paraquat; Proposed Tolerance 3/93
Pesticide Tolerance for Paraquat
AGENCY: Environmental Protection Agency (EPA).
ACTION: Proposed rule.
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
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
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-
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
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),
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
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
Therefore, it is proposed that 40 CFR part 180 be amended
1. The authority citation for part 180 continues to read
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
180.205 Paraquat; tolerances for residues.
(a) * * *
Commodity Parts per
* * * * *
Cacao beans.................................................... 0.05
* * * * *
* * * * *
[FR Doc. 93-5102 Filed 3-9-93; 8:45 am]
BILLING CODE 6560-50-F