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Isofenphos

Publication Date: 5/94

TRADE OR OTHER NAMES

Trade names for products containing isofenphos include Amaze, Oftanol and Pryfon. The insecticide may also be found in formulations with the fungicide thiram.

REGULATORY STATUS

Isofenphos is a Restricted Use Pesticide (RUP). Restricted Use Pesticides may be purchased and applied only by a certified applicator.

INTRODUCTION

Isofenphos is an organophosphate insecticide used to control soil- dwelling insects such as white grubs, cabbage root flies, corn roundworms, and wireworms. The product is used on vegetables including maize and carrots, on soil insects in fruit crops like bananas, and on soils with turfgrass. It is a selective contact and stomach poison in insects. It is applied as a preplant or preemergence soil treatment. It is also used to control termites in and around building structures.

Isofenphos is transported to a limited extent from the roots to plant leaves and stems. In the United States, it is mostly used in the corn- growing areas of the Ohio Valley.

TOXICOLOGICAL EFFECTS

ACUTE TOXICITY

Isofenphos is a highly toxic insecticide that requires the signal words DANGER-POISON on its label. Typical of other organophosphate insecticides, this compound is a cholinesterase inhibitor (8). Cholinesterase inhibitors are a general group of enzymes that inhibit the activity of specific cells within the organisms. One typical enzyme, acetyl cholinesterase, regulates inter-cellular nerve activity.

Although no mention of acute toxic effects were found in the reference material, acute effects would likely be similar to those from other organophosphates. These include increased secretions, breathing difficulty, diarrhea, urination, pupil contraction and slowness of the heart. At very high doses, convulsions and coma may ensue. Other parts of the body where cholinesterase is found include the blood stream (butrylcholinesterase) and the brain. During its use in a Japanese beetle eradication program in California, no illnesses were found attributable to the insecticide (8).

In the studies described below, isofenphos was administered in polyethylene glycol which is also a toxic compound. In rats, isofenphos has an oral LD50 between 28 to 38 mg/kg. In other species the LD50 for isofenphos is 91.3 to 127 mg/kg (mice), 150 mg/kg (female rabbits), and greater than 25 mg/kg (female dogs). All of these values indicate high acute toxicity (3).

In one study, the dermal LD50 for isofenphos was 188 mg/kg for rats and for rabbits it was 162 mg/kg when applied over a seven day period (4). However, in another study, the rat dermal LD50 for a four hour period was greater than 1,000 ug/kg (2). The compound caused no damage to the skin or membranes. In rabbits, the acute dermal LD50 ranges from 162 to 315 mg/kg (3).

The rat LC50 is between 0.144 mg/l and 1.3 mg/l (2). The four hour inhalation LC50 for hamsters was 0.23 mg/l (2). These values indicate that the compound is highly toxic to organisms which inhale even small amounts of isofenphos.

Isofenphos becomes more toxic when it is combined with the insecticide malathion. This increased effect did not occur when the compound was combined with fensulfothion, fenamiphos or phoxim.

CHRONIC TOXICITY

The primary chronic effect of isofenphos in animals and in humans is in the suppression of cholinesterase activity in the bloodstream (plasma). Dietary doses in rats below 0.05 mg/kg and in mice of 0.16 mg/kg/day had no effect on blood stream (plasma) cholinesterase activity. In dogs, the No Observable Effect Level (NOEL), based on plasma cholinesterase activity was also very low. Rats and dogs fed relatively small amounts (1 mg/kg) of isofenphos for 3 months exhibited no compound-induced dose related effects. Rats fed low doses of isofenphos for two years showed no compound-related effects on cholinesterase activity below the 1 mg/kg dose (1).

Isofenphos has the potential to adversely affect the nervous system. However, the large single dose which produced this effect in hens is substantially higher than its LD50. Repeated doses of 2 mg/kg for 90 days did not affect the nerves of the hens (5). Tests on rats, however, showed evidence of nerve damage due to repeated low-level exposures to some organophosphates (5).

Reproductive Effects

Female rats fed low to moderate amounts of isofenphos (0.05 to 5.0 mg/kg) through three successive litters exhibited no adverse reproductive effects at the lowest dose. The female rats experienced a reduction in their body weight gains at doses above 0.05 mg/kg. At slightly higher doses (0.5 mg/kg) isofenphos produced a decrease in the pregnancy rate. The FAO has reported that the no-effect-level in a multi-generation rat study was 0.5 mg/kg. There was, however, some evidence of abnormalities associated with toxicity to the developing embryos at the low dose of 0.15 mg/kg (2).

Teratogenic Effects

There were no isofenphos related malformations in the offspring of pregnant rats fed low to moderate amounts (0.3 to 3.0 mg/kg) of this pesticide during gestation (10). Pregnant rabbits fed isofenphos over a similar range of doses (1 to 5 mg/kg) during gestation had offspring with no teratogenic effects (11). For these two species, the compound does not appear to cause any birth defects at low to moderate levels of exposure.

Mutagenic Effects

A number of tests on the mutagenic potential of isofenphos were all negative (12, 13). It is unlikely that the compound is mutagenic to humans.

Carcinogenic Effects

Mice fed moderate to large amounts of isofenphos (up to 5 mg/kg) for two years in their food had no dose-related increases in tumors. There was however, high mortality in all of the groups in the study, including the controls (2). Rats fed low to high doses of isofenphos (0.05 mg/kg to 5 mg/kg) for two years had decreased body and organ weights though no presence of tumors (14). Isofenphos has shown no potential for carcinogenicity.

Organ Toxicity

Three male pesticide applicators working 5 to 11 days (not more than three consecutive days) had no significant changes in blood cholinesterase activity when compared to control subjects (8).

Fate in Humans and Animals

Rats, pigs and cows all eliminate isofenphos rapidly. Rats excreted nearly all of the compound in urine and the remaining small amount in feces within three days of the initial dosing. Pigs, within one day, eliminated eighty percent in urine and most of the remaining amount in feces. Cows had a very similar pattern of excretion over a two day interval. Less than one percent of the initial dose was detected in the milk (8).

When domestic hens were fed moderate doses of isofenphos (4 mg/kg) for three days, a significant amount of the compound was eliminated within two days. Residues of the compound in the tissues and eggs were less than three percent of the administered dose. The major residues found in excreta, tissues, and eggs were isofenphos and isopropyl salicylate (8).

Though the compound can be stored in tissues, the concentrations drop after exposure to the compound ceases. Rats fed isofenphos at high doses (15 mg/kg/day) for six days had small amounts of the compound in muscle, liver tissue, fat, and in the kidneys. Within five days after dosing, the concentration in these tissues had fallen to very low levels (8). Cows had a peak blood plasma level two hours after the dose and these levels fell sharply within a day.

ECOLOGICAL EFFECTS

Effects on Birds

The wide range of toxicity for isofenphos in birds makes any general characterization of its toxicity to this group of animals difficult.

Bobwhite quail were fed isofenphos in their diet for five days and this was followed by three days of no isofenphos. Their LC50 in this study was 145 ppm. Studies indicated a dietary LC50 of 299 ppm for Japanese quail and an eight-day LD50 for Japanese quail from 5.0 to 12.5 mg/kg (1). For white Leghorn hens, the LD50 ranges from 3 and 6 mg/kg (5). These values indicate that the compound is highly toxic to quail and to hens.

Red-winged blackbirds are also susceptible to isofenphos (6). Male blackbirds were fed granules containing 15% active ingredient of isofenphos. Forty percent of the blackbirds died after eating 20 granules and none after eating 5 or 10 granules (6).

Effects on Aquatic Organisms

Isofenphos is moderately toxic to fish. The LC50 values of the compound for various species of fish are relatively consistent. The 96- hour LC50 in goldfish is 2 mg/l. In carp the LC50 ranged between 2 mg/l and 4 mg/l and for rainbow trout the LC50 is 1.8 mg/l (1). There are some possible effects on aquatic protozoa at concentrations exceeding 20 mg/l (9).

The potential of the compound to significantly bioaccumulate, as predicted from its solubility in water, is relatively low.

Effects on Other Organisms (Nontarget species)

No other information is available.

ENVIRONMENTAL FATE

Breakdown of Chemical in Soil and Groundwater

Isofenphos is moderately persistent in soil. At a normal field-use rate, a single application of isofenphos had a half-life of 30 to 300 days with a typical time of 150 days (7).

The first step in the breakdown of the compound requires the presence of oxygen (oxidation). The products of this process are isopropyl salicylate and cyclic isofenphos. This first step is relatively slow. Degradation was not greatly influenced by the addition of organic matter to the soil (7). The evaporation of breakdown products account for a substantial portion of the loss of these residues from the soil.

Isofenphos exposed to sunlight has a half-life of 72 days in sandy loam soil (9).

Breakdown of Chemical in Surface Water

The maximum concentrations expected as the result of runoff following a field application of the compound would be very low in water (0.00007 mg/l) and in sediment (0.00004 mg/l) (9).

Isofenphos is relatively stable in acidic and neutral solutions. Half of the compound dissolved in 263 days at pH 2 and in 525 days at pH 7. The half-life is much shorter in alkaline solutions, 52 hours at pH 11.5 (1).

Breakdown in Vegetation

Plants, such as corn and onions, absorb isofenphos from the soil and convert the compound to its oxygen analog. The oxygen analog is then moved within the plant to the upper plant parts where further changes occur. Cereal grains, leafy and root vegetables, and edible oil crops grown in soil treated nine months earlier can take up the residues of the insecticide even when it is present at very low concentrations (0.005 mg/kg). The principal residues found in plants are isofenphos and an isofenphos-oxygen analog.

PHYSICAL PROPERTIES AND GUIDELINES

Isofenphos is a colorless oil, and the technical grade active ingredient is a yellow-brown liquid.

Exposure Guidelines:

RfD: NA
HA: NA
ADI: 0.001 mg/kg (WHO)
PEL: NA

Physical Properties:

CAS #: 25311-71-1
Chemical name: 0-ethyl 0-2-isopropoxycar-bonylphenylisopropylphosphoramid-othioate
Molecular weight: 345.40 g/mol
Solubility in water: 24 mg/l
Solubility in solvents: cyclohexanone, toluene > 600g/kg
Melting point: < -12 degrees C
Vapor pressure: 0.53 mPa at 20 degrees C
Partition coefficient (octanol/water) (log): 4.04
Adsorption coefficient: 600
Chemical class/use: organophosphate insecticide

BASIC MANUFACTURER

Miles Inc.
Agricultural Chemicals Division
8400 Hawthorn Road
P.O. Box 4913
Kansas City, MO 64120
Telephone: (816) 242-2000
Emergency: (816) 242-2582
FAX: (816) 242-2592

Review by Basic Manufacturer:

Comments solicited: April, 1993
Comments received: June, 1993

REFERENCES

  1. The Agrochemicals Handbook: Third Edition. (1991). Royal Society of Chemistry, Unwin Brothers Ltd., Surrey, England.
  2. Food and Agriculture Organization of the United Nations. (1981). Pesticide Residues in Food - 1981. FAO Plant Production and Protection Paper 42.
  3. Smith, Gregory J. (1993). Pesticide Use and Toxicology in Relation to Wildlife: Organophosphorus and Carbamate Compounds. United States Department of the Interior, Fish and Wildlife Service, Resource Publication 170.
  4. National Institute for Occupational Safety and Health. (1985-86). Registry of Toxic Effects of Chemical Substances. U.S. Department of Health and Human Services, Centers for Disease Control.
  5. Wilson, B.W., M. Hooper, E. Chow, R.J. Higgins and J.B. Knaak. (1984). Antidotes and Neuropathic Potential of Isofenphos. Bulletin of Environmental Contamination and Toxicology, 33: 386-394.
  6. Balcomb, R., R. Stevens and C. Bowen. (1984). Toxicity of 16 Granular Insecticides to Wild-caught Songbirds. Bulletin of Environmental Contamination and Toxicology, 33: 302-307.
  7. Somasundaram, L., K.D. Racke and J.R. Coats. (1987). Effects of Manuring on the Persistence and Degradation of Soil Insecticides. Bulletin Environ. Toxicol., 39: 579-586.
  8. Broadberg, R.K. (1990). Estimation of Exposure of Persons in California to Pesticide Products Containing Isofenphos. California Department of Food and Agriculture. Division of Pest Management, Environmental Protection and Worker Safety. Sacramento, CA.
  9. Environmental Fate and Effects Division. U.S. Environmental Protection Agency. (1990). Pesticide Environmental Fate One Line Summary for Isofenphos.
  10. Bayer AG Institute fur Toxicologie. (1977). Rat Teratology study. Unpublished study #35482. 10/25/77. EPA Accession No. 096657.
  11. Bayer AG Institute fur Toxicologie. (1977). Rabbit Teratology study. Unpublished study #46931. 11/10/75. EPA Accession No. 096657.
  12. Bayer AG Institute fur Toxicologie. (1977). Mice Mutagenicity study. Unpublished study #39567. 11/07/77. EPA Accession No. 096657.
  13. Oesch, F. (1977). Ames Mutagenicity test. Unpublished study #53954. 9/29/77. EPA Accession No. 096657.
  14. Bayer AG Institute fur Toxicologie. (1977). Two Year Rat Feeding Oncogenicity study. Unpublished study #6979. EPA Core Grade Document No. 002490.