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
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).
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).
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).
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
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).
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).
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).
No information was found.
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
No information was found.
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.
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).
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).
|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)
AgriDyne Technologies Inc.
2401 S. Foothill Dr.
Salt Lake City, Utah 84109
Review by Basic Manufacturer:
Comments solicited: April, 1995
Comments received: May, 1995
Farm Chemicals Handbook. 1995. Meister Publishing Co. Willoughby, OH.
Thomson, W.T. Agricultural Chemicals. Book I: Insecticides. 1992.
Thomson Publications, Fresno, CA.
U.S. Environmental Protection Agency. 1993. Azadirachtin: Tolerance
Exemption. Federal Register. Vol. 58, No. 30. Rules and Regulations.
Wednesday, February 17, 1993.
National Research Council. 1992. Neem: A tree for solving global
problems. National Academy Press, Washington, DC.
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.
Grace-Sierra Crop Protection Co. 1990. Margosan-O technical bulletin.
Grace-Sierra Crop Protection Co., Milpitas, CA.
W. R. Grace & Co. 1991. MSDS for Margosan-O. Washington Research
Center, Columbia, MD.
Martineau, Jess. AgriDyne Technologies, Inc. January 26, 1994. MSDS
for Azatin-EC Biological Insecticide.
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.
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.
Review by AgriDyne Technologies, Inc. May, 1995.
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