathology which showed an increase of squamous cell hyperplasia 
in males and of basal cell hyperplasia in the forestomach at this dose 
level; (f) a higher incidence of cellular hyperplasia was observed in 
the thyroid in the mid-high and high dose levels for male and female 
rats; and (g) no increased incidence of neoplasms occurred at any dose 
levels tested in this study.
    iii. Oncogenicity - Mice. A carcinogenicity study in B6C3F1 mice 
fed dosages of 0, 55, 279, 2,847, and 5,911 mg/kg/day for male mice and 
0, 68, 351, 3,489, and 7334 mg/kg/day for female mice with a NOAEL of 
279 mg/kg/day for male mice and 351 mg/kg/day for female mice based on 
the following effects: (a) statistically significant decreases in body 
weights were observed in male mice at the 2,847 and 5,911 mg/kg/day 
dose levels and in female mice at the 7,334 mg/kg/day dose levels 
tested; (b) a variety of changes in hematological parameter was noted 
in the respective investigations at weeks 52, 78, and 104, however, 
most of the changes were not dose related or consistent over time; (c) 
increased absolute and/or relative heart, brain, testes, liver, ovary, 
and kidney weights

[[Page 41835]]

were observed in the mid-high and highest dose group test with a slight 
progression of severity to the highest dose group tested; (d) a higher 
incidence of splenomegaly was observed only in the male mice of the 
highest dose group; (e) histopathological examinations revealed an 
ectopic proliferation of the mucosal and glandular epithelium in the 
submucosal layer of the glandular stomach in male and female mice in 
the highest dose group tested, these changes were assessed to represent 
heteroplastic, ectopic proliferative changes accompanied by lumen 
dilatation and cytological degeneration; (f) a higher incidence of 
hyperkeratosis of the forestomach was observed in both male and female 
mice and hyperplasia of the squamous epithelium of the forestomach of 
female male mice was observed in the highest dose group tested; (g) 
vacuolic changes in the exocrine pancreas of the high dose female was 
observed; (h) no increased incidence of neoplasms occurred at any dose 
levels tested in this study.
    iv. Carcinogenicity. Prohexadione calcium was shown to be non-
carcinogenic in mice, rats, and dogs. Therefore, based on the results 
of the carcinogenicity studies in mice, rats, and dogs and the results 
of genotoxicity testing, the threshold approach to regulating 
prohexadione calcium is appropriate
    5. Animal metabolism. The metabolism in animals (goats and poultry) 
is adequately understood.
    6. Endocrine disruption. No specific tests have been conducted with 
prohexadione calcium to determine whether the chemical may have an 
effect in humans that is similar to an effect produced by a naturally 
occurring estrogen or other endocrine effects. However, there were no 
significant findings in other relevant toxicity studies, i.e., 
teratology and multi-generation reproductive studies, which would 
suggest that prohexadione calcium produces endocrine related effects.

C. Aggregate Exposure

    1. Dietary exposure. For purposes of assessing the potential 
dietary exposure, K-I has estimated aggregate exposure based on the 
Theoretical Maximum Residue Contribution (TMRC) from the proposed 
tolerance for prohexadione calcium in/on peanut nutmeat at 0.8 ppm. The 
TMRC is a ``worse case'' estimate of dietary exposure since it is 
assumed that 100% of all crops for which tolerances are established are 
treated and that pesticide residues are always found at the tolerance 
levels. Dietary exposure to residues of prohexadione calcium in or on 
food will be limited to residues on peanut nutmeat. Peanut hay and meal 
are fed to animals; thus exposure of humans to residues in peanut hay 
and meal might result if such residues carry through to meat, milk, 
poultry, or eggs. However, K-I has concluded that there is no 
reasonable expectation that measurable residues of prohexadione calcium 
will occur in meat, milk, poultry, or eggs from this use. There are no 
other established U.S. tolerances for prohexadione calcium, and there 
are no currently registered uses for prohexadione calcium on food or 
feed crops in the U.S.
    Dietary exposure to residues of prohexadione calcium from the 
proposed tolerances on peanuts would account for less than 0.14% of the 
RfD (0.20 mg/kg/day) for the general population of the US and all 
subpopulation groups. The most highly exposed group in the 
subpopulation groups would be non-nursing infants (< 1 year old), which 
uses 0.39% of the RfD.
    2. Drinking water. Other potential sources of exposure to 
prohexadione calcium for the general population are residues in 
drinking water and exposure from non-occupational sources. Exposure to 
residues of prohexadione calcium in drinking water is not anticipated. 
There is no established Maximum Concentration Level (MCL) or Health 
Advisory Level (HAL) for prohexadione calcium under the Safe Drinking 
Water Act (SDWA).
    3. Non-dietary exposure. Prohexadione calcium is not currently 
registered for any nonagricultural use. The potential for non-
occupational exposure to the general population is therefore not 
present.

D. Cumulative Effects

    The potential for cumulative effects of prohexadione calcium and 
other substances that have a common mechanism of toxicity has been 
considered. No evidence or information exists to suggest that toxic 
effects produced by prohexadione calcium would be cumulative with those 
of any other chemical compound.

E. Safety Determination

    1. U.S. population-- Reference dose (RfD). Using the conservative 
exposure assumptions described above and based on the completeness and 
the reliability of the toxicity data, it has estimated that aggregate 
exposure to prohexadione calcium will utilize 0.14% of the RfD for the 
U.S. population. K-I concludes that there is a reasonable certainty 
that no harm will result from the aggregate exposure to residues of 
prohexadione calcium, including anticipated dietary exposure and non-
occupational exposures.
    2. Infants and children. Since developmental and reproductive 
toxicity occurs at levels at or above the levels shown to exhibit 
parental toxicity and since these levels are significantly higher than 
those used to calculate the RfD, K-I believes the RfD of 0.20 mg/kg/day 
is an appropriate measure of safety for infants and children.
    Using the conservative exposure assumptions described above, it is 
concluded that the portion of the RfD that will be utilized by 
aggregate exposure to residues of prohexadione calcium resulting from 
the proposed tolerances will be less than 0.14% for all populations of 
infants and children. The most highly exposed group in the 
subpopulation groups would be non-nursing infants (< 1 year old) which 
uses 0.39% of the RfD. Therefore, based on the completeness and 
reliability of the toxicity data and the conservative exposure 
assessment, it is concluded that there is a reasonable certainty that 
no harm will result to infants and children from aggregate exposure to 
the residues of prohexadione calcium, including all anticipated dietary 
exposure and all other non-occupational exposures.

F. International Tolerances

    A maximum residue level has not been established for prohexadione 
calcium by the Codex Alimentarius Commission.
[FR Doc. 98-20768 Filed 8-4-98; 8:45 am]
BILLING CODE 6560-50-F


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