United States Office of Pesticides
Environmental Protection and Toxic Substances
Agency (H7 O1C) 540/FS—89—055
&EPA Pesticide
Fact Sheet
Name of Chemical: Avermectin B 1
Reason for Issuance: Update — First Food Use (Cotton)
Date Issued: y 1989
Fact Sheet Number: 89.1
1. Description of Chemical
Generic Name: Avermectin B 1 [ A mixture of avermectins
containing > 80% avermectin B 18 (5—0—
dimethyl avermectin Aia) and < 20% avermectin
Bib (5—0—demethyl—25—de(1—methylpropyl)—25—
(1—methylethyl) avermectin Aja)]
Common Name: None assigned
Trade Names: Affirm®, Agrimec®, Avid®, MK—936, Zephyr®
Other Name: Abamectin
EPA Shaughnessy Code: 0122804
Chemical Abstracts Service (CAS) Numbers: 65195—55—3 and
Year of Initial Registration: 1986
Pesticide Type: Insecticide/Miticide
Chemical Family: Avermectins (macrocylic lactones isolated
from soil organism Streptomyces avermitilis) .
U.S. producers: Merck and Co., Inc.
2. Use Patterns and Formulations
Application Sites: Control of Imported fire ants on turf,
lawns, and other non—crop areas; control of mites and
other Insects on shadehouse, greenhouse, and field—grown
flowers, foliage plants, and other ornamentals, and on
Type of Formulations: 0.011% insecticide bait, 2.0% Spray
(0.15% EC), 70% technical.
Method of Application: Bait broadcast (ground or air application)
and individual mound to mound treatment (fire ants). Foliar
spray (ground application) mixed with water for use on field
grown flowers, foliage plants and ornamentals. Follar spray
(ground or air application) mixed with water for use on cotton.
Rates of Application: For Fire Ants — Use rate is 50mg active
ingredient (ai) per acre (1 pound (lb) product/acre);
For Field Grown Flowers ands Ornamentals — Use rate is
0.005 to 0.01 lb ai/acre (4 to 8 oz product/acre);
For Cotton — Use rate is 0.01 to 0.02 lb al/acre (8 to 16 oz
product/acre) and 3 applications per season.

Usual Carriers: Pregelled defatted corn grit carrier
and water.
3. Science Findings
Summary Science Statement
Technical avermectin exhibits high mammalian acute
toxicity. It is not considered to be rnutagenic and
does not sensitize skin. It is not readily absorbed
by mammals and the majority of the residue is excreted
in the feces within 2 days. The 24—month rat chronic
feeding /oncogenicity study and 94-week mouse chronic
toxicity oncogenicity study were negative for oncogenic
potential. The results of a series of developmental
toxicity studies (rat, rabbit, mouse) have been
evaluated and showed that avermectin B 1 produces
developmental toxicity (cleft palate) in the CF 1
mouse. Toxicology data were also evaluated for the
delta—8,9—isomer of avermectin B 1 which is a plant
photodegradate that can range between 5 and 20 percent
of the residu on/in cottonseed. This isomer ossesses
avermectinlike toxicological activity. It was
concluded that the delta 8,9—isomer also produces
developmental toxicity (cleft palate) in mice, but
not in rats.
In addition to avermectin and its delta 8,9—isomer,
toxicology data were also evaluated for the “polar
degradates” of avermectin, which constitute a large
percentage (up to 70%) of the total residue on cotton-
seed. Review of the toxicology data indicated that
these polar degradates do not possess avermectin—like
toxicological activity and for this reason need not
be included in the tolerance expression for residues
in/on cottonseed.
Sufficient data are available to characterize
avermectin from an environmental fate and ecological
standpoint. Avermectin is extremely toxic to mammals
and aquatic invertebrates and highly toxic to fish
and bees. Avermectin is relatively non—toxic to birds.
Based upon terrestrial residue analysis, aguatic run-
off modeling and cluster analysis it appears that
certain endangered species may be impacted by the
use of avermectin on cotton. EPA and the Fish and
Wildlife Service are in the process of updating the

cotton cluster. The results when available will be
applicable to the registration of avermectin on cotton.
Avermectifl undergoes rapid photolysis, is readily
degraded by soil microorganisms and, due to its
binding properites and low water solubility, is
expected to exhibit little or no potential for leaching;
however, a complete assessiDent cannot be made until
additional leaching and soil dissipation data are
Chemical Characteristics (Technical Grade) :
Physical State: Crystalline powder
Color: Yellowish-white
Odor: Odorless
Melting Point: 155 — 157 °C
Vapor Pressure: Being tested, expected to be
extremely low
Density: 1.16 + 0.05 at 21 °C
Solubility: Insoluble in water (c 5 ug/mL),
readily soluble in organic solvents
pH: NA. The avermectin molecule has neither acidic
nor basic functional groups
Octanol/Water Partition Coefficient: 9.9 x lO
Toxicological Characteristics:
Technical Grade Averm’ectifl B
o Derinal Sensitization: Negative for skin sensitization
o Acute Oral LD 50 — Rat: 10.6 mg/kg (males),
11.3 mg/kg (females)
o 14-Week Oral Study - Rat: NOEL > 0.4 mg/kg/day (HDT)
o 18-Week Oral Study - Dog: NOEL = 0.25 mg/kg/day
o TeratolOgY Study — Rat: Negative for terata up to
1.0 mg/kg/day.
o Teratology Study - Rabbit: Negative for
terata up to 1.0 mg/kg/day.
o Teratology Studies — Mouse: Teratogeflic LEL = 0.4 mg/
kg/day (cleft palate); Teratogenic NOEL =

o Maternotoxicity St ..dies — Mouse: LEL = 0.075 mg/kg!
day (lethality); NOEL = 0.05 mg/kg/day
o 2—Generation Reproduction Study — Rat: NOEL = 0.12
mg/kg/day; LEL = 0.40 mg/kg/day (increased retinal
folds in weanhings, increased dead pups at birth,
decreased viability indices, decreased lactation
indices, decreased pup body weights)
o 1—Year Oral Study — Dog: NOEL = 0.25 mg/kg/day;
LEL = 0.50 mg/kg! day (mydriasis in males and
o 94—Week Chronic Toxicity/Oncogenicity Study — Mice:
Oncocienic potential: Negative up to 8 mg/kg/day
(HDT): Systemic NOEL = 4 mg/kg/day; Systemic LEL =
8 mq/kg/ day (Dermatitis in males, extramedullary
hematopoiesis in the spleen in males, increased
mortality in males, tremors and body weight loss
in females)
o 2—Year Chronic Toxicity/Oncogenicity Study — Rats:
Oncogenic potential: Negative up to 2.0 mg/kg/day
(HDT); Systemic NOEL = 1.5 mg/kg/day; Systemic
LEL = 2.0 mg/kg/day tremors in both sexes)
o Metabolism Study — Rat: The metabolic T
1/2 in rats is 1P2 days
o Ames Mutagenicity Assay: Negative
o Mutagenicity Assay for Chrornosomal Aberrations
in vitro in Chinese Hamster Ovary Cells
o Rat Hepatocyte Mutagenicity Study: Under conditions
of the study, abamectin (0.3 and 0.6 mM) caused
an induction of single strand DNA breaks in rat
hepatocytes in vitro ; no effect was observed when
the assay was carried out on hepatocytes from rats
dosed in vivo at the LD 50 dose level (10.6 mg/kg)
o In Vivo Bone Marrow Mutagenicity Cytogenic Study:
Negative in male mice at doses of 1.2 and 12.0

Toxicity Studies on the Delta-8,9--Isomer of Averrnectin
o Acute Oral LD 50 — Mouse: > 80 mg/kg (HDT)
(males and females)
o Teratology Study — Rat: Negative for terata
up to 1.0 mg/kg/day (HDT)
o Teratology Studies — Mouse: Teratogenic LEL =
0.10 mg/kg/day (cleft palate); Teratogenic NOEL =
0.06 mg/kg/day
o Maternotoxicity Studies — Mouse: LEL = 0.50 mg/kg!
day (lethality); NOEL = 0.10 mg/kg/day
o 1-Generation Reproduction Study — Rat: NOEL =
0.4 mg/kg/day (EDT)
o Ames Mutagenicity Assay: Negative
Toxicity Studies on the “Polar Degradates” of Avermectin
o Acute Oral LD 50 — Mouse: > 5000 mg/kg (HDT)
o Teratology Study - Mouse: Negative for terata up
to 1.0 mg/kg/day (HDT)
o Teratology Study, (polar degradates derived from
citrus—treated fruit) — Mouse: Negative for
terata up to 1.0 mg/kg/day (HDT)
o Ames Mutagenicity Assay: Negative
Ecological Characteristics :
Avian Oral (Bobwhite quail): LD 50 > 2000 mg/kg;
LC 50 = 3102 ppm
Avian Dietary (Mallard duck): LC 50 = 383 ppm
Freshwater Fish (Bluegill): LC 50 = 9.6 ppb
Rainbow trout: LC 50 = 3.2 ppb
Estuarine Fish (Fathead minnow): LC 50 = 15 ppb
Oyster Embryo Larvae: LC 50 = 430 ppb.
Acute Freshwater Invertebrate (Daphnia):
LC 50 = 0.22 ppb
Acute Estuarine Invertebrate (Shrimp, mysid):
LC 50 = 0.02 ppb

Environmental Characteristics :
AverrneCtifl is stable to hydrolysis at ph 5, 7, and 9
and thus is not expected to hydrolyze in the environment.
It photodegradeS rapidly in water and soil with half—
lives of less than 12 hours and 1 day respectively.
Soil metabolism studies conducted in darkness indicate
degradation does occur with a half—life of 2 weeks
to 2 months under aerobic conditions. Anaerobic
degradation is slower. It is not expected to accumulate
in fish. Avermectiri’S solubility in water is determined
to be 7.8 ppb. The field dissipation study indicates
that avermectin, when applied in the bait formulation
directly to the soil, dissipates with a half—life of
about a week but may persist longer if the bait is
shaded. Due to its binding properties and low water
solubility, Avermectin is expected to exhibit little
or no potential for leaching; however, a determination
cannot be made until the results of the analyses of
the three remaining soil core replicates are submitted
and evaluated. .Also an absorptiOfl/deSOrPtiOfl leaching
study must be conducted since avermectin has sho n
conflicting results in soil thin—layer chromatographiC
(TLC) (immobile) and soil column studies.
Tolerance Assessment
A Section 408 tolerance under the Federal Food, Drug,
and Cosmetic Act has been established for residues
of avermectin B 1 and its delta 8,9—isomer in/on
the following raw agricultural commodity (RAC) (40
CFR 180.
Commodity ppm
Cottonseed 0.005
The acceptable daily intake (ADI), based on a NOEL of
0.12 mg/kg/day from a 2—generation rat reproduction
study and safety factor of 300, is 0.0004 mg/kg/body
weight (bwt) day.
Because of developmental effects seen in animal
studies the Agency used the rat reproduction study
with a 300 fold safety factor to assess chronic
dietary exposure and establish an ADI. The 300 fold
safety factor was employed to account for (1)
inter— and intra-speCies differences (2) and pup
death observed in the reproduction study. (3)

maternal toxicity (lethality) NOEL = 0.05 mg/kg/day,
and (4) cleft palate in the mouse teratology study
with the isomer, NOEL = 0.06 mg/kg/day. The theore-
tical maximum residue contribution (TMRC) from the
proposed tolerance as well as pending tolerances on
celery, pears and tomatoes and temporary tolerances
on citrus with secondary residues in meat and milk
is 0.000052 mg/kg/day. This is equivalent to about
13 percent of the A.DI. This analysis used tolerance
level residues and 100 percent of crop treated.
The TMRC from cotton only is .000001 representing
less than 0.1 of the ADI.
Because of adverse developmental effects seen in
animal studies detailed acute dietary exposure analysis
for this tolerance and pending tolerances for this
chemical was also conducted using a NOEL of 0.06
mg/kg body weight for developmental effects. The
food uses evaluated were the same as those evaluated in
the chronic exposure analysis. The acute exposure
analysis estimated the djstribution of single—day
exposures for the overall U.S. population and certain
population subgroups. The analysis evaluated the
individual food consumption, as reported by respondents
in the 1977—78 USDA Food Consumption Survey, and
accumulated exposure to avermectin for each food
consumed for which a tolerance is being evaluated.
Each analysis assumed that avermectin residues were
present at tolerance level in all foods consumed.
The toxicologic endpoint pertained to developmental
toxicity. The subgroup of interest in this analysis
was women aged 13 and above, which has the subgroup
most closely approximating women of child—bearing
age. Based upon this analysis the Margin of Safety
(MOS) for the average woman of child bearing age was
calculated to be 1579. None of the target population
is expected to have a MOS less than 250.
The nature of the residue in cottonseed is adequately
defined. The residue of concern is the parent and
its delta 8,9—isomer. Based on (1) no accumulation
of avermectin in tissues or milk (from a ruminant
metabolism study) (2) absence of measurable residues
(<2 ppb) in cottonseed treated at exaggerated
application rates and (3) feeding restrictions for

cotton foliage the Agency has concluded that there
is no reasonable expectation of finite residues in
milk, eggs, meat, or poultry and no processing
data or food/feed additive tolerances are needed
for the use on cotton.
There are no Canadian or Mexican tolerances and no
Codex Maximum Residue Limits (MRLS) have been
established for avermectin B 1 and its delta 8,9—isomer
in/on cotton. Therefore, no compatibility problem
4. Summary of Regulatory Position and Rationale
o The Agency has determined that it should allow the
conditional registration of abamectin for agricultural use
to control mites on cotton. Adequate data are available
to assess the acute and chronic toxicological effects
of abamectin to humans. However since long—term fish,
aquatic and mammalian data are lacking and additional
leac-hing and soil dissipation data are required, the
registration is being conditionally approved with an
expiration date of March 31, 1992. Due to the conditional
status of the registration the Agency is also establishing
the tolerance for this pesticide on cottonseed with an
expiration date of March 31, 1993 to cover residues
expected to be present during and for one year after the
period of conditional registration.
o In view of the high toxicity of technical abamectin
to fish, aquatic invertebrates and mammals and the potential
hazard associated with exposure from the use on cotton the
risk criteria for restricted use classification is exceeded
and thus the Agency, is restricting use on cotton to certified
o Additional data are required to more adequately define
the hazards to mammals, fish, and aquatic invertebrates.
According to EPA’s Ecological Effects Standard Evaluation
procedures presumption of unacceptable risk is triggered when
the estimated environmental concentration (EEC) exceeds
the bird or mammal LC 50 , or 1/2 the aquatic LC 50 or EC 50 .
According to EPA’s assessments, these criteria are exceeded
for mammals and aquatic invertebrates for the cotton use
(mammal 1—day LC 50 = 2.5 ppm, EEC = 4.8 ppm, aquatic inverte-
brate (freshwater) EC 50 = 0.22 ppb, EEC = 0.6 ppb; estuarine
invertebrate EC 50 = 0.02 ppb, EEC = 0.6 ppb).

o Because of adverse developmental effects seen in animal
studies non—dietary exposure analysis was also conducted
with respect to exposure to mixer/loaders, applicators and
harvesters. Based upon surrogate exposure data; persons
wearing long pants, long—sleeved shirts, rubber gloves and
dermal absorption data in the monkey the calculated MOS for
cotton crop applicators and workers were found to exceed 100
in all instances. This MOS is sufficient to adequately
protect these workers.
5. Summary of Data Gaps
Name of Study Number Due Date
Fish Life Cycle Test §72—5 October 1991
Mesocosm Aquatic Study §72—7 October 1991
Simulated Mammal Field Test §71—5 October 1991
Soil Absorption/Desorptiofl §163—1 June 1990
Results of the Analysis of §164—1 July 1989
the Remaining Soil Core
Samples for the Field
Dissipation Study
6. Required Unique Labeling Summary
o All products registered for use on cotton must bear the
following restricted use labelin.g statements:
Toxic to Fish, Mammals and Aquatic Organisms
For Retail sale to and use only by Certified Applicators
or Persons under their direct supervision and only
for those uses covered by the Certified Applicator;s
o The following use limitiations must appear on products
registered for use on cotton:

Do not apply more than 48 fi oz per acre per year.
Do not apply within 20 days of harvest.
Do not graze or feed cotton foliage.
Do not reenter treated areas until sprays have dried.
Do not apply when weather conditions favor drift from
target areas.
Do not apply this product through any type of irrigation
o Personal protective equipment and work safety statements
must appear on the label of products registered for use
on cotton and shade house, greenhouse and field grown
flowers, foliage plants and ornamentals.
6. Contact Person at EPA
George T. LaRocca
Product Manager 15
Insecticide—Rodentjcjde Branch
Registration Division (H7505C)
Office of Pesticide Program
U.S. Environmental Protection Agency
401 M Street SW.
Washington, DC 20460
Office location and telephone number:
Rn. 204, CM #2
1921 Jefferson Davis Highway
Arlington, VA 22202
(703) 557—2400
DISCLAIMER: The information presented in this Chemical
Information Fact Sheet is for informational purposes
only and may not be used to fulfill data requirements
for pesticide registration and reregistration.