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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460 

OFFICE OF CHEMICAL SAFETY 

AND POLLUTION PREVENTION

MEMORANDUM

DATE: December 14, 2015

 

SUBJECT: Chlorophacinone. Human Health Scoping Document in Support of Registration Review. 

PC Code: 067707 DP Barcode: D426549

Decision No.: 502937 Registration No.: NA

Petition No.: NA Regulatory Action: Registration Review

Scoping Document

Risk Assessment Type: NA Case No.: 2100

TXR No.: NA CAS No.: 3691-35-8

MRID No.: NA 40 CFR: NA

FROM: Barry O’Keefe, Senior Biologist

Vincent Chen, Toxicologist

Risk Assessment Branch III (RAB3)

Health Effects Division (7509P)

THROUGH: Matthew Crowley, Biologist

Chemistry and Exposure Branch (CEB)

Health Effects Division (7509P)

Chris Schlosser, Biologist

Risk Assessment Branch VI (RAB6)

Health Effects Division (7509P)

Christine Olinger, Branch Chief

Risk Assessment Branch III (RAB3)

Health Effects Division (7509P)

TO: Christina Motilall, Chemical Review Manager

Thomas Moriarty, Team Leader

Neil Anderson, Branch Chief

Risk Management and Implementation Branch 1 (RMIB1)

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

Following is the Health Effects Division’s (HED’s) human health scoping document for the 

rodenticide chlorophacinone to support Registration Review. To evaluate the scope of work 

necessary to support Registration Review, HED has considered previous risk assessments for 

chlorophacinone; updates to its toxicity, exposure, and usage databases; and the latest Agency

science policy and risk assessment methodologies. The most recent HED assessment for 

chlorophacinone is the HED Chapter of the Reregistration Eligibility Decision (RED) Document 

completed in 1997 (J. Redden, 04/25/1997).

Chlorophacinone, an indandione, is a first generation anticoagulant rodenticide that disrupts the 

vitamin K cycle necessary for blood-clotting factors to function. The toxicity database supports 

the mechanism of action by demonstrating that animals exposed to chlorophacinone have 

increased blood coagulation times and mortality. Chlorophacinone is highly toxic through oral, 

dermal, and inhalation routes of exposure. Chorophacinone is formulated into numerous baits in 

packs, blocks, granulars, pellets, tablets, grains, granules, tracking powders/dusts, and impregnated 

materials. 

The toxicology database is adequate for risk assessment of most currently registered 

formulations and use patterns, with the exception of tracking powder formulation uses. A 90-day

subchronic inhalation toxicity study is still required, due to expected higher exposures from the 

tracking powder formulation products. For the tracking powder products, it is difficult to 

determine the specific use pattern and maximum application rates from the registered labels. It is 

therefore difficult to assess and estimate the inhalation exposure risks from these products. As 

part of Registration Review, toxicity endpoints, PODs, and uncertainty factors will be reevaluated according to current HED approaches in hazard characterization.

Occupational and residential handler dermal and inhalation exposures are possible from existing 

uses of chlorophacinone. Residential post-application exposures to small children should not be 

possible for those products that are in childproof tamper resistant packaging; however, a few 

products are not in tamper resistant packaging and tracking powder products may be an exposure

concern for small children. Dermal and inhalation exposures are possible for occupational and/or 

residential handlers as they refill bait stations, distribute products into rodent burrows, as they apply 

tracking powders, or as they load and apply broadcasted products to orchards. 

At the time of Registration Review, HED will reevaluate the points of departure, toxicity

endpoints, and uncertainty factors used for risk assessment purposes. Based upon that 

reevaluation, HED will determine if occupational and residential handler exposure risk 

assessments are needed. Additionally, in order to adequately and appropriately assess 

occupational exposures from the use of tracking powders at the time of Registration Review, the 

registrant will need to provide more information on the use pattern.
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Introduction

Chlorophacinone, an indandione, is a first generation anticoagulant rodenticide that disrupts the 

vitamin K cycle necessary for blood-clotting factors to function. Chlorophacinone is formulated 

into numerous baits in packs, blocks, granules, pellets, tablets, grains, tracking powders/dusts, and 

impregnated materials (e.g., EPA Reg. Nos. 7173-287 and 7173-289). Most of the end-use products 

contain 0.005% active ingredient (ai). However, the two tracking powder products contain 0.2% 

ai. The labelled target pests are rats, mice, and pocket gophers. Use sites include in and around 

residential, industrial, and agricultural buildings; rangeland; residential lawns; golf courses; orchards;

and non-crop areas. Application equipment includes spoons, scoops, probe dispensers, burrow 

builders, dusters. Application rates are numerous and vary widely depending upon formulation and 

product types. The most recent HED assessment for chlorophacinone is the HED Chapter of the 

Reregistration Eligibility Decision (RED) Document completed in 1997 (J. Redden, 04/25/1997).

In 2008, the Agency issued a risk mitigation decision for ten rodenticides, of which 

chlorophacinone was included. The mitigation decision set restrictions in order to minimize

exposure to children, wildlife and domestic animals. The risk mitigation decision does not apply 

to rodenticide field (non-commensal rodents) uses or tracking powder products.

 Consumer-based products (≤ 1 lb.),

o Second-generation anticoagulants are prohibited as well as loose 

baits/pellets/meal as a form for above ground outdoor uses.

o When applied outdoors above ground and in areas accessible to children, 

non-target wildlife or domestic animals, baits must be contained in bait 

stations. 

o Products for use outdoors and above-ground must be placed within 50 feet 

of a building. 

 Professional-based products 

o Must be sold in quantities of ≥ 4 lbs. (first-generation anticoagulants/nonanticoagulants), ≥ 8 lbs. (second-generation anticoagulants; agricultural 

building use) and ≥ 16 lbs. (second generation anticoagulants; above 

ground outdoor use)

o May not be offered for sale in consumer stores (hardware, grocery, etc.).

o Must also be placed within 100 feet of a structure (fence and perimeter 

baiting beyond 100 feet of a man-made structure are prohibited) when 

used outdoors and above ground, see 50 foot Document Clarification 

Letter to Bell (03.20.12) (signed) in docket number EPA-HQ-OPP-2006-

0955-0820 found at www.regulations.gov.

o For uses of first-generation or non-anticoagulants, product labels require 

bait stations if children, wildlife or domestic animals may be exposed.

o For uses of second-generation anticoagulants, labels require bait stations 

for all outdoors above grounds placements and/or indoor placements 

where children, wildlife or domestic animals may be exposed.
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Several of the chlorophacinone products are currently registered as restricted use pesticides

(RUPs). Products intended for occupational use are packaged as 4 pounds (lbs) or more. The 

majority of chlorophacinone products are applied using tamper resistant bait stations, which are 

required for all rodenticides where children and pets may be present per 2008 anticoagulant 

rodenticide mitigation. This is, however, one chlorophacinone end use product that is applied to 

orchards by ground broadcast equipment at a maximum rate of 20 lb of product per acre or 0.001

lb active ingredient (ai) per acre in post-harvest fruit tree orchards. Also, tamper resistant bait 

stations are not required for burrow, canopy, and tracking powder applications. In addition, for 

chlorophacinone, there are two registered products, EPA Reg. Nos. 7173-287 and 7173-289, that 

do not appear to adhere to these mitigation stipulations, since they are labelled for non-tamper 

resistant bait stations. See use profile table in the appendix (Attachment 1) for more information 

on application rate and application methods of chlorophacinone products.

Refer to Attachment 2 (Table A.2) for the chemical identity and Attachment 3 (Table A.3) for 

the physiochemical properties of chlorophacinone.

Hazard Identification/Toxicology

The toxicology studies available for risk assessment include an acute toxicity battery; subchronic 

oral toxicity studies in rats; a subchronic dermal toxicity study in rabbits; prenatal developmental 

toxicity studies in rats and rabbits; a battery of mutagenicity studies; a companion animal safety 

study in rats; and a metabolism and pharmacokinetic study in rats.

The available absorption, distribution, metabolism, and excretion (ADME) database enabled 

evaluation of systemic availability; the database included evaluations of rats exposed to single or 

repeated oral doses. In the single oral dose evaluation, chlorophacinone absorption peaked 

between 4 and 6 hours with a half-life (T1⁄2) of ~10 hours; additionally, chlorophacinone was 

systemically distributed and found in the highest concentration within the liver and kidneys. In 

the repeat oral dose evaluation, blood concentration measurements indicate that chlorophacinone 

bioaccumulation occurred in the test animals; additionally, chlorophacinone excretion evaluated 

over 4 days was predominately through feces (94.7-108.6% administered dose) with a far lesser 

excretion (<1% administered dose) through urine and respiration. In a biliary excretion assay, 

chlorophacinone excretion evaluated for 8 hours post-dosing through bile was significant (~26% 

administered dose).

In the repeated dose oral and dermal toxicity studies with rats, the most sensitive effect was an 

increase in coagulation times observed at the lowest dose with mortality occurring at higher 

doses. In the oral toxicity study, treated animals exhibited dose-related increases in coagulation 

times starting at 10 mg/kg/day (28% increased coagulation time) and led to mortality. In the 

dermal toxicity study, treated animals exhibited dose-related increases in coagulation times (i.e., 

PT and APTT) starting at 0.4 mg/kg/day (28% increase in PT and 61% increase in APTT). The 

toxicity in both the oral and dermal toxicity studies support the pesticide’s mechanism of action 

as an anticoagulant.

In the rat prenatal developmental toxicity study, there was evidence for increased susceptibility; 

developmental toxicity (i.e., increased incidences of hydroureter, distended ureter, and total 
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ureter anomalies) occurred at doses lower than those that caused maternal toxicity (i.e., doserelated increases in mortality). In the rabbit prenatal developmental toxicity study, there was no 

evidence for increased susceptibility; maternal toxicity (i.e., increased coagulation times) 

occurred at doses lower than those that caused developmental toxicity. Although increased 

susceptibility was seen in the developmental rat study, there is no residual uncertainty for pre 

and/or post-natal toxicity since there are no food uses for chlorophacinone, and thus no potential 

for human dietary exposure.

There is no concern for mutagenicity as demonstrated by in vivo and in vitro assays.

Chlorophacinone has high acute toxicity via the oral (Toxicity Category I), dermal (Toxicity

Category I), and inhalation (Toxicity Category I) routes of exposure; is not a dermal irritant 

(Toxicity Category IV) or eye irritant (Toxicity Category IV); and is not a dermal sensitizer.

Please refer to Attachment 4 for the summary of the toxicity endpoints and points of departure 

(PODs) and Attachment 5 for the complete toxicity profile table.

HED’s Hazard and Science Policy Council (HASPOC) based on hazard and exposure 

considerations has granted waiver to the following studies: 1) the 90-day oral toxicity in nonrodents study: 2) the reproduction and fertility effects study; 3) the acute neurotoxicity screen 

battery; 4) the subchronic neurotoxicity screening battery; and 5) the immunotoxicity study since 

chlorophacinone is acutely toxic at low doses with a distinct mechanism of action (i.e., 

disrupting blood clotting) that is unlikely to have different toxicity in repeat oral dose studies

(TXR# 0057326, U. Habiba, 12/15/2015). However, the HASPOC has determined that a 90-day

subchronic inhalation toxicity study (OCSPP 870.3465) is required based on the current use 

profile of chlorophacinone (TXR# 0057326, U. Habiba, 12/15/2015). Specifically, the 90-day

inhalation study will be used to assess potential risk from inhalation exposure to occupational 

handlers from the use of registered tracking powder end use products.

Conclusions: The toxicology database is adequate for risk assessment of most currently

registered formulations and use patterns, with the exception of tracking powder formulation uses. 

A 90-day subchronic inhalation toxicity study is required to assess risk via inhalation exposure 

from occupational use (i.e., tracking powder endues products). As part of Registration Review, 

toxicity endpoints, PODs, and uncertainty factors will be re-evaluated according to current HED 

approaches in hazard characterization.

Residue Chemistry and Dietary Exposure

All uses of chlorophacinone are non-food uses; therefore, no tolerances are established or 

needed. In addition, a dietary exposure assessment from food is not needed. However, the 

broadcast application to orchards may result in the need for a drinking water assessment in 

Registration Review.

Conclusions: A dietary exposure assessment is not anticipated to be needed during Registration 

Review unless there are drinking water exposure estimates.
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Residential Exposure

Several chlorophacinone end use products are labelled for use in residential settings. Some of 

these products are labelled as restricted use pesticides (RUP), but some are not. Based upon 

existing labels, residential handlers can be exposed to chlorophacinone by the dermal and 

inhalation routes during the refilling of bait stations with pelleted, tableted, or granular products. 

Residential handler exposures have not previously been quantitatively assessed. However, for 

tracking powders, post-application episodic incidental oral exposure may be possible. There is 

no residential handler exposure for tracking powders because they are RUPs. Residential 

exposure is expected to be short-term only; intermediate-term exposures are not likely because of 

the intermittent nature of applications in residential settings. 

For short-term inhalation exposures, the 1997 HED RED chapter did not establish a point of 

departure for use in computing risk estimates. Therefore, as a point of reference for short-term 

inhalation exposures HED recommends the point of departure and endpoints from an oral study, 

the rabbit developmental toxicity study; i.e. a POD of 0.005 mg/kg/day (maternal NOEL) based 

on elevated prothrombin and activated partial thromboplastin times seen at 0.01 mg/kg/day. Use 

of this POD may result in risk estimates of concern for the tracking powder products. During 

Registration Review, residential handler exposure from loading loose formulations into bait 

stations will need to be assessed. Additionally, for tracking powders, an episodic incidental oral 

post-application assessment may be needed during Registration Review; however, further 

investigation/information should be considered for these scenarios to determine if the assessment 

is indeed applicable.

Non Occupational Spray Drift or Volatilization

Residential bystander exposures resulting from off-site transport (i.e., spray drift or 

volatilization) is unlikely due to how chlorophacinone is formulated and used except for the 

granular broadcast applications of chlorophacinone in commercial orchards (and others as 

appropriate). The approach is outlined in the revised (2012) Standard Operating Procedures for 

Residential Risk Assessment (SOPs) – Residential Exposure Assessment Standard Operating 

Procedures Addenda 1: Consideration of Spray Drift. This guidance indicates that drift is not a 

concern when solid materials are applied (e.g., by aerial equipment). Therefore, only the 

potential for volatilization will be evaluated for each pesticide during the Registration Review 

process which ensures that all uses for that pesticide will be considered concurrently. In terms of 

volatilization, the agency has developed a Volatilization Screening Tool and a subsequent 

Volatilization Screening Analysis (http://www.regulations.gov/#!docketDetail;D=EPA-HQOPP-2014-0219). During Registration Review, the Agency will utilize this analysis to determine 

if data (e.g., flux studies or route-specific inhalation toxicological studies) or further analysis is 

required for diphacinone.

Conclusions: Short-term residential handler dermal and inhalation exposures from loading loose 

formulations into bait stations will need to be assessed during Registration Review. At the time 

of Registration Review, HED will reevaluate the points of departure, toxicity endpoints, and 

uncertainty factors currently used for risk assessment purposes. Based upon that reevaluation, 

HED will determine if a risk assessment is necessary for residential handler exposures. 
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Additionally, at the time of Registration Review, HED will determine if an episodic incidental 

oral post-application assessment is needed for tracking powder products.

Aggregate Risk Assessment

In accordance with the Food Quality Protection Act, HED must consider and aggregate pesticide 

exposures and risks from three major sources: food, drinking water, and residential exposures. 

For chlorophacinone, there are no dietary food exposure. However, drinking water exposure 

may be a possibility due to the ground broadcast applications to fruit tree orchards. For adults, 

the pathways leading to exposure are residential handler dermal and inhalation exposures. 

Residential handler exposure and quantitative drinking water estimates for chlorophacinone may

be aggregated if deemed appropriate at the time of Registration Review. A short-term aggregate 

risk assessment is not anticipated for children, unless there is drinking water exposure, and/or if

it is determined that an episodic incidental oral post-application assessment is needed for 

tracking powders. Whether this post-application assessment is needed for tracking powders, or 

not, must be determined during Registration Review through further investigation/information.

Chronic exposure from the residential pathway is not anticipated based on the current 

chlorophacinone use pattern (i.e., tamper resistant packaging).

Conclusions: If computing drinking water estimates is deemed appropriate from the ground 

broadcast use in fruit orchards, then a short-term aggregate assessments would be needed during 

the Registration Review. Additionally, if an episodic incidental oral post-application assessment 

is needed for tracking powder products, then a short-term aggregate assessment for small 

children would be needed during the Registration Review.

Occupational Exposure

Occupational Handler Exposure

Occupational handler exposures have not previously been quantitatively assessed. Handlers can 

be exposed by the dermal and inhalation routes at short- or intermediate-term durations.

As detailed above in the residential exposure section, the 1997 HED RED chapter did not 

establish a point of departure to estimate handler risks. Therefore, HED recommends using the 

POD and endpoints from the oral rabbit developmental toxicity study; i.e. a POD of 0.005 

mg/kg/day (maternal NOEL) based on elevated prothrombin and activated partial thromboplastin 

times seen at 0.01 mg/kg/day. 

For the tracking powder products, it is difficult to determine the specific use pattern and 

maximum application rates from the registered labels. It is therefore difficult to assess and 

estimate the dermal and inhalation exposure risks from these products. These are restricted use 

products. In order to adequately and appropriately assess these exposures at the time of 

Registration Review, the registrant will need to provide information on use pattern, including 

application rates. Additionally, based upon the tracking powder registrations of 

chlorophacinone, HED still requires a 90-day inhalation toxicity study (TXR# 0057326, U. 

Habiba, 12/15/2015).
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Occupational Post-Application Exposure

There is no anticipated occupational post-application exposure to the current use pattern of 

chlorophacinone.

Conclusions: Occupational handler dermal and inhalation exposures are possible from existing 

uses of chlorophacinone. During Registration Review, HED will reevaluate the points of 

departure, toxicity endpoints, and uncertainty factors used for risk assessment purposes. Based 

upon that reevaluation, HED will update the occupational handler risk assessments. 

Additionally, in order to adequately and appropriately assess exposures from the use of tracking 

powders at the time of Registration Review, the registrant will need to provide information on 

the use pattern and application rates.

Public Health and Pesticide Epidemiology Data

As part of the Rodenticide Risk Mitigation Decision (RMD), and the subsequent Notice of Intent 

to Cancel (NOIC), the Environmental Protection Agency’s Office of Pesticide Programs’ 

Pesticide Re-evaluation Division requested an analysis of human incidents involving exposure to 

rodenticides in 2011 (D395567, S. Recore, 10/28/2011) and then updated in 2015 (D426573, S. 

Recore, 11/24/2015). Summary reports listing incidents for chlorophacinone are reported to the 

OPP Incident Data System (IDS), the National Pesticide Information Center (NPIC), 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), and Agricultural Health Study (AHS) databases. 

For the Main OPP Incident Data System (IDS), from January 1, 2010 to May 27, 2015, there was 

1 incident reported for chlorophacinone in the database. This incident involved an adult female 

suicide attempt and was classified as moderate severity. 

In Aggregate IDS, from January 1, 2010 to May 27, 2015, there was 1 incident reported 

involving chlorophacinone. This incident was classified as having no or unknown effects. 

Overall, there are few incidents reported to IDS involving chlorophacinone.

A query of the Centers for Disease Control and Prevention/National Institute for Occupational 

Safety and Health (CDC/NIOSH) Sentinel Event Notification System for Occupational RiskPesticides (SENSOR)-Pesticides from 1998-2011, identifies 12 cases involving chlorophacinone. 

Of these, nine cases involved chlorophacinone alone, as opposed to incidents involving 

chlorophacinone in combination with other active ingredients. One case was moderate in 

severity and eight cases were low in severity. Eight of the nine cases involved inhalation of the 

product “dust.” 

The moderate severity case occurred after an insulation worker was working in a school 

attic. The insulation work was generating dust in the attic. That evening the case 

experienced shakiness, fever and vomiting but felt better after a few hours. The case 

experienced respiratory, neurological, gastrointestinal, renal, and cardiovascular 
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symptoms following exposure. “Rat pellets” were found throughout the attic and the 

school but the workers were not notified of this.

Eight cases experienced respiratory symptoms after exposure, and eight cases 

experienced neurological symptoms after exposure. Five cases experienced 

gastrointestinal symptoms. Eight cases were occupational and one case was a 

homeowner. The homeowner case occurred when the case opened a can of gopher bait 

and inhaled it, experienced shortness of breath and coughing and called Poison Control.

The American Association of Poison Control Centers (AAPCC) is a non-profit, national 

organization founded in 1958 that represents the poison control centers of the United States and 

the interests of poison prevention and treatment of poisoning. All of the calls to a poison control 

center are managed by a medical professional trained to answer questions about poisons. 

AAPCC produces an annual summary report giving statistics and information on all the 

poisonings reported to PCCs in a calendar year. 

Although AAPCC data was reviewed by HED for the 2011 human incidents report (D395567)

analyzing exposure to commensal rodenticides, it was not reviewed for this incident analysis. At 

the time of this report there is insufficient information available to determine if the mitigations

have impacted the frequency of incidents occurring. The most current AAPCC annual report 

available is for year 2013 and the phase out of the remaining non-compliant products began in 

June 2014 and was complete as of March 31, 2015.

However, AAPCC data is reviewed annually for reduction in reported rodenticide incidents as a 

Strategic Measure. For FY 2014 (using the 2013 AAPCC annual report data), there was a 

reduction of 17% incidents reported to the AAPCC annual reports compared to the number of 

rodenticide exposures to children ages 1 to 6 years old in 2011. The reductions in child 

exposures are expected to become more prominent beginning in the 2016 AAPCC annual report; 

which will be reflected in the FY 2018 Strategic Measure. The target reduction for FY 2018 is to 

reduce rodenticide exposure incidents by 75% in children ages 1 to 6 years old.

The Agricultural Health Study (AHS) is a high quality, prospective epidemiology study

evaluating the link between pesticide use and various health outcomes, including cancer. The 

AHS includes private and commercial pesticide applicators and their spouses. The commensal 

rodenticides are not included in the AHS.

In order to minimize children and wildlife exposure to rodenticide products the 2008 RMD 

included risk mitigation measures requiring rodenticide products used in homes and marketed to 

general residential consumers be sold only with bait stations. Most rodenticide products 

complied with the mitigation measures required in the RMD as of June 4, 2011. The phase out 

production of the final 12 non-compliant products began in June 2014 and production of these 

products stopped on December 31, 2014. Distribution to retailers ended March 31, 2015. 

Due to the fact that these safety measures were only recently fully implemented, there is 

insufficient information available to determine if the mitigations have impacted the frequency of 

incidents occurring. However, the Agency will continue to monitor the incident information and
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during Registration Review provide an updated review of incidents, considering pre- and postmitigation incidents separately, when the information becomes available.

Tolerance Assessment and International Harmonization

There are no tolerances for chlorophacinone.

Environmental Justice

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

human health risk assessment, in accordance with U.S. Executive Order 12898, "Federal Actions 

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

http://www.epa.gov/compliance/environmentaljustice/resources/policy/exec_order_12898.pdf. 

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

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

risks to pesticide exposures that are based on activities in and around the home that involve 

pesticide use in a residential setting. Whenever appropriate, these non-dietary exposures are 

calculated 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 post-application are 

evaluated.

Cumulative

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

common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as 

to chlorophacinone and any other substances and chlorophacinone does not appear to produce a 

toxic metabolite produced by 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 HED anticipates being conducted during Registration Review for 

chlorophacinone will rely 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 Agricultural 

Handler Exposure Task Force (AHETF) database, and the Outdoor Residential Exposure Task 

Force (ORETF). 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 
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EPA’s Rule for the Protection of Human Subjects of Research (40 CFR Part 26) have been 

satisfied, and there is no regulatory barrier to continued reliance on these studies.

Data Deficiencies

The following toxicology data are needed to support the registered uses of chlorophacinone:

870.3465 Subchronic Inhalation Study

A 90-day subchronic inhalation study is required in order to adequately assess inhalation 

exposures from the use of tracking powders.

References

Recent Memoranda Relevant to Registration Review of Chlorophacinone.

Author DP/TXR # Date Title

Human Health Risk Assessments

J. Redden Not Available 04/25/1997 HED Chapter of the Reregistration Eligibility Decision Document 

(RED) for Chlorophacinone (Case No. 2100)

Incident Report

S. Recore D426573 11/24/2015 Rodenticide: Tier I (Scoping) Review of Human Incidents and 

Epidemiology Assessment

S. Recore D395567 10/28/2011 Rodenticides Tier II: Review of Human Incidents

Hazard and Science Policy Council

U. Habiba TXR# 0057326 12/15/2015

Rodenticides: Summary of Hazard and Science Policy Council 

(HASPOC) Meeting on October 1, 2015: Recommendations on Data 

Requirements for Rodenticides. 

Attachments

1. Use Profile

2. Chemical Identity Table

3. Physicochemical Properties of Technical Grade Chlorophacinone Table

4. Endpoint Selection Table

5. Toxicity Profile Tables

6. Toxicology Data Requirements Table
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Attachment 1

Use	Profile	for	Chlorophacinone

Table A.1. Use Profile for Chlorophacinone.

Product Name

EPA 

Reg. 

No.

Formulation % Active 

Ingredient Target Pests Application Rate

Tamper 

Resistant 

Bait Station

Personal 

Protective 

Equipment

1

Restricted 

Use 

Pesticide

AC Formula 90 

Rodenticide 56-58 Granular 0.005 Norway rats, roof rats & house mice

4 oz place packs at 1 to 4 

packs per placement Yes

LSS, LP, SS, 

WG

No

AC Formula 90 

Ready-to-Use 

Rodenticide

56-70 Pelleted/Tableted 0.005 Norway rats, roof 

rats & house mice

1.5 oz place packs at 3 to 

10 place packs per 

placement

Yes

LSS, LP, SS, 

WG

No

Rozol® Tracking 

Powder 7173-113 Tracking Powder 0.2 Norway rats, roof rats & house mice

1 to 2 oz per 2.5 ft2

indoors & in burrows 

leading into buildings

NA

LSS, LP, SS, 

WG, PE, D/M 

FR

Yes

Rozol Pellets 7173-151 Pelleted/Tableted 0.005 Norway rats, roof 

rats & house mice

Mice 1⁄4 to 1⁄2 oz per 

placement up to 2 oz; 

Rats 4 to 16 oz per 

placement

Yes

LSS, LP, SS, 

WG

No

Rozol® Blue 

Tracking Powder 7173-172 Tracking Powder 0.2 Norway rats, roof rats & house mice

1 to 2 oz per 2.5 ft2

indoors & in burrows 

leading into buildings

NA

LSS, LP, SS, 

WG, PE, D/M 

FR

Yes

Rozol Pocket 

Gopher Bait 7173-184 Granular 0.005 Pocket Gophers 1⁄2 cup of bait per hole NA

S, LP, SS, 

WG

No

Rozol Vole Bait 7173-242 Pelleted/Tableted 0.005

Voles in Orchards, 

Nurseries & Tree 

Plantations

Mice 1⁄4 to 1⁄2 oz per 

placement up to 2 oz; 

Rats 4 to 16 oz per 

placement

NA

LSS, LP, SS, 

WG

Yes

Rozol Mini Blocks 7173-243 Pelleted/Tableted 0.005 Norway rats, roof 

rats & house mice

Mice 1 block per 

placement up to 2 blocks. 

Rats 3 to 16 blocks per 

placement 

Yes

LSS, LP, SS, 

WG

No

Rozol Pocket 

Gopher Bait II 7173-244 Pelleted/Tableted 0.005 Pocket Gophers 1⁄2 cup of bait per hole, 8 lb/A NA

LSS, LP, SS, 

WG

Yes

Rozol Prairie Dog 

Bait 7173-286 Granular 0.005 Black-Tailed Prairie Dogs 1⁄4 cup per burrow NA SS, G Yes

Chlorophacinone 

Bait Station 7173-287 Impregnated Material 0.005 House Mice Bait Station No None No

Chlorophacinone 

Block 0803 Bait 

Station

7173-289 Impregnated 

Material 0.005 House Mice Bait Station No None No

Chlorophacinone 7173-293 Pelleted/Tableted 0.005 House Mice Bait Station, can refill Yes WG No
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Table A.1. Use Profile for Chlorophacinone.

Product Name

EPA 

Reg. 

No.

Formulation % Active 

Ingredient Target Pests Application Rate

Tamper 

Resistant 

Bait Station

Personal 

Protective 

Equipment

1

Restricted 

Use 

Pesticide

Refillable Bait 

Station

with bait blocks

Rozol Pocket 

Gopher Bait III 7173-294 Pelleted/Tableted 0.005 Pocket Gophers 2/3 cup of bait per hole, 8 lb/A NA

LSS, LP, SS, 

WG

Yes

Chlorophacinone 

Block 0803 Bait 

Station

7173-295 Pelleted/Tableted 0.005 House Mice Bait Station Yes None No

Rozol Mini Blocks 

0803 7173-299 Pelleted/Tableted 0.005 Norway rats, roof rats & house mice

Mice 1 block per 

placement up to 2 blocks. 

Rats 3 to 16 blocks per 

placement

Yes

LSS, LP, SS, 

WG

Yes

Rozol Mini Blocks 

0803 Refillable 

Bait Station

7173-303 Granular 0.005 House Mice 2 Bait Stations Yes None No

1 LSS = long sleeved shirt, S = shirt, LP = long pants, SS = shoes & socks, WG = waterproof gloves, PE = protective eyewear, D/M FR = dust/mist filtering respirator
Page 14 of 21

Attachment 2

Chemical Identity Table

TABLE A.2. Chlorophacinone Nomenclature.

Chemical structure

Common name chlorophacinone

IUPAC name 2-[2-(4-Chlorophenyl)-1-oxo-2-phenylethyl]indane-1,3-dione

CAS name 2-[2-(4-chlorophenyl)-2-phenylacetyl]-1H-indene-1,3(2H)-dione

CAS registry number 3691-35-8
Page 15 of 21

Attachment 3

Table A.3. Physicochemical Properties of Chlorophacinone.

Parameter Value Reference

Melting point 141-145oC Rodenticide Cluster RED, 

1998 Physical State Pale Yellow Microcrystalline Powder

Density 0.58 g/cm2

Solvent solubility (g/L at 25oC) Water 0.002

Dichloromethane 30.2

Chloroform 28.7

Ethyl Acetate 3.08

Acetone 1.93

Diethyl Ether 1.13

Hexane 0.113

Methanol 0.109

Ethanol 0.074

Vapor pressure Negligible at 20oC http://pubchem.ncbi.nlm.nih.go

v/compound/chlorophacinone#

section=Substances

Dissociation constant, pKa 3.40 at 25oC

Octanol/water partition coefficient 

Log(POW)

4.22 Rodenticide Cluster RED, 

1998

Stability Stable for 14 days at 54oC
Page 16 of 21

Attachment 4

Summary of Toxicity Endpoints and Points of Departure of Chlorophacinone

Table A.4.1. Summary of Toxicological Doses and Endpoints for use in Dietary and Non-Occupational Human Health 

Risk Assessments

Exposure Scenario Point of 

Departure (PoD)

Uncertainty / 

FQPA Safety 

Factors

RfD, PAD, Level 

of Concern for 

Risk Assessment

Study and Toxicological Effects

Dermal 

Short Term 

(1-30 days)

NOEL = 

0.08 mg/kg/day

UFA = 10x

UFH = 10x

FQPA = 1x

Residential LOC 

for MOE = 100

21-Day Dermal Toxicity Study –

Rabbits

LOEL = 0.4 mg/kg/day

Based on increased prothrombin times 

in both sexes on Day 21.

Inhalation 

Short Term 

(1-30 days)

Intermediate Term

(1-6 months)

NA UFA = 10x

UFH = 10x

FQPA = 1x

Residential LOC 

for MOE = 100

The TESC says risk via inhalation is 

not likely - but the OREB chapter is

requiring a respirator.

Cancer (oral, dermal, 

and inhalation)

Cancer risk assessment was not been conducted because long-term studies are not available and chronic 

exposure is not likely to occur.

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). MOE = margin of exposure. LOC = 

level of concern. N/A = not applicable.

Table A.4.2. Summary of Toxicological Doses and Endpoints for use in Occupational Human Health Risk Assessments

Exposure Scenario Point of 

Departure (PoD)

Uncertainty / 

FQPA Safety 

Factors

Level of Concern 

for Risk 

Assessment

Study and Toxicological Effects

Dermal 

Short Term 

(1-30 days)

Intermediate Term

(1-6 months)

NOEL = 

0.08 mg/kg/day

UFA = 10x

UFH = 10x

Occupational LOC 

for MOE = 100

21-Day Dermal Toxicity Study –

Rabbits

LOEL = 0.4 mg/kg/day

Based on increased prothrombin times 

in both sexes on Day 21.

Inhalation 

Short Term 

(1-30 days)

Intermediate Term

(1-6 months)

NA UFA = 10x

UFH = 10x

Occupational LOC 

for MOE = 100

The TESC says risk via inhalation is 

not likely - but the OREB chapter is

requiring a respirator.

Cancer (oral, dermal, 

and inhalation)

Cancer risk assessment was not been conducted because long-term studies are not available and chronic 

exposure is not likely to occur.

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).

MOE = margin of exposure. LOC = level of concern. N/A = not applicable.
Page 17 of 21

Attachment 5

Toxicity Profile for Chlorophacinone

Table A.5.1. Acute Toxicity Profile

Guideline Study Type MRID (year) / Doses / 

Classification Results

870.1100 Acute Oral Toxicity

(Rat)

41875301 (1988)

Gavage Doses (mg/kg):

M: 0, 2.0, 3.2, 5.2, 8.2, 13.2, 21.0

F: 0, 2.0, 3.2, 5.2, 8.2, 13.2, 21.0

Acceptable / Guideline

Toxicity Category: I

LD50 (mg/kg): M = 3.15

F = 10.95

Combined = 6.26

870.1200 Acute Dermal 

Toxicity

(Rabbit)

41702801 (1990)

Applied Dose (mg/kg):

M: 0.25, 0.5, 0.75

Acceptable / Guideline

Toxicity Category: I

LD50 (mg/kg): M = 0.329

F = NA

870.1300 Acute Inhalation 

Toxicity

(Rat)

41981102 (1991)

Inhalation Dose (g/L):

M: 1.33, 10.3, 11.5, 14.5

F: 1.33, 10.3, 11.5, 14.5

Acceptable / Guideline

Toxicity Category: I

LC50 (g/L): M = 7.0

F = 12.0

Combined = 9.3

870.2400 Acute Eye Irritation

(Rabbit)

41874001 (1989)

Applied Dose (g):

F: 0.1

Acceptable / Guideline

Toxicity Category: IV

No eye irritation for up to 72 hours.

870.2500 Acute Dermal 

Irritation

(Rabbit)

41702801 (1990)

Applied Dose (mg/kg):

M: 0.25, 0.5, 0.75

Acceptable / Guideline

Toxicity Category: IV

Primary Irritation Score (PIS) = 0

870.2600 Skin Sensitization

(Guinea Pig)

41578601 (1990)

Applied Dose (g):

0.003, 0.005, 0.01, 0.2

Acceptable / Guideline

Not a dermal sensitizer

Table A.5.2. Repeat-Dose and Other Toxicity Profile

Guideline Study Type MRID (year) / Doses / 

Classification Results

870.3100 90-Day Oral 

Toxicity in Rodents 

(Rat)

92018013 (1990)

Gavage Dose (g/kg/day):

M: 0, 5, 10, 20, 40, 80, 160

F: 0, 5, 10, 20, 40, 80, 160

Acceptable / Guideline

NOEL (g/kg/day): M = 5 F = 5

LOEL (g/kg/day): M = 10 F = 10

Based on increased coagulation time for both males 

and females, with males more sensitive than females.

870.3150 90-Day Oral 

Toxicity in NonRodents

NA Study not needed at this time (TXR3 0057326, U. 

Habiba, 12/15/2015)

870.3200 21/28-Day

Dermal Toxicity

(Rabbit)

42237402 (1992)

Dermal Dose (mg/kg/day):

M: 0.08, 0.40, 2.0

F: 0.08, 0.40, 2.0

Acceptable / Guideline

Dermal Irritation

NOAEL (mg/kg/day): M = NA F = NA

LOAEL (mg/kg/day): M = NA F = NA

Systemic

NOEL (mg/kg/day): M = 0.08 F = 0.08

LOEL (mg/kg/day): M = 0.4 F = 0.4

Based on increased prothrombin times in both sexes 

on Day 21.

870.3465 90-Day 

Inhalation Toxicity

NA NA
Page 18 of 21

Table A.5.2. Repeat-Dose and Other Toxicity Profile

Guideline Study Type MRID (year) / Doses / 

Classification Results

870.3700 Prenatal 

Developmental 

Toxicity Study

(Rat)

43349501 (1994)

Range Finding Study

Gavage Dose (g/kg/day):

F: 0, 1, 5, 25, 50, 100, 200

Main Study

Gavage Dose (g/kg/day):

F: 0, 12.5, 25, 50, 100

Acceptable / Guideline

Maternal

NOEL (g/kg/day) = 50

LOEL (g/kg/day) = 100

Based on mortality.

Developmental

NOEL (g/kg/day) < 12.5

LOEL (g/kg/day) = 12.5

Based on increased incidences of hydroureter, 

distended ureter, and total ureter anomaly.

Prenatal 

Developmental 

Toxicity Study

(Rabbit)

43570801 (1995)

Range Finding Study

Gavage Dose (g/kg/day):

F: 0, 1, 2, 5, 10, 50, 100

Main Study

Gavage Dose (g/kg/day):

F: 0, 5, 10, 25, 75

Acceptable / Guideline

Maternal

NOEL (g/kg/day) = 5

LOEL (g/kg/day) = 10

Based on increased prothrombin and activated partial 

thromboplastin times in the preliminary range-finding 

study (these measurements were not made in the main 

study).

Developmental

NOEL (g/kg/day) = 10

LOEL (g/kg/day) = 25

Based on the lack of sufficient fetuses/litters available 

for evaluation

870.3800 Reproduction and 

Fertility Effects

NA Study not needed at this time (TXR# 0057326, U. 

Habiba, 12/15/2015)

870.4100 Chronic Toxicity in 

Rodents

NA Study not needed at this time (TXR# 0057326, U. 

Habiba, 12/15/2015)

870.4200 Carcinogenicity

(Mouse)

NA Study not needed at this time (TXR# 0057326, U. 

Habiba, 12/15/2015)

Carcinogenicity

(Rat)

NA Study not needed at this time (TXR# 0057326, U. 

Habiba, 12/15/2015)

870.5100 Bacterial Reverse 

Mutation Test

(Salmonella 

typhimurium)

43284001 (1994)

Applied Dose (μg/plate):

+S9: 1 – 5000

-S9: 0.5 – 5000

Acceptable / Guideline

Under the conditions of this assay, there was no

indication of any mutagenic activity in the test strains 

associated with exposure to chlorophacinone

(analytically determined concentration: 101%). In the 

S. typhimurium strains at the highest dose levels there 

were adequate indications of cytotoxicity (reductions

in numbers of revertants and/or reductions in the 

background lawn). It is concluded that there was no

evidence that chlorophacinone induced a mutagenic 

response in any strain at any nonactivated or S9-

activated dose level.

42937133 (1989)

Applied Dose (μg/plate):

S9: 5, 16, 50, 158, 500 

Acceptable / Guideline

There was no evidence of induced revertant colonies 

over background at any dose tested, either with or 

without S9.

870.5300 in vitro Mammalian 

Cell Gene Mutation 

Test

(Chinese Hamster 

Ovary (CHO) Cells)

41611701 (1990)

Applied Dose (g/mL):

S9: 5 – 200

Acceptable / Guideline

Test material doses ≥100 g/mL S9 were cytotoxic.

It is concluded that there was no indication of a

mutagenic response from exposure to technical

chlorophacinone under the conditions of this assay.
Page 19 of 21

Table A.5.2. Repeat-Dose and Other Toxicity Profile

Guideline Study Type MRID (year) / Doses / 

Classification Results

870.5375 in vitro Mammalian 

Chromosome 

Aberration Test

(Human 

Lymphocytes)

43825601 (1995)

Applied Dose (μg/mL):

S9: 0, 6.25, 12.5, 25, 50

Acceptable / Guideline

There were no biologically significant increases in

incidences of chromosomally aberrant cells/dose level 

or mean number of aberrations/metaphase spread. The 

positive controls induced the expected high yields of 

metaphase spreads with chromosome aberrations.

Based on the above considerations, it is concluded 

that chlorophacinone, at doses up to and including 

those associated with cytotoxicity (50 g/mL), did not 

induce a clastogenic response in human lymphocytes 

under the conditions of this assay either in the 

presence or absence of S9.

870.5395 Mammalian 

Erythrocyte 

Micronucleus Test

(Mouse)

43285901 (1994)

Intraperitoneal Injection

(mg/kg/day):

M: 0, 3.75, 7.5, 15

F: 0, 3.75, 7.5, 15

Acceptable / Guideline

There was no indication of any increased incidence of 

micronucleated polychromatic erythrocytes (MPCEs) 

associated with exposure to chlorophacinone. Positive 

controls (which were sacrificed 24 hours after 

receiving a single oral dose of 80 mg/kg 

cyclophosphamide) showed significant increases in 

incidences of MPCEs. Although there was some 

variation between dose groups with respect to mean 

PCE:NCE ratios, this seems to have been due to 

considerable variation between individual animals 

(possibly an indication that some of these mice might 

have subsequently died if they had not been 

sacrificed) rather than a direct effect of exposure to 

chlorophacinone.

870.5550 Unscheduled DNA 

Synthesis in 

Mammalian Cells in 

Culture

(Rat Hepatocytes)

43018510 (1989)

Applied Dose (μg/mL):

Run 1: 0.391, 1.24, 3.91, 12.4, 39.1

Run 2: 0.391, 1.24, 3.91, 12.4, 39.1, 

 124

Acceptable / Guideline

There was no evidence of UDS induction at any tested 

concentration as measured by incorporation of 

tritiated thymidine into DNA (using liquid 

scintillation counting).

42937138 (1993)

Applied Dose (μg/mL):

189.7, 600

Acceptable / Guideline

The mean net nuclear grain count was below zero for 

both doses at both treatment times indicating no 

induction of UDS as tested in this study. There was a 

2.5 fold increase in the proportion of cells in S-phase 

in cultures from treated rats of both dosage groups 

sacrificed at 12-14 hours. Only slides from the 12-14 

hour time point were analyzed for S-phase synthesis.

870.6200 Acute Neurotoxicity 

Screening Battery

NA Study not needed at this time (TXR# 0057326, U. 

Habiba, 12/15/2015)

90-Day 

Neurotoxicity 

Screening Battery

NA Study not needed at this time (TXR# 0057326, U. 

Habiba, 12/15/2015)
Page 20 of 21

Table A.5.2. Repeat-Dose and Other Toxicity Profile

Guideline Study Type MRID (year) / Doses / 

Classification Results

870.7200 Companion Animal 

Safety

(Rat)

41981101 (1991)

Gavage Doses (mg/kg):

M: 5.28, 4.73, 5.03

Acceptable / Guideline

All rats which ate the chlorophacinone-containing 

pellets and did not receive vitamin K1 died. All rats 

treated with vitamin K1 after 24-hour exposure to the 

chlorophacinone diet survived, as did 3/5 rats fed the 

chlorophacinone-containing diet for 48 hours. All of 

the vitamin K1-treated rats which had been fed the 

chlorophacinone-containing diet for 72 hours died.

While vitamin K1 has been shown to be a somewhat 

effective treatment following chlorophacinone 

ingestion, there were some mortalities among the rats 

which were given vitamin K1 at 48 hours. This 

suggests a potential hazard if incidents occur 

involving pets or small children in which it is not 

known or realized that ingestion has occurred. It is 

noted that this antidotal study does not include 

prothrombin times; and that such information, while 

not necessary for purposes of reregistration, could be 

useful to the Agency in defining hazards associated 

with exposure to chlorophacinone.

870.7485 Metabolism and 

Pharmacokinetics 

(Rat)

00155540 (1981)

Gavage Dose (mg/kg):

Single: 1

Repeated: 1.43 (3 Days)

Acceptable / Guideline

Chromatography and autoradiography demonstrated

that the chlorophacinone remained unchanged in 

plasma, with a blood half-life of about 10 hours.

Chlorophacinone was distributed systemically (e.g., 

liver, kidney, lung, heart, muscle, fat, and in the 

residual carcass).

Urine and CO2 radioactivity were less than 1% of the 

total dose. Most of the radioactivity was excreted in 

the feces (94.7% in one rat and 108.6% in the other 

over the 4-day period). Excretion reached 90% in the 

first two days.

Two hours after administration of chlorophacinone in 

the duodenum, biliary elimination was constant. At 

the end of 8 hours, an average of 26% of the 

administered radioactivity was eliminated in the bile.

Although it is reported that there is over 90% 

excretion in the two days following dosage, the 

findings in the subchronic study (MRID 92018013) 

indicate there is a potential for bioaccumulation (or 

cumulative toxicity). In the subchronic study, there 

were mortalities at 40 g/kg/day in 10/10 males

(deaths occurred days 29-82) and 4/10 females

(deaths on days 69-111), and there were also 

mortalities at 20 g/kg/day in 4/10 males (deaths on 

days 105-111).

870.7600 Dermal Penetration NA No dermal absorption data is available. Therefore, the 

Agency assumes that the dermal absorption factor 

(DAF) = 100%.

870.7800 Immunotoxicity NA Study not needed at this time (TXR# 0057326, U. 

Habiba, 12/15/2015)
Page 21 of 21

Attachment 6

Toxicology	Data	Requirements

The requirements (40 CFR §158.340) for food and non-food uses for Chlorophacinone are in 

Table A.6. Use of the new guideline numbers does not imply that the new (1998) guideline 

protocols were used.

Table A.6. Toxicology Data Requirements

Guideline Study Type Required Submitted Satisfied

870.1100 Acute Oral Toxicity Yes Yes Yes

870.1200 Acute Dermal Toxicity Yes Yes Yes

870.1300 Acute Inhalation Toxicity Yes Yes Yes

870.2400 Acute Eye Irritation Yes Yes Yes

870.2500 Acute Dermal Irritation Yes Yes Yes

870.2600 Skin Sensitization Yes Yes Yes

870.3100 90-Day Oral Toxicity in Rodents CR Yes Yes

870.3150 90-Day Oral Toxicity in Non-Rodents CR No Yes2

870.3200 21/28-Day Dermal Toxicity No Yes Yes

870.3250 90-Day Dermal Toxicity Yes No NA

870.3465 90-Day Inhalation Toxicity CR No No3

870.3700 Prenatal Developmental Toxicity Study (Rat) Yes Yes Yes

Prenatal Developmental Toxicity Study (Rabbit) Yes Yes Yes

870.3800 Reproduction and Fertility Effects Yes No Yes2

870.4100 Chronic Toxicity (Rodent) CR No Yes2

870.4200 Carcinogenicity (Rat) CR No Yes2

Carcinogenicity (Mouse) CR No Yes2

870.5100 Bacterial Reverse Mutation Test Yes Yes Yes

870.5300

870.5375

in vitro Mammalian Cell Gene Mutation Test

in vitro Mammalian Chromosome Aberration Test Yes1 YesYes Yes

870.5385

870.5395

Mammalian Bone Marrow Chromosomal Aberration Test

Mammalian Erythrocyte Micronucleus Test Yes1 NoYes Yes

870.6100 Delayed Neurotoxicity of Organophosphorus Substances (Acute, Hen) CR No NA

Delayed Neurotoxicity of Organophosphorus Substances (28-Day, Hen) CR No NA

870.6200 Neurotoxicity Screening Battery (Acute, Rat) Yes No Yes2

Neurotoxicity Screening Battery (90-Day, Rat) Yes No Yes2

870.6300 Developmental Neurotoxicity Study CR No NA

870.7200 Companion Animal Safety CR Yes NA

870.7485 Metabolism and Pharmacokinetics CR Yes Yes

870.7600 Dermal Penetration CR No NA

870.7800 Immunotoxicity Yes No Yes2

CR Conditionally Required

NA Not Applicable

1 Either guideline study type may be used to satisfy the data requirement (e.g., 870.5300 or 870.5375)

2 Study requirements are not needed to provide further hazard characterization (TXR# 0057326, U. Habiba, 12/15/2015).

3 Study required due to potential exposure and risks from tracking powders (TXR# 0057326, U. Habiba, 12/15/2015).