E X T O X N E T
Extension Toxicology Network
A Pesticide Information Project of Cooperative Extension Offices of
Cornell University, Michigan State University, Oregon State University, and
University of California at Davis. Major support and funding was provided
by the USDA/Extension Service/National Agricultural Pesticide Impact
Publication Date: 9/93
TRADE OR OTHER NAMES
Trade names for products containing carboxin include Cadan, Padan,
Sanvex, Thiobel, and Vegetox. It is very often used in combination with
other fungicides such as thiram or captan.
Carboxin is a systemic anilide fungicide. It is used as a seed
treatment for control of smut, rot, and blight on barley, oats, rice,
cotton, vegetables, corn and wheat. It is also used to control fairy
rings on turf grass. The product may be used to prevent the formation
of these diseases or may be used to cure existing plant diseases (9).
Carboxin is a general use pesticide.
Carboxin is a slightly toxic compound and carries the signal word
CAUTION on the label. Symptoms of acute poisoning can include vomiting
and headache. Recovery is very rapid if the exposed individual is
treated quickly. One study reported a rat oral LD50 of 430 mg/kg (4).
Since chronic studies have been successfully completed at doses higher
than this, the LD50 of 3,820 mg/kg which was reported in another study
seems more reasonable (5) and is consistent with the oral LD50 of 3,550
mg/kg in mice (2).
The compound produces very little skin irritation, however it can
seriously irritate the eyes. Rabbits which had been exposed to carboxin
on their skin for three weeks showed no irritation.
A 28-day study with rats fed doses up to 311 mg/kg showed some
fluid accumulation in the liver even at low doses (2). Another rat
study showed kidney changes at somewhat higher doses (1,000 mg/kg) fed
for 90 days (2). A two-year rat study with levels of up to 30 mg/kg
produced no compound-related effects in terms of physical appearance,
behavior, blood chemistry, or urinalysis (2). However, there were
changes in organ weights.
Male and female mice also showed liver effects after being fed high
doses (912 mg/kg) of carboxin for a year and a half (2). Beagle dogs
showed no effects at the highest dose tested, 15 mg/kg for two years
(2). Carboxin has an unusually broad range between the maximum
tolerated dose and the dosage that produces no effects.
A three-generation study with rats showed treatment-related effects
on reproductive performance at levels from 5 to 30 mg/kg/day. However,
at the highest dose, there was only moderate growth suppression in
nursing pups (2). It is unlikely that the compound would produce any
reproductive effects in humans at expected exposure levels.
At the highest dose tested, 40 mg/kg administered to pregnant rats
on days 6 through 15, there were no birth defects in the offspring (2).
Pregnant rabbits treated with very high doses on days 6 through 27 of
gestation had increased abortions but no fetal malformations (2).
Carboxin is either a non-mutagen or is a very weak mutagen based on
information from several studies on bacteria and mammalian cells.
A two-year study with rats fed up to 30 mg/kg/day showed no
evidence of increased tumor frequency (2). Another two-year study at
levels up to 3,000 ppm (approximately 180 mg/kg/day), had similar
Mice fed up to 900 mg/kg for 84 weeks had no apparent compound-
related increase in tumor formation. It is not likely that carboxin
would cause cancer in humans.
In an adolescent human, ingestion of carboxin treated seeds
resulted in headache and vomiting within one hour, with the patient
recovering quickly (within two hours). There was no mention of the
ingested dose (10).
Fate in Humans and Animals
Rats excreted almost all of a carboxin dose in 24 hours, with most
excreted in urine and some in feces (5). Rabbits showed a similar
excretion pattern. Carboxin is incompletely absorbed in the gut,
especially in rats (2). The compound does not acumulate in animal
tissues. The main breakdown product is carboxin sulfoxide for which
the rat oral LD50 is 2,000 mg/kg. Carboxin sulfoxide is sold as a
pesticide also and is known as oxycarboxin (5).
Only trace amounts of carboxin were found in rat tissues 48 hours
after dosing (2). In milk cows fed up to 5 ppm for 10 days, less than
2% of the administered dose was found in tissues. However, significant
levels were found in milk a few days after exposure.
The oral LD50 in chickens is very high at 24 grams/kg indicating
that it has a very low acute toxicity (1). In chronic, low exposure
experiments of 5.5 months, changes were noted in the digestive tract,
cardiovascular system and blood of chickens (3).
Carboxin is highly toxic to fish. The 96-hour LC50 for rainbow
trout was greater than 0.1 mg/l (1), however the specific values were
not given. Carboxin is practically non-toxic to freshwater
invertebrates. Juvenile crayfish in a similar test had a 217 mg/l LC50
(3). The compound is non-toxic to bees.
Carboxin is rapidly degraded to carboxin sulfoxide in soil. In one
study, after seven days, 95% of the parent was gone and the sulfoxide, a
breakdown product, represented 31 to 45% of the amount applied. Minor
products formed were carboxin sulfone, hydroxy carboxin and CO2.
Carboxin does not readily adsorb to soil. Both parent and sulfoxide are
very mobile and could possibly leach to groundwater (2).
In water, carboxin oxidizes to the sulfoxide and sulfone within
seven days (2). This happens both under ultraviolet light and in the
dark (5). Blue-green algae like Anabaena and Nostoc degrade the
pesticide extensively. Other algae can also break down carboxin, but
not to the same extent (1).
Although the distribution pattern of the parent and sulfoxide
metabolite vary, carboxin is found systemically (throughout the plant)
in all species of plants studied (5). Plants grown from treated seed
had no carboxin present six weeks after emergence. Carboxin sulfoxide
found in plants can come either from the soil or through oxidation
within the plant.
|NOEL (rats): ||10 mg/kg/day
|HA: ||0.7 mg/l (lifetime)
|RfD: ||0.1 mg/kg/day
|LEL: ||30 mg/kg/day
|DWEL: ||4 mg/l
|CAS #: ||5234-68-4
|Chemical Name: ||5,6-dihydro-2-methyl-N-phenyl-1,4-oxathiin-3-carbamil
|Chemical class/use: ||carboxanilide fungicide
|Solubility in water: ||195 mg/l at 25 degrees C
|Solubility in other solvents: ||acetone 600 g/kg; benzene 150 g/kg; methanol 210 g/kg
|Melting Point: ||93-95 degrees C
|Vapor Pressure: ||11.8 x 10 to the minus 7 power mm Hg
|Absorption Coefficient: ||260 ml/gram
Uniroyal Crop Protection Div
Middlebury, CT 06749
Review by Basic Manufacturer:
Comments solicited: November, 1992
National Library of Medicine (1992). Hazardous Substances
Databank. TOXNET, Medlars Management Section, Bethesda, MD.
U.S. Environmental Protection Agency (1987). Health Advisory,
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U.S. Environmental Protection Agency (1968-81). Pesticide
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Division, 79-0210, 81-3526.
National Institute for Occupational Safety and Health (1983
Supplement) Registry of Toxic Effects of Chemical Substances, U.S. Dept
of Health and Human Services, Public Health Service, Centers for Disease
Control, Cincinnati, OH.
Food and Drug Administration (1986). The FDA Surveillance Index.
Bureau of Foods, Dept of Commerce, National Technical Information
Service, Springfield, VA.
Occupational Health Services, Inc. (1988). Hazardline, New York,
Hartley, D., and H. Kidd, Editors (1986). The Agrochemicals
Handbook. The Royal Society of Chemistry, The University, Nottingham,
Chin, Wei-Tsung, G. M. Stone and A. E. Smith (1970). Metabolism of
Carboxin (Vitavax) by Barley and Wheat Plants, J Agric Food Chem
Ware, George W. (1986). Fundamentals of Pesticides, A Self
Instruction Guide. ThomsonPublications, Fresno, Ca.
U.S. Environmental Protection Agency (1987). Carboxin. Health
Advisory. Office of Drinking Water.