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cyprodinil Notice of Filing of Pesticide Petitions 3/97

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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:

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                                                         Office location/
Product Manager        telephone number                  Address
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Connie Welch (PM 21)   703-305-6226                      Rm. 227, CM #2,
                       e-mail:                           1921 Jefferson 
                       welch.connie@epamail.epa.gov      Davis Hwy,
                                                         Arlington, VA

Cynthia Giles-Parker (PM 22)                             Rm. 229, CM #2, 
                       703-305-5540                      Do. 
                       e-mail: 
                       giles-parker.cynthia@epamail.epa.gov.
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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 record is located at the address in 
"ADDRESSES" at the beginning of this document.

Electronic comments can be sent directly to EPA at: opp-docket@epamail.epa.gov

Electronic comments must be submitted as an ASCII file avoiding the use of 
special characters and any form of encryption. Comment and data will also be 
accepted on disks in Wordperfect 5.1 file format or ASCII file format. All 
comments and data in electronic form must be identified by the docket 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.

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 
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 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]