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benomyl (Benlate) NAPIAP Profile on Benomyl 8/92

                                                               August 31, 1992
INFORMATION FROM NAPIAP
BENOMYL
BACKGROUND.  In Spring 1991, complaints began about possible phytotoxicity 
associated with use of the fungicide benomyl.  Complaints have continued, and 
recently a number of human health problems have been attributed to benomyl as 
well.  Most of the phytotoxicity and health problems have been reported from 
Florida.  The Department has responded to a number of inquiries related to 
these concerns.  Since this issue has the potential of blossoming into a 
national crisis such as Alar, NAPIAP is providing this information so you will 
be prepared to address the situation if necessary.
-- Benomyl (Benlate) is a systemic fungicide that is used to control a wide
   range of diseases on many plants (see Attachment 1).  DuPont introduced
   this compound in 1968, and it was first used in the United States in 1969.
-- Benlate was sold as a wettable powder (WP) until 1986, when the formulation
   was changed to a dry flowable (DF).  In 1989, there was an atrazine
   contamination of the Benlate DF, followed by a recall.  With this problem
   corrected, the fungicide went back on the market.  The first reported
   incident of phytotoxicity thought to result from the Benlate DF was in
   March 1991.  DuPont has withdrawn the label for ornamental use since many
   of the reported incidents involved use on ornamentals.
-- In plants, benomyl is converted to butyl isocyanate and carbendazim (MBC)
   (see Attachment 2); the carbendazim is the primary fungitoxic compound.
   Fungitoxicity results from a disruption of the cell division process.
   Carbendazim binds to tubulin, thus interfering with the mitotic apparatus
   and inhibiting nuclear division as a result. Carbendizim does not have a
   high affinity for mammalian tubulin.  Concentrations of toxicant present,
   as well as binding affinity, may determine selectivity between a plant and
   a pathogenic fungus.
-- The highly specific mode of action, coupled with widespread, intensive use,
   resulted in the occurrence of fungal resistance to benomyl a few years
   after it was introduced.  Resistance management strategies have kept
   benomyl as an important tool in disease control.
-- Mammals rapidly metabolize benomyl and carbendzim; metabolites are excreted
   via urine and feces.  Metabolism and excretion are important factors in
   reducing toxicity and preventing accumulation in tissues.
-- Benomyl is not acutely toxic to mammals.  Due to the low toxicity, it has
   not been feasible to administer large enough doses in animal studies to
   firmly establish the LD50.  The level is given as greater than 10,000
   mg/kg for oral doses to rats.  WHO gives benomyl a Class O rating, which
   means it is unlikely to present an acute hazard in normal use.
-- In EPA's classification system for carcinogens, benomyl is placed in Group 
   C (possible human carcinogen, see Attachment 3).
-- The half-life of benomyl residue is approximately 3 to 6 months in turf and
   6 to 12 months in bare soil.  The behavior of benomyl in soils indicates
   that the breakdown product carbendazim degrades gradually.  Benomyl and
   carbendazim residues are strongly retained by soil particles and do not
   constitute a hazard to water sources; through leaching.  Tests have shown
   that crops planted subsequently to those treated with benomyl do not take
   up benomyl residues from the previously treated soil.
-- NAPIAP has conducted two assessments on benomyl.  The first was in 1978-
   1979 in response to EPA's rebuttable presumption against registration of
   benomyl.  This document is available as USDA Technical Bulletin Number
   1678.  The second assessment took place in conjunction with a general
   assessment of fungicides in U.S. agriculture. This material is available in
   a series of documents published in 1991.
--------------------
The information provided in this information sheet was derived from the 
following sources.  EXTOXNET (Extension Toxicology Network); USDA Technical 
Bulletin #1678, "The Biologic and Economic Assessment of Benomyl" (1978); 
NAPIAP Fungicide Assessment (1991), and information from the organization 
"Resources for the Future" provided by Mr. Leonard P. Gianessi.
The tables at the end of this information sheet, which list benomyl usages in 
the United States, (Attachment #1) were provided from the organization 
Resources for the Future.  According to Mr. Gianessi, this is the most current 
data available at this time on benomyl.
This sheet was prepared by Thomas J. Kergel, Technical Writer, USDA NAPIAP.
                                                                  Attachment 3
The EPA's Classification System for Carcinogens
     The EPA classification system for carcinogens is adapted from a similar 
system developed by the International Agency for Research on Cancer.  It is 
used by the EPA to classify all potential human carcinogens, not just 
pesticides.  The purpose of the system is to characterize a compound's
carcinogenic hazard to humans.  Substances are classified based on the
evaluation of such factors as the results of mutagenicity tests, consideration
of any negative oncogenicity results, the types and diversity of tumors
induced, the structural similarity of the compound to other carcinogens, and
whether positive results have been replicated.
GROUP A -- Human carcinogen
     Sufficient evidence from epidemiologic studies to support a causal
association between exposure to agents and cancer
GROUP B -- Probable human carcinogen
B1 -- Sufficient evidence of carcinogenicity from animal studies with limited
      evidence of carcinogenicity from epidemiologic studies
B2 -- Sufficient evidence of carcinogenicity from animal studies, with
      inadequate or no epidemiologic data
GROUP C -- Possible human carcinogen
     Limited evidence of carcinogenicity in the absence of human data
GROUP D -- Not classifiable as to human carcinogenicity
     Inadequate or no human and animal data for carcinogenicity
GROUP E -- Evidence of noncarcinogenicity for humans
     No evidence of carcinogenicity in at least two adequate animal tests in
different species in adequate epidemiologic and animal studies.  This
classification is based on available evidence and does not mean that the agent
will not be a carcinogen under any circumstances.

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