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Acrylic acid
CASRN 79-10-7
Contents
0002
Acrylic acid; CASRN 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
CASRN -- 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 Risk Information Hotline for all questions concerning this
assessment or IRIS, in general, at (513)569-7254 (phone), (513)569-7159 (FAX)
or RIH.IRIS@EPAMAIL.EPA.GOV (internet address).
__I.B. REFERENCE CONCENTRATION FOR CHRONIC INHALATION EXPOSURE (RfC)
Substance Name -- Acrylic acid
CASRN -- 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 Risk Information Hotline for all questions concerning this
assessment or IRIS, in general, at (513)569-7254 (phone), (513)569-7159 (FAX)
or RIH.IRIS@EPAMAIL.EPA.GOV (internet address).
_II. CARCINOGENICITY ASSESSMENT FOR LIFETIME EXPOSURE
Substance Name -- Acrylic acid
CASRN -- 79-10-7
Not available at this time.
_VI. BIBLIOGRAPHY
Substance Name -- Acrylic acid
CASRN -- 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
CASRN -- 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)
VIII. SYNONYMS
Substance Name -- Acrylic acid
CASRN -- 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
Last updated: 5 May 1998
URL: http://www.epa.gov/iris/SUBST/0002.HTM
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