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EC number: 212-454-9
CAS number: 818-61-1
oral toxicity (OECD TG 401), LD50 = 540 mg/kg bw
Acute dermal toxicity (OECD TG 402),
> 1000 mg/kg bw.
Under the conditions of this study the acute
dermal median lethal dose (LD50) of 2 -Hydroxyethyl acrylate was found
to be greater than 1000 mg/kg body weight for the male animals. Due to
animal welfare reason (necrosis of the skin) the other sex was not
tested. In a study performed in parallel with the similar test substance
Hydroxypropyl acrylate (Project-No. 11A0185/981043) no mortality
occurred after application of 1000 mg/kg body weight to 5 female
animals. Therefore the acute dermal median lethal dose (LD50) of 2
-Hydroxyethyl acrylate is considered to be greater than 1000 mg/kg body
weight for the male and female animals.
Dose [mg/kg bw]
Oral exposure route:
There are several valid studies
available that are acceptable for assessing the acute oral toxicity of
2-hydroxyethyl acrylate in rats.
The key acute toxicity oral study was
performed with Sherman rats (Dow Chem. Co., 1980). Groups of 5 male
Sherman rats were administered doses of 126, 252, 500, 1000, and 2000
mg/kg bw by gavage. The animals were observed for lethality, changes in
general appearance and demeanor and body weight gain during a 14-day
post-exposure period. No data were given concerning clinical signs or
necropsy findings and LD50 was determined to be 540 mg/kg bw with 95 %
confidence limits of 390 to 750.
In another acute toxicity study
conducted by BASF (1974) according to an internal protocol comparable to
the OECD TG 401 groups of 5 Sprague-Dawley rats/sex/dose were
administered doses of approx. 202, 404, 809, 1137, and 1618 mg/kg bw by
gavage and observed for 7 days for lethality and clinical signs of
intoxication. The mortality rate was 0/10, 0/10, 3/10, 7/10, and 10/10
in the low, mid and high dose groups, respectively. The LD50 was found
to be approx. 960.5 mg/kg bw. Clinical symptoms were unspecific:
dyspnoea, slight apathy, closed eyes, and squatting posture. In the
surviving animals, reduction of body weight as compared to weights
determined at test start was noted. At necropsy acute dilatation of the
right heart chamber, acute congestive hyperemia of the heart, and
stomach dilatation with distinctly injected vessels were recorded in the
deceased animals. The sacrificed animals of the mid dose group showed at
necropsy dilatation of the gastro-oesophageal vestibule, adhesion to the
peritoneum, and alterations of the epithelium of the glandular stomach
(epithelial foldings plump and irregular). These data indicate, that the
substance causes local skin damage in the GI-tract due its corrosivity,
which might at least partially be responsible for the effects noted
(BASF AG, 1974).
Similar LD50 values were observed in three
other studies (Union Carbide Corporation (1966), Smyth et al (1951), and
The Dow Chemical Company (1962)).
Based on these test results (LD50 >
500 - < 1000 mg/kg bw), 2-hydroxyethyl acrylate is assessed to be of
moderate toxicity after a single ingestion, which might be at least
partially due to the local tissue damage.
Dermal exposure route:
The key acute dermal toxicity study of
the test substance was a GLP-compliant study according to OECD Guideline
402 (BASF, 1999a). A group of 5 male and 5 female Wistar rats (400 mg/kg
bw) and a second group of 5 male rats (1000 mg/kg bw) were tested. The
test material was applied in undiluted form (400 mg/kg bw) or as an
emulsion in olive oil DAB 10 (1000 mg/kg bw) to the clipped epidermis
(dorsal and dorsolateral parts of the trunk) of each animal and was
covered by a semi-occlusive dressing for 24 hours. No systemic signs of
toxicity were noted in all animals. Local effects, observed in the 400
and 1000 mg/kg bw dose groups comprised very slight, well-defined and
moderate to severe erythema, very slight, slight and moderate edema,
scaling, severe scaling, crust formation, bleeding (in some cases
extending beyond the area of exposure), petechiae extending beyond the
area of exposure, ulcer, alopecia, erosion and eczematoid skin change
(in one case extending beyond the area of exposure). Visual necrosis was
observed in 2 female animals of the 400 mg/kg bw dose group and in 4
male animals of the 1000 mg/kg bw dose group. Although the skin barrier
was almost completely destroyed under the given test conditions and
severe local skin damage was noted, no mortality occurred. Under the
conditions of this study the acute dermal median lethal dose (LD50) of
2-hydroxyethyl acrylate was found to be greater than 1000 mg/kg body
weight for the male animals. Due to animal welfare reason (necrosis of
the skin) the other sex as well as higher doses were not tested.
In a supporting study performed in
parallel with the structural analogue hydroxypropyl acrylate (CAS 25584
-83 -2) no mortality occurred after application of 1000 mg/kg body
weight to 5 female animals. Therefore the acute dermal median lethal
dose (LD50) of 2-hydroxyethyl acrylate is considered to be greater than
1000 mg/kg body weight for the male and female animals (BASF, 1999).
In addition, there are several older
studies with 2-HEA conducted in rabbits which demonstrate without
exception a higher toxicity of 2-HEA in rabbits in comparison to rats
with LD50 values > 50 - < 200 mg/kg bw (Dow Chemical Company 1980 and
1981, BASF 1979, Union Carbide Corporation 1966). However,
2-hydroxyethyl acrylate is a corrosive substance and is classified and
labelled as Skin Corrosion Category 1B, H314. More recent experimental
experience has shown that rabbits are quite susceptible to stress, e. g.
caused by local skin damage due to the application of corrosive
substances like 2-HEA. Emotional stress and intense pain can lead to
cardiac failure in rabbits. Therefore it is unclear if death was due to
stress as a response to severe local effects, or due to systemic
toxicity of the compound.
Lethality was also observed after an
exposure period of 4 hours in skin irritation studies with rabbits if
undiluted material was tested, whereas no systemic effects were noted if
a 10 % solution was applied (Dow, Chemical Company, 1980).
However, assumed that bioavailability
after dermal application of 2-HEA was 100 % due to damage of the skin
barrier a LD50 value comparable to that after oral administration (100 %
bioavailability has been demonstrated (BAMM, 1992)) would be expected.
Since there are no indications for interspecies differences in the
toxicological profile of 2-HEA (as can been seen in the sections for
repeated dose toxicity) the lower LD50 values from rabbit studies are
assessed to be a secondary reaction due to severe local effects.
Moreover, bioavailability after dermal application of non-corrosive test
substance concentrations has been shown to be definitively lower than
after oral administration (BAMM, 1992).
Although evaluation and classification
of a test substance should be based on the most sensitive species,
rabbits are assessed to be hypersensitive towards corrosive test
substances causing severe skin damage and do not adequately reflect the
acute dermal toxicity potential of such substances. Therefore, rabbits
are considered to be inappropriate for the evaluation of dermal toxicity
of 2-HEA and the respective studies are considered invalid (reliability
In contrast, based on data from
rats, even under test conditions at which the skin barrier is
compromised and severe local tissue damage is noted, however in the
absence of mortality, this species is assessed to be the most
appropriate one for the evaluation of acute dermal toxicity of 2-HEA.
Furthermore, the rat is one of the recommended test species according to
OECD TG 402. It should be noted, that even in rats, the noted effects at
necropsy (rather unspecific toxicity) might at least partially due to
severe local skin damage caused by 2-HEA.
A retrospective analysis of data from
acute oral and dermal toxicity testing, performed on pesticide active
substances and new chemical entities has demonstrated that there is a
relationship between dermal acute toxicity and oral acute toxicity, and
there are no significant numbers of compounds that are classified as a
potential hazard only via the dermal route (Creton et al. 2010). Thus, a
comparable acute oral and dermal hazard can be expected.
This assessment is supported by data
from acrylic acid (AA), one of the main metabolites of 2-HEA. For AA the
situation regarding skin effects and acute dermal toxicity is
comparable: skin corrosivity and pronounced acute dermal toxicity noted
in rabbits based on results with undiluted material. A recently
performed acute dermal toxicity study with diluted acrylic acid in
rabbits shows however, that all animals survived exposure to the test
substance up to the limit dose of 2000 mg/kg bw. At 2000 mg/kg (20%
dilution) all animals survived and gained body weight as expected. From
Day 1 through Day 14, animals were observed with areas of brown
discoloration, blanching, edema, erythema, eschar, fissuring, mechanical
damage and/or small areas of necrosis. Besides clear skin damage, no
gross abnormalities were noted during the gross necropsy. These results
clearly show that the pronounced toxic effects of acrylic acid and in
consequence also 2-HEA are due to local corrosion/tissue damage, but not
or only to a minor degree due to systemic toxicity (BAMM, 2011).
Inhalation exposure route:
Data on acute toxicity of
2-hydroxyethyl acrylate by the inhalation route are limited. There are
several inhalation hazard tests available where groups of rats were
exposed to vapour atmospheres saturated with the volatile parts of the
substance. In one study groups of 3 rats/sex were exposed for 8 hrs to a
vapour atmosphere and observed for a post-exposure period of 7 days. No
mortality occurred, clinical signs of toxicity were dyspnoea and
irritation of mucous membranes (nose, respiratory tract) (BASF, 1974).
Inhalation exposures to 333 and 394
ppm (corresponding to approx. 1.58 and 1.87 mg/L exceeding by far the
saturated vapour concentration, indicating a vapour / aerosol mixture)
for 8 and 4 hours respectively caused irritation and were in the
threshold area for lethality. In both trials 1/6 rats died within 24 hrs
of exposure to a saturated vapour atmosphere (Union Carbide Corporation,
A 7-hour exposure to a saturated
vapour atmosphere of approx. 300 ppm (corresponding to approx. 1.45
mg/L; exceeding by far the saturated vapour concentration, indicating a
vapour / aerosol mixture) at room temperature had no lethal effect on 5
female Sherman rats. No signs of toxicity were observed. In parallel, 5
female rats were exposed to an atmosphere saturated with test substance
vapours at 100 °C. 5/5 rats died within 5 hrs of exposure (Dow Chem.
Co., 1980). Similar results were observed in another study by The Dow
Chemical Company (1962).
Based on the available information the
substance is classified as Acute Tox. 4 H302: Harmful if swallowed
and Acute Tox. 4 H312: Harmful if in contact with skin, in
accordance with EU Classification, Labelling and Packaging of Substances
and Mixtures (CLP) Regulation (EC) No. 1272/2008.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
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