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** Ric h ard P. Keigwi n , Jr. D irector Pesticide Re

- evalu ation Divis i on

### Table of Contents 

### C

ontents I . Introduction ...................................... . ............ .. ..... .. .. ..... . ......... ..... ............... .. ................. ... 3 I I . S cientific Assessments ................................................................................ .. ..................... 4 A. Envi ronmental Assessment ......................................................................... .. ..................... 4 B. Endangered Species Assessment .... .............. ..... ... . ...................................... .. ..................... 5 C. Human Health Assessment........................................................................... .. .. .. ................ 5 D. Endocrine Disruptor Screening Program .......................................... :....... .. ..................... 6 I II. Final Registration Review Decision ........................................................... . ..................... 6 IV. Next Steps .................................................................................................... . ............ .. .. . .. . . 7

Refe rences: T his 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 Endangere d Sp e cies Assessment in S upport of the Registration Revie w of Acetaminophen ; N. Ma s trota, 

### J. Wolf , R. Louie-Juzwiak, April 12 , 2013.

• Administrative Ord er, E xemption of Acetaminoph e n from the Requir e m e nt s of the Endocrine Disruptor Screening Program; Jim J ones , 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 sec tions 155 .56 and 1 55.58. A registration review decision is the Agency's determination that a pes ticide meets , or do es not meet, the standard for reg istration in the Federal Inse cti c ide , F ungicide, and Rodenticide Act (FIFRA). Further information on acetaminophen can be found i n EPA's public docket (EPA-HQ-OPP

- 20 12-0 145) at www.regulation s .gov . FIFRA, as amended by the Food Quality Protection Act (FQPA) of 1996, mandated the c ontinuous review of existing pesticides. All pesticides distributed or sold in the United States ge nerally must be regi stered by the EPA based on scientific data showing that the y will not cause u

nreasonable ri sks to human heal th or to the environme nt when used as directed on product l abeling. The registration review program is intended to make sure that , as the ab i li ty to assess and reduce risk evolves and as policies and practic es change, all registered pesticides continue to mee t the statutory standard of no unreasonable adverse effects. Changes in sc ience, public p olicy, and pesticide use practices wi ll occur over time. Through the registration review p ro gram, the Agency periodically reevaluate s pesticides to make sure that as these changes occur, products in the marketplace can continue to be used safely. Inf ormation on this program i s provided as www.epa.gov/ oppsrrdl /registration review/

. In 2006 , the Agency implemented the registration review program pursuan t to FIFRA section 3(g) and will review each registered pe sticide every 15 years to determine whethe r it co ntinues to meet the FIFRA standard for registration. Pursuant to 40 CFR § 1 55.50, the Agency f ormally initiated regi stration review for acetaminophen (Case 761 0) in March 2012. Acetaminophen (N

- (4-hydroxyphenyl) -ac etamide) is a widely used analgesic and antipyretic agent that has been available as an over-the-counter drug since 1960. It is a c ommonly used active in gred ient in many drugs regulated by the U.S. Food and Drug Admini stration. Acetaminophen is registered with EPA for control of the invasive brown tree s nake in the U.S. territories of Guam and the Commonwea lth of Northern Mariana I s lands (CNMI). Dead mou se pup s are baited with acetaminophen, and the snake i s killed when it i ngests a baited mou se carcass. The brown tree snake is an inva sive species that has decimated the native bird popul a tion s of Guam and other areas where it has become established. Highlights of significant actions during the registration review of acetaminophen are li sted below. Rele vant documentation can be found in the public docket:

• March 28, 20 12

- The Agency posted th e Acetaminophen Summary Document to the acetaminophen registration review docket for a 60-day publi c comment period. The Summary Document included the Agency's Preliminary Work Planfor Acetaminophen, and was acc ompanied by the Problem Formulationfor the Environmental Fate, Ecological Risk, and Enda ngered Species and Drinking Wate r Assessments for Acetaminophen ; and the Human Health Assessment Scoping Document in Suppo rt of Registration R eview.

3• August 31 , 20 1 2

- The Acetaminoph e n Final Work Plan (FWP) wa s i s sued. Since no comments were received during the comment period, the FWP did not modify the Preliminary Work Plan. T he FWP indicated that the Agency planned to c o nduct a qualita t iv e eco log ical and endangered species ri sk assessment and would no t conduct a human health ri sk assessme nt for acetaminophen. The Agency did not anti c ipate requ irin g any additional data on acetaminophen for the registration review

.
• June 26 , 2013

- T he Agency posted th e Preliminary Ecological Ris k and Endange red Species Risk A ssessm e nt in Support of th e R e gistration Review o f A ce taminophen to th e d ocket. 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 Acet aminoph en Proposed Interim Registration Review Decision was publishe d in the Federal Register for a 60-day comment period. Based on t he findings from t he eco l ogica l and e ndan gered spec i es risk assessment and the minimal risks to human health from the pesticidal use of acetaminophen , the Agency propo s ed that no changes were needed to the current regi strations for acetaminophen. Two c omments were rece iv ed during t h e comment period. These comments , submitted b y US DA' s Animal and Plant Health Inspect i on Service and the Center for Biolo g ical D i versity , indicated that both entities agreed with EPA ' s app roach and conclusions.

• The Agency h as exe mpted acetaminophen from the Endocrin e D isrup ter Screen i ng Program , concluding that th ere is no reason to believe the pesticidal use of acetaminophen will pose risks to h uman or wi ldlife endocrine systems.

• December 20 14

- The Agency is publi shi ng its Final Registration R ev iew Decision for acetaminophen. At this time, no changes are needed to the current pe stici d e registration of acetaminophen

. The do cument s cited above and additional inf o rmation on acetaminophen c an be f ound in E PA 's public docket, EPA -HQ-OPP

- 2012-014 5 , accesse d at www. regulations.gov

. 

### II. Scientific Assessments A . Envi ronmental Asses sment A summary o f the Agency's environmental risk assess ment is present e d below. For detailed discussions of all as p ects of the environmental risk assessment , see the Preliminary Eco logical Risk and Endangered Species Assessment in Supp ort o f the R eg is tra ti on Rev i e w of Acetaminoph en . T he potential for exposure of terrestrial plant and animal species in the treatment area is limited because ofthe way acetaminophe n is applied via baited mouse pup carcas ses , currently used in Guam to control the brown tree snake

. The potential for exposure of aquat ic spec ies is a lso very limited , becau se the acetaminophen pr oduct label prohibits direct application t o water and any incidental introduction of acetaminophen into aquatic habitats i s very limited

. · 4The Agency believes that the risks to non-target , non-listed terrestrial and aquatic organisms associated with the pesticidal use of acetaminophen are well below lev e ls of concern. E ven from inadvertent exposure, it is unlikely for aquatic organisms to be expose d to enough acetaminophen in the waterbody that would reach or exceed the level of concern . Given that mammalian species found on Guam are predominantl y 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 certa in 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 i nvertebrates and plants i s also expected to be very limited, and therefore , do not pose risks of concern . 

### Ecological Incidents A review of th e Ecological Incident Information System (EllS , version 2.1 ) , which is maintained by the Agency ' s Office of Pesticide Programs , indicates that no incide nts have been reported to the Agency that in cl uded acetaminophen

. 

### B. Endangered Species Assessment EPA has evaluated ri sks to federally-listed threatened and/or endangered (l is ted) species from use of acetaminophen for brown tree snake control in Guam under the Endan gered Species Act (ESA). This assessment was conducted in accordance with the Overview Document (USEPA , 2004) , provisions of the ESA , and the Services ' Endangered 

### Sp e ci es Consultation Handbook (USFWS/N MFS , 1998)

. The conclusion s of this assessment are consistent with the fi ndings in the November 2 , 20 1 1 U
. S

. Fish and Wi ldlife Service Biological Opi ni on (USFWS B iOp) issued as a result of the formal consultation between the USDA APHIS Wi ldlife Service (USDA WS) and the USFWS on the pesticidal use of acetaminophen to control the brown tree s nake in Guam. EPA has made a " No Effect" determination for all li sted species based on G uam. The listed species that occur or have previously been found within the action area consist of six birds , t wo fruit bats , two marine turtles , and one terre strial plant. EPA ' s determ ination i s based on fi ndings that: 1) the bird species have either been extirpated from the treatment area or are in c aptivity; 2) the two listed fruit bats feed strictly on plant matter and thus would no t consume the baited mouse pups or poisoned tree snakes; and 3) potential exposures for the listed marine turtles and plants are very limi ted. The Agency has made a "no adverse mod ification of critical habitat" determination for a ll designated critical habitats for the currently registere d use of acetami nophen. 

### C. Human Health Assessment The Agenc y did not conduct a human health risk assessment for acetaminophen b ecause acetaminophen ' s pharmaceutical use i s well-studied and opportunities for human
5exposure from its pesticidal use are not anticipated. Please refer to Ac e taminophen: 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 , m inimal p otential for exposure , low toxicity, and its use as a pharmaceutical drug , a quanti ta tive human h ealth risk assessment was not required under registration review. The Agency has determined that there are no dietary, residential , occupati onal, or aggregate risks of concern for acetaminophen. All toxicity data requirements were waived when acetaminophen was registered, except for acute toxicity studies; therefore endpo int s have not been se lected for acetaminophen. Acetaminophen has no pesticidal food uses and does not requ ire a tolerance. It has not been determined that ace taminophen shares a common mechani sm of toxicity with other chemical subs tanc es; therefore a cumulative risk assessment was also not required

. Human Incidents The Agency ' s incident database s how s no incidents involving acetaminophen use . D. Endocrine Disruptor Screening Program Pursuant to FFDCA Sectio n 408(p)(4) , EPA has exem pted acetaminophen from the requ irements ofthe Endocrine Disrupter Screening Program ( ED SP) in a n Adm in i strat i ve Order entitled Exemption of A c etaminophen/rom the Re quirements ofthe EDSP, dated 10 / 30 /2014. The Administrative O rder describes the analysis and rationale that the Agency use d to evaluate acetaminophen in order to determine that it does not have biological activity anticipated to p rodu ce in humans or any other organism an effect simi lar to that produ ced by a naturally occ urring estrogen, androgen, or thyroid horm on e. 

### 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 t he registration review o f acetaminophen. The Agency has made the following decision relative to registrati o ns 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 thi s time. EPA does not expect acetaminophen to have direct or indirect adverse effects to non-li sted a nd li sted species. EPA h as made a "no effect" determination under the E ndange red Species Act (ESA) for all li sted speci e s and des ignated critical habitat for suc h species. In addition, the EPA has exempted ac etaminophen from the requirements of the Endocrine Di srupter Screening Program.



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### IV. Next Steps This registration review decision closes out the reg istration review for acetaminophen

. The Agency is c h arged w ith making sure pesti cide reg i strations keep pac e with advancements in sc i e nce via regi s trati o n review. Acetaminophen will undergo re - evaluation in the future accord in g to the schedu le maintained by th e Agency.

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