methazole (Probe) Amendment of Cancellation Order 5/93
Methazole; Amendment of Cancellation Order
AGENCY: Environmental Protection Agency (EPA).
SUMMARY: This notice announces the Agency's decision to amend
the cancellation order of January 13, 1993, to allow the conditional
distribution, sale and use of all remaining stocks of methazole
In that earlier order, the Agency announced receipt and acceptance
of a request from Sandoz Agro, Inc. to voluntarily cancel the
remaining registrations of pesticide products containing methazole.
Sandoz Agro, Inc. was the sole registrant of methazole products.
EPA accepted the voluntary cancellation request based on Federal
Insecticide, Fungicide, and Rodenticide Act (FIFRA) section
6(a)(2) data submitted by the registrant to the Agency which
indicated that unreasonable worker risks may be associated with
the use of methazole. The cancellation order also announced
the restriction of distribution and sale of canceled methazole
products until additional toxicological data regarding the potential
risks were considered by the Agency. The Agency has since received
and evaluated the additional data and concluded that the level
of risk posed to workers exposed to the chemical are acceptable.
Based on the recent toxicological data, the Agency is allowing
the distribution, sale and use of remaining stocks conditioned
upon revised supplemental labeling being provided at the time
of sale of such existing stocks.
DATES: The restriction of distribution, sale, and use of existing
stocks is removed effective May 20, 1993. Distribution, sale,
and use of existing stocks will be permitted until December
FOR FURTHER INFORMATION CONTACT: By mail: Joseph Bailey, Special
Review and Reregistration Division (H7508W), Environmental Protection
Agency, 401 M St., SW., Washington, DC 20460. Office location
and telephone number: Special Review Branch, Rm. 2G6, Crystal
Station 1, 2800 Jefferson Davis Highway, Arlington, VA (703)
Methazole, a selective herbicide used to control several
varieties of weeds in cotton, was registered for preemergence
use west of the Mississippi and directed postemergence use both
east and west of the Mississippi. Most of the methazole produced
for cotton production is applied in Louisiana and Mississippi
with some use occurring in other cotton producing States. The
season for methazole use typically begins in April/May.
Under FIFRA section 6(f)(1)(A), registrants may request at
any time that EPA cancel any of their pesticide registrations.
If the pesticide for which cancellation was requested is registered
for any minor agricultural use, section 6(f)(1)(C) dictates
that EPA publish in the Federal Register a notice of the receipt
of the cancellation request, and allow 90 days for public comment
before granting the request unless either the registrants request
a waiver of the 90-day period or the Administrator determines
that the continued use of the pesticide would pose an unreasonable
adverse effect on the environment.
On May 18, 1992, Sandoz Agro., Inc. requested voluntary cancellation
of the remaining two registered methazole products. Prior to
the submission of the voluntary cancellation request, Sandoz
Agro, Inc. had submitted to the Agency, pursuant to FIFRA section
6(a)(2), preliminary results from a rat reproduction study indicating
that a high percentage of the dosed generation's offspring developed
cataracts. The Agency concluded from these test results that
an unacceptable risk is possible to those workers exposed to
methazole, particularly mixer/loaders and applicators. The products
for which cancellation was requested are listed in Table 1 below.
On August 12, 1992, the Agency notified Sandoz Agro, Inc.
that it had accepted their request for voluntary cancellation;
however, due to the potential risks posed to workers exposed
to methazole, the Agency waived the 90-day comment period usually
afforded to such voluntary cancellations. In the Agency's notice,
it was stated that a cancellation order establishing provisions
for existing stock disposition would be forthcoming.
Table 1.-Methazole Section 3 (national) Registrations: Voluntary
Company | | Product |
Registration | Company Name/Address | Registration | Product Name
Number | | Number |
| | |
55947 | Sandoz Agro, Inc., | 55947-22 | Technical
| | | Probe
| 1300 East Touhy | 55947-23 | Probe 75
| Avenue, | | Wettable
| | | Powder
| Des Plaines, IL, | |
| 60018 | |
In September 1992, Sandoz offered to conduct two studies,
a dermal absorption study and a developmental toxicity study,
in order to provide additional data on the potential risks.
The Agency agreed to wait and consider the additional data in
revising the risk assessment for worker exposure before making
a final decision on disposition of the existing stocks. In the
Federal Register of January 13, 1993 (58 FR 4167), the Agency
published a Notice of Receipt of Request for Voluntary
Order which announced acceptance of Sandoz's request for voluntary
cancellation of its methazole products and restricted the distribution
and sale of all remaining stocks of methazole until after the
Agency had considered the additional data.
In case the Agency's revised risk assessment indicated an
acceptable risk to workers, Sandoz requested the Agency to review
supplemental labeling revisions that would be applicable to
the existing stocks and would lower worker exposure to methazole.
The supplemental label revisions are as follows:
1. Deletion of all pre-emergence uses for methazole.
2. Use limited to post-emergence, directed band application
3. Reduction in rate of application to a maximum of 0.33
pound of product (0.25 pound of active ingredient) per acre
applied on a band.
The Agency reviewed the proposed supplemental labeling revisions
and on February 26, 1993, notified Sandoz that, should the Agency
allow any further distribution, sale, and use of the canceled
methazole products, it would condition such distribution, sale,
and use on the revised supplemental labeling being provided
at the time of sale of all existing stocks.
In March 1993, Sandoz provided the results of the two studies
as agreed upon with the Agency. The Agency's review of the dermal
absorption study indicated that the data were insufficient to
warrant any adjustments to the Agency's risk assessment based
on dermal absorption. The Agency also reviewed the data submitted
from the developmental study and based on it, concluded that
risks to adult workers are acceptable when exposed to methazole
used in accordance with the revised supplemental labeling. A
discussion of the toxicological findings in the developmental
study are provided in Unit II of this document.
Methazole, no longer being produced by Sandoz Agro, Inc.,
remains solely in the hands of sellers, distributors, and end-
users. FIFRA section 12(a)(1)(A) states that it is unlawful
for any person in any State to distribute or sell to any person
any pesticide whose registration has been canceled unless such
distribution or sale has been authorized by the Administrator.
Sandoz Agro, Inc. notified its customers who may have methazole
in their possession that they should not sell or distribute
any of the existing stocks until the Agency had reviewed the
additional data and reached a final determination regarding
the potential risk.
Methazole is no longer considered a registered active ingredient
and has been removed from List B reregistration chemicals. Once
an active ingredient is canceled, any person wishing to bring
the pesticide back on the market would need to apply to EPA
for a ``new chemical'' registration. Such a registration generally
would not be approved until all applicable data requirements
are satisfied and there are no unreasonable adverse effects
expected as a result of its use.
II. Toxicological Findings
The Agency based its decision to accept voluntary cancellation
of methazole products and interim restriction of existing stocks
on FIFRA section 6(a)(2) data submitted by Sandoz Agro, Inc.,
which indicated that cataracts may be associated with exposure
to methazole. At that time, the Agency agreed that a final decision
on disposition of existing stocks would be determined after
Sandoz conducted voluntary toxicological studies which may provide
additional information to clarify the potential risks from exposure
to methazole. The additional data for consideration were to
be obtained from a rat dermal absorption study and a rat developmental
toxicity study. Data from each study were received in March
The Agency's review of the data from the dermal absorption
study concluded that no further adjustments to the risk assessment
should be made based on the study results. The Agency concluded
that inconsistencies in the data did not warrant any changes.
The results from the developmental toxicity study proved
to be more useful and provided additional information which
the Agency considered in revising the risk assessment. This
study was designed to clarify the cause and course of cataract
formation in the test animals. In summary, the data indicated
1. Methazole-induced opacities in rat pups are probably not
a developmental effect but rather a direct toxic effect.
2. Lens opacities in pups is not a transient ``cloudiness''
in the developing eye and cannot be attributed to maternal toxicity.
They may be reversible to some degree.
3. In utero exposure to methazole for 6 days following eye
development did not induce opacities.
4. High-dose and control pup weights were similar on lactation
days 1 and 4, suggesting that in utero fetal exposure was not
sufficient to induce lens opacities.
5. Changes in body weight suggest that affected pups received
their greatest exposure to methazole around lactation day 8
when they began eating the formulated food. It is likely that
opacities developed within several days of eating the feed.
6. The threshold dose for adult rats is probably much higher
than for neonate pups.
Based on the results of the developmental toxicity study
and an earlier 90-day rat feeding study, the Agency concludes
that developmental toxicity concerns are essentially dismissed
and therefore, the likelihood of the fetus of a pregnant worker
being at particular risk is not of concern. Methazole-induced
lens opacities in pups appeared to be a direct toxic effect
that developed over a brief period of time (several days). Furthermore,
examination of the adult female eyes revealed no opacities at
the high-dose level, suggesting that these adults were not at
risk of developing opacities. The adult rat data from this study
are consistent with data from an earlier 90-day feeding study
in rats where no significant eye lesions were found pretest
or at study termination.
Available data indicate that adults are far less susceptible
to cataractogenic effects of methazole than are neonates. Since
workers are expected to be adults, and pregnant workers are
no longer considered to be a unique risk, the high-dose in the
90-day rat feeding study (500 parts per million; 25 milligrams/kilogram/day)
is used as a No-Observed-Adverse-Effects-Level (NOAEL) for lens
opacities in Margin of Exposure (MOE) calculations. The Agency
determined MOEs for dermal exposure, inhalation exposure, and
total exposure. Because inhalation exposure is minimal, the
calculations for dermal and total exposure are essentially the
same. Using the NOAEL from the high-dose in the 90-day rat feeding
study, the Agency has determined that for mixer/loader/applicators,
workers who would potentially receive the highest exposure while
handling methazole, the MOE for total exposure is 735. Generally,
the Agency believes an MOE of 100 or greater is adequately protective
of human health. Based on this risk assessment calculation,
the Agency has determined that worker exposure to methazole
does not present any unreasonable risks when used in accordance
with the revised supplemental labeling.
III. Amendment to Cancellation Order
In accordance with the Agency's June 26, 1991 Existing Stocks
of Pesticide Products Statement of Policy, distribution and
sale of existing stocks of canceled pesticide products that
raise risk concerns will not be allowed unless it is demonstrated
that such distribution, sale, and use would not result in unreasonable
adverse effects. In the cancellation order dated January 13,
1993, the Agency prohibited the distribution and sale of remaining
stocks of methazole products unless and until it could be demonstrated
that the distribution, sale, and use would not result in unreasonable
risks to health or environment. Subsequent to that order, Sandoz
submitted additional toxicological data to the Agency. The Agency
has considered these additional toxicological data concerning
risks posed to workers by exposure to methazole and has concluded
that short-term exposure to adult mixer/loader/applicators of
methazole does not present unreasonable adverse effects when
used in accordance with the revised supplemental labeling.
The Agency is therefore, allowing distribution, sale, and
use of the existing stocks of methazole products pursuant to
FIFRA section 6(a)(1). This distribution, sale, and use of existing
stocks of methazole is permitted only if the revised supplemental
labeling stated in Unit I of this document is provided at the
time of sale of the existing stocks. Furthermore, as a condition
of the distribution, sale, and use of the existing stocks of
methazole, the Agency is requiring Sandoz Agro, Inc. to notify
the EPA of: (1) The quantity of canceled methazole existing
stocks held by distributors and sellers and (2) the location
at which the canceled pesticide is stored. Existing stocks are
defined as those stocks of methazole (EPA Registration Number
55947-23) which are held in the hands of those who will distribute
and/or sell any of the end-use product. The reporting shall
include the number of pounds of product in possession of the
distributor or seller as of [insert date of signature] and the
number of pounds of product remaining with the distributor/seller
as of December 31, 1993. End-users are not required to report
their stocks of canceled methazole products. The reporting shall
identify each distributor and seller and the street address
of each location of existing stocks, including the name and
telephone number of a contact person at that location. The reporting
information is to be submitted to the following address: Director,
Compliance Monitoring Division, Office of Compliance Monitoring
(EN-342), U.S. Environmental Protection Agency, 401 M St., SW.,
Washington, DC 20460.
Dated: May 20, 1993.
Acting Director, Office of Pesticide Programs.
[FR Doc. 93-12480; Filed 5-25-93; 8:45 am]
BILLING CODE 6560-50-F