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Toxicological information

Acute Toxicity: dermal

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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:
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

Reference
Name:
Unnamed
Type:
Constituent
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 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:
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.

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