| Record Number: 0002
Record Type: IRIS Summary Record
Substance Name: Acrylic acid
CAS RN: 79-10-7
Contents
I.A. REFERENCE DOSE FOR CHRONIC ORAL EXPOSURE (RfD)
I.B. REFERENCE CONCENTRATION FOR CHRONIC
INHALATION EXPOSURE (RfC)
II. CARCINOGENICITY ASSESSMENT FOR LIFETIME EXPOSURE
VI. BIBLIOGRAPHY
VII. REVISION HISTORY
VIII. SYNONYMS
Acrylic acid; CAS RN 79-10-7
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 Acrylic acid
File on-line 01/31/1987
Category (section) Status Last Revised
----------------------------------------- -------- ------------
Oral RfD Assessment (I.A.) on-line 05/01/1994
Inhalation RfC Assessment (I.B.) on-line 05/01/1995
Carcinogenicity Assessment (II.) no data
_I. CHRONIC HEALTH HAZARD ASSESSMENTS FOR NONCARCINOGENIC EFFECTS
__I.A. REFERENCE DOSE FOR CHRONIC ORAL EXPOSURE (RfD)
Substance Name -- Acrylic acid
CAS RN -- 79-10-7
Last Revised -- 05/01/1994
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.
___I.A.1. ORAL RfD SUMMARY
Critical Effect Experimental Doses* UF MF RfD
-------------------- ----------------------- ----- --- ----------
Reduced pup weight NOAEL: 53 mg/kg-day 100 1 5E-1
(500 ppm in water) mg/kg-day
Rat Reproductive
Study LOAEL: 240 mg/kg-day
(2500 ppm in water)
BASF, 1993
*Conversion Factors and Assumptions: Dose in mg/kg-day was reported
based on measurements of actual drinking water concentrations and water
consumption.
___I.A.2. PRINCIPAL AND SUPPORTING STUDIES (ORAL RfD)
Note: The RfD for acrylic acid was originally verified in August 1985.
The RfD was revised because of the availability of new information,
including a two-generation reproductive study in rats, a chronic
drinking water study in rats, developmental studies by the inhalation
route in rats and rabbits, and a bioavailability study in rats and mice.
BASF (Badische Anilin- und Sodafabrik). 1993. Reproduction toxicity
study with acrylic acid in rats: Continuous administration in the
drinking water over 2 generations (1 litter in the first and 1 litter in
the second generation). Project No. 71R0114/92011. BASF
Aktiengesellschaft, Dept. of Toxicology, Rhein, FRG.
In a two-generation reproductive study in rats (BASF, 1993) acrylic
acid was administered in drinking water at concentrations of 0, 500,
2500, and 5000 ppm to groups of 25 male and 25 female Wistar rats (35
days old at the beginning of treatment). After at least 70 days of
treatment, the F0 parental generation animals were mated within the dose
groups to produce one litter. Litters were culled to eight pups at day 4
postparturition, and groups of 25 male and female F1 pups were selected
for the F1 parental generation and were mated after at least 98 days of
treatment. F2 litters were culled to eight pups and were raised to day
21 postpartum. Acrylic acid treatment was continuous throughout the
premating, gestational, and lactational periods. Pups from both
generations were necropsied at day 4 and 21 postpartum. In addition to
body weight, food and water consumption, and general reproductive
parameters, pups were monitored for behavior and developmental
milestones and some pups were examined for visceral and skeletal
abnormalities. The acrylic acid doses were estimated to be 53, 240, and
460 mg/kg-day in the animals receiving 500, 2500, and 5000 ppm in
drinking water, respectively. A consistent finding throughout the study
was decreased water consumption, possibly due to taste aversion, and
reduced body weight gains were observed in some of the groups dosed with
240 and 460 mg/kg-day. Water consumption was reduced 11-14% at 460
mg/kg-day in the F0 parental animals compared with controls throughout
premating, gestation, and lactation, but was not reduced in F0 animals
at 240 mg/kg-day. The F1 parental animals had water intake reduced by
18-27% throughout the study at 460 mg/kg-day and by 6-13% at 240
mg/kg-day. Reductions in body weight were reported that appear to
parallel the reductions in water intake and were more severe in the
pups. In the F0 parental generation exposed to 460 mg/kg-day, the males
showed decreased body weight to 91% of controls, but not until the
postmating period (12-21 weeks), but females were not affected. In the
F1 pups exposed to 460 mg/kg-day, significantly lower body weights were
observed at day 21 of the lactation period (65% of controls). Pup
weights in the 240-mg/kg-day group were reduced to 89% of controls at
day 21 of gestation. The F1 parental animals had reduced food
consumption during the premating period (87-92% of controls) and also
showed lower body weights than controls in the 460-mg/kg-day-dose group.
Because the F1 pups were so much lower in weight in the high-dose group,
the F1 parental generation in the high-dose group weighed 75% of the
controls at 14 weeks prior to mating. This difference was 85-89% of
controls at the time of mating. Thus, although the body weights were
significantly lower in the high-dose F1 parental generation, the overall
weight gain was similar in the F1 parental animals, suggesting that the
effect resulted primarily from the reduced weight during the preweaning
period. In the animals exposed to 240 and 460 mg/kg-day, body weights
were reduced in the F2 pups to 88 and 68% of controls, respectively, and
were associated with reduced maternal water consumption, compared with
controls. Reduced weight was not observed in the parental generations
exposed to 240 mg/kg-day. No changes in water consumption or body
weight were observed in the animals exposed to 53 mg/kg- day. The
reduced weight gain in the F0 generation was less than 10% of controls
in males and is not considered adverse, and the decreased body weight in
the F1 parental generation was greatest at the earliest recorded time
and likely reflects preweaning and early postweaning effects. Reduced
body weight in the F1 and F2 pups was observed at 240 and 460 mg/kg-day.
Although these changes occurred at the end of the period of active
nursing and are associated with decreases in maternal water consumption,
it is not clear that the reduced weight compared with controls can be
attributed only to reduced maternal water intake.
Other endpoints recorded in the two-generation reproductive study
included nesting, littering and lactation behavior, gripping reflex,
hearing startle reflex, pupillary reflex, pinna unfolding, auditory
canal opening, and eye opening. Slight reductions in the number of pups
with eye opening or auditory canal opening on time were statistically
significant in some groups, but are not considered to be adverse. There
were no adverse treatment-related effects on reproductive function. The
only clearly treatment-related adverse effects were histopathological
lesions in the forestomach and glandular stomach in animals exposed to
460 mg/kg-day. Hyperkeratosis of the limiting ridge of the forestomach
and edema of the submucosa of the glandular stomach were observed in
males and females. These lesions were observed in both the F0 and F1
parental generations at 460 mg/kg-day but not at 53 or 240 mg/kg-day.
No reproductive effects were found in the highest dose tested, 460
mg/kg-day. The NOAEL for reproductive effects is 460 mg/kg-day, and the
NOAEL for histological changes in the stomach is 240 mg/kg-day. The
effects on pup weights are considered to be treatment related and
adverse, and this study identifies a LOAEL of 240 mg/kg-day and a NOAEL
of 53 mg/kg-day for this effect.
___I.A.3. UNCERTAINTY AND MODIFYING FACTORS (ORAL RfD)
UF -- The uncertainty factor of 100 includes a factor of 10 for
interspecies extrapolation and a factor of 10 to protect sensitive
individuals. An uncertainty factor for an inadequate data base due to
the lack of a chronic study in a second species was not considered to be
necessary due to the results of the bioavailability study showing no
difference between rats and mice in the rapid rate of elimination of
acrylic acid from oral and intravenous routes.
MF -- None
___I.A.4. ADDITIONAL STUDIES / COMMENTS (ORAL RfD)
In a chronic study (Hellwig et al., 1993; BASF, 1989) acrylic acid
was administered in drinking water to groups of 50 male and female
Wistar rats at concentrations of 0, 120, 400, or 1200 ppm. Drinking
water consumption and body weights were determined regularly throughout
the study, which ran for 26 months for males and 28 months for females.
Blood samples for hematological evaluations were taken at 12, 18, and 24
months and at termination, and complete gross and histopathological
examinations were conducted at the terminal sacrifice. Based on
measurements of drinking water concentration and consumption the doses
were estimated to be 0, 8, 27, and 78 mg/kg-day. Drinking water
consumption was slightly reduced at 78 mg/kg-day, but the difference was
not significant. This result is consistent with the BASF (1993) study
that showed no effect on water consumption in rats exposed to 53
mg/kg-day acrylic acid in drinking water. No clinical signs of toxicity
or changes in body weights were observed in treated animals. No
exposure related changes were seen in the hematological measurements.
Histopathological examinations also showed no clear indications of
target organ pathology. Hyperkeratosis of the forestomach was reported
in a small number of animals, but the change is not clearly exposure
related because of the occurrence of this lesion in the control and
low-dose groups. This lesion also was observed at 460 mg/kg-day by BASF
(1993) in the parental animals, but not at 240 or 53 mg/kg-day acrylic
acid in drinking water. A slight increase in liver fatty change in the
high-dose group also was observed and may be treatment related, but is
not considered adverse because liver effects were not observed in other
drinking water studies at much higher doses. The high-dose group in
this study establishes a NOAEL at the highest dose tested, 78 mg/kg-day,
which supports the NOAEL identified in the critical study.
In a preliminary study to the chronic study (Hellwig et al., 1993;
BASF, 1988) acrylic acid was administered in drinking water to groups of
30 male and female Wistar rats for 3 months (10/sex/group) or 12 months
(20/sex/group). Acrylic acid concentration in drinking water was 0, 120,
800, 2000, and 5000 ppm. Food and drinking water consumption, body
weight, hematology, blood chemistry, and urinalysis were measured
periodically throughout the study. At termination of dosing,
histopathological examination was carried out on tissues from the
control and 2000- and 5000-ppm groups (10 tissues at 3 months and about
40 tissues at 12 months). The estimated doses were 9, 61, 140, and 331
mg/kg-day in the groups exposed to 120, 800, 2000, and 5000 ppm,
respectively. In the 12-month study, drinking water consumption was
reduced in males by 15-20% relative to controls in the 331-mg/kg-day
group during most of the study, and 10% relative to controls in the
140-mg/kg-day group during the first 14 weeks. Female drinking water
consumption was minimally affected. Body weight in males was reduced to
93% of controls at the end of the 3-month study. In the 12-month study,
male body weights were reduced to 94% of controls at 91 days and to
91-92% of controls in males dosed with 140 or 331 mg/kg-day. There was
no effect on body weight in females in the 3- or 12- month studies.
There were no clearly treatment-related effects on blood chemistry,
hematology, or urinalysis parameters. There were also no gross or
histological changes detected in any of the tissues examined. In
particular, the lack of effect in the 331-mg/kg-day-dose group in the
stomach contrasts with the finding of mild histological lesions in the
two-generation reproductive study in the same species at the same
drinking water concentration. This may be explained in part by the
higher dose estimated for the two studies (460 mg/kg-day in the
reproductive study vs. 331 mg/kg-day in the chronic study). This
difference in effect also may be explained by the increase in drinking
water consumption in females during lactation and by the fact that males
in the reproductive study were exposed for up to 20 weeks. These studies
suggest that doses in the 300-500-mg/kg range are near the threshold for
histological effects in the stomach in the subchronic study. Body weight
changes were observed in males at 3 and 12 months but were not more than
10% of control weight and are not considered adverse. Both the
subchronic and the 12-month studies identify a NOAEL for body weight
changes at 331 mg/kg-day (5000 ppm in water), and no specific target
organ effects were observed at this dose.
In contrast to the subchronic drinking water study, Hellwig et al.
(1993; also BASF, 1987) reported a gavage study in which Wistar rats
(10/sex/group) were dosed by gavage with 150 or 375 mg/kg-day in water.
When delivered as a bolus dose at approximately the same doses used in
the subchronic drinking water study, acrylic acid caused death in 10/20
animals at the low dose and 15/20 animals at the high dose (males and
females combined). Marked gross and microscopic effects, as well as
some respiratory tract effects, were observed in the gastrointestinal
tract and kidneys.
DePass et al. (1983) reported a subchronic drinking water study in
which Fischer 344 rats (15/sex/group) were administered doses of 0, 83,
250, or 750 mg/kg-day. Urinalysis, blood chemistry, and hematology were
assessed during the study, and, at study termination, histological
examination of tissues from the control and high-dose groups was
performed. A dose-related decrease in water consumption was observed
that was significant in all dose groups in males and in the 250- and
750-mg/kg-day group females. In males and females at 750 mg/kg-day,
food consumption was decreased and body weight was reduced to 81 and 84%
of controls in males and females, respectively, as were several organ
weights. These effects were not seen in males at 250 mg/kg-day. In
females at 250 mg/kg-day, a significant effect on body weight gain was
reported, but the final body weight was 95% of the controls. There were
no effects noted on histological examination of the high-dose animals. A
NOAEL for changes in body weight and organ weight is identified at 250
mg/kg-day, and there was no specific target organ pathology observed at
750 mg/kg-day. It is not clear whether the forestomach was examined in
this study.
A single generation reproductive study was conducted in which 10
male and 20 female rats were administered acrylic acid in drinking water
at concentrations resulting in doses of 83, 250, and 750 mg/kg-day for 3
months (DePass et al., 1983). After the exposure period, the animals
were mated within exposure groups and exposure was continued throughout
gestation and lactation. Water consumption was reduced to 95, 83, and
61% of controls in the 83-, 250-, and 750-mg/kg-day groups,
respectively, in males and 97, 83, and 58% of controls in females.
Decreases in food consumption and body weight (79% of controls in males
and females) were statistically significant only at the highest dose in
males and at the two higher doses in females. There were no
histological changes observed in high-dose animals in 26 tissues,
including respiratory tract, stomach, liver, and kidneys. An apparent
decrease in the fertility of females and a reduction in gestation index,
number of live pups per litter, and percentage of pups weaned in animals
at the highest dose were observed, but these differences were not
statistically significant compared with the control group. The
unusually low fertility in the control group makes interpretation
difficult. At the highest dose, there was a statistically significant
decrease in body weight of the male and female pups. The males also
exhibited significant decreases in absolute and relative liver weights
and absolute kidney and heart weights at 0.75 g/kg/day. The females
showed a significant decrease in absolute and relative spleen weight and
absolute liver weight at the highest dose. There was an increase in
relative brain weight in both sexes at this dose. This study identifies
a NOAEL for maternal and fetal toxicity and possibly for reproductive
effects at 250 mg/kg-day.
Developmental toxicity studies of inhaled acrylic acid in
Sprague-Dawley rats (Klimisch and Hellwig, 1991) and rabbits (Chun et
al., 1993; Neeper- Bradley and Kubena, 1993) have been reported. These
studies are described in detail in the inhalation RfC (U.S. EPA, 1994).
These studies did not show adverse developmental effects. The rat study
identifies a NOAEL for developmental effects at 360 ppm (1060 mg/cu.m).
The NOAEL for effects on body weight in rats was 40 ppm (120 mg/cu.m).
In the rabbit study, the NOAEL for developmental effects was 225 ppm
(663 mg/cu.m).
Studies of the bioavailability of acrylic acid in mice and rats
evaluated the disposition after administration by the inhalation, oral,
dermal, and i.v. doses (Frantz and Beskitt, 1993; Black, 1993; Kutzman
et al., 1982). These studies are described in detail in the inhalation
RfC (U.S. EPA, 1994). These studies show that acrylic acid administered
by various routes is highly bioavailable and is fairly rapidly
metabolized and excreted. The metabolism and elimination do not appear
to be so fast as to prevent widespread circulation of unchanged acrylic
acid to the body. However, the bioavailability studies have not
attempted to measure acrylic acid at less than 1 hour after exposure.
The half-time for elimination in the in vivo studies was on the order of
20-40 minutes.
Both in vitro and in vivo studies of acrylic acid metabolism have
produced strong evidence that the metabolism proceeds by a mitochondrial
biochemical pathway for propionic acid metabolism, which normally
functions in the body in the final stages of the breakdown of fatty
acids and in the production of intermediates for the tricarboxylic acid
cycle (Black et al., 1993; DeBethizy et al., 1987; Winter and Sipes,
1993; Finch and Frederick, 1992). Metabolism by this route was most
active in the liver and kidney (DeBethizy et al., 1987). This route of
metabolism would explain the rapid rate of elimination as carbon dioxde
and the presence of 3-hydroxypropionate in vitro and in vivo after
administration of acrylic acid. The limited reactivity of acrylic acid
in the body was suggested by the observation that acrylic acid does not
react with glutathione in vitro, nor does it deplete nonprotein
sulfhydryls in blood in vitro (Miller et al., 1981). After an oral dose
of 400 or 1000 mg/kg, nonprotein sulfhydryls (NPSH) were depleted in the
forestomach of rats, and a lower dose of 40 mg/kg also caused a
reduction in NPSH in the glandular stomach (DeBethizy et al., 1987), but
no changes in NPSH were seen in blood or liver. A theoretical analysis
of the potential reactivity of acrylic acid anion (the predominant form
at physiological pH) concluded that there would be very limited
potential for reaction of acrylic acid with cellular nucleophiles, such
as sulfhydryl and amino groups (Frederick and Reynolds, 1989).
The oral and inhalation toxicity studies show portal-of-entry
effects but no indication of specific target organ toxicity at other
sites. Mechanistic and kinetic studies show limited reactivity and
rapid detoxification, but no accumulation of the dose. The rapid
detoxification and the limited reactivity in the body are consistent
with low systemic toxicity. The portal-of-entry effects may result from
high local concentrations that lead to greater tissue reactivity or
changes in pH. The available evidence from both oral and inhalation
routes of exposure suggests that the portal-of-entry effects are true
sentinel effects in that they occur at much lower exposures than
systemic (non-portal-of-entry) effects. In addition, disposition
studies using radiolabeled acrylic acid administered by several routes
show that nearly all of the acrylic acid is absorbed and is metabolized
to carbon dioxide, with very little radioactivity excreted in the urine
or feces. This similarity suggests that it is reasonable to use the
developmental toxicity studies from the inhalation route to support the
data base requirements of the oral RfD. Because the dose of acrylic acid
is distributed fairly rapidly and metabolized similarly for several
routes of exposure, a crude extrapolation of the inhalation
developmental studies to the oral route is reasonable. Based on default
values for rat and rabbit respiration rates and body weights, the NOAELs
for developmental effects in the inhalation studies (in the presence of
respiratory tract effects) are 1140 and 250 mg/kg-day in the rat and
rabbit studies, respectively. This is based on a crude route
extrapolation and is done for the purpose of comparison only. It is
concluded that developmental effects are not critical to the RfD
derivation.
___I.A.5. CONFIDENCE IN THE ORAL RfD
Study -- High
Data Base -- High
RfD -- High
The confidence in the principal studies is high because a sufficient
number of animals were used and all relevant endpoints were reported
thoroughly. The data base contains two developmental studies and two
chronic studies of good quality, all of which are consistent in
identifying the critical effect, resulting in high confidence. High
confidence in the RfD follows.
___I.A.6. EPA DOCUMENTATION AND REVIEW OF THE ORAL RfD
Source Document -- This assessment is not presented in any existing U.S.
EPA document.
Other EPA Documentation -- U.S. EPA, 1984
Agency Work Group Review -- 08/19/1985, 02/17/1994
Verification Date -- 02/17/1994
___I.A.7. EPA CONTACTS (ORAL RfD)
Please contact the IRIS Information Hotline for all questions concerning
this assessment or IRIS, in general, at (301) 345-2870 (phone),
(301) 345-2876 (FAX) or Hotline.IRIS@epamail.epa.gov (internet address).
__I.B. REFERENCE CONCENTRATION FOR CHRONIC INHALATION EXPOSURE (RfC)
Substance Name -- Acrylic acid
CAS RN -- 79-10-7
Last Revised -- 05/01/1995
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
(portal-of-entry) and for effects peripheral to the respiratory system
(extrarespiratory effects). It is 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.
___I.B.1. INHALATION RfC SUMMARY
Critical Effect Exposures* UF MF RfC
-------------------- --------------------------- ----- --- ---------
Degeneration of the NOAEL: None 300 1 1E-3
nasal olfactory mg/cu.m
epithelium LOAEL: 14.94 mg/cu.m
LOAEL(ADJ): 2.67 mg/cu.m
Mouse Subchronic LOAEL(HEC): 0.33 mg/cu.m
Inhalation Study
Miller et al., 1981a
*Conversion Factors and Assumptions -- MW = 72.06. At 21.1 degrees C
and assuming 760 mmHg, LOAEL(mg/cu.m) = 5 ppm x 72.06/24.12 = 14.94.
LOAEL(ADJ) = 14.9mg/cu.m x 6 hours/24 hours x 5 days/7 days = 2.67. The
LOAEL(HEC) was calculated for a gas:respiratory effect in the
ExtraThoracic region. MVa = 0.04 cu.m, MVh = 20 cu.m, Sa(ET) = 2.9
sq.cm, Sh(ET) = 177 sq.cm. RGDR(ET) = (MVa/Sa)/(MVh/Sh) = 0.122.
LOAEL(HEC) = LOAEL(ADJ) x RGDR = 0.33 mg/cu.m.
___I.B.2. PRINCIPAL AND SUPPORTING STUDIES (INHALATION RfC)
Note: The RfC for acrylic acid was originally verified in August 1990.
The RfC was revised because of the availability of new information,
including a two-generation reproductive study in rats, a developmental
study in rabbits, and a bioavailability study in rats and mice. The
uncertainty factor used previously for the incomplete data base was
reduced based on the new data.
Miller, R.R., J.A. Ayres, G.C. Jersey, and M.J. McKenna. 1981a.
Inhalation toxicity of acrylic acid. Fund. Appl. Toxicol. 1(3):
271-277.
Fifteen Fischer 344 rats and 15 B6C3F1 mice of each sex/group were
exposed to actual concentrations measured by infrared analysis of 0, 5,
25, or 75 ppm acrylic acid (0, 14.9, 74.7, or 224 mg/cu.m) (Miller et
al., 1979b, 1981a). The exposure was 6 hours/day, 5 days/week for 13
weeks (duration-adjusted concentrations of 0, 2.66, 13.3, or 40.0
mg/cu.m). Animals were observed twice per day. Parameters monitored
for 10 animals of each sex from each exposure group included body
weight, organ weights, organ-to-body weight ratios, hematologic
parameters (packed-cell volume, erythrocyte count, hemoglobin
concentration, and differential leukocyte counts), clinical chemistry
parameters (urea nitrogen, glucose, SGPT, alkaline phosphatase), and
urinalysis (rats only). All rats and mice in the control and 75-ppm
exposure groups were examined for gross pathology and histopathology of
major tissues, including lung, trachea, and nasal turbinates; the other
exposure groups were examined when positive results were obtained at the
highest dose level. There were no treatment-related deaths of rats or
mice during the study period; three mice died, however, apparently from
traumatic injury due to handling. There were no significant differences
in organ weights, organ-to-body weight ratios, clinical chemistry
parameters, urinalysis parameters, or gross pathology that could clearly
be related to exposure. In mice only, mean hemoglobin was significantly
decreased relative to controls in the 25- and 75- ppm exposure groups
for males and in the 75-ppm exposure group for females; however, the
values were within normal limits for this strain of mice. Focal
degeneration of the olfactory epithelium was observed in 1/10, 2/10,
11/11, and 10/10 male mice and in 0/10, 4/10, 9/10, and 12/12 female
mice in the control and 5-, 25-, and 75-ppm exposure groups,
respectively. The LOAEL is therefore 5 ppm [LOAEL(HEC) = 0.33 mg/cu.m]
for effects in the nasal olfactory epithelium. The severity as well as
the incidence of the lesion increased with exposure concentration. A
NOAEL in mice was not determined in this study. No effects were
observed in the lungs, trachea, larynx, or GI tract. Rats first
demonstrated lesions of the nasal olfactory epithelium at 75 ppm; there
were no effects at 25 ppm [NOAEL(HEC) = 1.43 mg/cu.m].
___I.B.3. UNCERTAINTY AND MODIFYING FACTORS (INHALATION RfC)
UF -- A factor of 10 is used for protection of sensitive human
subpopulations. A factor of 3 is used for extrapolation from subchronic
to chronic duration due to limited progression between short-term and
subchronic exposures and due to rapid metabolism. A factor of 10 is
applied to account for both interspecies extrapolation, because
dosimetric adjustments were applied, and use of a LOAEL because the
effect is considered mild.
MF -- None
___I.B.4. ADDITIONAL STUDIES / COMMENTS (INHALATION RfC)
In a 2-week subacute inhalation study (Miller et al., 1979a), rats
and mice (5/sex/group) were exposed to actual concentrations of 0, 25,
74, or 223 ppm (0, 75, 220, or 666 mg/cu.m) acrylic acid for 6
hours/day, 5 days/week (duration-adjusted concentrations of 13, 40, or
119 mg/cu.m). Significant decreases in body weight gain were seen in
exposed groups at 223 ppm. Decreased body weight gains in male mice at
25 and 74 ppm are not considered exposure related because of the low
initial weights and unusually large weight gains in the controls. A
decrease in adipose tissue was observed in female rats at 223 ppm. Rats
had lesions of the nasal mucosa at 223 ppm. Mice had dose-related
lesions of the nasal mucosa, with lesions increasing in size, severity,
and incidence from 25 to 223 ppm. Comparison of the degenerative
lesions observed at the 25-ppm exposure in the 2-week and subchronic
studies (Miller et al., 1981a) reveals that there is an increase in
incidence (6/10 at 2 weeks vs. 19/20 subchronic; males and females
combined) and limited progression in severity. For this reason, the
likelihood of progression of the lesion with further exposure may be
limited as well, and the uncertainty in extrapolating from the
subchronic study to the chronic scenario is reduced. This study
identifies a NOAEL in rats for body weight changes at 74 ppm [NOAEL(HEC)
= 40 mg/cu.m for extrarespiratory effect assuming lambda(a)/lambda(h) =
1 and periodicity attained] and a LOAEL for nasal effects in rats at 74
ppm [LOAEL(HEC) = 4.2 mg/cu.m]. The LOAEL for extrathoracic respiratory
effects in mice is 25 ppm [LOAEL(HEC) = 1.6 mg/cu.m]. No effects on
lung or trachea were observed in rats or mice.
Alderly Park rats were exposed to several concentrations of acrylic
acid for different durations to determine the acute and subacute
toxicity of the chemical (Gage, 1970). One 5-hour exposure to an
atmosphere saturated with acrylic acid [6000 ppm (17,700 mg/cu.m)]
produced nose and eye irritation, respiratory difficulty, and
unresponsiveness in four rats (two males and two females). One rat
died. Eight rats (four males and four females) exposed to 1500 ppm for
6 hours/day for 4 days showed nasal discharge, lethargy, and weight
loss. Exposure to 80 or 300 ppm for 6 hours/day, 5 days/week, for 4
weeks produced some nose irritation, lethargy, retarded weight gain in
eight rats at the higher dose. Histopathology showed all organs were
normal in both groups, and no signs of toxicity were observed at the
lower dose; but limited information is reported. This study suggests
that concentrations much higher than those used in the principal study
are required to produce overt systemic toxicity.
Rats exposed for 1 hour to acrylic acid concentrations of 100, 300,
or 500 ppm exhibited dose-dependent decreases in both respiratory
frequency and minute volume (Silver et al., 1981). Buckley et al.
(1984) reported concentrations resulting in a 50% decrease in
respiratory rate of 685 ppm in B6C3F1 mice and 513 ppm in Fischer 344
rats. Respiratory irritation and reduced ventilation therefore are not
expected at the concentrations used in the principal study.
A developmental toxicity study of inhaled acrylic acid in
Sprague-Dawley rats was reported by Klimisch and Hellwig (1991). In a
preliminary study, groups of five pregnant animals were exposed to 0,
225, or 450 ppm acrylic acid for 6 hours/day on days 6-15 of gestation.
Signs of nasal and eye irritation were observed in both exposed groups
during exposure, and, at necropsy on day 20 of gestation, degeneration
of the olfactory epithelium of the nose with metaplasia of the
respiratory epithelium were observed in all exposed animals. Body weight
gain was reduced throughout exposure at 450 ppm. Assessment of
developmental endpoints was not done in the preliminary study. In the
definitive study, groups of 30 pregnant Sprague-Dawley rats were exposed
to 0, 40, 120, or 360 ppm acrylic acid (0, 120, 350, or 1060 mg/cu.m)
for 10 days during days 6-15 of gestation. Maternal toxicity was
evident in animals exposed to 120 and 360 ppm because body weight was
reduced in the 360- ppm group on days 15 and 20, and body weight minus
uterus weight was reduced in animals exposed to 120 or 360 ppm on day
20. Signs of irritation were observed throughout the exposure in the
360-ppm group, but not at 40 or 120 ppm. Histopathological examination
was not performed in the dams. No exposure-related adverse effects
were observed on implantations, live implantations, resorptions,
preimplantation loss, fetal length or weight, or on morphological
abnormalities (skeletal or soft tissue). This study identifies a NOAEL
for developmental effects at 360 ppm [NOAEL(HEC) = 1060 mg/cu.m] and a
LOAEL for maternal body weight effects at 120 ppm [LOAEL(HEC) = 88
mg/cu.m].
An inhalation developmental study was also reported in rabbits. In
the range-finding study (Chun et al., 1993), groups of eight pregnant
New Zealand white rabbits were exposed to 0, 30, 60, 125, or 250 ppm
acrylic acid on days 10-23 of gestation. Three animals per group were
necropsied on day 23 of gestation, and the remaining animals were
examined on day 29. Exposure- related maternal toxicity in the 125- and
250-ppm groups was observed, including signs of nasal irritation and
reduced body weight. Final body weight was reduced to a lesser degree
in animals exposed to 30 and 60 ppm. Histopathological examination of a
single section of the nose showed adverse effects in the olfactory
epithelium. The lesions included squamous metaplasia, epithelial
erosion, and ulceration of the epithelium and increased in severity with
increasing exposure concentration, with the effect first appearing in
the 30-ppm group at day 23 and in the 60-ppm group at day 29. In the
definitive developmental study (Neeper-Bradley and Kubena, 1993), groups
of 16 pregnant rabbits were exposed to 0, 25, 75, or 225 ppm acrylic
acid on gestation days 6-18. Maternal toxicity was evident in groups
exposed to 225 or 75 ppm, but not to 25 ppm. Signs of nasal irritation
including perinasal wetness and nasal congestion were observed.
Significant decrements in food consumption and body weight gain were
observed occasionally during exposure, but the body weights at the end
of the exposure were not significantly affected. Histological
examination of maternal tissues was not performed. No exposure-related
adverse effects were observed in the number of corpora lutea and total,
viable, or nonviable implantations; preimplantation loss; fetal length
or weight; or on morphological abnormalities (skeletal or soft tissue).
This study identifies a NOAEL for developmental effects at 225 ppm
[NOAEL(HEC) = 663 mg/cu.m].
In a two-generation reproductive study in rats (BASF, 1993) acrylic
acid was administered in drinking water at concentrations of 0, 500,
2500, and 5000 ppm to groups of 25 male and 25 female Wistar rats (35
days old at the beginning of treatment). This study is described in
more detail in the oral RfD (U.S. EPA, 1994). A consistent finding
throughout the study was decreased water consumption and body weight
gain in some of the groups dosed with 240 and 460 mg/kg-day. Reduction
in body weights paralleling the reductions in water intake were more
severe in the pups. The effect on pup weights are considered to be
treatment related and adverse, and this study identifies a LOAEL of 240
mg/kg-day and a NOAEL of 53 mg/kg-day for this effect.
A single-generation reproductive study was conducted by the oral
route of exposure in which 10 male and 20 female rats were administered
acrylic acid in drinking water at concentrations resulting in doses of
83, 250, and 750 mg/kg-day for 3 months (DePass et al. 1983). This
study is described in more detail in the oral RfD (U.S. EPA, 1994).
Decreases in food consumption and body weight gain were statistically
significant only at the highest dose in males and at the two higher
doses in females. This study identifies a LOAEL for maternal and fetal
toxicity and possibly for reproductive effects at 750 mg/kg-day.
A study of the bioavailability of acrylic acid in mice and rats
evaluated the disposition of oral, dermal, and i.v. doses (Frantz and
Beskitt, 1993). Carbon-14-labeled acrylic acid (carboxyl carbon) was
administered at 10 mg/kg i.v., 40 or 150 mg/kg orally, or 10 or 40 mg/kg
dermally, and expired air, urine, feces, and tissues were analyzed for
radioactivity at various times after dosing. Regardless of route, the
majority (more than 75%) of the recovered radioactivity was eliminated
as exhaled carbon dioxide within the first 24 hours after exposure. Most
of the i.v. dose was exhaled within the first hour. After oral dosing,
most of the dose was exhaled as carbon dioxide during the first hour,
but a significant amount remained in the gut 1 hour after dosing.
Analysis of the chemical form of the radioactivity measured in this
study was reported (Black, 1993). One hour after dosing with 150 mg/kg,
a very small amount of unchanged acrylic acid were found in the liver
and urine but was undetectable in the plasma. Unchanged acrylic acid
was not detected after 40 mg/kg. In contrast, 3-hydroxypropionate, a
product of acrylic acid metabolism, was found in plasma and tissues
after oral administration. In a study of acrylic acid disposition after
inhalation exposure, Kutzman et al (1982) exposed rats to
carbon-1-labeled acrylic acid for 1 minute. At 1.5 minutes following
exposure, most of the radioactivity was associated with the head,
suggesting a high degree of nasal deposition. By 65 minutes after
exposure, most of the acrylic acid had been expired as carbon dioxide.
These studies show that acrylic acid administered by various routes is
highly bioavailable and is fairly rapidly metabolized and excreted. The
metabolism and elimination do not appear to be so fast as to prevent
widespread circulation of unchanged acrylic acid to the body. The
half-time for elimination in the in vivo studies was on the order of
20-40 minutes.
Both in vitro and in vivo studies of acrylic acid metabolism have
produced strong evidence that the metabolism proceeds by a mitochondrial
biochemical pathway for propionic acid metabolism that normally
functions in the body in the final stages of the breakdown of fatty
acids and the production of intermediates for the tricarboxylic acid
cycle (Black et al., 1993; DeBethizy et al., 1987; Winter and Sipes,
1993; Finch and Frederick, 1992). This route of metabolism would
explain the rapid rate of elimination as carbon dioxide and the presence
of 3-hydroxypropionate in vitro and in vivo after administration of
acrylic acid. The limited reactivity of acrylic acid in the body was
suggested by the observation that acrylic acid does not react with
glutathione in vitro nor does it deplete nonprotein sulfhydryls in blood
in vitro (Miller et al., 1981b). After an oral dose of 400 or 1000
mg/kg, nonprotein sulfhydryls (NPSH) were depleted in the forestomach of
rats (88 or 54% of control, respectively), and a lower dose of 40 mg/kg
also caused a reduction in NPSH in the glandular stomach (77% of
control; 64 and 25% of control at 400 and 1000 mg/kg, respectively)
(DeBethizy et al., 1987), but no changes in NPSH were seen in blood or
liver. In these studies, increases in dose were achieved by increases
in gavage solution concentrations (0.8, 8, and 20% solutions were used).
A theoretical analysis of the potential reactivity of acrylic acid anion
(the predominant form at physiological pH) concluded that very limited
potential exists for reaction of acrylic acid with cellular
nucleophiles, such as sulfhydryl and amino groups (Frederick and
Reynolds, 1989).
The oral and inhalation toxicity studies show portal-of-entry
effects and no indication of specific target organ toxicity at other
sites. Mechanistic and kinetic studies show limited reactivity, rapid
detoxification, and no accumulation of the dose. The rapid
detoxification and the limited reactivity in the body are consistent
with low systemic toxicity. The portal-of-entry effects may result from
high local concentrations that lead to greater tissue reactivity or
changes in local pH. The available evidence from both oral and
inhalation routes of exposure suggest that the portal-of-entry effects
are true sentinel effects in that they occur at much lower exposures
than systemic (non-portal-of-entry) effects. In addition, disposition
studies using radiolabeled acrylic acid administered by several routes
show that nearly all of the acrylic acid is absorbed and is metabolized
to carbon dioxide, with very little excreted in the urine or feces. This
similarity suggests that it is reasonable to use the reproductive
toxicity study from the oral route to support the data base requirements
of the RfC. Because the dose of acrylic acid is distributed fairly
rapidly and metabolized similarly for several routes of exposure, a
crude extrapolation of the oral reproductive studies to the inhalation
route is reasonable. Based on default values for rat respiration rates
and body weight, the NOAEL for reproductive toxicity is much greater
than the NOAEL for nasal effects. This is based on a crude route
extrapolation and is done for purpose of comparison only. It is
concluded that reproductive effects are not critical to the RfC
derivation.
___I.B.5. CONFIDENCE IN THE INHALATION RfC
Study -- Medium
Data Base -- Medium
RfC -- Medium
The study by Miller et al. (1981a) was well conducted and identified
a LOAEL for a mild occurence of the most sensitive effect. The
confidence in the study was determined to be medium because a NOAEL was
not identified, a small number of animals was used, and there is limited
description of the nasal lesion reported. Although a subchronic
inhalation study in a second species, two inhalation developmental
studies in different species, and a two- generation reproductive study
by the oral route support the principal study, the confidence in the
data base is medium due to lack of chronic data. The confidence in the
RfC is medium.
___I.B.6. EPA DOCUMENTATION AND REVIEW OF THE INHALATION RfC
Source Document -- This assessment is not presented in any existing U.S.
EPA document.
Other EPA Documentation -- U.S. EPA, 1984
Agency Work Group Review -- 08/23/1990, 02/17/1994
Verification Date -- 02/17/1994
___I.B.7. EPA CONTACTS (INHALATION RfC)
Please contact the IRIS Information Hotline for all questions concerning
this assessment or IRIS, in general, at (301) 345-2870 (phone),
(301) 345-2876 (FAX) or Hotline.IRIS@epamail.epa.gov (internet address).
_II. CARCINOGENICITY ASSESSMENT FOR LIFETIME EXPOSURE
Substance Name -- Acrylic acid
CAS RN -- 79-10-7
Not available at this time.
_VI. BIBLIOGRAPHY
Substance Name -- Acrylic acid
CAS RN -- 79-10-7
Last Revised -- 04/01/1994
__VI.A. ORAL RfD REFERENCES
BASF (Badische Anilin- und Sodafabrik). 1987. Report on the study of
the toxicity of acrylic acid in rats after 3-month administration by
gavage. Project No. 35C0380/8250. BASF Aktiengesellschaft, Dept. of
Toxicology, Rhein, FRG.
BASF (Badische Anilin- und Sodafabrik). 1988. Report on the study of
the toxicity of acrylic acid in rats after 12-month administration in
drinking water. Project No. 74C0380/8239. BASF Aktiengesellschaft,
Dept. of Toxicology, Rhein, FRG.
BASF (Badische Anilin- und Sodafabrik). 1989. Study of a potential
carcinogenic effect of acrylic acid in rats after long term
administration in the drinking water. Project No. 72C0380/8240. BASF
Aktiengesellschaft, Dept. of Toxicology, Rhein, FRG.
BASF (Badische Anilin- und Sodafabrik). 1993. Reproduction toxicity
study with acrylic acid in rats: Continuous administration in the
drinking water over 2 generations (1 litter in the first and 1 litter in
the second generation). Project No. 71R0114/92011. BASF
Aktiengesellschaft, Dept. of Toxicology, Rhein, FRG.
Black, K.A. 1993. 14C-Acrylic acid comparative bioavailability study
in male mice and rats - analysis of tissues. Rohm and Haas Co. Report
No. 93R-200, Spring House, PA.
Black, K.A., L. Finch, and C.B. Frederick. 1993. Metabolism of acrylic
acid to carbon dioxide in mouse tissues. Fund. Appl. Toxicol. 21:
97-104.
Chun, J.S., M.F. Kubena, and T.L. Neeper-Bradley. 1993. Developmental
toxicity dose range-finding study of inhaled acrylic acid vapor in New
Zealand white rabbits. Bushy Run Research Center Report No. 92N1007,
Union Carbide Co., Export, PA.
DeBethizy, J.D., J.R. Udinsky, H.E. Scribner, and C.B. Frederick. 1987.
The disposition and metabolism of acrylic acid and ethyl acrylate in
male Sprague- Dawley rats. Fund. Appl. Toxicol. 8: 549-561.
DePass, L.R., M.D. Woodside, R.H. Garman, and C.S. Weil. 1983.
Subchronic and reproductive toxicology studies on acrylic acid in the
drinking water of the rat. Drug. Chem. Toxicol. 6(1): 1-20.
Finch, L. and C.B. Frederick. 1992. Rate and route of oxidation of
acrylic acid to carbon dioxide in rat liver. Fund. Appl. Toxicol. 19:
498-504.
Frantz, S.W. and J.L. Beskitt. 1993. 14C-Acrylic acid: Comparative
bioavailability study in male mice and rats. Bushy Run Research Center
Report No. 92N1005, Union Carbide Co., Export, PA.
Frederick, C.B. and C.H. Reynolds. 1989. Modeling the reactivity of
acrylic acid and acrylate anion with biological nucleophiles. Toxicol.
Lett. 47: 241-247.
Hellwig, J., K. Deckardt, and K.O. Freisberg. 1993. Subchronic and
chronic studies of the effects of oral administration of acrylic acid to
rats. Fd. Chem. Toxicol. 31(1): 1-18.
Klimisch, H.-J. and J. Hellwig. 1991. The prenatal inhalation toxicity
of acrylic acid in rats. Fund. Appl. Toxicol. 16: 656-666.
Kutzman, R.S., G.-J. Meyer, and A.P. Wolf. 1982. The biodistribution
and metabolic fate of [11C]acrylic acid in the rat after acute
inhalation exposure or stomach intubation. J. Toxicol. Environ. Health.
10: 969-979.
Miller, R.R., J.A. Ayres, L.W. Rampy, and M.J. McKenna. 1981.
Metabolism of acrylate esters in rat tissue homogenates. Fund. Appl.
Toxicol. 1: 410-414.
Neeper-Bradley, T.L. and M.F. Kubena. 1993. Developmental toxicity
evaluation of inhaled acrylic acid vapor in New Zealand white rabbits.
Bushy Run Research Center Report No. 92N1008, Union Carbide Co., Export,
PA.
U.S. EPA. 1984. Health and environmental effects profile for
2-propenoic acid. Office of Health and Environmental Assessment,
Environmental Criteria and Assessment Office, Cincinnati, OH.
EPA/600/X-84/146.
U.S. EPA. 1994. Integrated Risk Information System (IRIS). Online.
Office of Health and Environmental Assessment, Environmental Criteria
and Assessment Office, Cincinnati, OH.
Winter, S.M. and I.G. Sipes. 1993. The disposition of acrylic acid in
the male Sprague-Dawley rat following oral or topical administration.
Fd. Chem. Toxicol. 31(9): 615-621.
__VI.B. INHALATION RfC REFERENCES
BASF (Badische Anilin- und Sodafabrik). 1993. Reproduction toxicity
study with acrylic acid in rats: Continuous administration in the
drinking water over 2 generations (1 litter in the first and 1 litter in
the second generation). Project No. 71R0114/92011. BASF
Aktiengesellschaft, Dept. of Toxicology, Rhein, FRG.
Black, K.A. 1993. 14C-Acrylic acid comparative bioavailability study
in male mice and rats - analysis of tissues. Rohm and Haas Co. Report
No. 93R-200, Spring House, PA.
Black, K.A., L. Finch, and C.B. Frederick. 1993. Metabolism of acrylic acid
to carbon dioxide in mouse tissues. Fund. Appl. Toxicol. 21: 97-104.
Buckley, L.A., R.A. James, and C.S. Barrow. 1984. Differences in nasal
cavity toxicity between rats and mice exposed to acrylic acid vapor.
Toxicologist. 4: 1 (Abstract).
Chun, J.S., M.F. Kubena, and T.L. Neeper-Bradley. 1993. Developmental
toxicity dose range-finding study of inhaled acrylic acid vapor in New Zealand
white rabbits. Bushy Run Research Center Report No. 92N1007, Union Carbide
Co., Export, PA.
DeBethizy, J.D., J.R. Udinsky, H.E. Scribner, and C.B. Frederick. 1987. The
disposition and metabolism of acrylic acid and ethyl acrylate in male Sprague-
Dawley rats. Fund. Appl. Toxicol. 8: 549-561.
DePass, L.R., M.D. Woodside, R.H. Garman, and C.S. Weil. 1983. Subchronic
and reproductive toxicology studies on acrylic acid in the drinking water of
the rat. Drug. Chem. Toxicol. 6(1): 1-20.
Finch, L. and C.B. Frederick. 1992. Rate and route of oxidation of acrylic
acid to carbon dioxide in rat liver. Fund. Appl. Toxicol. 19: 498-504.
Frantz, S.W. and J.L. Beskitt. 1993. 14C-Acrylic acid: Comparative
bioavailability study in male mice and rats. Bushy Run Research Center Report
No. 92N1005, Union Carbide, Export, PA.
Frederick, C.B. and C.H. Reynolds. 1989. Modeling the reactivity of acrylic
acic and acrylate anion with biological nucleophiles. Toxicol. Lett. 47:
241-247.
Gage, J.C. 1970. The subacute inhalation toxicity of 109 industrial
chemicals. Br. J. Ind. Med. 27: 1-18.
Klimisch, H.-J. and J. Hellwig. 1991. The prenatal inhalation toxicity of
acrylic acid in rats. Fund. Appl. Toxicol. 16: 656-666.
Kutzman, R.S., G.-J. Meyer, and A.P. Wolf. 1982. The biodistribution and
metabolic fate of [11C]acrylic acid in the rat after acute inhalation exposure
or stomach intubation. J. Toxicol. Environ. Health. 10: 969-979.
Miller, R.R., J.A. Ayres, and G.C. Jersey. 1979a. Acrylic acid 10-day vapor
inhalation study with rats and mice, final report. No. 79RC-1015. Toxicology
Research Laboratory, Health and Environmental Science, Dow Chemical Co.,
Midland, MI.
Miller, R.R., J.A. Ayres, and G.C. Jersey. 1979b. Acrylic acid 90-day vapor
inhalation study with rats and mice, final report. No. 79RC-1024. Toxicology
Research Laboratory, Health and Environmental Science, Dow Chemical Co.,
Midland, MI.
Miller, R.R., J.A. Ayres, G.C. Jersey, and M.J. McKenna. 1981a. Inhalation
toxicity of acrylic acid. Fund. Appl. Toxicol. 1(3): 271-7.
Miller, R.R., J.A. Ayres, L.W. Rampy, and M.J. McKenna. 1981b. Metabolism of
acrylate esters in rat tissue homogenates. Fund. Appl. Toxicol. 1: 410-414.
Neeper-Bradley, T.L. and M.F.Kubena. 1993. Developmental toxicity evaluation
of inhaled acrylic acid vapor in New Zealand white rabbits. Bushy Run
Research Center Report No. 92N1008, Union Carbide Co., Export, PA.
Silver, E.H., D.E. Leith, and S.D. Murphy. 1981. Potentiation by
triorthotolyl phosphate of acrylate ester-induced alterations in respiration.
Toxicology. 22(3): 193-203.
U.S. EPA. 1984. Health and environmental effects profile for 2-propenoic
acid. Office of Health and Environmental Assessment, Environmental Criteria
and Assessment Office, Cincinatti, OH. EPA 600/X-84/146.
U.S. EPA. 1994. Integrated Risk Information System (IRIS). Online. Office
of Health and Environmental Assessment, Environmental Criteria and Assessment
Office, Cincinnati, OH.
Winter, S.M. and I.G. Sipes. 1993. The disposition of acrylic acid in the
male Sprague-Dawley rat following oral or topical administration. Fd. Chem.
Toxicol. 31(9): 615-621.
__VI.C. CARCINOGENICITY ASSESSMENT REFERENCES
None
_VII. REVISION HISTORY
Substance Name -- Acrylic acid
CAS RN -- 79-10-7
-------- -------- --------------------------------------------------------
Date Section Description
-------- -------- --------------------------------------------------------
03/01/1988 I.A.5. Confidence levels revised
03/31/1987 I.A.6. Documentation corrected
03/01/1988 I.A.2. Paragraph 3 deleted
08/01/1989 VI. Bibliography on-line
09/01/1990 I.B. Inhalation RfC now under review
10/01/1990 I.B. Inhalation RfC summary on-line
10/01/1990 VI.B. Inhalation RfC references added
01/01/1992 I.A.7. Primary contact changed
01/01/1992 IV. Regulatory actions updated
03/01/1994 I.A. Withdrawn; new oral RfD verified (in preparation)
03/01/1994 I.B. Withdrawn; new inhalation RfC verified (in preparation)
03/01/1994 VI. Bibliography withdrawn
04/01/1994 I.A. Oral RfD summary replaced; new RfD
04/01/1994 I.B. Inhalation RfC summary replaced; new RfC
04/01/1994 VI.A. Oral RfD references replaced
04/01/1994 VI.B. Inhalation RfC references replaced
05/01/1994 I.A.2. Note moved from Add. Com. Sec. to Prin. Sup. Stud. Sec
05/01/1994 I.B.1. Note moved from Add. Com. Sec. to Prin. Sup. Stud. Sec
05/01/1995 I.B.4. Text edited (9th paragraph)
04/01/1997 III.,IV., Drinking Water Health Advisories, EPA Regulatory Actions, and
V. Supplementary Data were removed from IRIS on or before April
1997. IRIS users were directed to the appropriate EPA Program
Offices for this information.
VIII. SYNONYMS
Substance Name -- Acrylic acid
CAS RN -- 79-10-7
Last Revised -- 01/31/1987
79-10-7
Acroleic acid
Acrylic Acid
Acrylic acid, glacial
Ethylenecarboxylic acid
Propene acid
Propenoic acid
2-Propenoic acid
RCRA waste number U008
UN 2218
## |
