Acrolein (CASRN 107-02-8) 

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Reference Dose for Chronic Oral Exposure (RfD)

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0364

Acrolein; CASRN 107-02-8

Health assessment information on a chemical substance is included in IRIS only after a 

comprehensive review of chronic toxicity data by U.S. EPA health scientists from several 

Program Offices and the Office of Research and Development. The summaries presented in 

Sections I and II represent a consensus reached in the review process. Background 

information and explanations of the methods used to derive the values given in IRIS are 

provided in the Background Documents. 

STATUS OF DATA FOR Acrolein

File First On-Line 09/07/1988
Category (section) Status Last Revised

Oral RfD Assessment (I.A.) on-line 06/03/2003

Inhalation RfC Assessment (I.B.) on-line 06/03/2003

Carcinogenicity Assessment (II.) on-line 06/03/2003

_I. Chronic Health Hazard Assessments for Noncarcinogenic 

Effects

_I.A. Reference Dose for Chronic Oral Exposure (RfD)

Substance Name — Acrolein

CASRN — 107-28-8

Last Revised — 06/03/2003 

The oral Reference Dose (RfD) is based on the assumption that thresholds exist for certain 

toxic effects such as cellular necrosis. It is expressed in units of mg/kg-day. In general, the 

RfD is an estimate (with uncertainty spanning perhaps an order of magnitude) of a daily 

exposure to the human population (including sensitive subgroups) that is likely to be 

without an appreciable risk of deleterious effects during a lifetime. Please refer to the 

Background Document for an elaboration of these concepts. RfDs can also be derived for 

the noncarcinogenic health effects of substances that are also carcinogens. Therefore, it is 

essential to refer to other sources of information concerning the carcinogenicity of this 

substance. If the U.S. EPA has evaluated this substance for potential human 

carcinogenicity, a summary of that evaluation will be contained in Section II of this file. 

An RfD for acrolein was not previously available on IRIS.

__I.A.1. Oral RfD Summary

Critical Effect Experimental Doses* UF MF RfD

Decreased survival

Chronic gavage rat study

Parent et al., 1992a

NOAEL: 0.05 mg/kg-day

FEL*: 0.5 mg/kg-day

100 1 5 x 10-4

mg/kg-day

* FEL — frank effect level (an objective, clinically evident effect)

__I.A.2. Principal and Supporting Studies (Oral RfD)
Parent et al. (1992a) administered acrolein in water daily via gavage to Sprague-Dawley 

rats, 70/sex/group, at dose levels of 0, 0.05, 0.5, and 2.5 mg/kg BW. Dosing volume was 

10 ml/kg. Ten animals from each group were sacrificed after one year and the remainder 

after two years. An extensive array of tissues was examined microscopically, including 

stomach tissue. Although it was not explicitly stated that both the glandular stomach and 

forestomach were examined, it is unlikely that both parts of the stomach were not 

examined. Daily observations were made and various clinical, hematological and urinary 

parameters were measured after 3, 6, 12, and 18 months of treatment and immediately 

prior to sacrifice. There were no statistically significant increased incidences of microscopic 

lesions in the treated rats, whether neoplastic or non-neoplastic. Food consumption and 

body weights were unaffected by treatment. With the exception of a statistically significant 

depression of creatinine phosphokinase (creatine kinase) at all dose levels and at most time 

intervals (except 12 months), clinical chemistry parameters, hematology and urinalysis 

measurements were unaffected by treatment. 

The most definitive responses reported were treatment-related increases in early 

cumulative mortality. Data were provided in the form of survival curves. Among high-dose 

males, survival was significantly reduced after one year (p<0.05), and marginally reduced 

among mid-dose males (p value not reported). Among high-dose males, a trend test for 

survival during the first year indicated a highly statistically significant (p=0.003) decrease; 

however, the statistical differences are nullified when the survival data for two years are 

included in the analysis. Survival among females during the first year corresponded closely 

to those obtained for males. A statistically significant decrease in survival (p<0.05) was 

reported in the high-dose group, while a decrease in survival in the mid-dose group was 

marginally significant (p value not reported). Unlike responses in males, the significant 

associations between dosing and survival persisted in females through the end of the study. 

After two years, a statistically significant reduction in survival was noted based on four 

different statistical tests for the mid-dose group and in three of four statistical tests in the 

high-dose group (p values not reported). Although the differences in survival were 

statistically significant in females after two years, it should be noted that the differences 

were relatively small. No differences in survival compared to controls were seen in either 

the male or female low-dose groups (0.05 mg/kg/day). Thus, 0.5 mg/kg/day is considered 

a frank effect level (FEL) for the rat, and 0.05 mg/kg/day the no-observed-adverse-effect 

level (NOAEL). The FEL is defined as "a level of exposure or dose which produces 

irreversible, adverse effects at a statistically or biologically significant increase in frequency 

or severity between those exposed and those not exposed" (IRIS, 2003). 

Other studies support the findings of reduced survival in laboratory animals exposed to 

acrolein as reported by Parent et al. (1992a). In a study designed to evaluate the potential 

carcinogenicity of acrolein (Parent et al., 1991), Swiss albino CD-1 mice (70-75/sex/group) 

were dosed via gavage (acrolein in distilled water and stabilized with hydroquinone) with 0, 
0.5, 2.0 or 4.5 mg/kg/day for 18 months. The primary effect was increased mortality only 

in high-dose males of the 4.5 mg/kg/day group; mortality in the mid- and low-dose groups 

was less than control. There were no dose-related adverse histopathological or clinical 

findings. 

In a 13-week daily gavage study of acrolein (in 0.5% methyl cellulose) in F344 rats and 

B6C3F1 mice conducted for the National Toxicology Program (NTP, 1995), 10 rats/sex/dose 

were administered 0, 0.75, 1.25, 2.5, 5.0, and 10 mg acrolein/kg; 10 mice/sex/dose 

received 0, 1.25, 2.5, 5.0, 10 and 20 mg/kg. Dose volume was 5 ml/kg for rats and 10 

ml/kg for mice. Treatment resulted in similar dose-related effects in both sexes of both 

species: hemorrhage and necrosis and other lesions of the forestomach and glandular 

stomach and secondary changes associated with acrolein-induced mortality in high-dose 

animals (NTP, 1995; Pathology Working Group Review, 1997). Abnormal breathing and 

nasal/eye discharge were among the clinical findings in high-dose rats. Nearly all high-dose 

animals died or were removed from study because of gastrointestinal toxicity. The NOAEL 

was 0.75 mg/kg for female rats and 1.25 mg/kg for males, based on forestomach 

squamous epithelial hyperplasia in the 1.25 mg/kg group and 2.5 mg/kg group, 

respectively. There were no clinical signs of toxicity in mice. The forestomach lesions in 

mice were similar to those in the rat. Glandular stomach lesions were only seen in the 10 

and 20 mg/kg males and in the 20 mg/kg females. Statistically significant increases in 

absolute and relative liver weights were seen in male mice at 10 mg/kg without attendant 

hepatic histopathology. There was no NOAEL for the male mouse (i.e., one male had 

squamous epithelial hyperplasia at the lowest dose of 1.25 mg/kg). The NOAEL for female 

mice was 1.25 mg/kg. Reasons for no reported observations of stomach lesions in SpragueDawley female rats at the highest dose (2.5 mg/kg) of the Parent et al. (1992a) study 

compared with forestomach squamous epithelial hyperplasia observed in female F344 rats 

in the NTP study at 1.25 mg/kg/day are not readily apparent, but may relate to differences 

in strain sensitivity or vehicle. The vehicle dose volume was 5 ml/kg in the NTP (1995) 

study and 10 ml/kg in the Parent et al. (1992a) study for rats, and there may have been a 

reduced local gastric mucosal irritation and pathology by virtue of dilution. There were also 

differences in the vehicle solution and, possibly, the stability of the dosing solutions. Parent 

et al. (1992a) conducted stability studies on acrolein in water, and monitored the stability of 

their dosing solutions (reporting losses of less than 10% for 3 hours at room temperature). 

They used a stabilizing agent, 0.25% hydroquinone, in the stock solution, and prepared 

dosing solutions daily. The NTP study used a dose vehicle of 0.5% methylcellulose in 

deionized water, and no information was available on stability or stabilizing agents. 

For the mouse results, there is a similar divergence between the absence of reported 

forestomach lesions in the CD-1 mice at 4.5 mg/kg in the Parent et al. (1991) study 

compared with effects observed in female B6C3F1 at 2.5 mg/kg in the NTP study. Species 

differences and dose volume again may have accounted for observed differences in 
response. Dose volume in the NTP study for mice was 10 ml/kg, and was unspecified in the 

Parent et al. (1991) study. 

A benchmark dose approach was unsuitable for RfD development because the data in the 

Parent et al. (1992a) study were presented graphically, with statistical evaluation at one 

and two-year time points, but no numerical values. Moreover, the NOAEL derived from the 

Parent et al. study and used as the basis for the RfD is from a statistically significant 

increase in mortality, a frank effect. A benchmark dose analysis would not be appropriate 

when the dose-response is for early cumulative mortality.

__I.A.3. Uncertainty and Modifying Factors (Oral RfD)

UF = 100. 

A default UFA of 10 was applied to account for interspecies differences between laboratory 

animals and humans. No information was available to support a change from the default. 

A default UFH of 10 was applied for intraspecies uncertainty to account for human variability 

and sensitive subpopulations, i.e., to account for human variability in the severity or range 

of response from any given acrolein exposure amongst different individuals. 

A UFD was not applied because the database for acrolein was considered complete. The 

available oral database includes chronic toxicity studies in the rat and mouse, an oral 

reproductive toxicity study in Sprague-Dawley rats and an oral developmental toxicity study 

in New Zealand white rabbits. The findings from the oral reproductive and developmental 

toxicity studies are supported by an inhalation reproductive toxicity study of acrolein in 

Fisher 344 rats that revealed no reproductive or developmental effects. Acrolein's high 

reactivity at the point of contact and the evidence for minimal systemic distribution of 

acrolein obviates the need for additional repeat dose studies. 

The RfD is based on a NOAEL from a chronic study, which obviates the need for an 

uncertainty factor for LOAEL to NOAEL extrapolation or for subchronic to chronic 

extrapolation. 

MF = 1.

__I.A.4. Additional Studies/Comments (Oral RfD)

Administration of acrolein in water by oral gavage at 0.05, 0.5, and 5.0 mg/kg to male and 

female Sprague-Dawley rats (30/sex/group) daily, 5 days per week for 13 weeks did not 

produce any significant adverse effects on mortality, on clinical, hematological, or urinalysis 
parameters, or on histopathology (Bioassay Systems Corp., 1981). This study was a 

precursor to Parent et al. (1992a), identified as the principal study. 

In a range-finding gavage study in artificially inseminated New Zealand white rabbits (3-

4/group), acrolein (0, 0.5, 1.0, 2.0, 4.0, and 6.0 mg/kg/day) produced high incidences of 

maternal mortality, spontaneous abortion, resorption, clinical signs, gastric ulceration, 

and/or sloughing of the gastric mucosa. The dose-response curve for mortality was steep. A 

factor of 2 in dose (from 2 to 4 mg/kg) resulted in 25% mortality in the high-dose animals 

compared to 0% in lower-dose animals (Parent et al., 1993). Mortality was 100% at 6 

mg/kg. 

In a two-generation reproductive toxicity study, four groups of 30 male and 30 female 

Sprague-Dawley rats were gavaged with 70 daily doses of acrolein at levels of 0, 1, 3, or 6 

mg/kg in a dosing volume of 5 ml/kg (Parent, 1992b). Rats within each dosing group (F0

generation) were then assigned to a 21-day period of cohabitation. Dosing continued for 

females through cohabitation, gestation, and lactation. A similar regime was carried out for 

F1 generation offspring, resulting in F2 generation pups. Mortality was significant (at 6 

mg/kg) in both males and female of the F0 and F1 generations with the pattern continuing 

with F1 mid-dose animals, the latter showing signs of respiratory distress and 

histopathological lesions in the lungs and stomach. 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 the F0 or F1 animals, and 

no gross abnormalities were observed in F2 generation pups. The data provide evidence that 

acrolein is not a selective reproductive toxicant but does produce toxicological effects at 

doses as low as 3 mg/kg/day. 

Arumugam et al. (1999) exposed male Wistar rats, 5 animals/group, daily to acrolein via 

intubation (2.5 mg/kg BW) for 45 days. The incidence of mortality, if any, was not reported 

in this study. This study clearly showed damage to mitochondria (through the loss of 

mitochondrial lamellae of the cristae), a decrease in the availability of reduced glutathione 

(a substrate for glutathione peroxidase), and a 30-56% decrease in activities of citric acid 

cycle enzymes, resulting in decreased energy production in liver cells. These results indicate 

that at least some uptake occurs from the oral route; however, the stomach was not 

examined by light microscopy. 

Because of the highly reactive nature of acrolein, the concentration of a dose administered 

by gavage can affect the time course and degree of severity of toxicity at the point of entry 

and the relevance of the gavage bolus dose to human exposure. Rats have both a 

forestomach and a glandular stomach, while humans have only a glandular stomach. The 

glandular stomach is more resistant than the forestomach to pH changes and irritation. The 

residence time in the forestomach (of approximately 2 hours) is sufficiently long compared 
to the reaction time for toxicity with airway tissue observed in inhalation studies (i.e., 

microseconds) so that the dose to the glandular stomach may be much lower than that to 

the forestomach (TERA, 1998). The dog is a better model for glandular stomach toxicity 

than the rat, however, Parent et al. (1992c) administered acrolein (0.1% aqueous) in 

gelatin capsules to beagle dogs, so the dose concentration to the glandular tissue is not 

known. In lieu of studies that provide data on glandular stomach toxicity, the Parent et al. 

(1992a) study in the rat remains the most suitable choice for the principal study.

For more detail on Susceptible Populations, exit to the toxicological review, 

Section 4.8 (PDF).

__I.A.5. Confidence in the Oral RfD

Study — Medium

Database — High

RfD — Medium to High

The overall confidence in this RfD assessment is medium to high. Confidence in the principal 

study is medium. Several supporting studies involving other species also indicated that 

mortality increases sharply with elevated dose. The research demonstrating acrolein's high 

reactivity, low systemic distribution, toxicity at the point of entry, pronounced decreases in 

serum creatinine phosphokinase (creatine kinase), citric acid cycle enzymes and liver GSH, 

and increased mitochondrial damage in the Wistar rat suggest interference with normal 

metabolic processes or possibly the absorption of essential nutrients sufficient to lead to 

early mortality. Further research is needed, however, to support a definitive mode of action. 

In the NTP (1995) study, glandular stomach and forestomach lesions were reported at 

higher doses and likely played a role in the observed mortality. Confidence in the database 

is judged high with chronic exposure studies in 2 species. Moreover, two studies (Parent et 

al., 1992b; Parent et al., 1993) provide evidence that reproductive and developmental 

effects are not critical endpoints although only one species was tested for reproductive 

effects (rat) and for developmental effects (rabbit). While the possibility of some transport 

of acrolein or a metabolite of acrolein to systemic sites remains, the critical target sites 

(discussed further in the Toxicological Review of Acrolein) are at the point of contact, e.g., 

the respiratory system, the gastrointestinal tract, mucous membranes, and skin. The high 

reactivity of acrolein and the lack of significant systemic distribution obviates the need to 

examine reproductive/developmental effects in a second species. The overall confidence in 

this RfD assessment is medium-to-high; a variety of studies across different durations of 

exposure and in several different laboratory animal species has been consistent in 

demonstrating that in the absence of mortality there are no clear indications of adverse 

effects.
For more detail on Characterization of Hazard and Dose Response, exit to the 

toxicological review, Section 6 (PDF).

__I.A.6. EPA Documentation and Review of the Oral RfD

Source Document - U.S. EPA (2003) 

This assessment was peer reviewed by external scientists. Their comments have been 

evaluated carefully and incorporated in finalization of the IRIS Summary. A record of these 

comments is included as an appendix to the Toxicological Review of Acrolein (U.S. EPA, 

2003). To review this appendix, exit to the toxicological review, Appendix A, 

Summary of External Peer Review Comments and Disposition (PDF).

Agency Consensus Date - 05/16/2003

__I.A.7. EPA Contacts (Oral RfD)

Please contact the IRIS Hotline for all questions concerning this assessment or IRIS, in 

general, at (202)566-1676 (phone), (202)566-1749 (FAX), or hotline.iris@epa.gov (email 

address).

Top of page

_I.B. Reference Concentration for Chronic Inhalation Exposure 

(RfC)

Substance Name — Acrolein

CASRN — 107-02-8

Last Revised — 06/03/2003

The inhalation Reference Concentration (RfC) is analogous to the oral RfD and is likewise 

based on the assumption that thresholds exist for certain toxic effects such as cellular 

necrosis. The inhalation RfC considers toxic effects for both the respiratory system (portalof-entry) and for effects peripheral to the respiratory system (extrarespiratory effects). It is 

generally expressed in units of mg/cu.m. In general, the RfC is an estimate (with 

uncertainty spanning perhaps an order of magnitude) of a daily inhalation exposure of the 

human population (including sensitive subgroups) that is likely to be without an appreciable 

risk of deleterious effects during a lifetime. Inhalation RfCs were derived according to the 

Interim Methods for Development of Inhalation Reference Doses (EPA/600/8-88/066F 
August 1989) and subsequently, according to Methods for Derivation of Inhalation 

Reference Concentrations and Application of Inhalation Dosimetry (EPA/600/8-90/066F 

October 1994). RfCs can also be derived for the noncarcinogenic health effects of 

substances that are carcinogens. Therefore, it is essential to refer to other sources of 

information concerning the carcinogenicity of this substance. If the U.S. EPA has evaluated 

this substance for potential human carcinogenicity, a summary of that evaluation will be 

contained in Section II of this file. 

The revised RfC is the same value as the previous RfC of 2 x 10-5 mg/m3 entered on IRIS 

10/01/1991; however, this new RfC is based on an updated interpretation of the database.

__I.B.1. Inhalation RfC Summary

Critical Effect Experimental Doses* UF MF RfC

Nasal lesions

Subchronic rat inhalation study

Feron et al., 1978

NOAEL: none

LOAEL: 0.4 ppm (0.9 mg/m3)

LOAEL (ADJ): 0.16 mg/m3

LOAEL (HEC): 0.02 mg/m3

1,000 1 2 x 10-5 mg/m3

*Conversion Factors and Assumptions: MW = 56.06 (HSDB, 2003). Assuming 25oC and 760 mm Hg, the LOAEL of 

0.4 ppm (0.9 mg/m3) was adjusted to a continuous exposure as follows: LOAEL (ADJ) = 0.9 mg/m3x 6/24 x 5/7 = 0.16 

mg/m3. The LOAEL(HEC) was calculated for a Category 1 gas:respiratory effect in the extra-thoracic region by 

multiplying the LOAEL (ADJ) by the Regional Gas Dosimetry Ratio (RGDR(ET)), to derive a comparable human 

exposure (U.S. EPA, 1994). The calculation for the RGDR(ET) = (MVa/SAa) / (MVh/SAh) where MVa = 0.20 m3/day, 

MVh = 20 m3/day, SAa(ET) = 15.0 cm2, SAh(ET) = 200 cm2 RGDR(ET) = (0.20/15)/(20/200) = 0.14. The LOAEL(HEC) 

= LOAEL(ADJ) x RGDR(ET) = 0.16 mg/m3x 0.14 = 0.02 mg/m3. Derivation of the RGDR is further described in the 

Toxicological Review for Acrolein.

__I.B.2. Principal and Supporting Studies (Inhalation RfC)

Feron et al. (1978) exposed 6 Wistar rats/sex/concentration, 10 Syrian golden 

hamsters/sex/concentration, and 2 Dutch rabbits/sex/concentration for 6 hr/day, 5 

days/week for 13 weeks to 0, 0.4, 1.4, or 4.9 ppm (0, 0.9, 3.2, or 11 mg/m3) acrolein in a 

whole-body exposure chamber. Incidence data were not reported, but histopathological 

changes in the nasal cavity, lung, larynx, and trachea were graded as slightly, moderately, 

or severely affected. In rats, hematological parameters were unaffected by acrolein. Body 

weight gain was significantly inhibited at the high dose in rats, and less so at the 

intermediate concentration, but food consumption appeared to be decreased in these 

groups as well. At the intermediate concentration, both male and female rats showed 

significantly retarded weight gain (p<0.05). Three male and 3 female rats died during 
exposure at the highest dose. No other deaths considered to be treatment-related were 

reported in any of the species or exposure groups. 

Histopathologic changes described as "slightly affected" were found in the nasal cavity of 1 

of 12 rats exposed to 0.4 ppm (0.9 mg/m3). Severity increased at the higher levels of 

exposure. No nasal lesions were reported in other species at 0.4 ppm (0.9 mg/m3). The 

severity of nasal lesions was concentration-related in all 3 species, most clearly so in the 

rat. In the 4.9 ppm (11 mg/m3) groups of all 3 species, slightly to markedly increased 

lesions were reported in the nasal cavity and trachea; moderate to marked effects were 

seen in the bronchi and lungs of rats and rabbits (but not hamsters). Based upon the 

concentration-related severity of lesions, the rat is clearly the most sensitive species, with 

hamsters and rabbits intermediate in sensitivity. 

Although the Feron et al. (1978) study was adequately designed, the incidence of nasal 

lesions for treated groups was not reported. However, histopathological grading allowed the 

determination of NOAELs, LOAELs and FELs for the 3 species, identification of the critical 

target site, and a comparison of sensitivities among the 3 species tested. Other limitations 

of this study include an exposure duration of 3 months rather than lifetime, 

histopathological examination of only 3 sections of the nasal cavity, lack of characterization 

of the type of nasal lesions by sex, and only 6 rats/sex exposed. 

A more recent study, Cassee et al. (1996) examined the nasal effects of inhalation exposure 

of formaldehyde, acetaldehyde, and acrolein on male Wistar rats (5-6/group) exposed 6 

hr/day, for 3 consecutive days, in a nose-only exposure chamber to acrolein at 

concentrations of 0, 0.25, 0.67, or 1.4 ppm (0, 0.6, 1.5, or 3.2 mg/m3). The Cassee et al. 

(1996) study was designed to evaluate the severity of effects from mixtures versus single 

chemical exposure, and analyzed six levels of the nasal tract for histopathological and 

biochemical changes immediately after the last exposure. After one 6-hour exposure, no 

treatment-related histopathological lesions were found in any of the treatment groups. Only 

the histopathology of the 0.25 and 0.67 ppm (0.6 or 1.5 mg/m3) groups were reported 

following 3 days of exposure; effects at 1.4 ppm (3.2 mg/m3) were not reported. After 3 

days, slight to moderate effects were observed from acrolein exposure in two of the four 

histopathology categories evaluated. In the category for disarrangement, necrosis, 

thickening and desquamation in the respiratory/transitional epithelium, 4/5 animals 

exposed to 0.25 ppm (0.6 mg/m3) were observed to have slight effects (characterized as 

mainly disarrangement) and 1/5 developed a moderate level of effect. In the 0.67 ppm (1.5 

mg/m3) group, 3/6 were classified as slightly affected and 3/6 rats developed a moderate 

degree of response. For rhinitis, 1/5 of the 0.25 ppm (0.6 mg/m3) rats developed a 

moderate response, and only 1/6 of the 0.67 ppm (1.5 mg/m3) rats had a response and it 

was scored as a slight response. For the other two categories, single cell necrosis or atrophy 

of the olfactory epithelium, no effects were observed in either the 0.25 ppm (0.6 mg/m3) or 
0.67 ppm (1.5 mg/m3

) group. After one 6-hr exposure, no treatment-related proliferative 

response (defined as basal cell proliferation and/or an increased number of mitotic figures 

in respiratory/transitional epithelium) was found in any of the treatment groups. After 3 

days, 3/5 rats at 0.25 ppm (0.6 mg/m3) developed a slight focal proliferative response, and 

all rats in the 0.67 ppm (1.5 mg/m3) group developed a slight or moderate response. 

Proliferative effects were not reported for the 1.4 ppm (3.2 mg/m3) exposure group. Among 

biotransformation enzymes measured in homogenates of nasal tissue, glutathione Stransferase activity was significantly depressed in the 1.4 ppm (3.2 mg/m3

) exposure group 

(p<0.01) while formaldehyde dehydrogenase and aldehyde dehydrogenase activities was 

significantly increased (p<0.05). No changes were reported in the lower dose groups, or for 

glutathione peroxidase activity in any of the dose groups. Non-protein sulfhydryl (NPSH) 

depletion was not observed in this study. No biochemical effects were observed in olfactory 

tissue. The LOAEL in this study was 0.25 ppm (0.6 mg/m3). 

The occurrence of lesions at lower doses in the Cassee et al. (1996) study than used in the 

Feron et al. (1978) study may be: (1) a consequence of nose-only exposure where, unlike 

whole-body exposure, the animals cannot minimize exposure by burying their noses in their 

fur, so that animals receive a full and uninterrupted dose; or (2) due to a higher resolution 

evaluation from the use of extended sectioning (6 sections) of the nasal tract compared to 

only 3 in the Feron et al. (1978) study. 

Cassee et al. (1996) do not discuss the persistence or reversibility of the observed 

histopathological changes in the low-dose group with exposures greater than 3 days (e.g., 

adaptive response). An adaptive response in nonprotein sulfhydryl levels after 3 days of 

exposure was observed and is discussed. Because the Feron et al. (1978) study was much 

longer in duration, it is possible that some adaptation to the irritant effects of acrolein 

occurred with increasing duration, or that cessation of exposure for 2 days each week 

provided a period during which partial recovery from nasal effects might have occurred. 

The rationale for choosing the Feron et al. (1978) study over the Cassee et al. (1996) study 

includes: (1) the higher number of test animals [12 (6/sex) vs. 6 male only]; (2) the longer 

duration [5 days/week for 13 weeks vs. 3 days]; (3) the testing of multiple species and 

both sexes in the Feron et al. study; and 4) the better characterization of multiple 

endpoints and the dose-response. Feron et al. evaluated many different end points and 

demonstrated dose response for all 3 dose groups in all 3 species tested. The Feron et al. 

study also evaluated a dose response over a 12-fold increase in dose from low to high dose. 

The Cassee et al. study used about a 6-fold increase in dose level from low to high. 

A benchmark dose approach for derivation of the RfC was not possible because nasal 

pathology incidence data were not provided. Therefore, the approach used to derive the RfC 
was the determination of a LOAEL as the point of departure and application of uncertainty 

factors.

__I.B.3. Uncertainty and Modifying Factors (Inhalation RfC)

UF = 1,000.

A UFA of 3 (101/2) was used for interspecies extrapolation, since this factor embodies two 

areas of uncertainty: pharmacokinetics and pharmacodynamics. In this assessment, the 

pharmacokinetic component was addressed by the calculation of the human equivalent 

concentration (HEC) according to the procedures in the RfC methodology (U.S. EPA, 

1994b). Accordingly, only the pharmacodynamic area of uncertainty remains as a partial 

factor for interspecies uncertainty (101/2 or approximately 3). 

A default UFH of 10 was applied for intraspecies uncertainty to account for human variability 

and sensitive subpopulations, i.e., to account for human variability in the severity or range 

of response from any given acrolein exposure amongst different individuals. 

A UFS of 10 was applied for adjustment from subchronic to chronic duration because the 

principal study involved a 13-week dosing period and because there are insufficient 

inhalation data to preclude an increase in severity (or incidence) with an increase in 

exposure duration from subchronic to chronic. 

A UFL of 3 (101/2) was applied for use of a minimal LOAEL of 0.4 ppm (0.9 mg/m3) in lieu of 

a NOAEL. Although the severity of the nasal effect at the 0.4 ppm level was minimal and in 

only 1 of 12 animals in the Feron et al. (1978) study, a 3-day study in the male Wistar rat 

by Cassee et al. (1996) also reported slight nasal effects in the respiratory/transitional 

epithelium from nose-only inhalation exposure at 0.25 ppm (0.6 mg/m3). An exposure 

concentration of 0.4 ppm (0.9 mg/m3) was designated a minimal LOAEL instead of a 

NOAEL, considering the Cassee et al. (1996) results and the observed increase in the 

severity of the effects with increasing dose in the Feron et al. (1978) study. 

A UFD was not applied because the database for acrolein was considered complete. The 

available inhalation database includes subchronic toxicity studies in multiple species, and an 

inhalation reproductive toxicity study of acrolein in Fisher 344 rats that revealed no 

reproductive or developmental effects. Acrolein's high reactivity at the point of contact and 

the evidence for minimal systemic distribution of acrolein obviates the need for additional 

studies of repeat-dose toxicity or reproductive/developmental toxicity. 

MF = 1. 
__I.B.4. Additional Studies/Comments (Inhalation RfC)

Studies by Kutzman (1981), Kutzman et al. (1985) and Costa et al. (1986) support the 

Feron et al. (1978) results with additional evidence of lung deficits from exposure to 

acrolein. The Kutzman studies were cited as co-principal studies in the assessment 

previously on IRIS. Male F344 rats exposed to 0, 0.4, 1.4, or 4.0 ppm (0, 0.9, 3.2, or 9.2 

mg/m3) 6 hr/day, for a total of 62 exposure days over a duration of 12.4 weeks were 

examined on the sixth day post-exposure (to minimize acute effects) (Kutzman, 1981; 

Kutzman et al., 1985). Mortality (32/57) was observed only in males at the highest 

concentration, with many displaying severe acute bronchopneumonia. The changes in the 

nasal region consisted of only minimal evidence of submucosal lymphoid aggregates at 0.4 

ppm (0.9 mg/m3); although degree of involvement increased to moderate at higher 

concentrations, more extensive damage to the nasal epithelium was not observed. Lungs 

from the 0.4 or 1.4 ppm (0.9 or 3.2 mg/m3) groups did not display treatment-related 

histopathological changes. At 4.0 ppm (9.2 mg/m3) the surviving animals demonstrated 

bronchiolar epithelial necrosis and sloughing, bronchiolar edema with macrophages, and 

focal pulmonary edema. 

Support for acrolein's respiratory effects and association with increased mortality is 

provided by Kutzman et al. (1984). Dahl rats (derived from the Sprague-Dawley rat) that 

were either susceptible (DS) or resistant (DR) to salt-induced hypertension were exposed in 

whole body inhalation chambers to 0.4, 1.4, and 4.0 ppm (0.9, 3.2, and 9.2 mg/m3) 

acrolein; increased mortality (100% and 40% in DS and DR rats, respectively) was reported 

at 4.0 ppm (9.2 mg/m3). Dose-response increases in the severity of epithelial lesions 

occurred in both species with the DS rats being more sensitive, and demonstrating a 

different pathological response at the high dose. 

A continuous 90-day inhalation study involving exposure of dogs, guinea pigs, rats and 

monkeys to acrolein did not include an examination of the nasal tract by light microscopy 

(Lyon et al., 1970). Exposure concentrations were 0.22, 1.0 and 1.8 ppm (0.5, 2.3, and 4.1 

mg/m3). There was no mention of the use of control animals in the report although Lyon 

(2001) indicated that controls (not concurrent) were used. Two of the four dogs exposed to 

0.22 ppm (0.5 mg/m3) acrolein in this study showed moderate emphysema, acute 

congestion and occasionally some degree of constriction of the bronchioles. Monkeys also 

showed some apparent inflammatory effects at this concentration. It is uncertain if the 

effects seen at this concentration were directly related to exposure given the absence of 

control results. No histopathologic effects were reported for rats or guinea pigs at 0.22 ppm 

(0.5 mg/m3). 

For more detail on Susceptible Populations, exit to the toxicological review, 

Section 4.8 (PDF).
__I.B.5. Confidence in the Inhalation RfC

Study — Medium

Database — Low to Medium

RfC — Medium 

The overall confidence in this RfC assessment is medium. The confidence in the principal 

study is medium. Although the principal study (3 species) was adequately designed and 

examined a wide range of endpoints, it had several shortcomings: (1) only 3 sections of the 

nasal cavity were examined, (2) there was low sample size, and (3) a lack of incidence 

data. Support for the minimal LOAEL is provided by subchronic studies in 2 other species 

(rabbit and hamster) and a 3-day study (Cassee et al., 1996) in the rat in which nasal 

lesions of similar type and severity were observed. The primary limitation in the database is 

the lack of a chronic inhalation study and the attendant uncertainty relating to the 

incidence/severity of nasal lesions at subchronic/chronic exposure levels lower than 0.4 

ppm (0.9 mg/m3). The high reactivity of acrolein at the point of contact, the lack of 

significant systemic distribution demonstrated in studies with the dog and rat, and the lack 

of effects in oral studies lessens the priority for an evaluation of 

reproductive/developmental endpoints in a two-generation inhalation study. Additional 

evaluation of immunological endpoints is warranted especially focusing on potential 

contribution to asthma or compromise in respiratory response. Thus, confidence in the 

database is judged low to medium. The confidence in the RfC is judged medium.

For more detail on Characterization of Hazard and Dose Response, exit to the 

toxicological review, Section 6 (PDF). 

__I.B.6. EPA Documentation and Review of the Inhalation RfC

Source Document — U.S. EPA (2003) 

This assessment was peer reviewed by external scientists. Their comments have been 

evaluated carefully and incorporated in finalization of this IRIS Summary. A record of these 

comments is included as an appendix to the Toxicological Review of Acrolein (U.S. EPA, 

2003). To review this appendix, exit to the toxicological review, Appendix A, 

Summary of External Peer Review Comments and Disposition (PDF).

Agency Consensus Date — 05/16/2003

__I.B.7. EPA Contacts (Inhalation RfC)
Please contact the IRIS Hotline for all questions concerning this assessment or IRIS, in 

general, at (202)566-1676 (phone), (202)566-1749 (FAX) or hotline.iris@epa.gov (internet 

address). 

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_II. Carcinogenicity Assessment for Lifetime Exposure

Substance Name — Acrolein

CASRN — 107-02-8

Last Revised — 06/03/2003 

Section II provides information on three aspects of the carcinogenic assessment for the 

substance in question: the weight-of-evidence judgment of the likelihood that the substance 

is a human carcinogen, and quantitative estimates of risk from oral exposure and inhalation 

exposure. Users are referred to Section I of this IRIS file for information on long-term toxic 

effects other than carcinogenicity. 

The rationale and methods used to develop the carcinogenicity information in IRIS is 

described in the Draft Revised Guidelines for Carcinogen Risk Assessment (U.S. EPA, 1999. 

Guidelines for carcinogen risk assessment. Review Draft, NCEA-F-0644, July. Risk 

Assessment Forum. http://www.epa.gov/ncea/raf/cancer.htm). The quantitative risk 

estimates result from application of a low-dose extrapolation procedure, and both the 

central estimate and upper bound estimate of risk per unit of exposure are presented. The 

quantitative risk estimates are presented in three ways to facilitate their use. The oral slope 

factor is the 95% upper bound on the estimate of risk per (mg/kg)/day of oral exposure. 

The unit risk is the 95% upper bound on the estimate of risk, either per μg/L drinking water 

or per μg/cu.m air breathed. The third form in which risk is presented is the 95% lower 

bound on the estimated concentration of the chemical in drinking water or air associated 

with cancer risks of 1 in 10,000, 1 in 100,000, or 1 in 1,000,000.

_II.A. Evidence for Human Carcinogenicity

__II.A.1. Weight-of-Evidence Characterization

Under the Draft Revised Guidelines for Carcinogen Risk Assessment (U.S. EPA, 1999), 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." 
There are no adequate human studies of the carcinogenic potential of acrolein. Collectively, 

experimental studies provide inadequate evidence that acrolein causes cancer in laboratory 

animals. Specifically, two inhalation bioassays in laboratory animals are inadequate to make 

a determination because of protocol limitations. Two gavage bioassays failed to show an 

acrolein-induced tumor response in 2 species of laboratory animals. Suggestive evidence of 

an extra-thoracic tumorigenic response in a drinking water study in female rats was not 

supported in the reanalysis of data by an independently-convened pathology working group. 

Questions were also raised about the accuracy of the reported levels of acrolein in the 

drinking water from this study. A skin tumor initiation-promotion study was negative, and

the findings from an intraperitoneal injection study were of uncertain significance. Although 

acrolein has been shown to be capable of inducing sister chromatid exchange, DNA crosslinking and mutations under certain conditions, its highly reactive nature and the lack of 

tumor induction at portals of entry make it unlikely that acrolein reaches systemic sites at 

biologically-significant exposure levels. The observations of positive mutagenic results in 

bacterial systems occurred at high concentrations near the lethal dose. 

This evaluation replaces the cancer assessment for acrolein added to the IRIS database in 

1988. Under the Risk Assessment Guidelines of 1986 (EPA/600/8-87/045) applied at that 

time, acrolein was classified as a possible human carcinogen (Category C). The 1988 

classification for acrolein was based on the increased incidence of adrenal cortical adenomas 

in female rats and carcinogenic potential of an acrolein metabolite, its mutagenicity in 

bacteria, and its structural relationship to probable or known human carcinogens. The 

updated cancer characterization considered new study results and reevaluated previous 

studies. 

For more detail on Characterization of Hazard and Dose Response, exit to the 

toxicological review, Section 6 (PDF).

For more detail on Susceptible Populations, exit to the toxicological review, 

Section 4.8 (PDF).

__II.A.2. Human Carcinogenicity Data

No data are available on carcinogenicity in humans exposed solely to acrolein. The only 

study relating to cancer was a nested case control study by Ott et al. (1989), in which 

individuals were classified as having been exposed to one of a large number of chemicals in 

the work environment. The study investigators reported non-Hodgkin's lymphoma (52 

cases), multiple myeloma (20 cases), nonlymphocytic leukemia (39 cases), and lymphocytic 

leukemia (18 cases) within a cohort of employed men from two chemical manufacturing 

facilities and a research and development center. Exposure odds ratios were examined in 

relation to 111 work areas, 21 specific chemicals, and 52 chemical activity groups. Odds 
ratios of 2.6 (2 cases) for non-Hodgkin's lymphoma, 1.7 (1 case) for multiple myeloma, and 

2.6 (3 cases) for nonlymphocytic leukemia were reported for workers exposed to acrolein. 

None of the lower 95% confidence limits exceeded 1.0. Because of a lack of a statistically 

significant increase in the cancer endpoints and the likelihood of confounding by 

concomitant exposure to other chemicals in the workplace, the results must be considered 

equivocal.

__II.A.3. Animal Carcinogenicity Data

Feron and Kryusse (1977) reported negative findings for lung cancer induction in Syrian 

golden hamsters exposed 35 hours/week for 52 weeks to 4.0 ppm (9.2 mg/m3) acrolein via 

inhalation, followed by sacrifice at 81 weeks. Le Bouffant et al. (1980) exposed 20 female 

Sprague-Dawley rats to 8 ppm (18 mg/m3) acrolein, 5 hours/week for 10 or 18 months, 

with negative results. These findings, while negative, nevertheless fail to provide conclusive 

evidence that acrolein is not carcinogenic by the inhalation route. Both the rat and hamster 

studies were (1) less than lifetime, (2) the maximum tolerated dose may not have been 

achieved, and (3) only one concentration was used. 

Negative results for carcinogenicity were reported for Sprague-Dawley rats, 70/sex/group, 

exposed via gavage to acrolein at doses of 0.0, 0.05, 0.5 and 2.5 mg/kg BW for 24 months 

(Parent et al., 1992a). Parent et al. (1991) also reported negative results in Swiss albino 

mice, 70-75/sex/group, administered acrolein via gavage at doses of 0.2, 2.0 and 4.5 

mg/kg/day for 18 months. 

The only suggestive evidence for carcinogenicity of acrolein was marginally significant 

increases in adrenal cortical tumors in a drinking water study reported by Lijinsky and 

Reuber (1987), and weak evidence for tumor initiating ability of acrolein reported by Cohen 

et al. (1992). Because no increase in adrenal cortical tumors was noted for either species in 

the Parent et al. (1991, 1992a) studies, an independent pathology working group (PWG) 

was convened to reevaluate the adrenocortical tumors reported by Lijinsky and Reuber 

(1987). According to the PWG (cited in Parent et al., 1992a), the "slightly elevated 

incidence of pheochromocytomas (3/20; 15%) in the treated females were well within limits 

for historical controls (3/34; 9%) and were of no biological significance (sic)." Parent et al. 

(1992a) further suggested that acrolein at a high dose may not have been as stable as 

assumed in the Lijinsky and Reuber study. Based on some assumptions about water intake 

and rat weight, Parent et al. estimated that the daily dose at the highest concentration 

administered by Lijinsky and Reuber would have exceeded the LD50 for rats. These 

questions concerning the stability of acrolein in high dose solutions and the rate of intake 

render the results of the Lijinsky and Reuber study less certain. Moreover, concurrent 

controls were not used in the Lijinsky and Reuber study. 
Cohen et al. (1992) administered acrolein via intraperitoneal injection, 2 mg/kg/twice 

weekly to male Fischer 344 rats, 30/group, for either 53 weeks or for six weeks followed by 

an additional 47 weeks without treatment. Because of extreme toxicity, the animals were 

sacrificed after 53 weeks, rather than two years as originally planned. No increases in 

tumor incidences were reported. In an additional group administered acrolein for six weeks 

followed by tumor promotion with 3% uracil in the drinking water for 20 weeks, urinary 

bladder papillomas were reported in 18 of 30 and carcinoma in 1 of 30 rats, compared with 

papillomas in 8 of 30 and carcinoma in 1 of 30 rats treated with uracil alone (p<0.05). 

While it appears that acrolein may have some tumor initiating capability, when the 

incidence of nodular hyperplasias (considered precursors to papillomas) and papillomas 

were combined, there were no significant differences between the two groups. Acrolein was 

too toxic to evaluate its tumor promoting potential, and the impact of its cytotoxicity on 

conclusions about its tumor initiating potential cannot be determined from this study alone. 

No sarcomas were reported in a group of 15 female albino mice administered 0.2 mg 

acrolein by subcutaneous injection, weekly for 24 weeks, then held for a lifetime (Steiner et 

al., 1943). No evidence for skin tumor initiating capability was reported in S strain mice 

administered acrolein dermally in ten weekly applications for a total dose of 12.6 

mg/animal, followed by treatment with the tumor promoter croton oil (Salaman and Roe, 

1956).

__II.A.4. Supporting Data for Carcinogenicity 

In vitro, acrolein has been shown to induce DNA adducts in a variety of cell types as well as 

mutagenesis in Drosophila and microorganisms under certain conditions, but there is only 

limited information regarding the ability of acrolein to induce mutations in normal 

mammalian cells. In mammalian cell in vitro assays, acrolein has been shown to induce 

sister chromatid exchange, DNA cross-linking, and binding to DNA polymerase. Even in the 

in vitro assays, acrolein is so reactive that special techniques must generally be employed 

to reduce cytotoxicity and induce positive effects. While mutagenic activity has occasionally 

been shown, positive results generally occurred only in a narrow, near lethal, dose range. 

There have been conflicting results reported in the literature for in vitro mutagenicity. In a 

series of Ames assays, Parent et al. (1996b) proposed an explanation for the conflicting 

data by considering the presence or absence of non-DNA nucleophiles from the S9 

activation mixture, in the test chemical solution, or in the plating solutions. Parent et al. 

suggest that in the presence of non-DNA nucleophiles, acrolein will rapidly and 

indiscriminately react with any available species and not reach the DNA target. 

According to Beauchamp et al. (1985), acrolein administered by the inhalation route is 

retained primarily in the upper respiratory tract because of its reactivity. Some evidence for 
systemic uptake following oral exposure was noted by Draminski et al. (1983); however, 

the large doses used (10 mg/kg) would be expected to induce cellular damage, which may 

allow for some absorption. Tissues at the site of contact are, therefore, expected to be most 

highly exposed, and no evidence of tumor induction in the respiratory tract, skin or 

gastrointestinal tract has been reported. Studies by Parent et al. (1996a, 1998) indicate 

little systemic distribution to tissues. 

The highly reactive nature of acrolein and studies supporting the lack of systemic 

distribution of acrolein suggest that acrolein is not likely to reach potential target sites at a 

sufficient concentration to initiate a carcinogenic process in mammalian species.

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_II.B. Quantitative Estimate of Carcinogenic Risk from Oral 

Exposure

Not applicable.

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_II.C. Quantitative Estimate of Carcinogenic Risk from Inhalation 

Exposure

Not applicable.

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_II.D. EPA Documentation, Review, and Contacts (Carcinogenicity 

Assessment)

__II.D.1. EPA Documentation

Source Document — U.S. EPA (2003). 

This assessment was peer reviewed by external scientists. Their comments have been 

evaluated carefully and incorporated in finalization of this IRIS Summary. A record of these 

comments is included as an appendix to the Toxicological Review of Acrolein (U.S. EPA, 
2003). To review this appendix, exit to the toxicological review, Appendix A, 

Summary of External Peer Review Comments and Disposition (PDF).

__II.D.2. EPA Review (Carcinogenicity Assessment)

Agency Consensus Date — 05/16/2003

__II.D.3. EPA Contacts (Carcinogenicity Assessment)

Please contact the IRIS Hotline for all questions concerning this assessment or IRIS, in 

general, at (202)566-1676 (phone), (202)566-1749 (FAX) or hotline.iris@epa.gov (email 

address). 

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_III. [reserved]

_IV. [reserved] 

_V. [reserved]

_VI. Bibliography 

Substance Name — Acrolein

CASRN — 107-02-8

Last Revised — 06/03/2003

_VI.A. Oral RfD References

Arumugam, N; Thanislass, J; Ragunath, K; et al. (1999) Acrolein-induced toxicity -

defective mitochondrial function as a possible mechanism. Arch Environ Contam Toxicol 

36(4):373-376. 

Bioassay Systems Corp. (1981) Subchronic oral toxicity of acrolein in rats. Project #10258. 

(Results section and tables). 

IRIS. (2003). Glossary of IRIS Terms. Available online at: 

http://www.epa.gov/ncea/iris/help_gloss.htm
National Toxicology Program (NTP). (1995) 13-week gavage toxicity studies of allyl acetate, 

allyl alcohol, and acrolein in Fischer 344 rats and B6C3F1 mice. Abstract with tables. 

Parent, RA; Caravello, HE; Long, JE. (1991) Oncogenicity study of acrolein in mice. J Am 

Coll Toxicol 10(6):647-659. 

Parent, RA; Caravello, HE; Long, JE. (1992a) Two-year toxicity and carcinogenicity study of 

acrolein in rats. J Appl Toxicol 12(2):131-139. 

Parent, RA; Caravello, HE; Hoberman, AM. (1992b) Reproductive study of acrolein on two 

generations of rats. Fundam Appl Toxicol 19(2):228-237. 

Parent, RA; Caravello, HE; Balmer, MF; et al. (1992c) One-year toxicity of orally 

administered acrolein to the beagle dog. J Appl Toxicol 12(5):311-316. 

Parent, RA; Caravello, HE; Christian, MS; et al. (1993) Developmental toxicity of acrolein in 

New Zealand white rabbits. Fundam Appl Toxicol 20(2):248-256. 

Pathology Working Group. (1997) Chairperson's report, Pathology Working Group review of 

acrolein 13-week subchronic gavage study in F344 rats and B6C3F1 mice conducted at 

Battelle-Columbus. 

TERA (Toxicology Excellence for Risk Assessment). (1998). ITER peer review meeting 

summary to review risk assessment documents on acrolein, acrylamide, and acrylonitrile. 

November 16-17, 1998. Available online: http://www.tera.org/peer/nov98final.htm

U.S. EPA (U.S. Environmental Protection Agency). (2003) Toxicological review of acrolein in 

support of summary information on Integrated Risk Information System (IRIS) National 

Center for Environmental Assessment, Washington, DC. EPA/635/R-03/003. Available online 

at: http://www.epa.gov/ncea/iris.

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_VI.B. Inhalation RfC References

Cassee, FR; Groton, JP; Feron, VJ. (1996) Changes in the nasal epithelium of rats exposed 

by inhalation to mixtures of formaldehyde, acetaldehyde, and acrolein. Fundam Appl Toxicol 

29:208-218. 
Costa, DL; Kutzman, RS; Lehmann, JR; et al. (1986) Altered lung function and structure in 

the rat after subchronic exposure to acrolein. Am Rev Resp Dis 133:286-291. 

Feron, VJ; Kryusse, A; Til, HP; et al. (1978) Repeated exposure to acrolein vapor: subacute 

studies in hamsters, rats and rabbits. Toxicology 9:47-57. 

Kutzman, RS. (1981) A subchronic inhalation study of Fischer 344 rats exposed to 0, 0.4 

1.4, or 4.0 ppm acrolein. Brookhaven National Laboratory, Upton, NY. Conducted for the 

National Toxicology Program: Interagency Agreement No. 222-Y01-ES-9-0043. 

Kutzman, RS; Wehner, RW; Haber, SB. (1984) Selected responses of hypertensionsensitive and resistant rats to inhaled acrolein. Toxicology 31(1):53-65. 

Kutzman, RS; Popenoe, EA; Schmaeler, M; et al. (1985) Changes in rat lung structure and 

composition as a result of subchronic exposure to acrolein. Toxicology 34(2):139-151. 

Lyon, JP; Jenkins, LJ, Jr; Jones, RA; et al. (1970) Repeated and continuous exposure of 

laboratory animals to acrolein. Toxicol Appl Pharmacol 17(3):726-732. 

Lyon, JP. (2001) Personal communication with Mark Greenberg, USEPA. 

U.S. EPA (U.S. Environmental Protection Agency). (1994) Methods for derivation of 

inhalation reference concentrations and application of inhalation dosimetry. EPA/600/8-

90/066F. 

U.S. EPA. (2003) Toxicological review of acrolein in support of summary information on 

Integrated Risk Information System (IRIS). National Center for Environmental Assessment, 

Washington, DC. EPA/635/R-03/003. Available online at: http://www.epa.gov/ncea/iris.

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_VI.C. Carcinogenicity Assessment References

Beauchamp, RO, Jr; Andjelkovich, DA; Kligerman, AD; et al. (1985) A critical review of the 

literature on acrolein toxicity. CRC Crit Rev Toxicol 14:309-378. 

Cohen, SM; Garland, EM; St John, M; et al. (1992) Acrolein initiates rat urinary bladder 

carcinogenesis. Cancer Res 52(13):3577-3581. 
Draminski, W; Eder, E; Henschler, D. (1983) A new pathway of acrolein metabolism in rats 

(Short communication). Arch Toxicol 52(3):243-247. 

Feron, VJ; Kryusse, A. (1977) Effects of exposure to acrolein vapor in hamsters 

simultaneously treated with benzo(a)pyrene or diethylnitrosamine. J Toxicol Environ Health 

3:379-394. 

Le Bouffant, L; Martin, JC; Daniel, H; et al. (1980) Actions of intensive cigarette smoke 

inhalations on the rat lung. Role of particulate and gaseous cofactors. J. Natl Cancer Inst 

64(2):273-281. 

Lijinsky, W; Reuber, MD. (1987) Chronic carcinogenesis studies of acrolein and related 

compounds. Toxicol Ind Health 3(3):337-345. 

Ott, MG; Teta, J; Greenberg, HL. (1989) Lymphatic and hematopoietic tissue cancer in a 

chemical manufacturing environment. Am J Ind Med 16:631-643. 

Parent, RA; Caravello, HE; Long, JE. (1991) Oncogenicity study of acrolein in mice. J Am 

Coll Toxicol 11:91-95. 

Parent, RA; Caravello, HE; Long, JE. (1992a) Two-year toxicity and carcinogenicity study of 

acrolein in rats. J Appl Toxicol 12(2):131-139. 

Parent, RA; Caravello, HE; Sharp, DE. (1996a) Metabolism and disposition of [2,3-14C] 

acrolein in Sprague-Dawley rats. J Appl Toxicol 16(5):449-457.

Parent, RA; Caravello, HE; San, RH (1996b) Mutagenic activity of acrolein in S. 

typhimurium and E. coli. J Appl Toxicol 16(2):103-8. 

Parent, RA; Paust, DE; Schrimpf, MK; et al. (1998) Metabolism and distribution of [2,3-

14C]acrolein in Sprague-Dawley rats. II. Identification of urinary and fecal metabolites. 

Toxicol Sci 43(2):110-120. 

Salaman, MH; Roe, FJC. (1956) Further tests for tumour initiating activity: N,N-di(2-

chloroethyl)-p-aminophenylbutyric acid (CB1348) as an initiator of skin tumour formation in 

the mouse. Br J Cancer 10:363-378. 

Steiner, PE; Steele, R; Koch, FC. (1943) The possible carcinogenicity of overcooked meats, 

heated cholesterol, acrolein and heated sesame oil. Cancer Res 3:100-143. 
U.S. EPA (U.S. Environmental Protection Agency). (1999) Guidelines for carcinogen risk 

assessment. Review draft. NCEA-F-0644, July 1999. Risk Assessment Forum. 

U.S. EPA. (2003) Toxicological review of acrolein in support of summary information on 

Integrated Risk Information System (IRIS). National Center for Environmental Assessment, 

Washington, DC. EPA/635/R-03/003. Available online at: http://www.epa.gov/ncea/iris.

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_VII. Revision History

Substance Name — Acrolein

CASRN — 107-02-8 

Date Section Description

09/07/1988 II. Carcinogen summary on-line

04/01/1989 V. Supplementary data on-line

07/01/1989 I.B. Inhalation RfD now under review

03/01/1990 II.A.4. Citations clarified (3rd paragraph)

03/01/1990 VI. Bibliography on-line

05/01/1990 VI.C. Hemminki et al., 1980 citation corrected

10/01/1991 I.B. Inhalation RfC summary on-line

10/01/1991 I.B. Inhalation RfC references added

01/01/1992 IV. Regulatory Action section on-line

07/01/1993 I.B.1. LOAEL(ADJ) corrected

02/01/1994 II.D.3. Secondary contact's phone number changed

04/01/1997 III., IV., V. Drinking Water Health Advisories, EPA Regulatory Actions, and 

Supplementary Data were removed from IRIS on or before April 

1997. IRIS users were directed to the appropriate EPA Program 

Offices for this information.

01/12/2000 I., II. This chemical is being reassessed under the IRIS Program.

06/03/2003 I., II., VI. RfD, RfC and cancer sections updated

12/2/2004 Toxicological 

Review

Technical correction to Toxicological Review describing units for 

ambient exposure levels (section 2) and acute exposure regimen 

in Weber-Tschopp et al. (1977)

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_VIII. Synonyms
Substance Name — Acrolein

CASRN — 107-02-8

Last Revised — 06/03/2003

107-02-8 

acralaldehyde 

acrylaldehyde 

allyl aldehyde 

ethylene aldehyde 

propenal 

prop-2-en-l-al 

2-propenal