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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)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Specific details on test material used for the study:
- Name of test material (as cited in study report): 2-Hydroxyethyl acrylate
- Analytical purity: 99.1 area % (GC)
- Lot/batch No.: Beh. 11, 15 :30
- Substance No.: 98/184-1

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Boehringer Ingelheim Pharma KG
- Strain: Wistar / chbb: thom (SPF)
- Age at study initiation: young adult animals
- Weight at study initiation: 200 g - 300 g (± 20 % of the mean weight)
- Fasting period before study: no fasting
- Housing: single housing
- Diet (ad libitum): Labordiaet, Klingentalmuehle AG, Kaiseraugst, Switzerland
- Water (ad libitum): tap water
- Acclimation period: at least 1 week


ENVIRONMENTAL CONDITIONS
- Temperature: 20 - 24 °C
- Humidity: 30 - 70 % relative humidity
- 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 (clipped)
- Application area: 50 cm2 (corresponds to at least 10 % of the body surface area)
- Type of wrap if used: The bandage consisted of four layers absorbent gauze, Ph. Eur. Lohmann GmbH & Co. KG and Fixomull stretch (adhesive
fleece), Beiersdorf AG


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


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.36 mL/kg bw (undiluted, 400 mg/kg bw) and as an emulsion 4.0 mL/kg bw (1000 mg/kg bw)
- Concentration (if solution): 25 g / 100 mL (dose: 1000 mg/kg bw)
- Constant volume or concentration used: yes/no



VEHICLE
- Amount(s) applied (volume or weight with unit): 4.0 mL/kg bw emulsion
- Lot/batch no.: DAB 10
Duration of exposure:
24 hrs
Doses:
400 and 1000 mg/kg bw
No. of animals per sex per dose:
400 mg/kg bw: 5 males, 5 females; 1000 mg/kg bw: 5 males
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Individual body weights were determined shortly before application (day 0), weekly thereafter and at the end of the study (before fasting period). Recording of signs and symptoms was performed several times on the day of administration, and at least once each workday for the individual animals. A check for any dead or moribund animal was made twice each workday and once on saturdays, sundays and on public holidays.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, histopathology, scoring 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)
Statistics:
no data

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 1 000 mg/kg bw
Mortality:
No mortality occurred.
Clinical signs:
No systemic signs of toxicity were noted in any animals.
Body weight:
The expected body weight gain was observed in the course of the study with the exception of 2 male animals of the 1000 mg/kg bw dose group and 2 female rats of the 400 mg/kg bw dose group, which showed weight reduction in the first week of observation.
Gross pathology:
Necropsy findings noted in the animals sacrificed at the end of the study comprised: focal lesion with incrusted surface of the skin (400 mg/kg bw), lesion or necrosis of the skin in the region of application area (1000 mg/kg bw). 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 findings: The following 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.

Any other information on results incl. tables

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.

Body weights [g]:

Dose [mg/kg bw]

400

1000

male

female

male

Day 0

250

230

270

Day 7

270

232

273

Day 13

302

248

305

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria