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Administrative data

Description of key information

Hydroxypropyl acrylate was concluded to to be of moderate toxicity after a single ingestion and after a single skin contact. The inhalation of a highly saturated vapour-air-mixture represents an unlikely acute hazard.
Oral: LD50 = ca. 1001 mg/kg bw (Sprague-Dawley rat, BASF test comparable to OECD TG 401)
Oral: LD50 = 820 mg/kg bw (CRCD rat, Standard acute method)
Dermal: LD50: > 1000 mg/kg bw (Wistar rat, OECD TG 402)
Data from the structural analogue 2-Hydroxyethyl acrylate:
Dermal: LD50: > 1000 mg/kg bw (Wistar rat, OECD TG 402)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Basic data given (comparable to guidelines/standards). Data were audited by QAU but no reference to GLP standard. Original report not available. Data, reliability and rationale as cited in OECD SIDS (2006).
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
other: CRCD
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 220 - 235 g
- Fasting period before study: yes
Route of administration:
oral: gavage
Vehicle:
water
Doses:
0, 710, 840, 1000, 1410 and 2000 mg/kg bw
No. of animals per sex per dose:
10 animals/dose (all dose groups except 710 mg/kg bw) and 20 animals/dose (710 mg/kg bw dose group), respectively
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily
- Necropsy of survivors performed: yes
Sex:
male
Dose descriptor:
LD50
Effect level:
820 mg/kg bw
95% CL:
760 - 910
Mortality:
For details see Remarks on results including tables and figures.
Clinical signs:
Signs of toxicity, including passiveness, ataxia and salivation, were observed in several animals.
Body weight:
No data
Gross pathology:
No gross lesions were observed in any animal that was sacrificed at the end of the 14-day observation period. The following observations were noted in animals that died during the study: stained muzzle, lungs, stomach and intestines red and fluid-filled, and enlarged stomach.

Mortality:

 

Dose group [mg/kg bw]

No. dead / No. dosed

0

0/10

710

4/20

840

5/10

1000

9/10

1410

10/10

2000

10/10

Interpretation of results:
Category 4 based on GHS criteria
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
820 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study meets generally accepted scientific standards with restrictions due to the limited documentation in the summary report
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Principles of method if other than guideline:
This test (also called inhalation hazard test) was performed in principle as described in OECD Guideline 403.

Several groups of 3 rats per sex were exposed sequentially to the vapours, generated by bubbling 200 L/h air through a substance column of about 5 cm above a fritted glass disc in a glass cylinder for different time periods (8 hours). The temperature chosen for vapour generation was 20 °C and the exposure time not causing lethality was determined.
No analytical determination of the atmosphere concentrations was performed. The nominal concentration can be calculated as quotient of the amount of test substance weight loss during the exposure, which is given in the raw data, and the amount of air used during the exposure.
Group-wise documentation of clinical signs was performed over the 7-day study period. The clinical signs and findings were reported in summarized form.
GLP compliance:
no
Test type:
other: Inhalation Hazard Test
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: no data
- Mean body weight at study initiation:
- males: 151 (test group 1), 249 (test group 2), and 153 (control group) g;
- females: 166 (test group 1), 180 (test group 2), and 159 (control group) g
Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
8 h
Concentrations:
0.38 mg/L
Calculated vapour saturation: based on the vapour pressure and molecular weight of the test substance, the vapour saturation was calculated to be 0.05 mg/L at 20 °C.
No. of animals per sex per dose:
3
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 7 days
- Frequency of observations and weighing: daily on workdays; group-wise determination of body weights at test start and termination
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
no statistics
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 0.38 mg/L air (nominal)
Exp. duration:
8 h
Remarks on result:
other: IHT
Mortality:
0/12 rats died after exposure to an atmosphere that had been saturated at 20 degrees centigrade with the volatile parts of the compound.
Clinical signs:
During exposure: distinct eye and nose secretion, gasping.
Post-exposure: slight dyspnoea, bloody eyelid crusts and bloody eschar formation around noses. Two days after exposure, the animals had recovered completely and were without finding.
Body weight:
- males: 173 (test group 1), 270 (test group 2), and 176 (control group) g;
- females: 185 (test group 1), 206 (test group 2), and 178 (control group) g
Gross pathology:
At necropsy no abnormalities were observed.

The test substance concentration was estimated to be approx. 0.38 mg/L at 20 °C. Vapour saturation was calculated to be approx. 0.05 mg/L at 20 °C. Thus, the animals were exposed to a saturated vapour atmosphere, possibly in the presence of some aerosol particles.

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Well documented study report which meets basic scientific principles.
Principles of method if other than guideline:
Substantially saturated vapour was prepared by spreading 50 grams of chemical over a 200 cm2 area on a shallow tray placed near the top of a 200-liter glass chamber which was then sealed for at least 16 hrs while an intermittently operated fan agitated the internal chamber atmosphere. Rats were then introduced in a gasketed drawer-type cage designed and operated to minimize vapour loss.
GLP compliance:
no
Test type:
other: Inhalation hazard test
Limit test:
yes
Species:
rat
Strain:
not specified
Sex:
not specified
Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
8 h
Concentrations:
substantially saturated vapours
No. of animals per sex per dose:
6
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
Sex:
not specified
Dose descriptor:
other: IHT
Exp. duration:
8 h
Remarks on result:
other: 0/6 rats died after exposure to an atmosphere that had been saturated at 20 degrees centigrade with the volatile parts of the compound.
Mortality:
During the exposure period of 8 hours none of the six rats died.
Clinical signs:
Extremities irritated within 4 hrs; slight loss of coordination at 6 hrs, but normal at 8 hrs.
Body weight:
No substance-related effect.
Gross pathology:
No abnormalities found at necropsy.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Principles of method if other than guideline:
The acute dermal toxicity was investigated in a group af 5 male and 5 female rats (treated with the undiluted liquid test substance, 400 mg/kg bw). Since no mortality occurred, a dose of 1000 mg/kg (test substance emulsion in olive oil) was tested with 5 female rats.
Due to necrotic skin changes caused by the test substance preparation, a further application of 1000 mg/kg with 5 male rats was not performed.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Strain: Wistar / chbb: thom (SPF)
- Source: Boehringer Ingelheim Pharma KG
- Age at study initiation: Young adult animals
- Weight at study initiation: 200 g - 300 g
- Fasting period before study: no
- Housing: Single housing
- Diet (ad libitum): Kliba-Labordiaet, Klingentalmuehle AG Kaiseraugst, Switzerland
- Water (ad libitum): Tap water
- Acclimation period: at least 1 week.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12 / 12

Type of coverage:
semiocclusive
Vehicle:
olive oil
Details on dermal exposure:
TEST SITE
- Area of exposure: dorsal and dorsolateral parts of the trunk
- % coverage: About 50 cm2 (corresponds to at least 10 % of the body surface area
- Type of wrap if used: four layers absorbent gauze, Ph. Eur. Lohmann GmbH & Co. KG and Ficomull stretch (adhesive fleece), Beiersdorf AG


REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, with warm water
- Time after start of exposure: 24 hr


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.38 mL/kg bw undiluted (= 400 mg/kg bw) and 4 mL/kg bw in olive oil (= 1000 mg/kg bw)
- Concentration (if solution): 25 g/ 100 mL
- Constant volume or concentration used: no


VEHICLE
- Lot/batch no.: Olive oil DAB 10
Duration of exposure:
24 hr
Doses:
400 mg/kg (undiluted test substance), 1000 mg/kg (emulsion in olive oil)
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
- A check for any dead or moribund animal was made twice each workday and once on saturdays, sundays and on public holidays.
- Individual body weights shortly before application (day 0), weekly thereafter and at the end of the study (before fasting period).
- Recording of signs and symptoms several times on the day of administration, at least once each workday for the individual animals.
- Individual readings of skin findings 30 - 60 minutes after removal of the semiocclusive dressing (day 1), day 4 (only 400 mg/kg), day 7 and at the end of the study (last day of the observation period).
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, histopathology, assessment of skin findings according to Draize JH (1959): Appraisal of the safety of chemicals in foods, drugs and cosmetics. The association of food and drug officials of the United States Austin, Texas.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 1 000 mg/kg bw
Mortality:
No mortality occurred.
Clinical signs:
No systemic toxicity was noted in any of the animals.
Body weight:
Body weight gain: The expected body weight gain was observed in the course of the study with the exception of 1 female of the 1000 mg/kg bw group which showed weight reduction in the first week of observation.
Gross pathology:
- Necropsy: lesions or necrosis in the region of the application area were noted at the end of the study at 1000 mg/kg bw.
- Histopathology: Histopathological examination of 1 animal of the 1000 mg/kg bw dose group revealed focal necrosis (full thickness necrosis), perifocal hyperplasia, squamous cell and perifocal inflammation.
Other findings:
Local skin effects:
Local effects observed in the 400 and 1000 mg/kg bw dose groups were very slight, well-defined and moderate to severe erythema, very slight and slight edema, scaling, severe scaling, crust formation, bleeding and petechiae. Visual necrosis was seen in 1 female rat of the 400 mg/kg bw group and in 2 females of the 1000 mg/kg bw group.

In the present study, the acute LD50 was found to be > 1000 mg/kg bw for the female animals. Due to animal welfare reason (necrosis of the skin) male animals were not tested. However, in another study performed in parallel with a similar test substance (2-Hydroxyethyl acrylate), no mortality occurred after application of 1000 mg/kg bw to 5 male rats. Thus, the acute dermal LD50 of Hydroxypropyl acrylate is considered to be > 1000 mg/kg bw for male and female animals.

Body weights [g]:

Dose [mg/kg bw]

400

1000

 

male

female

female

Day 0

264

217

227

Day 7

288

227

230

Day 13

316

244

284

Interpretation of results:
Category 4 based on GHS criteria
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
discriminating dose
1 000 mg/kg bw

Additional information

Oral exposure route:

For the key study evaluating the acute oral toxicity of hydroxypropyl acrylate in rats, the LD50 was determined to be approx. 1001 mg/kg bw (BASF AG 1974). Groups of 5 Sprague-Dawley rats/sex/dose were administered by gavage doses of approx. 210.8, 421.6, 843.2, 1054, 1317.5, and 1686.4 mg/kg bw hydroxypropyl acrylate. The study was conducted according to an internal protocol similar to OECD TG 401. The animals were observed for clinical signs for 7 days.

At the highest dose, all animals died within 24 hrs after administration. At 1317.5, 1054.0 and 843.2 mg/kg bw 7/10, 6/10 and 2/10 animals died within 24, 24 and 48 hr, respectively. At the two lower doses, no mortality was observed. Clinical signs comprised dyspnoea, slight apathy, staggering, lateral-abdominal position, and reddish crust formation at the nose. In addition, some animals showed timidity. At necropsy, the following findings were made in deceased animals: acute dilatation of the heart, acute congestive hyperemia, dilatation of the stomach, severe injection of the stomach vessels, extensive haemorrhages in the stomach, diarrhoeic contents of the intestines. In some animals additionally aszites and nephrosis were observed. At the two low doses no abnormalities were detected in the sacrificed animals.

In another oral gavage study performed with CRCD rats, the LD50 was 820 mg/kg body weight (Rohm and Haas, 1983). In this study, groups of 10 male rats were administered hydroxypropyl acrylate at 0 (distilled water, control), 840, 1000, 1410, and 2000 mg/kg and a group of 20 male rats were dosed at 710 mg/kg. The animals were observed for 14 days. The mortality was 0/10, 4/20, 5/10, 9/10, 10/10 and 10/10 for the 0, 710, 840, 1000, 1410 and 2000 mg/kg groups, respectively. The clinical signs included ataxia, salivation, and passiveness. Animals that died during the study showed stained muzzle; lungs, stomach and intestines red and fluid filled; and enlarged stomach.

Similar LD50 values were observed in three other studies (Union Carbide Corporation (1971), Vodicka (1986), and The Dow Chemical Company (1967)).

Based on these test results, the substance is assessed to be of moderate toxicity after a single ingestion.

Dermal exposure route:

The acute dermal toxicity of hydroxypropyl acrylate was investigated in a group of 5 male and 5 female Wistar rats (400 mg/kg bw) and in a group of 5 female rats (1000 mg/kg bw) in a GLP-compliant acute toxicity study performed according to OECD TG 402 (BASF AG, 1999). 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 semiocclusive 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 and slight edema, scaling, severe scaling, crust formation, bleeding and petechiae. Visual necrosis was seen in 1 female rat of the 400 mg/kg bw group and in 2 females of the 1000 mg/kg bw group. No mortality occurred. Under the conditions of this study the acute dermal median lethal dose (LD50) of hydroxypropyl acrylate was found to be greater than 1000 mg/kg body weight for the female animals. Due to animal welfare reason (necrosis of the skin) the other sex was not tested.

In a study performed in parallel with the structural analogue 2-hydroxyethyl acrylate no mortality occurred after application of 1000 mg/kg body weight to 5 male animals. Therefore the acute dermal median lethal dose (LD50) of hydroxypropyl acrylate is considered to be greater than 1000 mg/kg body weight for the male and female animals.

In addition, there are several older studies with HPA conducted in rabbits which demonstrate without exception a higher toxicity of HPA in rabbits in comparison to rats with LD50 values > 50 - < 200 mg/kg bw (Dow Chemical Company 1967 and 1981, BASF AG 1979, Rohm & Haas 1983, Union Carbide Corporation 1971). Based on these experimental findings, hydroxypropyl acrylate is classified as T, R24 (“Toxic in contact with skin”) according to the Annex I of Directive 67/548/EEC. 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 the corrosive substance HPA. Emotional stress and intense pain can lead to cardiac failure in rabbits which makes it impossible to distinguish between lethalities due to stress and lethalities due to systemic toxicity of the compound. Therefore, rabbits are not the appropriate test species for dermal toxicity studies with corrosive substances and the respective studies are considered invalid (reliability 3). According to the information requirements of REACH, testing of corrosive substances by the dermal route is not requested.

Inhalation exposure route:

Data on acute toxicity 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 Wistar rats/sex were exposed for 8 hrs to a vapour atmosphere (nominal 0.38 mg/L) and observed for a post-exposure period of 7 days. No mortality occurred, clinical signs of toxicity were distinct eye and nose secretion, gasping; and during the post-exposure slight dyspnoea, bloody eyelid crusts and bloody eschar formation around noses (BASF AG, 1974).

Inhalation exposure to vapours substantially saturated with the test substance for 8 hours caused irritation of the extremities and hyperactivity. No mortality occurred (Union Carbide Corporation, 1971). Similar effects and results were observed in another study by the Dow Chemical Company (1967).

Conclusion:

Taking all the presented data into consideration, hydroxypropyl acrylate was concluded to be of moderate toxicity after a single ingestion and after a single skin contact. The inhalation of a highly saturated vapour-air-mixture represents an unlikely acute hazard.


Justification for classification or non-classification

Harmonized classification:

According to current EU regulations hydroxypropyl acrylate is classified for Acute Toxicity Category 3* for the oral, dermal and inhalative route (Table 3.1 of the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008, respectively.

Self classification:

Based on the reliable experimental data, the substance should be classified for Acute Toxicity Category 4: H302: Harmful if swallowed and H312: Harmful in contact with skin according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008, respectively.