UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

OFFICE OF CHEMICAL SAFETY 

AND POLLUTION PREVENTION 

MEMORANDUM 

Date: 6-JUN-20 13 

SUBJECT: Abamectin. Human Health Assessment Scoping Document in Support of Registration 

Review. 

PC Code: 122804 

Decision No.: 473543 

Petition No.: NA 

DP Barcode: D407955 

Registration No.: NA 

Regulatory Action: Registration Review 

Risk Assessment Type: NA Case No.: 7430 

TXRNo.:NA 

MRIDNo.:NA 

CAS No.: 71751-41-2 

40 CFR: 180.449 

FROM: Nancy Dodd, Chemist ~''%;It~ Whang Phang, Toxicologist _,_· _ __....__~ 

Nancy Tsaur, Chemist 

Risk Assessment Branch III (RAB III) 

Health Effects Division (7509P) 

Office of Pesticide Programs 

THROUGH: Christine 

Risk Assessment 

Olinger, 

Branch 

Branch 

III 

Ch~'ef ~ 

' 

Health Effects Division (7509 -

Office of Pesticide Programs 

TO: Neil Anderson!Khue Nguyen, Risk Manager #51 

Risk Management and Implementation Branch I (RMIB 1) 

Pesticide Re-Evaluation Division (PRD) (7508P) 

Office of Pesticide Programs 

Page 1 of26 
Executive Summary 

The HED Registration Review Team has evaluated human health assessments for the 

insecticide/miticide/nematicide abamectin to determine whether sufficient data are available and 

whether any updates are needed to support Registration Review. HED has considered the most 

recent human-health risk assessments for abamectin, updates to the toxicity, exposure, and usage 

databases, and current Agency science policy and risk assessment methodologies to determine 

the scope of work necessary to support Registration Review. In addition, HED performed a 

screening literature search to identify studies relevant to the human health risk assessment and 

found no relevant toxicity or exposure information. 

The registered uses of abamectin include agricultural crops, food handling establishments, cattle 

ear tags, ornamentals, and lawns. Abamectin is also registered for use as a bait to control fire 

ants around buildings and in landscapes (including lawns) of residential, recreational, 

commercial, industrial, and public areas. 

Abamectin has high to moderate acute toxicity by the oral route (depending on the vehicle), high 

acute toxicity by the inhalation route, and low acute toxicity by the dermal route. It is slightly 

irritating to the skin, but is not an ocular irritant or a dermal sensitizer. The main target organ is 

the nervous system, and the reduced body weight effect is one of the most frequent findings. 

Neurotoxicity and developmental effects were detected in multiple studies and species of test 

animals. The dose/response curve is steep in several studies, with effects (including death and 

morbid sacrifice) seen at dose levels as low as 0.4 mg/kg/day and 0.1 mg/kg/day in rats and 

mice, respectively, following repeated/chronic exposures. The combined data from several rat 

reproduction toxicity and developmental neurotoxicity studies have documented a very narrow 

dose range from NOAEL (0.12 mg/kg/day) to adverse effect (0.2 mg/kg/day) to severe adverse 

effect (0.4 mg/kg/day). Increased susceptibility (qualitative and/or quantitative) was seen in 

prenatal developmental toxicity studies in mice and rabbits, and an increase in quantitative and 

qualitative susceptibility was seen in the rat reproductive toxicity study. Review of acceptable 

oncogenicity and mutagenicity studies provides no indication that abamectin is carcinogenic or 

mutagenic. 

In the most recent risk assessment, the Food Quality Protection Act (FQPA) safety factor was 

reduced to lx for the acute dietary assessment and was reduced to 3x to address residual 

concerns as to all risk assessments other than acute dietary. For all risk assessments involving 

repeat exposures, the selected toxicity endpoint is based on the decrease in pup body weight seen 

in the developmental neurotoxicity study (2007) and three reproduction studies in the rat. With 

respect to acute dietary exposure, the endpoint selected for risk assessment is based on mydriasis 

observed in dogs. The additional 3x factor applied to chronic and other exposure scenarios is not 

applicable to acute exposure because steepness of the dose/response curve and severity of effects 

were not seen in the studies where mydriasis occurred. In addition, the reduced body weights as 

toxicity endpoints for other exposure scenarios are not a single dose effect. 

The toxicology database is currently considered to be adequate. The requirement for an 

immunotoxicity study has been waived (Hazard and Science Policy Council [HASPOC], 6/6/13). 

Based on a weight of the evidence (WOE) approach and considering all of the available 

Page 2 of26 
Page 3 of 26

abamectin hazard and exposure information, the HASPOC concluded in a meeting on November 

8, 2012 that a subchronic inhalation toxicity study in mice and a subchronic dermal toxicity 

study are not required at this time. However, the HASPOC recommended that the points of 

departure (PODs) and scenarios for risk assessment be reevaluated. Depending on the results, a

new risk assessment may be needed. 

A new dietary exposure and risk assessment is not expected to be needed in the registration 

review process unless toxicological endpoints/PODs are revised.

There is sufficient information available to assess residential exposure. All residential exposure 

scenarios have been assessed using current HED Residential Standard Operating Procedures 

(SOPs) and current policies. A new residential assessment is not expected to be needed in the 

registration review process unless toxicological endpoints/points of departure are revised or the 

Agency develops new policies/procedures to quantitate residential post-application inhalation 

exposure.

A new aggregate risk assessment is not expected to be needed in the registration review process 

unless the toxicological endpoints/points of departure are revised or the Agency develops new 

policies/procedures to quantitate residential post-application inhalation exposure.

.

There is sufficient information available to assess occupational handler and post-application 

exposures. While all occupational exposure scenarios were not assessed based on current HED 

policies, the most recent assessments are protective of the previously unassessed scenarios. An 

up-to-date quantitative occupational risk assessment may be required to account for the currently 

registered application rates, changes in unit exposures, changes in transfer coefficients (TCs), 

and any possible changes to endpoints and safety factors. Updated risk estimates are unlikely to 

result in risks of concern.

Introduction

Abamectin is a mixture of avermectin B1 [a mixture of avermectins containing greater than or 

equal to 80% avermectin B1a (5-O-demethyl avermectin A1) and less than or equal to 20% 

avermectin B1b (5-O-demethyl-25-de(1-methylpropyl)-25-(1-methylethyl) avermectin A1)] and 

its delta-8,9-isomer. Abamectin is a natural fermentation product of the soil bacterium 

Streptomyces avermitilis. Abamectin acts as an insecticide/miticide/nematicide by interfering 

with the nervous system of the pest, causing the pest to become paralyzed.

The registered formulation types include emulsifiable concentrate, suspension concentrate, 

granular, bait, gel, and dust formulations. The registered uses include agricultural crops, food 

handling establishments, cattle ear tags, ornamentals, and lawns. Abamectin is also registered 

for use as a bait to control fire ants around buildings and in landscapes (including lawns) of 

residential, recreational, commercial, industrial, and public areas.

The most recent risk assessment for abamectin was conducted in 2012 (DP# D402677, N. Dodd, 

12/20/12). Refer to Attachment 1 for the chemical identity of abamectin.
Page 4 of 26

Hazard Identification/Toxicology

Abamectin has high to moderate acute toxicity by the oral route (depending on the vehicle), high 

acute toxicity by the inhalation route, and low acute toxicity by the dermal route. It is slightly 

irritating to the skin, but is not an ocular irritant or a dermal sensitizer. The main target organ is 

the nervous system but reduced body weight is one of the most frequent findings in the 

experimental toxicology database. Neurotoxicity and developmental effects were detected in 

multiple studies and species of test animals. The dose/response curve is steep in several studies, 

with effects (including death and morbid sacrifice) seen at dose levels as low as 0.4 mg/kg/day

and 0.1 mg/kg/day in rats and mice, respectively, following repeated/chronic exposures. The 

combined data from several rat reproduction toxicity and developmental neurotoxicity studies 

have documented a very narrow dose range from NOAEL (0.12 mg/kg/day) to adverse effect 

(0.2 mg/kg/day) to severe adverse effect (0.4 mg/kg/day). Increased susceptibility (qualitative 

and/or quantitative) was seen in prenatal developmental toxicity studies in mice and rabbits, and 

an increase in quantitative and qualitative susceptibility was seen in the rat reproductive toxicity 

study. Review of acceptable oncogenicity and mutagenicity studies provides no indication that 

abamectin is carcinogenic or mutagenic. Refer to Attachment 3 for a summary of toxicity 

endpoints and points of departure and to Attachment 4 for the toxicity profile tables. HED 

anticipates re-assessing all the endpoints and uncertainty factors.

An additional 3x FQPA safety factor was used in the previous risk assessment to address residual 

concerns as to all risk assessments other than acute dietary. The additional 3x FQPA safety 

factor was retained for the steepness of the dose-response curve and the severity of the effects.

For all risk assessments involving repeat exposures, the selected toxicity endpoint is based on the 

decrease in pup body weight seen in the developmental neurotoxicity study (2007) and three 

reproduction studies in the rat. 

With respect to acute dietary exposure, the endpoint selected for risk assessment is based on 

mydriasis observed in dogs. The additional 3x factor applied to chronic dietary exposures and 

other exposure scenarios is not applicable to acute exposure because steepness of the 

dose/response curve and severity of effects were not seen in the studies where mydriasis 

occurred. In addition, the reduced body weights as toxicity endpoints for other exposure 

scenarios are not a single dose effect.

The immunotoxicity study (OCSPP 870.7800) required under 40 CFR Part 158 has been waived 

after HED examined the entire toxicity database of abamectin. For abamectin, a complete 

battery of subchronic, chronic, carcinogenicity, developmental and reproductive studies as well 

as acute and subchronic neurotoxicity screening studies are available for consideration. In 

addition, two developmental neurotoxicity studies have been conducted on abamectin. At the 

dose levels tested, abamectin did not induce effects which can be associated with 

immunotoxicity, and abamectin does not belong to a class of chemicals that would be expected 

to be immunotoxic. Because HED does not believe that conducting a special series 870.7800 

immunotoxicity study will result in a NOAEL that is less than any which is used for point of 

departure for risk assessment, an additional uncertainty factor for database uncertainties (UFDB) 

is not needed to account for potential immunotoxicity. Additionally, results of a retrospective 

analysis conducted by the agency of 170 immunotoxicity studies provide strong support for not 
Page 5 of 26

applying a UFDB as no immunotoxicity study available thus far provided sensitive endpoints of 

use in driving the POD. The HASPOC determined on 6/6/13 that the current points of departure 

(based on neurotoxicity and developmental endpoints) are protective of any immune effects, and 

an additional uncertainty factor is not needed at this time.

Under the 2007 revised 40 CFR Part 158 data requirements, a subchronic dermal toxicity study is 

required for food use chemicals for which there is repeated human dermal exposure from 

occupational/residential uses. No dermal toxicity studies are available for abamectin. The 

HASPOC met on November 8, 2012 (K. Rury, MPH, 1/30/13, TXR # 0056509) to discuss the 

need for a subchronic dermal toxicity study. Based on a WOE approach, the HASPOC

concluded that neither a subchronic dermal toxicity study nor a subchronic dermal 

developmental toxicity study is required at this time. In addition, the HASPOC recommended

that the Toxicology Science Advisory Council (ToxSAC) reevaluate the need for a dermal 

exposure assessment and appropriate PODs for abamectin. 

Under the 2007 revised 40 CFR Part 158 data requirements, a subchronic inhalation toxicity 

study is also required due to the potential for repeated inhalation exposure. An inhalation 

toxicity study is available in rats. On November 8, 2012, the HASPOC discussed the need for an 

inhalation toxicity study in mice to support abamectin. Based on a WOE approach, the 

HASPOC concluded that a subchronic inhalation toxicity study in CF-1 mice is not required at 

this time. The HASPOC recommended that the abamectin endpoints and the rat inhalation 

toxicity study be revisited with the ToxSAC. 

Conclusions: The toxicology database is currently considered to be adequate. The requirement 

for an immunotoxicity study has been waived. The HASPOC determined on 6/6/13 that the 

current points of departure (based on neurotoxicity and developmental endpoints) are protective 

of any immune effects, and an additional uncertainty factor is not needed at this time. Based on 

a WOE approach and considering all of the available abamectin hazard and exposure 

information, the HASPOC concluded in a meeting on November 8, 2012 that a subchronic 

inhalation toxicity study in mice and a subchronic dermal toxicity study are not required at this 

time. However, the HASPOC recommended that the PODs and scenarios for risk assessment be 

reevaluated. Depending on the results, a new risk assessment may be needed.

Dietary Exposure

The residue chemistry database is sufficient to support current registrations. The nature of the 

residue in plants and livestock has been defined, and adequate enforcement methods are 

available. Adequate storage stability, field trial, and rotational crop data are available. Since 

residues of concern are not expected to occur in rotational crops, rotational crop tolerances and 

restrictions are not required for abamectin.

The most recent dietary (food and drinking water) exposure assessment (DP# D403715, N.

Dodd, 12/19/12) was conducted using the Dietary Exposure Evaluation Model software with the 

Food Commodity Intake Database (DEEM-FCID), Version 3.16. This software uses 2003-2008 

food consumption data from the National Health and Nutrition Examination Survey, What We 

Eat in America (NHANES/WWEIA).
Page 6 of 26

 

Although tolerance-level residues and 100% crop treated were used for bulb onion, chives, dry 

bean, and okra, the acute and chronic dietary exposure assessments were refined assessments 

using anticipated or average residues derived from field trial data for most crops. Default 

processing factors and percent crop treated (%CT) were used as available. Estimated drinking 

water concentrations (EDWCs) were provided by the Environmental Fate and Effects Division 

(EFED). The maximum (acute) concentration of abamectin and its major soil degradate (a 

mixture of an 8-alpha-hydroxy and a ring opened aldehyde derivative) in surface water is not 

likely to exceed 2.3 ppb. The mean (chronic) estimated surface water concentration is 1.3 ppb.

The acute dietary exposure estimates for food and drinking water are below HED’s level of 

concern [<100% of the acute population adjusted dose (aPAD)] at the 99.9th percentile of 

exposure for the general U.S. population and all population subgroups. Abamectin dietary 

exposure at the 99.9th percentile for food and drinking water is 15% of the aPAD for the general 

U.S. population and 24% of the aPAD for children 1-2 years old, the most highly exposed 

population subgroup.

The chronic dietary exposure estimates for food and drinking water are below HED’s level of 

concern [<100% of the chronic population adjusted dose (cPAD)] for the general U.S. population 

and all population subgroups. Abamectin dietary exposure for food and drinking water is 17% of 

the cPAD for the general U.S. population and 53% of the cPAD for children 1-2 yrs old, the 

most highly exposed population subgroup.

HED classified abamectin as “not likely to be carcinogenic to humans;” therefore, quantification 

of human cancer risk was not conducted. 

Conclusions: A new dietary exposure and risk assessment is not expected to be needed in the 

registration review process unless toxicological endpoints/points of departure are revised.

Residential Exposure

The products registered for residential use sites include several formulations of homeowner bait 

and bait station products registered under multiple companies. These products include outdoor 

granular bait (GB) and indoor ready-to-use bait (RB) of both dust and gel formulations. 

The existing residential uses were reassessed in the last risk assessment (D402677, N. Dodd, 

12/20/12) to reflect updates to HED’s 2012 Residential SOPs1along with policy changes for 

body weight assumptions. 

For residential exposure, the duration of exposure is expected to be short-term (1-30 days);

intermediate-term (1-6 months) and long-term exposures are not anticipated. The level of 

concern (LOC) for risk estimates is a margin of exposure (MOE) of less than 300 for short-term 

exposure.

 

1 Available: http://www.epa.gov/pesticides/science/residential-exposure-sop.html
Page 7 of 26

Residential Handlers

Residential handlers are likely to be exposed to abamectin residues via dermal and inhalation 

routes during handling activities. The exposures and risk from applying outdoor granular baits 

were assessed. Exposure from indoor ready-to-use gel baits is expected to be negligible; 

however, exposure data for hand dispersal of granular/dust bait was chosen as a surrogate to 

calculate risk estimates from indoor RBs.

The quantitative exposure/risk assessment developed for residential handlers is based on the 

following scenarios: loading/applying GB outdoors via (1) push-type spreaders, (2) belly 

grinders, (3) spoons, (4) hand, and (5) cup or shaker; and (6) applying granular bait indoor by 

hand (as a surrogate for a ready-to-use dust bait).

There are no registered products that would lead to any residential handler risk estimates of 

concern. Short-term combined (dermal + inhalation) residential handler MOEs range from 

320,000 to 1,100,000,000.

Residential Post-Application

Residential post-application exposure to adults and children is unlikely for all registered uses of 

abamectin. For outdoor treatments, adults and children are not expected to directly contact fire 

ant mounds. For indoor pest control, bait placements are intended to be placed in cracks and 

crevices where direct contact by adults and children is unlikely.

Based on the Agency’s current practices, a quantitative residential post-application inhalation 

exposure assessment was not performed for abamectin primarily because of the low proposed 

use rate and low vapor pressure. 

If there are Agency policy changes regarding residential exposures resulting from off-site 

transport (e.g. spray drift or volatilization), the Agency will re-examine the need for spray drift 

and volatilization assessments for abamectin during registration review. 

A Turf Transferable Residue (TRR) study is not required for abamectin at this time because

neither dermal nor hand-to-mouth exposure is expected following the registered fire ant mound 

uses on turf.

Conclusions: There is sufficient information available to assess residential exposure. All 

residential exposure scenarios have been assessed using HED’s 2012 Residential SOPs along 

with policy changes for body weights and current toxicological endpoints. A new residential 

assessment is not expected to be needed in the registration review process unless toxicological 

endpoints/points of departure are revised or the Agency develops new policies/procedures to 

quantitate residential post-application inhalation exposure.

 

Aggregate Risk Assessment

In the most recent human health risk assessment (DP# D402677, N. Dodd, 12/20/12), acute, 

chronic, and short-term aggregate exposures were assessed. The aggregate assessments 
Page 8 of 26

considered exposures from food, drinking water, and residential uses (as appropriate). All risk 

estimates were below the level of concern. 

A cancer aggregate risk assessment was not performed because abamectin is classified as “not 

likely to be carcinogenic to humans.”

Conclusions: A new aggregate risk assessment is not expected to be needed in the registration 

review process unless the toxicological endpoints/points of departure are revised or the Agency 

develops new policies/procedures to quantitate residential post-application inhalation exposure.

Occupational Exposure

Abamectin is registered for several agricultural uses and non-crop areas. The durations of 

exposure are expected to be short-term (1-30 days) and intermediate-term (1-6 months); longterm exposures are not anticipated. The LOC for dermal and inhalation risk estimates is a MOE 

of less than 300 for short- and intermediate-term exposure. Occupational handler and postapplication exposure and risk assessments have been conducted on a majority of the registered 

occupational (agricultural and non-crop) uses, resulting in risk estimates that are not of concern, 

with the required PPE.

Based on the Agency's current practices, a quantitative occupational post-application inhalation 

exposure assessment has not been performed for abamectin at this time.

Dislodgeable Foliar Residue (DFR): In accordance with the updated Part 158 data requirements 

(2007), one or more DFR studies are required when a pesticide has residential or occupational 

uses that could result in post-application dermal exposure. As part of the recent revision to the 

Health Effects Division’s 2012 Standard Operating Procedures for Residential Pesticide 

Exposure Assessment, HED analyzed a number of DFR studies and selected a new default value 

for the fraction of the application rate available to be dislodged after a foliar application (FAR). 

This default value is 25% and is based on an analysis of 19 DFR studies where the FAR value 

ranged from 2% to 89%. This value is recommended for use in both residential and occupational 

postapplication assessments. Of the analyzed DFR studies, the maximum FAR value seen was 

89% or 3.6 times higher than the default residue transfer value. Therefore, the HED has decided 

that a calculated MOE of approximately 4 times higher than the level of concern (e.g., an MOE > 

400 if the LOC = 100) using the default dislodged residue values would provide an adequate 

margin of safety for any potentially higher residues seen in a chemical-specific DFR study 

(Guidance for Requiring/Waiving Turf Transferrable Residue (TTR) and Dislodgeable Foliar 

Residue (DFR) Studies. 6/7/2012, Exposure Science Advisory Council). A DFR study is not 

required for abamectin at this time since dermal MOEs are greater than 1200 based on default 

values for the fraction of application rate available for transfer after a foliar application.

Dermal and Inhalation Exposure: Due to a lack of information about the seed treatment 

industry, HED cannot characterize the broad range of handler MOEs in any probabilistic 

distributional context. Since there is potential for risks of concern based on the Helix® study, 

dated August 2000, and Avicta® 500FS is currently registered for use on cottonseed and corn 

seed in closed systems, HED previously required the registrant to submit an exposure monitoring 
Page 9 of 26

study of Avicta® 500FS as a condition of registration (COR). This study must be submitted 

under guideline numbers 875.2400 and 875.2500.

Conclusions: There is sufficient information available to assess occupational handler and postapplication exposures. While all occupational exposure scenarios were not adequately assessed 

based on current HED policies, the most recent assessments are protective of the previously 

unassessed scenarios. An up-to-date quantitative occupational risk assessment may be required 

to account for the currently registered application rates, the changes in unit exposures, the 

changes in transfer coefficients (TCs), and any possible changes to endpoints and safety factors.

Updated risk estimates are unlikely to result in risks of concern.

Endocrine Disruptor Screening Program (EDSP)

As required by the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and the Federal 

Food, Drug, and Cosmetic Act (FFDCA), EPA reviews numerous studies to assess potential 

adverse outcomes from exposure to chemicals. Collectively, these studies include acute, 

subchronic and chronic toxicity, including assessments of carcinogenicity, neurotoxicity, 

developmental, reproductive, and general or systemic toxicity. These studies include endpoints 

which may be susceptible to endocrine influence, including effects on endocrine target organ 

histopathology, organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, 

reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates 

acute tests and chronic studies that assess growth, developmental and reproductive effects in 

different taxonomic groups. As part of its most recent registration decision, EPA reviewed these 

data and selected the most sensitive endpoints for relevant risk assessment scenarios from the 

existing hazard database. However, as required by FFDCA section 408(p), abamectin is subject 

to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP). 

EPA has developed the EDSP to determine whether certain substances (including pesticide 

active and other ingredients) may have an effect in humans or wildlife similar to an effect 

produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator 

may designate.” The EDSP employs a two-tiered approach to making the statutorily required 

determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a 

chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal 

systems. Chemicals that go through Tier 1 screening and are found to have the potential to 

interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA 

will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 

testing is designed to identify any adverse endocrine-related effects caused by the substance, and 

establish a dose-response relationship between the dose and the E, A, or T effect. 

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between 

October 2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 

chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. Abamectin

was included on that list and has been issued an order to conduct the Tier 1 testing. Once all 

required Tier 1 asssay data have been received and reviewed, the endpoints and safety factors 

used for risk assessment purposes will be examined and a new risk assessment performed if 

necessary. For further information on the status of the EDSP, the policies and procedures, the 
Page 10 of 26

list of 67 chemicals, future lists, the test guidelines and the Tier 1 screening battery, please visit 

our website: http://www.epa.gov/endo/. 

Public Health and Pesticide Epidemiology Data

A database search was conducted to identify potential patterns in the frequency and severity of 

the health effects attributed to abamectin exposure (D409003, S. Recore, 2/20/13). Both the OPP 

Incident Data System (IDS) and the Centers for Disease Control and Prevention/National 

Institute for Occupational Safety and Health (CDC/NIOSH) Sentinel Event Notification System 

for Occupational Risk-Pesticides (SENSOR) databases were consulted for pesticide incident data 

on the active ingredient abamectin (PC Code: 122804). Abamectin is not included in the 

Agricultural Health Study (AHS); therefore, the AHS did not provide information for this report.

Based on the relatively low frequency and severity of incident cases reported for abamectin in 

both IDS and NIOSH SENSOR-Pesticides, there does not appear to be a concern that would 

warrant further investigation at this time. The Agency notes that there were three incidents that 

occurred due to allergic reactions to peanut products in two RAID Ant Baits. The Agency will 

continue to monitor the incident information and if a concern is triggered, additional analysis 

will be included in the risk assessment.

Tolerance Assessment and International Harmonization

Tolerances are established under 40 CFR §180.449 for residues of abamectin (avermectin), 

including its metabolites and degradates, in or on various crop and livestock commodities at 

levels ranging from 0.005 ppm to 0.20 ppm. Several tolerances are pending, including a 

tolerance on cotton gin byproducts at 1.0 ppm. Compliance with the tolerance levels is to be 

determined by measuring only avermectin B1 [a mixture of avermectins containing greater than 

or equal to 80% avermectin B1a (5- O -demethyl avermectin A1 ) and less than or equal to 20% 

avermectin B1b (5- O -demethyl-25-de(1-methylpropyl)-25-(1-methylethyl) avermectin A1 )] and 

its delta-8,9-isomer.

There are some Codex, Canadian, or Mexican maximum residue limits (MRLs) established for 

residues of abamectin in crop or livestock commodities (see Attachment 2). The tolerance 

expressions for the US and Canada as compared to Codex include the same analytes for plants 

but differ for livestock commodities, i.e., the residue definitions are harmonized for plants but 

not for livestock commodities. There are some differences in established tolerance levels among 

the US, Canada, and Codex. The database will be examined during registration review to 

determine if these differences can be harmonized.

Environmental Justice

Potential areas of environmental justice concerns, to the extent possible, will be considered in the 

registration review, in accordance with US Executive Order 12898, "Federal Actions to Address 

Environmental Justice in Minority Populations and Low-Income Populations," 

http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf).

As a part of every pesticide risk assessment, OPP considers a large variety of consumer 
Page 11 of 26

subgroups according to well-established procedures. In line with OPP policy, HED estimates 

risks to population subgroups from pesticide exposures that are based on patterns of that 

subgroup’s food and water consumption, and activities in and around the home that involve 

pesticide use in a residential setting. Extensive data on food consumption patterns are compiled 

under the National Health and Nutrition Examination Survey, What We Eat in America 

(NHANES/WWEIA) and are used in pesticide risk assessments for all registered food uses of a 

pesticide. These data are analyzed and categorized by subgroups based on age and ethnic group. 

Additionally, OPP is able to assess dietary exposure to smaller, specialized subgroups and 

exposure assessments are performed when conditions or circumstances warrant. Whenever 

appropriate, non-dietary exposures based on home use of pesticide products and associated risks 

for adult applicators and for toddlers, youths, and adults entering or playing on treated areas 

postapplication are evaluated. Further considerations are currently in development as OPP has 

committed resources and expertise to the development of specialized software and models that 

consider exposure to bystanders and farm workers as well as lifestyle and traditional dietary 

patterns among specific subgroups.

Cumulative 

Unlike other pesticides for which EPA has followed a cumulative risk approach based on a 

common mechanism of toxicity (CMT), EPA has not made a common mechanism of toxicity 

finding as to abamectin and any other substances and abamectin does not appear to produce a 

toxic metabolite produced by other substances. EPA has evaluated the available mechanistic 

information available for abamectin and determined that there is not sufficient information to 

establish the key biological steps leading to adverse health outcomes (i.e., mammalian 

mechanism of action). Therefore, EPA has not assumed that abamectin has a common 

mechanism of toxicity with other substances.

For information regarding EPA’s efforts to determine which chemicals have a common 

mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see the policy 

statements released by EPA’s Office of Pesticide Programs concerning common mechanism 

determinations and procedures for cumulating effects from substances found to have a common 

mechanism on EPA’s website at http://www.epa.gov/pesticides/cumulative/.

Human Studies

The risk assessments which have been previously conducted for abamectin have relied in part on 

data from studies in which adult human subjects were intentionally exposed to a pesticide to 

determine their dermal and inhalation exposure. Many such studies, involving exposure to many 

different pesticides, comprise generic pesticide exposure databases such as the Pesticide 

Handlers Exposure Database (PHED), the Outdoor Residential Exposure Task Force (ORETF), 

and the Agricultural Reentry Task Force (ARTF) Database. EPA has reviewed all the studies 

supporting these multi-pesticide generic exposure databases, and has found no clear and 

convincing evidence that the conduct of any of them was either fundamentally unethical or 

significantly deficient relative to the ethical standards prevailing at the time the research was 

conducted. All applicable requirements of EPA’s Rule for the Protection of Human Subjects of 
Page 12 of 26

Research (40 CFR Part 26) have been satisfied, and there is no regulatory barrier to continued 

reliance on these studies.

Data Requirements

As shown in References below, fourteen human health risk assessments have been conducted for 

abamectin between 1997 and 2012. 

The outstanding data gaps associated with the Section 3 assessments are shown below. The 

registrants should be aware that they are responsible for replacing analytical reference standards 

at the EPA National Pesticide Standards Repository when the dates expire or the supplies are 

depleted.

Toxicology

None.

Residue Chemistry

None.

Occupational and Residential Exposure

875.2400 Dermal Exposure and 875.2500 Inhalation Exposure

A dermal and inhalation exposure study is required for chemical-specific abamectin seed 

treatment of cotton or corn in a closed system.

References

Memoranda Relevant to Registration Review of Abamectin

Author Barcode 

(DP#)

Date Title

Risk Assessments

N. Dodd D402677 12/20/12 Abamectin. Human Health Risk Assessment for Uses of the 

SC Formulation on Cotton and Strawberry

N. Dodd D393232 8/24/11 Abamectin. Amendment to the Human Health Risk 

Assessment for Proposed Uses on the Bulb Onion Subgroup 3-

07A, Chives, and Dry Beans to include Cowpea in the Dry 

Bean Tolerance

N. Dodd D380523 7/18/11 Abamectin. Human Health Risk Assessment for Proposed 

Uses on the Bulb Onion Subgroup 3-07A, Chives, and Dry 

Beans
Page 13 of 26

Memoranda Relevant to Registration Review of Abamectin

Author Barcode 

(DP#)

Date Title

N. Dodd D374426 2/18/10 Abamectin. Human Health Risk Assessment Analysis

for Proposed Use as: (1) a Soybean Seed Treatment

(Non-food); and (2) Bridging Studies from Emulsifiable

Concentrate (EC) to Suspension Concentrate (SC)

Formulations to Support SC Use on Almonds, Walnuts,

Apples, Pears, Avocadoes, Celeriac, Citrus Fruit, Cotton,

Cucurbit Vegetables, Fruiting Vegetables, Grapes, Herbs

(except Chives), Hops, Leafy Vegetables, Mint, Plums,

Prunes, and Potatoes

N. Dodd D365712 6/2/09 Abamectin. Addendum to Revised Human Health Risk

Assessment for Proposed Uses on Pasture and

Rangeland Grass, Stone Fruit Crop Group 12, Tree Nut

Crop Group 14, Pistachio, Tuberous and Corm

Vegetables Subgroup 1C and Request for Cattle Ear Tag

Use

N. Dodd D362615 3/11/09 Abamectin. Revised Human Health Risk Assessment for

Proposed Uses on Pasture and Rangeland Grass, Stone

Fruit Crop Group 12, Tree Nut Crop Group 14,

Pistachio, Tuberous and Corm Vegetables Subgroup 1C

and Request for Cattle Ear Tag Use

N. Dodd D315734 1/27/09 Abamectin. Human Health Risk Assessment for

Proposed Uses on Pasture and Rangeland Grass, Stone

Fruit Crop Group 12, Tree Nut Crop Group 14,

Pistachio, Tuberous and Corm Vegetables Subgroup 1C

and Request for Cattle Ear Tag Use

K. O’Rourke D317742 Abamectin 9/15/05 Abamectin (Avermectin B1). Human Health Risk Assessment 

for the New Use Seed Treatment of Cucurbits and Tomatoes 

N. Dodd D313175 2/16/05 Abamectin. Human Health Risk Assessment for Proposed 

Uses on Pasture and Rangeland Grass, Stone Fruit Crop Group 

12, Tree Nut Crop Group 14, Pistachio, Tuberous and Corm 

Vegetables Subgroup 1C and Request for Cattle Ear Tag Use

K. O’Rourke D297225 11/2/04 Abamectin (Avermectin B1). Human Health Risk Assessment 

for New Uses on Plums/Prunes, Leafy Vegetables, Fruiting 

Vegetables, Herb Subgroup (except chives), Avocado, Mint, 

and Food Handling Establishments

G. J. Herndon D259195 9/3/99 Avermectin. Revised Risk Estimates for Human Health

Risk Assessment for the Request for Tolerances on

Grapes, Raisins, and Peppers. Update of Memo of G.J.

Herndon Dated 6/28/99

G. J. Herndon D257267 6/28/99 Avermectin. Revised Risk Estimates for Human Health

Risk Assessment for the Request for Tolerances on

Grapes, Raisins, and Peppers

W. Cutchin D248844 2/24/99 Avermectin. Human Health Risk Assessment for the Request 

for Tolerances on Grapes, Raisins, and Peppers

G.J. Herndon D232674 1/24/97 PP#5F04508. Use of Averrmectin B1 on Potatoes. Section 3 

Registration and Permanent Tolerance Request
Page 14 of 26

Memoranda Relevant to Registration Review of Abamectin

Author Barcode 

(DP#)

Date Title

Residue Chemistry

N. Dodd D401832 12/17/12 Abamectin. Petition to Increase the Established Permanent 

Tolerances on Strawberry and Cotton and to Add Uses on 

Strawberry and Cotton to Agri-Mek® SC and Epi-MekTM SC 

Labels. Summary of Analytical Chemistry and Residue Data

Dietary Exposure Assessment

N. Dodd D403715 12/19/12 Abamectin. Acute and Chronic Aggregate Dietary (Food and 

Drinking Water) Exposure and Risk Assessments for the 

Section 3 Registration Action for Use of a Suspension 

Concentrate (SC) Formulation on Cotton and Strawberry

Occupational Residential Exposure

N. Tsaur D405841 12/20/12 Abamectin. Occupational Exposure Assessment for a Label 

Amendment for Use on Cotton and Strawberries with an 

Updated Residential Exposure Assessment of All Existing 

Residential Uses (Lawns/Turf and Indoor Environments)

Toxicology

S. Recore D409003 2/20/13 Abamectin: Review of Human Incidents

K. Rury, MPH TXR # 

0056509

1/30/13 Abamectin: Summary of Hazard and Science Policy Council 

(HASPOC) Meeting of November 8, 2012: Recommendations 

on the Requirement of a Subchronic Inhalation Study and 

Dermal Toxicity Study. 

Van Alstine, 

J., MPH

410367 June

2013

Abamectin – Report of the Hazard and Science Policy Council 

(HASPOC) Meeting of June 6, 2013; Waiver for the 

Immunotoxicity Study (870.7800)

Attachments

1. Chemical Identity Table

2. Tolerance/MRL Summary Table

3. Endpoint Selection Table

4. Toxicity Profile Tables
Page 15 of 26

Attachment 1

Chemical Identity Table

Table 1. Chemical Identity - Abamectin 

Common Name abamectin, avermectin B1

Chemical Name (CAS) avermectin B1

PC Code 122804

Chemical Abstracts No. avermectin B1 - 71751-41-2; avermectin B1a - 65195-55-3; avermectin B1b -

65195-56-4

Registration Review Case No. 7430

Chemical Class avermectin insecticide/miticide/nematicide

Chemical Structure

Abamectin
Page 16 of 26

Attachment 2

Tolerance/MRL Summary Table

The Codex, Canadian, or Mexican maximum residue limits (MRLs) established for residues of 

abamectin in crop or livestock commodities are shown in the table below.

ABAMECTIN (122804; 2/04/2013)

Table 2. Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico1 Codex2

40 CFR §180.449: 

Plants/Livestock: avermectin B1 [a mixture of 

avermectins containing greater than or equal 

to 80% avermectin B1a (5- O -demethyl 

avermectin A1 ) and less than or equal to 20% 

avermectin B1b (5- O -demethyl-25-de(1-

methylpropyl)-25-(1-methylethyl) avermectin 

A1 )] and its delta-8,9-isomer 

avermectin B1 (a mixture 

of avermectins containing 

greater than or equal to 

80% avermectin B1a (5-Odemethyl avermectin A1a) 

and less than or equal to 

20% avermectin B1b (5-

O-demethyl-25-de(1-

methylpropyl)-25-(1-

methylethyl) avermectin 

A1a) and its delta-8,9-

isomer)

Plants: sum of 

avermectin B1a, 

avermectin B1b, 

8,9-Z-avermectin 

B1a and 8,9-Zavermectin B1b. 

Animal 

commodities: 

sum of 

avermectin

B1a and 8,9-Zavermectin B1a.

Commodity Tolerance (ppm) /Maximum Residue Limit (mg/kg)

US Canada Mexico1 Codex2

Almond, hulls 0.10 0.1

Apple 0.020 0.02 0.02

Apple, wet pomace 0.10

Avocado 0.020

Bean, dry, seed 0.01

Cattle, fat 0.03 0.13

Cattle, meat 0.02 0.01 (*)

Cattle, meat byproducts 0.06 0.053cattle 

kidney

0.13cattle liver

Celeriac, roots 0.05

Celeriac, tops 0.05

Chive, dried leaves 0.02

Chive, fresh leaves 0.01

Citrus, dried pulp 0.10

Citrus, oil 0.10

Citrus 0.02 0.02 citrus fruits 0.01 (*) citrus 

fruits 

Cotton, gin byproducts 0.15

Cotton, undelinted seed 0.005 0.01 (*)

Food products in food handling 

establishments (other than those 

already covered by higher 

tolerances as a result of use on 

growing crops, and other than 

those already covered by tolerances 

on milk, meat, and meat 

byproducts)

0.01

Fruit, stone, group 12 0.09
Page 17 of 26

Table 2. Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico1 Codex2

Goat, fat 0.01

Goat, meat 0.02 0.01 (*)

Goat, meat byproducts 0.02 0.1 goat, edible 

offal of

Grape 0.02 0.02

Herb subgroup 19A, except chive 0.030

Hog, fat 0.01

Hog, meat 0.02

Hog, meat byproducts 0.02

Hop, dried cones 0.20 0.1 hops, dry

Horse, fat 0.01

Horse, meat 0.02

Horse, meat byproducts 0.02

Milk 0.005 0.005 cattle milk

Nut, tree, group 14 0.01 0.005 almond nuts, 

walnuts

0.01 (*) almonds, 

walnuts

Onion, bulb, subgroup 3-07A 0.01

Pear 0.02 0.02 0.02

Peppermint, tops 0.010

Pistachio 0.01

Plum, prune, dried 0.025

Poultry, meat 0.02

Poultry, meat byproducts 0.02

Sheep, fat 0.01

Sheep, meat 0.02

Sheep, meat byproducts 0.02

Spearmint, tops 0.010

Strawberry 0.02 0.02 0.02

Vegetable, cucurbit, group 9 0.005 0.005 cucumbers 0.01 cucumber

0.01 (*) melons, 

except 

watermelon; 

watermelon, 

squash summer

Vegetable, fruiting, group 8 0.020 0.01 peppers, tomatoes 0.2 peppers chili, 

dried

0.02 Peppers, 

sweet (including 

pimento or 

pimiento), tomato

Vegetable, leafy, except brassica, 

group 4

0.10 0.05 celery, head lettuce 0.05 lettuce leaf

Vegetable, tuberous and corm, 

subgroup 01C

0.01 0.01 potatoes 0.01 (*) potato

MRLs with NO US Equivalent

Goat milk 0.005

Completed by: M. Negussie; 2/06/13
Page 18 of 26

1 Mexico adopts US tolerances and/or Codex MRLs for its export purposes.

2 * = absent at the limit of quantitation; Po = postharvest treatment, such as treatment of stored grains. PoP = 

processed postharvest treated commodity, such as processing of treated stored wheat. (fat) = to be measured on the 

fat portion of the sample. MRLs indicated as proposed have not been finalized by the CCPR and the CAC.

3 The MRL accommodates external animal treatment.
Page 19 of 26

Attachment 3

Summary of Toxicity Endpoints and Points of Departure of Abamectin

Table 3. Summary of Toxicological Doses and Endpoints for Abamectin for Use in Dietary and NonOccupational Human Health Risk Assessments

Exposure/ 

Scenarios

Point of 

Departure

Uncertainty/

FQPA Safety 

Factor

RFD, PAD, 

Level of 

Concern 

(LOC) 

Study and Toxicological Effects

Acute Dietary

(General 

population, 

including infants 

and children)

NOAEL = 

0.5 

mg/kg/day

UFA = 10x

UFH = 10x

FQPA SF=1x

aRfD = 0.005 

mg/kg/day

12-Week dose-range finding study in dogs

LOAEL = 1.0 mg/kg/day based on mydriasis 

seen 1-5 times during the first week of 

treatment. 

Acute neurotoxicity study in rats

LOAEL= 1.5 mg/kg/day based on increased 

incidence of foot splay.

Chronic Dietary

(All populations)

NOAEL = 

0.12 

mg/kg/day

UFA = 10x

UFH = 10x

FQPA SF=3x*

cPAD = 

0.0004 

mg/kg/day

Combined data from three reproduction 

studies and two developmental 

neurotoxicity studies (please see the 

discussion on Chronic Dietary Endpoint)

LOAEL = 0.2 mg/kg/day based on decreased 

pup body weight in pups at 0.2 mg/kg/day. 

Short-Term and 

Intermediate 

Term

Incidental Oral 

NOAEL = 

0.12 

mg/kg/day

UFA = 10x

UFH = 10x

FQPA SF=3x*

Residential 

LOC for 

MOE = 300

Combined data from three reproduction 

studies and two developmental 

neurotoxicity studies (please see the 

discussion on Chronic Dietary Endpoint)

LOAEL = 0.2 mg/kg/day based on decreased 

pup body weight. 

Dermal (All 

Durations)

NOAEL = 

0.12 

mg/kg/day

UFA = 10x

UFH = 10x

FQPA SF=3x*

Residential 

LOC for 

MOE = 300

Combined data from three reproduction 

studies and two developmental 

neurotoxicity studies (please see the 

discussion on Chronic Dietary Endpoint)

LOAEL = 0.2 mg/kg/day based on decreased 

pup body weight. 

Inhalation (All 

durations)

NOAEL = 

0.12 

mg/kg/day

UFA = 10x

UFH = 10x

FQPA SF=3x*

Residential 

LOC for 

MOE = 300

Combined data from three reproduction 

studies and two developmental 

neurotoxicity studies (please see the 

discussion on Chronic Dietary Endpoint)

LOAEL = 0.2 mg/kg/day based on decreased 

pup body weight. 

Cancer (oral, 

dermal, 

inhalation)

Classification: Not likely to be carcinogenic to humans based on the absence of significant 

increase in tumor incidence in two adequate rodent carcinogenicity studies.

Point of Departure (POD) = A data point or an estimated point that is derived from observed dose-response data and 

used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human 

exposures. NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = 

uncertainty factor. UFA = extrapolation from animal to human (interspecies). UFH = potential variation in 

sensitivity among members of the human population (intraspecies). FQPA SF = FQPA Safety Factor. PAD = 

population adjusted dose (a = acute, c = chronic). RfD = reference dose. MOE = margin of exposure. LOC = level 

of concern. N/A = not applicable.

* The additional FQPA safety factor of 3x is for the steepness of the dose-response curve and the severity of effects.
Page 20 of 26

Table 4. Summary of Toxicological Doses and Endpoints for Abamectin for Use in Occupational Human 

Health Risk Assessments

Exposure/ Scenarios Point of 

Departure

Uncertainty/ 

Safety Factor

RFD, PAD, 

LOC* Study and Toxicological Effects

Dermal (Short-Term 

and IntermediateTerm)

NOAEL = 0.12 

mg/kg/day

1% Dermal 

Absorption 

Factor

UFA = 10X

UFH = 10X

SF = 3X

LOC: MOE = 300

Combined data from three 

reproduction studies and two 

developmental neurotoxicity 

studies.

LOAEL = 0.2 mg/kg/day based 

on decreased pup body weight in 

pups. 

Inhalation (ShortTerm and 

Intermediate-Term)

NOAEL = 0.12 

mg/kg/day

UFA = 10X

UFH = 10X

SF = 3X

LOC: MOE = 300

Combined data from three 

reproduction studies and two 

developmental neurotoxicity 

studies.

LOAEL = 0.2 mg/kg/day based 

on decreased pup body weight in 

pups. 

Cancer (oral, dermal, 

inhalation)

Classification: Not likely to be carcinogenic to human based on the absence of significant 

increase in tumor incidence in two adequate rodent carcinogenicity studies.

Point of Departure (PoD) = A data point or an estimated point that is derived from observed dose-response data and 

used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human 

exposures. NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = 

uncertainty factor. UFA = extrapolation from animal to human (interspecies). UFH = potential variation in 

sensitivity among members of the human population (intraspecies). SF = Safety Factor. PAD = population adjusted 

dose (a = acute, c = chronic). RfD = reference dose. MOE = margin of exposure. LOC = level of concern. N/A = 

not applicable. 

* Level of Concern (LOC): For occupational exposure risk assessments, the uncertainty factor is 300X (10X for 

interspecies extrapolation; 10X for intraspecies variations; and 3X for the steepness of the dose-response curve in 

several studies and the severity of effects [death] seen at the slightly higher dose level).
Page 21 of 26

Attachment 4

Toxicity Profile Tables

Table 5. Acute Toxicity Profile of Abamectin Technical

Guideline No. Study Type MRID # Results Toxicity Category

870.1100 Acute Oral - rat 

(sesame oil vehicle)

006894 LD50 = 13.6 mg/kg I

870.1100 Acute Oral - rat

(methyl cellulose vehicle)

45607202 LD50=214-232 mg/kg II

870.1200 Acute Dermal - rabbit 00255978 LD50 = 2000 mg/kg III

870.1300 Acute Inhalation - rat 45623501 LC50 =<0.21 mg/L (nose only) I

870.2400 Primary Eye Irritation 45063501 not an irritant IV

870.2500 Primary Skin Irritation 41123904 slight irritation III

870.2600 Dermal Sensitization 00139564 negative in Buehler Negative

870.6200a Acute Neurotoxicity none none none

Table 6. Toxicity Profile of Abamectin Technical for Repeated Dosing and Genotoxicity Studies

Guideline No./ 

Study Type

MRID No. (year)/ 

Classification /Doses

Results

870.3100

Subchronic feeding 

study-rats

00131081 (1982)

Acceptable/Non-guideline

0, 0.10, 0.20, 0.40 

mg/kg/day

NOAEL > 0.40 mg/kg/day

LOAEL = not established

870.3150

Subchronic toxicity

Dogs (18 week 

gavage study)

00131082 (1982)

Acceptable/Guideline

0, 0.25, 0.5, 2.0, 8.0 

mg/kg/day

NOAEL = 0.25 mg/kg/day

LOAEL = 0.50 mg/kg/day based on body tremors, one death, 

liver pathology, decreased body weight. Mydriasis was seen 

during week one in one dog.

870.3150

12-Week dose range 

finding study-dogs 

(feeding) 

00164152 (1982)

0.25, 0.50, 1.0, and 4.0/2.0 

mg/kg/day (during week 4, 

4.0 mg/kg/day was reduced 

to 2.0 mg/kg/day due to 

tremor, weakness, 

incoordination, and 

disorientation) 

The report stated that mydriasis was seen in 1.0 and 4.0 

mg/kg/day dogs during week 1.The effect was not seen at each 

examination day for any dog, but it was generally noted from 1 to 

5 times a week. However, mydriasis was never noted at 0.5 and 

0.25 mg/kg/day. 

870.3200

21/28-Day dermal 

toxicity

Study not available. Study requirement was waived due to very low dermal absorption 

(<1%).
Page 22 of 26

Table 6. Toxicity Profile of Abamectin Technical for Repeated Dosing and Genotoxicity Studies

Guideline No./ 

Study Type

MRID No. (year)/ 

Classification /Doses

Results

870.3465

30-Day inhalation 

tox.-rats

46921502 (2006)

Acceptable/Guideline

NOAEL = >2.5 μg/L (0.0025 mg/L) (HDT) (≈0.68 mg/kg/day)

.

870.4300a

Combined Chronic 

toxicity/carcinogenici

ty- rats

40069601, 40375511, 

40517801 (1985)

Acceptable/Guideline 

0, 0.75, 1.5, 2.0 mg/kg/day

NOAEL = 1.5 mg/kg/day

LOAEL = 2.0 mg/kg/day based on tremors

No evidence of carcinogenicity

870.4100b

Chronic toxicity dogs

40375510 (1987)

Acceptable/Guideline

0, 0.25, 0.5, 1.0 mg/kg/day

NOAEL = 0.25 mg/kg/day

LOAEL = 0.5 mg/kg/day based on mydriasis during week one, 

death at 1.0 mg/kg/day

870.4300b

Combined Chronic 

toxicity/Carcinogenic

ity- mice

40069602, 40375512, 

40517801 (1985)

Acceptable/Guideline

0, 2, 4, 8 mg/kg/day

NOAEL = 4.0 mg/kg/day

LOAEL = 8.0 mg/kg/day based on increased mortality in males, 

tremors, body weight decreases in females, dermatitis in males, 

extramedullary hematopoiesis in spleen of males

No evidence of carcinogenicity

870.3700a

Prenatal 

developmental

in rodents-rats

Accession: 00130819 

(1982)

Acceptable/Guideline

0, 0.4, 0.8, 1.6 mg/kg/day

Maternal NOAEL > 1.6 mg/kg/day

Maternal LOAEL = not established

Developmental NOAEL > 1.6 mg/kg/day

LOAEL = not established

870.3700a

Prenatal 

developmental in 

rodents-CD-1 mouse

44179901 (1999)

Acceptable/Non-guideline

0, 0.75, 1.5, 3.0 mg/kg/day

Maternal NOAEL = 1.5 mg/kg/day

Maternal LOAEL = 3.0 mg/kg/day based on hind limb splay

Developmental NOAEL < 0.75 mg/kg/day

Developmental LOAEL = 0.75 mg/kg/day based on hind limb 

extension

870.3700b

Prenatal 

developmental

in nonrodents-rabbits

Accession: 00130819 

(1982)

Acceptable./Guideline

0, 0.5, 1.0, 2.0 mg/kg/day 

Maternal NOAEL = 1.0 mg/kg/day

Maternal LOAEL = 2.0 mg/kg/day based on decreased body 

weight, food consumption and water consumption 

Developmental NOAEL = 1.0 mg/kg/day

LOAEL = 2.0 mg/kg/day based on cleft palate, clubbed foot, 

delayed ossification of sternebrae, metacarpals, phalanges 

870.3800a

2-Generation 

Reproduction and 

fertility effects-rat

00164151 (1984)

Acceptable/Guideline

0, 0.05, 0.12, 0.40 

mg/kg/day

Parental/Systemic NOAEL = 0.40 mg/kg/day

LOAEL =not established

Reproductive NOAEL = 0.40 mg/kg/day

LOAEL = not established

Offspring NOAEL = 0.12 mg/kg/day

LOAEL = 0.40 mg/kg/day based on increased retinal folds, 

increased dead pups at birth, decreased viability and lactation 

indices, decreased pup body weight
Page 23 of 26

Table 6. Toxicity Profile of Abamectin Technical for Repeated Dosing and Genotoxicity Studies

Guideline No./ 

Study Type

MRID No. (year)/ 

Classification /Doses

Results

870.3800b

1-Generation 

Reproduction and 

fertility effects-rat 

00096450

Unacceptable/Nonguideline

0, 0.5, 1.0, 1.5/2.0 

mg/kg/day

Parental/Systemic NOAEL = 1.0 mg/kg/day. 

LOAEL=1.5/2.0 based on whole body tremors, ataxia, ptyalis, 

ocular/nasal discharges and mortality

Reproductive NOAEL = 3.0 mg/kg/day

Offspring NOAEL < 0.5 mg/kg/day

LOAEL = 0.5 mg/kg/day based on decreased pup survival and 

body weight between days 1-21 and delay in opening of eyes

870.3800c

1-Generation 

Reproduction and 

fertility effects- rat

00096451

Unacceptable/Nonguideline

0, 0.1, 0.2, 0.4 mg/kg/day

Parental/Systemic NOAEL = 0.4 mg/kg/day

LOAEL = not established

Reproductive NOAEL = 0.4 mg/kg/day

Offspring NOAEL =0.1 mg/kg/day

LOAEL = 0.2 mg/kg/day based on spastic movements and, 

delayed incisor eruption

870.3800c

1-Generation 

Reproduction and 

fertility effects- rat

40713404 (1988)

Acceptable/Non-guideline

0, 0.1, 0.2, 0.4 mg/kg/day

with delta-8,9 isomer

0, 0.06, 0.12, 0.40 

mg/kg/day

Parental/Systemic NOAEL = 0.4 mg/kg/day

LOAEL = not established

Reproductive NOAEL = 0.4 mg/kg/day

Offspring NOAEL =0.4 mg/kg/day

LOAEL = not established

Gene Mutation

870.5100

Ames/Salmonella

E.coli/mammalian 

gene mutation assay

Accession: 246894, 

265568, 265569 (1986)

Acceptable/Guideline

Three studies: (1) 0, 3, 10, 

30, 100, 1000 ug/plate, (2) 

0, 100, 300, 1000, 3000, 

10,000 ug/plate both with 

and without S-9, (3) doses 

not specified.

negative both with and without S-9

870-6100 

Acute neurotoxicity 

in rats (gavage)

46959202 (2006)

Acceptable/Guideline

0.5, 1.5, and 6.0 mg/kg

NOAEL = 0.5 mg/kg/day

LOAEL = 1.5 mg/kg/day based on reduced splay reflex in males 

and females. At high dose, decreased motor activity, reduced 

splay reflex, & tip toe gait were seen. No death or 

histopathological changes in nervous system were found.

870-6200

Subchronic 

neurotoxicity in rats 

(gavage)

46959201 (2006)

Acceptable/Guideline

0.4, 1.6, and 4.0 mg/kg/day

NOAEL = 1.6 mg/kg/day

LOAEL = 4.0 mg/kg/day based on upward curvature of the spine, 

tip-toe gate, decreased fore- and hind-limb grip strength. 

Decreased body was also seen. This dose group was terminated 

prematurely at week 7. 

870-630

Developmental 

neurotoxicity study in 

rats 

46727403, 46727402, 

46727401 (2005)

Acceptable/Nonguideline

0.12, 0.20, and 0.40 

mg/kg/day. Pups were not 

directly dose.

Maternal NOAEL = 0.4 mg/kg/day (HDT)

Offspring NOAEL = 0.2 mg/kg/day.

Offspring LOAEL= 0.4 mg/kg/day based on decreased body 

weight in males and females.. 
Page 24 of 26

Table 6. Toxicity Profile of Abamectin Technical for Repeated Dosing and Genotoxicity Studies

Guideline No./ 

Study Type

MRID No. (year)/ 

Classification /Doses

Results

870-6200

Developmental 

neurotoxicity study in 

rats 

47116201 (2007)

Acceptable/Nonguideline

0.12, 0.20, and 0.40 

mg/kg/day. Pups were not 

directly dosed. 

Maternal NOAEL = 0.4 mg/kg/day (HDT)

Offspring NOAEL =0.12 mg/kg/day.

Offspring LOAEL = 0.2 mg/kg/day based on slight but 

statistically significant decrease in pup body weight. 

Gene Mutation

870.5100

Ames/Salmonella

E.coli/mammalian 

gene mutation assay

40713402 (1988)

Acceptable/Guideline

doses not specified up to 

3000 ug/plate both with 

and without S-9 using 

delta-8,9 isomer

negative both with and without S-9 up to 3000 ug/plate

Gene Mutation

870.5100

Ames/Salmonella

E.coli/mammalian 

gene mutation assay

40713405 (1988)

Acceptable/Guideline

doses up to 10,000 ug/plate 

both with and without S-9 

using polar degradates

negative both with and without S-9

Gene Mutation

870.5300

CHO/HGPRT

Forward Mutation 

Assay

265570 (1986)

Acceptable/Guideline

both with and without S-9

Negative

Gene Mutation

870.5300

Mammalian cells in 

culture in V79 cells

MRID Unavailable

1983

Acceptable/Guideline

Not mutagenic for V79 cells in absence of S-9, but in the 

presence of S-9 appeared to have a mutagenic potential, provided 

the test cells had an appropriate level of sensitivity

Cytogenetics 

870.5395

in vivo micronucleus 

assay -male mice

MRID Unavailable

Acceptable/Non-guideline

0, 1.2, 12.0 mg/kg i.p.

No chromosomal aberrations in male mice, but females not tested

Other Effects 

870.5550 

MRID Unavailable

(1983)

0.3 and 0.6 mM

single strand DNA breaks at 0.3 and 0.6 mM in rat hepatocytes in 

vitro, but negative when hepatocytes from rat at LD50 dose level 

was used

Metabolism Accession: 252114

Unacceptable/Nonguideline

69-82% of label is excreted in feces by day 7; T1⁄2=1.2 days. The 

reliability of these data is questionable.

Metabolism No MRID

(1985)

Nonguideline

Avermectin B1a did not bioaccumulate in rat tissues. Half-life 

slightly longer in females than in males for several tissues.

Metabolism No MRID

(1985)

Nonguideline

The metabolism of avermectin B1 in rats results in the formation 

of 24-OH-Me-B1a and accounts for most of the radiolabeled 

residues. Avermectin B1a does not bioaccumulate.
Page 25 of 26

Table 6. Toxicity Profile of Abamectin Technical for Repeated Dosing and Genotoxicity Studies

Guideline No./ 

Study Type

MRID No. (year)/ 

Classification /Doses

Results

870.7600

Dermal penetration

Accession: 265590 (1986)

Acceptable/

Nonguideline in Monkeys

The result showed the dermal absorption to be <1% of the 

applied dose. For risk assessment, a dermal penetration factor of 

1% was recommended.

Table 7. Toxicity Profile of Abamectin Technical - for CF1 Mice

Guideline No./ 

Study Type

MRID No. / Classification /Doses Results

870.3700a

Prenatal 

developmental in 

rodents- CF1 

mouse

44160501 (1996)

Acceptable/Non-Guideline

0, 1.5 mg/kg/day on gestation days 

(GD) 6-15 to females which were 

heterozygous (+/-) and homozygous 

(-/-, +/+) for p-glycoprotein and then 

mated to heterozygous and 

homozygous males 

Maternal NOAEL = 1.5 mg/kg/day

Maternal LOAEL = not established

97% of (-,-) fetuses, 40% of (+,-) fetuses, and 0% of (+,+) 

fetuses had cleft palate. It was determined that the 

observed increase in cleft palate in CF-1 mice following 

treatment appears to be a consequence of fetal Pglycoprotein genotype.

870.3700a

Prenatal 

developmental

in rodents-CF1 

mouse

Accession: 265564 (1986)

Acceptable/Guideline

0, 1.5, 3.0, 6.25, 12.5, 25, 50 

mg/kg/day with delta-8,9 isomer

Maternal NOAEL < 1.5 mg/kg/day

Maternal LOAEL = 1.5 mg/kg/day (mortality)

Developmental NOAEL < 1.5 mg/kg/day

LOAEL = 1.5 mg/kg/day based on increased cleft palate

870.3700a

Prenatal 

developmental in 

rodents-CF1 

mouse

Accession: 265564 (1986)

Acceptable/Guideline

0, 0.03, 0.1, 0.5 mg/kg/day with 

delta-8,9 isomer

Maternal NOAEL = 0.1 mg/kg/day

Maternal LOAEL = 0.5 mg/kg/day (mortality)

Developmental NOAEL = 0.03 mg/kg/day

LOAEL = 0.1 mg/kg/day based on increased cleft palate

870.3700a

Prenatal 

developmental in 

rodents-CF1 

mouse

Accession: 265564 (1985)

Acceptable/Guideline

0, 0.05, 0.1, 0.5, 1.0 mg/kg/day with 

deta-8,9 isomer

Maternal NOAEL = 0.1 mg/kg/day

Maternal LOAEL = 0.5 mg/kg/day (mortality)

Developmental NOAEL = 0.05 mg/kg/day

LOAEL = 0.1 mg/kg/day based on increased cleft palate

870.3700a

Prenatal 

developmental in 

rodents-CF1 

mouse

Accession: 40912701 (1988)

Acceptable/Guideline

0, 0.25, 0.50, 1.0 mg/kg/day with 

citrus derived polar degradates

Maternal NOAEL > 1.0 mg/kg/day

Maternal LOAEL = not established

Developmental NOAEL > 1.0 mg/kg/day

LOAEL =not established

870.3700a

Prenatal 

developmental in 

rodents-CF1 

mouse

Accession: 073759, 073761 (1984)

Acceptable/Non-Guideline

0, 0.1, 0.3, 0.6 mg/kg/day

Maternal NOAEL = 0.1 mg/kg/day

Maternal LOAEL = 0.3 mg/kg/day (mortality, tremors)
Page 26 of 26

Table 7. Toxicity Profile of Abamectin Technical - for CF1 Mice

Guideline No./ 

Study Type

MRID No. / Classification /Doses Results

870.3700a

Prenatal 

developmental in 

rodents-CF1 

mouse

00096446 (1986)

Acceptable/Guideline

0, 0.1, 0.2, 0.4, 0.8 mg/kg/day

Maternal NOAEL < 0.1 mg/kg/day

Maternal LOAEL = 0.1 mg/kg/day (mortality)

Developmental NOAEL = 0.2 mg/kg/day

LOAEL = 0.4 mg/kg/day based on increased cleft palate

870.3700a

Prenatal 

developmental in 

rodents-CF1 

mouse

Accession: 265564 (1985)

Acceptable/Guideline

0, 0.01, 0.03, 0.06 mg/kg/day with 

delta-8,9 isomer

Maternal NOAEL > 0.06 mg/kg/day

Maternal LOAEL = not established

Developmental NOAEL > 0.06 mg/kg/day

LOAEL = not established

870.3700a

Prenatal 

developmental in 

rodents-CF1 

mouse

Accession: 40713406 (1986)

Acceptable/Guideline

0, 0.25, 0.50, 1.0 mg/kg/day with 

polar degradates of abamectin

Maternal NOAEL > 1.0 mg/kg/day

Maternal LOAEL = not established

Developmental NOAEL > 1.0 mg/kg/day

LOAEL = not established