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Azadirachtin

TRADE OR OTHER NAMES

The active ingredient azadirachtin is found in commercial insect growth regulators. Some trade names for products containing azadirachtin include Align, Azatin and Turplex (1, 2). Formulations include a 10% plant extract (technical) and a 3% EC (2).

REGULATORY STATUS

Azadirachtin is registered in the United States as a general use pesticide with a toxicity classification of IV (relatively non-toxic). Check with specific state regulations for local restrictions which may apply. Products containing azadirachtin must bear the signal word "Caution" or "Warning" on their label (1).

INTRODUCTION

The key insecticidal ingredient found in the neem tree is azadirachtin, a naturally occurring substance that belongs to an organic molecule class called tetranortriterpenoids (6). It is structurally similar to insect hormones called "ecdysones," which control the process of metamorphosis as the insects pass from larva to pupa to adult. Metamorphosis requires the careful synchrony of many hormones and other physiological changes to be successful, and azadirachtin seems to be an "ecdysone blocker." It blocks the insect's production and release of these vital hormones. Insects then will not molt, thus breaking their life cycle (4, 5). Azadirachtin may also serve as a feeding deterrent for some insects. Depending on the stage of life-cycle, insect death may not occur for several days. However, upon ingestion of minute quantities, insects become quiescent and stop feeding. Residual insecticidal activity is evident for 7 to 10 days or longer, depending on insect and application rate (1, 2). Azadirachtin is used to control whiteflies, aphids, thrips, fungus gnats, caterpillars, beetles, mushroom flies, mealybugs, leafminers, gypsy moths and others on food, greenhouse crops, ornamentals and turf (2, 11).

TOXICOLOGICAL EFFECTS

ACUTE TOXICITY

The acute oral toxicity in rats fed technical grade azadirachtin ranged from greater than 3,540 mg/kg to greater than 5,000 mg/kg, the highest dose tested when administered undiluted to albino rats (1, 2, 3).

The single-dose oral toxicity LD50 of the formulated product Azatin-EC fed to rats was 4,241 mg/kg; considered practically nontoxic (8).

The acute inhalation toxicity study in rats exposed to technical azadirachtin showed that the acute inhalation LD50 is greater than 2.41 mg/L per animal, the highest dose tested. Although this figure is below the 5.0 mg/L limit test dose for an acute inhalation study, the reported concentration was the maximum dose possible under the test conditions. No deaths occurred during the course of the study. Azadirachtin was given a toxicity classification of Category III (3).

The 4-hour acute inhalation LC50 in rats exposed to the formulated product Azatin-EC was >2.18 mg/kg (8).

A primary eye irritation study in rabbits exposed to technical azadirachtin was rated mild to moderately irritating after instillation of 0.1 gm of the undiluted material. At one hour post-instillation, the maximum eye irritation score was 15.3/110; by 24, 48, and 72 hours the scores were 6.2/110, 0.3/110, and 0/110, respectively. It was given a toxicity category of III (3).

Primary dermal irritation in rabbits when tested at a single dose (0.5 gm) by applying it to the shaved backs of rabbits, did not cause any dermal irritation after 4 hours of exposure. The dermal score was zero for all treated rabbits at all examination times. A toxicity category of IV, mild to slightly irritating,was assigned.

An acute dermal toxicity study of rabbits exposed to technical azadirachtin was performed. The material was applied for 24 hours at a single dose of 2.0 gm/kg to the shaved backs of the rabbits, that caused dermal irritation which resolved by day nine. Azadirachtin was classified as a mild irritant (3). Another study reported the dermal LD50 for rabbits to be >2,000 mg/kg (1, 2).

Dermal sensitization in guinea pigs found the technical end-use product to be categorized as a mild sensitizer when administered undiluted to albino guinea pigs. The test material was considered a weak dermal sensitizer to albino guinea pigs (3).

CHRONIC TOXICITY

A 90-day oral toxicity study in rats fed levels of 500, 2500, and 10,000 ppm of azadirachtin showed no signs of overt systemic toxicity at any dose level after 90 days of feeding. Mean body weight was significantly decreased in the 10,000 ppm males and females at weeks 3 and 4, respectively. This persisted for the duration of the 90-day feeding period (11).

Reproductive Effects

Male antifertility activity of neem leaf extract was studied in mice, rats, rabbits and guinea pigs by daily oral feeding of a cold-water extract of fresh green neem leaves. The infertility effect was seen in treated male rats as there was a 66.7% reduction in fertility after 6 weeks, 80% after 9 weeks, and 100% after 11 weeks. There was no inhibition of spermatogenesis. During this period there was no decrease in body weight and no other manifestation of toxicity observed. There was a marked decrease in the mortality of spermatozoa. The infertility in rats was not associated with loss of libido or with impotence and the animals maintained normal mating behavior. The male antifertility activity was reversible in 4 to 6 weeks. Neem extract also shows reversible male antifertility activity in mice without inhibition of spermatogenesis. In guinea pigs and rabbits, however, it exhibited toxicity as demonstrated by 66.6% and 74.9% mortality in guinea pigs and 80 and 90% mortality in rabbits at the end of 4 and 6 weeks, respectively (9).

Teratogenic Effects

No information was found.

Mutagenic Effects

Technical azadirachtin was evaluated for the potential to cause gene mutations in the S. typhimurium strains at any dose (5, 50, 500, 5,000 micrograms/plate) with or without S-9 activation. The study was negative (3).

The Ames test was negative with or without metabolic activation for the formulated product Azatin-EC. The UDS and Mouse Lymphoma studies were also negative (8).

Carcinogenic Effects

No information was found.

Organ Toxicity

Rats dosed with 600 mg/kg/day of the formulated product Azatin-EC for 90 days showed no overt adverse effects on target organs (8).

Fate in Humans and Animals

No information was found.

ECOLOGICAL EFFECTS

Effects on Birds

No significant effects on other wildlife were reported (8).

Effects on Aquatic Organisms

The formulated product Azatin-EC is not expected to kill fish at recommended rates. The LC50 for rainbow trout exposed to azadirachtin is 0.48 ppm (11). It may cause significant fish kill if large concentrations reach waterways. It breaks down rapidly (in 50-100 hours) in water or light, and is not likely to accumulate or cause long-term effects (8, 11).

Effects on Other Animals (Nontarget species)

Azadirachtin is relatively harmless to spiders, butterflies, and insects such as bees that pollinate crops and trees, ladybugs that consume aphids, and wasps that act as parasites on various crop pests. This is because neem products must be ingested to be effective. Thus, insects that feed on plant tissue succumb, while those that feed on nectar or other insects rarely contact significant concentrations of neem products.

Another study found that only after repeated spraying of highly concentrated neem products onto plants in flower were worker bees at all affected. Under these extreme conditions, the workers carried contaminated pollen or nectar to the hives and fed it to the brood. Small hives then showed insect-growth-regulating effects; however, medium-sized and large bee populations were unaffected (4).

A study of neem products and their effect on mortality, growth and reproduction of earthworms in soils was conducted. Positive effects on weight and survival were found in soil treated with ground neem leaves and ground seed kernals under greenhouse conditions. Reproduction was slightly favored over a period of 13 weeks in a neem-enriched substrate in rearing cages. Various neem products were incorporated in the upper 10-cm soil layer of tomato plots. None of the materials had negative side effects on seven species of earthworms (10).

No significant effects on other wildlife were reported (8).

ENVIRONMENTAL FATE

Breakdown of Chemical in Soil and Groundwater

Potential for mobility in soil is very low for the formulated product Azatin-EC. Accumulation in the environment is not expected (8).

Breakdown of Chemical in Surface Water

The formulated product Azatin-EC which contains the active ingredient azadirachtin is considered a water pollutant. It breaks down rapidly (in 100 hours) in water or light, and will not cause long-term effects (8).

Breakdown of Chemical in Vegetation

Azadirachtin is considered non-phytotoxic when used as directed (2).

PHYSICAL PROPERTIES AND GUIDELINES

Azadirachtin is a tetranortriterpenoid botanical insecticide of the liminoid class extracted from the neem tree Azadirachta indica. It is a yellow-green powder, with a strong garlic-sulfur odor. Hazardous combustion products include carbon monoxide and carbon dioxide (1, 2, 8, 11).

Physical Properties:

CAS No: 11141-17-6
Chemical name: azadirachtin (1)
Chemical Class/Use: Tetranortriterpenoid/Insect growth regulator (1, 8)
Specific gravity: 1.066 (Azatin-EC) (8)
Solubility in water: 0.00005 (1)
Boiling point: 78-212 degrees F (Margosan-O) (7)
Flashpoint: >140 degrees F (1); >145 F (Azatin-EC) (8); 55.6 degrees F (Margosan-O) (7)
Vapor pressure: >2 mmHg @ 25 degrees C (Azatin-EC) (8); 44mm @ 20 degrees C (Margosan-O) (7)
Kow: 12.3; partitioning from water to oil is relatively high (Azatin-EC) (8)

BASIC MANUFACTURER

AgriDyne Technologies Inc.
2401 S. Foothill Dr.
Salt Lake City, Utah 84109
Phone: 800-657-3090
Fax: 801-467-1090

Review by Basic Manufacturer:

Comments solicited: April, 1995
Comments received: May, 1995

REFERENCES

  1. Farm Chemicals Handbook. 1995. Meister Publishing Co. Willoughby, OH.
  2. Thomson, W.T. Agricultural Chemicals. Book I: Insecticides. 1992. Thomson Publications, Fresno, CA.
  3. U.S. Environmental Protection Agency. 1993. Azadirachtin: Tolerance Exemption. Federal Register. Vol. 58, No. 30. Rules and Regulations. Wednesday, February 17, 1993.
  4. National Research Council. 1992. Neem: A tree for solving global problems. National Academy Press, Washington, DC.
  5. AgriDyne Technologies, Inc. March, 1994. Greenhouse Grower. Floritech report: Tough on pests, easy on crops--and the environment. AgriDyne Technologies, Inc., Salt Lake City, UT.
  6. Grace-Sierra Crop Protection Co. 1990. Margosan-O technical bulletin. Grace-Sierra Crop Protection Co., Milpitas, CA.
  7. W. R. Grace & Co. 1991. MSDS for Margosan-O. Washington Research Center, Columbia, MD.
  8. Martineau, Jess. AgriDyne Technologies, Inc. January 26, 1994. MSDS for Azatin-EC Biological Insecticide.
  9. Sadre, N. L., V. Y. Deshpande, K. N. Mendulkar and D. H. Nandal. 1983. "Male antifertility activity of azadirachta indica in different species" (paper presented at the Proceedings of the 2nd International Neem Conference, Rauischholzhausen, Germany, 1983). pp. 473-482.
  10. Rossner, J. and C. P. W. Zebitz. 1986. "Effect of soil treatment with neem products on earthworms (Lumbricidae)" (paper presented at the Proceedings of the 3rd International Neem Conference, Nairobi, 1986). pp. 627-632.
  11. Review by AgriDyne Technologies, Inc. May, 1995.