[Federal Register Volume 60, Number 70 (Wednesday, April 12, 1995)]
[Proposed Rules]
[Pages 18558-18560]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 95-8729]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[PP 8F3671/P610; FRL-4945-3]
RIN 2070-AC18
Alachlor; Pesticide Tolerance
AGENCY: Environmental Protection Agency (EPA).
ACTION: Proposed rule.
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SUMMARY: This document proposes to establish an increased tolerance for
residues of the herbicide alachlor (2-chloro-2',6'-dimethyl-N-
(methoxymethyl) acetanilide) and its metabolites in or on the raw
agricultural commodity (RAC) sorghum forage at 2.0 parts per million
(ppm). The Monsanto Co. requested the establishment of this maximum
permissible residue of the herbicide.
DATES: Comments, identified by the document control number [PP 8F3671/
P610], must be received on or before May 12, 1995.
ADDRESSES: By mail, submit written comments to: Public Response and
Program Resources Branch, Field Operations Division (7506C), 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, Robert J. Taylor, Product
Manager (PM 25), Registration Division (7505C), Office of Pesticide
Programs, Environmental Protection Agency, 401 M St., SW., Washington,
DC 20460. Office location and telephone number: Rm. 241, CM #2, 1921
Jefferson Davis Hwy., Arlington, VA 22202, (703)-305-6800; e-mail:
taylor.robert@epamail.epa.gov. [[Page 18559]]
SUPPLEMENTARY INFORMATION: EPA issued a notice in the Federal Register
of October 12, 1988 (53 FR 39785), that announced that the Monsanto
Co., 1101 17th St., NW., Washington, DC 20036, proposed amending 40 CFR
180.249 by establishing a regulation under section 408 of the Federal
Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a, to permit the
residues of the herbicide alachlor (2-chloro-2',6'-dimethyl-N-
(methoxymethyl) acetanilide) and its metabolites in or on sorghum
forage at 2.0 parts per million (ppm) (pesticide petition (PP) 8F3671).
This increased tolerance was necessary because review of additional
data submitted in response to reregistration indicated that the current
tolerance of 1.0 for sorghum forage was not adequate and needed to be
increased. EPA issued a notice in the Federal Register of March 23,
1989 (54 FR 12010), which announced that the Monsanto Co. proposed
amending 40 CFR parts 185 and 186 by establishing a regulation under
section 409 of the FFDCA, 21 U.S.C. 348, permitting residues of the
herbicide alachlor in or on sorghum milling fractions at 0.5 ppm,
sorghum milling fractions (except germ) at 0.3 ppm, and sorghum germ at
0.5 ppm (food/feed additive (FAP) 9H5576).
No comments were received in response to these notices of filing.
During the course of its review, the Agency determined that the
food/feed additive tolerances for sorghum milling fractions and sorghum
germ were not needed and that there is no current evidence of use of
sorghum milling fractions as a human food and very limited evidence of
use of soghum milling fractions as livestock feed. The petitioner
subsequently withdrew FAP No. 9H5576. Because it has been longer than 5
years since the original proposal, the tolerance of 2.0 ppm for sorghum
forage is being proposed for 30 days following the date of publication
in the Federal Register to allow for public comment.
The data submitted in the petition and other relevant material have
been evaluated. The pesticide is considered useful for the purpose for
which the tolerance is sought. The toxicological data listed below were
considered in support of the proposed tolerance.
1. Several acute toxicology studies place technical alachlor in
acute toxicity category IV for primary eye and dermal irritation and,
acute toxicity category III for acute oral, dermal, and inhalation.
2. A 1-year feeding study with dogs fed dose levels of 0, 1, 3, and
10 milligrams/kilograms/day (mg/kg/day) with a no-observed effect level
(NOEL) of 1.0 mg/kg/day based on hemosiderin storage in kidney and
spleen in males at 10 mg/kg.
3. A 2-year chronic feeding/carcinogenicity study in rats fed
epichlorohydrin-free alachlor at dose levels of 0, 0.5, 2.5, and 15 mg/
kg/day with a NOEL for nonneoplastic toxicity at 2.5 mg/kg/day based on
ocular lesions and hepatoxicity at 10 mg/kg/day. Carcinogenic effects
included a nasal turbinate tumor in females at 2.5 mg/kg/day,
significant increases in nasal turbinate tumors in both males and
females at 15 mg/kg/day (highest dose tested (HDT)) and a significant
increase in thymus lymphosarcomas and adrenal pheochromocytomas in
high-dose females.
4. A second chronic feeding/carcinogenic study with rats fed
alachlor, with epichlorohydrin, at dose levels of 0, 14, 42, and 126
mg/kg/day with a systemic NOEL of less than 14 mg/kg/day based on
ocular lesions and hepatotoxicity at 14 mg/kg/day. Carcinogenic effects
included increased number of nasal turbinate tumor in males and females
at 42 mg/kg/day and mg/kg/day, an increase in stomach tumors in both
sexes at 126 mg/kg/day, and an increase in thyroid follicular tumors in
males at 126 mg/kg/day (HDT).
5. A special chronic feeding study in rats fed a dose level of 126
mg/kg/day. Ocular lesions, mainly, the uveal degeneration syndrome
(UDS) occurred in 100% of the animals at the end of the study. This
syndrome was irreversible once it began. Alachlor was a positive
oncogen with increased nasal turbinate tumors, stomach tumors, and
thyroid tumors.
6. An 18-month carcinogenicity study in mice fed dose levels of 0,
26, 78, and 260 mg/kg/day with carcinogenic effects (increased lung
bronchiolaraveolar tumors in females at 260 mg/kg/day).
7. A three-generation reproduction study with rats fed dose levels
of 0, 3, 10, 11, and 30 mg/kg/day with a reproductive NOEL of 10 mg/kg/
day based on kidney effects in F2 and F3 pups at 30 mg/kg/day (HDT).
8. A developmental toxicity study in rats fed dose levels of 0, 50,
150, and 400 mg/kg/day with a developmental toxicity equal to a greater
than 400 mg/kg/day with a fetotoxic NOEL of 150 mg/kg/day based on an
increase in post-implantation loss and a slight decrease in mean number
of viable fetuses at 400 mg/kg/day . The maternal toxicity NOEL for
this study is 150 mg/kg/day based on soft stools, hair loss, anogenital
staining, and death at 400 mg/kg/day.
9. A developmental toxicity study in rabbits fed doses of 50, 100,
and 150 mg/kg/day with a developmental NOEL greater than 150 mg/kg/day
greater than 150 mg/kg/day. The maternal NOEL was 100 mg/kg/day based
on reduced body weight gain.
10. Mutagenicity studies include several Ames Tests. Alachlor and
its metabolites were negative in four Ames assays with Salmonella with
and without S9 activation at 0.1 to 10 mg/plate. Two metabolites of
alachlor were positive in an Ames test with and without S9 activation
at 0.01 to 10 mg/plate. Bile from alachlor-treated rates did not induce
a mutagenic response towards Salmonella strains TA98, TA100, TA1535,
and TA1537. Other mutagenicity tests include DNA damage/repair in rat
positive for UDS at the HDT = LD50 at the 4 doses tested (50, 200,
and 1,000 mg/kg)--weakly genotoxic; gene mutation in CHO/HGPRT--
negative, and in vivo bone marrow chromosome aberration assay--
negative.
Alachlor has been classified as a B2 carcinogen--``Probable
Human Carcinogen'' by the Agency. Alachlor met all but one of the
criteria specified for the B2 classification. Alachlor produced an
increased incidence of nasal turbinate tumors (mostly benign) at the
mid and high doses, in both sexes, thyroid follicular tumors in male
rats and malignant stomach tumors in male and female rats in Long-Evans
rats in three different experiments at more than one dose level via
dietary administration. Alachlor also produced a statistically
significant increase in lung tumors in female CD-1 mice at two dose
levels. In another experiment with Long-Evans rats, nasal turbinate
tumors occurred only 5 to 6 months after exposure. The tumor incidence
was as high at 50% and tumor site was unusual, i.e., not an increase of
normal high background tumor type. A metabolite of alachlor was
mutagenic in the Ames Test at 6 dose levels, and alachlor is
structurally similar to acetochlor and metolachlor, two other known
carcinogens. A detailed discussion of the Agency's classification of
alachlor as a B2 carcinogen was published in the Federal Register
of December 31, 1987 (52 FR 49480). The publication was entitled
``Alachlor, Notice of Intent to Cancel Registrations, Conclusion of
Special Review.''
For the purpose of risk characterization of alachlor, the use of
the linearized multi-stage model, as recommended to EPA's Carcinogenic
Risk Assessment Guidelines, was applied to the rat oncogenicity data
discussed above. As a result, the cancer potency value for alachlor,
known as the ``Q*1'', was calculated to be 8 X 10-2 or 0.08
(mg/kg/day)-1. Refer to the [[Page 18560]] document published in
the Federal Register of December 31, 1987 (54 FR 49484) for details.
The reference dose (RFD) based on a NOEL of 1.0 mg/kg/day (1-year
feeding study in dogs) and an uncertainty factor of 100 was calculated
to be 0.01 mg/kg/day. The theoretical maximum residue contribution
(TMRC) for the overall U. S. population from published and proposed
uses recommended through reregistration is 0.000532 mg/kg/day or 5.3%
of the RfD. For the most highly exposed subgroup, nonnursing infants
less than 1 year old, the published and proposed use recommended
through reregistration is 0.002184 mg/kg/day or 21.8% of the RfD. The
current action of increasing the tolerance on sorghum forage to 2.0
does not contribute any additional TMRC or utilize additional RfD
because sorghum forage is not a human food and current tolerances in
livestock commodities will not be exceeded as a result of the proposed
increase in the tolerance for sorghum forage.
Refinements in residue and percent-crop treated information were
considered in calculating the Anticipated Residue Contribution (ARC)
for the same population groups above. The ARC is considered the more
accurate estimate of dietary exposure. These exposure estimates were
then compared to the RfD for alachlor to get estimates of chronic
dietary risk. The ARC for the overall U. S. population for published
tolerances is 1.3 X 10-5 or 0.1% of the RfD. For the most highly
exposed subgroup, nonnursing infants, the ARC is 5.4 X 10-5 or
less than 1% of the RfD. The current action does not contribute
additional ARC or utilize additional RfD. Other tolerances proposed by
reregistration result in an ARC of 4.0 X 10-6 mg/kg/day or 0.04%
of the RfD for the overall U.S. population and an ARC of 5.3 X 10-
5 mg/kg/day or 0.5% of the RfD for nonnursing infants, less than 1 year
old.
Based on a Q*1 of 0.08 (mg/kg/day)-1 the upper-bound
cancer risk was calculated to be 1.4 X 10-6 and contributed
through all published and proposed uses for alachlor. The current
action for sorghum forage contributes no additional risks.
There are currently no regulations against the registration of this
chemical for use on sorghum forage. Even though alachlor is classified
as a probable human carcinogen, EPA believes the establishment of this
tolerance will not pose an unreasonable risk to humans as a result of
dietary exposure.
The pesticide is useful for the purposes for which tolerances are
sought. The nature of the residues is adequately understood for the
purposes of establishing tolerances. Adequate analytical methods (high-
pressure liquid chromatography and gas chromatography) are available
for enforcement purposes (PAM II, Method III).
Based on the information considered by the Agency, the Agency has
determined that when used in accordance with good agricultural
practice, this ingredient is useful and that the tolerance established
by amending 40 CFR part 180 would protect the public health. It is
proposed, therefore, 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 document 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 8F3671/P610]. All written comments filed
in response to this petition will be available in the Public Response
and Program Resources 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 12866. 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
Environmental protection, Administrative practice and procedure,
Agricultural commodities, Pesticides and pests, Reporting and
recordkeeping requirements.
Dated: March 30, 1995.
Stephen L. Johnson,
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 Sec. 180.249, by amending the table therein by revising the
entry for sorghum forage, to read as follows:
Sec. 180.249 Alachlor; tolerances for residues.
* * * * *
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Parts per
Commodity million
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* * * * *
Sorghum, forage............................................ 2.0
* * * * *
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[FR Doc. 95-8729 Filed 4-11-95; 8:45 am]
BILLING CODE 6560-50-F
