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U.S. Food and Drug Administration, is registered by EPA for use to control the invasive brown 

tree snake in the U.S. territories, Guam and the Commonwealth of Northern Mariana. The 

product, Brown Tree Snake Control (EPA Reg. No. 56228-34) is the only registration for 

acetaminophen. The Section 18 quarantine emergency exemption (July 1999) and application 

for registration of end use product (July 2002) were identified as the primary resources for this 

evaluation. In addition, a qualitative human health risk assessment was submitted by U.S. 

Department of Agriculture (USDA) Animal and Plant Health Inspection Service (APHIS) as a 

part of a data requirement waiver for human health effects from acetaminophen, and in support 

of the 2002 application. The waiver request was accepted. HED anticipates no dietary, drinking 

water, or occupational and residential exposure from the use of acetaminophen as a pesticide. 

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. Centrilobular hepatocyte 

necrosis in humans is a well-recognized consequence of overdose for acetaminophen. 

Nephrotoxicity in humans has also been reported as a consequence of acetaminophen drug use. 

Toxicity data requirements have been waived for this acetaminophen pesticide use because of the 

extensive literature database and the approval by FDA for use as an over-the-counter drug. 

Because no dietary, drinking water, or occupational and residential exposure are anticipated, a 

quantitative human health risk assessment is not required under registration review for the 

existing use of acetaminophen. 

No data deficiencies were identified during the scoping process for toxicology, residue 

chemistry, or occupational and residential exposure. There are no outstanding data requirements. 

There are no aggregate, dietary, occupational or residential risks of concern for this Registration 

Review chemical. 

Introduction

The HED Acetaminophen Registration Review Team has evaluated the potential for human 

exposure from use of the Brown Tree Snake Control product. The purpose of this screen is to 

determine whether sufficient data are available and whether a human health risk assessment is 

required to support Registration Review. HED considered the most recent documentation from 

OPP activity on acetaminophen and conducted an open literature search. The primary sources 

for the status update were the Section 18 quarantine emergency exemption and application for 

registration submitted in support of the brown tree snake use by USDA APHIS in 1999 and 

2002, respectively. Other supporting documentation includes a publication of the scientific 

journal Environmental Science Technology as submitted by USDA APHIS, which assesses the

risk of the acetaminophen baiting program for control of brown tree snakes on Guam. A 

comprehensive list of all documentation considered is presented in the reference section of this 

document. 

Acetaminophen is used as a pesticide to control the invasive brown tree snake in two U.S. 

territories, Guam and the Commonwealth of Northern Mariana. The brown tree snake (Boiga 

irregularis) is a significant ecological, agricultural, and economic pest on Guam. Originally, the 

species’ range included the northern and eastern coasts of Australia, Papua New Guinea, and 

nearby islands. It is believed that sometime in the 1950s brown tree snakes were inadvertently 
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transported from New Guinea to Guam, where they proliferated. By the mid-1960s, marked 

decreases in Guam’s bird life were observed. By the mid-1980s, brown tree snake densities were 

estimated at levels higher than those recorded for any other snake. 

Acetaminophen is applied by hand or aerially via helicopter and/or fixed-winged aircraft. Single 

baits (dead mouse pup) are prepared by manually inserting one 80 mg or two 40 mg 

acetaminophen tablets into the throat of the mouse pup. Bait stations are prepared by manually 

inserting a single mouse pup bait in a PVC pipe that are hung in trees or on fences (4.9 feet 

above the ground) in and around forested areas and fence lines. Baits can also be hand broadcast 

or dropped from helicopters and fixed-wing aircraft. Netting or other material may be attached 

to the dropped bait for placement in the forest canopy. 

Hazard Identification/Toxicology

Acetaminophen is a widely used analgesic and antipyretic agent. Recommended oral drug doses 

for acetaminophen range from 12 mg/kg every 6-8 hours for pre-term neonates to 1000 mg every 

6-8 hours for adults. Centrilobular hepatocyte necrosis in humans is a well-recognized 

consequence of overdose for acetaminophen. The FDA web site advises: "Acetaminophen is 

one of the most commonly used medicines in the United States. When used according to the 

label directions, it has a well-established record of safety and efficacy. Although acetaminophen 

overdose is very rare in the context of its broad usage, overdose can be toxic and lead to acute 

liver failure". There is also the potential for interaction with ethanol and labels require 

consumers to consult with their physician if they drink 3 or more alcohol drinks a day. 

Nephrotoxicity in humans has also been reported as a consequence of acetaminophen drug use. 

Toxicity data requirements have been waived for this acetaminophen pesticide use because of the 

extensive literature database and the approval by FDA for use as an over-the-counter drug. 

Residue Chemistry

Acetaminophen is not currently registered as a pesticide for uses in food commodities; therefore, 

evaluation of residues in crops is not needed.

Dietary Exposure

The proposed pesticide use for brown tree snake control is not expected to result in any dietary 

exposure. No food-based exposure is anticipated as there are no registered food-uses in 

agricultural commodities. Also, any drinking water exposures are expected to be negligible. . 

The primary source of exposure to acetaminophen among the U.S. population is likely through 

analgesic drug use, which is regulated by the U.S. Food and Drug Administration. Based on 

these considerations, a dietary exposure assessment is not required for registration review. 

Residential Exposure
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No residential exposure (adult or child) is anticipated from the use of acetaminophen for brown 

tree snake control. The product as labeled does not preclude professional application in 

residential areas (i.e., bait stations and broadcast in non-crop areas); however, its use should not 

result in the potential for residential exposure. The label states, “DO NOT apply this product in 

a manner where it is accessible to children,” and, therefore, the potential for exposure to children 

is unlikely. It is possible that an adult or child could come upon a mouse bait preparation 

dropped via broadcast application (helicopter or fixed-winged aircraft) into a residential area; 

however, the probability of an adult or child accessing and contacting or the child ingesting the 

tablets lodged in the throats of the dead mouse pups is very low. It is also unlikely that adults or 

children in residential areas will contact the bait stations, which are required by the product label 

to be hung in trees and on fences and contained in PVC pipes. A residential assessment is not 

required for the registration review of acetaminophen for the reasons described. 

Aggregate Risk Assessment

Dietary, drinking water, and residential exposure to acetaminophen have not been assessed. As 

stated above, these routes of exposure are not anticipated given the use pattern (i.e., brown tree 

snake control) of the chemical and, therefore, an aggregate risk assessment will not be needed to 

support the registration review of acetaminophen.

Occupational Exposure

An occupational human health assessment of the use of acetaminophen for brown tree snake 

control in Guam has not been previously conducted. Acetaminophen can be applied by single 

bait preparation, bait stations, or broadcast only by employees of the US State and Federal 

governments, the Government of Guam or the Commonwealth of the Northern Mariana Islands 

trained in brown tree snake control, or persons under their direct supervision. 

Based on the use profile and the potential for exposure, an assessment of occupational handler 

and applicator is not required under registration review. While the handling of acetaminophen 

tablets is anticipated during insertion into dead mouse pups, the product label requires that 

handlers of the product wear: long-sleeved shirt and long pants, socks and shoes, and waterproof 

or rubber gloves. The handling of acetaminophen tablets with the required gloves is anticipated 

to minimize the potential for any dermal contact with the product. The application of the mouse 

pup baits by hand, the creation of bait stations (PVC pipe) or aerial broadcast will not result in 

direct contact with acetaminophen tablets. Because dermal and inhalation exposure are not 

anticipated, an occupational risk assessment is not required for acetaminophen. 

Public Health and Pesticide Epidemiology Data

The evaluation of the OPP Main Incident Data System (IDS) indicated no incidents identified in 

the United States from January 1, 2006, through November 2, 2011, for the single chemical 

acetaminophen. In Aggregate IDS, from January 1, 2006 to November 2, 2011, there are no 

incidents reported for acetaminophen. For acetaminophen, there appears to be a low potential for 

exposure. Acetaminophen is not included in the Agricultural Health Study (AHS), and therefore, 
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does not provide information for this report. There does not appear to be a concern at this time 

that would warrant further investigation. 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 not established for acetaminophen since no registered pesticide uses in food 

commodities exist at this time. No Codex maximum residue limits (MRLs) have been 

established for acetaminophen. Therefore, there are no international harmonization issues.

Environmental Justice 

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

accordance with U.S. Executive Order 12898, "Federal Actions to Address Environmental 

Justice in Minority Populations and Low-Income Populations," 

http://www.eh.doe.gov/nepa/tools/guidance/Volume1/2-6-EO_12898envjustice.pdf). The Office 

of Pesticide Programs (OPP) typically considers the highest potential exposures from the legal 

use of a pesticide when conducting human health risk assessments, including, but not limited to, 

people who obtain drinking water from sources near agricultural areas, the variability of diets 

within the U.S., and people who may be exposed when harvesting crops. Should these highest 

exposures indicate potential risks of concern, OPP further refines the risk assessments to ensure 

that the risk estimates are based on the best available information.

Cumulative

The Food Quality Protection Act (FQPA) requires the Agency to consider the cumulative risks of 

chemicals sharing a common mechanism of toxicity. At this time, a cumulative risk assessment 

to support registration review is not required for acetaminophen. 

Human Studies

No human studies were relied upon for the registration of the pesticide use of acetaminophen. 

Endocrine Disruption

As required by FIFRA and 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 2002 decision, EPA reviewed these data and selected the most 

sensitive endpoints for relevant risk assessment scenarios from the existing hazard database. 
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However, as required by FFDCA section 408(p), acetaminophen 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. 

Acetaminophen is not among the group of 58 pesticide active ingredients on the initial list to be 

screened under the EDSP. Accordingly, as part of registration review, EPA will issue future 

EDSP orders/data call-ins, requiring the submission of EDSP screening assays for 

acetaminophen. For further information on the status of the EDSP, the policies and procedures, 

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

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

Data Requirements

No data deficiencies were identified during the scoping process for toxicology, residue 

chemistry, or occupational and residential exposure. There are no outstanding data requirements. 

References

Author Barcode/MRID Date Title

S. Recore D399584 December 

2011 Acetaminophen: Review of Human Incidents

Carl Bausch 

to Meredith 

Laws

NA July 2002

Application for Registration of an End Use Product Containing a 

New Active Ingredient: Acetaminophen for Brown Tree snake 

Control 

J.J. Johnston, 

et al NA July 2002

Risk assessment of an acetaminophen baiting program for 

chemical control of brown tree snakes on Guam: evaluation of 

baits, snake residues, and potential to primary and secondary 

hazards (Environmental Science and Technology, 2002, 36 (17), 

pp. 3827-3833)
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Author Barcode/MRID Date Title

USDA 

APHIS NA May 2002 Request for Data Requirement Waiver: Human Health Effects

J. Jones NA July 1999

Section 18 – Quarantine Exemption for the use of Acetaminophen 

to control the invasive brown tree snake in Guam and the 

Commonwealth of Northern Mariana Islands (99-DA-10) by 

USDA/APHIS 

B. Petersen, 

J. Eisemann 45716715 2002 Acetaminophen Data Requirements: Human Health Effects

Textbooks

C. Klaassen NA November 

2007 Casarett and Doull’s Toxicology, 7th Edition

L. Goodman, 

L. Limbird NA 1995 Goodman and Gilman’s The Pharmacological Basis of Therapeutics, 9th Edition

Websites

http://www.fda.gov/Drugs/DrugSafety/InformationbyDrugClass/ucm165107.htm

Attachments

Attachment 1: Chemical Identity Table

Chemical Identity of Acetaminophen.

Structure

Reference: 

D286621, S. 

Mathur, 16-DEC2002

IUPAC Name N-(4-hydroxyphenyl) acetamide

Common Name Acetaminophen or paracetamol

Molecular Formula C8H9NO2

Molecular Weight 151.16 g/mole

CAS Registry Number 103-90-2

PC Code Number 109509

Physical State Solid

Color White

Odor Odorless

Melting Point 170 C

Solubility 1 g in 70 mL water @ 25 C

pH 6.0
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Tolerance/MRL Table

Not required for this action.

DCI Justifications

Not required for this action.