_ __ ···-----~~?!~P.i~!~~Registration Review !2uman-Health Assessmen~ Sc~_e~-~~?~~~~.!2! ______________ _ 

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

MEMORANDUM 

Date: September 3, 2013 

OFFICE OF 

CHEMICAL SAFETY AND 

POLLUTION PREVENTION 

SUBJECT: Chloropicrin. Human-Health Assessment Scoping Document in Support of 

Registration Review. 

PC Code: 081501 DP Barcode: 0410119 

Decision No.: Lf7C.'I31 Registration No.: N/A 

Petition No.: N/A Regulatory Action: Registration Review Scoping Document 

Risk Assessment Type: N/A Case No.: 0040 

TXR No.: N/A CAS No.: 76-06-2 

MIDD~:NM ~cr~NM 

FROM: CharlesSmith,BranchChief /' ~"'-(!>(0 Risk Assessment Branch 1 (RAB 1~ 

and V\ A~~ .,{ >/!:? 

Shalu Shelat, Industrial Hygienist -10~ '-

Nancy McCarroll, Toxicologist .;/ ~~,... ......... 

Christopher Schlosser, Toxicologist -:~L:.--- ./ ------

Risk Assessment Branch 6 (RABVl) 

Health Effects Division (7509P) 

J 1£:1 JJ ~ .-Ht' '1 /g /t.> Nathan Mottl, Biologist IU. P'f/W1.,{{ 

Risk Assessment and Science Support Branc 

Antimicrobials Division (751 OP) 

THROUGH: Felecia Fort, Branch Chief .1_ ' C/O ~-/., q/3{1'3 

R

Health 

isk Assessment 

Effects Division 

Branch 

(7509P) 

6 (RABV 1) ~ 

Steve Weiss, Branch Chief 5f{{//~ ~ Tim 

Risk 

Leighton

Assessment 

, Senior 

and Science 

Scientist 

Support 

:?'£ ~ 

Branch 

Antimicrobials Division (751 OP) 

TO: Carolyn Schroeder, Chemical Review Manager 

Risk Management and Implementation Branch IV 

Pesticide Re-Evaluation Division (7508P) 

Attached is the combined HED and AD human-health risk assessment seeping document for 

chloropicrin to support registration review. 

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.. S:~~?!opicrin Re~~~~!ion Review Hu_!ll~!l_-Health Asse_s.~~nt Scoe in~_!)()~U~~~! _________ ____ _ 

Executive Summary 

Chloropicrin is a non-selective pre-plant soil fumigant with fungicidal, herbicidal, insecticidal, 

and nematicidal properties. Chloropicrin is also an active ingredient in antimicrobial wood 

preservative products. The Health Effects Division (HED) and the Antimicrobial Division (AD) 

have evaluated the status of the human-health assessments for chloropicrin to determine whether 

sufficient data are available to support Registration Review. HED and AD have also considered 

the most recent human-health risk assessments for chloropicrin with respect to toxicity, 

exposure, and usage databases, and the most updated Agency science policy and risk assessment 

methodologies to determine the scope of work necessary to support Registration Review. 

The Amended Chloropicrin Reregistration Eligibility Decision (RED) document was issued in 

May 2009. The Amended RED focused on three main use categories of chloropicrin: ( 1) preplant soil fumigations (e.g., agricultural and commercial greenhouse); (2) residential uses 

(warning agent for sulfuryl fluoride); and (3) other specialized fumigations (e.g., spot tree replant 

sites and remedial wood treatments). Chloropicrin use in empty grain bins and empty potato 

storage/house cellars were voluntarily cancelled as part of the chloropicrin RED process. Since 

the Amended RED was issued, no new uses of chloropicrin have been registered and the Agency 

determined that the use of chloropicrin as a warning agent prior to sulfuryl fluoride residential 

fumigations is not a pesticidal use. 

The toxicity database for chloropicrin is adequate for Registration Review. HED's Hazard and 

Science Policy Council (HASPOC) has determined that a neurotoxicity battery is not required 

for chloropicrin. An Immunotoxicity study was required as part of the 2009 Amended RED but 

this requirement was subsequently waived (Reaves; D382316; 4/27/201 1). The focal points for 

the assessment of chloropicrin are occupational and residential inhalation exposure. There is no 

route specific dermal study available for chloropicrin; however, HED has not previously 

performed a dermal exposure assessment for chloropicrin since it is category I for primary skin 

irritation and acute dermal toxicity and significant dermal exposure is not expected. There are a 

number of route specific inhalation studies available for chloropicrin including an acute 

inhalation/irritation study in humans, an acute inhalation study in rats, developmental inhalation 

studies in rats and rabbits, a 2-generation reproduction inhalation study in rats, 13-week 

inhalation studies in rats and mice, a 78-week inhalation cancer study in mice, and a 2-year 

inhalation cancer study in rats. The Agency does not anticipate the need to reevaluate the points 

of departure (PODs) and uncertainty factors (UFs) for the residential and occupational exposure 

assessments during Registration Review. 

The residue chemistry and dietary-exposure database is adequate to support current registration 

requirements. The current uses of chloropicrin have previously been determined to be non-food 

uses. In addition, based on environmental fate data, the residual contents in soils, and 

monitoring data, chloropicrin is not expected to adversely impact the drinking water sources such 

as surface water and ground water. The Agency does not anticipate the need to perform dietary 

or drinking water assessments during Registration Review. 

The residential exposure database for chloropicrin is adequate for Registration Review with the 

exception of an ambient air study measuring chloropicrin from soil fumigant applications. The 

Agency does not anticipate the need to perform additional or updated PERFUM modeling during 

Registration Review unless new field volatility studies become available or points of departure 

(PODs) or uncertainty factors (UFs) for the residential exposure assessment change. 

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The occupational exposure database for chloropicrin is adequate for Registration Review. The 

Agency does not anticipate the need to perform additional or updated occupational exposure 

assessments during Registration Review unless new occupational exposure studies become 

available or points of departure (PODs) or uncertainty factors (UFs) for the occupational 

exposure assessment change.

No new data deficiencies outside those previously required through reregistration were 

identified for chloropicrin. 

HED and AD anticipate conducting the following risk assessment updates during Registration 

Review:

Toxicology: None

Residue Chemistry: None

Dietary Exposure: None

Occupational/Residential Exposure:

o HED will be required to perform an ambient air assessment during Registration 

Review once the chloropicrin ambient air study is submitted to the Agency.

 

1.0 Introduction

Chloropicrin is a non-selective pre-plant soil fumigant with fungicidal, herbicidal, insecticidal, 

and nematicidal properties. Chloropicrin is also an active ingredient in antimicrobial wood 

preservative products. The Health Effects Division (HED) and the Antimicrobial Division (AD) 

have evaluated the status of the human-health assessments for chloropicrin to determine whether 

sufficient data are available to support Registration Review. HED and AD have also considered 

the most recent human-health risk assessments for chloropicrin with respect to toxicity, 

exposure, and usage databases, and the most updated Agency science policy and risk assessment 

methodologies to determine the scope of work necessary to support Registration Review.

The Amended Chloropicrin Reregistration Eligibility Decision (RED) document was issued in 

May 2009. The Amended RED focused on three main use categories of chloropicrin: (1) preplant soil fumigations (e.g., agricultural and commercial greenhouse); (2) residential uses 

(warning agent for sulfuryl fluoride); and (3) other specialized fumigations (e.g., spot tree replant 

sites and remedial wood treatments). Chloropicrin use in empty grain bins and empty potato 

storage/house cellars were voluntarily cancelled as part of the chloropicrin RED process (75 FR 

24699). Since the Amended RED was issued, no new uses of chloropicrin have been registered 

and the agency determined that the use of chloropicrin as a warning agent prior to sulfuryl 

fluoride residential fumigations is not a pesticidal use. 

2.0 Hazard Identification/Toxicology

The toxicity database for chloropicrin is adequate for Registration Review. HED’s Hazard and 

Science Policy Council (HASPOC) has determined that a neurotoxicity battery is not required 

for chloropicrin (Dunbar; 5/22/13; TXR 0056662). The 2009 Amended RED required an 

Immunotoxicity study for chloropicrin but this requirement was subsequently waived (Reaves; 

D382316; 4/27/2011). Attachment 2 provides a summary of the acute, subchronic, and chronic 

toxicity profile for chloropicrin. Attachment 3 provides a summary of the relevant toxicological 

endpoints used in the chloropicrin 2009 risk assessment.
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No inhalation pharmacokinetic or metabolism studies are available at this time for chloropicrin 

and the metabolic pathway has not been determined. However, studies from the open literature 

indicate glutathione and thiol proteins may play a role in the metabolism of chloropicrin. 

Chloropicrin is a sensory irritant with a clear mode of action and target. Stimulation of the 

trigeminal nerve mediates sensations in the nose, eyes, throat, and upper respiratory tract. 

Furthermore, a human sensory irritation study for chloropicrin revealed that eye irritation was the 

most sensitive endpoint. Specifically, phase three of the human study identified a range of 

concentrations in which sensitive subjects (e.g., young adults) were capable of detecting 

chloropicrin in the eyes without changes in the upper respiratory tract. The human study also 

suggests that the transient eye irritation experienced from an hour of exposure does not carry 

over from day to day. Protection of eye irritation therefore likely protects against changes in 

upper respiratory parameters. The Human Studies Review Board (HSRB) concluded the human 

study was conducted under ethical standards and is scientifically robust for estimating a safe 

level of inhalation exposure. 

The robust animal database for chloropicrin provides insight into the dose-response and 

progression of respiratory irritation that occurs at higher concentrations. Chloropicrin is 

classified as category I (highly toxic) for acute inhalation, primary skin irritation, and acute 

dermal toxicity. There is no route specific dermal study available for chloropicrin however, 

HED has not previously performed a dermal exposure assessment for chloropicrin since it is 

category I for primary skin irritation and acute dermal toxicity and significant dermal exposure is 

not expected. For the major route of concern, the inhalation rodent database is robust with a 

number of route specific inhalation studies available for chloropicrin including an acute 

inhalation/irritation study in humans, an acute inhalation study in rats, developmental inhalation 

studies in rats and rabbits, a 2-generation reproduction inhalation study in rats, 13-week 

inhalation studies in rats and mice, a 78-week inhalation cancer study in mice, and a 2-year 

inhalation cancer study in rats. In developmental inhalation toxicity studies with chloropicrin 

(MRID 42740601, 42740602), no evidence of quantitative or qualitative susceptibility in 

developing animals was observed. 

There is no quantitative or qualitative susceptibility observed in the developmental and 

reproductive inhalation toxicity studies with chloropicrin. All of the developmental NOAELs 

are equal to or larger than the NOAELs for maternal toxicity.

In vitro mutagenicity assays for chloropicrin have mixed positive and negative results; however, 

in vivo data for chloropicrin are negative. Currently, chloropicrin is not considered a carcinogen 

by the inhalation route of exposure since there were no treatment-related increases in tumor 

incidence when compared to control animals in two acceptable inhalation carcinogenicity studies 

in the mouse and rat.

Conclusions: The toxicity database for chloropicrin is adequate for Registration Review. The 

Agency does not anticipate the need to reevaluate the points of departure (PODs) and uncertainty 

factors (UFs) for the residential and occupational exposure assessments during Registration 

Review.

3.0 Residue Chemistry

The residue chemistry database for chloropicrin is adequate for Registration Review. The 

qualitative nature of the residue in plants is adequately understood based on an acceptable plant 

metabolism study (S. Knizner, D200326 and D202185, 8/25/94). The plant metabolism and 
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environmental fate studies demonstrated that when used as a preplant soil fumigant, chloropicrin 

is degraded in both aerobic and anaerobic soil to carbon dioxide (CO2). The CO2 generated from 

the chloropicrin is subsequently taken up by the plant and incorporated into starch, proteins, 

pectin, lignin, hemicellulose, and cellulose. Therefore, the use of chloropicrin as a preplant soil 

fumigant is considered to be a non-food use and tolerances are not needed (J. Abbots, Memo, 

8/15/96).

Conclusions: The residue chemistry database for chloropicrin is adequate for Registration 

Review.

4.0 Dietary Exposure

The dietary exposure database for chloropicrin is adequate for Registration Review. As 

described in Section 3.0, the Agency previously decided that the currently registered uses of 

chloropicrin are non-food uses.

Chloropicrin may potentially transport to nearby surface water through runoff and erosion, 

especially if an application of chloropicrin coincides with, or is closely followed by a rain event. 

However, rapid volatilization of chloropicrin from surface water is expected to be an important 

route of dissipation. Chloropicrin is very soluble in water and has low adsorption into soil and 

thus it can potentially leach into shallow ground water and leaky aquifers. Chloropicrin has 

beenpreviously detected in non-targeted monitoring wells. Based on the database of pesticides in 

groundwater (U.S. EPA, 19921), chloropicrin was found at levels less than 1.00 μg/L in three 

wells out of 15,175 wells in Florida and was not found at any measurable levels in 1,386 wells in 

California. Based on environmental fate data, modeling estimates, and monitoring data, the 

Agency does not expect chloropicrin to adversely impact ground water or surface water.

Based on the discussion above, no dietary or drinking water assessments have been 

previouslyperformed for chloropicrin.

Conclusions: The dietary exposure database for chloropicrin is adequate for Registration 

Review. The Agency does not anticipate the need to perform dietary or drinking water 

assessments during Registration Review.

5.0 Residential Exposure

Following the 2009 Amended RED, the Agency required three residential exposure studies for 

the conventional uses of chloropicrin, including the following: 

a field volatility study for shank injection, bedded, untarped applications of chloropicrin

(835.8100), 

a field volatility study for applications of chloropicrin using a water seal (835.8100), and 

an ambient air monitoring study for chloropicrin (non-guideline).

Two field volatility studies (MRIDs 48033801 and 48087401) have been submitted to the 

Agency. The Agency reviewed and included these studies in a 2011 chloropicrin addendum 

memo (Smith; D348650; 1/11/2011) and thus these requirements are considered fulfilled. The 

Agency has not received the ambient air monitoring study at this time. Once this study is 

completed and submitted it will also be reviewed and incorporated during Registration Review.

 

1 U.S. Environmental Protection Agency. 1992. Pesticides in Groundwater Database, A compilation of monitoring studies: 1971-

1991, National Summary. EPA 734-12-92-0001.
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There are currently no registered residential uses of chloropicrin. However, there is the potential 

for residential bystander inhalation exposure to chloropicrin after a soil fumigation application. 

The Agency has specifically focused on assessing acute inhalation exposures resulting from 

chloropicrin applications because peak chloropicrin air concentrations typically occur in the first 

24 or 48 hours after application. There is also the potential for inhalation exposure to 

chloropicrin via ambient air. These exposures can be acute as well as longer-term in nature. 

There are two recent documents that analyzed acute residential bystander inhalation exposure to 

chloropicrin based on numerous field volatility studies and PERFUM (Probabilistic Exposure 

and Risk model for Fumigants) air modeling for a variety of chloropicrin applications (Smith 

and Reaves; D348637; 4/30/2009 and Smith; D348650; 1/11/2011). The results of these 

assessments show that bystander inhalation exposure to chloropicrin after a soil fumigation 

application can vary depending on a variety of factors such as application method, agricultural 

tarps, water seals, and a number of soil parameters (i.e., soil moisture, organic content, etc.). For 

many application scenarios, the PERFUM air modeling results showed that acceptable 

chloropicrin air concentrations were attainable at some distance from a treated field and thus 

buffer zones were required to protect residential bystanders. The 2009 Amended Reregistration 

Eligibility Decision (RED) Document for chloropicrin provides more information on buffer zone 

development.

There are two recent documents that analyzed ambient air inhalation exposure to chloropicrin 

using limited ambient air monitoring data from California (Smith and Reaves; D348637; 

4/30/2009 and Smith; D404798; 10/9/2012). The results of these assessments show that ambient 

air inhalation exposures to chloropicrin can occur for extended periods especially in areas of high 

use during the season of high use. In some cases, short- and intermediate-term risks exceed 

HED’s level of concern for chloropicrin (MOEs < 30 for short- and intermediate-term). In 

addition, no ambient air data are available for other regions/states that have high usage of 

chloropicrin like the southeast (Florida, North Carolina, South Carolina and Georgia) and the 

northwest (Washington, Oregon, and Idaho).

Conclusions: 

The residential exposure database for chloropicrin is adequate for Registration Review except for 

the outstanding exposure study (i.e., the ambient air study). HED will review and incorporate 

the ambient air monitoring study once it is submitted during Registration Review. The Agency 

does not anticipate the need to perform additional or updated PERFUM modeling during 

Registration Review unless new field volatility studies become available or points of departure 

(PODs) or uncertainty factors (UFs) for the residential exposure assessment change.

During Registration Review, HED also plans to update the fumigant factors document (Dawson, 

Smith, and Shelat; D385314; 1/11/2011). The fumigant factors document provides a discussion 

of values and parameters used as the basis for buffer reduction credits (i.e., tarps) as well as for 

establishing GAPs (i.e., soil moisture) for the fumigants. This document impacts all of the soil 

fumigants including chloropicrin.

6.0 Aggregate-Risk Assessment

Acute and chronic aggregate-risk assessments were not previously performed for chloropicrin

because no dietary and drinking water assessments were performed (see Section 3.0 and 4.0 

above).
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Conclusions: 

Acute and chronic aggregate risk assessments are not anticipated during Registration Review.

7.0 Occupational Exposure

The occupational exposure database for chloropicrin is adequate for Registration Review. No 

occupational exposure data were required for chloropicrin as part of the 2009 Amended RED. 

The Amended RED focused on three main use categories of chloropicrin: (1) pre-plant soil 

fumigations (e.g., agricultural and commercial greenhouse); (2) residential uses (warning agent 

for sulfuryl fluoride); and (3) other specialized fumigations (e.g., spot tree replant sites and 

remedial wood treatments). Chloropicrin use in empty grain bins and empty potato 

storage/house cellars were voluntarily cancelled as part of the chloropicrin RED process. 

Since the Amended RED was issued, no new uses of chloropicrin have been registered and the 

agency determined that the use of chloropicrin as a warning agent prior to sulfuryl fluoride 

residential fumigations is not a pesticidal use. 

Occupational Handlers

Conventional Uses

There is potential for occupational handler inhalation exposure to chloropicrin to occur based on 

the registered conventional uses of chloropicrin. HED has not previously performed a dermal 

exposure assessment for chloropicrin since it is category I for primary skin irritation and acute 

dermal toxicity and significant dermal exposure is not expected (see Section 2.0 for more 

information). The most recent HED document that analyzed the potential occupational handler 

risks to chloropicrin is the 2009 risk assessment (Smith and Reaves; D348637; 4/30/2009). HED 

assessed the acute and short- and intermediate-term chloropicrin inhalation exposure for the

conventional uses of chloropicrin.

For soil fumigation, HED utilized a number of chloropicrin specific inhalation exposure studies 

to assess occupational handler inhalation exposures to chloropicrin in the 2009 assessment. 

These studies examined a variety of tasks associated with soil fumigation such as loading and 

applying. In some cases, acute as well as short- and intermediate-term risks exceeded HED’s 

level of concern for chloropicrin at baseline (MOEs < 1 for acute and MOEs < 30 for short- and 

intermediate-term). Even with the addition of an organic vapor respirator, some short- and 

intermediate-term risks exceeded HED’s level of concern for chloropicrin.

Antimicrobial Uses

The potential for occupational dermal exposure from application of chloropicrin may occur 

during the injection or pouring up to 2 pints per pole of the undiluted product directly into the 

pre-drilled holes or by filling vials to be placed into holes in timber. Potential dermal exposure 

may also occur during the process of pouring chloropicrin from original packaging containers 

into smaller containers prior to injecting or pouring into the pre-drilled holes. The most recent 

AD document that analyzed the potential occupational handler risks to chloropicrin is the 2007 

risk assessment (Leighton and Walls; D314399; 4/20/2007). The risks associated with dermal 

applicator exposure are not quantified in that document. The PPE on current labels such as long 

pants, long sleeved shirts, and chemical resistant gloves mitigate skin irritation effects resulting 

from potential dermal exposure to chloropicrin.
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As with the dermal exposure above, the potential for inhalation exposure to chloropicrin vapor 

may occur during the transfer from original packaging into smaller application containers or 

vials and during the injection or pouring of up to 2 pints per pole of the undiluted product 

directly into the pre-drilled holes. Exposure during the placement of prefilled vials into drilled 

holes should not occur unless the vials are accidentally damaged. Based on the use pattern (i.e., 

intermittent exposures throughout the work shift), the acute inhalation endpoint selected for 

chloropicrin is a good indicator of the need for respiratory and eye protection. However, ambient 

conditions would presumably result in a minimal concentration over a long-term duration. 

Workers are expected to be exposed to various concentrations of chloropicrin throughout the 

workday with peak concentrations occurring during open pouring of the products. Applications 

are performed outdoors and the product is capped into pre-drilled holes, thereby reducing the 

potential for off gassing immediately after the application.

To mitigate the potential inhalation risks to applicators, respiratory protection was recommended 

during the actual pouring of chloropicrin from containers into vials and during pouring/injecting 

into the pre-drilled holes. Current labels provide specific instructions for workers using (1) airpurifying respirators, (2) supplied air respirators, and (3) self contained breathing apparatuses 

(SCBAs). In general, applicators must wear air-purifying respirators. However, certain exposure 

scenarios such as filling vials in enclosed areas may trigger the need for the use of a supplied air 

or SCBA respirators. These recommendations that were stated in the RED were based on the 

need to protect applicators when air concentrations are above the acute level-of-concern of 0.073 

ppm and the TWA of 0.0005 ppm. The RED also states that the minimum type of respiratory 

protection to require is difficult to determine because the actual air concentration in the vicinity 

of the applicator is unknown and would be hard to quantify in the field. The current labels have 

been adjusted based on mitigation in the 2009 amended RED. Additional label statements for 

respiratory protection that are not already present in the 2009 amended RED label table are not

anticipated as needed for registration review. 

Occupational Post-Application

Conventional Uses

HED previously determined there were chloropicrin inhalation risk concerns for workers 

reentering chloropicrin fumigated fields 48 hours after application. As part of the 2009 

Amended RED, the Agency placed various restrictions on reentry of workers into fumigated 

fields. With these restrictions, HED believes that risks to reentry workers will not exceed the 

HED’s level of concern.

Antimicrobial Uses

In general, remedial wood treatment for poles and beams on bridges do not occur in high traffic 

areas for bystanders. However, distribution poles are numerous and often located in people’s 

front yards. Therefore, any potential bystander exposure would be best represented by the acute 

duration. The most recent AD document that analyzed the potential post-application risks to 

chloropicrin is the 2007 risk assessment (Leighton and Walls; D314399; 4/20/2007). There is no 

air monitoring data available to determine if chloropicrin vapor is released near treated poles. To 

minimize the escape of the chloropicrin gas from treated poles the 2009 amended RED specified 

instructions to minimize potential bystander exposures. EPA confirmed that the current labels 
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incorporated specific 2009 amended RED statements to minimize the potential for vapors. The 

specifications include the following instructions:

plug the pre-drilled holes immediately after chloropicrin applications;

use a barrier wrap on treated wood, where needed, to confine the vapor;

do not treat drilled holes if they intersect internal rot pockets or splits; and

do not treat structures/beams indoors.

Conclusions: The occupational exposure database is adequate to support the Registration 

Review process for the conventional and antimicrobial uses of chloropicrin. HED and AD do 

not anticipate the need to perform additional or updated occupational exposure assessments 

during Registration Review unless new occupational exposure studies become available or points 

of departure (PODs) or uncertainty factors (UFs) for the occupational exposure assessment.

8.0 Public Health and Pesticide Epidemiology Data

An updated review of chloropicrin incident reports was recently prepared by HED (Recore and 

Evans, D414490, 8/29/2013). For this evaluation, both OPP Incident Data System (IDS) and the

Centers for Disease Control and Prevention/National Institute for Occupational Safety and 

Health (CDC/NIOSH) Sentinel Event Notification System for Occupational Risk-Pesticides 

(SENSOR) databases was consulted for pesticide incident data on the active ingredient 

chloropicrin. Chloropicrin is not included in the Agricultural Health Study (AHS) and therefore 

no information from AHS was included in this report.

The IDS includes reports of alleged human health incidents from various sources, including 

mandatory Federal Insecticide, Fungicide and Rodenticide Act (FIFRA) Section 6 (a) (2) reports 

from registrants, other federal and state health and environmental agencies and individual 

consumers. IDS contain reports from across the U.S. and most incidents have all relevant 

product information recorded. Reports submitted to the IDS represent anecdotal reports or 

allegations only, unless otherwise stated in the report. IDS records incidents resulting in higher

severity outcomes in more detail, in a module called the Main IDS module. This system stores 

incident data for death, major and moderate incidents, and it includes more details about the 

location, date and nature of the incident.

In Aggregate IDS, from January 1, 2008 to February 19, 2013, there were 18 reported incidents 

involving chloropicrin. These incidents were classified as minor severity. For the Main IDS, 

from January 1, 2008 to February 19, 2013, there were 12 incidents reported for the single 

chemical only in the database. One incident was classified as major severity; six incidents were 

classified as moderate severity; four incidents were classified as minor severity; one incident was 

unspecified classification. There were 30 additional incidents reported involving more than one 

chemical.

 

The SENSOR-Pesticides database covers 11 states from 1998-2009, although reporting varies 

from state to state. Cases of pesticide-related illnesses are ascertained from a variety of sources, 

including: reports from local Poison Control Centers, state Department of Labor workers’ 

compensation claims when reported by physicians, reports from State Departments of 

Agriculture, and physician reports to state Departments of Health. Although both occupational 

and non-occupational incidents are included in the database, SENSOR-Pesticides focuses on 

occupational pesticide incidents, and is of particular value in providing that information. The 

state coordinator at the 11 respective state Departments of Health conducts case follow-up 
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activities such as obtaining medical records to verify symptoms and severity. Using standardized 

protocol and case definitions derived from poison center reporting, the state SENSOR-Pesticide 

coordinator enters the incident information into the state-based system which is sent to NIOSH 

annually to be aggregated. 

A query of SENSOR-Pesticides 1998-2009 indentifies 78 cases, stemming from 31 events, 

involving chloropicrin; 10 cases are single active ingredient and 68 are multiple active ingredient 

cases. There was one case fatality; two cases were high in severity; 25 cases were moderate in 

severity; and 50 cases were low in severity.

Based on the number of incidents reported for chloropicrin, the effects noted in the incidents, and 

the recently implemented safety measures put into place in 2012 for all soil fumigant pesticides; 

chloropicrin warrants further incident analysis during registration review. This further analysis 

will include reviewing chloropicrin incident data from other sources as well as cases studies and 

a medical literature search on human health effects of chloropicrin.

9.0 Tolerance Assessment and International Harmonization

There are currently no tolerances for chloropicrin (see Section 3.0 above).

 

10.0 Environmental Justice

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

most recent chloropicrin human-health risk assessment, in accordance with U.S. Executive Order 

12898, “Federal Actions to Address Environmental Justice in Minority Populations and LowIncome Populations,” 

(http://www.hss.energy.gov/nuclearsafety/env/guidance/justice/eo12898.pdf). The 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.

11.0 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 chloropicrin and any other substances. For the purposes of this assessment, therefore, EPA 

has not assumed that chloropicrin has a common mechanism of toxicity with other substances. 

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

existing hazard database. However, as required by FFDCA section 408(p), chloropicrin 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. Chloropicrin 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 chloropicrin. 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/.

13.0 Human Studies

Past chloropicrin risk assessments rely on an intentional dosing human sensory irritation study 

(Cain, 2004; MRID 46443801) as the basis for the acute chloropicrin endpoint. The Human 

Studies Review Board (HSRB) evaluated the ethical conduct and scientific validity of the 

chloropicrin human study at a June 2006 meeting. The HSRB concluded that there was not clear 

and convincing evidence that the conduct of the research was either fundamentally unethical or 

significantly deficient relative to the ethical standards prevailing when the study was conducted. 

The chloropicrin human study also was considered scientifically sound for the purpose of 

estimating a safe level of inhalation exposure to chloropicrin (HSRB Final Report, October 2006; 

http://www.epa.gov/osa/hsrb/files/june2006mtgreportfinal100606). 
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14.0 Risk Assessment Updates and Data Deficiencies

No new data deficiencies outside those previously required through reregistration were identified 

for chloropicrin. 

HED and AD anticipate conducting the following risk assessment updates during Registration 

Review:

Toxicology: None

Residue Chemistry: None

Dietary Exposure: None

Occupational/Residential Exposure:

o HED will be required to perform an ambient air assessment during Registration 

Review once the chloropicrin ambient air study is submitted to the Agency.

15.0 References

Memoranda Relevant to Registration Review.

Author Barcode Date Title

S. Knizner D200326, 

D202185 8/25/94 Chloropicrin. Reregistration Case No. 0040. Chemical No. 081501. MRID #43185602

J. Abbotts None 8/15/96 Chloropicrin (081501), Reregistration Case No. 0040. 

Tolerances and Residue Chemistry Data Requirements. 

T. Leighton and 

C. Walls D314399 4/20/2007

C. Smith and E. 

Reaves D348637 4/30/2009 Chloropicrin: Third Revision of the HED Human Health Risk Assessment. 

J. Dawson, C. 

Smith, and S. 

Shelat

D385314 1/11/2011

Methyl Bromide (PC Code 053201), Chloropicrin (PC 

Code 081501), Dazomet (PC Code 035602), Metam 

Sodium and Potassium (PC Codes 039003 & 039002), 

MITC (PC Code 068103), DP Barcode 385314, Second 

Update To Health Effects Division Recommendations for 

Good Agricultural Practices and Associated Buffer Credits

C. Smith D348650 1/11/2011 Chloropicrin: Addendum to the Third Revision of the HED 

Human Health Risk Assessment.

C. Smith D404798 10/9/2012

The Health Effects Division’s Review of the Chloropicrin 

Manufacturers’ Task Force Request for a Waiver for 2012 

Chloropicrin Ambient Air Monitoring Study (GDCI081501-1155)

A. Dunbar TXR 

0056662 5/22/13

Chloropicrin: Summary of Hazard and Science Policy 

Council (HASPOC) Meeting of May 9, 2013: 

Recommendations on the need for acute and subchronic 

neurotoxicity studies (870.6200).

S. Recore and E. 

Evans D414490 8/29/2013 Chloropicrin: Review of Human Incidents

Attachments: 

Attachment 1: Chemical Identity Table.

Attachment 2: Chloropicrin Acute, Subchronic, and Chronic Toxicity Profile

Attachment 3: Chloropicrin Endpoint Selection Tables.
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Attachment 1: Chemical Identity Table.

Physical and Chemical Properties of Chloropicrin

Parameter Value/Description Reference

Physical State Near colorless, oily liquid

Melting point/range -69.2oC Merck Index

Boiling point/range 112oC at 757 mm H Merck Index

Density 1.7 g/ml at 25oC D268927

Water Solubility Very soluble

Solvent Solubility 70.5 g/mL at 25oC in acetone, ethyl alcohol, hexane, and xylene D268927

Vapor Pressure 23.8 mm Hg at 25oC D268927

Dissociation constant (pKa) Not applicable, nonpolar D268927

Octanol/water partition coefficient Log (KOW) = 2.58 D268927
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Attachment 2: Chloropicrin Acute, Subchronic, and Chronic Toxicity Profile (as of May 

2013)

Chloropicrin Toxicity Profile

Guideline No./Study 

Type

MRID No. 

(year)/Classification/Exposure 

Conditions

Results

Special Human Study:

Odor Threshold, Nose, 

Eye, Throat Irritation

46443801 (2004)

Acceptable/Non-Guideline

3 Phases

Phase 1: 62 subjects (356, 533, 

800, and 1200 ppb) for 1-2 

seconds from a vapor delivery 

devise

Phase 2: 62 subjects (0, 50, 75, 

100, 150 ppb) for 30 minutes in 

a walk-in chamber

Phase 3: 32 subjects (100, 150 

ppb) for 60 mins/day for 4 

consecutive days in a walk-in 

chamber

Phase I:

Registrant Analysis:

median odor threshold: 700 ppb; (M=590 ppb and 

F=810 ppb)

median eye irritation: 900 ppb; (M=790 ppb and 

F=1010 ppb)

No localization of the throat; >1200ppb

HED Analysis:

Odor: 10th percentile 216 ppb; median 406 ppb; 90th

764 ppb

Eye: 10th percentile 37 ppb; median 242 ppb; 90th

1565 ppb

Phase 2: 38% of subjects (8M/8F) detected 

chloropicrin initially at 50 ppb and consistently up to 

150 ppb. Severity of eye irritation not examined. 

NOAEL not determined. Nose and throat irritation not 

as sensitive as in eyes.

Phase 3: NOAEL not established. However, BMCL10

of 73 ppb, based on eye irritation scores of 1.5 during 

the maximal response period of 30-55 minutes. Nasal 

nitric oxide increased and changes in air flow both at 

100 ppb and 150 ppb. Nose and throat irritation less 

sensitive endpoints.

870.1100 

Acute Oral - Rat

05014376 (1976)

Acceptable/Guideline.

LD50 = 37.5 mg/kg

Toxicity Category I

870.1200

Acute Dermal - Rat

05014376 (1976)

Acceptable/Guideline.

LD50 = 100 mg/kg

Toxicity Category I

870.1300

Acute Inhalation - Mouse

45117901 (1999)

Acceptable/Non-Guideline

Head only study, 4 Albino 

Swiss- Webster male mice/grp

exposed to 0.99, 3.20, 4.20, 7.25, 

10.00, 14.50 ppm (analytical 

concen.)or 0.00664, 0.0215, 

0.0282, 0.0486, 0.0671, 0.0973 

mg/L (calculated analytical 

concen.)of gaseous CP for 30 

mins.

No deaths seen at any dose level. Clinical obs. normal 

before and after exposure. Body wt. gains may been 

decreased at HDT only (8% of initial body wt. in 

control and 2% at the HDT).

-The exposure level at 50% RD (RD50) was 2.34 ppm 

with 95% CI of 1.84 to 2.98 ppm or RD50 of 0.016 

mg/L and 95% CI of 0.012 mg/L to 0.020 mg/L.

-0% depression in the respiration rate was plotted by 

the % depression in the respiration rate reported in the 

study versus log exposure level and extrapolating the 

graph to 0% depression. The RD0 respiratory 

depression occurs around 0.0017 to 0.0019 mg/L
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Chloropicrin Toxicity Profile

Guideline No./Study 

Type

MRID No. 

(year)/Classification/Exposure 

Conditions

Results

870.1300

Acute Inhalation - Rat

45117902 (1999)

Acceptable/Non-Guideline

Whole body inhalation study, 5 

Sprague Dawley rats/sex/grp

were exposed to 0, 10.6, 18.0, or 

28.5 ppm (analytical) or 0, 

0.071, 0.121, 0.158 mg/L 

(calculated) of aerosolized CP 

for 4-hrs and held for 2 days 

after exposure. Particle sizes had 

a MMAD from 4.85 ·m to 6.1·m 

with a GDS of 1.4 to 1.6. 

LC50 was 17 ppm (M) and 19 ppm (F).

Death only occurred at 2 top dose levels up to 2 days 

post-exposure. 

Clinical signs: obs noted at all dose levels, labored 

breathing, gasping, decreased activity, nasal 

discharge, salivation, moist rales. Top 2 levels 

produced gasping for last 2 hrs of exposure.

Gross pathology: Liver, adrenal wts, and histological 

findings increased at HDT. Histological findings of 

respiratory tract were seen at all dose levels and 

damage to the lungs, such as congestion, bronchiole 

mucosal edema, necrosis, and cellular infiltrates.

-No NOAEL demonstrated.

LOAEL = 10.6 ppm or 0.071 mg/L (LDT).

870.2400

Primary Eye Irritation -

Rabbit

N/A Reserved

870.2500

Primary Skin Irritation -

Rabbit

05014376 (1976)

Acceptable/Guideline

Corrosive

Toxicity Category I

870.2600

Dermal Sensitization 

N/A Reserved

870.3100

Subchronic Feeding - Rat

Not required by the Agency

870.3100

Subchronic Feeding -

Mice 

Not required by the Agency

870.3100

Subchronic Feeding -

Mice

Not required by the Agency

870.3150

Subchronic Feeding - Dog

Not required by the Agency

870.3200

21-Day Dermal - Rat

Reserved

870.3465

13-Week Inhalation -

Mouse

43063201 (1993)

Acceptable/Guideline 

10 CD-1 mice/sex/concentration 

of 0, 0.3, 1.0, or 3.0 ppm in a 

whole-body chamber, 6 h/day, 5 

days/week for 13 weeks.

NOAEL = 0.3 ppm (0.002 mg/L/day)

LOAEL = 1.0 ppm (0.007 mg/L/day) based on 

decreased body weight and food consumption, 

increased absolute and relative lung weights in both 

sexes, and histopathological lesions of the nasal cavity 

and lungs of females.

870.3465

13-Week Inhalation - Rat

43063201 (1993)

Acceptable/Guideline 

10 CD rats/sex/concentration 0, 

0.3, 1.0, or 3.0 ppm in a wholebody chamber, 6 h/day, 5 

days/week for 13 weeks.

NOAEL = 0.3 ppm (0.002 mg/L/day)

LOAEL = 1.0 ppm (0.007 mg/L/day), based on 

increased lung weights of both sexes, and 

histopathological changes in the nose of females and 

lungs of males and females.
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Chloropicrin Toxicity Profile

Guideline No./Study 

Type

MRID No. 

(year)/Classification/Exposure 

Conditions

Results

870.3700

Inhalation Developmental 

Toxicity - Rat

42740602 (1993)

Acceptable/Guideline

30 mated female Crl:CD 

VAP/Plus rats to 0, 0.4, 1.2, or 

3.5 ppm in a whole-body 

inhalation chamber, 6 h/day on 

GDs 6-15

Maternal NOAEL = 0.4 ppm (0.003 mg/L/day)

Maternal LOAEL = 1.2 ppm (0.008 mg/L/day) based 

on mortality, decreased body weight and food 

consumption, and signs consistent with CP toxicity.

Developmental NOAEL = 1.2 ppm (0.008 mg/L)

Developmental LOAEL= 3.5 ppm (0.024 mg/L), 

based on decreased pup body weights.

870.3700

Inhalation Developmental 

Toxicity - Rabbit

42740601 (1993)

Acceptable/Guideline

20 inseminated female New 

Zealand white rabbits/group to 0, 

0.4, 1.2, or 2.0 ppm in a wholebody inhalation chamber, 6 

h/day, on GDs 7-29

Maternal NOAEL is 0.4 ppm (0.003 mg/L)

Maternal LOAEL is 1.2 ppm (0.008 mg/L), based on 

mortality, body weight loss, and decreased food 

consumption. 

Developmental NOAEL= 0.4 ppm (0.003 mg/L)

Developmental LOAEL= 1.2 ppm (0.008 mg/L), 

based on abortions and decreased fetal weights.

870.3800

Inhalation 2-Generation 

Reproductive Toxicity -

(Main study)

Rat

43391901 (1994)

Acceptable/guideline

26 Crl:CD VAF/Plus 

rats/sex/group to 0, 0.5, 1.0, or 

1.5 ppm in whole body 

inhalation chamber 

Note: Offspring not directly 

exposed until PND 28

Parental systemic NOAEL > 1.5 ppm (0.0101 mg/L)

Parental systemic LOAEL not identified

Offspring NOAEL > 1.5 ppm (0.0101 mg/L)

Offspring LOAEL not identified

Reproductive NOAEL > 1.5 ppm (0.0101 mg/L)

Reproductive LOAEL not identified

870.3800

Range-finding, Inhalation 

2-Generation 

Reproductive Toxicity -

Rat

46427801 (conducted 1992, 

study report 1996)

10 Crl:CD VAF/Plus 

rats/sex/group by whole body 

exposure 0, 0.4, 1.0, or 2.0 ppm 

for 6hrs/day, 7 days/week during 

premating (14 days) and 

gestation day 0-20

No treatment-related mortality, clinical signs, or 

necropsy findings in any parental males or females, 

and no treatment-related effects on reproductive 

parameters. Mean body weight and weight gain 

decreased in high-dose group (1-3% M& 5-6% F) 

beginning at week 1. Maternal body weight was 

decreased 5-8% and decreased 17% during gestation. 

Food consumption decreased 8-14% in males and 

14% in females during premating and 7% during 

gestation. Litter size decreased 33% and uterine 

implantation sites decreased 30% in the high-dose 

group.

870.4100

Chronic Feeding 

Toxicity-Rat

43744301 (1995)

Acceptable/guideline

30 Sprague-Dawley Crl: CD®

BR, VAF/Plus rats/sex/dose by 

gavage in corn oil at dose levels 

at 0, 0.1, 1.0, or 10 mg/kg/day 

for 104 weeks

Only clinical toxicity observed was salivation after 

dosing in high-dose male and female rats. Doserelated increase in incidence of subcutaneous masses 

of skin of females related to the increased incidence of 

mammary fibroadenomas. Hyper- keratosis and 

hyperplasia of the nonglandular stomach in both 

sexes. Females had dose-related increase in incidence 

of fibroadenoma of the mammary gland at high-dose. 

Increased rate of C- cell hyperplasia of the thyroid in 

high-dose females.

NOAEL = 0.1 mg/kg/day [F]

NOAEL = 1.0 mg/kg/day [M]

LOAEL = 1.0 mg/kg/day [F], based on periportal 

hepatocyte vacuolation and thyroid C-cell hyperplasia 

and stomach lesions at the high-dose.

LOAEL = 10 mg/kg/day [M], basedon on stomach 

lesions.
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Chloropicrin Toxicity Profile

Guideline No./Study 

Type

MRID No. 

(year)/Classification/Exposure 

Conditions

Results

870.4100

Chronic Feeding Toxicity 

- Dog

43196301(1994)

Acceptable/guideline

4 beagle dogs/sex/dose in corn 

oil by gelatin capsule to 0, 0.1, 

1.0, or 5.0 mg/kg/day for one 

year

NOAEL [M] = 0.1 mg/kg/day

NOAEL [F] = 1.0 mg/kg/day

LOAEL [M] = 1.0 mg/kg/day, based on 

gastrointestinal irritation (vomiting and diarrhea), and 

blood chemistry alterations, 

LOAEL [F] = 5.0 mg/kg/day, based on 

gastrointestinal irritation (vomiting and diarrhea), 

microcytic hypochromatic anemia, and blood 

chemistry alterations.

870.4200

Carcinogenicity 

Inhalation - Mouse (78 

weeks) 

43632201 (1997)

Acceptable/guideline

50 CD-1

®

mice/sex/concentration by 

dynamic whole body at 0, 0.1, 

0.5, or 1.0 ppm for 6hrs/day, 5 

days/week for 78 weeks

NOAEL = 0.1 ppm (0.0007 mg/L)

LOAEL = 0.5 ppm (0.0034 mg/L), based on systemic 

toxicity and irritation, based on decreased body 

weights and gains, increased lung weights, and 

histological changes in the nasal cavity, upper 

respiratory tract and lungs.

No significant treatment-related increase in tumors.

870.4200

Carcinogenicity/gavageMouse/Rat [bioassay]

05014915 (1978)

supplemental

Rats: [M]: 0, 25 or 26 mg/kg/day

[F]: 0, 20, or 22 mg/kg/day

Mice [M]: 0, 66 mg/kg/day

[F]: 0, 33 mg/kg/day

High-incidence of early death in CP dosed rats. No 

neoplasm observed at higher incidences in dosed rats 

from controls. Rapid decrease in survival after first 

year in both sexes of mice.

Proliferative lesions of squamous epithelium of the 

forestomach of mice included two carcinomas and a 

papilloma. Statistical analysis did not demonstrate 

related to CP. Bioassay of CP did not permit 

evaluation of carcinogenicity due to short survival 

time of mice and rats.

870.4300

Chronic Inhalation 

Toxicity/CarcinogenicityRat. (2 year)

43755301 (1995)

Acceptable/guideline

50 Sprague-Dawley CD 

rats/sex/concentration 0, 0.1, 0.5, 

or 1.0 ppm in a whole body 

inhalation chamber for 6 hrs/day, 

5days/week for up to 108 weeks

NOAEL =0.1 ppm (0.0007 mg/L)

LOAEL = 0.5 ppm (0.0034 mg/L), based on increased 

mortality rate and decreased mean survival time in 

males, and transiently decreased body weight gains in 

both sexes.

Port of entry NOAEL = 0.5 ppm

Port of entry LOAEL = 1.0 ppm (males), based on 

severe rhinitis of the anterior nasal cavity.

870.5100

Bacterial Reverse 

Mutation Test (Ames 

Assay)

41960801 (1990)

Acceptable/guideline

10-3333 μg/plate +/-S9 (2 

independent trials)

Positive: S9-activated CP is mutagenic in Salmonella 

typhimurium strains TA98, and TA100.

870.5300

Mutagenic-Lymphoma 

Mutation-Mouse

41960803 (1990)

Acceptable/guideline

0.038-0.75 nL/mL –S9

0.89-16.0 nL/mL +s9

Negative: CP ranging from 0.038 to 0.75 nL/mL-S9 

and 0.89 to 16 nL/mL +S9 did not induce a mutagenic 

response in two independently performed mouse 

lymphoma forward mutation assays up to cytotoxic 

concentrations.

870.5375

In Vitro Chromosomal 

Aberration in Chinese 

Hamster V79 Cells

41960802 (1990)

Acceptable/guideline

0.75 to 1 nL/mL –S9

4-6 nL/mL +S9 

Positive: Nonactivated doses of CP from 0.75 to 1 

nL/mL induced a reproducible and significant 

clastogenic response in CH V79 cells harvested 12 

hours post-treatment. S9-activated CP was negative.

Nonactivated CP was clastogenic over a narrow range 

of cytotoxic concentrations. CP in the absence of S9 

activation is a clastogen in this mammalian test 

system.

870.5395

Mammalian Erythrocyte 

Micronucleus TestMouse

48067601 (2010)

Acceptable/guideline

0, 62.5, 125 and 250 mg/kg(oral 

gavage); cell harvest at 24 

Negative up to an overtly toxic dose (250 mg/kg).
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Chloropicrin Toxicity Profile

Guideline No./Study 

Type

MRID No. 

(year)/Classification/Exposure 

Conditions

Results

and/or 48 hours post dosing 

870.5550

Unscheduled DNA 

Synthesis in mammalian 

cells in culture-Rat

hepatocytes

41960804 (1990)

Acceptable/guideline

0.3 to 6 nL/mL

Negative: CP was not genotoxic in primary rat 

hepatocytes over a concentration range (0.3 to 6 

nL/mL) that included moderately cytotoxic levels. 

No Guideline

In vivo Unscheduled 

DNA Synthesis-Rat

hepatocytes

48067501 (2010)

Acceptable

0, 85 sand 250 mg/kg (oral 

gavage); cell harvest at 2 & 14 

hours postdosing

Negative up to an overtly toxic dose (250 mg/kg).

870.6200

Inhalation Acute 

Neurotoxicity - Rats

Not required by the Agency1

870.6200

Feeding Subchronic 

Neurotoxicity - Rats

Not required by the Agency1

870.7485

Metabolism – Rat\

Not available

870.7600

Dermal Penetration - Rat

Not required by the Agency

870.7800

Immunotoxicity

Not required by the Agency2

1 HED’s Hazard and Science Policy Council (HASPOC) has determined that a neurotoxicity battery is not required 

for chloropicrin (Dunbar; 5/22/13; TXR 0056662).

2 The 2009 Amended RED required an Immunotoxicity study for chloropicrin but this requirement was subsequently 

waived (Reaves; D382316; 4/27/2011).
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Attachment 3: Chloropicrin Endpoints from 2009 Risk Assessment

Summary of Toxicological Dose and Endpoints for Use in Chloropicrin Human Health 

Inhalation Risk Assessment

Risk Assessment Study NOAEL/LOAEL Endpoint HED HC or HEC

Acute 

Inhalation

NonoccupationalHuman Irritation 

Study

BMCL10= 73 ppb

LOAEL = 100 ppb

Eye irritation, ↑ nasal 

nitric oxide & change in 

air flow 

HC = 73 ppb

UF = 1

Occupational Human Irritation 

Study

BMCL10= 73 ppb

LOAEL = 100 ppb

Eye irritation, ↑ nasal 

nitric oxide & change in 

air flow

HC = 73 ppb

UF = 1

Short- and 

IntermediateTerm 

Inhalation 

(1-6 months)

Nonoccupational13-Week 

Inhalation Study 

in Mice

NOAEL = 0.3 ppm

LOAEL = 1.0 ppm

Nasal and lung damage, 

increased lung weights

HEC = 0.008 ppm

UF = 30

Occupational 13-Week 

Inhalation Study 

in Mice

NOAEL = 0.3 ppm

LOAEL = 1.0 ppm

Nasal and lung damage, 

increased lung weights

HEC = 0.035 ppm

UF = 30

Long-term 

Inhalation

(> 6 months)

Nonoccupational78-Week Cancer 

Study in Mice

NOAEL = 0.1 ppm

LOAEL = 0.5 ppm

Nasal discharge, nasal and 

lung damage, increased 

lung weights, body weight 

loss

HEC = 0.004 ppm

UF = 30

Occupational 78-Week Cancer 

Study in Mice

NOAEL = 0.1 ppm

LOAEL = 0.5 ppm

Nasal discharge, nasal and 

lung damage, increased 

lung weights, body weight 

loss

HEC = 0.015 ppm

UF = 30

Cancer Chloropicrin is currently not considered a carcinogen.