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paraquat; Proposed Tolerance 3/93

Pesticide Tolerance for Paraquat 
AGENCY: Environmental Protection Agency (EPA). 
ACTION: Proposed rule. 
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SUMMARY: This document proposes that a tolerance be established 
for residues of the pesticide paraquat in or on the raw agricultural 
commodity cacao beans. The proposed regulation to establish 
a maximum permissible level for residues of the herbicide in 
or on the commodity was requested in a petition submitted by 
the Interregional Research Project No. 4 (IR-4). 
DATES: Comments, identified by the document control number [PP 
2E4056/P554], must be received on or before April 9, 1993.
ADDRESSES: By mail, submit written comments to: Public Response 
and Program Resource Branch, Field Operations Division (H7506C), 
Office of Pesticide Programs, Environmental Protection Agency, 
401 M St. SW, Washington, DC 20460. In person, bring comments 
to: Rm. 1132, CM #2, 1921 Jefferson Davis Hwy., Arlington, VA 
22202.
   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). Information 
so marked 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 a.m. to 4 p.m., Monday through Friday, excluding 
legal holidays. 
FOR FURTHER INFORMATION CONTACT: By mail: Hoyt L. Jamerson, 
Emergency Response and Minor Use Section (H7505C), Registration 
Division, Environmental Protection Agency, 401 M St., SW., Washington, 
DC 20460. Office location and telephone number: Rm. 716C, CM 
#2, 1921 Jefferson Davis Hwy., Arlington, VA 22202, (703)-305-
5310. 
SUPPLEMENTARY INFORMATION: The Interregional Research Project 
No. 4 (IR-4), New Jersey Agricultural Experiment Station, P.O. 
Box 231, Rutgers University, New Brunswick, NJ 08903, has submitted 
pesticide petition (PP) 2E4056 to EPA on behalf of the Agricultural 
Experiment Station of Hawaii. This petition requested that the 
Administrator, pursuant to section 408(e) of the Federal Food, 
Drug, and Cosmetic Act (21 U.S.C. 346a(e)), propose to establish 
a tolerance for residues of the herbicide paraquat (1,1'-dimethyl-
4,4'bipyridinium-ion) derived from application of either the 
bis(methyl sulfate) or the dichloride salt (both calculated 
as the cation) in or on the raw agricultural commodity cacao 
beans at 0.05 part per million (ppm).
   The data submitted in the petition and other relevant material 
have been evaluated. The 
toxicological data considered in support 
of the proposed tolerance include:
   1. A 1-year feeding study in dogs fed diets containing 0, 
0.45, 0.93, and 1.51 milligrams/kilogram (mg/kg) of body weight 
(bwt) day with a no-observed-effect level (NOEL) of 0.45 mg/kg/day 
based on increased severity and extent of chronic pneumonitis 
in both sexes, especially males, at 0.93 mg/kg/day.
   2. A 23-month chronic feeding/carcinogenicity study in mice 
fed diets containing 12.5, 37.5, and 100/125 ppm paraquat ion 
(the highest dose tested (HDT) was increased from 100 to 125 
ppm at week 36) with a systemic NOEL of 12.5 ppm (equivalent 
to 1.87 mg/kg/day) based on renal tubular degeneration in the 
male, and weight loss and decreased food intake in female mice. 
There were no carcinogenic effects observed under the conditions 
of the study.
   3. A 2-year chronic feeding/carcinogenicity study in Fischer 
rats fed diets containing 0, 1.25, 3.75, and 7.5 mg/kg/day with 
equivocal (uncertain) evidence of carcinogenicity (squamous 
cell carcinomas) in the head region (ear, nasal cavity, oral 
cavity, and skin) of male rats of the highest dose level group, 
and an approximate systemic NOEL of 1.25 mg/kg/day based on 
incidence of opacities, cataracts, and nonneoplastic lung lesions 
(alveolar macrophages and 
epithelialization and slight peribronchiolar 
lymphoid hyperplasia). The squamous cell carcinomas were not 
associated with oral exposure; they were the result of topical 
exposure (through powdered diet).
   4. A 2-year chronic feeding/carcinogenicity study in Wistar 
rats fed diets containing 6, 30, 100 and 300 ppm (paraquat dichloride) 
with a systemic NOEL of 100 ppm (equivalent to 5 mg/kg/day) 
based on increased mortality in males and females; decreased 
erythrocytes, hemoglobin, and serum protein in males and females; 
decreased hematocrit, glucose and corpuscular cholinesterase 
activity in males; decreased leukocytes, albumin to globulin 
ration and alkaline phosphatase; increased polymorphonucleocytes 
in males; increased potassium and glucose in females; decreased 
absolute and/or relative weights of heart (males and females), 
liver and brain (females); and increased absolute weights of 
kidneys (males and females) at the highest dose tested (HDT) 
(equivalent to 15 mg/kg/day). There was no evidence of carcinogenicity 
observed under the conditions of the study.
   5. A developmental toxicity study in rats given gavage dosages 
of 1, 5, and 10 mg paraquat ion/kg bwt from day 6 through day 
15 of pregnancy with a NOEL for fetotoxic effects of 1.0 mg/kg/day 
based on weight reduction and slight retardation in ossification 
at 5.0 mg/kg/day, and a 
maternal NOEL of 1.0 mg/kg/day based 
on piloerection, hunched appearance, and weight loss at 5.0 
mg/kg/day. There was no evidence of developmental toxicity observed 
under the conditions of the study.
   6. A developmental toxicity study in mice given gavage dosages 
of 1, 5, and 10 mg/kg/day with no developmental toxicity observed 
under the conditions of the study at any dosage level tested.
   7. A three-generation reproduction study with rats fed diets 
containing 25, 75, and 150 ppm with a systemic NOEL of 25 ppm 
(equivalent to 1.25 mg/kg/day) based on an increased incidence 
of alveolar histiocytosis in the lungs of male and female parents. 
There were no reproductive effects observed under the conditions 
of the study.
   8. Paraquat was negative in 10 mutagenicity studies (mostly 
gene mutation and chromosome aberration studies and one DNA 
damage/repair assay); weakly positive in four studies (two gene 
mutation, one chromosome aberration, and one DNA damage/repair 
assay); and positive in four studies (all DNA damage/repair 
assays).
   The Agency (Peer Review Committee) initially classified paraquat 
as a category "C" carcinogen based on the significant increase 
of squamous cell carcinomas in the head region of the high-dose 
males in the Fisher rat 
chronic feeding/carcinogenicity study. 
Review of the study by an independent laboratory concluded that 
those tumor sites should not be combined; without the combination, 
there were no statistically significant tumor increases for 
any particular tumor type. Discussion and review by the Agency 
(Peer Review Committee) concluded that these tumor sites normally 
should not be combined when the exposure to the chemical is 
by the oral route and that these tumors are likely the result 
of topical exposure to paraquat contained in the powdered diet 
(paraquat is a topical irritant), not the result of exposure 
through the gastrointestinal tract. 
   The Agency considered two additional studies (rat and mouse 
carcinogenicity studies done by the Japanese) and further evaluated 
the tumors in the male rats.
   Based on all the information, the Agency concluded that there 
is no evidence of carcinogenicity in male Wistar rats at 12 
mg/kg/day (HDT) and female Wistar rats at 15 mg/kg/day. The 
Agency concluded that there was at best equivocal evidence of 
carcinogenicity in male Fisher rats at 7.5 mg/kg/day and that 
this equivocal evidence was associated with irritation due to 
topical exposure, and not with oral exposure. Paraquat was, 
therefore, placed in Category E (not a human carcinogen). Because 
paraquat is a restricted-
use pesticide and precautionary measures 
are required to protect applicators from the acute toxicity 
of the chemical, the potential for carcinogenic effects by excessive 
(irritating) topical exposure is not a concern for applicators.
   The reference dose (RfD) is established at 0.0045 mg/kg bwt/day 
based on a NOEL of 0.45 mg/kg/day from the 1-year dog study 
and an uncertainity factor of 100. The theoretical maximum residue 
contribution (TMRC) from existing uses of paraquat is estimated 
at 42 percent of the RfD for the general U.S. population. Existing 
uses and the proposed use of paraquat utilize less than 100 
percent of the RfD for all population subgroups. The proposed 
tolerance for cocoa beans would utilize a maximum of 0.13 percent 
of the RfD.
   The nature of the residue is adequately understood and an 
adequate analytical method, colorimetry, is available for enforcement 
purposes. An analytical method for enforcing this tolerance 
has been published in the Pesticide Analytical Manual (PAM), 
Vol. II.
   No secondary residues in meat, milk, poultry, or eggs are 
expected since cacao beans are not considered a livestock feed 
commodity. There are currently no actions pending against the 
continued registration of this chemical.
   Based on the above 
information considered by the Agency the 
tolerance established by amending 40 CFR 180.205 would protect 
the public health. Therefore, it is proposed that the tolerance 
be established as set forth below.
   Any person who has registered or submitted an application 
for registration of a pesticide, under the Federal Insecticide, 
Fungicide, and Rodenticide Act (FIFRA) as amended, which contains 
any of the ingredients listed herein, may request within 30 
days after publication of this notice in the Federal Register 
that this rulemaking proposal be referred to an Advisory Committee 
in accordance with section 408(e) of the Federal Food, Drug, 
and Cosmetic Act.
   Interested persons are invited to submit written comments 
on the proposed regulation. Comments must bear a notation indicating 
the document control number, [PP 2E4056/P554]. All written comments 
filed in response to this petition will be available in the 
Public Response and Program Resource Branch, at the address 
given above from 8 a.m. to 4 p.m., Monday through Friday, except 
legal holidays.
   The Office of Management and Budget has exempted this rule 
from the requirements of section 3 of Executive Order 12291.
   Pursuant to the requirements of the Regulatory Flexibility 
Act (Pub. L. 96-354, 94 
Stat. 1164, 5 U.S.C. 601-612), the Administrator 
has determined that regulations establishing new tolerances 
or raising tolerance levels or establishing exemptions from 
tolerance requirements do not have a significant economic impact 
on a substantial number of small entities. A certification statement 
to this effect was published in the Federal Register of May 
4, 1981 (46 FR 24950).
List of Subjects in 40 CFR Part 180
   Administrative practice and procedure, Agricultural commodities, 
Pesticides and pests, Reporting and recordkeeping requirements.
Dated: February 24, 1993.
Stephanie R. Irene,
Acting Director, Registration Division, Office of Pesticide 
Programs.
   Therefore, it is proposed that 40 CFR part 180 be amended 
as follows:
PART 180-[AMENDED]
   1. The authority citation for part 180 continues to read 
as follows:
   Authority: 21 U.S.C. 346a and 371.
   2. In 180.205, by amending paragraph (a) in the table therein 
by adding and alphabetically inserting the commodity, to read 
as follows:
180.205   Paraquat; tolerances for residues.
   (a) * * * 
                                                                              
                                                                              
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                           Commodity                              Parts per   
                                                                   million    
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Cacao beans....................................................         0.05  
                                                                              
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[FR Doc. 93-5102 Filed 3-9-93; 8:45 am]
BILLING CODE 6560-50-F