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Methoprene

Publication Date: 9/95

TRADE OR OTHER NAMES

Some trade names include Altosid, Apex, Diacon, Dianex, Kabat, Minex, Pharorid, Precor, ZR-515.

REGULATORY STATUS

Methoprene is classified by the U.S. Environmental Protection Agency (EPA) for general use as both an insecticide and a growth regulator. Products containing methoprene must bear the signal word "Caution" (14). Check with specific state regulations for local restrictions which may apply.

INTRODUCTION

Methoprene is referred to as an insect growth regulator because it interferes with the maturation stages through which an insect goes: from egg, larvae, and pupa, to adult. Growth regulators make it impossible for insects to mature to the adult stage of development. Methoprene is considered a biochemical pesticide because rather than controlling target pests through direct toxicity, it interferes with the insects' life cycle and prevents them from reaching maturity or reproducing (2, 16). In order to be effective, it is essential that this growth inhibitor be administered at the proper stage of the target pest's life cycle (4). Methoprene is not toxic to the pupal or adult stages. Treated larvae will pupate but adults do not emerge from the pupal stage. Methoprene is also considered a larvicide since it is effective in controlling the larval stage of insects. Methoprene is used in the production of a number of foods including meat, milk, eggs, mushrooms, peanuts, rice and cereals. It is also used in aquatic areas to control mosquitoes and several types of ants, flies, lice, moths, beetles and fleas (7, 8, 16). It is available in liquid, solid and aerosol formulations (14).

TOXICOLOGICAL EFFECTS

ACUTE TOXICITY

Methoprene is relatively non-toxic when ingested or inhaled and slightly toxic by dermal absorption. No overt signs of poisoning have been reported in incidents involving accidental human exposure to methoprene (9). Methoprene is not an eye or skin irritant and it is not a skin sensitizer. It poses very little hazard to humans or other nontarget species with the exception of estuarine invertebrates (16).

The amount of methoprene that is lethal to one-half (50%) of exposed test animals is called its lethal dose fifty, or LD50. The oral LD50 for methoprene in rats is greater than 34,600 milligrams per kilogram (mg/kg). The oral LD50 for methoprene in dogs is between 5,000 and 10,000 mg/kg. The dermal LD50 for methoprene in rabbits is between 3,038 - 10,250 mg/kg (18).

The lethal concentration fifty (LC50) is that concentration of a material in air or water that kills half of a population that is experimentally exposed to the chemical for a given time period. The inhalation LC50 for methoprene in rats is greater than 210 mg/liter (1, 9). Labels on methoprene containers bear the signal word "CAUTION" (2).

CHRONIC TOXICITY

No methoprene-related effects were observed in two-year feeding trials with rats given up to and including a 5,000 ppm diet, nor in mice on a 250 ppm diet, daily for 18 months (18).

Reproductive Effects

Experimental data indicate that there are no reproductive hazards associated with methoprene (9, 16). No methoprene-related effects were observed in three-generation reproduction studies in rats on 2,500 mg/kg diets (10). Similarly, no effects were observed in the reproduction of bobwhite quail and mallard ducks at 30 parts per million (ppm) constant feeding of Altosid (11).

Teratogenic Effects

There are no teratogenic hazards associated with methoprene (9, 16). No teratogenic effects were seen in rats or rabbits at 500 mg/kg (10, 17).

Mutagenic Effects

Methoprene is not mutagenic (16). No methoprene-related mutagenic effects were observed in rats at 2,000 mg/kg (10, 17). This dose was given in a single acute experiment and in five-day repeated dosing experiments (11).

Carcinogenic Effects

Methoprene is not a carcinogenic compound (16). No tumors were formed in mice being fed daily diets containing methoprene up to and including 2,500 ppm, the highest dose tested, giving an approximate methoprene intake of 357 mg/kg/day in mice. In rats, the highest dose tested with no evidence of a carcinogenic effect was 5,000 ppm in diet giving a daily methoprene intake of approximately 250 mg/kg. NOELs (No-Observable-Effect-Level) for carcinogenicity in rats or mice, if any, are higher than the highest dose levels tested in these species. (18, 22)

Organ Toxicity

Liver changes were observed in mice fed diets containing methoprene at 1,000 and 2,500 ppm levels for 18 months (approximately equal to daily intakes of 143 and 357 mg/kg). Increased liver weights were observed in rats that were fed diets containing methoprene at 5,000 ppm (approximately equal to daily intake of 250 mg/kg) for 90 days but not when rats were fed the 5,000 ppm diet daily for 24 months, allowing approximately the same intake of methoprene (250 mg/kg/day). (18, 22)

Fate in Humans and Animals

In mammals, methoprene is rapidly and completely broken down and excreted, mostly in the urine and feces (1, 4, 16). Some evidence suggests that methoprene breakdown products, or 'metabolites,' are incorporated into natural body components (9). Methoprene is excreted unchanged in cattle feces in amounts that are sufficient to kill some fly larvae that breed in dung (4).

ECOLOGICAL EFFECTS

The use of methoprene as a mosquito larvicide should have no adverse effects on populations of endangered birds, mammals, or fish (9). However, it may kill shrimp and crabs (8), but the dose levels of Altosid Liquid Larvicide (A.L.L.), an (S)-methoprene based mosquito control product, currently on the market, required to produce such an effect is 105 times higher than the usual level of 10 ppb, generated by recommended rate for A.L.L. application (18).

Effects on Birds

According to a recent EPA evaluation of ecological effects, methoprene is considered practically non-toxic to mallard duck (16). This is because oral LD50 of methoprene for mallard is greater than 2,250 mg/kg with no mortality or any overt signs of toxicity at any dose level. Further, LC50 in 8-day feeding studies in both, mallard duck and bobwhite quail was more than 10,000 ppm, indicating again that methoprene is practically non-toxic to birds (3, 18, 21). Methoprene had no effect on quail reproduction (16).

Effects on Aquatic Organisms

Methoprene is moderately toxic to warm water, freshwater fish, and is slightly toxic to cold water, freshwater fish (16). Exposure of aquatic organisms will be limited by the low solubility (0.51 ppm) of methoprene in water and by its rapid degradation in aquatic environments.

The level of Altosid in water that was lethal for 50% of the test fish was 4.62 ppm in bluegill, 4.39 ppm in trout, and greater than 100 ppm for channel catfish and largemouth bass (14). Methoprene residues build up in the edible tissues of bluegill sunfish and crayfish (9).

Technical methoprene can be very highly acutely toxic to estuarine and marine invertebrates. Marine organisms are not likely to be exposed as a result of the use of methoprene as a mosquito larvicide (16). The LC50 of methoprene for fresh water shrimp was greater than 100 ppm. The LC50 for estuarine mud crabs was greater than 0.1 ppm (12). The effects of a methoprene based mosquito larvicide product that is actually used in the field (ALTOSID LIQUID LARVICIDE - A.L.L.), on the non-target aquatic crustaceans, such as adults and larvae of shrimp, crabs and adult ghost shrimp have been investigated under controlled conditions, only recently. These data indicate that a 96-hour LC50 for adult shrimp or adult crab was 105 times higher than the levels of 10 ppb, generally expected to be produced at recommended application rate of A.L.L. For larvae, the 48-hour LC50 was 103 times higher than the concentration of methoprene measured in water (2.5 ppb) at the recommended rate of A.L.L. application (19). Except when applied in slow- release briquettes, use of methoprene is not expected to result in exposure to aquatic invertebrates because methoprene is short-lived in aquatic environment and it does not have a high potential for bioaccumulation. Data regarding the use of briquette formulation is currently under review by the EPA (15), however, data provided by the manufacturer suggests that even briquettes do not produce methoprene levels higher than 10 ppb at any time (18, 20).

Effects on Other Animals (Nontarget species)

Methoprene is toxic to amphibians, such as frogs, toads, and salamanders. Reportedly, low application rates and rapid dissipation characteristics of this material should prevent water concentrations from reaching levels that are lethal to most amphibians. Methoprene use as mosquito larvicide poses some hazards to freshwater invertebrates, but major effects are unlikely (9).

Methoprene poses little danger to nontarget insects. It is likely, however, that Altosid could negatively affect some nontarget insects if it is applied at rates that far exceed those intended for use (12). While it is toxic to most insects, there is a distinct difference among the susceptibilities of various species to the adverse effects of this material. The critical factor is the timing of treatment in relation to the insect's stage of development (4). It can be used around bees with minimum injury (6). Altosid had very little effect, if any, on 35 species of exposed nontarget organisms including earthworms, waterfleas, damselflies, snails, tadpoles, and mosquito fish (12).

ENVIRONMENTAL FATE

Breakdown of Chemical in Soil and Groundwater

Methoprene is not persistent in soils and is unlikely to contaminate groundwater (2, 16). The breakdown, or degradation, of methoprene was rapid in experimental soil tests. In soil, microbial degradation is rapid and appears to be the major route of its disappearance from soil (9, 16). Methoprene also degrades rapidly in sunlight (16). In sandy loam, its half- life was calculated to be about 10 days (5). When Altosid was applied at an extremely high application rate of one pound per acre, its half-life was less than ten days. Methoprene is not likely to leach, since it is rapidly bound, or adsorbed, to soil. It was relatively immobile in four experimental soil types (9). In leaching studies, Altosid has been observed only in the top few inches of the soil, even after repeated washings with water (11).

Breakdown of Chemical in Water

Methoprene degrades rapidly in water (16). Studies have been conducted in a pond on the degradation of methoprene by microorganisms. The insecticide's half-life in pond water was about 30 hours at 0.001 ppm and 40 hours at 0.01 ppm (5). Under normal conditions of sunlight and temperature, technical methoprene rapidly degrades when it is applied to water. The half- life of this material is less than two days in the field. Aquatic microorganisms and sunlight degrade Altosid (12). Methoprene degrades rapidly in sunlight, both in water and on inert surfaces (16). Since methoprene is toxic to aquatic invertebrates, it should be used carefully and in accordance with label directions. Water can be contaminated and aquatic organisms harmed by inappropriate cleaning of equipment, or disposal of wastes, associated with methoprene (9).

Breakdown of Chemical in Vegetation

The half-life of methoprene on wheat was estimated to be three to seven weeks, depending on the level of moisture in the plant (5). Studies have shown that wheat grown in treated soil did not contain residues of methoprene. Methoprene is biodegradable and nonpersistent even in plants treated with very high rates. It has a half-life of less than two days in alfalfa when applied at a rate of one pound per acre. In rice, the half-life is less than one day (12).

PHYSICAL PROPERTIES AND GUIDELINES

Technical methoprene is an amber or pale yellow liquid with a faint fruity odor (9, 14).

Exposure Guidelines:

NOEL: 250 ppm for systemic toxicity, based on an 18-month oncogenicity study (9).
PADI: 0.0063 mg/kg/day based on a NOEL of 500 ppm in a 3-month dog feeding study using a 2,000-fold safety factor (17).
MPI: 0.3750 mg/day for a 60 kg person (17).

Physical Properties:

CAS #: 40596-69-8
Specific gravity: 0.9261 g/ml at 20 degrees C (14)
H20 solubility: practically insoluble, 0.51 ppm
Solubility in other solvents: soluble in organic solvents (2)
Boiling point: 100 degrees C at 0.05 mm Hg (14)
Vapor pressure: 2.37 x 10 to the minus 5 mm Hg at 25 degrees C (14); 1.60 x 10 to the minus 4 mm Hg at 40 degrees C (9, 14)
Chemical Class/Use: insect growth regulator; synthetic juvenile hormone; selective mosquito larvicide

BASIC MANUFACTURER

Sandoz Agro. Inc.
1300 E. Touhy Ave.
DesPlaines, IL 60018
Telephone: 708-390-3664

Review by Basic Manufacturer:

Comments solicited: October, 1992
Comments received: February, 1995

REFERENCES

  1. Berg, G. L., ed. 1986. Farm chemicals handbook. Willoughby, OH: Meister Publishing Co.
  2. _____. 1984. Farm chemicals handbook. Willoughby, OH: Meister Publishing Company.
  3. Hudson, R. H., et al. 1984. Handbook of toxicity of pesticides to wildlife. Second edition. United States Department of the Interior. Fish and Wildlife Service. Resource Publication 153. Washington, DC.
  4. McEwen, F. L. and G. R. Stephenson. 1979. The use and significance of pesticides in the environment. NY: John Wiley and Sons, Inc.
  5. Menzie, C. M. 1980. Metabolism of pesticides. Update III. U.S. Department of the Interior. Fish and Wildlife Service. Special Scientific Report. Wildlife No. 232. Washington, DC: U.S. Government Printing Office.
  6. Morse, R. A. 1987. Bee poisoning. 1988 New York State pesticide recommendations. Forty-ninth annual pest control conference. Nov. 9, 10, 11. Cornell University. Ithaca, NY.
  7. National Pest Control Association, Inc. 1980 (Nov.). Technical release on new pesticide - Precor 5E. Vienna, VA.
  8. Thomson, W. T. 1976. Insecticides, acaricides and ovicides. Agricultural Chemicals, Book I. Indianapolis, IN: Thomson Publications.
  9. U.S. Environmental Protection Agency. 1982 (Mar.). Guidance for the reregistration of pesticide products containing methoprene as the active ingredient. Office of Pesticide Programs, Registration Division. Washington, DC.
  10. Worthing, C. R., ed. 1983. The pesticide manual: A world compendium. Croydon, England: The British Crop Protection Council.
  11. Zoecon Corporation. 1974. Technical bulletin on Altosid. Toxicological properties.
  12. _____. 1973. Technical bulletin on Altosid. Environmental properties.
  13. Hayes, W. J. and E. R. Laws (ed.). 1990. Handbook of Pesticide Toxicology, Vol. 3, Classes of Pesticides. Academic Press, Inc., NY.
  14. Meister, R. T. (ed.). 1992. Farm Chemicals Handbook '92. Meister Publishing Company, Willoughby, OH.
  15. US Environmental Protection Agency. 1991 (June 12). Pesticide Reregistration Eligibility Document for methoprene; Availability for comment. Federal Register 56 (113): 27017-8.
  16. _____. 1991 (March). R.E.D. Facts: Methoprene. Pesticides and Toxic Substances, US EPA, Washington, DC.
  17. _____. 1981 (Dec. 4). Methoprene; Tolerances and exemptions from tolerances for pesticide chemicals in or on raw agricultural commodities. Federal Register 46 (233): 59248-9.
  18. Review by Sandoz Agro. February, 1995.
  19. Mortimer, M. R. and H. F. Chapman. 1994. A comparison of the toxic effects of Altosid® Liquid Larvicide (S-methoprene) and Abate® (temephos) to some non-target aquatic crustacean species common in eastern Australia. Griffith University, Queensland, Australia.
  20. Judy, D. and B. Howell. 1993. Concentrations of methoprene found in freshwater microcosms treated with sustained release Altosid formulations. Zoecon Study #1540. ABC Final Report #39541, MRID #42811202.
  21. US Environmental Protection Agency. December, 1994. Pesticide rejection rate analysis -- ecological effects. Washington, DC. EPA Doc. 738- R-94-035.
  22. Lehman, A. J. 1954. Approximate relation of parts per million in the diet to mg/kg D.W./day. Association of Food and Drug Officials Quarterly Bulletin 18:66.