UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

MEMORANDUM 

DATE: 9/9/2015 

OFFICE OF CHEMICAL SAFETY 

AND POLLUTION PREVENTION 

SUBJECT: Acrolein: Human Health Assessment Scoping Document in Support of Registration 

Review 

PC Code: 000701 DP Barcode: 427578 

MRID No.: Not Applicable 

Petition No.: Not Applicable 

Assessment Type: Single Chemical 

TXR No.: Not Applicable 

Registration No.: 10707-9, 10707-10, 71173-1 

Regulatory Action: Registration Review Scoping 

Case No.: 2005 

CAS No.: 107-02-8 

MRID No.: Not Applicable 40 CFR: Not Applicable 

FROM: 

THROUGH: 

r;,1 

TO: 

Wade Britton, MPH, Risk & ORE Assessor 

Austin Wray, Ph.D., Toxicologis ' 

Thurston Morton, Chemist 

Risk Assessment Branch IV ( BIV)' 

Health Effects Division (HED, 7509P) 

Risk 

Nathan 

Assessment 

Mottl, Biologist 

and Science 

/./~ Support Branch ~ (RASSB) 

Antimicrobial Division (AD, 751 OP) 

Charles W. Smith III, Acting Branch Chief .__."-----__.....,. 

RABIV/ HED(7509P) ~~,/~ 

Laura Parsons, Associate Branch Chief ~(,IVG 

RASSB/ AD (7510P) 

Kelly Ballard, Chemical Review Manager 

Risk Management and Implementation Branch V 

Pesticide Re-evaluation Division (7508P) 

Attached is AD's and HED's human health scoping document for acrolein to support 

Registration Review. 

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Page 2 of 23

Executive Summary

The AD and HED acrolein Registration Review teams have evaluated the scientific database for 

the pesticide acrolein [2-Propenal] to determine the scope of the work necessary to support the 

existing registrations. Acrolein has two pesticidal use patterns: 1) as an herbicide for control of 

vegetation in agricultural irrigation canals and, in some states, irrigation reservoirs and 2) as a 

bacteriocide in injection systems associated with petroleum production. Although the

bacteriocidal and herbicidal use patterns are assessed separately by AD and HED, respectively, 

this Registration Review document addresses both.

Currently, there are nine total active registrations of acrolein: one Section 3 registration (EPA 

Reg. No. 10707-9, Magnacide H Herbicide, 95% active ingredient) and six Special Local Needs 

(SLN) registrations (EPA Reg. Nos. CA780039, ID900005, NE030003, OR910018, UT030001, 

WA040017) for acrolein used as aquatic herbicide; and two Section 3 registrations as a 

bacteriocide (EPA Reg. No. 10707-10, Magnacide B Microbicide, 95% active ingredient; EPA 

Reg. No. 71173-1, AcroCideTM, 96% active ingredient). All products are packaged as liquids and 

stored under an inert gas blanket. There are currently no pending PRIA actions for acrolein. 

As an aquatic herbicide, acrolein is injected directly below the surface of moving water for 

control of submerged aquatic weeds and algae in irrigation canals and, in some states, irrigation 

reservoirs. It is used in oilfield water systems to reduce sulfate reducing bacteria that produces 

corrosive hydrogen sulfide in oilfield water systems including: hydraulic fracking fluids; oilfield 

water injection wells; water systems; water floods; oil production systems; and water disposal 

systems. Applications are conducted by pumping acrolein from pressurized containers into 

closed injection well piping systems. All acrolein products are applied through a closed system. 

AD and HED have evaluated the status of the human health risk assessments for acrolein to 

determine whether sufficient data are available, and whether any updates are required to support 

Registration Review. Further, all available data and human health risk assessments for acrolein 

with respect to its toxicity, exposure, and usage databases, as well as the most updated agency 

science policy and risk assessment methodologies to determine the scope of the work necessary

to support Registration Review have been considered. 

The most recent human health risk assessment was conducted for purpose of issuance of the 

reregistration eligibility document (RED) for acrolein in 20081

. The risk assessment was 

inclusive of both the bacteriocidal and herbicidal uses patterns

The acrolein toxicity database is adequate to conduct Registration Review for registered uses. 

The Hazard and Science Policy Council (HASPOC) waived the requirement for the neurotoxicity 

battery and immunotoxicity study and no other studies are required at this time2. Ocular, 

respiratory, stomach, and dermal tissues at the portal of entry are the primary targets of acrolein 

 1 B. Daiss. Acrolein HED Risk Assessment for Registration Eligibility Decision (RED) Document. 3/25/2008. 

D348777. 

2 U. Habiba. Acrolein: Summary of Hazard and Science Policy (HASPOC) Meeting of July 9, 2015: 

Recommendations on the Need for the Neurotoxicity Battery (Acute and Subchronic) and Immunotoxicity Study. 

7/9/2015. TXR #xxxxxx)
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toxicity and dictate endpoint selection. Co-critical endpoints for eye, nose, and throat irritation,

and decreased respiratory rate from a human health inhalation study were used to select points of 

departure for short-term occupational and residential bystander inhalation exposure. These are 

the only potential exposure scenarios that have previously been assessed based on the current use 

patterns. 

The residue chemistry database for acrolein is inadequate to support current Registration Review

data requirements. HED previously required an additional nature of the residue study in root and 

tuber as part of the RED. While HED reviewed a protocol for this study in 2011; the study has 

not been submitted to date. The need for additional residue chemistry data and tolerances will be 

evaluated when this study is submitted and reviewed. The acrolein RED also stated if the 

reservoir SLNs were supported that an enforcement method would be required however a 

method has not been submitted at this point in time. The need for tolerances in/on fish and 

shellfish will also be evaluated if the registrant continues to support the SLN use in reservoirs.

The dietary exposure database is adequate to support current registration requirements. A dietary 

risk assessment was not previously conducted for either the bactericidal or herbicidal uses of 

acrolein. Risks from drinking water exposures were not previously assessed because the 

Environmental Fate and Effects Division (EFED) did not establish estimated drinking water 

concentrations (EDWCs) for use in risk assessment. However, based on EFED’s problem 

formulation document in support of Registration Review, there is the potential for acrolein in 

irrigation water to leach into groundwater and, as a result, EFED may conduct a drinking water 

assessment if deemed necessary following further consideration of the available groundwater 

monitoring data. If a dietary assessment is required, the toxicity database will need to be 

reassessed for the establishment of dietary endpoints. 

In the 2008 human health risk assessment, a dietary cancer assessment was conducted in 

consideration of the Indigenous Peoples of the western region of the US who rely heavily on 

subsistence diets as their food source. The dietary cancer assessment considered exposures of 

subsistence fishermen to glycidol, a metabolite of acrolein in fish. The resulting dietary cancer 

risk estimate of 1.2 x 10-6 was calculated.

There are no proposed or current registrations for products containing acrolein that allow 

residential use. Therefore, residential handler and post-application exposure assessments will 

not be needed during Registration Review. Residential bystander exposures resulting from spray 

drift are not anticipated for acrolein since all applications are required to be conducted by means 

of closed systems. However, residential bystander exposures resulting from volatilization may 

occur as supported by air monitoring data collected for the herbicidal use. During Registration 

Review, the agency will consider all available air monitoring data and determine whether there is 

the need for a volatilization risk assessment for acrolein. Residential exposures from swimming 

in acrolein treated irrigation canals are not expected. Per label changes required by the acrolein 

RED, the current Magnacide H label states that acrolein can only be applied in canals/reservoirs 

with posted no swimming signs. 

A quantitative or qualitative aggregate assessment was not previously required for acrolein since 

there were no anticipated dietary (food or drinking water) exposure to residues of acrolein, and 
Page 4 of 23

there are no residential uses of the chemical. Further, the metabolite of acrolein, glycidol, only 

forms in fish and depurates quickly. Although a dietary cancer assessment was conducted for 

glycidol from exposures to subsistence fishermen, exposures to glycidol via drinking water, 

inhalation, and dermal pathways are not expected. Therefore, a quantitative aggregate assessment 

was not required. An aggregate assessment may be necessary if EDWCs are deemed necessary by 

EFED, or to reflect the most recent dietary exposure policies.

Occupational handler exposures were assessed in the most recent occupational risk assessments 

conducted by AD and HED in 2008. All acrolein products are applied through a closed 

application system and, therefore, dermal exposures are not anticipated. The principal

registrants, Baker Petrolite and Multi-Chem, both have comprehensive training programs to 

ensure that applicators are competent in the application, handling, and storage procedures 

required for the bacteriocidal and herbicidal uses. Further, stringent personal protective 

equipment are required throughout all application activities. With use of the label required 

inhalation PPE, an organic vapor respirator, inhalation handler risks are not of concern. 

Occupational post-application exposures to acrolein may also occur depending on the length of 

time the worker remains in the area following completion of the application and equipment 

disassembly. For the herbicidal use, depending on the extent to which workers remain in the 

vicinity of the treated canal after acrolein has been applied and that the requirement for use of a 

respirator is no longer applicable, worker post-application inhalation exposures to acrolein 

vapors may potentially exceed HED’s level of concern. Occupational post-application exposures 

could also occur from the bacteriocidal use. Acrolein vapors could potentially result from 

underground flow back water draining out of the well into water holding ponds after fracking. 

During registration review, post-application air monitoring data are needed for the antimicrobial 

oil well use pattern. 

An updated occupational exposure assessment may be required during Registration Review to 

incorporate any additional air monitoring data of acrolein following the 2008 risk assessments to 

determine if the PPE required during set up and breakdown of application equipment are 

adequately protective of potential inhalation exposures, and to determine what impact these data 

have on inhalation risks for applicators present between set up and break down of application 

equipment, as well as for the post-application workers remaining in the vicinity of treated canals. 

1.0 Introduction

Acrolein is an herbicide used for control of vegetation in agricultural irrigation canals and in 

some states, irrigation reservoirs, and as a bacteriocide in injection systems associated with 

petroleum production. There are currently nine total active registrations of acrolein: one Section 

3 registration (EPA Reg. No. 10707-9, Magnacide H Herbicide) and six Special Local Needs 

(SLN) registrations for acrolein used as aquatic herbicide; and two Section 3 registrations as a 

bacteriocide (EPA Reg. No. 10707-10, Magnacide B Microbicide; EPA Reg. No. 71173-1, 

AcroCideTM, 96% active ingredient). The most recent risk assessments were conducted by AD 

and HED for purpose of issuance of the RED for acrolein in 2008. The RED was inclusive of 

both the herbicidal and microbiocidal use patterns. There are currently no pending PRIA actions

for acrolein.
Page 5 of 23

2.0 Hazard Characterization/Assessment

The acute, sub-chronic, and chronic toxicity profile tables for acrolein are included in 

Attachment 2. Few guideline studies were available to select endpoints for risk assessment; 

therefore, non-guideline studies from a 2005 review of acrolein toxicity by Agency for Toxic 

Substances and Disease Registry (ATSDR) were used to address the gaps in the toxicity 

database. 

Acrolein induces toxicity in exposed organisms through formation of irreversible adducts with 

macromolecules. It is acutely toxic after exposure via dermal, inhalation, or oral route and is a 

strong dermal and eye irritant (all Category I). Sub-chronic and chronic toxicity manifests 

initially in tissues at the portal of entry. Eye, throat, and nasal irritation, and depressed 

respiratory rate were common symptoms of acrolein toxicity in humans after inhalation 

exposure. Similarly, ocular and respiratory tissue damage (discharge, squamous metaplasia of 

trachea, necrosis and hemorrhage of lungs, pulmonary edema) were characteristic of inhalation 

exposure at higher doses in rodents and non-rodents. Oral exposure in rodents and non-rodents 

induced epithelial hyperplasia and lesions in the stomach. Skin irritation was the primary 

adverse effect following dermal exposure. Changes in body weight, body weight gain, and 

serum chemistry were secondary to, or concurrent with, damage in the stomach and respiratory 

tissues. Acrolein exposure to pregnant rodents disrupted fetal skeletal development and led to 

reduced fetal weight at doses engendering maternal toxicity. No reproductive effects were 

observed. No obvious or egregious instances of neurotoxic and immunotoxic effects were 

reported in the database to indicate increased sensitivity in the immune or nervous system. 

Equivocal results from the guideline and literature studies preclude definitive characterization of 

acrolein mutagenicity and its carcinogenicity potential. As a result, the International Agency for 

Research on Cancer (IARC) and EPA concluded the database is not adequate to classify the 

carcinogenicity of acrolein. Despite ambiguous results in the database, HED does not believe 

cancer studies are required for reregistration based on registered use patterns, anticipated 

exposure levels, and available data which does not indicate carcinogenicity. However, glycidol, 

a metabolite of acrolein, is considered a probable human carcinogen to humans by the IARC. 

Previously, toxicity endpoints, points of departure (PODs), and uncertainty/safety factors, were 

selected for inhalation exposure pathways only. These same values will be used for the 

Registration Review and are presented in Attachment 3. The Environmental Fate and Effects 

Division (EFED) is currently reviewing the available monitoring data to determine if leaching of 

contaminated irrigation water into groundwater poses a drinking water risk for humans. Pending 

the EFED recommendation, the toxicity database may need to be reassessed and new endpoints 

established for dietary exposure.

Conclusions: The toxicity database is adequate to assess risk for the registered uses of acrolein.

The following studies are required for acrolein in accordance with current toxicology data 

requirements (40 CFR 158.500): acute neurotoxicity study (870.6200), sub-chronic neurotoxicity 

study (870.6200), and immunotoxicity study (870.7800). HASPOC waived the requirement for 

these studies based on the following considerations: 1) its known corrosive mode of action in 
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portal of entry tissues at doses lower than those required to elicit systemic toxicity, 2) a lack of 

evidence in guideline and literature studies for biologically significant neurotoxic and 

immunotoxic effects at doses lower than the current human inhalation points of departure, 3) and 

the abundance of resources available for assessing dietary exposure that can be used in lieu of an 

oral guideline study, if necessary. No new data is required for this assessment and we do not 

anticipate modifying the PODs and endpoints from previous risk assessments unless a dietary 

assessment is required.

3.0 Residue Chemistry

The following paragraphs are a summary of the residue chemistry database. 

Nature/Magnitude of the Residue - Crops: 14C-Acrolein was applied to lettuce leaves in four 

applications, each at a rate of 0.1 lb. a.i./acre. Acrolein is readily incorporated into natural 

products in lettuce. The only residue of concern is acrolein on the day of application. Previous 

to the acrolein RED, two additional plant metabolism studies were required to demonstrate that 

the metabolism observed in lettuce is typical of general metabolism of acrolein in plants. 

However, in support of the RED, HED determined only one additional study on a root and tuber 

crop (preferably radish) was required (T. Morton, D334663, 9/27/2007) and subject to Data CallIn (DCI). This study should reflect furrow irrigation. If this outstanding study demonstrates 

metabolism consistent with the lettuce metabolism then no tolerances or additional data will be 

required. However, if metabolism is not consistent an enforcement analytical method will be 

required along with magnitude of the residue in irrigated crops.

A protocol was reviewed in 2011 for a radish nature of the residue study. HED reiterated that all 

residues over 0.01 ppm total radioactive residue (TRR) or 10% of the TRR should be 

identified/characterized. Exhaustive attempts should be taken to identify >70% of the TRR 

including but not limited to acid hydrolysis, base hydrolysis, and enzyme extraction. 

Nature/Magnitude of the Residue - Ruminants: Baker Performance Chemicals Inc. submitted 

data depicting the metabolism of [14C]acrolein in lactating goats. The qualitative nature of the 

residue in ruminants is adequately understood. The TRR, expressed as [

14C]acrolein equivalents, 

were 1.67-9.41 ppm in milk, 9.14 ppm in liver, 1.71 ppm in kidney, 0.36 ppm in muscle, and 

0.16 ppm in fat of a lactating goat orally dosed with [14C]acrolein at 8.7 ppm (based on water 

consumption) for five consecutive days. Radioactive residues peaked on day 4 in milk. Acrolein 

was not found in any tissue sample.

Analytical Enforcement Methods: Currently there are no established tolerances for acrolein 

residues. Therefore, no enforcement method has been submitted. The acrolein RED stated if the 

SLN use of acrolein in reservoirs were supported, as is the case currently for California, Oregon, 

and Utah, an enforcement method is required. These data are outstanding since the reservoir use

continues to be supported. 

Conclusions: The need for additional residue chemistry data will be evaluated once the root and 

tuber nature of the residue study is submitted. The need for tolerances in crops will be 

reevaluated once the nature of the residue study in a root and tuber crop is submitted. In 
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addition, the need for tolerances in/on fish and shellfish will be evaluated if the registrant 

continues to support the SLN use in reservoirs. 

4.0 Dietary Exposure

An acute and chronic dietary risk assessment of acrolein was not previously conducted as dietary 

exposures to acrolein are not expected based on the use pattern, available data on metabolism, 

and post-irrigation reentry intervals. Acrolein is not applied directly to any crops; however, 

water from the irrigation canal systems may be used on cropland immediately after application of 

the herbicide. A specific holding time is required before irrigation water can be discharged into 

natural water systems. The antimicrobial use pattern of oil and gas is not expected to result in 

exposure to drinking water. Risks from drinking water exposures were not previously assessed 

because OPP’s EFED did not establish quantitative estimated EDWCs for use in risk assessment. 

However, based on EFED’s problem formulation document in support of Registration Review, 

there is the potential for acrolein in irrigation water to leach into groundwater and, as a result, 

EFED may conduct a drinking water assessment if deemed necessary following further 

consideration of the available groundwater monitoring data. 

The Indigenous Peoples of the western region of the U.S. rely heavily on subsistence diets as 

their food source. In the 2008 human health risk assessment, a cancer assessment of dietary 

exposure of subsistence fishermen in irrigation districts of the western United States was 

conducted for glycidol, a metabolite of acrolein. The assessment was based on data provided by 

EFED on acrolein concentrations in fishable waters and data from EPA on the location and 

fishing habits of tribes living in areas proximate to treated canals. HED used the mean 

subsistence fish intake amounts, glycidol radioactive residues from the nature of the residue 

study in fish, the number of times acrolein would be used per year, and the glycidol Q1* to 

determine the exposure and risk from the use of acrolein to Native American subsistence 

fishermen. The resulting risk estimate was 2.4 x 10-6

. An average LC50 of 0.34 ppb was 

calculated from a range of LC50s for edible fish. When this average LC50 was used, a dietary

risk estimate of 1.2 x 10-6 was calculated.

Conclusions: The dietary exposure database is adequate to support current registration 

requirements. As a part of Registration Review, dietary endpoints may need to be selected, a 

non-cancer dietary exposure assessment may be required, and a revised cancer dietary 

assessment for subsistence fisherman may also be required if EDWCs are deemed necessary by 

EFED. 

5.0 Residential Exposure

There are no proposed or current registrations for products containing acrolein that allow 

residential use. Therefore, residential handler and post-application exposure assessments will 

not be needed during Registration Review. Residential exposures from swimming in acrolein 

treated irrigation canals are not expected. Per label changes required by the acrolein RED, the 

current Magnacide H label states that acrolein can only be applied in canals/reservoirs with 

posted no swimming signs. 
Page 8 of 23

Spray Drift and Volatilization: Residential bystander exposures resulting from spray drift are not 

anticipated for acrolein since all applications are required through means of closed systems. 

Applications of the herbicide use are metered via closed system into irrigation canals and 

reservoirs, and the bacteriocide application is pumps acrolein from pressurized containers into 

closed injection well piping systems. Residential bystander exposures resulting from 

volatilization may occur as supported by air monitoring data collected by the California Air 

Resources Board (CARB) and industrial hygiene monitoring data submitted by the registrant, 

Baker Petrolite. During Registration Review, the agency will consider all available air 

monitoring data and determine whether there is the need volatilization risk assessment for 

acrolein.

Conclusions: There are no proposed or current registrations for products containing acrolein that 

allow residential use and, therefore, a residential exposure assessment will not be needed during 

Registration Review. Bystander exposures from spray drift are not anticipated from acrolein use 

and will not be examined during Registration Review. The need for a volatilization risk 

assessment for acrolein will be examined during Registration Review.

6.0 Aggregate Risk Assessment

A quantitative or qualitative non-cancer aggregate assessment was not previously required for 

acrolein since there were no anticipated dietary (food or drinking water) exposures to residues of 

acrolein, and there are no residential uses of the chemical. Further, the metabolite of acrolein, 

glycidol, only forms in fish and depurates quickly. Although a dietary cancer assessment was 

previously conducted for glycidol from exposures to subsistence fishermen, exposures to glycidol 

via drinking water, inhalation, and dermal pathways are not expected.

Conclusions: As a part of Registration Review, a non-cancer aggregate assessment may be 

required if EDWCs are deemed necessary by EFED. 

7.0 Occupational Exposure

Acrolein has two pesticidal use patterns that could result in the potential for occupational 

exposures: 1) as an herbicide for control of vegetation in agricultural irrigation canals and, in 

some states, irrigation reservoirs and 2) as a bacteriocide used in injection systems associated 

with petroleum production. The assessment of occupational risks from these use patterns are 

considered by HED an AD, respectively. The most recent qualitative occupational risks 

assessments for these use patterns were conducted to support the 2008 acrolein RED. 

Occupational exposures are expected from the herbicidal use of acrolein in irrigation canals and, 

in some states, reservoirs. The application of acrolein is required by means of a closed 

application system and, as a result, dermal exposure is not anticipated. Further, comprehensive 

training programs are required by both of the principal registrants, Baker Petrolite and MultiChem, and stringent personal protective equipment (PPE) are required (i.e., full face air 

purifying respirator, chemical resistant gloves made of butyl rubber) throughout all application 

activities. With use of the label required inhalation PPE, full face air purifying respirator, the 

estimated MOEs are ≥ 30 and, therefore, are not of concern. Post-application exposures to 
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acrolein from the herbicidal use may also occur depending on the length of time the worker 

remains in the area following completion of the application and equipment 

disassembly. Therefore, depending on the extent to which workers remain in the vicinity of the 

treated canal after acrolein has been applied and that the requirement for use of a respirator is no 

longer applicable, MOEs for worker post-application exposure may potentially exceed HED’s 

level of concern.

Occupational exposures are also expected from the bacteriocide use of acrolein in oilfield water 

systems to reduce sulfate reducing bacteria that produces corrosive hydrogen sulfide in oilfield 

water systems. The products are applied by pumping acrolein from pressurized containers into 

closed injection well piping systems. The current product labeling requires closed delivery and 

loading systems with cylinders or skids that utilize dry coupling and metering pumps by certified 

applicators wearing appropriate PPE (i.e., organic vapor respirator, long pants and long-sleeved 

shirt, chemical resistant gloves made of butyl rubber, and shoes and socks) in case of leaks 

during setup. Assuming certified applicators follow the proper label precautions for PPE and 

engineering controls specified in the RED and the guidance from the comprehensive training 

program, the agency expects that occupational handler exposures to the oil field uses will be 

negligible.

Although acrolein bacteriocide applications are conducted using closed systems, occupational 

bystander post-application exposure to acrolein vapors could potentially occur from underground 

flowback water draining out of the well into water holding ponds after fracking. Most of the 

flowback water used is pumped into storage tanks and later injected deep underground, recycled,

or transported to a wastewater treatment facility. However, some of the flowback water can be 

found in water holding ponds. There could be potential concern from acrolein vapors from 

flowback water based on the inhalation toxicity and the high vapor pressure of acrolein (220 mm 

Hg at 20o C). Accordingly, post-application air monitoring data are need for the oil well use

pattern.

Conclusions: An updated occupational exposure assessment may be required during Registration 

Review to incorporate any additional air monitoring data of acrolein following the 2008 risk 

assessments to determine if the PPE required during set up and breakdown of application 

equipment are adequately protective of potential inhalation exposures, and to determine what 

impact these data have on inhalation risks for applicators present between set up and break down 

of application equipment, as well as for the post-application workers remaining in the vicinity of 

treated canals and the vicinity of oil/gas wells. During registration review, post-application air 

monitoring data are needed for the antimicrobial oil well use pattern.

8.0 Public Health and Pesticide Epidemiology Data

The agency has reviewed the available incident data for acrolein3 and concludes that based on 

the low frequency and low severity of cases involving acrolein reported in both the Incident Data 

System (IDS) and Sentinel Event Notification System for Occupational Risk (SENSOR)-

Pesticides, there does not appear to be a concern at this time that would warrant further 

investigation. The agency will continue to monitor the incident information and if a concern is 

 3 S. Recore and E. Evans. Acrolein: Tier I Review of Human Incidents and Epidemiology. 6/30/2015. D427918.
Page 10 of 23

triggered, additional analysis will be included in the risk assessment.

9.0 Tolerance Assessment and International Harmonization

There are no US/Codex/Canadian MRLs established on Acrolein.

10.0 Environmental Justice

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

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

12898, “Federal Actions to Address Environmental Justice in Minority Populations and LowIncome Populations4

.” 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.

The 2008 human health risk assessment included an assessment of dietary exposure of 

subsistence fishermen to glycidol, a metabolite of acrolein in fish. This assessment was based on 

data on acrolein concentrations in fishable waters and the location and fishing habits of tribes 

living in areas proximate to treated canals. 

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 for 

acrolein and any other substance; and acrolein does not appear to produce a toxic metabolite 

produced by other substances. For the purposes of this tolerance action, therefore, EPA has 

assumed that acrolein does not have 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/.

12.0 Human Studies

Past acrolein risk assessments 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. One 

such study (listed below) was determined to require a review of its ethical conduct and was

subject to review by the Human Studies Review Board (HSRB). The HSRB reviewed the study 

at a June 2007 meeting and determined it to be ethically acceptable and sufficiently sound from a 

scientific perspective to be used to estimate a safe level of acute inhalation exposure to acrolein5. 

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

5 http://epa.gov/osainter/hsrb/files/meeting-materials/jun-27-29-2007-public-meeting/june2007hsrbfinal121807.pdf
Page 11 of 23

MRID 46769601: Weber Tschopp, T. Fischer, R. Gierer and E. Grandjean (1977) 

Experimentally Induced Irritating Effects of Acrolein on Man. Int. Arch. Occup. Environ. 

Hlth. 1977 (40): 117-130 Institute for Hygiene and Occupational Physiologe, Swill Federal 

Engineering College, Zurich.

Many other 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 Agricultural Reentry Task Force 

(ARTF) Database. 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 

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.

13.0 Risk Assessment Updates and Data Deficiencies

No data deficiencies were identified for acrolein. EPA notes the following risk assessment 

updates will need to be completed during Registration Review:

o Toxicology: 

o No new data is required for acrolein and we do not anticipate modifying the PODs 

and endpoints from the previous risk assessment unless a dietary assessment is 

required based on EFED analysis of available groundwater data.

o Residue Chemistry/Dietary Exposure: 

o The need for additional residue chemistry data and potential tolerances in crops 

will be evaluated once the previously reuired root and tuber nature of the residue 

study is submitted. 

o The need for an enforcement method and tolerances in/on fish and shellfish will 

be evaluated if the registrant continues to support the SLN use in reservoirs. 

o A revised dietary exposure assessment may be required if EDWCs are deemed 

necessary by EFED, or to reflect the most recent dietary exposure policies. 

o Occupational/Residential Exposure: 

o Updated occupational exposure assessments may be required to incorporate any 

additional air monitoring data of acrolein following the 2008 risk assessments to 

determine if the PPE required during set up and breakdown of application 

equipment are adequately protective of potential inhalation exposures, and to 

determine what impact these data have on inhalation risks for applicators present 

between set up and break down of application equipment and the post-application 

workers remaining in the vicinity of treated canals. 

o The need for a volatilization risk assessment will be evaluated following 

consideration of all available air monitoring data for acrolein. 

o Post-application air monitoring data are needed for the oil well (bacteriocide) use 

pattern (GDLN 875.2500).
Page 12 of 23

14.0 References

Table 14.0. Memoranda Relevant to Registration Review

Author Barcode Date Title

U. Habiba TXR ??? July 9, 2015

Acrolein: Summary of Hazard and Science Policy 

Council (HASPOC) Meeting of July 9, 2015: 

Recommendations on the Need for the Neurotoxicity 

Battery (Acute and Subchronic) and Immunotoxicity 

Study.

S. Recore and 

E. Evans D427918 June 30, 2015 Acrolein: Tier I Review of Human Incidents and Epidemiology

T. Morton D334828 October 13, 2011 Acrolein: Review of The Nature of the Residue in 

Radish Study Draft Protocol.

A. Johnson, J. 

Pates NA September 2008 Reregistration Eligibility Decision (RED) for Acrolein. List B. Case No. 2005.

B. Diass

et al. D348777 March 25, 2008 Acrolein: HED Risk Assessment for Reregistration Eligibility Decision (RED). 

B. Diass D348776 March 25, 2008

Acrolein: Occupational and Residential Exposure 

Assessment and Recommendations for the 

Reregistration Eligibility Decision (RED)

T. Morton D350876 March 25, 2008 Acrolein: Revised Dietary Risk and Exposure Estimate 

For Acrolein Through Subsistence Diets for Indigenous 

People of United States.

T. Morton D334663 September 27, 

2007

Acrolein: Revised Product and Residue Chemistry 

Considerations

T. Morton D225281 

and D94393 July 26, 2007 Acrolein. Nature of the Residue in Poultry and Ruminants 

N. Mottl D321012 August 24, 2007 Acrolein: Occupational Risk Assessment of 

Antimicrobial Uses for the Reregistration Eligibility 

Decision (RED) Document. 

Attachment 1: Chemical Identity Tables

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

Attachment 3: Summary of Toxicity and Endpoints for Acrolein (from the 2008 Risk 

Assessment)

Attachment 4: Summary of Residues of Concern for Acrolein. 
Page 13 of 23

Attachment 1: Chemical Identity Tables

The nomenclature and physicochemical properties of acrolein and the metabolite of acrolein, 

glycidol, are provided in Tables A.1.1-A.1.3. 

Table A.1.1. Test Compound Nomenclature

Compound Acrolein

Chemical Structure O

Common Name acrolein

Synonyms 2-propenal, acrylaldehyde, acraldehyde, acrylic aldehyde, allyl aldehyde, 

propenal, trans acrolein, acquinite, aqualin, aqualine, biocide, crolean, 

ethylene aldehyde, MAGNACIDE, MAGNACIDE H, NSC 8819, prop-2-en1-al, 2-propene-1-one, slimicide, prop-2-enal

CAS # 107-02-8

PC Code 000701

Table A.1.2. Physicochemical Properties of Acrolein

Molecular Weight 56.1

Boiling Point 53°C

Melting Point -81°C

Specific Gravity 0.0839

Vapor Density 1.94 (air = 1)

Vapor Pressure 220 torr 20° C

Flashpoint -15oF (-26.1oC)

Solubility 208 g/L at 20oC soluble in water, alcohol, ether, and acetone.

Description Clear, colorless to yellow liquid

.

Table A.1.3. Physicochemical Properties of Glycidol (CAS 556-52-5)

Chemical Structure 

HO O

Synonyms 1,2-Epoxy-3-Hydroxy Propane; 2,3-Epoxy-1-propanol; 2,3-epoxypropanol; 

2-hydroxymethyloxirane; 3-hydroxy-1,2-epoxypropane;; glycide; glycidyl 

alcohol; Glycidol; 

Molecular Weight 74.1

Boiling Point 166° C (decomposes)

Melting Point -45°C

Specific Gravity 0.0839

Vapor Density 2.15 (air = 1)

Vapor Pressure 120 Pa 25° C

Flashpoint 72 oC)

Solubility Miscible.

Octanol Water Partition 

Coefficient (Log pow) - 0.95

Description Clear, colorless liquid
Page 14 of 23

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

Table A.2.1. Acute Toxicity Profile - Acrolein 

Guideline No. Study Type MRID(s) Results Toxicity 

Category

870.1100 Acute oral - rat 41257001 LD50 = 11 mg/kg I

870.1200 Acute dermal - rabbit 00141028 LD50 = 231 mg/kg I

870.1300 Acute inhalation - rat 40945404 LC50 = 0.019 mg/L I

870.2400 Eye irritation - rabbit 00141025 Severely irritating I

870.2500 Dermal irritation - rabbit 00141026 Severely irritating I

870.2600 Skin sensitization Sustin and 

Breienstein, 1990

Suggestive/

limited data 
Page 15 of 23

Table A.2.2 Subchronic, Chronic and Other Toxicity Profile - Acrolein

Guideline No./ Study 

Type/Animal Species 

and Strain

MRID No. or Study Authors 

(year)/ Classification /Doses Results

870.3100

Subchronic oral toxicity -

rat

NTP (1995)

Non-guideline

0.75, 1.25, 2.5, 5.0 or 10 

mg/kg/d in 0.5% methyl 

cellulose via gavage for 13 

wks

LOAEL = 2.5 mg/kg/day in males; 1.25 mg/kg/day in 

females, based on forestomach squamous epithelial 

hyperplasia 

NOAEL = 1.25 mg/kg/day in males; = 0.75 mg/kg/day in 

females

Abnormal breathing and nasal discharge, hemorrhage, and 

necrosis and chronic-active inflammation of the forestomach 

and glandular stomach and mortality at 10 mg/kg/day. 

Hemorrhage of glandular stomach at 5 mg/kg/day. 

870.3100

Subchronic oral toxicity -

mice

NTP (1995)

Non-guideline

0, 1.25, 2.5, 5.0, 10.0, 20.0 

mg/kg/d in 0.5% methyl 

cellulose via gavage for 13 

wks

LOAEL = 2.5 mg/kg/day in females; 1.25 mg/kg/day in 

males, based on forestomach squamous epithelial 

hyperplasia 

NOAEL = 1.25 mg/kg/day in females, No NOAEL for 

males.

No clinical signs of toxicity. Glandular stomach lesions in 

the 10 and 20 mg/kg/day males and 20 mg/kg/day females.

870.3100

Subchronic oral toxicity -

rat

Arumugam et al (1999)

Non-guideline

0, 2.5 mg/kg/day for 45 days 

via intubation in distilled 

water to 5 male rats/group.

Acrolein resulted in severe depletion of liver cystolic GSH. 

Electron microscopy revealed loss of mitochondrial lamellae 

of the cristae accompanied with a 41% decrease in 

mitochondrial GSH. Citric acid cycle enzymes were also 

reduced 30 to 56%. The activities of GSH peroxidase and 

superoxide dismutase were increased significantly 

(p<0.001). Because GSSG was unchanged, GSH depletion 

was presumed to result from conjugation with acrolein.

870.3200

21 day dermal toxicity -

rabbit

00141030 (1982)

Acceptable/Guideline,

0, 7, 21 or 63 mg/kg/day. 6 

hrs/day, 5 days/week for 3 

weeks.

Systemic LOAEL = 7 mg/kg/day based on decreased body 

weight gain, and food consumption in both sexes, and 

minimal to moderate multifocal interstitial pneumonia and 

moderate bilateral interstitial nephritis in the females. 

Systemic NOAEL was not established

Dermal LOAEL = 7 mg/kg/day based on dermal irritation: 

slight to moderate reddening with swelling and firmness of 

the test site, and scab formation with peeling and 

microscopic findings in the treated skin (minimal to marked 

necrosis, hyperkeratosis, parakeratosis, and acanthosis). 

Dermal NOAEL was not established.

870.4100a

Chronic oral toxicity –

rats

Male Fischer 344 rats

Lijinsky and Reuber (1987)

Non-guideline

0, 6, 14, or 36 mg/kg/day, 5 

days/week for 104-124 weeks 

via drinking water. One group 

of 20 female rats administered 

the high dose only. (Note: The 

two highest doses exceed the 

oral LD50 in rats) 

Adrenocortical tumors (5/20) and hyperplastic nodules of the 

adrenal cortex (2/20) were found only in females in the high 

concentration group. The increased incidence of 

adrenocortical tumors was considered by the authors to be 

marginally significant as judged by the Fisher’s exact test 

(p=0.091) and significant for adrenocortical tumors plus 

hyperplastic nodules (p=0.022). According to the authors, 

this type of tumor is rare in untreated female Fischer 344 

rats; there was one reported in concurrent controls. The 

historical incidence is approximately 4.8% based on the 

findings of Solleveld et al. (1984) for untreated female F-344 

rats allowed to die naturally. Significant increases in tumor 

incidence were not found in male rats. There was no 

treatment-related mortality.
Page 16 of 23

Table A.2.2 Subchronic, Chronic and Other Toxicity Profile - Acrolein

Guideline No./ Study 

Type/Animal Species 

and Strain

MRID No. or Study Authors 

(year)/ Classification /Doses Results

870.4100b

Chronic oral toxicity –

dog

41071701 (1987)

Acceptable/Guideline

0, 0.1, 0.5, 1.5 - 2 mg/kg/day 

in gelatin capsules for 53 

weeks

LOAEL = 2.0 mg/kg/day based on vomiting in both sexes. 

In the range finding study, 2 mg/kg/day for 2-6 days resulted 

in dose dependent weight loss, decreased food consumption 

and vomiting (occasionally red-tinged). At a dose of 10 

mg/kg/day and above in the range finding study, vomiting 

preceded death of animals.

NOAEL = 0.5 mg/kg/day

870.3465

Inhalation - humans

47060601 (1997)

Acceptable/Non-guideline

Human volunteers were 

exposed to acrolein in a 30 

cubic meter chamber at a 0.1 

hourly air exchange rate in 3

trials: (1) A continuous 

exposure at constantly 

increasing acrolein 

concentrations, (2) 

Discontinuous short exposures 

to successively increasing 

concentrations, and (3) 

Constant concentration for one 

hour.

Threshold for measured effects: 

Eye irritation 0.09 ppm 

Nasal irritation 0.15 ppm 

Eye blink frequency 0.26 ppm 

Breathing frequency 0.30 ppm 

Throat irritation 0.30 ppm 

870.3465

Inhalation – rats

F344

Kutzman (1981);

Kutzman et al (1985);

Costa et al(1986)

Non-guideline

0, 0.4, 1.4, or 4.0 ppm (0, 0.9, 

3.2, 9.2 mg/m3

)/6 hr/day, 5 

days/week for 13 weeks

1. High mortality at 4 ppm.

2. Increase in lung collagen at 1.4 and 4 ppm (p<0.05).

3. Elastin content in 4 ppm group twice controls.

4. Bronchial necrosis and pulmonary edema at 4 ppm.

5. Parenchymal restriction at 0.4 ppm and obstructive lesions 

at 4.0 ppm.

6. No cytogenic or sperm abnormalities

870.3465

Inhalation - Rats 

Female dahl, selected for 

susceptibility or

resistance to salt induced

hypertension

Kutzman et al (1984, 1986) 

Non-guideline

0, 0.4, 1.4, or 4.0 ppm (0, 0.9, 

3.2, 9.2 mg/m3

)/6 hr/day, 5 

days/week for 13 weeks

1. All susceptible 4 ppm rats died after 11 days and 60% of 

resistant rats survived to end of study.

2. Lungs of susceptible rats had severe airway necrosis with 

edema and hemorrhage but only proliferative changes with 

resistant rats.

3. No differences in histopath between rat groups at lower 

doses.

4. No effect of exposure on blood pressure changes.

870.3465

Inhalation – rats, 

monkeys, guinea pigs, 

dogs

Lyon et al. (1970)

Non-guideline

0, 0.22, 1.0 and 1.8

ppm (0, 0.5, 2.3, and 4.1 mg/ 

m3

) acrolein for 24 hr/day for 

90 days

1. Ocular and nasal discharges in dogs and monkeys at 1 

ppm; severe at 1.8 ppm.

2. Squamous metaplasia of trachea in all monkeys at 1.8 

ppm.

3. Two dogs at 1.8 ppm had confluent bronchopneumonia.

4. Evidence of pulmonary inflammation (guinea pigs at 1 

ppm) and focal liver necrosis (rats and guinea pigs at 1 

ppm).

5. Nonspecific inflammatory changes in a variety of tissues 

in both rats and guinea pigs at 1.8 ppm.

LOAEL = 1 ppm (2.3 mg/m3

) based on inflammation in 

several organs of one or more species.

NOAEL = 0.22 ppm (0.5 mg/m3

)
Page 17 of 23

Table A.2.2 Subchronic, Chronic and Other Toxicity Profile - Acrolein

Guideline No./ Study 

Type/Animal Species 

and Strain

MRID No. or Study Authors 

(year)/ Classification /Doses Results

870.3465

Inhalation – rats

Male SPF OFA rats

Bouley et al. (1975, 1976, 

cited in IRIS 2003),

Non-guideline

0 or 0.55 ppm (0 and 1.3 

mg/m3

) acrolein. Exposure 

length and duration not stated, 

measurements were reported 

for exposures up to 77 days.

Study limitation: one exposure 

and histopathology.

Decreased body weight (<80% of controls) by Day 60. Nasal 

irritation (sneezing) in exposed rats between Days 7 and 21. 

Sneezing subsequently disappeared. A significant decrease 

in the number of alveolar macrophages in exposed rats. 

Liver weights not affected after 22 days of exposure but 

liver/body weight ratios were decreased in exposed animals 

after Day 15. Lung/body weight ratios were unchanged after 

Day 15 or 32, but were significantly elevated (p<0.002) after 

77 days. No effect on hepatic alcohol dehydrogenase after 15 

days of exposure. Serum alkaline phosphatase was 

unchanged at days 15, 32 and 77. On the other hand, serum 

acid phosphatase was increased on day 15 (p<0.001), but not 

on days 32 and 77. An LD50 inhaled dose of Salmonella 

enteritidis resulted in a higher death rate in treated animals 

than controls at 18 days, but not at 63 days. 

870.3465

Inhalation - rats

Catilina et al (1966)

Non-guideline

262 ppm for 10 minutes/day 

over 8 wks 

Caused peribronchial hemorrhage and bronchial lumen 

obstruction

870.3465

Inhalation – rats, 

hamsters, rabbits

Feron et al. (1978) 

Non-guideline

0, 0.4, 1.4 or 4.9 ppm (0, 0.9, 

3.2, 9.2 mg/C) to groups of 12 

rats, 20 hamsters, and 4 rabbits 

6 hours/day, 5 days/week for 

13 weeks

At 4.9 ppm mortality in rats, ocular and nasal irritation, 

growth depression and histologic changes in the respiratory 

tract in all species. At mid dose, squamous metaplasia and 

neutrophilic infilitration of the nasal mucosa in the rat; 

minimal inflammatory changes in the hamster. No effects in 

the mid and low dose rabbits. Intermediate-duration MRL

of 0.00004 ppm based on LOAEL of 0.4 ppm of nasal 

epithelial metaplasia. The rat was the most sensitive at the 

lowest exposure. The duration adjusted LOAEL in humans 

+ 0.4 ppm x 24 hr x 5/7 days = 0.071 ppm. Adjusting for the 

rat and human respiratory surface area for rat (15 cm2) and 

human (200 cm2), the LOAELHEC = 0.012 ppm. Adjusting 

for 300 UF (10 X for LOAEL, 3X for extrapolation from 

animals to Humans using domestric adjustments, 10 X for 

human variability), the MRL is 0.012/300 = 0.00004 ppm.

NOAEL is less than 0.4 ppm

870.3800

Inhalation Reproduction 

– rats

Fischer 344 rats

Kutzman (1981) 

Non-guideline

0, 0.4, 1.4, or 4.0 ppm 0, 0.9, 

3.2 or 9.2 mg/ m3 ) via 

inhalation to 8/sex/group for 6 

hr/day, 5 days/week (62 

exposure days) and the 

animals were evaluated 13.3 

weeks after initiation of 

exposure.

Exposed and control male rats were mated with unexposed 

females for 6 days and also exposed females were mated 

with unexposed and exposed males. Parameters evaluated 

were corpora lutea, viable embryos, early and late deaths, 

and preimplantation losses. There were no treatment-related 

effects on reproductive performance. Decreased pulmonary 

function was observed at 4 ppm.
Page 18 of 23

Table A.2.2 Subchronic, Chronic and Other Toxicity Profile - Acrolein

Guideline No./ Study 

Type/Animal Species 

and Strain

MRID No. or Study Authors 

(year)/ Classification /Doses Results

870.3800

Inhalation Reproduction 

– rats

3 male and 21 female 

SPF OFA rats

Bouley et al (1975)

Non-guideline

1.3 mg/ m3 (0.6 ppm) 

continuously via inhalation, 

mated on the 4th day of 

exposure. Exposures continued 

for 22 more days when 

females sacrificed. 

No significant differences in the number of and mean weight 

of fetuses (no data given) were reported. While the results 

were negative, the minimal results reporting limits 

conclusions that can be drawn from this study.

870.3800 

2 generation reproduction 

– rats

Crl:CD (SD)BR rats

41869101 (1992)

Acceptable/Guideline

0, 1, 3, or 6 mg/kg/d via oral 

gavage 

Maternal LOAEL = 6 mg/kg/day based on mortality at 6 

mg/kg in both F0 and F1 males and females and F1 mid-dose 

animals, most of the latter showing signs of respiratory 

distress and histopathological lesions in the lungs and 

stomach (erosions of glandular mucosa and 

hyperplasia/hyperkeratosis of the forestomach). Respiratory 

effects may be attributed to possible aspiration of gavage 

solution. . Significant depressions in body weight gains 

were noted in the high-dose groups and achieved statistical 

significance in the mid-dose animals on several occasions.

Maternal NOAEL = 3 mg/kg/day

Reproductive LOAEL was not observed. Reproductive 

parameters (i.e., mating performance and fertility indices) 

were unaffected. No treatment-related gross or microscopic 

effects were observed in the reproductive tissues of any of 

the F0 or F1 animals.

Reproductive NOAEL = 6 mg/kg/day (HDT) 

Offspring LOAEL = 6 mg/kg/day based on mortality and 

decreased pup body weights in the F1 generation 

Offspring NOAEL = 3 mg/kg/day

870.3700 Developmental 

study – rabbits

Pregnant New Zealand 

white rabbits (20/group)

40392401 (1987)

Acceptable/Guideline,

0, 0.1, 0.75, or 2.0 mg/kg-day 

via gavage for days 7 through 

19 of presumed gestation and 

subjected to caesarean 

sectioning on day 29. Range 

finding study at 0, 0.5, 1.0, 2.0 

4.0 or 6.0 mg/kg/day.

Maternal LOAEL = 2 mg/kg/day based on decreased body 

weights, body weight gains and food consumption. In the 

range finding study, maternal death, abortion, clinical signs, 

gastric ulceration, sloughing of the gastric mucosa, and 

complete litter resorption at ≥4 mg/kg/day

Maternal NOAEL = 0.75 mg/kg/day 

Developmental LOAEL was not observed. Fetal 

malformations were distributed evenly among the groups 

and were consistent with historical control data.

Developmental NOAEL = 2 mg/kg/day, highest dose 

tested. 
Page 19 of 23

Table A.2.2 Subchronic, Chronic and Other Toxicity Profile - Acrolein

Guideline No./ Study 

Type/Animal Species 

and Strain

MRID No. or Study Authors 

(year)/ Classification /Doses Results

870.3700

Developmental ToxicityRat

Sprague-Dawley CD (40 

time-mated 

females/group) 

00156438 (1982)

Acceptable/Guideline,

0, 3.6, 6 or 10 mg/kg/day via 

gavage from GD 7 through 19

Maternal LOAEL = 3.6 mg/kg/day based on mortality with 

no clinical signs but in a 2-gen repro study,(MRID 

41869101) mortality at 3 mg/kg/day with histopathology in 

the forestomach was observed.

Maternal NOAEL = < 3.6 mg/kg/day

Developmental LOAEL = 10 mg/kg/day based on 

decreased fetal weights and litter weights and on incomplete 

ossification of the skeleton and general retarded 

development of fetuses.

Developmental NOAEL = 6 mg/kg/day. 

870.4100

24-Month 

Chronic/Carcinogenicity 

Feeding-Rats

Sprague-Dawley (70-

75/sex/dose)

41306401 (1989)

46568001 (2002)

46568002 (2005)

Acceptable/guideline

95-98% a.i. 

0, 0.05, 0.50, or 2.5 mg/kg/day 

via gavage for 2 years

LOAEL = 0.5 mg/kg/day based on increased mortality in 

both sexes.

NOAEL = 0.05 mg/kg/day 

Equivocal evidence of carcinogenicity. After 24 months in 

the 2.5 mg/kg/day males, there was increased incidence of 

mammary gland adenoma (8% vs. 3% in concurrent 0-1.5% 

in. Combined adenoma and carcinoma (<=10%) 

approximated the historical control range (<=7.1%). 

Hepatocellular adenoma (8%) exceeded the concurrent (1%) 

and historical (0-3.5%) controls. Combined adenoma and 

carcinoma in the liver (<=8%) was within the historical 

control range (<=14.5%). Initial analysis of the pancreatic 

neoplasm suggested an increase in the incidence of pancreas 

acinar cell adenoma but a revised diagnosis according the 

criteria of Eustis et al. (1990) showed it was not related to 

treatment. Dosing was considered adequate based on 

increased mortality in both sexes.

870.4200

Carcinogenicity – Mice

CD-1 Swiss albino mice 

(70-75/sex/dose)

41334901 (1989)

Acceptable/guideline,

96.0% a.i.

0, 0.5, 2.0 or 4.5 mg/kg/day by 

gavage for 78 weeks

LOAEL = 4.5 mg/kg/day based on increased mortality. No 

adverse treatment-related effects were observed on clinical 

signs, body weights, body weight gains, food consumption, 

hematology, and organ weights, gross or microscopic 

pathology.

NOAEL = 2.0 mg/kg/day 

Not carcinogenic in mice in this test.

870.7485

Metabolism and 

pharmacokinetics - rats

42031001 (1991)

43177101 (1994)

73275901 (1994)

Parent et al (1996)

Parent et al 1998)

Single dose 2.5 mg/kg (iv or 

oral), or 2.5 mg/kg after 14

days of unlabeled acrolein 

(oral), or single 15 mg/kg 

(oral). Radiolabel monitored in 

expired air, urine, and feces.

>96% of radioactivity was recovered in excreta within the 

first 24 hours. Tissue concentrations (including blood) of 

radioactivity were minimal. Time course of excretion for all 

groups was similar except for delayed excretion in the highdose group. No acrolein detected in excreta or tissues. The 

radiolabel in feces associated with a homopolymer of 

acrolein, apparently formed in the gastrointestinal tract. The 

main pathway of acrolein metabolism is the addition of GSH 

to the activated double bond followed by conversion to 

mercapturic acid. A second pathway is epoxidation of the 

double bond followed by attack on the epoxide by 

glutathione. A third pathway is addition of water to acrolein 

to form 3-hydroxypropionaldehyde, which can be further 

metabolized and ultimately incorporated into normal 

metabolic pathways.
Page 20 of 23

Table A.2.2 Subchronic, Chronic and Other Toxicity Profile - Acrolein

Guideline No./ Study 

Type/Animal Species 

and Strain

MRID No. or Study Authors 

(year)/ Classification /Doses Results

870.5900

In vitro sister chromatid 

exchange

CHO cell cultures

00141032 (1982)

Acceptable/Guideline

0, 0.3, 0.5, or 0.75 μg /mL (-

S9) for 29-31 hrs or 0, 0.1, 0.3, 

or 0.5 μg /mL (+S9) for 4 

hours. 

Acrolein was tested up to cytotoxic concentrations (0.75 μg 

/mL -S9 and 0.5 μg /mL +S9). No significant increases 

(p<0.01) in the number of SCEs/cell were observed at any 

concentration in either condition. The positive controls 

induced the appropriate response. There was no evidence 

of SCE induced over background.

870.5900

In vitro sister chromatid 

exchange

Cultured human 

lymphocytes

Wilmer et al. (1986) – IRIS

Non-guideline

0.001 - 40 μM

Acrolein at concentrations of 5, 15, and 20 μM, but not 

lower doses, induced significant increases in sister chromatid 

exchanges. 

870.5375

In vitro mammalian 

chromosomal aberration 

assay - 

CHO cell cultures

00141033 (1982)

Acceptable/Guideline

0, 0.0, 0.2, 0.4, 0.6, 0.8, 1.0 or 

2.0 μg /mL (-S9) for 6 hrs or 

0, 0.6, 0.8, 1.0, 1.5 or 2.0 μg 

/mL (+S9) for 2 hours.

Acrolein was tested up to cytotoxic concentrations (2.0 μg 

/mL without S9 and >1.5 μg /mL with S9). No marked 

increases in break frequency were observed at any 

concentration in the presence or absence of S9. The positive 

controls induced the appropriate response. There was no 

evidence that Acrolein induced a clastogenic effect in the 

presence or absence of S9-activation.

870.5300

In vitro mammalian cell 

gene mutation assay 

CHO cell cultures –

HGPRT locus: 

hypoxanthineguanine

phosphoribosyl 

transferase

41579501 (1989)

Acceptable/Guideline

0 to .002 uL/mL (-S9) at 0 to 

0.006 2.0 uL/mL (+S9).

Acrolein was tested up to cytotoxic concentrations (>0.003 

μL/mL +S9 and >0.0008 μL/mL -S9). No reproducible 

significant increases in the mutant frequency were observed 

in the presence or absence of S9. The positive controls 

induced the appropriate response in all trials. There was no 

evidence that Acrolein induced mutant colonies over 

background in the presence or absence of S9-activation.

870.5100

Bacterial reverse 

mutation assay

Salmonella TA100 and 

TA104

Foiles et al (1989) 

Non-guideline

4, 7, and 10 μM

Acrolein induced formation of deoxyguanosine adducts at 

concentrations of 10 μM, but not 4 or 7 μM, in Salmonella 

tester strain TA104. Lack of response at the lower doses 

suggests the presence of a saturable repair mechanism. 

Increasing adduct formation with dose was seen in tester 

strain TA100 at concentrations of 4 mM and greater. 

870.5300

In vitro mammalian cell 

gene mutation assay 

CHO cell culture

Foiles et al (1990) 

Non-guideline

0.1 – 1 mM

Deoxyguanosine adduct formation increased progressively at 

concentrations ranging from 0.1 to 1 mM in Chinese hamster 

ovary cells (CHO).

870.5300

In vitro mammalian cell 

gene mutation assay 

Human fibroblast cells

Curren et al (1988) 

Non-guideline

0.2 – 5 μM

Acrolein was highly mutagenic to human fibroblast cells that 

were deficient in DNA repair (cells from xeroderma 

pigmentosum patients). It induced a positive dose-response 

between 0.2 and 0.8 μM but it did not induce an increase in 

the mutant frequency of normal fibroblasts
Page 21 of 23

Table A.2.2 Subchronic, Chronic and Other Toxicity Profile - Acrolein

Guideline No./ Study 

Type/Animal Species 

and Strain

MRID No. or Study Authors 

(year)/ Classification /Doses Results

870.5300

In vitro mammalian cell 

gene mutation assay 

V79 cells deficient in 

DNA repair

Smith et al (1990) 

Non-guideline

0.1, 0.5, 1, and 2 μM

Acrolein was mutagenic in V79 cells deficient in DNA 

repair. Normal V79 cells were not tested.

870.5375

In vitro mammalian 

chromosome aberration 

test

CHO cells

Au et al (1980) 

Non-guideline

In vitro chromosomal studies of acrolein have produced 

weakly positive findings in Chinese hamster ovary (CHO) 

cells

870.5300

In vitro mammalian cell 

gene mutation

Human fibroblast cells

Kawanishi et al (1998) 

Non-guideline

0 – 54 mM

The majority of the mutations in human fibroblasts were 

base substitutions (76%) followed by deletions and 

insertions (24%). Single base substitutions were most 

frequently found (46%), multiple base substitutions 

accounted for 18%, and tandem (two adjacent) base 

substitutions were 12%. Of the base substitutions, G:C to 

T:A transversions accounted for 44% of the total and G:C to 

A:T transitions for 24%. 

870.5100

Bacterial reverse assay

E. coli LM102, LM103, 

LM119

Vander Veen et al (2001) 

Non-guideline

Acrolein reacts with guanine residues to form 8-

hydroxypropanodeoxyguanosine that was not mutagenic in 

either wild-type or DNA repair deficient E. coli

870.5100

Bacterial reverse 

mutation assay

E. coli 

AB1157, 1886; ES1481; 

MO199, 211, 220, 221, 

230, 232, 233, 234, 933, 

934, 936, 937, 939; 

MV1185, 11932; 

NR9232; RK1517; 

SH2101; YG7210

Yang et al. (2001) 

Non-guideline Acrolein was non-mutagenic in E. coli 

870.5300

In vitro mammalian cell 

gene mutation

S. typhimurium TA98, 

TA100, TA104, TA1535, 

TA1538

IRIS literature summary 

(2003) 

Non-guideline

In tests for frameshift mutation TA98 gave some positive 

responses while TA1538 was negative with S-9 and all 

negative with S+9 except one positive for TA98. Tests for 

base repair and point mutations (TA100, TA104 and 

TA1535) were positive in

some tests with TA100, in most tests with TA104, but not 

with TA1535. TA104 has been

reported to be more sensitive to carbonyl compounds 

(Marnett et al., 1985). 
Page 22 of 23

Attachment 3: Summary of Toxicity and Endpoints for Acrolein (from the 2008 Risk 

Assessment)

Table A.3.1. Summary of Toxicological Doses and Endpoints for Acrolein for Use in Human Risk Assessments

Exposure Scenario Dose Used in Risk 

Assessment

Uncertainty/Safety 

Factor 

Study and Toxicological Effect

Acute Dietary

(General Population including 

infants and children)

Acute oral (dietary and drinking water) exposure to acrolein is not expected based on use 

patterns, physical-chemical properties, and plant metabolism data. Therefore, acute RfDs are 

not required and were not selected for this assessment.

Chronic Dietary

(All Populations)

Chronic oral (dietary and drinking water) exposure to acrolein is not expected based on use 

patterns, physical-chemical properties, and plant metabolism data. Therefore, chronic RfDs 

are not required and were not selected for this assessment.

Incidental Oral (all durations) There are no residential uses for acrolein. Therefore, incidental oral exposure endpoints are 

not required and not selected for this assessment.

Dermal (all durations) Worker dermal exposures are not expected based on use patterns and personal protective 

equipment requirements. There are no residential uses for acrolein and dermal exposures to 

residential bystanders are not expected based on use patterns and physical-chemical 

properties. Therefore dermal exposure endpoints are not required and have not been selected 

for this assessment. 

Short –Term Inhalation (1-30 

days)

Minimal LOAEL = 

0.09 ppm (0.21 mg/m3

)

LOC = 30

10X for intraspecies 

variation and 3X for lack 

of a NOAEL

Human volunteers exposed by 

inhalation for 60 minutes (WeberTschopp et al. 1977) based on a 

minimal effect LOAEL of 0.09 ppm 

for eye irritation. The LOAEL of 0.3 

ppm for nasal and throat irritation and 

decreased respiratory rate is 

considered co-critical for endpoint 

selection. 

Cancer (oral, dermal and 

inhalation)

“The potential carcinogenicity of acrolein cannot be determined because the existing “data 

are inadequate for an assessment of human carcinogenic potential for either the oral or 

inhalation route of exposure.” (IRIS 2003). 

To quantify the carcinogenic response of glycidol, a multistage model analysis was 

performed to derive a cancer slope factor of 0.16 mg-1

kg-1day-1 at a 0.95 confidence level. 

(See Appendix)
Page 23 of 23

Attachment 4: Summary of Residues of Concern for Acrolein

Table 4.1. Parent, Metabolites and Degradates Considered for Risk Assessment 

Matrix Compound of Potential Concern Residue included in Risk Assessment

Plant Acrolein No

Livestock Acrolein No

Fish Glycidol Yes

Drinking Water Acrolein, 3-Hydroxypropanal No