E X T O X N E T
Extension Toxicology Network
A Pesticide Information Project of Cooperative Extension Offices of
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Pesticide
Information
Profile
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Clethodim
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TRADE OR OTHER NAMES
Trade or other names include Cletodime, RE-45601 and Select, (1).
REGULATORY STATUS
Clethodim is a General Use Pesticide in EPA Toxicity Class II and
products containing it must bear the signal word WARNING (1, 2). Clethodim
was first registered in 1992 (3, 4).
INTRODUCTION
Clethodim is a selective post-emergence cyclohexenone herbicide used to
control annual and perennial grasses in a wide variety of broad leaf crops
including soybeans, cotton, flax, peanuts, sunflowers, sugarbeets, potatoes,
alfalfa and most vegetables (1, 2, 3). It is available in both the technical
form and an emulsifiable concentrate (2). Unless otherwise stated, data
presented herein refer to the technical product.
Clethodim has shown antagonism when used with Basagran (bentazon) or
Blazer (acifluorfen-sodium) (2, 3), and should be used with a non-phytotoxic
crop oil concentrate (1, 2). Clethodim is very well-tolerated by broad-leaved
crops, showing little if any phytotoxic effect (2, 3, 4). Formulations of
clethodim may include trimethylbenzene, xylenes, cumene and emulsifier as
inert ingredients (5).
TOXICOLOGICAL EFFECTS
ACUTE TOXICITY
Clethodim is moderately toxic by ingestion. The reported oral LD50s are
1,630 mg/kg and 1,360 mg/kg in male and female rats, respectively (2).
Reported LD50s for Select 2 EC formulation are 3,610 mg/kg and 2,920 mg/kg in
male and female rats, respectively (1, 3).
Clethodim is practically non-toxic by dermal absorption. The reported
dermal LD50 is greater than 5,000 mg/kg in rabbits for the technical product
as well as the formulation (1, 2, 3). The technical product did not cause
skin irritation in the rabbit (3), but the formulation (Select) caused
moderate skin as well as eye irritation in the rabbit (3). Eye irritation was
reversible within 8-21 days (3). Select formulation caused no skin
sensitization in guinea pigs (3). No data regarding skin sensitization or eye
irritation were available for the technical product.
Clethodim is practically non-toxic by the inhalation route as well. The
reported rodent 4-hour inhalation LC50s for clethodim technical and Select
formulation are greater than 3.9 mg/L and 4.4 mg/L, respectively (3, 4).
Effects of acute exposure to clethodim or Select may include eye or skin
irritation or central nervous system effects, e.g., salivation, decreased
motor activity, incoordination, unsteady gait and hyperactivity (3, 5). These
latter effects may be in large measure due to the aromatic constitutents of
the formulation, as these effects commonly occur upon exposure to such
compounds (6).
CHRONIC TOXICITY
In a one-year feeding study of dogs, doses of 75 mg/kg/day resulted in
increased relative and absolute liver weights, with anemia-like alterations in
blood chemistry such as reduced hemoglobin, erythrocyte and hematocrit counts
(4, 5). In a two-year chronic study of rats, no compound-related effects on
the structure and function of the liver were observed, and no changes in liver
weights were observed at the highest dose tested , approximately 100 mg/kg/day
(3, 4). Reduced body weight gain was observed in another study on rats at 350
mg/kg/day, but not at 100 mg/kg/day, over an unspecified period (3, 4).
Reproductive Effects
No effects on fertility, length of gestation or growth and development of
offspring were observed at doses up to and including the highest dose tested,
263 mg/kg/day (3, 4). No other data were available regarding reproductive
effects; while these data are insufficient, it appears unlikely that
reproductive effects would occur in humans under normal circumstances.
Teratogenic Effects
Reductions in fetal body weights and increases in skeletal abnormalities
were observed in rats at doses of 350 mg/kg/day (3, 4) and higher. In another
study of rats, there were significant reductions in fetal body weight, litter
size and significant increases in cervical rib deformation at doses of 700
mg/kg/day, but not at lower doses (3, 4). In rabbits, no teratogenic or
developmental effects were seen in offspring at doses up to and including the
highest dose tested, 300 mg/kg/day (3, 4).
The evidence suggests that while there have been documented teratological
effects in animal studies, such effects are unlikely in humans under normal
conditions of exposure.
Mutagenic Effects
Results of the Ames mutagenicity assay indicated that clethodim did not
show mutagenic potential (3, 4). Testing for unscheduled DNA synthesis in
mouse liver cells following oral administration of 5,000 mg/kg were negative
(7). Tests for structural chromosomal damage in rat bone marrow cells after
oral administration of 1,500 mg/kg were also negative (8). The available data
for mutagenicity and genotoxicity yield no evidence for mutagenic or genotoxic
activity.
Carcinogenic Effects
No carcinogenic effects were observed in mice administered clethodim at
doses of 24 mg/kg/day over an 18 month period (4). No carcinogenic effects
were observed in rats fed up to the highest dose tested, approximately 100
mg/kg/day, in a two-year carcinogenicity study (4). Based on the available
data, it appears that clethodim is not carcinogenic.
Organ Toxicity
The liver was the primary organ affected in chronic animal studies.
Although potential effects associated with acute exposure are reported to
include central nervous system effects (3, 5), no available chronic data
pointed to such effects.
Fate in Humans & Animals
Clethodim is readily absorbed in the gastrointestinal tract, with
approximately 90% absorption of oral doses (4). It is rapidly metabolized and
eliminated (primarily sulfoxide metabolites, ca 63%) with less than 1%
recoverable unchanged (4).
ECOLOGICAL EFFECTS
Effects on Birds
Clethodim is practically non-toxic to birds. Reported 8-day dietary
LC50s are greater than 6,000 ppm in the mallard duck and bobwhite quail (1)
and greater than 5,000 ppm for the Japanese quail (2). Under likely
conditions of use, it is unlikely to pose a hazard to avian species.
Effects on Aquatic Organisms
Clethodim is slightly toxic to fish and aquatic invertebrate species.
Reported 96-hour LC50s ranged from 18 mg/L (3) to 56 mg/L in rainbow trout
(2), and 33 mg/L in bluegill sunfish (3). A 48-hour LC50 of 20.2 mg/Lhas been
reported for Daphnia species (3) for the formulation. No effects were seen at
concentrations of 5.5 mg/L in Daphnia (4). No significant bioaccumulation has
been observed in fish (4). Under likely conditions of use, it is unlikely to
pose a hazard to aquatic species.
Effects on Other Animals (Nontarget species)
Clethodim is practically non-toxic to honeybees with reported LD50s of
greater than 100 ug/bee for both the technical product and Select formulation
(1, 3). EPA has stated that "available...wildlife data indicate that the
proposed uses on cotton and soybeans will result in minimal hazard to
nontarget and endangered beneficial insect, avian and freshwater fish and
mammalian species" (4).
Clethodim is selectively toxic to plants, affecting only grass species
(4).
ENVIRONMENTAL FATE
Breakdown of Chemical in Soil and Groundwater
Clethodim is of low persistence in most soils with a reported half-life
of approximately 3 days (3). Breakdown is mainly by aerobic processes,
although photolysis may make some contribution (4). Volatilization loss and
hydrolysis are probably not important processes in the soil breakdown of
clethodim (3). The main breakdown products in soils under aerobic conditions
are sulfoxide, sulfone and oxazole sulfone (4).
Clethodim and these degradates are weakly bound to soils, with reported
soil Kd (soil-water partition coefficient unadjusted for soil organic matter)
values of 0.05 and 0.23 over a range of five soils (3). Thus, while it may be
somewhat mobile in the soil environment , it is very short-lived. EPA has
stated "under present use patterns and under most circumstances clethodim does
not appear to threaten groundwater" (4). In field studies, no vertical
movement of the parent compound or residues was observed below the top 20 cm
of the soil (4).
Breakdown of Chemical in Surface Water
Clethodim may be highly persistent in the aquatic environment. Reported
half-lives for clethodim in the aquatic environment are 128 days in the
aqueous phase and 214 days in the sediment (4). The reported hydrolysis
half-life at pH 7-9 is approximately 300 days. The main pathway for
degradation of clethodim in the aquatic environment is anaerobic metabolism by
microorganisms (4). However, due to the low persistence and mobility of the
compound, it is unlikely to be found in surface waters.
Breakdown of Chemical in Vegetation
Clethodim is rapidly degraded on the leaf surfaces by an acid-catalyzed
reaction and photolysis (3). Remaining clethodim will rapidly penetrate the
cuticle and enter the plant. (3). Little information is available regarding
translocation and accumulation, but it is hypothesized that it may translocate
and accumulate at growing points (3). Within soybeans, cotton and lettuce it
is rapidly metabolized (3).
PHYSICAL PROPERTIES AND GUIDELINES
Clethodim is a clear, viscous, amber liquid at room temperature (2).
Exposure Guidelines:
| ADI: | Not Available |
| HA: | Not Available |
| RfD: | Not Available |
| TLV: | 1 mg/meters cubed (8-hour) (for Select 2 EC; manufacturer suggested; 5) |
Physical Properties:
| Chemical Name: | (+/-) 2-{(E)-1-{3-chloroallyloxyimino]propyl]-5-{2-(ethylthio)propyl}-hydroxycyclohexen-2-one (2) |
| CAS: | 99129-21-2 (2) |
| Molecular Weight: | 359.9 (2) |
| Water solubility: | Highly dependent on pH (2) |
| Solvent solubility: | Soluble in most organic solvents (2) |
| Melting Point: | Not Available |
| Vapor Pressure: | negligible @ 20 degrees C (2) |
| Partition Coefficient (octanol/water): | 0.49 @ pH=9; 40 @ pH=7; >3,000 @ pH=5 (9) |
| Adsorption Coefficient: | Kd =0.05 - 0.23 over a range of five soils (3, 4). |
BASIC MANUFACTURER
Valent USA Corp.
1333 N. California Blvd.
Walnut Creek, CA 94596-8025
510-256-2700
800-892-0099 (Emergency)
Review by Basic Manufacturer:
Comments solicited: June, 1995
Comments received: July, 1995
REFERENCES
Meister, R.T. (ed.) 1992. Farm Chemicals Handbook '92. Meister
Publishing Co., Willoughby, OH.
Royal Society of Chemistry. 1991 (as updated). The Agrochemicals
Handbook, Royal Society of Chemistry Information Services, Cambridge, UK.
Weed Science Society of America. 1994. Herbicide Handbook, Seventh
Edition. Weed Science Society of America. Champaign, IL.
US Environmental Protection Agency. 1992. Office of Pesticides and
Toxic Substances, Fact Sheet Number 230: Clethodim. Washington, DC.
Valent USA. 1993. Material Safety Data Sheet for Valent Select 2 EC
Herbicide. Valent USA Corporation. Walnut Creek, CA.
Sullivan, J.B. and Krieger, G.R. 1992. Hazardous Materials Toxicology,
Clinical Principles of Environmental Health. Williams & Wilkins, Baltimore,
MD.
Mirsalis, J.C. and Steinmetz, K.L. 1986. In Vivo-In Vitro Hepatocyte
DNA Repair Assay: In Vitro Evaluation of Unscheduled DNA Synthesis (UDS)
Following Oral Administration of Chevron RE-45601 Technical to B6C3F1 Mice
(Study No. LSC-1960). Stanford Research Institute, Menlo Park, CA.
Putnam, D.L. 1987. Cytogenetic Assay in Bone Marrow Cells of Rats
Following Acute Oral Exposure to RE-45601 Technical (Study T-5072.105).
Microbiological Associates. Fremont, CA.
Ashworth, D. J. 1988. Clethodim Technical Product Chemistry: Series 63
(Study No. 8828545). Chevron Chemical Company. Richmond, CA.
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criticism of unnamed products implied. Most of this information is historical
in nature and may no longer be applicable.
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