[Federal Register Volume 62, Number 63 (Wednesday, April 2, 1997)]
[Notices]
[Pages 15690-15698]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-8397]


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ENVIRONMENTAL PROTECTION AGENCY
[PF-723; FRL-5593-9]


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 agricultural commodities.
DATES: Comments, identified by the docket control number PF-723, must 
be received on or before May 2, 1997.
ADDRESSES: By mail submit written comments to: Public Response and 
Program Resources Branch, Field Operations Divison (7505C), Office of 
Pesticides Programs, Environmental Protection Agency, 401 M St., SW., 
Washington, DC 20460. In person bring comments to: Rm. 1132, CM #2, 
1921 Jefferson Davis Highway, Arlington, VA.
    Comments and data may also be submitted electronically by following 
the instructions under ``SUPPLEMENTARY INFORMATION.'' No confidential 
business information should be submitted through e-mail.
    Information submitted as a comment concerning this document may be 
claimed confidential by marking any part or all of that information as 
``Confidential Business Information'' (CBI). CBI should not be 
submitted through e-mail. Information marked as CBI will not be 
disclosed except in accordance with procedures set forth in 40 CFR part 
2. A copy of the comment that does not contain CBI must be submitted 
for inclusion in the public record. Information not marked confidential 
may be disclosed publicly by EPA without prior notice. All written 
comments will be available for public inspection in Rm. 1132 at the 
address given above, from 8:30 a.m. to 4 p.m., Monday through Friday, 
excluding legal holidays.

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

------------------------------------------------------------------------
                                   Office location/                     
        Product Manager            telephone number          Address    
------------------------------------------------------------------------
Connie Welch (PM 21)..........  Rm. 227, CM #2, 703-    1921 Jefferson  
                                 305-6226, e-            Davis Hwy,     
                                 mail:welch.connie@epa   Arlington, VA  
                                 mail.epa.gov.                          
Cynthia Giles-Parker (PM 22)..  Rm. 229, CM #2, 703-    Do.             
                                 305-5540, e-mail:                      
                                 giles-
parker.cynthia@epamai
l.epa.gov.                             
------------------------------------------------------------------------

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 raw 
agricultural commodities under section 408 of the Federal Food, Drug, 
and Comestic Act (FFDCA), 21 U.S.C. 346a. EPA has determined that these 
petitions contain data or information regarding the elements set forth 
in section 408(d)(2); however, EPA has not fully evaluated the 
sufficiency of the submitted data at this time or whether the data 
supports grantinig 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-723 (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

[[Page 15691]]

record is located at the address in ``ADDRESSES'' at the beginning of 
this document.
    Electronic comments can be sent directly to EPA at:
    [email protected]


    Electronic comments must be submitted as an ASCII file avoiding the 
use of special characters and any form of encryption. 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 this proposed rule 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: March 24, 1997.

Stephen L. Johnson,

Director, Registration Division, Office of Pesticide Programs.

Summaries of Petitions

    Below summaries of the pesticide petitions are printed. The 
summaries of the petitions were prepared by the petitioners. The 
petition summary announces the availability of a description of the 
analytical methods available to EPA for the detection and measurement 
of the pesticide chemical residues or an explanation of why no such 
method is needed.

1. Bayer's Corporation

PP 6F4631

    EPA has received a pesticide petition (PP 6F4631) from Bayer 
Corporation, 8400 Hawthorne Road, Kansas City, MO 64120-0013, 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, FOE 5043, N-(4-Fluorophenyl)-N-(1-
methylethyl)-2[[5-(trifluoromethyl)-1,3,4-thiadiazol-2-yl]oxy]acetamide 
in or on the raw agricultural commodities, field corn grain at 0.05 
parts per million (ppm), field corn forage at 0.4 ppm, field corn 
stover (fodder) at 0.4 ppm, soybean seed at 0.1 ppm, milk at 0.01 ppm, 
meat at 0.05 ppm, and meat byproducts at 0.05 ppm. The proposed 
analytical method is gas chromatography/mass spectrometry with selected 
ion monitoring. (PM 22)
    1. Chemical uses. FOE 5043 use on field corn and soybeans provides 
selective weed control for a wide spectrum of annual grasses and small-
seeded broadleaf weeds, with exceptional strength on barnyard grass, 
large crabgrass, fall panicum and foxtail species. Application 
technique: Products containing FOE 5043 can be applied preplant 
surface, preplant incorporated, or preemergence for control of emerging 
weeds. Applications can be made up to 45 days before planting. 
Applications may be made using standard low pressure ground herbicide 
boom sprayers equipped with suitable nozzles and screens. The products 
containing FOE 5043 may be applied either as a single or a split 
application. Application rates range from 0.442 to 0.884 pounds active 
ingredient (a.i.) of FOE 5043 per acre depending on the soil texture 
and soil organic matter content. Tank mix combinations with selected 
products may provide additional weed control.
    2. FOE 5043 Safety. Bayer has submitted over 65 separate toxicology 
studies in support of tolerances for FOE 5043. Among the submissions, a 
finding of particular interest was the observation that in the long-
term data compiled for FOE 5043, provided no indications of a potential 
to induce either carcinogenic or reproductive signs of toxicity. In 
addition, developmental no-observed-adverse effects levels (NOAELs) of 
25 milligrams body weight per day (mg/kg bwt/day) were established for 
both the rat and rabbit.
    The following mammalian toxicity studies have been conducted to 
support the tolerance of AXIOM DF (contains FOE 5043 and metribuzin):
    i. A rat acute oral study with an LD50 of 2,347 mg/kg (male) 
and 2,027 mg/kg (female).
    ii. A rabbit acute dermal with an LD50 of > 2,000 mg/kg.
    iii. A rat acute inhalation with an LD50 of > 977 mg/m3.
    iv. A primary eye irritation study in the rabbit which showed mild 
irritation.
    v. A primary dermal irritation study which showed no irritation.
    vi. A primary dermal sensitization study which showed no 
sensitization.
    The following mammalian toxicity studies, derived from exposure to 
the technical form of the chemical, have been conducted to support the 
tolerance of FOE 5043:
    i. A rat acute oral study with an LD50 of 1,617 mg/kg (male) 
and 589 mg/kg (female).
    ii. A rat acute dermal LD50 of 2,000 mg/kg bwt.
    iii. A rat acute inhalation LC50 of 3,740 mg/m3 (male and 
female).
    iv. A primary eye irritation study in the rabbit which showed no 
irritation.
    v. A primary dermal irritation study which showed no irritation.
    vi. A primary dermal sensitization study which showed no 
sensitization.
    vii. An acute neurotoxicity study with a no-observed effect level 
(NOEL) for FOB, motor and locomotor activity of 75 mg/kg bwt/day for 
males and females.
    viii. A 90-day feeding study in the rat with a NOEL of 1.7 mg/kg 
bwt/day.
    ix. A 90-day subchronic neurotoxicity study in the rat with a 
neurotoxicity and overall NOEL of 120 ppm.
    x. A 24-months chronic feeding/oncogenicity study in the rat with 
an overall NOEL of 1.2 mg/kg bwt/day in males and females based on 
liver, kidney, hematologic and thyroid effects. There was no evidence 
of an oncogenic response.
    xi. A 90-day feeding study in dogs with a NOEL of 50 ppm, based on 
liver hematology, and thyroid effects.
    xii. A 12-month feeding study in dogs with a NOEL of 40 ppm, based 
on hematology and thyroid effects.
    xiii. A mouse oncogenicity study which provided no evidence of 
oncogenicity.
    xiv. An oral teratology study in the rat with maternal and 
developmental NOAELs of 25 mg/kg bwt/day.
    xv. An oral teratology study in the rabbit with maternal and fetal 
NOELs of 5 and 25 mg/kg bwt/day respectively.
    xvi. An two-generation reproduction study in the rat with a NOEL 
for reproductive and parental toxicity of 500 and 20 ppm, respectively.
    xvii. Ames assay: Negative
    xviii. Unscheduled DNA synthesis: Negative
    xix. Mouse Micronucleus Assay: Negative.
    3. Threshold effects-- chronic effects. Based on the available 
chronic toxicity data, Bayer believes the Reference Dose (RfD) for FOE 
5043 should be 0.0114 mg/kg/day. The RfD for FOE 5043 is based on a 1 
year chronic toxicity study in the dog with a threshold No Observed 
Effect Level (NOEL) of 1.14 mg/kg/day and an uncertainty factor of 100.
    Acute toxicity. EPA recently proposed a tiered approach to estimate 
acute dietary exposure. The methods proposed by the EPA were reviewed 
and supported by the FIFRA Scientific Advisory Panel (SAP, 1995). EPA's 
Tier 1 method is based on the assumption that residue concentrations do 
not vary. The analysis assumes that all residues have the same 
magnitude, typically the highest field trial residue or tolerance 
value. This value is assumed for all

[[Page 15692]]

points along the consumption distribution, resulting in a distribution 
of dietary exposure.
    For the acute analysis for FOE 5043, a Tier 1 analysis was 
conducted for the overall U.S. population, infants, children 1 to 6 
years of age, females 13 years and older, and males 13 years and older. 
Using the NOEL of 138 mg/kg derived from the acute oral toxicity study 
in rats, the following margins of exposure were calculated (margins of 
exposure of 100 or more are considered satisfactory):

------------------------------------------------------------------------
             Population Group                    Margin of Exposure     
------------------------------------------------------------------------
U.S. Population-All Seasons...............  94,741                      
Infants...................................  64,986                      
Children 1 to 6...........................  76,494                      
Women 13 to 50 years old..................  191,418                     
Men 13 years and older....................  109,805                     
------------------------------------------------------------------------

    4. Non-threshold Effects-- carcinogenicity. Using the Guidelines 
for Carcinogen Risk Assessment, Bayer believes FOE 5043 to be in Group 
E for carcinogenicity--no evidence of carcinogenicity--based on the 
results of carcinogenicity studies in three species. There was no 
evidence of carcinogenicity in an 18-month feeding study in mice, a 2-
year feeding study in rats, or a 1-year feeding study in dogs at the 
dose levels tested. The doses tested are adequate for identifying a 
cancer risk. Thus, a cancer risk assessment should not be necessary for 
FOE 5043.
    5. Aggregate Exposure. For purposes of assessing the potential 
dietary exposure under the proposed tolerances for FOE 5043, the 
estimated aggregate exposure was based on the Theoretical Maximum 
Residue Concentrations (TMRC) and the proposed tolerances (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 present at the tolerance levels.). 
Registration for FOE 5043 and AXIOM are currently being sought on field 
corn and soybeans. FOE 5043 and AXIOM are not registered for any uses. 
Tolerances are proposed (pesticide petition number 6F 4631) for FOE 
5043 on the following Raw Agricultural Commodities (RAC); field corn 
grain (0.05 ppm), forage (0.4 ppm) and stover (fodder) (0.4 ppm), 
soybean seed (0.1 ppm), milk (0.01 ppm), meat (0.05 ppm), and meat 
byproducts (0.05 ppm). The TMRC is obtained by multiplying the 
tolerance level for these commodities by consumption data which 
estimates the amounts of corn and soybean products eaten by various 
human population subgroups. Tolerances are proposed for milk, meat and 
meat byproducts because residues for FOE 5043 can be transferred from 
corn and soybean based feeds through livestock to humans.
    This dietary exposure estimate assumes that 100% of these crops are 
treated with FOE 5043 and that the residues of FOE 5043 found in these 
crops would occur at the proposed tolerance levels. These assumptions 
result in an overestimate of exposure. In making a safety determination 
for these tolerances this conservative exposure estimate has been taken 
into account.
    Other potential sources of exposure of the general population to 
residues of FOE 5043 are residues in drinking water and exposure from 
non-occupational sources. In ongoing ground water monitoring studies, 
trace levels of FOE 5043 residues (less that 1 part per billion (ppb) 
total residues) have been detected in ground water. These studies are 
being performed at sites with vulnerable shallow aquifers and large 
amounts of irrigation are being applied monthly. The highest residue 
level detected is well below the anticipated life-time Health Advisory 
Level of 84 ppb. If residues of FOE 5043 do occur in ground water used 
for drinking water they will be far below the level which causes 
concern. Based on the available data, no significant residues of FOE 
5043 are anticipated to occur in surface water used for drinking water. 
Since registration is not being sought for any residential or homeowner 
uses no other potential for exposure to FOE 5043 residues exists.
    The toxicological profile for FOE 5043 is fundamentally 
characterized by structural- and functional-related alterations in 
thyroid, hematologic and hepatic parameters. These sort of changes are 
not uncommon among herbicides. Since residues of FOE 5043 and its 
degradates will occur in raw agricultural commodities and processed 
foods in the high parts per billion or low parts per million range 
there is no compelling evidence that suggests a cumulative effect 
(i.e., potentiated, additive, or synergistic response) might occur or 
be anticipated in the human following exposure to multiple chemical 
agents with similar toxicological profiles and/or mechanisms of 
toxicity.
    6. Determination of safety for U.S. population--Reference dose 
(RfD). Using the conservative exposure assumptions described above, 
based on the completeness and reliability of the toxicity data, the 
aggregate exposure to FOE 5043 will utilize 2.1% 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, Bayer concludes 
that there is a reasonable certainty that no harm will result from 
aggregate exposure to residues of FOE 5043, including all anticipated 
dietary exposure and all other non-occupational exposures.
    7. Determination of Safety for Infants and Children. The 
possibility of FOE 5043 induced developmental toxicity was suggested in 
preliminary and non-definitive toxicity studies using rats (> 175 mg/kg 
bwt/day) and rabbits (> 125 mg/kg bwt/day). However NOAELs for 
developmental effects were ultimately established in the definitive 
studies. Those values, as mentioned previously, were 25 mg/kg bwt/day 
in the rat and 25 mg/kg bwt/day in the rabbit.
    Reference Dose (RfD). Using the conservative exposure assumptions 
described previously, Bayer has concluded that the percent of the RfD 
utilized by aggregate exposure to residues of FOE 5043 ranges from 1.1 
% for non-nursing infants, up to 5.2 % for children 1 to 6 years old. 
EPA generally has no concern for exposure below 100 % of the Reference 
Dose. Therefore, based on the completeness and reliability of the 
toxicity data and the conservative exposure assessment, Bayer concludes 
that there is a reasonable certainty that no harm will result to 
infants and children from aggregate exposure to the residues of FOE 
5043, including all anticipated dietary exposure and all other non-
occupational exposures.
    8. Estrogenic Effects. No specific tests have been conducted with 
FOE 5043 to determine whether the pesticide may have an effect in 
humans that is similar to an effect produced by a naturally occurring 
estrogen or other endocrine effects.
    9. Chemical Residue. The qualitative nature of the residues in 
plants and animals is adequately understood for the purposes of 
registration. Residues of FOE 5043 do concentrate slightly (1.6x) in 
the processed commodity of corn grits. No tolerance has been proposed 
for residue of FOE 5043 in corn grits because anticipated residues are 
less than two times the limit of quantitation for the analytical 
method. There are no Codex maximum residue levels established for 
residues of FOE 5043 on any crop. Bayer has submitted a practical 
analytical method for detecting and measuring levels of FOE 5043 in or 
on food with a limit of detection that allows monitoring of food with 
residues at or above the proposed tolerance levels. EPA will provide 
information on

[[Page 15693]]

this method to FDA. The method is available to anyone who is interested 
in pesticide residue enforcement from the EPA's Field Operations 
Division, Office of Pesticide Programs.
    Fifty-five separate residue trials have been conducted with FOE 
5043 on corn and soybeans. Analysis of these trials shows that the 
maximum total combined residue for FOE 5043 and its major metabolites 
in any commodity will be at/below 9.75 ppm. Residues occurred at this 
level in soybean dry hay. However, no tolerances have been proposed for 
residues of FOE 5043 on soybean hay because the proposed labels for 
products containing FOE 5043 do not allow livestock to be fed with FOE 
5043 treated soybean hay.
    Tolerances have been requested for residues of FOE 5043 and its 
major metabolites on field corn grain (0.05 ppm), forage (0.4 ppm) and 
stover (fodder) (0.4 ppm) and soybean seed (0.1 ppm), milk (0.01 ppm), 
meat (0.05 ppm), and meat byproducts (0.05 ppm).
    The proposed tolerance levels are adequate to cover residues likely 
to be present from the proposed use of FOE 5043. Therefore, no special 
processing to reduce the residues will be necessary.
    There is no need for tolerances in poultry or eggs since there is 
no reasonable expectation of residues in these materials based on the 
results of poultry metabolism studies, as well as the corn and soybean 
metabolism and rotational crop studies. Calculated transfer factors are 
extremely low and maximum expected residues in poultry and eggs would 
be in the low parts per billion or high parts per trillion range. The 
anticipated residues in poultry tissues and eggs resulting from feeding 
poultry FOE 5043 treated corn and or soybeans would be far below the 
limit of quantitation of the analytical residue method.
    No FOE 5043 food additive tolerances are proposed for field corn 
starch (wet milling), field corn refined oil (wet milling), field corn 
flour (dry milling) and field corn refined oil (dry milling) because no 
residues were detected above the limit of quantitation in this 
processed commodity.
    Additionally, no FOE 5043 food additive tolerances are proposed in 
field corn grits (dry milling) field corn meal (dry milling), soybean 
meal, soybean hulls, and soybean refined oil because the measured 
concentration, when adjusted for the exaggerated application rate, was 
less that two times the limit of quantitation.
    No feed additive tolerances are proposed for FOE 5043 in the 
aspirated grain fractions of corn and soybeans. With pre-plant and or 
pre-emergent modes of application for AXIOM DF and FOE 5043 DF, no 
residues were expected on the seed surface in the corn and soybean 
magnitude of residue studies. Therefore, no aspirated grain fractions 
were collected for analysis. A tolerance has not been proposed for 
soybean forage because feeding soybean hay and forage (silage) to 
livestock animals is not permitted by the proposed label.
    Also, no feed additive tolerances are proposed for soybean meal or 
hulls since the measured concentration in the soybean processing study 
for these feeds, when adjusted for the exaggerated application rate, 
was less that two times the limit of quantitation.
    No tolerances are proposed for corn milled by-products. Table II 
(September 1995) advises use residue data for corn dry-milled processed 
commodities having the highest residues, excluding oils. No residues 
were detected in the dry-milled processed commodities above the limit 
of quantitation.
    10. Environmental Fate. Laboratory studies indicate that FOE 5043 
residue has the potential to be moderately mobile in soil. However the 
results of field dissipation studies performed in Wisconsin and North 
Carolina, both corn and/or soybean producing states, indicate that 
downward movement of FOE 5043 residue is limited, with no quantifiable 
residues being found below 18 inches. These studies were conducted 
under conditions conducive to downward movement of FOE 5043 and 
degradates (very high sand content, low organic matter, and large 
volumes of applied irrigation).
    FOE 5043 has been found to be stable to chemical hydrolysis in the 
pH range of environmental concern. The compound is also stable in water 
and soil when exposed to artificial sunlight.
    Microbial degradation is the principal means of dissipation in 
soil. Half-lives for aerobic microbial degradation range from 10 to 34 
days in varying soil types at the anticipated field application rate. 
Degradation of FOE 5043 in soil under aerobic conditions occurs by 
cleavage of the thiadiazole ring to form 3-trifluoromethyl-1,3,4-
thiadiazol-2(3H)one (FOE thiadone) and the corresponding alcohol, N-(4-
flurophenyl)-2-hydroxy-N-(1-methylethyl)acetamide. The FOE thiadone is 
further metabolized to CO2, and the alcohol is subsequently oxidized to 
[4-flurophenyl)(1-methylethyl)amino]oxoacetic acid. Another major 
degradation product of FOE 5043 is 4-fluoro-N-methylethylaniline-
sulfoacetamide which is proposed to form through the oxidation of a 
cysteine conjugate intermediate. (PM 22)

PP 5F4577

    EPA has received a pesticide petition (PP) 5F4577 from Bayer 
Corporation, 8400 Hawthorn Rd., P.O. Box 4913, Kansas City, MO 64120-
0013 proposing, pursuant to section 408(d) of the Federal Food, Drug 
and Cosmetic Act (FFDCA), 21 U.S.C. 346a, to amend 40 CFR 180.474 by 
establishing tolerances for residues of the fungicide tebuconazole in 
or on the raw agricultural commodities grass forage at 8.0 ppm and 
grass hay at 25.0 ppm and tolerances for residues of the fungicide 
tebuconazole in or on the raw agricultural commodities cattle liver at 
0.2 ppm, cattle kidney at 0.2 ppm, cattle meat byproducts at 0.2 ppm, 
and milk at 0.1 ppm. The proposed analytical method for determining 
residues uses gas-liquid chromatography coupled with a thermionic 
detector. EPA has determined that the petition contains data or 
information regarding the elements set forth in section 408(d)(2); 
however EPA has not fully evaluated the sufficiency of the submitted 
data at this time or whether the data supports granting of the 
petition. Additional data may be needed before EPA rules on the 
petition. (PM 21)
    Tebuconazole is a sterol demethylation inhibitor (DMI) fungicide. 
It is systemic and shows activity against rusts (Puccinia spp.) and 
powdery mildew infecting grasses grown for seed. Tebuconazole provides 
protective activity by preventing completion of the infection process. 
It is rapidly absorbed by plants and is translocated systemically in 
the young growing tissues.

A. Residue Chemistry

    1. Plant and livestock metabolism. Bayer believes the nature of the 
residue in plants and animals is adequately understood. The residue of 
concern is the parent compound only, as specified in 40 CFR 180.474.
    2. Analytical method. Bayer has submitted an enforcement method for 
plant commodities has been validated on various commodities. It has 
undergone successful EPA validation and has been submitted for 
inclusion in PAM II. The method should be adequate for grasses grown 
for seed. The animal method has also been approved as an adequate 
enforcement method and will be submitted to FDA for inclusion in PAM 
II.
    3. Magnitude of residue. Nine separate residue trials have been 
conducted and submitted to the EPA with tebuconazole on grasses grown 
for seed. The EPA has

[[Page 15694]]

determined that these data show that residues of 
tebuconazole,-[2-(4-Chlorophenyl)ethyl]--(1,1-
dimethylethyl)-H-1,2,4-triazole-1-eth anol, are not expected to exceed 
8 ppm in grass forage and 25 ppm in grass hay as a result of the 
proposed use. In addition, the EPA has determined that tolerances are 
needed for the following animal commodities: cattle liver, kidney and 
meat byproducts at 0.2 ppm and milk at 0.1 ppm. The tolerance 
expression for the animal commodities will include the HWG 2061 
metabolite,-[2-(4-Chlorophenyl)-ethyl]--[(2-hydroxy-
1,1-dimethyl)ethyl]-1H-1,2,4triazole-1-ethanol, in addition to the 
parent.
    No processed commodities are associated with the proposed use on 
grasses grown for seed. In addition, due to the nature of the crop, 
rotational crops will not be an issue.

B. Toxicological Profile of Tebuconazole

    1. Acute toxicity. i. Rat acute oral study with an LD50 of > 
5,000 mg/kg (male) and 3,933 mg/kg (female)
    ii. Rabbit acute dermal of LD50 of > 5,000 mg/kg
    iii. Rat acute inhalation of LC50 of > 0.371 mg/l
    iv. Primary eye irritation study in the rabbit which showed mild 
irritation reversible by day 7
    v. Primary dermal irritation study which showed no skin irritation
    vi. Primary dermal sensitization study which showed no 
sensitization
    2. Genotoxicity. i. An Ames mutagenesis study in Salmonella showed 
no mutagenicity with or without metabolic activation.
    ii. A micronucleus mutagenesis assay study in mice showed no 
genotoxicity.
    iii. A sister chromatid exchange mutagenesis study using CHO cells 
was negative at dose levels 4 to 30 g/mL without activation or 
15 to 120 g/mL with activation.
    iv. An unscheduled DNA synthesis (UDS) study was negative for UDS 
in rat hepatocytes.
    3. Reproductive and developmental toxicity. i. A rat oral 
developmental toxicity study with a maternal NOEL of 30 milligrams per 
kilogram of body weight per day (mg/kg bwtt/day) and an LEL of 60 mg/kg 
bwtt/day based on elevation of absolute and relative liver weights. For 
developmental toxicity, a NOEL of 30 mg/kg bwtt/day and an LEL of 60 
mg/kg bwtt/day was determined, based on delayed ossification of 
thoracic, cervical and sacral vertebrae, sternum, fore and hind limbs 
and increase in supernumerary ribs.
    ii. A rabbit oral developmental toxicity study with a maternal NOEL 
of 30 mg/kg bwt/day and an LEL of 100 mg/kg bwt/day based on depression 
of body weight gains and food consumption. A developmental NOEL of 30 
mg/kg bwt/day and an LEL of 100 mg/kg bwt/day were based on increased 
post-implantation losses, from both early and late resorptions and 
frank malformations in eight fetuses of five litters.
    iii. A mouse oral developmental toxicity study with a maternal NOEL 
of 10 mg/kg bwt/day and an LEL of 20 mg/kg bwt/day based on a 
supplementary study indicating reduction in hematocrit and histological 
changes in liver. A developmental NOEL of 10 mg/kg bwt/day and an LEL 
of 30 mg/kg bwt/day based on dose-dependent increases in runts/dam at 
30 and 100 mg/kg bwt/day.
    iv. A mouse dermal developmental toxicity study with a maternal 
NOEL of 30 mg/kg bwt/day and an LEL of 60 mg/kg bwt/day based on a 
supplementary study indicating increased liver microsomal enzymes and 
histological changes in liver. The NOEL for developmental toxicity in 
the dermal study in the mouse is 1,000 mg/kg bwt/day, the highest dose 
tested (HDT).
    v. A two-generation rat reproduction study with a dietary maternal 
NOEL of 15 mg/kg bwt/day (300 ppm) and an LEL of 50 mg/kg bwt/day 
(1,000 ppm) based on depressed body weights, increased spleen 
hemosiderosis, and decreased liver and kidney weights. A reproductive 
NOEL of 15 mg/kg bwt/day (300 ppm) and an LEL of 50 mg/kg bwt/day 
(1,000 ppm) were based on neonatal birth weight depression.
    4. Subchronic toxicity. i. 28-day feeding study in the rat with a 
NOEL of 30 mg/kg/day and a LEL of 100 mg/kg/day based on changes in 
hematology and clinical chemistry parameters.
    ii. A 90-day rat feeding study with a no-observed-effect level 
(NOEL) of 34.8 (mg/kg bwt/day) (400 ppm) and a lowest-effect-level 
(LEL) of 171.7 mg/kg bwt/day (1,600 ppm) in males, based on decreased 
body weight gains and histological changes in the adrenals. For 
females, the NOEL was 10.8 mg/kg bwt/day (100 ppm) and the LEL was 46.5 
mg/kg bwt/day (400 ppm) based on decreased body weights, decreased body 
weight gains, and histological changes in the adrenals.
    iii. A 90-day dog-feeding study with a NOEL of 200 ppm (73.7 mg/kg 
bwt/day in males and 73.4 mg/kg bwt/day in females) and an LEL of 1,000 
ppm (368.3 mg/kg bwt/day in males and 351.8 mg/kg bwt/day in females). 
The LEL was based on decreases in mean body weights, body weight gains, 
and food consumption, and an increase in liver N-demethylase activity.
    5. Chronic toxicity i. A 2-year rat chronic feeding study defined a 
NOEL of 7.4 mg/kg bwt/day (100 ppm) and an LEL of 22.8 mg/kg bwt/day 
(300 ppm) based on body weight depression, decreased hemoglobin, 
hematocrit, MCV and MCHC, and increased liver microsomal enzymes in 
females. Tebuconazole was not oncogenic at the dose levels tested (0, 
100, 300, and 1,000 ppm).
    ii. A 1-year dog feeding study with a NOEL of 1 mg/kg bwt/day (40 
ppm) and an LEL of 5 mg/kg bwt/day (200 ppm), based on lenticular and 
corneal opacity and hepatic toxicity in either sex (the current 
Reference Dose was determined based on this study). A subsequent 1-year 
dog feeding study, using lower doses to further define the NOEL for 
tebuconazole, defines a systemic LOEL of 150 ppm (based on adrenal 
effects in both sexes) and a systemic NOEL of 100 ppm.
    iii. A mouse oncogenicity study at dietary levels of 0, 20, 60, and 
80 ppm for 21 months did not reveal any oncogenic effect for 
tebuconazole at any dose tested. Because the maximum-tolerated-dose 
(MTD) was not reached in this study, the study was classified as 
supplementary. A follow-up mouse study at higher doses (0, 500, and 
1,500 ppm in the diet), with an MTD at 500 ppm, revealed statistically 
significant incidences of hepatocellular adenomas and carcinomas in 
males and carcinomas in females. The initial and follow-up studies, 
together with supplementary data were classified as core minimum.
    6. Animal metabolism. A general rat metabolism study at dietary 
levels of 2 and 20 mg/kg showed rapid elimination from the rat in 3 
days (some 99% excreted by the feces and urine and 0.0304% in expired 
air). Increased concentrations of radioactivity from the active 
ingredient and metabolites were found only in the liver. The bones and 
the brain were among the tissues showing the least amount of 
radioactivity.
    7. Metabolite toxicity. The residue of concern in plants is the 
parent compound, tebuconazole, only. For animal commodities, the EPA 
has determined that the tolerance expression should include the HWG 
2061 metabolite, -[2-(4 -Chlorophenyl)-ethyl]--[(2-
hydroxy-1,1-dimethyl)ethyl]-1H-1,2,4triazole-1-ethanol. An acute oral 
toxicity study has been submitted to the EPA on this metabolite. This 
study shows an oral LD50 of > 5,000 for female rats. This value 
indicates that the HWG 2061 metabolite is relatively innocuous and less 
acutely toxic than tebuconazole.

[[Page 15695]]

    8. Endocrine effects. No special studies investigating potential 
estrogenic or endocrine effects of tebuconazole have been conducted. 
However, the standard battery of required studies has been completed. 
These studies include an evaluation of the potential effects on 
reproduction and development, and an evaluation of the pathology of the 
endocrine organs following repeated or long-term exposure. These 
studies are generally considered to be sufficient to detect any 
endocrine effects but no such effects were noted in any of the studies 
with either tebuconazole or its metabolites.
    9. Carcinogenicity. EPA's Carcinogenicity Peer Review Committee 
(CPRC) has classified tebuconazole as a Group C carcinogen (possible 
human carcinogen). This classification is based on the Agency's 
``Guidelines for Carcinogen Risk Assessment'' published in the Federal 
Register of September 24, 1986 (51 FR 33992). The Agency has chosen to 
use the reference dose calculations to estimate human dietary risk from 
tebuconazole residues. The decision supporting classification of 
tebuconazole as a possible human carcinogen (Group C) was primarily 
based on the statistically significant increase in the incidence of 
hepatocellular adenomas, carcinomas, and combined adenomas/carcinomas 
in both sexes of NMRI mice both by positive trend and pairwise 
comparison at the highest dose tested.

C. Aggregate Exposure

    1. Dietary (food) exposure. For purposes of assessing the potential 
dietary exposure from food under the proposed tolerances, Bayer has 
been advised that the EPA has estimated exposure based on the 
Theoretical Maximum Residue Contribution (TMRC) derived from the 
previously established tolerances for tebuconazole on cherries, 
peaches, bananas, barley, oats, wheat, and peanuts as well as the 
proposed tolerances for tebuconazole on milk at 0.1 ppm and cattle 
liver, kidney and meat byproducts at 0.2 ppm. The TMRC is obtained by 
using a model which multiplies the tolerance level residue for each 
commodity by consumption data which estimate the amount of each 
commodity and products derived from the commodities that are eaten by 
the U.S. population and various population subgroups. In conducting 
this exposure assessment, the EPA has made very conservative 
assumptions--100% of all commodities will contain tebuconazole 
residues, and those residues would be at the level of the tolerance--
which result in a large overestimate of human exposure. Thus, in making 
a safety determination for these tolerances, the Agency took into 
account this very conservative exposure assessment.
    2. Dietary (drinking water) exposure. There is no Maximum 
Contaminant Level established for residues of tebuconazole. Bayer was 
advised by the Environmental Fate and Ground Water Branch's (EFGWB) May 
26, 1993 memorandum for our application for use on bananas and peanuts 
that all environmental fate data requirements for tebuconazole were 
satisfied. The EFGWB had determined that tebuconazole is resistant to 
most degradative processes in the environment, including hydrolysis, 
photolysis in water and aerobic and anaerobic metabolism. Only minor 
degradation occurred in soil photolysis studies. The photolytic half-
life of tebuconazole is 19 days. Laboratory and field studies have 
shown that the mobility of tebuconazole in soil is minimal. Therefore, 
Bayer concludes that tebuconazole bears no apparent risk to ground 
water under most circumstances.
    3. Non-dietary exposure. Although current registrations and the 
proposed use for grasses grown for seed are limited to commercial crop 
production, Bayer has submitted an application to register tebuconazole 
on turf. Bayer has conducted an exposure study designed to measure the 
upper bound acute exposure potential of adults and children from 
contact with tebuconazole treated turf. The population considered to 
have the greatest potential exposure from contact with pesticide 
treated turf soon after pesticides are applied are young children. 
Margins of exposure (MOE) of 1,518 8,561 for 10-year-old children and 
1,364 - 7,527 for 5-year-old children were estimated by comparing 
dermal exposure doses to the tebuconazole no-observable effect level of 
1,000 mg/kg/day established in a subacute dermal toxicity study in 
rabbits. The estimated safe residue levels for tebuconazole on treated 
turf for 10-year-old children ranged from 4.8 - 27.3 g/
cm2 and for 5-year-old children from 4.4 - 24.0 g/
cm2. This compares with the average tebuconazole transferable 
residue level of 0.319 g/cm2 present immediately after 
the sprays have dried. Bayer concludes that these data indicate that 
children can safely contact tebuconazole-treated turf as soon after 
application as the spray has dried.

D. Cumulative Effects

    At this time, the EPA has not made a determination that 
tebuconazole and other substances that may have a common mechanism of 
toxicity would have cumulative effects. Therefore, for this tolerance, 
Bayer has considered only the potential risks of tebuconazole in its 
aggregate exposure.

E. Safety Determination

    1. U.S. population. Chronic Dietary Exposure: Based on a complete 
and reliable toxicity database, the EPA has adopted an RfD value of 
0.03 mg/kg/day. This RfD is based on a 1-year dog study with a NOEL of 
2.96 mg/kg/day and an uncertainty factor of 100. Using the conservative 
exposure assumptions described above, Bayer has been advised that the 
EPA has concluded that aggregate dietary exposure to tebuconazole from 
the previously established and the proposed tolerances will utilize 5.1 
% of the RfD for the U.S. population (48 states) and 30.7% of the RfD 
for the most highly exposed population subgroup (non-nursing infants, 
<1 year old). There is generally no concern for exposures below 100 % 
of the RfD because the RfD represents the level at or below which daily 
aggregate exposure over a lifetime will not pose appreciable risks to 
human health. Therefore, Bayer concludes that there is a reasonable 
certainty that no harm will result from aggregate exposure to 
tebuconazole.
    2. Acute dietary exposure. EPA recently proposed a tiered approach 
to estimate acute dietary exposure. The methods proposed by the EPA 
were reviewed and supported by the FIFRA Scientific Advisory Panel 
(SAP, 1995). EPA's Tier 1 method is based on the assumption that 
residue concentrations do not vary. The analysis assumes that all 
residues have the same magnitude, typically the highest field trial 
residue or tolerance value. This value is assumed for all points along 
the consumption distribution, resulting in a distribution of dietary 
exposure. Bayer has been advised that the EPA conducted an acute 
dietary analysis using the NOEL of 10 mg/kg/day for developmental 
toxicity in the mouse. The EPA has calculated a high end Margin of 
Exposure (MOE) value of 1,000 for the population subgroup of concern 
(females 13+). In addition, Bayer has calculated 95th percentile MOE 
for the following population groups: overall U.S. population (MOE = 
2,528), infants (MOE = 711), children 1 to 6 years of age (MOE = 1,145) 
, females 13 years and older (MOE = 4,285), and males 13 years and 
older (MOE = 3,685). Therefore, since EPA considers values of 100 or 
more satisfactory, there is no concern from acute dietary exposure.
    3. Infants and children. In assessing the potential for additional 
sensitivity of

[[Page 15696]]

infants and children to residues of tebuconazole, the data from 
developmental studies in both rat and rabbit and a two-generation 
reproduction study in the rat should be considered. The developmental 
toxicity studies evaluate any potential adverse effects on the 
developing animal resulting from pesticide exposure of the mother 
during prenatal development. The reproduction study evaluates any 
effects from exposure to the pesticide on the reproductive capability 
of mating animals through two generations, as well as any observed 
systemic toxicity. A developmental toxicity study in the rat, a 
developmental toxicity study in the rabbit, two developmental studies 
in the mouse and a 2-generation rat reproduction study have been 
conducted with tebuconazole. Maternal and developmental toxicity NOELs 
of 30 mg/kg/day were determined in the rat and rabbit studies. An oral 
mouse developmental toxicity study had maternal and developmental 
toxicity NOELs of 10 mg/kg/day while the mouse dermal developmental 
study had a maternal NOEL of 30 mg/kg/day and a developmental toxicity 
NOEL of 1,000 mg/kg/day. The parental and reproductive NOELs in the 2-
generation rat reproduction study were determined to be 15 mg/kg/day 
(300 ppm). In all cases, the reproductive and developmental NOELs were 
greater than or equal to the parental NOELs. This indicates that 
tebuconazole does not pose any increased risk to infants or children. 
FFDCA Section 408 provides that EPA may apply an additional safety 
factor for infants and children in the case of threshold effects to 
account for pre- and post- natal effects and the completeness of the 
toxicity database. Based on current toxicological data requirements, 
the toxicology database for tebuconazole relative to pre- and post-
natal effects is complete. Further for tebuconazole, the NOEL of 2.96 
mg/kg/bwtt from the 1-year dog study, which was used to calculate the 
RfD, is already lower than the NOELs from the developmental studies in 
rats (30 mg/kg bwt/day) and rabbits (30 mg/kg bwt/day) by a factor of 
10 times. Since a hundredfold uncertainty factor is already used to 
calculate the RfD, Bayer surmises that an additional uncertainty factor 
is not warranted and that the RfD at 0.03 mg/kg/bwtt/day is appropriate 
for assessing aggregate risk to infants and children. Using the 
conservative exposure assumptions, Bayer has concluded from the EPA's 
recent chronic dietary analysis that the percent of the RfD utilized by 
aggregate exposure to residues of tebuconazole ranges from 14.2% for 
children 1 to 6 years old up to 30.7% for non-nursing infants. EPA 
generally has no concern for exposure below 100 % of the RfD. 
Therefore, based on the completeness and reliability of the toxicity 
data and the conservative exposure assessment, Bayer concludes that 
there is a reasonable certainty that no harm will result to infants and 
children from aggregate exposure to the residues of tebuconazole, 
including all anticipated dietary exposure and all other non-
occupational exposures.

F. International Issues

    No CODEX Maximum Residue Levels (MRLs) have been established for 
residues of tebuconazole on any crops at this time. Data have not been 
submitted to the Joint Meeting of the Food and Agriculture Organization 
Panel of Experts on Pesticide Residues in Food and the Environment and 
the World Health Organization Expert Group on Pesticide Residues (JMPR) 
to establish Codex MRLs for grasses grown for seed.

G. Mode of Action

    Tebuconazole, the active ingredient of Folicur 3.6 F is a sterol 
demethylation inhibitor (DMI) fungicide. It is systemic and shows 
activity against rusts (Puccinia spp.) and powdery mildew infecting 
grasses grown for seed. Tebuconazole provides protective activity by 
preventing completion of the infection process by direct inhibition of 
sterol synthesis. It is rapidly absorbed by plants and translocated 
systemically in the young growing tissues.

2. Ciba Crop Protection

6F4656/6H5746

    EPA has received pesticide petitions (PP) 6F4656/6H5746 from Ciba 
Crop Protection, Ciba-Geigy Corporation, P.O. Box 18300, Greensboro, NC 
27419, proposing pursuant to section 408(d) of the Federal Food, Drug 
and Cosmetic Act (FFDCA), 21 U.S.C 346a, to amend 40 CFR part 180 by 
establishing tolerances for residues of the fungicide cyprodinil (4-
cyclopropyl-6-methyl-N-phenyl-2-pyrimidinamine) in or on the 
agricultural commodities almond nutmeats at 0.04 ppm, almond hulls at 
0.1 ppm, grapes at 3.0 ppm, raisins at 3.0 ppm, the pomefruit crop 
grouping at 0.1 ppm, apple pomace - wet at 0.4 ppm, and the stone fruit 
crop grouping at 2.0 ppm. The proposed analytical method for 
determining residues uses high performance liquid chromatography with 
UV detection. EPA has determined that the petition contains data or 
information regarding the elements set forth in section 408(d)(2); 
however EPA has not fully evaluated the sufficiency of the submitted 
data at this time or whether the data supports granting of the 
petition. Additional data may be needed before EPA rules on the 
petition. (PM 21)

A. Cyprodinil Uses

    Cyprodinil is the first fungicide in a new chemical class known as 
the anilinopyrimidine and is active against important Botrytis, 
Monilinia and Venturia diseases of deciduous fruit and nut crops. 
Cyprodinil with a unique mode of action, controls pathogens resistant 
to other chemical classes. Application rates range from 0.125 to 0.5 lb 
active ingredient per acre per application depending upon disease and 
time of application.

B. Residue Chemistry

    1. Metabolism. Ciba believes the metabolism of cyprodinil has been 
well characterized in plants and animals. The metabolism profile 
supports the use of an analytical enforcement method that accounts for 
only parent cyprodinil.
    2. Analytical methodology. Ciba has submitted a practical 
analytical method involving extraction, filtration, and solid phase 
cleanup of samples with analysis by HPLC and UV. The limits of 
quantitation (LOQ) for various commodities are as follows: fruit, 
grain, juice - 0.02 ppm; forage, fodder, straw - 0.05 ppm; and grapes - 
0.01 ppm.

C. Magnitude of Residue

    This petition is supported by field residue trials conducted on 
almonds, grapes, and representative members of the Pome Fruit and the 
Stone Fruit Crop Groupings. All samples were analyzed for parent 
residues of cyprodinil.
    Residues found in the almond nutmeats and hulls were all less than 
respective LOQ's of 0.02 ppm and 0.05 ppm. Tolerances at twice the LOQ 
for these commodities have been proposed. In grapes, the maximum 
residues found for fresh fruit and raisins were 2.0 ppm and 2.9 ppm, 
respectively. Residues did not concentrate in grape juice. Tolerances 
of 3.0 ppm for grapes and raisins have been requested. In pome fruit, 
maximum residues ranged from 0.030 ppm to 0.061 ppm. The results of a 
processing study on apples using exaggerated rates showed concentration 
of residues in wet pomace with an average concentration factor of 4X. 
Residues in apple juice were not detectable at the LOQ (< 0.01 ppm). 
Tolerances of 0.1 ppm for the RAC of the Pome Fruit Crop Grouping and 
0.4 ppm for wet apple pomace have been proposed. In stone fruit, 
maximum

[[Page 15697]]

residues ranged from 0.82 ppm to 1.7 ppm. A tolerance of 2.0 ppm has 
been proposed for the Stone Fruit Crop Grouping. Based upon the results 
of a three level dairy feeding study, Ciba believes no transfer of 
residue to animals is expected through their diet and that tolerances 
in milk, meat, poultry, and eggs are not required.

D. International Tolerances

    There are no Codex Alimentarius Commission (CODEX) maximum residue 
levels (MRL's) established for residues of cyprodinil in or on raw 
agricultural commodities.

E. Toxicological Profile of Cyprodinil

    The following mammilian toxicity studies have been conducted to 
support the tolerances of cyprodinil:
    1. A rat acute oral study for cyprodinil with a LD50 of 2,796 
mg/kg.
    2. A rat acute dermal study for cyprodinil with a LD50 > 2,000 
mg/kg.
    3. A rat inhalation study for cyprodinil with a LC50 > 1.2 mg/
liter air.
    4. A primary eye irritation study in rabbits showing cyprodinil as 
minimally irritating.
    5. A primary dermal irritation study in rabbits showing cyprodinil 
as slightly irritating.
    6. A skin sensitization study in guinea pigs showing cyprodinil as 
a weak sensitizer.
    7. A 28-day dermal study in the rat with a NOEL of 5 mg/kg based on 
clinical signs.
    8. A 90-day feeding study in the dog with a NOEL of 1500 ppm (37.5 
mg/kg) based on reduced food intake and body weight.
    9. A 90-day feeding study in the mouse with a NOEL of 500 ppm (75 
mg/kg) based on liver histologic changes.
    10. A 90-day feeding study in the rat with a NOEL of 50 ppm (5 mg/
kg) based on hematologic and histologic findings.
    11. A 12-month feeding study in the dog with a NOEL of 2,500 ppm 
(62.5 mg/kg) based on liver histologic changes.
    12. An 18-month oncogenicity feeding study in the mouse with a NOEL 
of 2,000 ppm (300 mg/kg). The MTD was 5,000 ppm based on reduction in 
body weight gain and no evidence of oncogenicity was seen.
    13. A 24-month chronic feeding/oncogenicity study in the rat with a 
NOEL of 75 ppm (3.75 mg/kg) based on hematologic and histologic 
findings. The MTD was 2,000 ppm based on liver histopathology and no 
evidence of oncogenicity was seen.
    14. An oral teratology study in the rat with a maternal NOEL of 200 
mg/kg based on reductions in body weight gain and food consumption and 
a fetal NOEL of 200 mg/kg based on decreased pup weight and delayed 
skeletal growth at 1,000 mg/kg.
    15. An oral teratology study in the rabbit with a maternal NOEL of 
150 mg/kg based on reduction in body weight gain and a fetal NOEL of 
400 mg/kg based on the absence of any fetal effects.
    16. A 2-generation reproduction study in the rat with a systemic 
NOEL of 100 ppm and a fetal NOEL of 1,000 ppm (100 mg/kg). A slight 
decrease in pup weight at birth and subsequent body weight gain during 
the lactation phase was observed only at the maternally toxic dose of 
4,000 ppm without any effects on reproduction and fertility.
    17. In vitro gene mutation test: Ames assay - negative; Chinese 
hamster V79 cell test - negative; rat hepatocyte DNA repair test - 
negative.
    18. In vitro chromosome test: Chinese hamster ovary cell 
cytogenetic test - negative.
    19. In vivo mutagenicity test: mouse bone marrow test - negative.

F. Threshold Effects

    1. Chronic effects. Based on the available chronic toxicity data, 
Ciba Crop Protection believes the Reference dose (RfD) for cyprodinil 
is 0.0375 mg/kg/day. This RfD is based on a 2-year feeding study in 
rats with aNo-Observed Effect Level (NOEL) of 3.75 mg/kg/day (75 ppm) 
and an uncertainly factor of 100. No additional modifying factor for 
the nature of effects was judged to be necessary as liver sinusoidal 
dilatation was the most sensitive indicator of toxicity in that study.
    2. Acute toxicity. The risk from acute dietary exposure to 
cyprodinil is considered to be very low. The lowest NOEL in a short 
term exposure scenario, identified as 150 mg/kg in the rabbit 
teratology study, is fortyfold higher than the chronic NOEL. Since 
chronic exposure assessment did not result in any margin of exposure 
less than 400 for even the most impacted population subgroup, Ciba 
believes the margin of exposure is greater than 100 for any population 
subgroups; EPA considers margins of exposure of 100 or more as 
satisfactory.

G. Non-threshold Effects

    Using the Guidelines for Carcinogenic Risk Assessment published 
September 24, 1986 (51 FR 33992), Ciba believes cyprodinil to be in 
Group ``E''( no evidence of carcinogenicity. There was no evidence of 
carcinogenicity in an 18-month feed study in mice and a 24-month 
feeding in rats. Dosage levels in both the mouse and the rat studies 
were adequate for identifying a cancer risk.

H. Aggregate Exposure

    1. Dietary exposure. For the purposes of assessing the potential 
dietary exposure under the proposed tolerances, Ciba has estimated 
aggregate exposure based upon the Theoretical Maximum Residue 
Concentration (TMRC) from the requested tolerances: Almonds -- 0.04 ppm 
for the raw agricultural commodity (RAC) and 0.1 ppm for hulls; Grapes 
-- 3.0 ppm for the RAC and 3.0 ppm for raisins; Pome Fruit Crop 
Grouping -- 0.1 ppm for the RAC and 0.4 ppm for apple wet pomace; and 
Stone Fruit Crop Grouping -- 2.0 ppm for the RAC. The TMRC is a ``worst 
case'' estimate of dietary exposure since it assumes 100 % of all crops 
for which tolerances are established are treated and that pesticide 
residues are at the tolerance levels. In conducting this exposure 
assessment, Ciba has made very conservative assumptions -- 100% of all 
almonds, grapes, pome fruit and stone fruit commodities will contain 
cyprodinil residues at tolerance levels -- which result in an 
overestimate of human exposure.
    2. Drinking water exposure. Cyprodinil is rapidly degraded in the 
environment via photolysis and microbial degradation; aqueous and soil 
photolysis half lives for cyprodinil are 12 days and 67 days, 
respectively. The aerobic metabolism half life is 25 days and the 
leaching potential for cyprodinil is low (Koc = 1,550 to 2,030). 
Based on these data, Ciba does not anticipate exposure to residue of 
cyprodinil in drinking water.
    3. Non-dietary exposure. Ciba believes that the potential for non-
occupational exposure to the general public is unlikely except for 
potential residues in food crops discussed above. The proposed uses for 
cyprodinil are for agricultural crops and the product is not used 
residentially in or around the home.
    Ciba believes that consideration of a common mechanism of toxicity 
is not appropriate at this time since there is no information to 
indicate that toxic effects produced by cyprodinil would be cumulative 
with those of any other chemicals. Consequently, Ciba is considering 
only the potential exposure to cyprodinil in its aggregate risk 
assessment.

I. Safety To the U.S. Population

    Reference dose. Using the conservative exposure assumptions 
described above and based on the completeness and reliability of the 
toxicity data base for cyprodinil, Ciba

[[Page 15698]]

has calculated aggregate exposure levels for this chemical. Based on 
chronic toxicity endpoints, only 4% of the RfD will be utilized for the 
U.S. general population. EPA usually has no concern for exposures below 
100 % of the RfD because the RfD represents the level at or below which 
daily aggregate dietary exposure over a lifetime will not pose 
appreciable risks to human health. Ciba concludes that there is a 
reasonable certainty that no harm will result from aggregate exposure 
to cyprodinil residues.

J. Safety to Infants and Children

    Developmental delays (reduced pup weight and ossification) were 
observed in the rat teratology study and 2-generation rat reproduction 
study at maternally toxic doses. The lowest NOEL for this effect was 
established in the 2-generation study at 100 mg/kg (1,000 ppm). The 
finding is judged to be a nonspecific, secondary effect of maternal 
toxicity. No developmental toxicity was observed in the rabbit 
teratology study.
    Reference dose. Using the same conservative exposure assumptions as 
employed for the determination in the general population, Ciba has 
calculated the utilization of RfD by aggregate exposure to residues of 
cyprodinil to be 12% for nursing infants less than 1 year old, 22% for 
non-nursing infants less than 1 year old, 12% for children 1 to 6 years 
old, and 6% for children 7 to 12 years old. Ciba believes that under 
the worst case assumptions which overestimate exposure to infants and 
children, there is a reasonable certainty that no harm will result to 
infants and children from aggregate exposure to cyprodinil residues.

K. Estrogenic effects

    Cyprodinil does not belong to a class of chemicals known or 
suspected of having adverse effects on the endocrine system. 
Developmental toxicity studies in rats and rabbits and a reproduction 
study in rats gave no indication that cyprodinil might have any effects 
on endocrine function related to development and reproduction. The 
chronic studies also showed no evidence of a long-term effect related 
to the endocrine system.

[FR Doc. 97-8397 Filed 4-1-97; 8:45 am]
BILLING CODE 6560-50-F