Docket ID EPA-HQ-OPP-2012-0145 

www.regulations.gov 

Acetaminophen 

Final Registration Review Decision 

Case Number 7610 

Approved by: 

Date: 

December 2014 

o..u:LP ;n 

Richard P. Keigwin, Jr. 

Director 

Pesticide Re-evaluation Division 
Table of Contents 

Contents 

I. Introduction ....................................................................................................................... 3 

II. Scientific Assessments ....................................................................................................... 4 

A. Environmental Assessment ................................................................................................ 4 

B. Endangered Species Assessment ........................................................................................ 5 

C. Human Health Assessment ................................................................................................. 5 

D. Endocrine Disruptor Screening Program .......................................... : .............................. 6 

III. Final Registration Review Decision ................................................................................. 6 

IV. Next Steps .......................................................................................................................... 7 

References: 

This Final Registration Review Decision document discusses the Environmental Protection 

Agency's current position based on the work plan for acetaminophen and other supporting 

documents, including: 

• Preliminary Ecological Risk and Endangered Species Assessment in Support of the 

Registration Review of Acetaminophen; N. Mastrota, J. Wolf, R. Louie-Juzwiak, April 12, 

2013. 

• Administrative Order, Exemption of Acetaminophen from the Requirements of the Endocrine 

Disruptor Screening Program; Jim Jones, dated October 30, 2014. 

This and other relevant documents can be found in the public docket at www.regulations.gov 

under Docket ID EPA-HQ-OPP-2012-0145. 

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I. Introduction 

This document is the Envirorunental Protection Agency's (EPA or the Agency) Final 

Registration Review Decision for acetaminophen and is being issued pursuant to 40 CFR 

sections 155.56 and 155.58. A registration review decision is the Agency's determination that a 

pesticide meets, or does not meet, the standard for registration in the Federal Insecticide, 

Fungicide, and Rodenticide Act (FIFRA). Further information on acetaminophen can be found 

in EPA's public docket (EPA-HQ-OPP-2012-0145) at www.regulations.gov. 

FIFRA, as amended by the Food Quality Protection Act (FQPA) of 1996, mandated the 

continuous review of existing pesticides. All pesticides distributed or sold in the United States 

generally must be registered by the EPA based on scientific data showing that they will not cause 

unreasonable risks to human health or to the environment when used as directed on product 

labeling. The registration review program is intended to make sure that, as the ability to assess 

and reduce risk evolves and as policies and practices change, all registered pesticides continue to 

meet the statutory standard of no unreasonable adverse effects. Changes in science, public 

policy, and pesticide use practices will occur over time. Through the registration review 

program, the Agency periodically reevaluates pesticides to make sure that as these changes 

occur, products in the marketplace can continue to be used safely. Information on this program 

is provided as www.epa.gov/oppsrrdl/registration review/. 

In 2006, the Agency implemented the registration review program pursuant to FIFRA 

section 3(g) and will review each registered pesticide every 15 years to determine whether it 

continues to meet the FIFRA standard for registration. Pursuant to 40 CFR § 155.50, the Agency 

formally initiated registration review for acetaminophen (Case 761 0) in March 2012. 

Acetaminophen (N-(4-hydroxyphenyl)-acetamide) is a widely used analgesic and 

antipyretic agent that has been available as an over-the-counter drug since 1960. It is a 

commonly used active ingredient in many drugs regulated by the U.S. Food and Drug 

Administration. Acetaminophen is registered with EPA for control of the invasive brown tree 

snake in the U.S. territories of Guam and the Commonwealth of Northern Mariana Islands 

(CNMI). Dead mouse pups are baited with acetaminophen, and the snake is killed when it 

ingests a baited mouse carcass. The brown tree snake is an invasive species that has decimated 

the native bird populations of Guam and other areas where it has become established. 

Highlights of significant actions during the registration review of acetaminophen are 

listed below. Relevant documentation can be found in the public docket: 

• March 28, 20 12 - The Agency posted the Acetaminophen Summary Document to the 

acetaminophen registration review docket for a 60-day public comment period. The 

Summary Document included the Agency's Preliminary Work Plan for Acetaminophen, 

and was accompanied by the Problem Formulation for the Environmental Fate, 

Ecological Risk, and Endangered Species and Drinking Water Assessments for 

Acetaminophen; and the Human Health Assessment Scoping Document in Support of 

Registration Review. 

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• August 31 , 2012 - The Acetaminophen Final Work Plan (FWP) was issued. Since no 

comments were received during the comment period, the FWP did not modify the 

Preliminary Work Plan. The FWP indicated that the Agency planned to conduct a 

qualitative ecological and endangered species risk assessment and would not conduct a 

human health risk assessment for acetaminophen. The Agency did not anticipate 

requiring any additional data on acetaminophen for the registration review. 

• June 26, 2013 - The Agency posted the Preliminary Ecological Risk and Endangered 

Species Risk Assessment in Support of the Registration Review of Acetaminophen to the 

docket. The Agency concluded· that, in general, the use of acetaminophen on Guam does 

not pose risks of concern to either listed or non-listed species. 

• July 28, 2014 - The Acetaminophen Proposed Interim Registration Review Decision was 

published in the Federal Register for a 60-day comment period. Based on the findings 

from the ecological and endangered species risk assessment and the minimal risks to 

human health from the pesticidal use of acetaminophen, the Agency proposed that no 

changes were needed to the current registrations for acetaminophen. Two comments 

were received during the comment period. These comments, submitted by USDA's 

Animal and Plant Health Inspection Service and the Center for Biological Diversity, 

indicated that both entities agreed with EPA's approach and conclusions. 

• The Agency has exempted acetaminophen from the Endocrine Disrupter Screening 

Program, concluding that there is no reason to believe the pesticidal use of 

acetaminophen will pose risks to human or wildlife endocrine systems. 

• December 20 14 - The Agency is publishing its Final Registration Review Decision for 

acetaminophen. At this time, no changes are needed to the current pesticide registration 

of acetaminophen. 

The documents cited above and additional information on acetaminophen can be found in 

EPA's public docket, EPA-HQ-OPP-2012-0145, accessed at www.regulations.gov. 

II. Scientific Assessments 

A. Environmental Assessment 

A summary of the Agency's environmental risk assessment is presented below. For 

detailed discussions of all aspects of the environmental risk assessment, see the Preliminary 

Ecological Risk and Endangered Species Assessment in Support of the Registration Review of 

Acetaminophen. 

The potential for exposure of terrestrial plant and animal species in the treatment area is 

limited because ofthe way acetaminophen is applied via baited mouse pup carcasses, currently 

used in Guam to control the brown tree snake. The potential for exposure of aquatic species is 

also very limited, because the acetaminophen product label prohibits direct application to water 

and any incidental introduction of acetaminophen into aquatic habitats is very limited. · 

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The Agency believes that the risks to non-target, non-listed terrestrial and aquatic 

organisms associated with the pesticidal use of acetaminophen are well below levels of concern. 

Even from inadvertent exposure, it is unlikely for aquatic organisms to be exposed to enough 

acetaminophen in the waterbody that would reach or exceed the level of concern. Given that 

mammalian species found on Guam are predominantly exotic (introduced) invasive species that 

are considered to be pest species, and that the two endangered mammals found in Guam are bats 

that only feed on fruit and other plant matter, there are no risks of concern for mammals. Based 

on available data, risk to birds is below the EPA's level of concern. While there is a potential for 

certain birds that feed on carrion (that could swallow an entire acetaminophen bait) to be 

exposed to acetaminophen, all known listed birds have been extirpated from Guam; therefore, 

any inadvertent exposure of acetaminophen to listed birds is not expected. Exposure to terrestrial 

invertebrates and plants is also expected to be very limited, and therefore, do not pose risks of 

concern. 

Ecological Incidents 

A review of the Ecological Incident Information System (EllS, version 2.1 ), which is 

maintained by the Agency's Office of Pesticide Programs, indicates that no incidents have been 

reported to the Agency that included acetaminophen. 

B. Endangered Species Assessment 

EPA has evaluated risks to federally-listed threatened and/or endangered (listed) species 

from use of acetaminophen for brown tree snake control in Guam under the Endangered Species 

Act (ESA). This assessment was conducted in accordance with the Overview Document 

(USEPA, 2004), provisions of the ESA, and the Services' Endangered Species Consultation 

Handbook (USFWS/NMFS, 1998). The conclusions of this assessment are consistent with the 

findings in the November 2, 2011 U.S. Fish and Wildlife Service Biological Opinion (USFWS 

BiOp) issued as a result of the formal consultation between the USDA APHIS Wildlife Service 

(USDA WS) and the USFWS on the pesticidal use of acetaminophen to control the brown tree 

snake in Guam. 

EPA has made a "No Effect" determination for all listed species based on Guam. The 

listed species that occur or have previously been found within the action area consist of six birds, 

two fruit bats, two marine turtles, and one terrestrial plant. EPA's determination is based on 

findings that: 1) the bird species have either been extirpated from the treatment area or are in 

captivity; 2) the two listed fruit bats feed strictly on plant matter and thus would not consume the 

baited mouse pups or poisoned tree snakes; and 3) potential exposures for the listed marine 

turtles and plants are very limited. The Agency has made a "no adverse modification of critical 

habitat" determination for all designated critical habitats for the currently registered use of 

acetaminophen. 

C. Human Health Assessment 

The Agency did not conduct a human health risk assessment for acetaminophen 

because acetaminophen's pharmaceutical use is well-studied and opportunities for human 

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exposure from its pesticidal use are not anticipated. Please refer to Acetaminophen: Human 

Health Assessment Scoping Document in Support of Registration Review, March 7, 2012 in the 

public docket EPA-HQ-OPP-2012-0145, which can be accessed at www.regulations.gov. 

Hazard Characterization and Risk 

After consideration, the Agency found that, because of the limited uses, minimal 

potential for exposure, low toxicity, and its use as a pharmaceutical drug, a quantitative human 

health risk assessment was not required under registration review. 

The Agency has determined that there are no dietary, residential, occupational, or 

aggregate risks of concern for acetaminophen. All toxicity data requirements were waived when 

acetaminophen was registered, except for acute toxicity studies; therefore endpoints have not 

been selected for acetaminophen. Acetaminophen has no pesticidal food uses and does not 

require a tolerance. It has not been determined that acetaminophen shares a common mechanism 

of toxicity with other chemical substances; therefore a cumulative risk assessment was also not 

required. 

Human Incidents 

The Agency's incident database shows no incidents involving acetaminophen use. 

D. Endocrine Disruptor Screening Program 

Pursuant to FFDCA Section 408(p)(4), EPA has exempted acetaminophen from the 

requirements ofthe Endocrine Disrupter Screening Program (EDSP) in an Administrative Order 

entitled Exemption of Acetaminophen/rom the Requirements ofthe EDSP, dated 10/30/2014. 

The Administrative Order describes the analysis and rationale that the Agency used to evaluate 

acetaminophen in order to determine that it does not have biological activity anticipated to 

produce in humans or any other organism an effect similar to that produced by a naturally 

occurring estrogen, androgen, or thyroid hormone. 

III. Final Registration Review Decision 

In accordance with 40 CFR Sections 155.56 and 155.58, the Agency is issuing this Final 

Registration Review Decision Document, thus concluding the registration review of 

acetaminophen. The Agency has made the following decision relative to registrations of 

acetaminophen: 1) no additional data are required at this time and 2) no cbanges to the affected 

registrations or their labeling are needed at this time. EPA does not expect acetaminophen to 

have direct or indirect adverse effects to non-listed and listed species. EPA has made a "no 

effect" determination under the Endangered Species Act (ESA) for all listed species and 

designated critical habitat for such species. In addition, the EPA has exempted acetaminophen 

from the requirements of the Endocrine Disrupter Screening Program. 

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IV. Next Steps 

This registration review decision closes out the reg istration review for acetaminophen. 

The Agency is charged with making sure pesticide registrations keep pace with advancements in 

science via registration review. Acetaminophen will undergo re-evaluation in the future 

according to the schedule maintained by the Agency. 

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