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methazole (Probe) Amendment of Cancellation Order 5/93

[OPP-66171A; FRL-4588-6]
Methazole; Amendment of Cancellation Order 
AGENCY: Environmental Protection Agency (EPA).
ACTION: Notice.
.
------------------------------------------------------------
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 
(2-(3,4-dichlorophenyl)-4-methyl-1,2,4-oxadiazolidine-3,5-dione). 
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 
31, 1993.
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) 
308-8173.
SUPPLEMENTARY INFORMATION:
I. Background
   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      
                            Cancellation Requests                           
                                                                            
-----------------+----------------------+----------------+------------------
     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 
Cancellation/Cancellation 
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 
only.
   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 
1993. 
   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 
the following:
   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. 
Daniel Barolo,
Acting Director, Office of Pesticide Programs.
[FR Doc. 93-12480; Filed 5-25-93; 8:45 am]
BILLING CODE 6560-50-F