PMEP Home Page --> Pesticide Active Ingredient Information --> EXTOXNET: The Extension Toxicology Network --> Carbaryl to Dicrotophos --> Clethodim

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 Assessment Program.

  Pesticide
Information
Profile
Clethodim

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

  1. Meister, R.T. (ed.) 1992. Farm Chemicals Handbook '92. Meister Publishing Co., Willoughby, OH.
  2. Royal Society of Chemistry. 1991 (as updated). The Agrochemicals Handbook, Royal Society of Chemistry Information Services, Cambridge, UK.
  3. Weed Science Society of America. 1994. Herbicide Handbook, Seventh Edition. Weed Science Society of America. Champaign, IL.
  4. US Environmental Protection Agency. 1992. Office of Pesticides and Toxic Substances, Fact Sheet Number 230: Clethodim. Washington, DC.
  5. Valent USA. 1993. Material Safety Data Sheet for Valent Select 2 EC Herbicide. Valent USA Corporation. Walnut Creek, CA.
  6. Sullivan, J.B. and Krieger, G.R. 1992. Hazardous Materials Toxicology, Clinical Principles of Environmental Health. Williams & Wilkins, Baltimore, MD.
  7. 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.
  8. 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.
  9. Ashworth, D. J. 1988. Clethodim Technical Product Chemistry: Series 63 (Study No. 8828545). Chevron Chemical Company. Richmond, CA.