Acrylic acid, monoester with propane-1,2-diol

Acute Toxicity: dermal

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1999

Report date:

1999

Materials and methods

Test guideline

Qualifier:

according to guideline

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

Test material

Test material information

Constituent 1

Reference substance name:

Acrylic acid, monoester with propane-1,2-diol

EC Number:

247-118-0

EC Name:

Acrylic acid, monoester with propane-1,2-diol

Cas Number:

25584-83-2

Molecular formula:

C6H10O3

IUPAC Name:

Reaction mass of 2-hydroxy-1-methylethyl acrylate and 2-hydroxypropyl acrylate

Details on test material:

- Name of test material (as cited in study report): Hydroxypropyl acrylate
- Analytical purity: 98.9 area % (GC)
- Substance No.: 98/185-1
- Lot/batch No.: Beh. 10, 15:30

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system 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

Administration / exposure

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.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 1 000 mg/kg bw

Mortality:

No mortality occurred.

Clinical signs:

other: No systemic toxicity was noted in any of the animals.

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.

Any other information on results incl. tables

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

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria